A short delirium caregiver questionnaire for triage of elderly outpatients with cognitive impairment:a development and test accuracy study

OBJECTIVES: Delirium is often missed in older outpatients. Caregivers can give valuable information that might improve identification rates. The aim of this study was to develop a short and sensitive delirium caregiver questionnaire (DCQ) for triage of elderly outpatients with cognitive impairment by telephone.DESIGN, SETTING, AND PARTICIPANTS: The pilot questionnaire was administered to 112 caregivers of patients who were referred for dementia screening to our clinic for geriatric psychiatry, and the final DCQ to 234 other caregivers.MEASUREMENTS: In phase I (2013-2014), we tested a pilot questionnaire with 17 items. Health professionals who established delirium diagnoses were blinded to the results. We then used the results and other information available at referral to construct the final DCQ with seven items. During phase II (2015-2016), we investigated the test accuracy of the final DCQ in a subsequent cohort. In both phases, the patients received a structured diagnostic workup. Time between referral and first visit was a secondary outcome.RESULTS: The final DCQ consisted of the following items: emergency visit required, sleeping disorder, fluctuating course, hallucinations, suspicious thoughts, previous delirium, and recent discharge from hospital. DCQ results indicated that urgent intake was required in 85 of 234 patients. Sensitivity was 73.5% (95% CI: 58.9-85.1%) and specificity 73.5% (95% CI: 66.5-79.7%). The mean number of days to first visit dropped from 31.6 to 11.2 in delirious patients (p = 0.001).CONCLUSIONS: Triage with the easy-to-use DCQ among patients referred for cognitive screening leads to earlier assessment and higher detection rates of delirium.</p

Brown-Vialetto-Van Laere and Fazio Londe syndrome is associated with a riboflavin transporter defect mimicking mild MADD: a new inborn error of metabolism with potential treatment

We report on three patients (two siblings and one unrelated) presenting in infancy with progressive muscle weakness and paralysis of the diaphragm. Metabolic studies revealed a profile of plasma acylcarnitines and urine organic acids suggestive of a mild form of the multiple acyl-CoA dehydrogenation defect (MADD, ethylmalonic/adipic acid syndrome). Subsequently, a profound flavin deficiency in spite of a normal dietary riboflavin intake was established in the plasma of all three children, suggesting a riboflavin transporter defect. Genetic analysis of these patients demonstrated mutations in the C20orf54 gene which encodes the human homolog of a rat riboflavin transporter. This gene was recently implicated in the Brown-Vialetto-Van Laere syndrome, a rare neurological disorder which may either present in infancy with neurological deterioration with hypotonia, respiratory insufficiency and early death, or later in life with deafness and progressive ponto-bulbar palsy. Supplementation of riboflavin rapidly improved the clinical symptoms as well as the biochemical abnormalities in our patients, demonstrating that high dose riboflavin is a potential treatment for the Brown-Vialetto-Van Laere syndrome as well as for the Fazio Londe syndrome which is considered to be the same disease entity without the deafnes

Maroon Archaeology Beyond the Americas: A View From Kenya

Archaeological research on Maroons—that is, runaway slaves—has been largely confined to the Americas. This essay advocates a more global approach. It specifically uses two runaway slave communities in 19th-century coastal Kenya to rethink prominent interpretive themes in the field, including “Africanisms,” Maroons’ connections to indigenous groups, and Maroon group cohesion and identity. This article’s analysis demonstrates that the comparisons enabled by a more globalized perspective benefit the field. Instead of eliding historical and cultural context, these comparisons support the development of more localized and historically specific understandings of individual runaway slave communities both in Kenya and throughout the New World

Beyond humanization and de-immunization: tolerization as a method for reducing the immunogenicity of biologics

Immune responses to some monoclonal antibodies (mAbs) and biologic proteins interfere with their efficacy due to the development of anti-drug antibodies (ADA). In the case of mAbs, most ADA target ‘foreign’ sequences present in the complementarity determining regions (CDRs). Humanization of the mAb sequence is one approach that has been used to render biologics less foreign to the human immune system. However, fully human mAbs can also drive immunogenicity. De-immunization (removing epitopes) has been used to reduce biologic protein immunogenicity. Here, we discuss a third approach to reducing the immunogenicity of biologics: introduction of Treg epitopes that stimulate Treg function and induce tolerance to the biologic protein. Supplementing humanization (replacing xenosequences with human) and de-immunization (reducing T effector epitopes) with tolerization (introducing Treg epitopes) where feasible, as a means of improving biologics ‘quality by design’, may lead to the development of ever more clinically effective, but less immunogenic, biologics

