Despite its importance in the lived experience of dementia, symptom fluctuation has been little studied outside Lewy body dementia. We aimed to characterize symptom fluctuation in patients with Alzheimer's disease (AD) and mixed dementia.

A qualitative analysis of health records that included notations on good days and bad days yielded 52 community-dwelling patients (women, n = 30; aged 39–91 years; mild dementia, n = 26, chiefly AD, n = 36).

Good days/bad days were most often described as changes in the same core set of symptoms (e.g. less/more verbal repetition). In other cases, only good or only bad days were described (e.g. no bad days, better sense of humor on good days). Good days were typically associated with improved global cognition, function, interest, and initiation. Bad days were associated with frequent verbal repetition, poor memory, increased agitation and other disruptive behaviors.

Clinically important variability in symptoms appears common in AD and mixed dementia. Even so, what makes a day “good” is not simply more (or less) of what makes a day “bad”. Further investigation of the factors that facilitate or encourage good days and mitigate bad days may help improve quality of life for patients and caregivers.

Service planning for people with younger onset dementia (YOD; an onset of symptoms before the age of 65 years) relies on prevalence estimates, with existing models based upon older people. This pilot study investigated the prevalence and causes of YOD in a defined catchment area of Eastern Sydney, Australia.

The study was conducted in three stages: publicity building, case finding, and case validation. A brief structured questionnaire was sent to health professionals in the catchment area asking how many patients with YOD they had seen over the previous 12 months. Memory clinics and hospital records were also searched for YOD patients. Clinicians assigned a Statistical Linkage Key to each patient to prevent double counting, and indicated the cause of dementia. The majority of patients were validated by a review of medical case notes. Prevalence data were calculated for the following age groups: 30–64, 30–44, and 45–64 years.

Two hundred and four potential patients were identified, of which 141 met inclusion criteria. The primary clinical subtypes were alcohol-related dementia (18.4%), Alzheimer's disease (17.7%), vascular dementia (12.8%), and frontotemporal dementia (11.3%). Eighty-eight patients were aged 30 to 64 years on census date and were therefore included in the prevalence calculations. The overall prevalence was 68.2 per 100,000 population at risk for the 30–64-year age group (95% Confidence Interval (CI): 54.9–83.4); 11.6 per 100,000 for the 30–44-year age group (95% CI: 5.3–21.7); and 132.9 per 100,000 for the 45–64 age group (95% CI: 105.8–164.2).

Younger onset dementia affects a significant number of people in Eastern Sydney with a diverse range of clinical types. This prevalence rate is higher than previous reports from the United Kingdom and Japan, with a different distribution of etiologies, which have important implications for service planning for this group.

Reports of attitudes to aging from older people themselves are scarce. Which life course factors predict differences in these attitudes is unknown.

We investigated life course influences on attitudes to aging in healthy, community-dwelling people in the UK. Participants in the Lothian Birth Cohort 1936 completed a self-report questionnaire (Attitudes to Aging Questionnaire, AAQ) at around age 75 (n = 792, 51.4% male). Demographic, social, physical, cognitive, and personality/mood predictors were assessed, around age 70. Cognitive ability data were available at age 11.

Generally positive attitudes were reported in all three domains: low Psychosocial Loss, high Physical Change, and high Psychological Growth. Hierarchical multiple regression found that demographic, cognitive, and physical variables each explained a relatively small proportion of the variance in attitudes to aging, with the addition of personality/mood variables contributing most significantly. Predictors of attitudes to Psychosocial Loss were high neuroticism; low extraversion, openness, agreeableness, and conscientiousness; high anxiety and depression; and more physical disability. Predictors of attitudes to Physical Change were: high extraversion, openness, agreeableness, and conscientiousness; female sex; social class; and less physical disability. Personality predictors of attitudes to Psychological Growth were similar. In contrast, less affluent environment, living alone, lower vocabulary scores, and slower walking speed predicted more positive attitudes in this domain.

Older people's attitudes to aging are generally positive. The main predictors of attitude are personality traits. Influencing social circumstances, physical well-being, or mood may result in more positive attitudes. Alternatively, interventions to influence attitudes may have a positive impact on associated physical and affective changes.

An increasing number of studies have examined the effects of training of cognitive and other tasks on brain structure, using magnetic resonance imaging.

