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Introduction: The National Institute for Health and Clinical Excellence (NICE) has previously recommended pemetrexed plus cisplatin for the treatment of patients with advanced malignant pleural mesothelioma (MPM) and WHO performance status 0-1. Subsequent to this appraisal, randomised controlled trial (RCT) data for raltitrexed plus cisplatin and comparing chemotherapy to active symptom control (ASC) has become available, allowing a more complete analysis of the comparative efficacy and cost-effectiveness of first-line chemotherapy in MPM., Methods: An adjusted indirect comparison is used to estimate the relative efficacy of raltitrexed plus cisplatin and pemetrexed plus cisplatin. A cost-effectiveness model is used to assess the lifetime costs and health outcomes associated with these comparators and ASC. Patient level data from the EORTC 08983 trial are used to estimate baseline progression and survival rates. Relative treatment effects are taken from RCTs; cost and utility data from the literature., Results: Raltitrexed plus cisplatin and pemetrexed plus cisplatin were not found to be statistically significantly different with respect to overall response, progression free survival or overall survival. The cost-effectiveness analysis found raltitrexed plus cisplatin to be cost-effective at a cost per quality adjusted life year of £13,454 compared to cisplatin and £27,360 compared to ASC. Pemetrexed plus cisplatin is dominated by raltitrexed plus cisplatin as the raltitrexed combination offers marginally higher quality adjusted life years (QALYs) and life years (LYs) at a substantially lower total cost., Conclusion: Raltitrexed plus cisplatin is a cost-effective first-line treatment for MPM. This conclusion was maintained across a number of sensitivity analyses., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Adult Epiphyas postvittana Walker were irradiated using a Cobalt 60 source to determine the dose needed to achieve complete egg sterility of mated female moths, and egg sterility of female moths mated to F1 generation males. Adult male and female E. postvittana were irradiated at 100, 200, 250, and 300 Gy and their fertility (when crossed with normal moths) was compared with nonirradiated moths. Viable progeny (determined by egg hatch) were found at doses of 100 and 200 Gy, but very little at 250 and 300 Gy. In particular, there was no survival of female progeny into the F1 generation. Males irradiated at 250 and 300 Gy had very low egg eclosion rates (2.25 and 1.86% at 250 and 300 Gy, respectively) when mated with normal females. The F2 generation from those male progeny had a mean percent hatched of < 1.02%. Based on our results, a dose of 250-300 Gy is recommended for irradiation of E. postvittana adults used for sterile insect technique (SIT) if sterility of parental moths is the desired outcome. Our data also suggests that inclusion of F1 hybrid sterility rather than parental generation sterility into programs using the SIT may allow for doses lower than what we have reported, especially during initial phases of an eradication program where increase fitness of moths might be desirable. Further research is needed to verify the use of F1 hybrid sterility in light brown apple moth SIT programs.

Signs of sensory and perceptual awareness can be observed in people with very severe dementia, and may be influenced by the extent to which the environment offers appropriate stimulation. We developed an observational tool, AwareCare, which care staff can use to identify signs of awareness in residents with very severe dementia, based on the concept of the Wessex Head Injury Matrix (WHIM). Using WHIM items as a guide, and following focus groups with care staff and family members, an expert panel identified 28 environmental stimuli and 35 response categories for the initial version of AwareCare. After baseline assessments of cognition, well-being and quality of life were taken, 40 residents were observed individually for 30 minutes on 5 occasions. Based on the observational data, 10 stimulus categories and 14 response categories were identified for further analysis and formed the final version of AwareCare. All participants showed awareness to varying degrees. Social stimuli elicited the most responses. Greater awareness was associated with better cognitive function, self-care, mobility, and responsiveness, but not with proxy-rated quality of life. Understanding the nature of awareness in this group is an important element in ensuring appropriate levels of interaction and stimulation, and hence enhancing quality of care.

Objective: The effectiveness of psychosocial interventions in treating people with dementia and their carers is increasingly emphasised in the literature. Dementia guidelines should summarise the scientific evidence and best practice that is currently available, therefore, it should include recommendations for psychosocial interventions. The aims of our study were (1) to collate dementia guidelines from countries across Europe and to check whether they included sections about psychosocial interventions, and (2) to compare the methodological quality and the recommendations for specific psychosocial interventions in these guidelines., Methods: The European dementia guidelines were inventoried. The methodological quality of the guideline sections for psychosocial interventions was assessed with the (AGREE) Appraisal of Guidelines Research and Evaluation instrument. The recommendations for specific psychosocial interventions were extracted from each of these guidelines and compared., Results: Guidelines for psychosocial interventions were found in five of 12 countries. Guideline developers, methodological quality and appreciation of available evidence influenced the inclusion of psychosocial interventions in dementia guidelines from Germany, Italy, the Netherlands, Spain and the UK. The UK NICE SCIE guideline had the best methodological quality and included the most recommendations for psychosocial interventions. Physical activity and carer interventions were recommended the most across all guidelines., Conclusion: The inclusion of psychosocial interventions in dementia guidelines is limited across Europe. High-quality guidelines that include psychosocial interventions and are kept up to date with the emerging evidence are needed. Throughout Europe, special attention to the implementation of evidence-based psychosocial care is needed in the next few years., (Copyright © 2011 John Wiley & Sons, Ltd.)

Objectives: To demonstrate how value of information (VOI) analysis can be used to establish research priorities regarding the use of pharmacogenetic tests using CYP2D6 testing to select adjuvant hormonal therapy in early stage breast cancer as a case study., Methods: The following four treatment pathways are compared in a Markov model: tamoxifen treatment; CYP2D6 test and treat homozygous and heterozygous wild type patients (wt/wt; wt/*4) with tamoxifen and *4/*4 patients with anastrozole (HetTam); CYP2D6 test and treat homozygous wild type patients with tamoxifen and others with anastrozole (HomTam); and anastrozole treatment. Pharmacogenetic testing efficacy is estimated by synthesizing randomized controlled trial data comparing tamoxifen to anastrozole with observational data linking CYP2D6 genotype to tamoxifen outcomes., Results: In order of increasing effectiveness the comparators are tamoxifen, HetTam, HomTam, anastrozole. Health outcomes for test and treatment strategies are highly uncertain. Differences in comparator costs depend on assumptions made regarding anastrozole patent expiry. The expected value of a decision taken with perfect information is £69 to £106 million (pound sterling) for the United Kingdom depending on patent expiry assumptions and the acceptable cost-effectiveness threshold. The most valuable research (VOI £53-£82 million) elucidates the relationship between CYP2D6 genotype and tamoxifen effectiveness. It is uncertain whether values of other research designs would exceed their costs., Conclusions: Retrospective analysis of one of the large adjuvant aromatase inhibitor trials is warranted to better understand any association between CYP2D6 genotype and tamoxifen outcomes. VOI approaches may be helpful for prioritising evidence needs and structuring coverage with evidence development agreements for pharmacogenetics., (Copyright © 2011 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.)

