The performance of FIT-based and other risk prediction models for colorectal neoplasia in symptomatic patients: a systematic review.

Background: Colorectal cancer (CRC) incidence and mortality are increasing internationally. Endoscopy services are under significant pressure with many overwhelmed. Faecal immunochemical testing (FIT) has been advocated to identify a high-risk population of symptomatic patients requiring definitive investigation by colonoscopy. Combining FIT with other factors in a risk prediction model could further improve performance in identifying those requiring investigation most urgently. We systematically reviewed performance of models predicting risk of CRC and/or advanced colorectal polyps (ACP) in symptomatic patients, with a particular focus on those models including FIT. Methods: The review protocol was published on PROSPERO (CRD42022314710). Searches were conducted from database inception to April 2023 in MEDLINE, EMBASE, Cochrane libraries, SCOPUS and CINAHL. Risk of bias of each study was assessed using The Prediction study Risk Of Bias Assessment Tool. A narrative synthesis based on the guidelines for Synthesis Without Meta-Analysis was performed due to study heterogeneity. Findings: We included 62 studies; 23 included FIT (n = 22) or guaiac Faecal Occult Blood Testing (n = 1) combined with one or more other variables. Twenty-one studies were conducted solely in primary care. Generally, prediction models including FIT consistently had good discriminatory ability for CRC/ACP (i.e. AUC >0.8) and performed better than models without FIT although some models without FIT also performed well. However, many studies did not present calibration and internal and external validation were limited. Two studies were rated as low risk of bias; neither model included FIT. Interpretation: Risk prediction models, including and not including FIT, show promise for identifying those most at risk of colorectal neoplasia. Substantial limitations in evidence remain, including heterogeneity, high risk of bias, and lack of external validation. Further evaluation in studies adhering to gold standard methodology, in appropriate populations, is required before widespread adoption in clinical practice. Funding: National Institute for Health and Care Research (NIHR) [Health Technology Assessment Programme (HTA) Programme (Project number 133852).

Assessing Ethnic Inequalities in Diagnostic Interval of Common Cancers: A Population-Based UK Cohort Study.

BACKGROUND: This study investigated ethnic differences in diagnostic interval (DI)-the period between initial primary care presentation and diagnosis. METHODS: We analysed the primary care-linked data of patients who reported features of seven cancers (breast, lung, prostate, colorectal, oesophagogastric, myeloma, and ovarian) one year before diagnosis. Accelerated failure time (AFT) models investigated the association between DI and ethnicity, adjusting for age, sex, deprivation, and morbidity. RESULTS: Of 126,627 eligible participants, 92.1% were White, 1.99% Black, 1.71% Asian, 1.83% Mixed, and 2.36% were of Other ethnic backgrounds. Considering all cancer sites combined, the median (interquartile range) DI was 55 (20-175) days, longest in lung [127, (42-265) days], and shortest in breast cancer [13 (13, 8-18) days]. DI for the Black and Asian groups was 10% (AFT ratio, 95%CI 1.10, 1.05-1.14) and 16% (1.16, 1.10-1.22), respectively, longer than for the White group. Site-specific analyses revealed evidence of longer DI in Asian and Black patients with prostate, colorectal, and oesophagogastric cancer, plus Black patients with breast cancer and myeloma, and the Mixed group with lung cancer compared with White patients. DI was shorter for the Other group with lung, prostate, myeloma, and oesophagogastric cancer than the White group. CONCLUSION: We found limited and inconsistent evidence of ethnic differences in DI among patients who reported cancer features in primary care before diagnosis. Our findings suggest that inequalities in diagnostic intervals, where present, are unlikely to be the sole explanation for ethnic variations in cancer outcomes.

Ethnic inequalities in routes to diagnosis of cancer: a population-based UK cohort study.

BACKGROUND: UK Asian and Black ethnic groups have poorer outcomes for some cancers and are less likely to report a positive care experience than their White counterparts. This study investigated ethnic differences in the route to diagnosis (RTD) to identify areas in patients' cancer journeys where inequalities lie, and targeted intervention might have optimum impact. METHODS: We analysed data of 243,825 patients with 10 cancers (2006-2016) from the RTD project linked to primary care data. Crude and adjusted proportions of patients diagnosed via six routes (emergency, elective GP referral, two-week wait (2WW), screen-detected, hospital, and Other routes) were calculated by ethnicity. Adjusted odds ratios (including two-way interactions between cancer and age, sex, IMD, and ethnicity) determined cancer-specific differences in RTD by ethnicity. RESULTS: Across the 10 cancers studied, most patients were diagnosed via 2WW (36.4%), elective GP referral (23.2%), emergency (18.2%), hospital routes (10.3%), and screening (8.61%). Patients of Other ethnic group had the highest proportion of diagnosis via the emergency route, followed by White patients. Asian and Black group were more likely to be GP-referred, with the Black and Mixed groups also more likely to follow the 2WW route. However, there were notable cancer-specific differences in the RTD by ethnicity. CONCLUSION: Our findings suggest that, where inequalities exist, the adverse cancer outcomes among Asian and Black patients are unlikely to be arising solely from a poorer diagnostic process.

