https://archive-ouverte.unige.ch/unige:111231/ATTACHMENT01

ESPEN guideline clinical nutrition in neurology

BACKGROUND: Agitation is common, persistent and distressing in dementia and is linked with care breakdown. Psychotropic medication is often ineffective or harmful, but the evidence regarding non-pharmacological interventions is unclear. OBJECTIVES: We systematically reviewed and synthesised the evidence for clinical effectiveness and cost-effectiveness of non-pharmacological interventions for reducing agitation in dementia, considering dementia severity, the setting, the person with whom the intervention is implemented, whether the effects are immediate or longer term, and cost-effectiveness. DATA SOURCES: We searched twice using relevant search terms (9 August 2011 and 12 June 2012) in Web of Knowledge (incorporating MEDLINE); EMBASE; British Nursing Index; the Health Technology Assessment programme database; PsycINFO; NHS Evidence; System for Information on Grey Literature; The Stationery Office Official Documents website; The Stationery National Technical Information Service; Cumulative Index to Nursing and Allied Health Literature; and The Cochrane Library. We also searched Cochrane reviews of interventions for behaviour in dementia, included papers' references, and contacted authors about 'missed' studies. We included quantitative studies, evaluating non-pharmacological interventions for agitation in dementia, in all settings. REVIEW METHOD: We rated quality, prioritising higher-quality studies. We separated results by intervention type and agitation level. As we were unable to meta-analyse results except for light therapy, we present a qualitative evidence synthesis. In addition, we calculated standardised effect sizes (SESs) with available data, to compare heterogeneous interventions. In the health economic analysis, we reviewed economic studies, calculated the cost of effective interventions from the effectiveness review, calculated the incremental cost per unit improvement in agitation, used data from a cohort study to evaluate the relationship between health and social care costs and health-related quality of life (DEMQOL-Proxy-U scores) and developed a new cost-effectiveness model. RESULTS: We included 160 out of 1916 papers screened. Supervised person-centred care, communication skills (SES = -1.8 to -0.3) or modified dementia care mapping (DCM) with implementing plans (SES = -1.4 to -0.6) were all efficacious at reducing clinically significant agitation in care home residents, both immediately and up to 6 months afterwards. In care home residents, during interventions but not at follow-up, activities (SES = -0.8 to -0.6) and music therapy (SES = -0.8 to -0.5) by protocol reduced mean levels of agitation; sensory intervention (SES = -1.3 to -0.6) reduced mean and clinically significant symptoms. Advantages were not demonstrated with 'therapeutic touch' or individualised activity. Aromatherapy and light therapy did not show clinical effectiveness. Training family carers in behavioural or cognitive interventions did not decrease severe agitation. The few studies reporting activities of daily living or quality-of-life outcomes found no improvement, even when agitation had improved. We identified two health economic studies. Costs of interventions which significantly impacted on agitation were activities, £80-696; music therapy, £13-27; sensory interventions, £3-527; and training paid caregivers in person-centred care or communication skills with or without behavioural management training and DCM, £31-339. Among the 11 interventions that were evaluated using the Cohen-Mansfield Agitation Inventory (CMAI), the incremental cost per unit reduction in CMAI score ranged from £162 to £3480 for activities, £4 for music therapy, £24 to £143 for sensory interventions, and £6 to £62 for training paid caregivers in person-centred care or communication skills with or without behavioural management training and DCM. Health and social care costs ranged from around £7000 over 3 months in people without clinically significant agitation symptoms to around £15,000 at the most severe agitation levels. There is some evidence that DEMQOL-Proxy-U scores decline with Neuropsychiatric Inventory agitation scores. A multicomponent intervention in participants with mild to moderate dementia had a positive monetary net benefit and a 82.2% probability of being cost-effective at a maximum willingness to pay for a quality-adjusted life-year of £20,000 and a 83.18% probability at a value of £30,000. LIMITATIONS: Although there were some high-quality studies, there were only 33 reasonably sized (> 45 participants) randomised controlled trials, and lack of evidence means that we cannot comment on many interventions' effectiveness. There were no hospital studies and few studies in people's homes. More health economic data are needed. CONCLUSIONS: Person-centred care, communication skills and DCM (all with supervision), sensory therapy activities, and structured music therapies reduce agitation in care-home dementia residents. Future interventions should change care home culture through staff training and permanently implement evidence-based treatments and evaluate health economics. There is a need for further work on interventions for agitation in people with dementia living in their own homes. PROTOCOL REGISTRATION: The study was registered as PROSPERO no. CRD42011001370. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

A systematic review of the clinical effectiveness and cost-effectiveness of sensory, psychological and behavioural interventions for managing agitation in older adults with dementia

Parkinson's Disease Therapeutics: New Developments and Challenges Since the Introduction of Levodopa

This letter indicates that there is long-lasting skeletal accumulation of bisphosphonate, and ongoing use appears to be the dominant risk factor for rare fractures.

