Leveraging Comprehensive Cancer Registry Data to Enable a Broad Range of Research, Audit and Patient Support Activities.

Traditional cancer registries have often been siloed efforts, established by single groups with limited objectives. There is the potential for registry data to support a broad range of research, audit and education initiatives. Here, we describe the establishment of a series of comprehensive cancer registries across the spectrum of common solid cancers. The experience and learnings of each registry team as they develop, implement and then use collected data for a range of purposes, that informs the conduct and output of other registries in a virtuous cycle. Each registry is multi-site, multi-disciplinary and aims to collect data of maximal interest and value to a broad range of enquiry, which would be accessible to any researcher with a high-quality proposal. Lessons learnt include the need for careful and continuous curation of data fields, with regular database updates, and the need for a continued focus on data quality. The registry data as a standalone resource has supported numerous projects, but linkage with external datasets with patients in common has enhanced the audit and research potential. Multiple projects have linked registry data with matched tissue specimens to support prognostic and predictive biomarker studies, both validation and discovery. Registry-based biomarker trials have been successfully supported, generating novel and practice-changing data. Registry-based clinical trials, particularly randomised studies exploring the optimal use of available therapy options are now complementing the research conducted in traditional clinical trials. More recent projects supported by the registries include health economic studies, personalised patient education material, and increased consumer engagement, including consumer entered data.

Chronic widespread pain in children and adolescents presenting in primary care: prevalence and associated risk factors.

ABSTRACT: A significant proportion of children/adolescents report chronic widespread pain (CWP), but little is known about clinically relevant CWP or what factors lead to onset in this population. Objectives were to report the primary care consultation prevalence of CWP and investigate risk factors associated with onset. A validated algorithm for identifying CWP status from primary care electronic healthcare records was applied to a child or adolescent population (aged 8-18 years). The algorithm records patients who have recurrent pain consultations (axial skeleton and upper or lower limbs) or those with a nonspecific generalised pain disorder (eg, fibromyalgia). Prevalence was described, and a nested case-control study was established to identify risk factors associated with CWP onset using logistic regression producing odds ratios (ORs) and 95% confidence intervals (95% CIs). Two hundred seventy-one children or adolescents were identified with CWP, resulting in a 5-year consultation prevalence of 3.19%. Risk factors significantly associated with CWP onset were as follows: mental health (eg, anxiety/neurosis consultations), neurological (eg, headaches), genitourinary (eg, cystitis), gastrointestinal (eg, abdominal pain), and throat problems (eg, sore throats). Children or adolescents with 1 or 2 risk factors (OR 2.15, 95% CI 1.6-2.9) or 3 or more risk factors (OR 9.17, 95% CI 5.9-14.3) were at significantly increased odds of CWP onset compared with those with none. Findings show a significant proportion of the child or adolescent primary care population has CWP. Most risk factors involved pain-related conditions, suggesting potential pathways of pain development. Further work is now needed to better understand the development of CWP in children and adolescents.

Stratified versus usual care for the management of primary care patients with sciatica: the SCOPiC RCT.