The radiation biology of two geographically isolated populations of the light brown apple moth [Epiphyas postvittana (Walker)] was studied in Australia and New Zealand as an initiation of a SIT/F1 sterility program. Pharate and < or = 2 d pre-emergence pupae were exposed to increasing radiation doses up to a maximum dose of 300 Gy. Fertility and other life history parameters were measured in emerging adults (parental) and their progeny (F1-F3 adults). Parental fecundity was significantly affected by increasing irradiation dose in pharate pupae only. For both populations, parental egg fertility declined with increasing radiation. This was most pronounced for the irradiated parental females whose fertility declined at a higher rate than of irradiated males. At 250 Gy, females < or = 2 d preemergence pupae produced few larvae and no adults at F1. No larvae hatched from 250 Gy-irradiated female pharate pupae. At 300 Gy, males still had residual fertility of 2-5.5%, with pharate pupae being the more radio-sensitive. Radiation-induced deleterious inherited effects in offspring from irradiated males were expressed as increased developmental time in F1 larvae, a reduction in percent F1 female survival, decreased adult emergence and increased cumulative mortality over subsequent generations. Males irradiated at > or = 150 Gy produced few but highly sterile offspring at F1 and mortality was > 99% by F2 egg.

Endocycles are variant cell cycles comprised of DNA synthesis (S)- and gap (G)-phases but lacking mitosis. Such cycles facilitate post-mitotic growth in many invertebrate and plant cells, and are so ubiquitous that they may account for up to half the world's biomass. DNA replication in endocycling Drosophila cells is triggered by cyclin E/cyclin dependent kinase 2 (CYCE/CDK2), but this kinase must be inactivated during each G-phase to allow the assembly of pre-Replication Complexes (preRCs) for the next S-phase. How CYCE/CDK2 is periodically silenced to allow re-replication has not been established. Here, using genetic tests in parallel with computational modelling, we show that the endocycles of Drosophila are driven by a molecular oscillator in which the E2F1 transcription factor promotes CycE expression and S-phase initiation, S-phase then activates the CRL4(CDT2) ubiquitin ligase, and this in turn mediates the destruction of E2F1 (ref. 7). We propose that it is the transient loss of E2F1 during S phases that creates the window of low Cdk activity required for preRC formation. In support of this model overexpressed E2F1 accelerated endocycling, whereas a stabilized variant of E2F1 blocked endocycling by deregulating target genes, including CycE, as well as Cdk1 and mitotic cyclins. Moreover, we find that altering cell growth by changing nutrition or target of rapamycin (TOR) signalling impacts E2F1 translation, thereby making endocycle progression growth-dependent. Many of the regulatory interactions essential to this novel cell cycle oscillator are conserved in animals and plants, indicating that elements of this mechanism act in most growth-dependent cell cycles.

A population model was derived for light brown apple moth, Epiphyas postvittana (Walker) (Lepidoptera: Tortricidae), subject to the sterile insect technique (SIT). The model was parameterized from the literature and from recent laboratory studies conducted in New Zealand and Australia. Relationships were fitted for several model parameters that vary with irradiation dose, allowing the model to simulate effectively complete sterility at 300 Gy through inherited sterility occurring from lower doses. At 300 Gy, the model suggests that eventual population extinction is 95% probable when the ratio of released to wild males in monitoring traps exceeds 6.4. Higher overflooding rates would be required to achieve eradication more rapidly. The optimal release interval, in terms of minimizing the required rate of production of factory moths, is approximately weekly. There is little advantage in releasing males only compared with releasing both sexes. Female-only releases are unlikely to be a useful tool for inherited sterility eradication because there is no reduction in the fertility of F1 offspring. The critical release rate required to halt population increase declines with decreasing irradiation dose, but at doses of < 171 Gy there is a risk that irradiated-lineage moths may form a self-sustaining population, making eradication by SIT alone impossible. The model suggests that a dose of around 200 Gy may be optimal because the resulting inherited sterility would reduce by a third the number of factory moths required compared with 300 Gy.

Background: Peer support interventions can improve carer wellbeing and interventions that engage both the carer and person with dementia can have significant mutual benefits. Existing research has been criticised for inadequate rigour of design or reporting. This paper describes the protocol for a complex trial that evaluates one-to-one peer support and a group reminiscence programme, both separately and together, in a factorial design., Design: A 2 × 2 factorial multi-site randomised controlled trial of individual peer support and group reminiscence interventions for family carers and people with dementia in community settings in England, addressing both effectiveness and cost-effectiveness., Discussion: The methods described in this protocol have implications for research into psychosocial interventions, particularly complex interventions seeking to test both individual and group approaches.

Background: Public opposition to aerial application of sex pheromone for mating disruption of light-brown apple moth (LBAM), Epiphyas postvittana (Walk.), in California stopped its further use in the ca $74 million eradication programme in 2008, underscoring the need for other eradication tactics. It is demonstrated that pheromone-treated sterile Mediterranean fruit flies (medflies), Ceratitis capitata Wied., can disrupt communication in male moths., Results: Medflies topically dosed with moth pheromone (E)-11-tetradecenyl acetate showed a no observed effect level (NOEL) of ~10 µg fly(-1) , with increasing toxicity from 30 to 100 µg fly(-1) . Greater potency and longevity of attraction and lower mortality were achieved using microencapsulated pheromone. Releases of 1000 pheromone-treated medflies ha(-1) prevented male moth catch to synthetic lures in treated 4 ha plots for 1 day in suburban Perth, Australia. Releases of ca 3000 pheromone-treated medflies ha(-1) disrupted catch to single female moths in delta traps, and to synthetic pheromone lures. Percentage disruption on the first four nights was 95, 91, 82 and 85%., Conclusions: Disruption of moth catch using pheromone-treated medflies is a novel development that, with future improvement, might provide a socially acceptable approach for application of the insect mating disruption technique to control invasive insects in urban environments. Adequacy of payload and other issues require resolution., (Copyright © 2011 Society of Chemical Industry.)

