Robert Carse Correspondence

Entries include a typed letter of correspondence from Carse at the Hotel Chelsea with his reply that he shared the Maine Author Collection letter of introduction with the Children\u27s Book editor at Putnam and with research questions for an upcoming W.W. Norton book

Acupuncture for chronic neck pain: a pilot for a randomised controlled trial

Background: Acupuncture is increasingly being used for many conditions including chronic neck pain. However the evidence remains inconclusive, indicating the need for further well-designed research. The aim of this study was to conduct a pilot randomised controlled parallel arm trial, to establish key features required for the design and implementation of a large-scale trial on acupuncture for chronic neck pain. Methods: Patients whose GPs had diagnosed neck pain were recruited from one general practice, and randomised to receive usual GP care only, or acupuncture ( up to 10 treatments over 3 months) as an adjunctive treatment to usual GP care. The primary outcome measure was the Northwick Park Neck Pain Questionnaire (NPQ) at 3 months. The primary analysis was to determine the sample size for the full scale study. Results: Of the 227 patients with neck pain identified from the GP database, 28 (12.3%) consenting patients were eligible to participate in the pilot and 24 (10.5%) were recruited to the trial. Ten patients were randomised to acupuncture, receiving an average of eight treatments from one of four acupuncturists, and 14 were randomised to usual GP care alone. The sample size for the full scale trial was calculated from a clinically meaningful difference of 5% on the NPQ and, from this pilot, an adjusted standard deviation of 15.3%. Assuming 90% power at the 5% significance level, a sample size of 229 would be required in each arm in a large-scale trial when allowing for a loss to follow-up rate of 14%. In order to achieve this sample, one would need to identify patients from databases of GP practices with a total population of 230,000 patients, or approximately 15 GP practices roughly equal in size to the one involved in this study (i.e. 15,694 patients). Conclusion: This pilot study has allowed a number of recommendations to be made to facilitate the design of a large-scale trial, which in turn will help to clarify the existing evidence base on acupuncture for neck pain

Acupuncture, or non-directive counselling versus usual care for the treatment of depression: a pilot study

<p>Abstract</p> <p>Background</p> <p>Depression is one of the most common reasons for consulting in primary care. Acupuncture is a popular complementary therapy choice for depression but its evidence base is poor with more robust high quality trials being required. More than half of depressed patients experience painful symptoms, with severe pain being associated with poor response to antidepressants. Acupuncture may have much to offer as an intervention for depression that also helps alleviate pain. Non-directive counselling is the most widely used psychological approach for depression in NHS settings, and provides a useful pragmatic comparison for acupuncture that would, according to our pre-trial qualitative research, be of high interest to doctors and patients.</p> <p>Methods and design</p> <p>The pilot study uses five arms and involves a pragmatic design. All patients will continue to receive usual care. Four groups of patients will be allocated to acupuncture, or non-directive counselling, in addition to usual GP care. The acupuncture and counselling arms will be further split into two groups to explore different treatment regimens. The primary outcome measure is the BDI II. Potentially eligible patients will be screened for depression using the PHQ-9, which is also a secondary outcome measure. Other secondary measures include the SF 36 bodily pain subscale, the CORE OM, the WBQ-12 and the EQ5D. Health economic data will be collected and measures of therapeutic engagement will be used to compare patient's views of therapists and GPs. The study will employ a fully randomised preference design with collection of data on patient preferences and prior expectations.</p> <p>Discussion</p> <p>This study has been implemented, and data are currently being analysed to inform the design of a full scale trial. Two practical operational issues that impacted on study implementation are discussed. Firstly, the challenge of recruiting depressed patients via GP consultation. Secondly, the problem of poor uptake and high attrition for counselling and acupuncture, which appeared to be associated with poor questionnaire return, and resulted in missing data. These problems may be relevant to other researchers working in the area of depression, or similar illnesses, where patients may lack motivation and energy to engage in research, or attend for treatment.</p> <p>Trial Registration</p> <p>Current Controlled Trials (ISRCTN 59267538)</p

