Experiences of hospice dementia care: A qualitative study of bereaved carers and hospice clinicians.

BACKGROUND: Nearly 50 million people worldwide have dementia and the increasing numbers requiring end-of-life and palliative care, has led to national efforts to define standards of care for this patient group. Little research, however, has been done to date about the experience of hospice care for people with dementia accessing these services. This study explores the views of hospice dementia care for bereaved carers of people with dementia and hospice clinicians. METHODS: We used purposive sampling for participant recruitment. Semi-structured qualitative interviews were conducted with bereaved carers and hospice clinical staff. Interviews were audio recorded and the transcriptions were analysed through thematic analysis. A total of 12 participants were interviewed from one service in the Northwest region in the UK. All were female and white British. RESULTS: Participants described their experience of hospice dementia care in three main themes: Pre-access to service, roles and responsibility within hospice care, ease and difficulty of last period of end-of-life care. CONCLUSION: Rapid response teams delivering hospice home care could represent a better option to inpatient care and may be preferred by patients. This type of service, however, may require joined-up care with other community services, and this type of care needs to be considered and planned. Future studies should evaluate this type of community care.

The use of a mobile app to motivate evidence-based oral hygiene behaviour.

INTRODUCTION: Mobile apps are software programmes that run on smartphones and other mobile devices. Mobile health apps can help people manage their own health and wellness, promote healthy living and gain access to useful information when and where they need it. The Brush DJ oral health app was developed to use the opportunity mobile apps offer to motivate an evidence-based oral hygiene routine. A literature review has found no research investigating the use of a mobile app to motivate evidence-based oral hygiene behaviour. OBJECTIVE: The objective of this preliminary investigation was to assess user perception of an oral health app to give a basis for future research and development of app technology in relation to oral health. METHOD: A cross-sectional qualitative user perception questionnaire.RESULTS :One hundred and eighty-nine people responded to the questionnaire. Seventy percent (n = 113) of respondents reported that their teeth felt cleaner since using the app. Eighty-eight percent (n = 133) reported the app motivated them to brush their teeth for longer and 92.3% (n = 144) would recommend the app to their friends and family. Four broad themes relating to how the app helped toothbrushing were reported. These themes were motivation, education, compliance and perceived benefits. CONCLUSION: A mobile app is a promising tool to motivate an evidence-based oral hygiene routine.

Consensus paper: pathological mechanisms underlying neurodegeneration in spinocerebellar ataxias.

Intensive scientific research devoted in the recent years to understand the molecular mechanisms or neurodegeneration in spinocerebellar ataxias (SCAs) are identifying new pathways and targets providing new insights and a better understanding of the molecular pathogenesis in these diseases. In this consensus manuscript, the authors discuss their current views on the identified molecular processes causing or modulating the neurodegenerative phenotype in spinocerebellar ataxias with the common opinion of translating the new knowledge acquired into candidate targets for therapy. The following topics are discussed: transcription dysregulation, protein aggregation, autophagy, ion channels, the role of mitochondria, RNA toxicity, modulators of neurodegeneration and current therapeutic approaches. Overall point of consensus includes the common vision of neurodegeneration in SCAs as a multifactorial, progressive and reversible process, at least in early stages. Specific points of consensus include the role of the dysregulation of protein folding, transcription, bioenergetics, calcium handling and eventual cell death with apoptotic features of neurons during SCA disease progression. Unresolved questions include how the dysregulation of these pathways triggers the onset of symptoms and mediates disease progression since this understanding may allow effective treatments of SCAs within the window of reversibility to prevent early neuronal damage. Common opinions also include the need for clinical detection of early neuronal dysfunction, for more basic research to decipher the early neurodegenerative process in SCAs in order to give rise to new concepts for treatment strategies and for the translation of the results to preclinical studies and, thereafter, in clinical practice.

Tobacco, alcohol and drug use among dental undergraduates at one English university in 1998 and 2008.