The Armed Forces Health Surveillance Center's Division of Global Emerging Infections Surveillance and Response System (AFHSC-GEIS) supports and oversees surveillance for emerging infectious diseases, including respiratory diseases, of importance to the U.S. Department of Defense (DoD). AFHSC-GEIS accomplishes this mission by providing funding and oversight to a global network of partners for respiratory disease surveillance. This report details the system's surveillance activities during 2009, with a focus on efforts in responding to the novel H1N1 Influenza A (A/H1N1) pandemic and contributions to global public health. Active surveillance networks established by AFHSC-GEIS partners resulted in the initial detection of novel A/H1N1 influenza in the U.S. and several other countries, and viruses isolated from these activities were used as seed strains for the 2009 pandemic influenza vaccine. Partners also provided diagnostic laboratory training and capacity building to host nations to assist with the novel A/H1N1 pandemic global response, adapted a Food and Drug Administration-approved assay for use on a ruggedized polymerase chain reaction platform for diagnosing novel A/H1N1 in remote settings, and provided estimates of seasonal vaccine effectiveness against novel A/H1N1 illness. Regular reporting of the system's worldwide surveillance findings to the global public health community enabled leaders to make informed decisions on disease mitigation measures and controls for the 2009 A/H1N1 influenza pandemic. AFHSC-GEIS's support of a global network contributes to DoD's force health protection, while supporting global public health.

Background: There is good evidence indicating that group Cognitive Stimulation Therapy (CST) leads to generalised cognitive benefits for people with dementia. However, little is known about whether some aspects of cognition might change more than others and why., Methods: Cognitive Stimulation Therapy, a 14-session group treatment, has been evaluated in a multi-centre, single-blind, randomised controlled trial. This study looks at the subscales of the ADAS-Cog (memory and new learning, praxis and language) and compares the outcome of CST with a treatment as usual control group., Results: There was a significant difference between treatment and control groups in total ADAS-Cog score (p = 0.01) and in the language subscale (p = 0.01). There were no significant changes in memory and orientation or praxis., Conclusions: CST appears to have particular effects in promoting language function, which is likely to lead to generalised benefits. This may be through generating opinions and creating new semantic links through categorisation. Future research might use more sensitive psychometric tests to assess these effects in more depth., (Copyright © 2010 John Wiley & Sons, Ltd.)

Background: There is lack of evidence about the unmet needs of people with dementia (PWD) living at home and the predictors of high levels of unmet needs. The main aim of this study was to identify the relationship between unmet needs, social networks and quality of life of PWD living at home., Methods: One hundred and fifty two community dwelling PWD and 128 carers were interviewed about PWD's needs, social networks, quality of life and other functional and psychological factors. All the interviews with PWD were carried out at their homes. Interviews with carers were undertaken either at PWD's home, their own home or at the health centre. Whenever possible, PWD and carers were interviewed separately. The data collection took place between November 2005 and July 2007. The majority of participants (129, 84.9%) were recruited from National Health Services (NHS) and the rest (23, 15.1%) were recruited from other organisations such as social services and voluntary organizations in the UK., Results: The most frequent unmet needs for PWD were daytime activities (77, 50.7%), company (60, 39.5%), and help with psychological distress (47, 30.9%). Higher number of behavioural and psychological symptoms, low-community involvement social networks, having a younger carer and higher carer's anxiety were found to be predictors of higher unmet needs in PWD. Social networks and behavioural and psychological symptoms had an indirect effect on PWD's self-rated quality of life through unmet needs., Conclusions: Interventions aiming to reduce unmet needs, through the treatment of behavioural and psychological symptoms and the involvement of PWD in the community, would potentially improve PWD's quality of life.

Background and Purpose: Accurate identification of the NP in MR images is crucial to properly and objectively assess the intervertebral disk. Therefore, computerized segmentation of the NP in T2WI is necessary to produce repeatable and accurate results with minimal user input., Material and Methods: A semiautomated CS method was developed to identify the NP in T2WI on the basis of intensity differences compared with the AF. The method was validated by segmenting computer-generated images with a known ROI. The method was tested by using 63 MR images of rabbit lumbar disks, which were segmented to detect disk degeneration. An ICC was used to assess the repeatability of this method compared with manual segmentation., Results: The error in the detected area of the rabbit NP by using CS was -3.49% ± 4.4% (mean ± SD) compared with 22.36% ± 5.55% by using manual segmentation. Moreover, the method was capable of detecting disk degeneration in a known rabbit puncture model of disk degeneration. Finally, this method had an ICC of 0.97 and 0.99 in regard to segmenting the area and calculating the MR imaging index of the NP, deeming it highly repeatable., Conclusions: The CS method is a semiautomated computer method able to segment the NP of the rabbit disk and detect disk degeneration. In addition, it could assist in clinical detection, assessment, and monitoring of early degeneration in human disks.

Background: Promoting the mental well-being of older people has been neglected., Aim: To examine the clinical and cost-effectiveness of exercise and physical activity interventions on mental well-being in people aged 65+., Design: Systematic review, meta-analysis, economic model., Methods: Reports published in English, identified by searching 25 databases, 11 websites and references lists of systematic reviews. Eligible studies were those with a comparison or control group or offering qualitative evidence; exercise and physical activity interventions for people aged 65 and above living at home, in the community, in supported housing or in residential care homes; including outcome measures of mental well-being, not simply measures of depression or anxiety. Low-quality studies were excluded from the data synthesis., Results: An overall effect of exercise on mental well-being was found (standardised effect size = 0.27; CI = 0.14-0.40). The included interventions were designed for older people, targeted those who are sedentary and delivered in a community setting, primarily through a group-based approach led by trained leaders. As a minimum, the evidence would suggest two exercise sessions per week, each of 45 min duration. There is some indication that exercise can also improve the mental well-being of frail elders. Economic evidence indicated incremental cost-effectiveness ratios (compared with minimal intervention) of pound 7300 and pound 12,100 per quality adjusted life year gained for community-based walking and exercise programmes, respectively., Conclusions: Mental well-being in later life is modifiable through exercise and physical activity. To generalise the findings, there is a need for more evidence of effectiveness from older people in the UK.

