Optimising physiotherapy for people with lateral elbow tendinopathy - Results of a mixed-methods pilot and feasibility randomised controlled trial (OPTimisE).

BACKGROUND: The OPTimisE intervention was developed to address uncertainty regarding the most effective physiotherapy treatment strategy for people with Lateral Elbow Tendinopathy (LET). OBJECTIVES: To assess the feasibility of conducting a fully-powered randomised controlled trial (RCT) evaluating whether the OPTimisE intervention is superior to usual physiotherapy treatment for adults with LET. DESIGN: A mixed-methods multi-centred, parallel pilot and feasibility RCT, conducted in three outpatient physiotherapy departments in the UK. METHOD: Patients were independently randomised 1:1 in mixed blocks, stratified by site, to the OPTimisE intervention or usual care. Outcomes were assessed using pre-defined feasibility progression criteria. RESULTS: 50 patients were randomised (22 Female, 28 Male), mean age 48 years (range 27-75). Consent rate was 71% (50/70), fidelity to intervention 89% (16/18), attendance rate in the OPTimisE group 82% (55/67) vs 85% (56/66) in usual care, outcome measure completion 81% (39/48) at six-month follow-up. There were no related adverse events. Patients and physiotherapists reported that the OPTimisE intervention was acceptable but suggested improvements to the trial design. 49 patients were recruited from physiotherapy referrals vs one from primary care records. Outcome measure return rates were higher when completed online (74%) compared to postal questionnaire (50%). Exploratory analysis showed improvements in both groups over time. CONCLUSIONS: It is methodologically feasible to conduct a fully powered RCT comparing the clinical and cost-effectiveness of the OPTimisE intervention versus usual physiotherapy treatment. Considering the similar improvements observed in both groups, careful consideration is needed regarding the priority research question to be addressed in future research.

The implementation of pharmacogenomics into UK general practice: a qualitative study exploring barriers, challenges and opportunities.

Pharmacogenomics describes interpatient genetic variability in drug responses. Information based on whole genome sequencing will soon open up the field of pharmacogenomics and facilitate the use of genomic information relating to drug metabolism and drug responses. We undertook a qualitative study, aiming to explore the potential barriers, opportunities and challenges facing the implementation of pharmacogenomics into primary care. Semi-structured interviews were undertaken with 18 clinical participants (16 GPs and 2 other clinicians). All interviews were recorded and transcribed verbatim. Using a thematic analysis approach, data items were coded, ordered and themes constructed. Most participants were aged 55-60 years and worked as part-time clinical GPs with other clearly defined roles. The emerging themes covered several areas of concern, including the following: the utility of pharmacogenomics and the value of introducing such testing into primary care; how to educate the primary care workforce and 'mainstream' pharmacogenomics; the ethical, legal and social aspects of pharmacogenomics and its impact on patients; and potential impacts on the healthcare system particularly around economics and informatics. Most participants had concerns about pharmacogenomics and felt that there were a number of barriers and challenges to its implementation into routine primary care. Most striking were their concerns around the cost-effectiveness of using pharmacogenomics in primary care. At the same time most recognised the increasing availability of direct-to-consumer testing, and felt that this would drive the need to understand the ethical and social implications of using genomic information in primary care. This study has raised important issues that need to be considered when planning the implementation of pharmacogenomics into clinical practice. Prior to the implementation of genomic testing into day-to-day practice in UK primary care, it is important that considerations around education, cost-effectiveness and informatics are addressed, as well as the impact on patients.

Utilization of bone mineral density testing among breast cancer survivors in British Columbia, Canada.

