Alcohol Use, Mental Health, and Functional Capacity as Predictors of Workplace Disability in a Cohort With Manifest Huntington's Disease.

OBJECTIVE: Huntington's disease (HD) is an inherited neurodegenerative disease involving motor, cognitive, psychiatric, and behavioral impairments that eventually affect work-role functioning. There is limited research regarding predictors of workplace disability in HD. The authors examined predictors of work impairment and disability in a cross-sectional cohort of employed persons with symptomatic HD participating in the worldwide Enroll-HD study. METHODS: The study sample (N=316) comprised individuals with manifest HD and a CAG repeat length range between 39 and 60 and were currently engaged in paid full- or part-time employment. Univariate and multivariate logistic regression analyses identified predictors and the effect of all predictors in a fully adjusted model. RESULTS: Of the sample, 20.3% reported missing work due to HD, 60.1% reported experiencing impairment while working due to HD, 79.1% reported having work-related activity impairment due to HD, and 60.8% reported impairment in overall work productivity due to HD. Individuals had 25% higher odds of missing work time if they had a higher level of functional impairment (odds ratio=0.76, 95% CI=0.64, 0.91) and had three times greater odds of missing work if they were current alcohol drinkers, compared with nondrinkers (odds ratio=2.86, 95% CI=1.62, 5.03). Individuals with lower self-perceived mental health were also 5% more likely to experience impairment at work due to HD. Motor impairment was not a strong predictor of workplace disability. CONCLUSIONS: These findings provide important new knowledge that can inform the development of strategies or targeted intervention trials to support persons with symptomatic HD to maintain their work roles.

Synthesis of ß-Ketosulfonamides Derived from Amino Acids and Their Conversion to ß-Keto-α,α-difluorosulfonamides via Electrophilic Fluorination.

ß-Ketosulfonamides derived from Boc or Cbz-protected amino acids bearing hydrophobic side chains were prepared in good to excellent yield by treating N-allyl, N-alkyl methanesulfonamides with n-BuLi, followed by reaction of the resulting carbanion with methyl esters of N-protected l-amino acids. The analogous reaction using the dianion derived from an N-alkyl methanesulfonamide proceeded in much lower yield. Electrophilic fluorination of the ß-ketosulfonamides using Selectfluor in the presence of CsF in DMF at room temperature for 15-60 min provided ß-keto-α,α-difluorosulfonamides in good to excellent yields. The allyl protecting group could be removed in good yield using cat. Pd(PPh)3)4 and dimethyl barbituric acid. When the fluorination reaction was performed with Cs2CO3 as base, ß-ketosulfonamides derived from Val, Leu or Ile gave the expected ß-keto-α,α-difluorosulfonamides, while ß-ketosulfonamides derived from Ala, Phe, or hPhe gave the hydrates of the imino ß-keto-α,α-difluorosulfonamides.

Disclosing a dementia diagnosis: what do patients and family consider important?

BACKGROUND: The literature available on the format of the feedback session following assessment of memory impairment is minimal. This study explored how this information should be presented from the perspective of patients and their families. METHODS: Thirty-two semi-structured interviews were conducted with memory clinic patients and their carer at the clinic visit that followed the feedback session, to ask: what they recalled, what they found helpful, and what they thought was the best way to disclose a diagnosis of dementia. A second interview was conducted with 14 patient/carer dyads at their next appointment. RESULTS: Recall of information from the feedback session was variable. Most respondents (76% of patients; 66% of carers) thought that a direct approach was best when informing the patient of a dementia diagnosis, and that both written information and compassion demonstrated by the doctor were helpful. Opinions on whether all the information should be given at once or in stages were divided. CONCLUSIONS: The current format of the feedback session needs revision to improve recall. Patients and their families want a direct approach to be used by a supportive and professional doctor with an opportunity to ask questions. They want the support of a family member or friend when they are told of their diagnosis and they would like a written summary to refer to afterwards.

Witchcraft and Huntington's disease: a salutary history of societal and medical stigmatisation.