Background: In the U.K. about 141,460 people with dementia (PWD) live alone. They are at risk of social isolation and inadequate social and medical supervision. The aims of this study were to identify the needs of PWD living alone and to compare the needs of PWD living alone versus those living with others. It was predicted that PWD living alone would have significantly more unmet needs than those living with others., Methods: 152 PWD were interviewed about their cognitive status and quality of life (QoL); and 128 informal carers were interviewed about the PWD's QoL, social networks, behavioral and psychological symptoms (BPSD), functional status, and services used. For 24 PWD no carer was available. Carers were also interviewed about their own symptoms of depression, anxiety, burden, and satisfaction. Researchers rated PWD's needs. One-third of the PWD (50) were living alone., Results: PWD living alone had significantly more unmet needs (M = 3.9, s.d. 3.1) than those living with others (M = 2.0, s.d. 2.0) (U = 1578, p < 0.01) particularly in the areas of looking after home (chi2 = 17.23, p < 0.001), food (chi2 = 13.91, p < 0.002), self-care (chi2 = 10.23, p < 0.002) and accidental self-harm (chi2 = 16.51, p < 0.001). The most frequent unmet needs were daytime activities (27, 54.0%), company (26, 52.0%), psychological distress (22, 44.0%), eyesight/hearing (16, 32.0%), and accidental self-harm (16, 32.0%)., Conclusion: PWD living alone are a vulnerable group who are at increased risk for unmet social, environmental, psychological and medical needs. This study illustrates the need to identify these individuals and to make provisions among social service agencies to monitor their well-being regularly and provide a higher level of support when needs are identified.

Introduction: Nonpharmacological therapies (NPTs) can improve the quality of life (QoL) of people with Alzheimer's disease (AD) and their carers. The objective of this study was to evaluate the best evidence on the effects of NPTs in AD and related disorders (ADRD) by performing a systematic review and meta-analysis of the entire field., Methods: Existing reviews and major electronic databases were searched for randomized controlled trials (RCTs). The deadline for study inclusion was September 15, 2008. Intervention categories and outcome domains were predefined by consensus. Two researchers working together detected 1,313 candidate studies of which 179 RCTs belonging to 26 intervention categories were selected. Cognitive deterioration had to be documented in all participants, and degenerative etiology (indicating dementia) had to be present or presumed in at least 80% of the subjects. Evidence tables, meta-analysis and summaries of results were elaborated by the first author and reviewed by author subgroups. Methods for rating level of evidence and grading practice recommendations were adapted from the Oxford Center for Evidence-Based Medicine., Results: Grade A treatment recommendation was achieved for institutionalization delay (multicomponent interventions for the caregiver, CG). Grade B recommendation was reached for the person with dementia (PWD) for: improvement in cognition (cognitive training, cognitive stimulation, multicomponent interventions for the PWD); activities of daily living (ADL) (ADL training, multicomponent interventions for the PWD); behavior (cognitive stimulation, multicomponent interventions for the PWD, behavioral interventions, professional CG training); mood (multicomponent interventions for the PWD); QoL (multicomponent interventions for PWD and CG) and restraint prevention (professional CG training); for the CG, grade B was also reached for: CG mood (CG education, CG support, multicomponent interventions for the CG); CG psychological well-being (cognitive stimulation, multicomponent interventions for the CG); CG QoL (multicomponent interventions for PWD and CG)., Conclusion: NPTs emerge as a useful, versatile and potentially cost-effective approach to improve outcomes and QoL in ADRD for both the PWD and CG., (Copyright © 2010 S. Karger AG, Basel.)

The incidence of asthma is increasing worldwide, but morbidity and mortality are decreasing because of improvements in medical care. Although the incidence of severe perioperative bronchospasm is relatively low in asthmatics undergoing anaesthesia, when it does occur it may be life-threatening. The keys to an uncomplicated perioperative course are assiduous attention to detail in preoperative assessment, and maintenance of the anti-inflammatory and bronchodilatory regimens through the perioperative period. Potential trigger agents should be identified and avoided. Many routinely used anaesthetic agents have an ameliorative effect on airway constriction. Nonetheless, acute bronchospasm can still occur, especially at induction and emergence, and should be promptly and methodically managed.

This article asks what sociological insights an analysis of food allergy and food intolerance might afford. We outline the parameters of debates around food allergy and food intolerance in the immunological, clinical and epidemiological literatures in order to identify analytic strands which might illuminate our sociological understanding of the supposed increase in both. Food allergy and food intolerance are contested and contingent terms and it is salient that the term true food allergy is replete throughout medico-scientific, epidemiological and popular discourses in order to rebuff spurious or 'nonallergic' claims of food-related symptoms. Complexity theory is introduced as a means of gaining analytic purchase on the food allergy debate. The article concludes that the use of this perspective provides a contemporary example of the 'double hermeneutic', in that the meanings and interpretations of contemporary explanations of food allergy are both permeated by, and can be made sense of, through recourse to complexity thinking.

Objectives: To explore the experiences of individuals with chronic conditions who are also caring for another person, usually a family member., Method: A postal questionnaire was distributed to carers across Wales on three occasions approximately 18 months apart. It included the SF-12v2 together with fixed-choice and open-ended questions relating to carer demographics, carer assessment, support needs, services received and care recipient's medical condition. A sub-sample of these carers was invited to take part in face-to-face interviews to allow for more in-depth exploration of their circumstances., Results: The carers with chronic conditions experienced a decline in their physical health over time whereas the physical health of carers without a chronic condition remained stable. There was also evidence of carers neglecting their own health because of their caring responsibilities. Despite their health problems, over time the carers with chronic conditions received no more support than other carers., Discussion: This article indicates that there are carers who are themselves suffering from a physical condition or conditions that suggest they are in need of care. Despite these difficulties, these carers are caring for people with quite severe conditions, without any help above that available to other carers.

