Palliative care and dementia—A time and place?

The current focus in dementia care places emphasis on the potential of people to live well with the condition. Given the historical tendency to neglect the full rights and citizenship of people with dementia, such an emphasis gives hope and optimism that there is life after diagnosis. This paper seeks to explore the potential compromise of effective preparation for the complexities of advanced illness that may be presented by this consistently up-beat message. Dementia is a life limiting condition, currently without cure. Therefore, the appropriateness of palliative care may seem obvious. Yet, until relatively recently, palliative care was seen as an adjunct to oncology in the minds of professionals and public alike. However, there is a growing recognition that specialist palliative care has much to offer people with a range of long term conditions, including people with dementia. So, whilst ‘living well’ is an important message—especially following diagnosis—planning for advanced dementia and dying well is equally important. The aim of this paper is to highlight policy on the living well and the palliative care approach for people with dementia. A word limited narrative literature review was conducted to explore how policies have or have not informed the literature on both messages. The findings emphasise the need for a continuum approach to dementia care, with discussion on when, where, and how can palliative care be delivered for people with dementia.     

'Palliative care': a contradiction in terms? A qualitative study of cancer patients with a Turkish or Moroccan background,their relatives and care providers

Background  

Palliative cancer care aims to improve quality of life and ultimately quality of dying, while prolonging life is not an objective anymore when death nears. The question is, however, whether these perspectives on palliative care are congruent with the perspectives of immigrant families with a Turkish or Moroccan background.     

Primary care physician treatment of low HDL: Rational approach or Pandora’s Box?

BackgroundGuidelines for treating high low-density lipoproteins are clear, whereas guidelines for treating low high-density lipoproteins (HDL) are less so. Physicians approach to treating low HDL cholesterol is not known.ObjectiveTo determine primary care physicians approach to managing low HDL.MethodsThree-thousand, nine-hundred and nineteen surveys were mailed to all primary care physicians in the State of Indiana, asking questions regarding demographics, case studies to assess the provider’s approach to managing low HDL, and direct questions regarding management of HDL levels and general lipid knowledge questions.ResultsSeven-hundred and eighty-one surveys were returned, for a response rate of 19.9%. Fifty-eight percent of participants would initiate HDL-raising therapy after achieving the appropriate low-density lipoprotein cholesterol goal. The approaches used to raise HDL included lifestyle changes (diet, exercise, smoking cessation) (85%), niacin (83%), fibric acid derivative (61%), and alcohol (31%). Reasons inhibiting initiating therapy for raising HDL included concern over side effects (56%), perceived lack of effectiveness of currently available drugs (24%), lack of clear guidelines (22%), and lack of evidenced-based trials demonstrating benefit of raising HDL (14%). For men, 40% of physicians use 40 mg/dL as a cutoff for initiating HDL-raising therapy, while 25% using a cutoff of 35 mg/dL. For women, 24% use a cutoff of 50 mg/dL for initiating HDL-raising therapy, while 12% use 45 mg/dL as a cutoff.ConclusionsThe majority of primary care physicians in the State of Indiana treated low HDL with appropriate approaches, although use of alcohol to raise HDL raises concerns.     

Management of colorectal cancer: A role for genetics in prevention and treatment?

Colorectal cancer remains one of the most common cancers in the Western world and amongst the top three causes of cancer morbidity and death. Cancer is caused by genetic mutations, but currently there is little use of genetic information in the clinic with the exception of establishing germline mutations for the uncommon predisposing syndromes. Rapid advances in technologies allowing high throughput analysis of germline and somatic mutations raises the possibility that genetics will find a major role in the clinic distinguishing individuals at low to high risk of cancer, allowing early intervention and stratification of cancers based on mutational pathways for therapeutic interventions. In the future, this will lead to treatment regimes tailored to the individuals and their tumor. Here, we summarize the genetics underlying colorectal cancer and the future role of genetics in prevention, diagnosis, classification and treatment.     

