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.

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.

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.

Clinical and Biomarker Changes in Premanifest Huntington Disease Show Trial Feasibility: A Decade of the PREDICT-HD Study.

There is growing consensus that intervention and treatment of Huntington disease (HD) should occur at the earliest stage possible. Various early-intervention methods for this fatal neurodegenerative disease have been identified, but preventive clinical trials for HD are limited by a lack of knowledge of the natural history of the disease and a dearth of appropriate outcome measures. Objectives of the current study are to document the natural history of premanifest HD progression in the largest cohort ever studied and to develop a battery of imaging and clinical markers of premanifest HD progression that can be used as outcome measures in preventive clinical trials. Neurobiological predictors of Huntington's disease is a 32-site, international, observational study of premanifest HD, with annual examination of 1013 participants with premanifest HD and 301 gene-expansion negative controls between 2001 and 2012. Findings document 39 variables representing imaging, motor, cognitive, functional, and psychiatric domains, showing different rates of decline between premanifest HD and controls. Required sample size and models of premanifest HD are presented to inform future design of clinical and preclinical research. Preventive clinical trials in premanifest HD with participants who have a medium or high probability of motor onset are calculated to be as resource-effective as those conducted in diagnosed HD and could interrupt disease 7-12 years earlier. Methods and measures for preventive clinical trials in premanifest HD more than a dozen years from motor onset are also feasible. These findings represent the most thorough documentation of a clinical battery for experimental therapeutics in stages of premanifest HD, the time period for which effective intervention may provide the most positive possible outcome for patients and their families affected by this devastating disease.

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.

Cortisol and depression in pre-diagnosed and early stage Huntington's disease.

Hypothalamic-pituitary-adrenal (HPA) axis dysfunction and depression have both been shown to occur in Huntington's disease (HD) gene carriers prior to diagnosis (pre-HD) and in diagnosed HD patients. However, the relationship between HPA axis dysfunction and the severity of depressive symptomatology in pre-HD and early-HD has not been systematically examined, despite morning hypercortisolism being a characteristic feature of some subtypes of idiopathic depression. The aim of this study was to investigate whether HPA axis function is related to levels of depression in pre-HD and early-HD. To assess HPA axis function we obtained salivary cortisol concentrations from 20 controls, 20 pre-HD, and 17 early-HD participants at four time points over a 24h period. Depression symptoms were assessed using the Inventory of Depressive Symptomatology - Self-Report. Of the participants who were found not to be depressed, the early-HD group had significantly lower morning cortisol levels relative to pre-HD and controls. In contrast, the early-HD group with at least mild or greater levels of depression symptoms had a comparable cortisol concentration to pre-HD and controls. The results suggest that early-HD may be associated with hypocortisolism. However when depressed, a hyperactive HPA axis response may still be induced in early-HD and lead to cortisol levels that are similar to pre-HD and controls. Our study reveals that cortisol levels in HD may be modified by the presence or absence of depressive symptomatology. Depression may be an important factor for understanding how the HPA axis is affected in HD, particularly in the morning.

Perception, experience, and response to genetic discrimination in Huntington's disease: the Australian results of The International RESPOND-HD study.

AIMS: This study examines elements of genetic discrimination among an at-risk, clinically undiagnosed Huntington's disease (HD) population. METHODS: Sixty at-risk individuals, either positive or negative for the HD genetic mutation, completed a survey regarding their experiences of genetic discrimination, adverse and unfair treatment, and knowledge about existing laws and policies surrounding genetic discrimination. RESULTS: Sixty eight percent of participants reported feeling "Great benefit" from knowing their genetic test results. Reported benefits of knowledge included planning for the future, making decisions, and many individuals found meaning in active participation in the HD community and in advocating for themselves or families at risk for HD. Many individuals found personal meaning and a sense of community from knowledge of this information and from the ability to participate in research. Despite these positive feelings toward gene testing, results demonstrated that 33% of participants perceived experiences of genetic discrimination, which occurred repeatedly and caused great self-reported distress. Significantly, more gene-positive respondents reported experiencing incidents of genetic discrimination, compared to gene-negative respondents. At least 58 separate incidents of discrimination were reported, the number of incidents ranged from 1 to 10, with 45% of individuals (9/20 respondents) indicating more than one event. Of the most significant events of discrimination, 58% were related to insurance, 21% to employment, 16% to transactions of daily life, and 5% to relationships. CONCLUSION: Results contribute toward validation of empirical data regarding genetic discrimination.

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.

Mental health system in China: history, recent service reform and future challenges.

This paper summarizes the history of the development of Chinese mental health system; the current situation in the mental health field that China has to face in its effort to reform the system, including mental health burden, workforce and resources, as well as structural issues; the process of national mental health service reform, including how it was included into the national public health program, how it began as a training program and then became a treatment and intervention program, its unique training and capacity building model, and its outcomes and impacts; the barriers and challenges of the reform process; future suggestions for policy; and Chinese experiences as response to the international advocacy for the development of mental health.

Medical comorbidity in psychogeriatric patients.

PURPOSE OF REVIEW: To undertake a systematic review of articles published in the years 2008-2010 related to medical comorbidities in psychogeriatric patients. This paper addresses selected research findings on the prevalence and causes of medical comorbidity in elderly patients with psychiatric illnesses. MEDLINE, EMBASE and PsychINFO databases were used to identify potential studies. Specific medical comorbidities which were studied included osteoporosis and diabetes. Several studies investigated general medical comorbidities. RECENT FINDINGS: Elderly patients with psychiatric illness generally had the presence of at least one medical comorbidity compared with elderly patients without a psychiatric illness. Depression in elderly patients was the most commonly studied psychiatric illness. SUMMARY: Elderly patients with psychiatric illness commonly have comorbid medical conditions. The presence, appropriate investigations and management of these are often suboptimal and can affect quality of life and increase mortality.

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.