Breast cancer survivors are at high osteoporosis risk. Bone mineral density testing plays a key role in osteoporosis management. We analyzed a historical utilization of bone mineral density testing in breast cancer survivors. The utilization remained low in the 1995-2008 period. Lower socio-economic status and rural residency were associated with lower utilization. INTRODUCTION: To evaluate the utilization of bone mineral density (BMD) testing for female breast cancer survivors aged 65+ surviving ≥ 3 years in British Columbia, Canada. METHODS: A retrospecitve population-based data linkage study. Trends in proportion of survivors with ≥ 1 BMD test for each calendar year from 1995 to 2008 were evaluated with a serial cross-sectional analysis. Associations between factors (socio-demographic and clinical) and BMD testing rates over the period 2006-2008 for 7625 survivors were evaluated with a cross-sectional analysis and estimated as adjusted prevalence ratios (PRadj) using log-binomial models. RESULTS: Proportions of survivors with ≥ 1 BMD test increased from 1.0% in 1995 to 10.1% in 2008. The BMD testing rate in 2006-2008 was 26.5%. Socio-economic status (SES) and urban/rural residence were associated with BMD testing rates in a dose-dependent relationship (p for trend< 0.01). Survivors with lower SES (PRadj = 0.66-0.78) or rural residence (PRadj = 0.70) were 20-30% less likely to have BMD tests, compared with survivors with the highest SES or urban residence. BMD testing rates were also negatively associated with older age (75+) (PRadj = 0.47; 95% CI = 0.42, 0.52), nursing home residency (0.05; 0.01, 0.39), recent osteoporotic fractures (0.21; 0.14, 0.32), and no previous BMD tests (0.26; 0.23, 0.29). CONCLUSION: Utilization of BMD testing was low for breast cancer survivors in BC, Canada. Lower SES and rural residence were associated with lower BMD testing rates. IMPLICATION FOR CANCER SURVIVORS: Female breast cancer survivors, especially those with lower SES or rural residence, should be encouraged to receive BMD tests as recommended by Canadian guidelines.

Defining migration and its health impact in China.

The scale and rapid expansion of urbanization resulting from socio-economic transformation in China at the beginning of the 21st century has accelerated rural-urban migration. Public health concerns from this increasing internal population mobility are now receiving attention from researchers. The health problems from internal migration pose particular demands on healthcare systems and relate to its demographic characteristics, with many younger and older people being left behind in the rural countryside. A review of literature, census, policy reports, government documents and media was undertaken to look at the classification system and health characteristics of China's internal migrants. It suggests that public health bears the consequences of political and economic decisions made elsewhere in society.

Severe hand, foot and mouth disease in Shenzhen, South China: what matters most?

Case report data and a matched case-control study were used to investigate the epidemiological characteristics of hand, foot and mouth disease (HFMD) in children in Shenzhen, China between 2008 and 2011. Multivariate analyses were used to evaluate factors associated with severity of infection. Laboratory tests were performed to determine aetiological identification for samples from 163 severe and fatal cases as well as an outpatient-based HFMD sentinel surveillance system (n = 446). All identified EV71 belonged to sub-genotype C4a. No major changes in the CA16 and EV71 viruses were found until the end of 2011. Annual attack rates and the case-severity ratios (CSRs) rose from 0.82/1000 and 0.56/1000, respectively, in 2008 to 2.12/1000 and 6.13/1000 in 2011. The CSR was higher in migrants than in local residents. The adjusted odds ratio (OR) of having a severe attack for being a migrant was 2.45, having a fever >39°C (OR 5.77), visiting a private clinic (OR 2.65), longer time from symptom onset to diagnosis (OR 1.49), visiting a doctor (OR 1.51), early use of intramuscular pyrazolone (OR 3.36), early use of intravenous glucocorticoids (OR 2.28), or the combination of both (OR 3.75). The mortality and increasing case severity appears to be associated with socioeconomic factors including migration and is of worldwide concern.

Phenological response of tundra plants to background climate variation tested using the International Tundra Experiment.