OBJECTIVE: To estimate the prevalence of tobacco, alcohol and drug use among dental undergraduates at one English university in 2008, and compare these with prevalence in 1998. DESIGN: Cross-sectional survey using an anonymous self-report questionnaire. SUBJECTS AND METHODS: In 2008 all 384 dental undergraduates at one English university were sent a questionnaire in order to obtain data on the frequency and amount of tobacco, alcohol, cannabis and other illicit drugs used before and during their time as a dental undergraduate. The same survey had been conducted on dental undergraduates at the university 10 years earlier. RESULTS: Tobacco smoking was reported by 27% of males and 13.5% of females, a reduction from 1998 (42% of males and 32% of females) being significant among females. 63% of males and 69.5% of females reported drinking alcohol: significantly fewer than in 1998 (82% males and 90% females). Binge drinking was reported by 69.5% of males compared to 56% in 1998. In females 66% binged compared to 58.5% in 1998. The increase in males was significant. 62% of males and 68% of females had never used cannabis compared to 38% in males and 50.5% of females in 1998, a significant reduction. A significant reduction in amphetamine use was reported among both male and female undergraduates in 2008 compared to 1998 and a significant increase in amyl nitrate use was reported by females. Reported illicit drug use was associated with alcohol drinking, and particularly with tobacco use. CONCLUSION: Dental undergraduates at one English university in 2008 when compared to those in 1998 are reported to be significantly less likely to drink alcohol, use cannabis and amphetamines. If female, they are significantly less likely to smoke tobacco and overestimate the number of units of alcohol they can safely consume in a week, but more likely to use amyl nitrate. If male, those who drink alcohol are significantly less likely to drink at a level of increased risk, but more likely to binge drink.

Smoking, alcohol and drug use among vocational dental practitioners in 2000 and 2005.

OBJECTIVE: To estimate the prevalence of tobacco smoking, alcohol and drug use among UK vocational dental practitioners (VDPs) in 2005, and compare these with prevalence in 2000. DESIGN: Cross-sectional survey using an anonymous self-report questionnaire. SUBJECTS AND METHODS: All 767 VDPs who started practice in the summer of 2004 were sent a questionnaire in order to obtain data on the frequency and amount of tobacco, alcohol, cannabis and other illicit drugs used before and during vocational training (VT). The same survey had been conducted on VDPs five years earlier. The analysis was based on 502 subjects who responded and completed the questionnaire in 2005 and 534 subjects in 2000. RESULTS: Regular tobacco use (10+ cigarettes per day) was reported by 5.4% of males and 4.0% of females in 2005. This is lower than reported in 2000 (9%) and a statistically significant reduction in males. Eighty-two percent of males and 81% of females reported alcohol use; a statistically significant reduction from 2000 (89% males and 88% females). Reported 'binge drinking' remained high with 44% of males and 39% of females drinking at least half the recommended weekly units of alcohol in one session, similar to those levels seen in 2000. Thirty-eight percent of males and 26% of females reported cannabis use during their VT, similar to levels seen in 2000. Reported use of illicit drugs other than cannabis was less than in 2000. Reported illicit drug use was associated with alcohol drinking, and particularly with tobacco use. CONCLUSION: This study has found the level of alcohol, tobacco and illicit drug use (excluding cannabis) among VDPs decreasing since 2000, but levels of binge drinking and cannabis use remaining similar.

Impaired cognition and decision-making in bipolar depression but no 'affective bias' evident.