BACKGROUND: Sciatica has a substantial impact on patients and society. Current care is 'stepped', comprising an initial period of simple measures of advice and analgesia, for most patients, commonly followed by physiotherapy, and then by more intensive interventions if symptoms fail to resolve. No study has yet tested a model of stratified care in which patients are subgrouped and matched to different care pathways based on their prognosis and clinical characteristics. OBJECTIVES: The objectives were to investigate the clinical effectiveness and cost-effectiveness of a stratified care model compared with usual, non-stratified care. DESIGN: This was a two-parallel group, multicentre, pragmatic, 1 : 1 randomised controlled trial. SETTING: Participants were recruited from primary care (42 general practices) in North Staffordshire, North Shropshire/Wales and Cheshire in the UK. PARTICIPANTS: Eligible patients were aged ≥ 18 years, had suspected sciatica, had access to a mobile phone/landline, were not pregnant, were not receiving treatment for the same problem and had not had previous spinal surgery. INTERVENTIONS: In stratified care, a combination of prognostic and clinical criteria associated with referral to spinal specialist services was used to allocate patients to one of three groups for matched care pathways. Group 1 received advice and up to two sessions of physiotherapy, group 2 received up to six sessions of physiotherapy, and group 3 was fast-tracked to magnetic resonance imaging and spinal specialist opinion. Usual care was based on the stepped-care approach without the use of any stratification tools/algorithms. Patients were randomised using a remote web-based randomisation service. MAIN OUTCOME MEASURES: The primary outcome was time to first resolution of sciatica symptoms (six point ordinal scale, collected via text messages). Secondary outcomes (at 4 and 12 months) included pain, function, psychological health, days lost from work, work productivity, satisfaction with care and health-care use. A cost-utility analysis was undertaken over 12 months. A qualitative study explored patients' and clinicians' views of the fast-track care pathway to a spinal specialist. RESULTS: A total of 476 patients were randomised (238 in each arm). For the primary outcome, the overall response rate was 89.3% (88.3% and 90.3% in the stratified and usual care arms, respectively). Relief from symptoms was slightly faster (2 weeks median difference) in the stratified care arm, but this difference was not statistically significant (hazard ratio 1.14, 95% confidence interval 0.89 to 1.46; p = 0.288). On average, participants in both arms reported good improvement from baseline, on most outcomes, over time. Following the assessment at the research clinic, most participants in the usual care arm were referred to physiotherapy. CONCLUSIONS: The stratified care model tested in this trial was not more clinically effective than usual care, and was not likely to be a cost-effective option. The fast-track pathway was felt to be acceptable to both patients and clinicians; however, clinicians expressed reluctance to consider invasive procedures if symptoms were of short duration. LIMITATIONS: Participants in the usual care arm, on average, reported good outcomes, making it challenging to demonstrate superiority of stratified care. The performance of the algorithm used to allocate patients to treatment pathways may have influenced results. FUTURE WORK: Other approaches to stratified care may provide superior outcomes for sciatica. TRIAL REGISTRATION: Current Controlled Trials ISRCTN75449581. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 49. See the NIHR Journals Library website for further project information.

Sciatica is pain that spreads into the leg because of a trapped nerve in the lower back. It can be a very painful condition that affects everyday life and ability to work. People with sciatica usually see their general practitioner first; if they do not get better over time, they may be referred to a physiotherapist or, eventually, to a spinal specialist. It is difficult to know which sciatica patient will do well without much treatment and who might need to see a physiotherapist or spinal specialist sooner. Stratified care is an approach aiming to help decide, early on, which patients need to see which health professionals. It has previously been shown to be helpful for patients with lower-back pain. In a trial of 476 patients with sciatica a stratified care model was tested to see if it led to faster improvements in sciatica-related leg pain, when compared with usual care. Adults seeing their general practitioner with sciatica were invited to attend a research clinic. Those willing to take part were randomly assigned to stratified care or usual care. Patients in the stratified care arm were referred either to physiotherapy for a short or a longer course of treatment, or to undergo magnetic resonance imaging and see a spinal specialist with the magnetic resonance imaging results within 4 weeks. Pain, function and quality-of-life data were collected over 12 months using text messages and questionnaires. Although patients in the stratified care arm improved slightly more quickly (2 weeks, on average), we did not find convincing evidence that stratified care led to better results than usual care. On average, most patients in both trial arms improved in a similar way over 12 months. The stratified care model tested in this trial did not lead to faster recovery for patients with sciatica than usual care.

Stratified care versus usual care for management of patients presenting with sciatica in primary care (SCOPiC): a randomised controlled trial.