Quality of Life (QoL) is now an established outcome measure for people with dementia. There is a need to understand if measures are sensitive to change and what factors are associated with change in QoL in dementia to develop interventions to improve QoL and identify who may be most likely to benefit. This study aimed to assess change in QoL in people living in 24-hour care homes using the Quality of Life-Alzheimer's Disease (QOL-AD) scale and investigated which clinical factors predicted changes in QoL in dementia. We used the QOL-AD scale to rate individual and staff perceptions of residents' QoL, for 238 people with dementia, recruited from 24 care homes in the United Kingdom. A follow-up interview was undertaken at 20 weeks. One hundred ninety-two (80.7%) of the 238 residents interviewed at baseline were followed up. A reduction in residents' QoL was predicted by lower baseline depression and anxiety symptoms, higher baseline QoL ratings, and an increase in depressive symptoms and cognitive deterioration at follow-up. Although QoL does not necessarily diminish as dementia progresses, it is strongly influenced by the person with dementia's mood. Improvement in cognition and mood may lead to increased QoL.

Objective: To examine serum markers of matrix turnover in an animal model of disk degeneration., Design: Randomized prospective in vivo study., Setting: Laboratory for Orthopaedic and Spine Research and Department of Large Animal Research., Participants: Twenty-one New Zealand White rabbits., Intervention: Rabbits were randomly grouped into control (n = 8), sham surgery (n = 5), or stab surgery (n = 8). The stab surgical group underwent annulotomy of L2-3, L3-4, and L4-5 to induce intervertebral disk degeneration. The sham surgical group underwent surgical exposure without annulotomy, and the control group received no intervention., Outcome Measurements: Lumbar spine magnetic resonance imaging (MRI) and serum samples were obtained before intervention and at 0, 3, 6, and 12 weeks thereafter. MRIs were analyzed for evidence of intervertebral disk degeneration via measurement of MRI index. The serum was assayed at 0, 3, 6, and 12 weeks for the aggrecan biosynthesis marker CS846 and the C-telopeptide of collagen II (CTX-II)., Results: The stabbed disks demonstrate degeneration apparent by MRI criteria. CTX-II increased with time in the stabbed group compared to the control and sham surgery groups regardless of baseline levels. Aggrecan showed no statistically significant difference among groups., Conclusions: CTX-II shows promise as a useful serum biomarker for intervertebral disk degeneration.

Background: Indirect evidence is particularly valuable in health care decision making when direct trial evidence comparing relevant treatments is absent or limited. Current approaches using a predetermined set of comparators in the search query may fail to identify all relevant indirect evidence., Purpose: To present a framework for the efficient design of search strategies for identifying clinical trials providing indirect evidence for a treatment comparison., Findings: The authors present 2 search strategies that differ from traditional search strategies in using a series of iterative searches to identify the set of relevant comparators. In both, the comparators included in each search are determined by the results of previous searches. For a given number of searches, the strategies presented will find all indirect comparisons that include a certain number of comparators linking the treatments of interest. Methods of estimating the value of indirect evidence via a given number of comparators linking the treatments of interest are presented, thus allowing the burden of additional searching to be traded off against the likely impact of finding more distant comparisons. A practical illustration of the search strategies in the context of informing a network meta-analysis of second-line treatments for non-small cell lung cancer is presented., Conclusions: The iterative strategies presented offer a means of identifying such evidence and allow the researcher to determine the optimal scope of the search by estimating the value of additional indirect evidence.

The aims of this study were to examine familiarization and reliability associated with a 40-m maximal shuttle run test (40-m MST), and to compare performance measures from the test with those of a typical unidirectional multiple sprint running test (UMSRT). 12 men and 4 women completed four trials of the 40-m MST (8 × 40-m; 20 s rest periods) followed by one trial of a UMSRT (12 × 30-m; repeated every 35 s); with seven days between trials. All trials were conducted indoors and performance times were recorded via twin-beam photocells. Significant between-trial differences in mean 40-m MST times were indicative of learning effects between trials 1 and 2. Test-retest reliability across the remaining trials as determined by coefficient of variation (CV) and intraclass correlation coefficient (ICC) revealed: a) very good reliability for measures of fastest and mean shuttle time (CV = 1.1 - 1.3%; ICC = 0.91 - 0.92); b) good reliability for measures of blood lactate (CV = 10.1 - 23.9%; ICC = 0.74 - 0.82) and ratings of perceived exertion (CV = 5.3 - 7.6%; ICC = 0.79 - 0.84); and c) poor reliability for measures of fatigue (CV = 38.7%; ICC = 0.59). Comparisons between performance indices of the 40-m MST and the UMSRT revealed significant correlations between all measures, except pre-test blood lactate concentration (r = 0. 47). Whilst the 40-m MST does not appear to provide more information than can be gleaned from a typical UMSRT, following the completion of a familiarization trial, the 40-m MST provides an alternative and, except for fatigue measures, reliable means of evaluating repeated sprint ability. Key pointsTests of multiple sprint performance are a popular means of evaluating repeated sprint ability.Multiple sprint tests incorporating changes of direction may be more ecologically valid than unidirectional protocols.The 40-m maximal shuttle run test is a reliable way of evaluating repeated sprint ability following the completion of one familiarization trial.The 40-m maximal shuttle run test shows no clear advantage over a standard unidirectional multiple sprint test.

Background: Relatively little attention has been given to the effects of caregiving context on the experience of family members providing care for a person with dementia. This review aims to examine the impact of caregiving on the quality of the relationship between caregiver and care-recipient and the impact of the quality of the relationship between the caregiver and care-recipient on the caregiver's and care-recipient's wellbeing., Methods: This was a systematic review. Fifteen quantitative studies were identified that examined the quality of the relationship between caregivers and care-recipients who had dementia, meeting the criterion of using a measure of relationship quality beyond a single item., Results: The findings show that caregiving can have an impact on the quality of the relationship between caregiver and care-recipient. In addition, pre-caregiving and current relationship quality appear to have an impact on caregiver's wellbeing. The care-recipient's needs for help with activities of daily living and level of behavioural problems were found to influence the caregiver's perceptions of relationship quality., Conclusions: Future research should examine both current and pre-caregiving relationship quality. A better understanding of the role of relationship quality in determining the outcomes of caregiving will aid the development of more effective interventions for caregivers.