BACKGROUND: Depression is usually the predominant affective state in bipolar disorder. There are few studies, with discrepant views, examining the extent of cognitive impairment in patients with bipolar depression. To our knowledge, there are no previous studies examining decision-making ability or whether there is an affective attentional bias in bipolar depression. METHOD: We ascertained 24 depressed bipolar I patients from acute psychiatric hospital wards and out-patient clinics and 26 age- and IQ-matched healthy controls. Using computerized tests we evaluated their performance on 'neutral' (non-emotional) cognitive tasks (i.e. memory, attention and executive function) and on novel tasks of emotional cognition (i.e. the decision-making task and the affective go/no-go task). RESULTS: Accuracy measures were significantly impaired on tests of visual and spatial recognition and attentional set-shifting in bipolar depression compared with age- and IQ-matched controls. The quality of decision-making was also significantly impaired in the patients. A mood-congruent attentional bias for 'sad' targets was not evident on the affective go/no-go task. CONCLUSIONS: We found widespread evidence of significant cognitive impairment and impaired quality of decision-making in symptomatically severe depressed bipolar patients. This cognitive impairment may contribute to difficulties with daily living, decision-making and the ability to engage and comply with psychological and drug treatments.

Alcohol and drug use among vocational dental practitioners.

OBJECTIVE: This study was designed to investigate the prevalence of alcohol and drug use in vocational dental practitioners (VDPs). DESIGN: Anonymous self-report questionnaire. SUBJECTS AND METHODS: All UK vocational dental practitioners (n = 719) who started practice in the summer of 1999 were questioned on their use of alcohol, tobacco, cannabis and other illicit drugs whilst a VDP and before graduation. RESULTS: Eighty-nine per cent of males and 88% of females reported alcohol use. Of these, 35% of males and 36% of females drank above sensible levels (up to 21 units per week for males, 14 units for females), with 48% of males and 52% of females "binge drinking". Thirty-three per cent of respondents reported cannabis use whilst a VDP. Regular drug use (use at least once a month) other than cannabis whilst a VDP was found to be highest among males, with regular ecstasy use reported by 4% and regular cocaine use reported by 2%. Regular tobacco use (ten or more cigarettes per day) was reported by 9% of VDPs. Regular tobacco users were found to be six times more likely to use cannabis on a regular basis, three times more likely to use ecstasy on a regular basis and four times more likely to use cocaine on a regular basis than those VDPs who reported non regular tobacco use. CONCLUSION: VDPs are drinking above sensible limits, binge drinking, using tobacco and indulging in illicit drug use to a degree that will cause health problems. However, use of all substances had reduced since qualification.

Upregulation of iNOS expression and phosphorylation of eIF-2alpha are paralleled by suppression of protein synthesis in rat hypothalamus in a closed head trauma model.

When the inducible form of nitric oxide synthase (iNOS) is expressed after challenge to the nervous system, it results in abnormally high concentrations of nitric oxide (NO). Under such conditions, NO could phosphorylate the eukaryotic translation initiation factor (eIF)-2alpha, thus suppressing protein synthesis in neurons that play a role in endocrine and autonomic functions. Using the Marmarou model of traumatic brain injury (TBI), we observed a rapid increase (at 4 h after TBI) of iNOS mRNA in magno- and parvocellular supraoptic and paraventricular neurons, declining gradually by approximately 30% at 24 h and by approximately 80% at 48 h. Western analysis indicated a trend towards increased iNOS protein synthesis at 4 h, which peaked at 8 h, and tended to decrease at the later time points. At the same time points, we detected immunocytochemically the phosphorylated form of eIF-2alpha (eIF-2alpha[P]) as cytoplasmic and more often as nuclear labeling. The incidence of double-labeled [iNOS and eIF-2alpha(P)] neuronal profiles, particularly at 24 h and 48 h after TBI, was high. De novo protein synthesis assessed quantitatively after infusion of 35S methionine/cysteine was reduced by approximately 20% at 4 h, remained depressed at 24 h, and did not return to control levels up to 48 h following the trauma. The results suggest that iNOS may trigger phosphorylation of eIF-2alpha, which in turn interferes with protein synthesis at the translational (ribosomal complex) and transcriptional (chromatin) levels. The depression in protein synthesis may include downregulation of iNOS itself, which could be an autoregulatory inhibitory feedback mechanism for NO synthesis. Excessive amounts of NO may also participate in dysfunction of hypothalamic circuits that underlie endocrine and autonomic alterations following TBI.