BACKGROUND: Sciatica has a substantial impact on individuals and society. Stratified care has been shown to lead to better outcomes among patients with non-specific low back pain, but it has not been tested for sciatica. We aimed to investigate the clinical and cost-effectiveness of stratified care versus non-stratified usual care for patients presenting with sciatica in primary care. METHODS: We did a two-parallel arm, pragmatic, randomised controlled trial across three centres in the UK (North Staffordshire, North Shropshire/Wales, and Cheshire). Eligible patients were aged 18 years or older, had a clinical diagnosis of sciatica, access to a mobile phone or landline number, were not pregnant, were not currently receiving treatment for the same problem, and had no previous spinal surgery. Patients were recruited from general practices and randomly assigned (1:1) by a remote web-based service to stratified care or usual care, stratified by centre and stratification group allocation. In the stratified care arm, a combination of prognostic and clinical criteria associated with referral to spinal specialist services were used to allocate patients to one of three groups for matched care pathways. Group 1 was offered brief advice and support in up to two physiotherapy sessions; group 2 was offered up to six physiotherapy sessions; and group 3 was fast-tracked to MRI and spinal specialist assessment within 4 weeks of randomisation. The primary outcome was self-reported time to first resolution of sciatica symptoms, defined as "completely recovered" or "much better" on a 6-point ordinal scale, collected via text messages or telephone calls. Analyses were by intention to treat. Health-care costs and cost-effectiveness were also assessed. This trial is registered on the ISRCTN registry, ISRCTN75449581. FINDINGS: Between May 28, 2015, and July 18, 2017, 476 patients from 42 general practices around three UK centres were randomly assigned to stratified care or usual care (238 in each arm). For the primary outcome, the overall response rate was 89% (9467 of 10 601 text messages sent; 4688 [88%] of 5310 in the stratified care arm and 4779 [90%] of 5291 in the usual care arm). Median time to symptom resolution was 10 weeks (95% CI 6·4-13·6) in the stratified care arm and 12 weeks (9·4-14·6) in the usual care arm, with the survival analysis showing no significant difference between the arms (hazard ratio 1·14 [95% CI 0·89-1·46]). Stratified care was not cost-effective compared to usual care. INTERPRETATION: The stratified care model for patients with sciatica consulting in primary care was not better than usual care for either clinical or health economic outcomes. These results do not support a transition to this stratified care model for patients with sciatica. FUNDING: National Institute for Health Research.

Risk factors for episodes of back pain in emerging adults. A systematic review.

BACKGROUND AND OBJECTIVE: The transition from adolescence to adulthood is a sensitive period in life for health outcomes, including back pain. The objective was to synthesize evidence on risk factors for new episodes of back pain in emerging adults (18-29 years). METHODS: The protocol was registered in PROSPERO (CRD42016046635). We searched Medline; EMBASE; AMED and other databases up to September 2018 for prospective cohort studies that estimated the association between risk factor(s) and self-reported back pain. Risk factors could be measured before or during the age range 18-29 years, and back pain could be measured during or after this age range, with at least 12 months between assessments. Risk factors assessed in ≥3 studies were summarized. Risk of bias was assessed using a 6-item checklist. RESULTS: Forty-nine studies were included with more than 150 different risk factors studied. Nine studies had low risk of bias, 26 had moderate and 14 had high risk of bias. Age, sex, height, body mass index (BMI), smoking, physical activity level, a history of back pain, job satisfaction and structural imaging findings were investigated in three or more studies. History of back pain was the only risk factor consistently associated with back pain after adjustment (nine studies). CONCLUSION: There is moderate quality evidence that a history of back pain is a risk factor for back pain. There are inconsistent associations for age, sex, height, BMI, smoking and activity level. No associations were found between job satisfaction and structural imaging findings and back pain. SIGNIFICANCE: Emerging adulthood is a transitional period of life with changes in life style, potentially influencing future musculoskeletal health. This systematic review included 49 articles evaluating more than 150 potential risk factors for back pain, one of the most prevalent musculoskeletal disorders. No consistent results were found for life style factors such as physical activity level or BMI, both highlighted as important risk factors in previous literature. Importantly, a previous episode of back pain was a consistent risk factor for a new episode of back pain across several studies, and further investigation of risk factors for the first back pain episode is needed.