Insights into the structure-function relationships of dimeric C3d fragments

Cleavage of C3 to C3a and C3b plays a central role in the generation of complement-mediated defences. Although the thioester-mediated surface deposition of C3b has been well-studied, fluid phase dimers of C3 fragments remain largely unexplored. Here we show C3 cleavage results in the spontaneous formation of C3b dimers and present the first X-ray crystal structure of a disulphide-linked human C3d dimer. Binding studies reveal these dimers are capable of crosslinking complement receptor 2 and preliminary cell-based analyses suggest they could modulate B cell activation to influence tolerogenic pathways. Altogether, insights into the physiologically-relevant functions of C3d(g) dimers gained from our findings will pave the way to enhancing our understanding surrounding the importance of complement in the fluid phase and could inform the design of novel therapies for immune system disorders in the future

Programmatic Evaluation of a Combined Antigen and Antibody Test for Rapid HIV Diagnosis in a Community and Sexual Health Clinic Screening Programme

Background A substantial proportion of HIV-infected individuals in the UK are unaware of their status and late presentations continue, especially in low prevalence areas. Fourth generation antigen/antibody rapid test kits could facilitate earlier diagnosis of HIV in non-clinical settings but lack data on performance under programmatic conditions. Methods and Findings We evaluated the performance of Determine HIV-1/2 Ag/Ab Combo Test (Determine Combo), a rapid test with indicators for both HIV antibodies and p24 antigen, in participants recruited from community outreach and hospital-based sexual health clinics. HIV infection was confirmed using laboratory enzyme-linked immunosorbent assay (EIA), Line Immuno Assay (LIA) and quantitative polymerase chain reaction (PCR). In total, 953 people underwent HIV testing. HIV antibody (Ab) prevalence was 1.8% (17/953). Four false positive rapid tests were identified: two antibody and two p24 antigen (Ag) reactions. Of participants diagnosed as HIV Ab positive, 2/17 (12%) were recent seroconverters based on clinical history and HIV antibody avidity test results. However, none of these were detected by the p24 antigen component of the rapid test kit. There were no other true positive p24 Ag tests. Conclusion These data lend support to an increasing body of evidence suggesting that 4th generation rapid HIV tests have little additional benefit over 3rd generation HIV kits for routine screening in low prevalence settings and have high rates of false positives. In order to optimally combine community-based case-finding among hard-to-reach groups with reliable and early diagnosis 3rd generation kits should be primarily used with laboratory testing of individuals thought to be at risk of acute HIV infection. A more reliable point of care diagnostic is required for the accurate detection of acute HIV infection under programmatic conditions

Factors associated with self-care activities among adults in the United Kingdom: a systematic review

Background: The Government has promoted self-care. Our aim was to review evidence about who uses self-tests and other self-care activities (over-the-counter medicine, private sector,complementary and alternative medicine (CAM), home blood pressure monitors). Methods: During April 2007, relevant bibliographic databases (Medline, Embase, Cumulative Index to Nursing and Allied Health Literature, Applied Social Sciences Index and Abstracts, PsycINFO,British Nursing Index, Allied and Complementary Medicine Database, Sociological Abstracts, International Bibliography of the Social Sciences, Arthritis and Complementary Medicine Database, Complementary and Alternative Medicine and Pain Database) were searched, and potentially relevant studies were reviewed against eligibility criteria. Studies were included if they were published during the last 15 years and identified factors, reasons or characteristics associated with a relevant activity among UK adults. Two independent reviewers used proformas to assess the quality of eligible studies. Results: 206 potentially relevant papers were identified, 157 were excluded, and 49 papers related to 46 studies were included: 37 studies were, or used data from questionnaire surveys, 36 had quality scores of five or more out of 10, and 27 were about CAM. Available evidence suggests that users of CAM and over-the-counter medicine are female, middle-aged, affluent and/or educated with some measure of poor health, and that people who use the private sector are affluent and/or educated. Conclusion: People who engage in these activities are likely to be affluent. Targeted promotion may, therefore, be needed to ensure that use is equitable. People who use some activities also appear to have poorer measures of health than non-users or people attending conventional services. It is, therefore, also important to ensure that self-care is not used as a second choice for people who have not had their needs met by conventional service

An economic evaluation of Alexander Technique lessons or acupuncture sessions for patients with chronic neck pain : A randomized trial (ATLAS)