Studies combining cognitive and other tasks training with longitudinal imaging designs were reviewed, with a view to identify paradigms potentially applicable to treatment of cognitive impairment.

We identified 36 studies, employing training as variable as juggling, working memory, meditation, learning abstract information, and aerobic exercise. There were training-related structural changes, increases in gray matter volume, decreases, increases and decreases in different regions, or no change at all. There was increased integrity in white matter following training, but other patterns of results were also reported.

Questions still to be answered are: Are changes due to use-dependent effects or are they specific to learning? What are the underlying neural correlates of learning, the temporal dynamics of changes, the relations between structure and function, and the upper limits of improvement? How can gains be maintained? The question whether neuroplasticity will contribute to the treatment of dementia will need to be posed again at that stage.

Delirium is a common neuropsychiatric syndrome associated with poor outcomes. Evidence supports a neuroinflammatory etiology, but the role of the inflammatory marker C-reactive protein (C-RP) remains unclear. We investigated the relationship between C-RP and delirium and its severity as well as interaction with medical diagnosis.

From an existing database (710 patients over 70 years old admitted to a Medical Acute Admissions Unit) we analyzed data which included C-RP levels, delirium (using the Confusion Assessment Method), and other clinical and demographic factors. Primary diagnoses were grouped (cardiovascular, musculoskeletal, infection, metabolic, and other).

There was a strong association between elevated C-RP and delirium (t = 5.09; p < 0.001), independent of other potential risk factors for delirium (odds ratio (OR) = 1.32 (95% CI: 1.10–1.58) p = 0.003). There was no significant association between C-RP and delirium severity, and between C-RP and delirium in the populations with cardiovascular disease, infection upon admission, or from the metabolic group despite an OR of 2.24 (95% CI: 0.92–5.45). There was an association in the musculoskeletal group (OR 2.19 (95% CI: 1.19–4.02)).

Conclusions: There is an association between elevated C-RP and delirium. This is strongest in patients admitted with musculoskeletal disease but not in others, implying that C-RP is involved in the genesis of delirium in musculoskeletal disease, but that other factors or processes may be more important in those with cardiovascular disease or infection.

There is limited research on factors that influence the rate of progression in Alzheimer's disease (AD). A history of traumatic brain injury (TBI) is associated with an increased risk for AD, but its role on the rate of dementia progression after the onset of AD has not been examined.

A population-based cohort of 325 persons with incident AD was followed for up to 11 years. The sample was 65% female with a mean (SD) age of dementia onset = 84.4 (6.4) years. History of TBI was categorized as number, severity (with or without loss of consciousness), and timing in relation to dementia onset (within ten years or more than ten years). Cognition was assessed by the Consortium to Establish a Registry of AD battery, and functional ability was assessed by the Clinical Dementia Rating Sum of Boxes.

In linear mixed models, a history of TBI within ten years of onset showed faster progression of functional impairment (LR x2 = 10.27, p = 0.006), while those with TBI more than ten years before dementia onset had higher scores on a measure of list learning (β = 1.61, p = 0.003) and semantic memory (β = 0.75, p = 0.0035).

History of TBI and its recency may be a useful factor to predict functional progression in the course of AD.

The Australian Imaging, Biomarkers and Lifestyle (AIBL) Flagship Study of Ageing is a prospective study of 1,112 individuals (211 with Alzheimer's disease (AD), 133 with mild cognitive impairment (MCI), and 768 healthy controls (HCs)). Here we report diagnostic and cognitive findings at the first (18-month) follow-up of the cohort. The first aim was to compute rates of transition from HC to MCI, and MCI to AD. The second aim was to characterize the cognitive profiles of individuals who transitioned to a more severe disease stage compared with those who did not.

Eighteen months after baseline, participants underwent comprehensive cognitive testing and diagnostic review, provided an 80 ml blood sample, and completed health and lifestyle questionnaires. A subgroup also underwent amyloid PET and MRI neuroimaging.

The diagnostic status of 89.9% of the cohorts was determined (972 were reassessed, 28 had died, and 112 did not return for reassessment). The 18-month cohort comprised 692 HCs, 82 MCI cases, 197 AD patients, and one Parkinson's disease dementia case. The transition rate from HC to MCI was 2.5%, and cognitive decline in HCs who transitioned to MCI was greatest in memory and naming domains compared to HCs who remained stable. The transition rate from MCI to AD was 30.5%.