Musculoskeletal pain in children and adolescents

ABSTRACT Introduction Musculoskeletal (MSK) pain in children and adolescents is responsible for substantial personal impacts and societal costs, but it has not been intensively or systematically researched. This means our understanding of these conditions is limited, and healthcare professionals have little empirical evidence to underpin their clinical practice. In this article we summarise the state of the evidence concerning MSK pain in children and adolescents, and offer suggestions for future research. Results Rates of self-reported MSK pain in adolescents are similar to those in adult populations and they are typically higher in teenage girls than boys. Epidemiological research has identified conditions such as back and neck pain as major causes of disability in adolescents, and in up to a quarter of cases there are impacts on school or physical activities. A range of physical, psychological and social factors have been shown to be associated with MSK pain report, but the strength and direction of these relationships are unclear. There are few validated instruments available to quantify the nature and severity of MSK pain in children, but some show promise. Several national surveys have shown that adolescents with MSK pain commonly seek care and use medications for their condition. Some studies have revealed a link between MSK pain in adolescents and chronic pain in adults. Conclusion Musculoskeletal pain conditions are often recurrent in nature, occurring throughout the life-course. Attempts to understand these conditions at a time close to their initial onset may offer a better chance of developing effective prevention and treatment strategies.

The role of sleep problems in the development of depression in those with persistent pain: a prospective cohort study.

STUDY OBJECTIVES: One theoretical model suggests a pathway between pain and the development of depression through sleep problems. Here, we prospectively test the hypothesis that incident sleep problems, in those with persistent pain, increase risk of new onset probable depression, and investigate the role of "pain that interferes with daily life" (pain interference) on this pathway. DESIGN: Prospective cohort study. SETTING: Community based population study within UK. PARTICIPANTS: Participants with persistent pain nested within a larger longitudinal community study. MEASUREMENTS: Participants were mailed health questionnaires at baseline (time 1) with follow-up at 3 years (time 2) and 6 years from baseline (time 3). Questionnaires at baseline and at follow up contained measures of sleep problems (Jenkins Sleep Questionnaire), depressive symptoms (Hospital Anxiety and Depressive Scale), and pain interference. RESULTS: In total, 2,622 participants returned health questionnaires at all time points and indicated the presence of pain at each time point. After adjustment for age, gender, marital status, employment status, alcohol intake, smoking status, and body mass index, having a new period of sleep problems at year 3 more than trebled the risk of a new period of probable depression at year 6 (relative risk 3.47, 95% CI 1.97 to 6.03). Mediation analysis showed that pain interference played a significant but relatively minor role in the pathway. CONCLUSION: Clinicians treating patients with persistent pain may wish to consider options that involve addressing the prevention or treatment of sleep problems, in addition to their primary focus of pain management.

Prognostic factors in non-surgically treated sciatica: a systematic review.

BACKGROUND: When present sciatica is considered an obstacle to recovery in low back pain patients, yet evidence is limited regarding prognostic factors for persistent disability in this patient group. The aim of this study is to describe and summarise the evidence regarding prognostic factors for sciatica in non-surgically treated cohorts. Understanding the prognostic factors in sciatica and their relative importance may allow the identification of patients with particular risk factors who might benefit from early or specific types of treatment in order to optimise outcome. METHODS: A systematic literature search was conducted using Medline, EMBASE and CINAHL electronic databases. Prospective cohort studies describing subjects with sciatica and measuring pain, disability or recovery outcomes were included. Studies of cohorts comprised entirely of surgically treated patients were excluded and mixed surgically and conservatively treated cohorts were included only if the results were analysed separately by treatment group or if the analysis was adjusted for treatment. RESULTS: Seven adequate or high quality eligible studies were identified. There were conflicting but mainly negative results regarding the influence of baseline pain severity, neurological deficit, nerve root tension signs, duration of symptoms and radiological findings on outcome. A number of factors including age, gender, smoking, previous history of sciatica and heaviness of work do not appear to influence outcome. In contrast to studies of low back pain and purely surgically treated sciatica cohorts, psychological factors were rarely investigated. CONCLUSIONS: At present, the heterogeneity of the available studies makes it difficult to draw firm conclusions about sciatica prognosis, and highlights the need for further research for this group of patients. Large scale prospective studies of high methodological quality, using a well-defined, consistent definition of sciatica and investigating psychosocial factors alongside clinical and radiological findings are recommended to identify prognostic factors in this population.