An informed decision?: Breast cancer patients and their knowledge about treatment

ObjectiveAlthough involving women in breast cancer treatment decisions is advocated, there is little understanding of whether women have the information they need to make informed decisions. The objective of the current study was to evaluate women's knowledge of survival and recurrence rates for mastectomy and breast conserving surgery (BCS) and the factors associated with this knowledge.MethodsWe used a population-based sample of women diagnosed with breast cancer in metropolitan Los Angeles and Detroit between December 2001 and January 2003. All women with ductal carcinoma in situ and a random sample of women with invasive disease were selected (N = 2382), of which 1844 participated (77.4%). All participants were mailed surveys. The main outcome measures were knowledge of survival and recurrence rates by surgical treatment type.ResultsOnly 16% of women knew that recurrence rates were different for mastectomy and BCS, and 48% knew that the survival rates were equivalent across treatment. Knowledge about survival and recurrence was improved by exposure to the Internet and health pamphlets (p < 0.01). Women who had a female (versus male) surgeon, and/or a surgeon who explained both treatments (rather than just one treatment) demonstrated higher survival knowledge (p < 0.01). The majority of women had inadequate knowledge with which to make informed decisions about breast cancer surgical treatment.ConclusionPrevious explanations for poor knowledge, such as irrelevance of knowledge to decision making and lack of access to information, were not shown to be plausible explanations for the low levels of knowledge observed in this sample.Practice implicationsThese results suggest a need for fundamental changes in patient education to ensure that women are able to make informed decisions about their breast cancer treatment. These changes may include an increase in the use of decision aids and in decreasing the speed at which treatment decisions are made.     

Veterans’ preferences for tobacco treatment in primary care: A discrete choice experiment

ObjectiveTo evaluate US veterans’ preferences for smoking cessation counseling and pharmacotherapy.MethodsA discrete choice experiment (DCE) was conducted in 123 Veterans Health Administration primary care outpatients who planned to quit smoking within 6 months. Key attributes of tobacco cessation treatment were based on literature review and expert opinion. We used a hierarchical Bayesian approach with a logit model to estimate the part-worth utility of each attribute level and used latent class logit models to explore preference heterogeneity.ResultsIn the aggregate, participants valued counseling options with the following attributes: higher quit rate at 1 year, emphasis on autonomy, familiarity of the counselor, counselor’s communication skills, and inclusion of printed materials on smoking cessation. Participants valued pharmacotherapy options with the following attributes: higher quit rate at 1 year, lower risk of physical side effects, zero copayment, monthly check-in calls, and less weight gain. Latent class analysis revealed distinct clusters of patients with a unique preference “phenotype.”ConclusionsVeterans have distinct preferences for attributes of cessation counseling and pharmacotherapy.Practice implicationsIdentifying patients’ preferences provides an opportunity for clinicians to offer tailored treatment options that better engage veterans in their own care and boost adherence to guideline-recommended counseling and pharmacotherapy.     

Dopamine D3 receptor: A neglected participant in Parkinson Disease pathogenesis and treatment?

Parkinson disease (PD) is a neurodegenerative disorder characterized by motor and non-motor symptoms which relentlessly and progressively lead to substantial disability and economic burden. Pathologically, these symptoms follow the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) associated with abnormal α-synuclein (α-Syn) deposition as cytoplasmic inclusions called Lewy bodies in pigmented brainstem nuclei, and in dystrophic neurons in striatal and cortical regions (Lewy neurites). Pharmacotherapy for PD focuses on improving quality of life and primarily targets dopaminergic pathways. Dopamine acts through two families of receptors, dopamine D1-like and dopamine D2-like; dopamine D3 receptors (D3R) belong to dopamine D2 receptor (D2R) family. Although D3R’s precise role in the pathophysiology and treatment of PD has not been determined, we present evidence suggesting an important role for D3R in the early development and occurrence of PD. Agonist activation of D3R increases dopamine concentration, decreases α-Syn accumulation, enhances secretion of brain derived neurotrophic factors (BDNF), ameliorates neuroinflammation, alleviates oxidative stress, promotes neurogenesis in the nigrostriatal pathway, interacts with D1R to reduce PD associated motor symptoms and ameliorates side effects of levodopa (L-DOPA) treatment. Furthermore, D3R mutations can predict PD age of onset and prognosis of PD treatment. The role of D3R in PD merits further research. This review elucidates the potential role of D3R in PD pathogenesis and therapy.     