OBJECTIVES: To assess the cost-effectiveness of acupuncture and usual care, and Alexander Technique lessons and usual care, compared with usual GP care alone for chronic neck pain patients. METHODS: An economic evaluation was undertaken alongside the ATLAS trial, taking both NHS and wider societal viewpoints. Participants were offered up to twelve acupuncture sessions or twenty Alexander lessons (equivalent overall contact time). Costs were in pounds sterling. Effectiveness was measured using the generic EQ-5D to calculate quality adjusted life years (QALYs), as well as using a specific neck pain measure-the Northwick Park Neck Pain Questionnaire (NPQ). RESULTS: In the base case analysis, incremental QALY gains were 0.032 and 0.025 in the acupuncture and Alexander groups, respectively, in comparison to usual GP care, indicating moderate health benefits for both interventions. Incremental costs were £451 for acupuncture and £667 for Alexander, mainly driven by intervention costs. Acupuncture was likely to be cost-effective (ICER = £18,767/QALY bootstrapped 95% CI £4,426 to £74,562) and was robust to most sensitivity analyses. Alexander lessons were not cost-effective at the lower NICE threshold of £20,000/QALY (£25,101/QALY bootstrapped 95% CI -£150,208 to £248,697) but may be at £30,000/QALY, however, there was considerable statistical uncertainty in all tested scenarios. CONCLUSIONS: In comparison with usual care, acupuncture is likely to be cost-effective for chronic neck pain, whereas, largely due to higher intervention costs, Alexander lessons are unlikely to be cost-effective. However, there were high levels of missing data and further research is needed to assess the long-term cost-effectiveness of these interventions

<i>Plasmodium falciparum </i>var genes expressed in children with severe malaria encode CIDRα1 domains

Most severe Plasmodium falciparum infections are experienced by young children. Severe symptoms are precipitated by vascular sequestration of parasites expressing a particular subset of the polymorphic P. falciparum erythrocyte membrane protein 1 (PfEMP1) adhesion molecules. Parasites binding human endothelial protein C receptor (EPCR) through the CIDRα1 domain of certain PfEMP1 were recently associated with severe malaria in children. However, it has remained unclear to which extend the EPCR‐binding CIDRα1 domains epitomize PfEMP1 expressed in severe malaria. Here, we characterized the near full‐length transcripts dominating the var transcriptome in children with severe malaria and found that the only common feature of the encoded PfEMP1 was CIDRα1 domains. Such genes were highly and dominantly expressed in both children with severe malarial anaemia and cerebral malaria. These observations support the hypothesis that the CIDRα1‐EPCR interaction is key to the pathogenesis of severe malaria and strengthen the rationale for pursuing a vaccine or adjunctive treatment aiming at inhibiting or reducing the damaging effects of this interaction

Race at the margins: A Critical Race Theory perspective on race equality in UK planning.

Despite evidence of the growing ethnic diversity of British cities and its impact on urban governance, the issue of racial equality in UK planning remains marginal, at best, to mainstream planning activity. This paper uses Critical Race Theory (CRT) to consider the reasons why the ‘race’ and planning agenda continues to stall. CRT, it is argued, offers a compelling account of why changes in practice over time have been patchy at best, and have sometimes gone into reverse

Protocol for a prospective cohort study of open tibia fractures in Malawi with a nested implementation of open fracture guidelines.

Background: Road traffic injury (RTI) is the largest cause of death amongst 15-39-year-old people worldwide, and the burden of injuries such as open tibia fractures are rapidly increasing in Malawi. This study aims to investigate disability and economic outcomes of people with open tibia fractures in Malawi and improve these with locally delivered implementation of open fracture guidelines. Methods: This is a prospective cohort study describing function, quality of life and economic burden of open tibia fractures in Malawi. In total, 160 participants will be recruited across six centres and will be followed-up with face-to-face interviews at six weeks, three months, six months and one year following injury. The primary outcome will be function at one year measured by the short musculoskeletal functional assessment (SMFA) score. Secondary outcomes will include quality of life measured by EuroQol EQ-5D-3L, catastrophic loss of income and implementation outcomes (acceptability, adoption, appropriateness, costs, feasibility, fidelity, penetration, and sustainability) at one year. A nested pilot pre-post implementation study of an interventional bundle for all open fractures will be developed based on other implementation studies from low- and middle-income countries (LMICs). Regression analysis will be used to model and investigate associations between SMFA score and fracture severity, infection and the pre- and post-training course period. Outcome: This prospective cohort study will report patient reported outcomes from open tibia fractures in low-resource settings. Subsequent detailed evaluation of both the clinical and implementation components of the study will promote sustainability of improved open fractures management in the study sites and further scale-up of open fracture management guidelines. Ethics: Ethics approval has been obtained from the Liverpool School of Tropical Medicine and College of Medicine Research and Ethics committee