The rapidly warming temperatures in high-latitude and alpine regions have the potential to alter the phenology of Arctic and alpine plants, affecting processes ranging from food webs to ecosystem trace gas fluxes. The International Tundra Experiment (ITEX) was initiated in 1990 to evaluate the effects of expected rapid changes in temperature on tundra plant phenology, growth and community changes using experimental warming. Here, we used the ITEX control data to test the phenological responses to background temperature variation across sites spanning latitudinal and moisture gradients. The dataset overall did not show an advance in phenology; instead, temperature variability during the years sampled and an absence of warming at some sites resulted in mixed responses. Phenological transitions of high Arctic plants clearly occurred at lower heat sum thresholds than those of low Arctic and alpine plants. However, sensitivity to temperature change was similar among plants from the different climate zones. Plants of different communities and growth forms differed for some phenological responses. Heat sums associated with flowering and greening appear to have increased over time. These results point to a complex suite of changes in plant communities and ecosystem function in high latitudes and elevations as the climate warms.

Systematic reviews of clinical decision tools for acute abdominal pain.

OBJECTIVES: To review for acute abdominal pain (AAP), the diagnostic accuracies of combining decision tools (DTs) and doctors aided by DTs compared with those of unaided doctors. Also to evaluate the impact of providing doctors with an AAP DT on patient outcomes, clinical decisions and actions, what factors are likely to determine the usage rates and usability of a DT and the associated costs and likely cost-effectiveness of these DTs in routine use in the UK. DESIGN: Electronic databases were searched up to 1 July 2003. REVIEW METHODS: Data from each eligible study were extracted. Potential sources of heterogeneity were extracted for both questions. For the accuracy review, meta-analysis was conducted. Among studies comparing diagnostic accuracies of DTs with unaided doctors, error rate ratios provided estimates of the differences between the false-negative and false-positive rates of the DT and unaided doctors' performance. Pooled error rate ratios and 95% confidence intervals (CIs) for false-negative rates and false-positive rates were computed. Metaregression was used to explore heterogeneity. RESULTS: Thirty-two studies from 27 articles, all based in secondary care, were eligible for the review of DT accuracies, while two were eligible for the review of the accuracy of hospital doctors aided by DTs. Sensitivities and specificities for DTs ranged from 53 to 99% and from 30 to 99%, respectively. Those for unaided doctors ranged from 64 to 93% and from 39 to 91%, respectively. Thirteen studies reported false-positive and false-negative rates for both DTs and unaided doctors, enabling a direct comparison of their performance. In random effects meta-analyses, DTs had significantly lower false-positive rates (error rate ratio 0.62, 95% CI 0.46 to 0.83) than unaided doctors. DTs may have higher false-negative rates than unaided doctors (error rate ratio 1.34, 95% CI 0.93 to 1.93). Significant heterogeneity was present. Two studies compared the diagnostic accuracies of doctors aided by DTs to unaided doctors. In a multiarm cluster randomised controlled trial (n = 5193), the diagnostic accuracy of doctors not given access to DTs was not significantly worse (sensitivity 28.4% and specificity 96.0%) than that of three groups of aided doctors (sensitivities of 42.4-47.9%, and specificities of 95.5-96.5%, respectively). In an uncontrolled before-and-after study (n = 1484), the sensitivities and specificities of aided and unaided doctors were 95.5% and 91.5% (p = 0.24) and 78.1% and 86.4% (p < 0.001), respectively. The metaregression of DTs showed that prospective test-set validation at the site of the tool's development was associated with considerably higher diagnostic accuracy than prospective test-set validation at an independent centre [relative diagnostic odds ratio (RDOR) 8.2; 95% CI 3.1 to 14.7]. It also showed that the earlier in the year the study was performed the higher the performance (RDOR 0.88, 0.83 to 0.92), that when developers evaluated their own DT there was better performance than when independent evaluators carried out the study (RDOR = 3.0, 1.3 to 6.8), and that there was no evidence of association between other quality indicators and DT accuracy. The one eligible study of the impact study review, a four-arm cluster randomised trial (n = 5193), showed that hospital admission rates of patients by doctors not allocated to a DT (42.8%) were significantly higher than those by doctors allocated to three combinations of decision support (34.2-38.5%) (p < 0.001). There was no evidence of a difference between perforation rates (p = 0.19) and negative laparotomy rates in the four trial arms (p = 0.46). Usage rates of DTs by doctors in accident and emergency departments ranged from 10 to 77% in the six studies that reported them. Possible determinants of usability include the reasoning method used, the number of items used and the output format. A deterministic cost-effectiveness comparison demonstrated that a paper checklist is likely to be 100-900 times more cost-effective than a computer-based DT, under stated assumptions. CONCLUSIONS: With their significantly greater specificity and lower false-positive rates than doctors, DTs are potentially useful in confirming a diagnosis of acute appendicitis, but not in ruling it out. The clinical use of well-designed, condition-specific paper or computer-based structured checklists is promising as a way to improve impact on patient outcomes, subject to further research.