There was a high retention rate after 18 months. Rates of transition from healthy aging to MCI, and MCI to AD, were consistent with established estimates. Follow-up of this cohort over longer periods will elucidate robust predictors of future cognitive decline.

Antipsychotic drugs (APD) are widely prescribed for people with dementia residing in long term care facilities (LTCFs). Concern has been expressed that such prescribing is largely inappropriate. The objective of this study is to examine if differences in facility-level prevalence of APD use in a sample of LTCFs for patients with dementia can be explained by patient and facility-related characteristics.

A point prevalence study was conducted using data from the VU University Resident Assessment Instrument (VURAI) database from nursing homes and residential care facilities in the Netherlands. Patients were selected who had a diagnosis of dementia. LTCF and patient characteristics were extracted from the VURAI; facility-level resident satisfaction surveys were provided by the National Institute for Public Health.

In total, 20 LTCFs providing care for 1,090 patients with dementia were investigated. Overall, 31% of patients used an APD. In facilities with a high prevalence of APD use behavioral symptoms were present in 62% of their patients. In facilities with medium APD use behavioral problems remained frequent (57%), and in facilities with low prevalence of APD use 54% of the patients had behavioral symptoms. Facilities with a high prevalence of APD use were often large, situated in urban communities, and scored below average on staffing, personal care, and recreational activities.

There was considerable variation between the participating LTCFs in the prevalence of APD use. Variability was related to LTCF characteristics and patient satisfaction. This indicates potential inappropriate prescribing because of differences in institutional prescribing culture.

Deathbed wills by their nature are susceptible to challenge. Clinicians are frequently invited to give expert opinion about a dying testator's testamentary capacity and/or vulnerability to undue influence either contemporaneously, when the will is made, or retrospectively upon a subsequent challenge, yet there is minimal discourse in this area to assist practice.

The IPA Capacity Taskforce explored the issue of deathbed wills to provide clinicians with an approach to the assessment of testamentary capacity at the end of life. A systematic review searching PubMed and Medline using the terms: “deathbed and wills,” “deathbed and testamentary capacity,” and “dying and testamentary capacity” yielded one English-language paper. A search of the individual terms “testamentary capacity” and “deathbed” yielded one additional relevant paper. A focused selective review was conducted using these papers and related terms such as “delirium and palliative care.” We present two cases to illustrate the key issues here.

Dying testators are vulnerable to delirium and other physical and psychological comorbidities. Delirium, highly prevalent amongst terminal patients and manifesting as either a hyperactive or hypoactive state, is commonly missed and poorly documented. Whether the person has testamentary capacity depends on whether they satisfy the Banks v Goodfellow legal criteria and whether they are free from undue influence. Regardless of the clinical diagnosis, the ultimate question is can the testator execute a specific will with due consideration to its complexity and the person's circumstances?

Dual ethical principles of promoting autonomy of older people with mental disorders whilst protecting them against abuse and exploitation are at stake here. To date, there has been scant discourse in the scientific literature regarding this issue.

Studies in memory clinics suggest that the majority of patients would like to know of a diagnosis of dementia. It is less clear what preferences are in the community. Our objective was to review the literature on preferences regarding disclosure of a diagnosis of dementia and to assess key arguments in favor of and against disclosure.

Systematic search of empirical studies was performed in Pubmed, Embase, and Psycinfo. We extracted preferences of individuals without cognitive impairment (general population; relatives of dementia patients; and physicians) and preferences of individuals referred to a memory clinic or already diagnosed with dementia. A meta-analysis was done using a random effects model. Our main conclusions are based on studies with a response rate ≥75%.

We included 23 articles (9.065 respondents). In studies with individuals without cognitive impairment, the pooled percentage in favor of disclosure was 90.7% (95%CI: 83.8%–97.5%). In studies with patients who were referred to a memory clinic or already diagnosed with dementia, the pooled percentage that considered disclosure favorable was 84.8% (95%CI: 75.6%–94.0%). The central arguments in favor of disclosure pertained to autonomy and the possibility to plan one's future. Arguments against disclosure were fear of getting upset and that knowing has no use.

The vast majority of individuals without and with cognitive impairment prefers to be informed about a diagnosis of dementia for reasons pertaining to autonomy.