OBJECTIVE: This paper examines the notions that psychiatry can be greatly influenced by what society considers as 'normal', and that psychiatric thoughts and beliefs ebb and flow according to history and the social and cultural values of the time. CONCLUSIONS: As part of the medical profession, psychiatrists have much power in determining treatment and outcomes for patients. Unfortunately, this also means psychiatry has also been involved with the darker aspects of humanity, such as during the Nazi regime, and the abuse of patients' human rights. Huntington's disease (HD) is a neuropsychiatric illness from which observation and little knowledge reported by the medical profession spanned decades of incorrect and sensationalised documentation, that was also influenced by the values of the time. Such was the atmosphere of society during this period that the ideas and notions regarding HD disseminated by the respected medical profession were believed and accepted as fact by the general population and other professions, who would have been ignorant of any other contrary information. We need to be aware of social and cultural values as these can influence our understanding of diagnoses and treatments of our patients.

A psychogeriatrician's home visit to the zoo: a case report.

Psychogeriatricians commonly undertake home visits, often under unusual and sometimes challenging circumstances. We report a home visit to a zoo to see an unusual case, a 49-year-old confused gorilla. A diagnosis of post-infarct delirium was made, subsequently validated by autopsy. We describe a primate observation scale which was used in the assessment of cognition this case, which may be helpful for use when cognitive assessment of primates is required.

Rapid detection of chromosomal translocation and precise breakpoint characterization in acute myeloid leukemia by nanopore long-read sequencing.

Detection of chromosomal translocation is a key component in diagnosis and management of acute myeloid leukemia (AML). Targeted RNA next-generation sequencing (NGS) is emerging as a powerful and clinically practical tool, but it depends on expression of RNA transcript from the underlying DNA translocation. Here, we show the clinical utility of nanopore long-read sequencing in rapidly detecting DNA translocation with exact breakpoints. In a newly diagnosed patient with AML, conventional karyotyping showed translocation t(10;12)(q22;p13) but RNA NGS detected NUP98-NSD1 fusion transcripts from a known cryptic translocation t(5;11)(q35;p15). Rapid PCR-free nanopore whole-genome sequencing yielded a 26,194 bp sequencing read and revealed the t(10;12) breakpoint to be DUSP13 and GRIN2B in head-to-head configuration. This translocation was then classified as a passenger structural variant. The sequencing also yielded a 20,709 bp sequencing read and revealed the t(5;11) breakpoint of the driver NUP98-NSD1 fusion. The identified DNA breakpoints also served as markers for molecular monitoring, in addition to fusion transcript expression by digital PCR and sequence mutations by NGS. We illustrate that third-generation nanopore sequencing is a simple and low-cost workflow for DNA translocation detection.

Increased cortical recruitment in Huntington's disease using a Simon task.

Cognitive deficits in Huntington's disease (HD) have been attributed to neuronal degeneration within the striatum; however, postmortem and structural imaging studies have revealed more widespread morphological changes. To examine the impact of HD-related changes in regions outside the striatum, we used functional magnetic resonance imaging (fMRI) in HD to examine brain activation patterns using a Simon task that required a button press response to either congruent or incongruent arrow stimuli. Twenty mild to moderate stage HD patients and 17 healthy controls were scanned using a 3T GE scanner. Data analysis involved the use of statistical parametric mapping software with a random effects analysis model to investigate group differences brain activation patterns compared to baseline. HD patients recruited frontal and parietal cortical regions to perform the task, and also showed significantly greater activation, compared to controls, in the caudal anterior cingulate, insula, inferior parietal lobules, superior temporal gyrus bilaterally, right inferior frontal gyrus, right precuneus/superior parietal lobule, left precentral gyrus, and left dorsal premotor cortex. The significantly increased activation in anterior cingulate-frontal-motor-parietal cortex in HD may represent a primary dysfunction due to direct cell loss or damage in cortical regions, and/or a secondary compensatory mechanism of increased cortical recruitment due to primary striatal deficits.