The smell map: commonality of odour perception confirmed.

We have examined the repeatability of a perceptual space, or smell map, initially developed in a sample of 20 people. A total of 110 normosmic people performed similarity ratings for pairs of the 11 commonly encountered odours used in the previous study. Multidimensional scaling was again used to analyse the relationships between odours. Some individual plots and an archetype, generated using the data from all participants, produced results similar to the previous study, confirming the ability to obtain reproducible results using a different tester and different participants. Exploration of the source space, that is, the spatial distribution of the individual plots relative to each other, suggests that the current model explains about 50% of the variation between subjects for the two-dimensional solution and 57% for the three-dimensional solution.

Global perspectives of contemporary epidemiological trends of cutaneous malignant melanoma.

During the past several decades, there has been a substantial increase in the incidence of cutaneous melanoma among all caucasian populations. The number of deaths due to cutaneous malignant melanoma has also increased in most fair-skinned populations throughout the world in the past few decades. Trends in melanoma incidence worldwide are examined. The most recent data on the mortality from cutaneous melanoma are reported. The role of different environmental, genetic and host factors in the aetiology of melanoma is discussed.

Management of regional lymph nodes in patients with malignant melanoma: questionnaire survey of UK current practice.

In 2001, a short postal questionnaire regarding the management of regional lymph nodes in patients with cutaneous malignant melanoma was sent to 69 NHS departments of plastic and reconstructive surgery in the UK. Questionnaires were returned by 53 units, giving a response rate of 76.8%. Of these 53 units, 49 reported that they treat patients with primary malignant melanoma. There was considerable variation in the number of melanoma patients managed by each unit. This survey confirmed that elective lymph-node dissection is not routinely practiced in the UK; observation and therapeutic lymph-node dissection for patients who develop regional metastasis is the preferred pattern of care. The majority of centres in the UK do not use sentinel lymph node mapping: only 15 of the 49 units do so (30.6%). The number of sentinel lymph node biopsies performed in each unit varied significantly. There was considerable variation in the materials used and the process of care for sentinel lymph node biopsy. On the basis of this current practice, we recommend the setting up of a prospective clinical melanoma register to record the surgical treatment of melanoma patients.

Tumour thickness as a predictor of occult lymph node metastases in patients with stage I and II melanoma undergoing sentinel lymph node biopsy.

BACKGROUND: Sentinel lymph node biopsy (SLNB) is a minimally invasive procedure used accurately to stage nodal basins at risk of occult metastases. There are no data as yet to show a survival benefit from SLNB and its use remains controversial. If Breslow thickness of the tumour correlates well with positive SLNB, it could be used to select patients for SLNB. METHODS: A quantitative systematic review of published studies on SLNB in patients with melanoma available by September 2001 was performed. RESULTS: Twelve studies containing 4218 patients with stage I and II melanoma were identified; 17.8 (95 per cent confidence interval 16.7 to 19.0) per cent of patients had nodal micrometastases detected by SLNB. The incidence of micrometastasis in sentinel nodes correlated directly with Breslow tumour thickness; it was 1.0 per cent for lesions of less than or equal to 0.75 mm, 8.3 per cent for 0.76-1.50 mm, 22.7 per cent for 1.51-4.0 mm and 35.5 per cent for more than 4.0 mm. CONCLUSION: The Breslow thickness of primary melanoma predicts the presence of a sentinel node metastasis. The published data are not sufficient to demonstrate a correlation between other known prognostic indicators and a positive SLNB.