Background: To investigate the prevalence of posterior tibial tendon dysfunction (PTTD) in women over the age of 40., Methods: A validated survey was posted to a random sample of 1000 women (over 40 years) from a GP group practice in Hertfordshire, England. Survey positive women were telephoned and when indicated, a detailed examination was performed., Results: There were 582 usable responses. The majority indicated they had minor forefoot or no problems. Telephone contact was made with 116 women and of those 79 required examination. The diagnosis of symptomatic flatfeet was made in 9 patients, 7 patients had stage I PTTD, 12 patients had stage II PTTD and 9 patients had an adult acquired flatfoot deformity., Conclusions: This is the first report of the prevalence of stage I and II PTTD in women (over 40 years). The prevalence is 3.3% and all patients were undiagnosed despite characteristic and prolonged symptoms.

Objective: The aim of this paper was to describe the Adolescent Intensive Management (AIM) team at the Austin Child and Adolescent Mental Health Service (CAMHS), a unique model of intensive outreach service with high-risk and difficult-to-engage adolescents, and describe the profile of clients referred to it., Method: This study used a retrospective review of clients' data, collected through file audit, over a 12-month period., Results: The result of the study showed that a 100% retention rate of adolescents with complex social, emotional and mental health needs is possible in a flexible and multi-system approach to service provision., Conclusion: Clients referred to the CAMHS' AIM team displayed a pattern of multiple risk factors and comorbidities. Low caseload of 8-10 clients per clinician allowed flexibility and a level of intensity to make any necessary changes in service provision to better suit the client's needs. The majority of clients showed improvement in functioning following intervention by the team.

Background: People with dementia in care homes are at risk of having their views ignored and decisions are often made on their behalf by care home staff and family carers. The aim of this study was to compare the ratings of needs of older people with dementia living in care homes, as assessed by the older person themselves, a family caregiver, and the staff of the care home., Method: The Camberwell Assessment of Need for the Elderly (CANE) was completed for 238 residents with dementia by care staff. In addition, 149 users and 81 family caregivers also completed the assessment of the person's met and unmet needs., Results: Many users were able to report their met and unmet needs despite having moderately severe dementia. The views of the person with dementia were commonly in agreement with the staff and family carers' views. However, user and carer pairs had the lowest average percentage agreement of 63% compared to that of 77% between user and staff pairs. In particular, users reported relatively higher unmet needs for psychological distress, company and information, and high unmet needs for daytime activities and eyesight/hearing problems., Conclusions: Users' views on their needs should be sought even when the person has dementia and lives in a care home. Reliance solely on assessment by staff or carers may lead to under recognition of unmet needs.

In recent years, there has been an increase in the recognition and use of psychosocial interventions for dementia. This has coincided with an increase in high-quality research in the area, and restrictions in the use of drug therapies for Alzheimer's disease in the UK. Cognitive stimulation therapy (CST) is a brief group treatment for people with mild-to-moderate dementia, based on the theoretical concepts of reality orientation and cognitive stimulation. It involves 14 sessions of themed activities which typically run twice a week over a 7-week period. A multicenter, randomized controlled trial showed significant benefits in cognition and participant-rated quality of life when comparing CST versus no treatment. These benefits in cognition were comparable to those gained through medication, and CST also proved to be cost-effective. Influenced by this research, the latest guidelines released by NICE recommended cognitive stimulation only as an intervention for treating the cognitive symptoms of dementia. This perspective describes how CST was developed and evaluated, its use in clinical settings and issues for future investigation, such as individualized CST.

This article provides an evidence-based review of open hernia repair. Technical considerations in general, including perioperative management of the patient, and the most currently used open repairs are addressed. Outcomes after repair are reviewed using the latest available literature. Current recommendations from this review include the routine use of mesh in primary repair of inguinal hernia and the need to counsel patients preoperatively about the risk of chronic postoperative groin pain.

In nanotechnology, strategies for the creation and manipulation of nanoparticles in the gas phase are critically important for surface modification and substrate-free characterization. Recent coherent diffractive imaging with intense femtosecond X-ray pulses has verified the capability of single-shot imaging of nanoscale objects at suboptical resolutions beyond the radiation-induced damage threshold. By intercepting electrospray-generated particles with a single 15 femtosecond soft-X-ray pulse, we demonstrate diffractive imaging of a nanoscale specimen in free flight for the first time, an important step toward imaging uncrystallized biomolecules.

Background: Older people with dementia living in residential care have complex unmet needs and decreased quality of life., Aim: To reduce unmet needs in older people with dementia in residential care compared to a 'care as usual' control group., Method: A single blind, multicentre, cluster randomised controlled trial recruited 238 people aged 60+ with dementia living in 24 residential homes from three areas. Unmet needs were measured using the Camberwell Assessment of Needs for the Elderly (CANE) and quality of life using the Quality of Life in Alzheimer's Disease (QoL-AD). Homes were randomised to the control (care as usual) or the intervention group 1 hour per week liaison input per home to deliver a personalised intervention package over a 20 weeks to meet the unmet needs., Results: A single blind follow-up included 192 (81%) available participants. At follow-up the total number of unmet needs was reduced in both the intervention and control groups, but analysing the groups by clusters there were no significant differences in either unmet needs or quality of life., Conclusions: The unmet needs of people with dementia can be identified using the CANE. The CANE assessment may have led to unmet needs being reduced at follow up, but the liaison intervention did not significantly reduce total unmet needs relative to the control group. Unmet needs such as sensory problems, mobility, drugs, and psychological distress were especially reduced in the intervention group at follow up., (Copyright 2007 John Wiley & Sons, Ltd.)