A survey of alcohol and drug use among UK based dental undergraduates.

OBJECTIVE: This study was designed to investigate the prevalence of alcohol and drug use. DESIGN: Anonymous self-report questionnaire. SETTING: A UK dental school in May 1998. SUBJECTS AND METHODS: 1st-5th year dental undergraduates (n = 264) were questioned on their use of alcohol and tobacco, cannabis and other illicit drugs whilst at dental school, and before entry. RESULTS: Eighty two per cent of male and 90% of female undergraduates reported drinking alcohol. Of those drinking, 63% of males and 42% of females drank in excess of sensible weekly limits (14 units for females, 21 units for males), with 56% of males and 58.5% of females 'binge drinking'. Regular tobacco smoking (10 or more cigarettes a day) was found to have a statistically significant association with year of study, 4th-5th year undergraduates being eight times more likely to regularly smoke than their junior colleagues. Fifty five per cent of undergraduates reported cannabis use at least once or twice since starting dental school, with 8% of males and 6% of females reporting current regular use at least once a week. CONCLUSION: Dental undergraduates are drinking above sensible weekly limits of alcohol, binge drinking and indulging in illicit drug use. Dental Schools should designate a teacher responsible for education of undergraduates regarding alcohol and substance abuse.

Effects of antiprogestins on the rate of proliferation of breast cancer cells.

We have examined the influence of progestins (progesterone, R5020) and antiprogestins (RU486, ZK98299, Org 31710 and Org 31806) on the rate of proliferation of wild type T47D cells cultured in whole fetal bovine serum (FBS) or in single charcoal stripped fetal bovine serum (SSFBS). All of the progesterone antagonists RU486, ZK98299 and two novel antiprogestins Org 31710 and Org 31806 inhibited cell proliferation when cells were cultured in FBS. In contrast, all of the antiprogestins with the exception of ZK98299 enhanced cell growth when cells were cultured in SSFBS. This stimulatory effect of RU486 was observed only at a high concentration of the ligand (1 microM). The effect of R5020, however, was concentration independent. The number of cells in the presence of RU486 was approximately 600% followed by R5020 approximately 400% above control values after a 28 day culturing period. In contrast, when the cells were grown in the presence of medium containing non-stripped whole serum, RU486 inhibited the extent of cell proliferation by 45%. Estradiol (E2) stimulated the rate of proliferation in cells cultured in SSFBS. Similar to when cells were cultured in whole serum, the antiprogestins inhibited cell growth in E2-supplemented SSFBS. Detection of the growth enhancement effects of progesterone receptor (PR) ligands such as RU486 and R5020 on the cells grown in charcoal-stripped medium appear to require the removal of E2 by charcoal stripping of the serum.

Micronutrient malnutrition: policies and programs for control and their implications.

Global progress in social and economic development is occurring, although slowly, in the most needy parts of the nonindustrialized world, where nutritional deficiencies, including micronutrients, remain significant public health problems. Until empowering benefits accrue from development spin-offs, policy guidance for purposeful public health actions can help reduce the unconscionable toll on health and quality of life from micronutrient malnutrition and can interrupt its intergenerational debilitating effects on national development. Narrowly focused control programs including homestead production, plant breeding, fortification, and supplementation are in effect, but in general, they have not been holistically planned and integrated into overall development programs. Such integration is needed to ensure sustainability into the next century. A new paradigm is needed, including a new way of thinking by nutrition scientists and program implementers that includes partnerships with the poor in all aspects of program planning and implementation.

Patterns of immediate early gene mRNA expression following rodent and human traumatic brain injury.