Several important systematic reviews and meta-analyses focusing on psychosocial interventions have been undertaken in the last decade. However, they have not focused specifically on the treatment of individual behavioral and psychological symptoms of dementia (BPSD) with personalized interventions. This updated systematic review will focus on studies reporting the effect of personalized psychosocial interventions on key BPSD in care homes.

Systematic review of the evidence for psychosocial interventions for BPSD, focusing on papers published between 2000 and 2012. All care home and nursing home studies including individual and cluster randomized controlled trials (RCTs) and pre-/post-test studies with control conditions were included.

641 studies were identified, of which 40 fulfilled inclusion and exclusion criteria. There was good evidence to support the value of personalized pleasant activities with and without social interaction for the treatment of agitation, and reminiscence therapy to improve mood. The evidence for other therapies was more limited.

There is a growing body of evidence indicating specific effects of different personalized psychosocial interventions on individual BPSD and mood outcomes.

Identifying dementia in primary care could minimize the impact of a late intervention; however, it shows high rates of misdiagnosis. One of the reasons seems to be the lack of knowledge of adequate cognitive screening instruments. This is a systematic review of the available instruments for the primary care context.

For this systematic review, articles were collected according to the following combined key terms: “cognitive screening” and “dementia” and “primary care” and “review”. Studies should be reviews focusing on cognitive screening instruments best used in primary care setting.

Thirteen reviews were selected. In total, it was considered 34 cognitive screening instruments. Half of the instruments can be applied in an adequate time-limit for primary care context. Memory is the most commonly assessed cognitive function (91%). Almost half of the tests are mentioned to have influence of education or cultural factors (44%).

Tests such as 6CIT, AMT, GPCOG, Mini-Cog, MIS, MoCA, and STMS seem to be good alternatives to the use of the Mini-Mental State Examination when considering factors such as application time, sensitivity, specificity, and number of studies. However, there is a wide range of tests with different characteristics, therefore it is recommended that the professional gets some expertise in a few number of instruments in order to be able to choose which to use, or use in combination, depending on the setting and the profile of the patient.

Previous studies in western countries have shown that about 30%–50% of patients with frontotemporal lobar degeneration (FTLD) have a positive family history, whereas the few epidemiological studies on FTLD done in Asia reported much lower frequencies. It is not clear the reason why the frequencies of FTLD with positive family history were lower in Asia. Furthermore, these findings were not from studies focused on family history. Therefore, it is necessary to conduct further studies on the family history of FTLD in Asia. This international multi-center research aims to investigate the family histories in patients with FTLD and related neurodegenerative diseases such as progressive supranuclear palsy (PSP), corticobasal syndrome (CBS), and motor neuron diseases in a larger Asian cohort.

Participants were collected from five countries: India, Indonesia, Japan, Taiwan, and Philippines. All patients were diagnosed with behavioral variant frontotemporal dementia (bvFTD), semantic dementia (SD), progressive non-fluent aphasia (PA), frontotemporal dementia with motor neuron disease (FTD/MND), PSP, and corticobasal degeneration (CBD) according to international consensus criteria. Family histories of FTLD and related neurodegenerative diseases were investigated in each patient.

Ninety-one patients were included in this study. Forty-two patients were diagnosed to have bvFTD, two patients had FTD/MND, 22 had SD, 15 had PA, one had PA/CBS, five had CBS and four patients had PSP. Family history of any FTLD spectrum disorder was reported in 9.5% in bvFTD patients but in none of the SD or PA.

In contrast to patients of the western countries, few Asian FTLD patients have positive family histories of dementia.

In clinical practice, Second Generation Antipsychotics (SGAs) are often used as first-line treatment for the Behavioral and Psychological Symptoms of Dementia (BPSD) in older adults due to their fewer neurological adverse events and similar effectiveness compared with First Generation Antipsychotics (FGAs). SGAs, however, are associated with more severe metabolic side effects (weight gain, hyperglycemia, diabetes risk, and hyperlipidemia) than FGAs are. In general, older patients, especially those affected by dementia, are at increased risk for malnutrition, and tend to have lower basal metabolism and reduced liver and kidney function. However, little is known about the metabolic side effects of antipsychotic drugs in this population.

A comprehensive review of the literature published between January 1996 and December 2012 investigating the metabolic side effects related to FGAs and SGAs use in old patients affected by dementia.

