Early psychosocial intervention in Alzheimer’s disease:Cost utility evaluation alongside the Danish Alzheimer’s Intervention Study (DAISY)

OBJECTIVE: To assess the cost utility of early psychosocial intervention for patients with Alzheimer's disease and their primary caregivers. DESIGN: Cost utility evaluation alongside a multicentre, randomised controlled trial with 3 years of follow-up. SETTING: Primary care and memory clinics in five Danish districts. PARTICIPANTS: 330 community-dwelling patients and their primary caregivers. INTERVENTION: Psychosocial counselling and support lasting 8–12 months after diagnosis and follow-up at 3, 6, 12 and 36 months in the intervention group or follow-up only in the control group. MAIN OUTCOME MEASURES: The primary outcome measure was the cost of additional quality-adjusted life years (QALYs). Costs were measured from a societal perspective, including the costs of healthcare, social care, informal care and production loss. QALYs were estimated separately for the patient and the caregiver before aggregation for the main analysis. RESULTS: None of the observed cost and QALY measures were significantly different between the intervention and control groups, although a tendency was noted for psychosocial care leading to cost increases with informal care that was not outweighed by the tendency for cost savings with formal care. The probability of psychosocial intervention being cost-effective did not exceed 36% for any threshold value. The alternative scenario analysis showed that the probability of cost-effectiveness increased over the range of threshold values used if the cost perspective was restricted to formal healthcare. CONCLUSIONS: A multifaceted, psychosocial intervention programme was found unlikely to be cost-effective from a societal perspective. The recommendation for practice in settings that are similar to the Danish setting is to provide follow-up with referral to available local support programmes when needed, and to restrict large multifaceted intervention programmes to patients and caregivers with special needs until further evidence for cost-effectiveness emerges. TRIAL REGISTRATION: The study was registered in the Clinical Trial Database as ISRCTN74848736

Clinical evaluation of dengue and identification of risk factors for severe disease: protocol for a multicentre study in 8 countries

Background: The burden of dengue continues to increase globally, with an estimated 100 million clinically apparent infections occurring each year. Although most dengue infections are asymptomatic, patients can present with a wide spectrum of clinical symptoms ranging from mild febrile illness through to severe manifestations of bleeding, organ impairment, and hypovolaemic shock due to a systemic vascular leak syndrome. Clinical diagnosis of dengue and identification of which patients are likely to develop severe disease remain challenging. This study aims to improve diagnosis and clinical management through approaches designed a) to differentiate between dengue and other common febrile illness within 72 h of fever onset, and b) among patients with dengue to identify markers that are predictive of the likelihood of evolving to a more severe disease course. Method/Design: This is a prospective multi-centre observational study aiming to enrol 7–8000 participants aged ≥ 5 years presenting with a febrile illness consistent with dengue to outpatient health facilities in 8 countries across Asia and Latin America. Patients presenting within 72 h of fever onset who do not exhibit signs of severe disease are eligible for the study. A broad range of clinical and laboratory parameters are assessed daily for up to 6 days during the acute illness, and also at a follow up visit 1 week later. Discussion: Data from this large cohort of patients, enrolled early with undifferentiated fever, will be used to develop a practical diagnostic algorithm and a robust clinical case definition for dengue. Additionally, among patients with confirmed dengue we aim to identify simple clinical and laboratory parameters associated with progression to a more severe disease course. We will also investigate early virological and serological correlates of severe disease, and examine genetic associations in this large heterogeneous cohort. In addition the results will be used to assess the new World Health Organization classification scheme for dengue in practice, and to update the guidelines for “Integrated Management of Childhood Illness” used in dengue-endemic countries. Trial registration: NCT01550016. Registration Date: March 7, 201

Validation of the 10/66 Dementia Research Group Diagnostic Assessment for Dementia in Arabic:A Study in Lebanon