Cell stimulation which leads to degeneration triggers a prolonged wave of immediate early gene (IEG) transcription that correlates with neuronal demise. In order to determine the relevance of the prolonged IEG response to human traumatic brain injury, we analyzed IEG mRNA levels in brain tissue isolated following a controlled penetrating injury and an injection of the excitotoxin Quinolinic acid (QA), as well as from tissue recovered during routine neurosurgery for trauma. Total RNA was extracted from tissue and subjected to Northern analysis of IEG mRNAs (c-fos and zif/268). Both models produced rapid and prolonged waves of IEG transcription that appeared to correlate with the severity of injury. Increases in zif/268 mRNA were observed within 1 h with levels reaching their peak at 6 h following excitotoxic injury and 3 h following a controlled penetration. In general, human traumatic brain injury resulted in variable increases in IEG mRNA levels following traumatic injury with the largest IEG mRNA increases observed in tissue collected 0-10 h after injury. This post-injury time corresponds to the peak of the prolonged IEG response observed in rodents following excitotoxic injury. Comparisons were made in IEG response between rodent frontal cortex and human cortex, because the majority of the human tissue originated from the cerebral cortex. These results further support the hypothesis that prolonged IEG transcription serves as a marker of traumatic brain injury and may play a role in neurodegeneration and/or glial activation. Moreover, observations of similar IEG patterns of expression reinforces the importance of rodent models of brain injury providing useful information directly applicable to human brain injury.

Patterns of heat-shock protein 70 biosynthesis following human traumatic brain injury.

Heat-shock protein 70 (hsp70) is activated upon cellular stress/injury and participates in the folding and intracellular transport of damaged proteins. The expression of hsp70 following CNS trauma has been speculated to be part of a cellular response which is involved in the repair of damaged proteins. In this study, we measured hsp70 mRNA and protein levels within human cerebral cortex subjected to traumatic brain injury. Specimens were obtained during routine neurosurgery for trauma and processed for Northern mRNA and Western protein analysis. The largest increase in hsp70 mRNA levels was detected in trauma tissue obtained 4-6 h following injury. By 24 h, hsp70 mRNA levels were similar to nontrauma comparison tissues. hsp70 protein expression exhibited its greatest increases at 12-20 h post-injury. Immunocytological techniques revealed hsp70 protein expression in cells with neuronal-like morphology at 12 h after injury. These results suggest a role for hsp70 in human cortex following TBI. Moreover, since the temporal induction pattern of hsp70 biosynthesis is similar to that reported in the rodent, our observations validate the importance of rodent brain injury models in providing useful information directly applicable to human brain injury.

Heat-shock protein 72 expression in excitotoxic versus penetrating injuries of the rodent cerebral cortex.

The induction of heat shock protein 72 (hsp72) has been described in various experimental models of brain injury. The present study examined hsp72 expression patterns within the rodent cerebral cortex in experimental paradigms designed to mimic two mechanisms of damage produced by penetration of the cerebral cortex: (1) tissue tearing from the missile track and (2) diffuse excitotoxicity during temporary cavitation and shock wave formation. Adult male Spaque-Dawley rats received controlled penetration (stab) or injection of the NMDA receptor excitotoxin, quinolinic acid (QA), into the frontal cortex and were killed 1-24 h later. Tissue from the lesioned, sham-operated, or contralateral uninjected cortex was processed for Western and immunocytochemical analyses of hsp72 protein expression. By 12 h, both controlled penetration and excitotoxic brain injuries produced significant increases in hsp72 immunoreactivity, which decreased toward control levels at 24 h. However, the severity and regional distribution of hsp72 expression varied between the two models. Specifically, the controlled penetration injury produced many hsp72-expressing cells near the needle track, while immunoreactive cells within the QA-injected cortex were found in the periphery of the lesion site. Morphological assessment of brain sections subjected to dual-labeling procedures demonstrated that cells expressing hsp72 were primarily neuronal in both models of injury. These results suggest that although controlled penetration and diffuse excitotoxicity may induce similar temporal and cellular patterns of hsp72 expression, the spatial location of hsp72-immunoreactive cells may differ between the two models.