Antipsychotic drugs currently used to treat BPSD in subjects with mild to moderate dementia are associated with weight gain. Currently, there are insufficient data to support a causal relationship between the use of FGAs and SGAs and changes in glucose homeostasis or lipid metabolism in older persons affected by severe dementia (MMSE <14).

A possible association between antipsychotic drugs use and weight gain might exist, in particular in subjects with mild to moderate dementia whereas no significant effects are demonstrated regarding glucose homeostasis and lipid metabolism. The antipsychotic drugs potential for causing metabolic abnormalities in older patients requires further specifically designed studies. Clinicians must be aware of this possibility even if the shorter periods of treatment administered in late-life might not be as harmful as it is in younger individuals.

Chronic stress negatively affects health and well-being. A growing population of informal dementia caregivers experience chronic stress associated with extraordinary demands of caring for a relative with dementia. This review summarizes physiological and functional changes due to chronic dementia caregiver stress.

A literature search for papers assessing effects of dementia caregiving was conducted focusing on publications evaluating differences between caregivers and non-caregivers in objective measures of health and cognition.

The review identified 37 studies describing data from 4,145 participants including 749 dementia caregivers and 3,396 non-caregiver peers. Objective outcome measures affected in dementia caregivers included markers of dyscoagulation, inflammation, and cell aging as well as measures of immune function, sleep, and cognition. Though diverse in designs, samples, and study quality, the majority of the studies indicated increased vulnerability of dementia caregivers to detrimental changes in health and cognition. Demographic and personality characteristics moderating or mediating effects of chronic stress in caregivers were also reviewed.

There is accumulating evidence that chronic dementia caregiver stress increases their vulnerability to disease and diminishes their ability to provide optimal care. Clinicians and society need to appreciate the extent of deleterious effects of chronic stress on dementia caregiver health.

The Addenbrooke's Cognitive Examination (ACE) and its Revised version (ACE-R) are relatively new screening tools for cognitive impairment that may improve upon the well-known Mini-Mental State Examination (MMSE) and other brief batteries. We systematically reviewed diagnostic accuracy studies of ACE and ACE-R.

Published studies comparing ACE, ACE-R and MMSE were comprehensively sought and critically appraised. A meta-analysis of suitable studies was conducted.

Of 61 possible publications identified, meta-analysis of qualifying studies encompassed 5 for ACE (1,090 participants) and 5 for ACE-R (1156 participants); of these, 9 made direct comparisons with the MMSE. Sensitivity and specificity of the ACE were 96.9% (95% CI = 92.7% to 99.4%) and 77.4% (95% CI = 58.3% to 91.8%); and for the ACE-R were 95.7% (95% CI = 92.2% to 98.2%) and 87.5% (95% CI = 63.8% to 99.4%). In a modest prevalence setting, such as primary care or general hospital settings where the prevalence of dementia may be approximately 25%, overall accuracy of the ACE (0.823) was inferior to ACE-R (0.895) and MMSE (0.882). In high prevalence settings such as memory clinics where the prevalence of dementia may be 50% or higher, overall accuracy again favored ACE-R (0.916) over ACE (0.872) and MMSE (0.895).

The ACE-R has somewhat superior diagnostic accuracy to the MMSE while the ACE appears to have inferior accuracy. The ACE-R is recommended in both modest and high prevalence settings. Accuracy of newer versions of the ACE remain to be determined.

Half a century after the inception of the term “successful aging (SA),” a consensus definition has not emerged. The current study aims to provide a comprehensive snapshot of operational definitions of SA.

A systematic review across MedLine, PsycInfo, CINAHL, EMBASE, and ISI Web of Knowledge of quantitative operational definitions of SA was conducted.

Of the 105 operational definitions, across 84 included studies using unique models, 92.4% (97) included physiological constructs (e.g. physical functioning), 49.5% (52) engagement constructs (e.g. involvement in voluntary work), 48.6% (51) well-being constructs (e.g. life satisfaction), 25.7% (27) personal resources (e.g. resilience), and 5.7% (6) extrinsic factors (e.g. finances). Thirty-four definitions consisted of a single construct, 28 of two constructs, 27 of three constructs, 13 of four constructs, and two of five constructs. The operational definitions utilized in the included studies identify between <1% and >90% of study participants as successfully aging.