Simvastatin treatment in the SLO syndrome: A safe approach?

Soon after the discovery of reduced cholesterol synthesis in the Smith‐Lemli‐Opitz syndrome (SLOS), several trials with dietary supplementation were initiated with the aim of increasing cholesterol and reducing the de novo synthesis and accumulation of 7‐ and 8‐dehydrocholesterol (DHC). Dietary cholesterol raises cholesterol levels in the circulation with only marginal effects on levels of DHC. Photosensitivity and polyneuropathy have been reported to be improved by the treatment, but other effects have been difficult to evaluate. In order to see whether inhibition of hydroxymethylglutaryl CoA reductase is of benefit, two of our patients have been treated with simvastatin in addition to the long‐term treatment with cholesterol and bile acids. Absolute as well as relative levels of DHC were reduced. In one patient, creatine kinase increased moderately after 2 months of treatment. In the other patient, the treatment had to be interrupted because of hepatotoxic side effects with a marked increase in alanine aminotransferase and aggravation of the hypocholesterolemia and photosensitivity. We conclude that even if the levels of accumulated intermediates can be reduced, treatment with a statin may be harmful in some patients with SLOS. © 2002 Wiley‐Liss, Inc.     

DLB and PDD: a role for mutations in dementia and Parkinson disease genes?

Based on the substantial overlap in clinical and pathological characteristics of dementia with Lewy bodies (DLB) and Parkinson disease with dementia (PDD) with Alzheimer disease (AD) and Parkinson disease (PD) we hypothesized that these disorders might share underlying genetic factors. The contribution of both sequence and copy number variants (CNVs) in known AD and PD genes to the genetic etiology of DLB and PDD however is currently unclear. Therefore, we performed a gene-based mutation analysis of all major AD and PD genes in 99 DLB and 75 PDD patients, including familial and sporadic forms, from Flanders, Belgium. Also, copy number variants in APP, SNCA, and PARK2 were determined. In the AD genes we detected proven pathogenic missense mutations in PSEN1 and PSEN2, and 2 novel missense variants in PSEN2 and MAPT. In the PD genes we identified 1 SNCA duplication, the LRRK2 R1441C founder mutation and 4 novel heterozygous missense variants with unknown pathogenicity. Our results suggest a contribution of established AD and PD genes to the genetic etiology of DLB and PDD though to a limited extent. They do support the hypothesis of a genetic overlap between members of the Lewy body disease spectrum, but additional genes still have to exist.     

Improving actigraphic sleep estimates in insomnia and dementia: how many nights?

In order to investigate how the duration of actigraphic recordings affects the reliability of actigraphic estimates of sleep and 24-h activity rhythm variables, two to 3 weeks of actigraphy were recorded, from which pairs of variables derived from two periods of increasing length (1-10 days) were compared. Two groups were studied: (1) 10 subjects suffering from primary insomnia; and (2) 12 demented elderly subjects living semi-independently in group care facilities of homes for the elderly. Actigraphic estimates of primary measures of sleep (duration and efficiency) and of the 24-h activity pattern (interdaily stability, intradaily variability and amplitude) were calculated on variable lengths of the actigraphic recordings. The average absolute difference of two estimates decreased - and reliability increased - strongly with an increasing number of days analysed. An acceptable reliability of the interdaily stability estimate required more than 7 days of recording. It can be concluded that a valuable improvement in the reliability of actigraphic sleep estimates can be obtained by simply increasing the number of recording nights. The results support the importance of day-to-day variability in insomnia and dementia that has already been previously noted by others, and even suggest the presence of 'week-to-week' variability. This variability may have been involved in the equivocal results of treatment studies in insomnia and dementia where outcome measures were based on a limited number of nights. Such studies could profit from extension of the recording duration to, e.g. 2 weeks, and from the inclusion of variability measures as measures of clinical interest.     