Relationship of opioid use and dosage levels to fractures in older chronic pain patients.

BACKGROUND: Opioids have been linked to increased risk of fractures, but little is known about how opioid dose affects fracture risk. OBJECTIVE: To assess whether risk of fracture increases with opioid dose among older patients initiating sustained use of opioids for chronic non-cancer pain. DESIGN: A cohort study that uses Cox proportional hazards models to compare fracture risk among current opioid users vs. persons no longer using opioids. PARTICIPANTS: Members of an integrated health care plan (N = 2,341) age 60 years and older who received 3+ opioid prescriptions within a 90-day period for chronic, non-cancer pain between 2000 and 2005. MEASUREMENTS: Time-varying measures of opioid use and average daily dose in morphine equivalents were calculated from automated data. Fractures were identified from automated data and then validated through medical record review. RESULTS: Compared with persons not currently using opioids, opioid use was associated with a trend towards increased fracture risk (1.28 (95% CI (0.99, 1.64 )). Higher dose opioid use (>or=50 mg/day) was associated with a 9.95% annual fracture rate and a twofold increase in fracture risk (2.00 (95% CI (1.24, 3.24)). Of the fractures in the study cohort, 34% were of the hip or pelvis, and 37% were associated with inpatient care. CONCLUSIONS: Higher doses (>or=50 mg/day) of opioids for chronic non-cancer pain were associated with a 2.00 increase in risk of fracture confirmed by medical record review. Clinicians should consider fracture risk when prescribing higher-dose opioid therapy for older adults.

Co-occurrence and associations of pain and fatigue in a community sample of Dutch adults.

Widespread pain and chronic fatigue are common in the general population. Previous research has demonstrated co-occurrence of syndromes that are associated with pain and fatigue (fibromyalgia and chronic fatigue syndrome), but there is limited existing data on the co-occurrence of these symptoms in general. This study investigates the co-occurrence of pain and fatigue, and characterises people with these symptoms individually, and in combination. A postal questionnaire was sent to a random sample of 4741 community dwelling Dutch adults registered with five general practices. There were 2447 participants (adjusted response=53.5%). Persistent fatigue was reported by 60% of the 451 subjects with chronic widespread pain. Chronic widespread pain was reported by 33% of the 809 responders with persistent fatigue. Anxiety and depression were more common in subjects who reported both symptoms than those who reported either one or neither. Participants who had chronic disease, high body mass index, low activity levels or did not perceive ability to influence health had higher adjusted odds of reporting both symptoms (but not one alone) than subjects not having these characteristics. Pain and fatigue occur more often than would be expected by chance and there are a number of reasons for this. Clinicians should be aware that co-occurrence of the symptoms is common, especially in people who have high BMI or chronic disease, and that people with both symptoms are often anxious or depressed. Further work should address longitudinal associations of pain and fatigue.

WITHDRAWN: Interventions for treating calcaneal fractures.