Nutrition and geriatric psychiatry: a neglected field.

PURPOSE OF REVIEW: Nutritional issues have received little attention in geriatric psychiatry research. This review focuses on literature published in 2003 and 2004 on nutritional factors in mental illness in the elderly and proposes directions for future research. RECENT FINDINGS: There has been more research on the role of micronutrients in psychiatric disorders of older adults but studies examining nutritional state in this population are lacking. The former research suggests associations between low folic acid/vitamin B12 status and depression in older adults whereas evidence for other micronutrients is still tentative. In the latter work, there is only one study that examines malnutrition in psychogeriatric patients despite the availability of well-validated screening tools for assessing nutritional state in the elderly and the known impact of undernutrition in ageing and the development of frailty. The role of obesity in ageing is also relevant especially as more people with schizophrenia live longer, although the current evidence in the non-mentally ill elderly suggests that being overweight may have protective effects in the elderly. SUMMARY: Malnutrition is likely to have considerable impact on the mental and physical state of the elderly.

Future directions in research with presymptomatic individuals carrying the gene for Huntington's disease.

Presymptomatic individuals carrying the gene for Huntington's disease (HD) provide researchers with a unique opportunity of learning more about the neuropathophysiology, symptom onset, behavioural functioning, and mediating factors of this fatal disease. In this review, we attempt to demonstrate that research over the last 8 years, since the isolation of the gene, has remained at large controversial. Although we are aware of some of the factors that can influence age at onset and disease progression, we are still unable to determine exactly when an individual will develop HD symptoms, and how fast these symptoms will progress. In an era rapidly advancing with respect to therapeutic intervention that could forestall the onset and progression of HD, systematic research with improved inclusion criteria is paramount. A greater understanding of the time course of the disease would be beneficial not only in monitoring the effectiveness of future treatments, but also in determining the most appropriate time to administer them. Finally, we present various ethical considerations, as well as put forward various recommendations that could assist in better diagnosing preclinical deficits in presymptomatic individuals.

Alzheimer disease. Current treatment options.

BACKGROUND: In the past Alzheimer disease (AD) has been presented to elderly people and their families as a very frightening condition, based on media representation of the worst possible case scenarios. OBJECTIVE: The current status of pharmacological and psychosocial Intervention in Alzheimer disease is reviewed from the recent literature. DISCUSSION: In the last decade, the picture of AD has turned to one of hope and optimism as a result of advances in developing pharmacological and psychological management.

Pastoral care in old age psychiatry: addressing the spiritual needs of inpatients in an acute aged mental health unit.

INTRODUCTION: Pastoral Care (PC) practitioners respond to the spiritual needs of patients and families of all spiritual orientations. The integrated PC service in an acute psychogeriatric inpatient ward at St Vincent's Aged Mental Health Service, Melbourne, Australia, was examined to investigate how PC was being accessed by inpatients. METHODS: A retrospective medical record file audit was undertaken of patients admitted over a 16-month period from 1 February 2009 to 30 June 30 2010 (n = 202). RESULTS: Sixty-eight percent were seen by PC practitioners during their admission. Sixty-six percent received PC assessments, 32% received PC ministry, and 10% received PC ritual or worship interventions. Other interventions (counseling/education, crisis situation, grief/ bereavement counseling) occurred infrequently. Seventy-five percent of Roman Catholic patients received PC compared to 57% of those patients with no religious affiliation. However, the overall association between religious grouping and receiving PC was not significant. Gender, religion, marital status, legal status, country of birth, language spoken, living situation, carer needs, or educational level were not related to PC contact. Whether or not an inpatient received PC assessment was unrelated to diagnostic category. Patients seen by PC were significantly more likely to engage in religious practice, have longer length of stay, and have neuropsychological, social work and occupational therapy assessments. DISCUSSION: Results suggest that PC practitioners can help optimize the clinical care of patients by developing a comprehensive understanding of their spiritual and religious needs and providing a more holistic service.