Risk of atypical femoral fracture during and after bisphosphonate use

Until the 1940s, when Albright associated osteoporosis with a defect of bone anabolism, it was not considered a disease entity but an inevitable consequence of the ageing process for which there was little remedy.1 Bisphosphonates, first synthesised in the 1800s but in clinical use only since the 1960s, demonstrated that this process of age-related decline in bone was, in fact, modifiable.2 More recently, a wealth of basic and clinical research has greatly enhanced our understanding of the complexity of bone metabolism, enabling the development of novel therapeutic strategies. The resultant reduction in fracture risk is greatest in those with more severe osteoporosis, suggesting that older people can have considerable gains from bone-sparing treatments.

Osteoporosis, now acknowledged as the most prevalent bone disorder in the world, is characterised by low bone mass, microarchitectural deterioration of bone tissue and decreased bone strength. Adult bone mass results from peak bone mass achieved during adolescence and subsequently maintained until perturbations in the bone remodelling cycle – usually a very tightly coupled process – occur and alter the balance between bone-forming osteoblasts and bone-resorbing osteoclasts. In a normal remodelling cycle, the amount of bone lost is the same as the amount of new bone formed. When this process becomes ‘uncoupled’ – as is the case in people with oestrogen deficiency, high levels of glucocorticoids, changes in serum calcium levels, fluctuations in levels of parathyroid hormone (PTH) and changes in levels of growth hormone – there is a net loss of bone.

Estimates indicate that 50% of women and 20% of men aged over 50 years will experience an osteoporosis-related fracture; hip fracture is the most devastating of these due to the consequent disability, mortality and costs – both personal and societal. Due to changing population demographics, estimates suggest a doubling of the number of people with osteoporosis in the next 20 years. Consequently, an exponential increase in the numbers of fractures is anticipated, with an inevitable increased financial burden for healthcare systems – the total economic burden of osteoporosis in the European Union in 2010 was estimated at A39 billion (about £32 billion).3 Without taking into account the personal cost to the individual, one can see why prevention and treatment of osteoporosis should be a priority for all those who care for older people. Osteoporosis is underdiagnosed and undertreated, particularly in those aged over 75 years, in whom treatment is probably most beneficial and cost effective.4 This fact suggests that treatment of the older cohort remains a challenge, not helped by the limited representation of older adults in major trials of osteoporosis treatments.

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Osteoporosis and fracture risk in older people

Background: Parkinson's disease (PD) is associated with a host of nonmotor symptoms, including psychosis, cognitive impairment, depression, sleep disturbance, swallowing disorders, gastrointestinal symptoms, and autonomic dysfunction. The nonmotor symptoms of PD have the potential to be more debilitating than the motor features of the disorder. Objective: The aim of this article was to review treatment options for the nonmotor manifestations of PD, including pharmacologic and nonpharmacologic interventions. Methods: The PubMed and MEDLINE databases were searched for articles published in English between January 1966 and April 2010, using the terms Parkinson's disease, nonmotor, psychosis, hallucination, antipsychotic, cognitive impairment, dementia, depression, sleep disturbance, sleepiness, REM (rapid eye movement) sleep behavior disorder, dysphagia, swallowing disorder, sialorrhea, gastrointestinal, constipation, autonomic dysfunction, orthostatic hypotension, gastroparesis, erectile dysfunction, sexual dysfunction, and urinary dysfunction . Articles were selected for review if they were randomized controlled trials (RCTs), meta-analyses, or evidence-based reviews of treatment of patients with PD, and/or expert opinion regarding the treatment of nonmotor symptoms of PD. Results: A total of 148 articles, including RCTs, meta-analyses, and evidence-based reviews, were included in this review. The treatment of hallucinations or psychosis in PD should include a stepwise reduction in medications for motor symptoms, followed by the use of quetiapine or clozapine. Dementia may be treated with acetylcholinesterase inhibitors. Evidence is lacking concerning the optimal pharmacologic treatment for depression in PD, with expert opinions indicating selective serotonin reuptake inhibitors as the antidepressants of choice. However, the largest study to date found nortriptyline therapy to be efficacious compared with placebo, whereas paroxetine controlled release was not. A variety of sleep disturbances may plague a person with PD, and treatment must be individualized to the patient's specific sleep disturbance pattern and contributing factors. Swallowing disorders may lead to aspiration and pneumonia, and patients with dysphagia should be referred to a speech therapist for further evaluation and treatment. Orthostasis may be treated with nonpharmacologic interventions as well as pharmacologic treatments (eg, fludrocortisone, midodrine, indomethacin). Other autonomic symptoms are managed in a manner similar to that in patients without PD, although careful attention must be aimed at avoiding dopamine-blocking therapies in the treatment of gastrointestinal dysfunction and gastroparesis. Conclusions: Various pharmacologic and nonpharmacologic strategies are available for the management of the nonmotor symptoms of PD. The challenges associated with nonmotor symptoms must not be forgotten in light of the motor symptoms of PD, and treatment of nonmotor symptoms should be encouraged.