The heterogeneity of these results strongly suggests the multidimensionality of SA and the difficulty in categorizing usual versus successful aging. Although the majority of operationalizations reveal a biomedical focus, studies increasingly use psychosocial and lay components. Lack of consistency in the definition of SA is a fundamental weakness of SA research.

Charles Bonnet syndrome (CBS) is defined as complex persistent visual hallucinations in the absence of mental disorder. It is common in conditions causing significant visual impairment. Many authors advise reassurance, considering the condition benign. However, others have suggested that CBS may in some patients represent the early stages of dementia. This review seeks to systematically examine the evidence for any link between CBS and cognitive impairment.

Literature search using OVID Medline, PsychINFO, and Embase.

Three studies where cognitive functioning was the primary focus of the research were found. All were small, did not properly apply diagnostic criteria, and reported conflicting results. Eight other studies commented on cognitive functioning, but none used tests sufficiently sensitive to detect changes seen in early dementia. One hundred and thirty four case reports were scrutinized, and reports found of 16 patients with CBS where dementia emerged. High rates of partial insight at diagnosis of CBS were seen in these patients.

There have been no adequately powered studies, using accepted diagnostic criteria, where changes in cognitive functioning were the primary outcome. Existing studies are of limited methodological quality and allow no conclusion regarding a relationship between cognitive impairment and CBS to be reached. Numerous case reports of dementia developing in patients with CBS and partial insight raise the possibility of a link between these conditions. There is a clear need for properly constructed studies to investigate this.

Mortality risk factors have attracted great research interest in recent years. Physical illness is strongly associated with mortality risk in elderly people. Furthermore, a relationship between mortality risk and psychiatric disease in the elderly has gained research interest.

This is a prospective longitudinal multicenter study. A sample of 324 participants was selected as a representative sample of community members aged 65 years and older and living in Huesca (Spain). The following information was collected: affiliation data, severity of physical illness, psychosocial, and psychiatric factors. Statistical analyses were completed with a multivariate analysis in order to control possible confounding variables related to mortality.

Of the initially selected sample, 293 participants were assessed. Sixty-four participants died (21.8%, 95% CI [16.9%, 26.7%]), 5.3% annual rate, and 46.1% showed symptomatology of mental disorders. Older people have eight times greater risk of mortality. The risk increased 53 times in patients affected by several physical illness. No relationship between cognitive dysfunction and depressive symptomatology was observed. In fact, physical condition was associated with depression, and the percentage of participants with depressive symptoms increased according to the severity of physical illness.

Severity of physical illness and age are independently and directly associated with mortality in the elderly people. Therefore, severity of physical illness seems to be a crucial factor in the bi-directional association between mortality and depression, acting as a risk factor independently for both. So the relationship between depression and mortality can be affected by the severity of physical illness.

As the population ages, it is increasingly important to use effective short cognitive tests for suspected dementia. We aimed to review systematically brief cognitive tests for suspected dementia and report on their validation in different settings, to help clinicians choose rapid and appropriate tests.

Electronic search for face-to-face sensitive and specific cognitive tests for people with suspected dementia, taking ≤ 20 minutes, providing quantitative psychometric data.

22 tests fitted criteria. Mini-Mental State Examination (MMSE) and Hopkins Verbal Learning Test (HVLT) had good psychometric properties in primary care. In the secondary care settings, MMSE has considerable data but lacks sensitivity. 6-Item Cognitive Impairment Test (6CIT), Brief Alzheimer's Screen, HVLT, and 7 Minute Screen have good properties for detecting dementia but need further validation. Addenbrooke's Cognitive Examination (ACE) and Montreal Cognitive Assessment are effective to detect dementia with Parkinson's disease and Addenbrooke's Cognitive Examination-Revised (ACE-R) is useful for all dementias when shorter tests are inconclusive. Rowland Universal Dementia Assessment scale (RUDAS) is useful when literacy is low. Tests such as Test for Early Detection of Dementia, Test Your Memory, Cognitive Assessment Screening Test (CAST) and the recently developed ACE-III show promise but need validation in different settings, populations, and dementia subtypes. Validation of tests such as 6CIT, Abbreviated Mental Test is also needed for dementia screening in acute hospital settings.

Practitioners should use tests as appropriate to the setting and individual patient. More validation of available tests is needed rather than development of new ones.