Simultaneous determination of F-beta-alanine and beta-alanine in plasma and urine with dual-column reversed-phase high-performance liquid chromatography

F-beta-Alanine and beta-alanine were detected in plasma and urine samples with fluorescence detection of orthophthaldialdehyde derivatives of F-beta-alanine and beta-alanine after separation with dual-column reversed-phase HPLC. The detection limits of F-beta-alanine and beta-alanine in the HPLC system were approximately 0.3 and 0.7 pmol, respectively. The procedure proved to be very reproducible with intra-assay RSDs and inter-assay RSDs being less than 8%. The usefulness of the method was demonstrated by the analysis of the F-beta-alanine and beta-alanine concentrations in plasma and urine samples from tumor patients treated with S-1 (Tegafur, 5-chloro-2,4-dihydroxypyridine and potassium oxonate in a molar ratio of 1:0.4:1

Detecting delirium in elderly outpatients with cognitive impairment

Background: Delirium may be more prevalent in elderly outpatients than has long been assumed. However, it may be easily missed due to overlap with dementia. Our aim was to study delirium symptoms and underlying somatic disorders in psycho-geriatric outpatients. Methods: We performed a case-control study among outpatients that were referred to a psychiatric institution between January 1st and July 1st 2010 for cognitive evaluation. We compared 44 cases with DSM-IV delirium (24 with and 20 without dementia) to 44 controls with dementia only. All participants were aged 70 years or older. We extracted from the medical files (1) referral characteristics including demographics, medical history, medication use, and referral reasons, (2) delirium symptoms, scored with the Delirium Rating Scale-Revised-98, and (3) underlying disorders categorized as: drugs/intoxication, infection, metabolic/endocrine disturbances, cardiovascular disorders, central nervous system disorders, and other health problems. Results: At referral, delirium patients had significantly higher numbers of chronic diseases and medications, and more often a history of delirium and a recent hospital admission than controls. Most study participants, including those with delirium, were referred for evaluation of (suspected) dementia. The symptoms that occurred more frequently in cases were: sleep disturbances, perceptual abnormalities, delusions, affect lability, agitation, attention deficits, acute onset, and fluctuations. Drug related (68%), infectious (61%), and metabolic-endocrine (50%) disturbances were often involved. Conclusions: Detection of delirium and distinction from dementia in older outpatients was feasible but required detailed caregiver information about the presence, onset, and course of symptoms. Most underlying disorders could be managed at home

Evidence for increased oxidative stress in peroxisomal D-bifunctional protein deficiency

Peroxisome biogenesis disorders (PBDs) and D-bifunctional protein (D-BP) deficiency are two types of inherited peroxisomal disorders. Patients with a PBD lack functional peroxisomes and patients with D-BP deficiency lack the enzyme, which is responsible for the second and third step of the peroxisomal beta-oxidation. The clinical presentation of these peroxisomal disorders is severe and includes several neurological abnormalities. The pathological mechanisms underlying these disorders are not understood and no therapies are available. Because peroxisomes have been associated with oxidative stress, as oxygen radicals are both produced and scavenged in peroxisomes, we have investigated whether oxidative stress is involved in the pathogenesis of PBDs and D-BP deficiency. We found in D-BP-deficient patients increased levels of thiobarbituric acid-reactive substances (TBARS) and 8-hydroxydeoxyguanosine (8-OHdG), which are markers for lipid peroxidation and oxidative DNA damage, respectively, whereas the levels of the lipophilic antioxidants alpha-tocopherol and coenzyme Q(10) were decreased. In addition, we found in skin fibroblasts from D-BP-deficient patients an imbalance between the activities of the peroxisomal H(2)O(2)-generating straight-chain acyl-CoA oxidase (SCOX) and the peroxisomal H(2)O(2)-degrading enzyme catalase. In conclusion, we have found clear evidence for the presence of increased oxidative stress in patients with D-BP deficiency, but not in patients with a PB