Background: Rural and urban differences in the effects of care-giving are not well documented. This paper reports data on 122 carers for people with stroke or dementia living in rural and urban settings in Wales., Method: Carers completed a postal questionnaire, including the SF-12v2 Health Survey. Definitions of rural and urban were based on the Urban/Rural Indicator from the Office of National Statistics (ONS) All Fields Postcode Directory 2004., Results: Carers' mean Mental Component Summary (MCS) score (adjusted for age and sex) was one standard deviation below the population mean (-12.03). Male carers living in urban areas reported better mental health than male carers in rural areas (p<0.05) and female carers in both settings (p<0.05). A full model and a parsimonious model were developed, using MCS scores as outcome variables. In the full model sitting service provision in rural and urban locations was linked to better carer mental health, while support from friends and family was linked to better mental health for urban carers only., Conclusion: Our findings indicate the existence of both gender and location differences in carer experiences.

Background: Reality Orientation (RO) was first described as a technique to improve the quality of life of confused elderly people, although its origins lie in an attempt to rehabilitate severely disturbed war veterans, not in geriatric work. It operates through the presentation of orientation information (eg time, place and person-related) which is thought to provide the person with a greater understanding of their surroundings, possibly resulting in an improved sense of control and self-esteem. There has been criticism of RO in clinical practice, with some fear that it has been applied in a mechanical fashion and has been insensitive to the needs of the individual. There is also a suggestion that constant relearning of material can actually contribute to mood and self-esteem problems. There is often little consistent application of psychological therapies in dementia services, so a systematic review of the available evidence is important in order to identify the effectiveness of the different therapies. Subsequently, guidelines for their use can be made on a sound evidence base., Objectives: To assess the evidence of effectiveness for the use of Reality Orientation (RO) as a classroom-based therapy on elderly persons with dementia., Search Strategy: Computerised databases were searched independently by 2 reviewers entering the terms 'Reality Orientation, dementia, control, trial or study'. Relevant web sites were searched and some hand searching was conducted by the reviewer. Specialists in the field were approached for undocumented material, and all publications found were searched for additional references., Selection Criteria: All randomized controlled trials (RCTs), and all controlled trials with some degree of concealment, blinding or control for bias (second order evidence) of Reality Orientation as an intervention for dementia were included. The criteria for inclusion/exclusion involved systematic assessment of the quality of study design and the risk of bias, using a standard data extraction form. A measure of cognitive and/or behavioural change was needed., Data Collection and Analysis: Data were extracted independently by both reviewers, using a previously tested data extraction form. Authors were contacted for data not provided in the papers. Psychological scales measuring cognitive and behavioural changes were examined., Main Results: 6 RCTs were entered in the analysis, with a total of 125 subjects (67 in experimental groups, 58 in control groups). Results were divided into 2 subsections: cognition and behaviour. Change in cognitive and behavioural outcomes showed a significant effect in favour of treatment., Authors' Conclusions: There is some evidence that RO has benefits on both cognition and behaviour for dementia sufferers. Further research could examine which features of RO are particularly effective. It is unclear how far the benefits of RO extend after the end of treatment, but and it appears that a continued programme may be needed to sustain potential benefits.

Background: The self-regulation model of adjustment to illness suggests that individual differences in coping and responding are related to the illness representations people hold. The present study explored the feasibility of applying this concept with people with early-stage dementia., Method: Understanding of the illness was explored in semi-structured interviews with 22 people who had a diagnosis of mild to moderate Alzheimer's disease or mixed dementia, and a measure of mood was administered. Interview transcripts were subjected to content analysis., Results: Representations covering illness identity, cause, course, cure/control and consequences were successfully elicited, but diverged from professional constructs in some important respects. Most participants regarded their difficulties as part of normal ageing, and one-third viewed their condition as stable or improving. Almost all participants described some positive coping strategies; participants who believed that nothing could be done to help were more likely to score above clinical cut-offs for depression or anxiety., Conclusions: The findings offer a preliminary insight into the nature of illness representations in early-stage dementia, and support the relevance of the self-regulation model as a basis for understanding and intervention.

Background: Psychological therapy groups for people with dementia are widely used, but their cost-effectiveness has not been explored., Aims: To investigate the cost-effectiveness of an evidence-based cognitive stimulation therapy (CST) programme for people with dementia as part of a randomised controlled trial., Method: A total of 91 people with dementia, living in care homes or the community, received a CST group intervention twice weekly for 8 weeks; 70 participants with dementia received treatment as usual. Service use was recorded 8 weeks before and during the 8-week intervention and costs were calculated. A cost-effectiveness analysis was conducted with cognition as the primary outcome, and quality of life as the secondary outcome. Cost-effectiveness acceptability curves were plotted., Results: Cognitive stimulation therapy has benefits for cognition and quality of life in dementia, and costs were not different between the groups. Under reasonable assumptions, there is a high probability that CST is more cost-effective than treatment as usual, with regard to both outcome measures., Conclusions: Cognitive stimulation therapy for people with dementia has effectiveness advantages over, and may be more cost-effective than, treatment as usual.

Quality of life (QoL) is now seen as a key outcome in many aspects of dementia care. In a recent randomized controlled trial of Cognitive Stimulation Therapy (CST) groups, significant improvements in self-reported QoL were identified as well as changes in cognitive function. This further analysis of results from the trial examines whether the changes in these two domains occurred independently, perhaps for different reasons, or whether the effect of treatment on QoL was mediated by the changes in cognition. In all, 201 people with dementia living in residential homes or attending day centres were assessed using the Quality of Life-Alzheimer's Disease (QOL-AD) scale and a range of measures of cognition, dementia level, mood, dependency and communication. Participants were randomized to receive an intervention programme of CST or to receive treatment as usual. The QoL-AD and other measures were repeated eight weeks later. At baseline, higher QoL in dementia was significantly correlated with lower levels of dependency and depression, but not with cognitive function or dementia severity. Improvement in quality of life was associated with being female, low quality of life at baseline, reduced depression and increased cognitive function. Changes in cognitive function mediated the effects of treatment in improving QoL. These results suggest that whilst QoL in dementia appears to be independent of level of cognitive function, interventions aimed at improving cognitive function can, nonetheless, have a direct effect on QoL.