BACKGROUND: Fracture of the calcaneus (os calcis or heel bone) comprises one to two per cent of all fractures. OBJECTIVES: To identify and evaluate randomised trials of treatments for calcaneal fractures. SEARCH STRATEGY: MEDLINE, EMBASE, CINAHL, the Cochrane Controlled Trials Register, and the Cochrane Musculoskeletal Injuries Group Trials Register were searched. We checked reference lists of relevant articles and contacted trialists and experts in the field. Date of the most recent search: October 1998. SELECTION CRITERIA: Randomised and quasi-randomised trials comparing interventions for treating patients with calcaneal fractures. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality, using a 12 item scale, and extracted data. Wherever appropriate and possible, results were pooled. MAIN RESULTS: Of the six relevant randomised trials identified, four were included, one excluded and one is ongoing.All four included trials had methodological flaws.Three trials, involving 134 patients, compared open reduction and internal fixation with non-operative management of displaced intra-articular fractures. Pooled results showed no apparent difference in residual pain (24/40 versus 24/42; Peto odds ratio 0.90, 95% confidence interval 0.34 to 2.36), but a lower proportion of the operative group was unable to return to the same work (11/45 versus 23/45; Peto odds ratio 0.30, 95% confidence interval 0.13 to 0.71), and was unable to wear the same shoes as before (12/52 versus 24/54; Peto odds ratio 0.37, 95% confidence interval 0.17 to 0.84).One trial, involving 23 patients, evaluated impulse compression therapy. At one year there was a mean difference of 1.40 pain units on a visual analogue score (scale 0-10) (95% confidence interval 0.02 to 2.82) in favour of the treated group. The impulse compression group had greater subtalar movement (mean difference 14.0 degrees, 95% confidence interval 3.2 to 24.6) at three months. On average, patients in the impulse compression group returned to work three months earlier than those in the control group. AUTHORS' CONCLUSIONS: Randomised trials of management of calcaneal fractures are few, small and generally of poor quality.Even where there is some evidence of benefit of operative compared with non-operative treatment, it remains unclear whether the possible advantages of surgery are worth its risks. Given this it seems best to wait for the results of one large ongoing trial on open reduction and internal fixation against conservative treatment.One very small trial suggests that impulse compression therapy for intra-articular calcaneal fractures may be beneficial.More large-scale, high quality randomised controlled trials are needed to confirm these results, and to test other interventions in the treatment of calcaneal fractures.

A primary care back pain screening tool: identifying patient subgroups for initial treatment.

OBJECTIVE: To develop and validate a tool that screens for back pain prognostic indicators relevant to initial decision making in primary care. METHODS: The setting was UK primary care adults with nonspecific back pain. Constructs that were independent prognostic indicators for persistence were identified from secondary analysis of 2 existing cohorts and published literature. Receiver operating characteristic curve analysis identified single screening questions for relevant constructs. Psychometric properties of the tool, including concurrent and discriminant validity, internal consistency, and repeatability, were assessed within a new development sample (n = 131) and tool score cutoffs were established to enable allocation to 3 subgroups (low, medium, and high risk). Predictive and external validity were evaluated within an independent external sample (n = 500). RESULTS: The tool included 9 items: referred leg pain, comorbid pain, disability (2 items), bothersomeness, catastrophizing, fear, anxiety, and depression. The latter 5 items were identified as a psychosocial subscale. The tool demonstrated good reliability and validity and was acceptable to patients and clinicians. Patients scoring 0-3 were classified as low risk, and those scoring 4 or 5 on a psychosocial subscale were classified as high risk. The remainder were classified as medium risk. CONCLUSION: We validated a brief screening tool, which is a promising instrument for identifying subgroups of patients to guide the provision of early secondary prevention in primary care. Further work will establish whether allocation to treatment subgroups using the tool, linked with targeting treatment appropriately, improves patient outcomes.

Bacterial [Cu,Zn]-cofactored superoxide dismutase protects opsonized, encapsulated Neisseria meningitidis from phagocytosis by human monocytes/macrophages.

Superoxide dismutase cofactored by copper and zinc ([Cu,Zn]-SOD) contributes to the protection of opsonized serogroup B Neisseria meningitidis against phagocytosis by human monocytes/macrophages, with sodC mutant organisms being endocytosed in significantly higher numbers than are wild-type organisms. The influence of [Cu,Zn]-SOD was found to be exerted at the stage of phagocytosis, rather than at earlier (modulating surface association) or later (intracellular killing) stages.