Gabapentin does not interact with a contraceptive regimen of norethindrone acetate and ethinyl estradiol.

Anticonvulsants that induce hepatic metabolism increase clearance of oral contraceptive hormones and thereby cause contraceptive failure. Gabapentin is not metabolized in humans and has little liability for causing metabolic-based drug-drug interactions. In healthy women receiving 2.5 mg norethindrone acetate and 50 microg ethinyl estradiol daily for three consecutive menstrual cycles, concurrent gabapentin administration did not alter the steady-state pharmacokinetics of either hormone. Thus, gabapentin is unlikely to cause contraceptive failure.

PIP: Anticonvulsants that induce hepatic metabolism increase the clearance of synthetic estrogens and progestogens used in oral contraceptives (OCs), thereby potentiating contraceptive failure. In contrast, the anticonvulsant drug gabapentin is not metabolized in humans and has little liability for metabolic-based drug interactions. The present study sought to confirm whether concurrent administration of gabapentin would alter the pharmacokinetics of norethindrone acetate (2.5 mg) and ethinyl estradiol (50 mcg) in healthy US women. A total of 13 women were enrolled for three menstrual cycles each. Pharmacokinetic values did not change appreciably as a result of the addition of gabapentin. The rate and extent of absorption of both hormones were unaffected by the anticonvulsant. Gabapentin plasma concentration time profiles and pharmacokinetic values from this study were similar to historical values after administration of gabapentin alone. The observed lack of interaction between gabapentin and norethindrone acetate or ethinyl estradiol is consistent with the fact that gabapentin is not metabolized, is not an inducer or inhibitor of hepatic drug metabolizing enzymes, is absorbed via a specific transport system for amino acids, and is not bound to plasma proteins. Anticonvulsant drugs that do not interact with OCs should be considered for the treatment of epileptic women of childbearing age who are using this method of fertility control.

From research to global reality: the micronutrient story.

The professional life history of E. V. McCollum exemplifies how sound nutrition-related laboratory research was translated into practical realities that influenced individual and national nutrition-related decisions. Public health and educational programs emerging in the first third of this century improved health and nutritional well-being in the United States. Characteristics that surrounded pioneering efforts early in the century are similar to those that have reinvigorated global micronutrient concerns in the last third of the century. Sound community-oriented scientific research revealed the true consequences of iodine, vitamin A and iron micronutrient malnutrition. Repositioning the image of these three micronutrients from that of a clinical problem affecting relatively few to one with consequences for individual, national and global development affecting many more, and disseminating these facts through high-level political forums incited attention, commitment and actions. As in the early days of McCollum and his contemporaries, current nutrition scientists played a significant role, interacting with politically oriented counterparts, in taking micronutrient research to reality for improving health and quality of life globally. Lessons learned from the process, both past and present, should guide future nutrition-oriented endeavours in moving research to reality for betterment of global community health.

Perspectives from micronutrient malnutrition elimination/eradication programmes.

Micronutrient malnutrition cannot be eradicated, but the elimination and control of iron, vitamin A and iodine deficiencies and their health-related consequences as public health problems are currently the targets of global programmes. Remarkable progress is occurring in the control of goitre and xerophthalmia, but iron-deficiency anaemia (IDA) has been less responsive to prevention and control efforts. Subclinical consequences of micronutrient deficiencies, i.e. "hidden hunger", include compromised immune functions that increase the risk of morbidity and mortality, impaired cognitive development and growth, and reduced reproductive and work capacity and performance. The implications are obvious for human health and national and global economic and social development. Mixes of affordable interventions are available which, when appropriately adapted to resource availability and context, are proven to be effective. These include both food-based interventions, particularly fortification programmes, such as salt iodization, and use of concentrated micronutrient supplements. A mix of accompanying programmes for infection control, community participation, including education, communication and information exchange, and private sector involvement are lessons learned for overcoming deterrents and sustaining progress towards elimination.