Background: People with dementia often move into care homes as their needs become too complex or expensive for them to remain in their own homes. Little is known about how well their needs are met within care homes., Method: The aim of this study was to identify the unmet needs of people with dementia in care and the characteristics associated with high levels of needs. Two hundred and thirty-eight people with dementia were recruited from residential care homes nationally. Needs were identified using the Camberwell Assessment of Needs for the Elderly (CANE)., Results: Residents with dementia had a mean of 4.4 (SD 2.6) unmet and 12.1 (SD 2.6) met needs. Environmental and physical health needs were usually met. However, sensory or physical disability (including mobility problems and incontinence) needs, mental health needs, and social needs, such as company and daytime activities, were often unmet. Unmet needs were associated with psychological problems, such as anxiety and depression, but not with severity of dementia or level of dependency., Conclusion: Mental health services and residential home staff need to be aware that many needs remain unmet and much can be done to improve the quality of life of the residents with dementia., (Copyright 2005 John Wiley & Sons, Ltd.)

Our improved understanding of the experience of people with dementia provides a new impetus to address legal and ethical issues. This paper explores emerging issues in relation to awareness in dementia and its impact on legal and ethical matters. The different approaches and principles demonstrated in relation to ethical issues are discussed, with an exploration of the concepts of beneficence, non-maleficence, autonomy, and paternalism. Application of these concepts is discussed in relation to advance directives, capacity, and decision making, participation in research and treatment, including informed consent, and truth telling. The tensions that exist between the imperatives of doing no harm and of maintaining autonomy in addressing legal and ethical issues are highlighted, and attention drawn to the manner in which the attribution of unawareness is used to justify withholding autonomy. The review emphasizes the importance of considering competency and awareness as being multi-faceted, to be understood in the context of social interaction.

Background: A recent randomised controlled trial on Cognitive Stimulation Therapy (CST) identified the need to evaluate its more long-term benefits for people with dementia. This study evaluates the effectiveness of a weekly maintenance CST programme for people with dementia in residential care., Method: Thirty-five people with dementia were included, following on from a seven-week twice-weekly study of CST. The maintenance CST sessions ran in two residential homes using a once a week programme of CST over an additional 16 weeks. Two control homes did not receive the maintenance intervention., Results: Using repeated measures ANOVAS, there was a continuous, significant improvement in cognitive function (MMSE) for those receiving MCST (CST+maintenance CST sessions) as compared to CST alone or no treatment (p = 0.012). There were no effects on quality of life, behaviour or communication following maintenance sessions. The initial cognitive improvements following CST were only sustained at follow-up when followed by the programme of maintenance CST sessions., Conclusions: The cognitive benefits of CST can be maintained by weekly sessions for around 6 months. A large-scale, multi-centre maintenance CST trial is required to clarify potential longer-term benefits of maintenance CST for dementia., (Copyright 2005 John Wiley & Sons, Ltd.)

Background: Reminiscence Therapy (RT) involves the discussion of past activities, events and experiences with another person or group of people, usually with the aid of tangible prompts such as photographs, household and other familiar items from the past, music and archive sound recordings. Reminiscence groups typically involve group meetings in which participants are encouraged to talk about past events at least once a week. Life review typically involves individual sessions, in which the person is guided chronologically through life experiences, encouraged to evaluate them, and may produce a life story book. Family care-givers are increasingly involved in reminiscence therapy. Reminiscence therapy is one of the most popular psychosocial interventions in dementia care, and is highly rated by staff and participants. There is some evidence to suggest it is effective in improving mood in older people without dementia. Its effects on mood, cognition and well-being in dementia are less well understood., Objectives: The objective of the review is to assess the effects of reminiscence therapy for older people with dementia and their care-givers., Search Strategy: The trials were identified from a search of the Specialised Register of the Cochrane Dementia and Cognitive Improvement Group on 4 May 2004 using the term "reminiscence". The CDCIG Specialized Register contains records from all major health care databases (MEDLINE, EMBASE, PsycLIT, CINAHL) and many ongoing trials databases and is regularly updated. We contacted specialists in the field and also searched relevant Internet sites. We hand-searched Aging and Mental Health, the Gerontologist, Journal of Gerontology, Current Opinion in Psychiatry, Current Research in Britain: Social Sciences, British Psychological Society conference proceedings and Reminiscence database., Selection Criteria: Randomised controlled trials and quasi-randomized trials of reminiscence therapy for dementia., Data Collection and Analysis: Two reviewers independently extracted data and assessed trial quality., Main Results: Five trials are included in the review, but only four trials with a total of 144 participants had extractable data. The results were statistically significant for cognition (at follow-up), mood (at follow-up) and on a measure of general behavioural function (at the end of the intervention period). The improvement on cognition was evident in comparison with both no treatment and social contact control conditions. Care-giver strain showed a significant decrease for care-givers participating in groups with their relative with dementia, and staff knowledge of group members' backgrounds improved significantly. No harmful effects were identified on the outcome measures reported., Authors' Conclusions: Whilst four suitable randomized controlled trials looking at reminiscence therapy for dementia were found, several were very small studies, or were of relatively low quality, and each examined different types of reminiscence work. Although there are a number of promising indications, in view of the limited number and quality of studies, the variation in types of reminiscence work reported and the variation in results between studies, the review highlights the urgent need for more and better designed trials so that more robust conclusions may be drawn.

People Nursing in association with Journal of Clinical Nursing 13, 6b, 57-67 Community mental health nursing and early intervention in dementia: developing practice through a single case history This paper reports on a single case history taken from the 'Dementia Action Research and Education' project, a 15-month primary care intervention study that was undertaken in North Wales in the early part of 2000. The study sought to address the meaning, context and diversity of early intervention in dementia care and employed a community mental health nurse and a psychiatric social worker to undertake early and psychosocial interventions with older people with dementia (aged 75 years and over) and their families. The workers tape-recorded, documented and analysed their interventions with 27 older people with dementia and their families over the 15-month duration of the study. Clinical supervision was also undertaken during the intervention phase. One case history is presented in this paper to illustrate the work of the community mental health nurse and to identify areas of practice development. Greater role transparency, collaborative working and improvement in educational preparation for practice are called for.