Quantitative aspects of the inhibition by N(G)-monomethyl-L-arginine of responses to endothelium-dependent vasodilators in human forearm vasculature.

1. N(G)-monomethyl-L-arginine (L-NMMA) constricts human forearm resistance vasculature and selectively attenuates vasodilator responses to endothelium-dependent vasodilators. Incomplete inhibition of such responses could be due to an inadequate dose of L-NMMA or to NO-independent vasodilator mechanisms. 2. This study sought to determine doses of L-NMMA that are maximally effective in reducing basal and stimulated forearm blood flow. Drugs were infused via the brachial artery in 32 healthy men. Acetylcholine (11 - 330 nmol min(-1)) was compared with albuterol (0.33 - 10 nmol min(-1)), and nitroprusside (1.7 - 20 nmol min(-1)). 3. The effect of L-NMMA on basal flow approached maximum (53+/-2% reduction) at a dose of 16 micromol min(-1). L-NMMA (16 micromol min(-1)) did not significantly influence responses to nitroprusside, but antagonized acetylcholine and albuterol (each P<0.001, by repeated measures analysis of variance). 4. Inhibition of acetylcholine by L-NMMA (16 micromol min(-1)) was strongly influenced by acetylcholine dose (73+/-7% inhibition at 11 nmol min(-1), P<0.01; 4+/-11% inhibition at 330 nmol min(-1), P=NS, Student's paired t-test). Significant inhibition of albuterol was observed at all doses. 5. A higher dose of L-NMMA (64 micromol min(-1)) did not significantly inhibit the response to acetylcholine (330 nmol min(-1)). Responses to this dose of acetylcholine were unaffected by a cyclo-oxygenase (COX) inhibitor (indometacin) alone but combined COX and NO inhibition attenuated acetylcholine responses by 42+/-19%, implying that there is a compensatory increase in the contribution of prostaglandins or NO to acetylcholine-induced dilatation when one or other pathway is inhibited.

The community prevalence of chronic pelvic pain in women and associated illness behaviour.

BACKGROUND: Chronic pelvic pain has often been described as a major women's health issue, but no information exists on the extent of the problem in the United Kingdom. AIM: To investigate the community prevalence of chronic pelvic pain and its effect on the lives of consulting and non-consulting women. DESIGN OF STUDY: Postal questionnaire survey. SETTING: Women aged 18 to 49 (n = 3916) randomly selected from the Oxfordshire Health Authority Register. METHOD: The questionnaire response rate (adjusted for non-deliveries) was 74% (2304/3106). Chronic pelvic pain was defined as recurrent or constant pelvic pain of at least six months' duration, unrelated to periods, intercourse, or pregnancy. Case subgroups comprised recent consulters, past consulters, and non-consulters. Women who reported dysmenorrhoea alone formed a comparison group. RESULTS: The three-month prevalence of chronic pelvic pain was 24.0% (95% CI = 22.1% to 25.8%). One-third of women reported pain that started more than five years ago. Recent consulters (32% of cases) were most affected by their symptoms in terms of pain severity, use of health care, physical and mental health scores, sleep quality, and pain-related absence from work. Non-consulters (41% of cases) did not differ from women with dysmenorrhoea in terms of symptom-related impairment. Irrespective of consulting behaviour, a high rate of symptom-related anxiety was found in women with chronic pelvic pain (31%) compared with women with dysmenorrhoea (7%). CONCLUSIONS: This study showed a high community prevalence of chronic pelvic pain in women of reproductive age. Cases varied substantially in the degree to which they were affected by their symptoms. The high symptom-related anxiety in these women emphasises the need for more information about chronic pelvic pain and its possible causes.