OBJECTIVES: In the North Africa and Middle East region, the illiteracy rates among older people are high, posing a great challenge to cognitive assessment. Validated diagnostic instruments for dementia in Arabic are lacking, hampering the development of dementia research in the region. The study aimed at validating the Arabic version of the 10/66 Dementia Research Group (DRG) diagnostic assessment for dementia to determine if it is suitable for case ascertainment in epidemiological research. METHODS: 244 participants older than 65 years were included, 100 with normal cognition and 144 with mild to moderate dementia. Dementia was diagnosed by clinicians according to DSM-IV criteria. Depression was diagnosed using the Geriatric Mental State. Trained interviewers blind to the cognitive status of the participants administered the 10/66 DRG diagnostic assessment to the participants and interviewed the caregivers. The discriminatory ability of the 10/66 DRG assessment and its subcomponents were evaluated against the clinical diagnoses. RESULTS: Half of the participants had no formal education and 49% of them were depressed. The 10/66 DRG diagnostic assessment showed excellent sensitivity (92.0%), specificity (95.1%), positive predictive value (PPV, 92.9%), and low false positive rates (FPR) among controls with no formal education (8.1%) and depression (5.6%). Each subcomponent of the 10/66 DRG diagnostic assessment independently predicted dementia diagnosis. The predictive ability of the 10/66 DRG assessment was superior to that of its subcomponents. CONCLUSION: 10/66 DRG diagnostic assessment for dementia is well suited for case ascertainment in epidemiological studies among Arabic speaking older population with high prevalence of illiteracy

Early diagnostic indicators of dengue versus other febrile illnesses in Asia and Latin America (IDAMS study): a multicentre, prospective, observational study

BACKGROUND: Improvements in the early diagnosis of dengue are urgently needed, especially in resource-limited settings where the distinction between dengue and other febrile illnesses is crucial for patient management. METHODS: In this prospective, observational study (IDAMS), we included patients aged 5 years and older with undifferentiated fever at presentation from 26 outpatient facilities in eight countries (Bangladesh, Brazil, Cambodia, El Salvador, Indonesia, Malaysia, Venezuela, and Viet Nam). We used multivariable logistic regression to investigate the association between clinical symptoms and laboratory tests with dengue versus other febrile illnesses between day 2 and day 5 after onset of fever (ie, illness days). We built a set of candidate regression models including clinical and laboratory variables to reflect the need of a comprehensive versus parsimonious approach. We assessed performance of these models via standard measures of diagnostic values. FINDINGS: Between Oct 18, 2011, and Aug 4, 2016, we recruited 7428 patients, of whom 2694 (36%) were diagnosed with laboratory-confirmed dengue and 2495 (34%) with (non-dengue) other febrile illnesses and met inclusion criteria, and were included in the analysis. 2703 (52%) of 5189 included patients were younger than 15 years, 2486 (48%) were aged 15 years or older, 2179 (42%) were female and 3010 (58%) were male. Platelet count, white blood cell count, and the change in these variables from the previous day of illness had a strong association with dengue. Cough and rhinitis had strong associations with other febrile illnesses, whereas bleeding, anorexia, and skin flush were generally associated with dengue. Model performance increased between day 2 and 5 of illness. The comprehensive model (18 clinical and laboratory predictors) had sensitivities of 0·80 to 0·87 and specificities of 0·80 to 0·91, whereas the parsimonious model (eight clinical and laboratory predictors) had sensitivities of 0·80 to 0·88 and specificities of 0·81 to 0·89. A model that includes laboratory markers that are easy to measure (eg, platelet count or white blood cell count) outperformed the models based on clinical variables only. INTERPRETATION: Our results confirm the important role of platelet and white blood cell counts in diagnosing dengue, and the importance of serial measurements over subsequent days. We successfully quantified the performance of clinical and laboratory markers covering the early period of dengue. Resulting algorithms performed better than published schemes for distinction of dengue from other febrile illnesses, and take into account the dynamic changes over time. Our results provide crucial information needed for the update of guidelines, including the Integrated Management of Childhood Illness handbook. FUNDING: EU's Seventh Framework Programme. TRANSLATIONS: For the Bangla, Bahasa Indonesia, Portuguese, Khmer, Spanish and Vietnamese translations of the abstract see Supplementary Materials section