Why do superantigens care about peptides?

Superantigen (SAg)-mediated activation of T cells is enhanced by the ability of the SAg to bind to major histocompatibility complex (MHC) class II molecules outside the peptide-binding groove, thereby bypassing the normal constraints of MHC restriction. However, recent studies have shown that SAg binding is acutely sensitive to the MHC class II-associated peptide. Here, David Woodland, Renren Wen and Marcia Blackman argue that this feature has evolved to optimize T-cell responses by more closely mimicking conventional antigen recognition.     

Combination of monoclonal antibodies and DPP-IV inhibitors in the treatment of type 1 diabetes: A plausible treatment modality?

Regulatory T cells (Tregs) are crucial for the maintenance of immunological tolerance. Type 1 diabetes (T1D) occurs when the immune-regulatory mechanism fails. In fact, T1D is reversed by islet transplantation but is associated with hostile effects of persistent immune suppression. T1D is believed to be dependent on the activation of type-1 helper T (Th1) cells. Immune tolerance is liable for the activation of the Th1 cells. The important role of Th1 cells in pathology of T1D entails the depletion of CD4⁺ T cells, which initiated the use of monoclonal antibodies (mAbs) against CD4⁺ T cells to interfere with induction of T1D. Prevention of autoimmunity is not only a step forward for the treatment of T1D, but could also restore the β-cell mass. Glucagon-like peptide (GLP)-1 stimulates β-cell proliferation and also has anti-apoptotic effects on them. However, the potential use of GLP-1 as a possible method to restore pancreatic β-cells is limited due to rapid degradation by dipeptidyl peptidase (DPP)-IV. We hypothesize that treatment with combination of CD4 mAbs and DPP-IV inhibitors could prevent/reverse T1D. CD4 mAbs have the ability to induce immune tolerance, thereby arresting further progression of T1D; DPP-IV inhibitors have the capability to regenerate the β-cell mass. Consequently, the combination of CD4 mAbs and DPP-IV inhibitor could avoid or at least minimize the constraints of intensive subcutaneous insulin therapy. We presume that if this hypothesis proves correct, it may become one of the plausible therapeutic options for T1D.     

Can antiviral treatment for hepatitis C be safely and effectively delivered in primary care?: A narrative systematic review of the evidence base

Background

The burden of hepatitis C (HCV) treatment is growing, as is the political resolve to tackle the epidemic. Primary care will need to work more closely with secondary care to succeed in reducing the prevalence of chronic HCV.

Aim

To identify research relating to the provision of antiviral treatment for HCV in primary care.

Design and setting

A narrative systematic review of six databases.

Method

Medline, Embase, Cinahl, PsycINFO, Web of Science, and Cochrane were searched. Relevant journals were searched by hand for articles to be included in the review. Reference lists of relevant papers were reviewed and full-text papers were retrieved for those deemed to potentially fulfil the inclusion criteria of the review.

Results

A total of 683 abstracts led to 77 full-text articles being retrieved, of which 16 were finally included in the review. An evidence base emerged, highlighting that community-based antiviral treatment provision is feasible and can result in clinical outcomes comparable to those achieved in hospital outpatient settings. Such provision can be in mainstream general practice, at community addiction centres, or in prisons. GPs must be trained before offering such a service and there is also a need for ongoing specialist supervision of primary care practice. Such training and supervision can be delivered by teleconference, although, even with such ready availability of training and supervision, only a minority of GPs are likely to want to provide antiviral treatment.

Conclusion

There is emerging evidence supporting the effectiveness of antiviral treatment provision for patients with chronic hepatitis C in a wide variety of primary care and wider community settings. Training and ongoing supervision of primary care practitioners by specialists is a prerequisite. There is an opportunity through future research activity to evaluate typologies of patients who would be best served by primary care-based treatment and those for whom hospital-based outpatient treatment would be most appropriate.