Clinical review of treatment options for select nonmotor symptoms of Parkinson's disease

Background: Fractures are a significant problem in geriatric patients, and understanding the evidence for benefit and possible harm of osteoporosis treatments is critical to appropriate management of this patient population.

Objective: The purpose of this article was to review the evidence and treatment considerations related to use of the approved osteoporosis treatments in the United States across the continuum of ages in the geriatric population.

Methods: MEDLINE and the Web of Science were searched to find English-language articles published from 2000 through July 2009. Search terms included: practice guideline, osteoporosis, calcium, vitamin D, pharmacoeconomics, ethnicity, and treatment. The generic names of each of the osteoporosis treatments approved in the United States were searched to find relevant clinical trials and randomized controlled trials (RCTs). Pivotal trials that included fracture data or focused specifically on elderly patients (≥60 years of age) were selected. Bibliographies in the identified articles were searched for additional articles, and the prescribing information for each of the approved treatments was reviewed.

Results: Many osteoporosis studies have a mean patient age >60 years, but data for older patients are limited. Subanalyses of older patient groups have found risedronate to be beneficial for vertebral fractures in patients aged 70 to 79 years (absolute risk reduction [ARR], 8.4%; P < 0.001) and teriparatide to be beneficial for both vertebral (ARR, 6.4%; P < 0.05) and new nonvertebral fragility fractures (ARR, 9.9%; P < 0.05) in women aged ≥75 years. However, no RCTs of geriatric patients who were either nonambulatory or had multiple comorbidities were identified in the literature.

Conclusions: Evidence indicates that the osteoporosis treatments currently available in the United States are beneficial for treating osteoporosis in geriatric patients. However, data are limited for the oldest patients (≥80 years) and those with significant comorbidities. Because of the limited availability of data for geriatric patients with significant comorbidities, the properties of the various agents, including efficacy, tolerability, and potential contraindications, should be considered carefully for each geriatric patient.

Review of osteoporosis pharmacotherapy for geriatric patients.

Objective Review Huntington's disease (HD) and the role of tetrabenazine (TBZ) in treating chorea associated with this disease. Discuss the pharmacology, side-effect profile, drug interactions, precautions, and contraindications of TBZ. Data sources Literature identified within MEDLINE and PubMED. Study selection Two manuscripts specifically regarding the management of chorea in patients with HD were identified. Additionally, studies involving the clinical use of TBZ were reviewed. Data synthesis The literature identified provided information regarding the efficacy, safety, and pharmacological actions of TBZ. Conclusion HD is often accompanied by chorea, and the treatment with TBZ in this patient population often results in decreased chorea. Pharmacists managing patients on TBZ need to be well versed in TBZ's potential side effects, drug interactions, and unique dosing considerations.

Treatment of chorea associated with Huntington's disease: focus on tetrabenazine.

OBJECTIVE Discuss geriatric considerations in the treatment of diabetes mellitus and review the advantages and disadvantages of the various pharmacologic agents, including oral medications and insulin, currently available for the treatment of type 2 diabetes mellitus (T2DM). DATA SOURCES Literature identified within MEDLINE and PubMED, with an emphasis on material published since 2000, were reviewed. STUDY SELECTION Overall, 67 primary study manuscripts, clinical reviews, and dosing guidelines were identified and reviewed based on their clinical relevance to the geriatric population. DATA EXTRACTION Literature searches were performed for studies and reviews that included information on the use of antidiabetic medications in the geriatric population. Information was gathered from the available literature base for each medication class included in the review. DATA SYNTHESIS The literature identified provided guidelines and considerations for the treatment of the older patient with diabetes mellitus to optimize patient outcomes while minimizing the risk for adverse events. This review provides a systematic outline of these considerations and suggests treatment pearls. CONCLUSION The approach to managing T2DM in the elderly should be conservative and methodical in nature, with careful consideration of side effects, drug-disease and drug-drug interactions, and the risk of inducing hypoglycemia in this at-risk population.

Erin K. Dobbins

Papers

Clinical review of treatment options for select nonmotor symptoms of Parkinson's disease

Review of osteoporosis pharmacotherapy for geriatric patients.

Treatment of chorea associated with Huntington's disease: focus on tetrabenazine.

Pharmacological management of glycemic control in the geriatric patient with type 2 diabetes mellitus.