AAHKS Best Podium Presentation Research Award: Femoral Perforation During Direct Anterior Approach Total Hip Arthroplasty: Incidence, Cohort Characteristics, and Management.

BACKGROUND: Cortical perforation during femoral preparation is a recognized complication of total hip arthroplasty (THA) but the incidence, patient characteristics, management, and outcome have not been described for the direct anterior approach (DAA). METHODS: A database query of all primary and conversion DAA THAs performed by a single surgeon from 2009 to 2021 was used to identify hips that sustained a recognized intraoperative femoral perforation. Radiographs were used to assess stem subsidence, Dorr femur type, and Canal Flare Index. RESULTS: Among 3,973 THAs, 16 patients (0.4%) sustained perforations during broaching including 8 males and 8 females with a mean age at surgery of 65.6 (range 41-81) years and a mean body mass index of 31.0 (range 19.0-44.4). Two hips were converted to longer primary cementless stems to bypass the perforation. For the remaining 14, the broach was redirected and the same primary stem was implanted. Limited weight-bearing (6 patients) or protected weight-bearing as tolerated with a walker/cane (10 patients) was advised postoperatively. At a mean follow-up of 18.7 (range 4-105) months, all stems were stable with no fractures, subsidence, or revisions. Factors associated with perforation included difficulty with exposure (body mass index >40 or a contracture), measurable osteoporosis (Canal Flare Index <3.0), and abnormal proximal femoral anatomy due to prior trauma, retained hardware, or Perthes disease. CONCLUSION: In this case series, isolated perforation of an otherwise intact femur during DAA was successfully managed with redirection of the broach, implantation of a primary stem that achieved axial/rotational stability, and protected weight-bearing. LEVEL OF EVIDENCE: IV, Case Series.

No association between breast pain and breast cancer: a prospective cohort study of 10 830 symptomatic women presenting to a breast cancer diagnostic clinic.

BACKGROUND: Women with breast pain constitute >20% of breast clinic attendees. AIM: To investigate breast cancer incidence in women presenting with breast pain and establish the health economics of referring women with breast pain to secondary care. DESIGN AND SETTING: A prospective cohort study of all consecutive women referred to a breast diagnostic clinic over 12 months. METHOD: Women were categorised by presentation into four distinct clinical groups and cancer incidence investigated. RESULTS: Of 10 830 women, 1972 (18%) were referred with breast pain, 6708 (62%) with lumps, 480 (4%) with nipple symptoms, 1670 (15%) with 'other' symptoms. Mammography, performed in 1112 women with breast pain, identified cancer in eight (0.7%). Of the 1972 women with breast pain, breast cancer incidence was 0.4% compared with ∼5% in each of the three other clinical groups. Using 'breast lump' as reference, the odds ratio (OR) of women referred with breast pain having breast cancer was 0.05 (95% confidence interval = 0.02 to 0.09, P<0.001). Compared with reassurance in primary care, referral was more costly (net cost £262) without additional health benefits (net quality-adjusted life-year [QALY] loss -0.012). The greatest impact on the incremental cost-effectiveness ratio (ICER) was when QALY loss because of referral-associated anxiety was excluded. Primary care reassurance no longer dominated, but the ICER remained greater (£45 528/QALY) than typical UK National Health Service cost-effectiveness thresholds. CONCLUSION: This study shows that referring women with breast pain to a breast diagnostic clinic is an inefficient use of limited resources. Alternative management pathways could improve capacity and reduce financial burden.

Primary care use by men with symptoms of possible prostate cancer: A multi-method study with an ethnically diverse sample in London.

OBJECTIVE: The objective of this study is to investigate primary care use by men with recent onset of lower urinary tract symptoms (LUTS) to identify differences in presentation and investigation that may explain ethnic inequality in prostate cancer outcomes. METHODS: This is a multi-method study of men presenting LUTS to primary care. Two hundred seventy-four men completed a self-administered questionnaire, and 23 participated in face-to-face interviews. Regression analyses investigated ethnic differences in (a) the period between symptom onset and first primary care presentation (patient interval) and (b) the interval between first primary care presentation and investigation with prostate-specific antigen (PSA) and digital rectal examination (DRE). Interview data were analysed using thematic analysis. RESULTS: Half (144, 53%) reported a solitary first symptom, although multiple first symptoms were also common, particularly in Asian and Black men. There was no difference between ethnicities in patient interval or time from presentation to investigation. However, Asian men were offered less PSA testing (odds ratio 0.39; 95% confidence interval 0.17-0.92; p = 0.03). Qualitative data revealed ethnic differences in general practitioners' offer of DRE and PSA testing and highlighted limitations in doctor-patient communication and safety netting. CONCLUSION: Our study showed only small differences in primary care experiences, insufficient to explain ethnic inequalities in prostate cancer outcomes.

Targeted encouragement of GP consultations for possible cancer symptoms: a randomised controlled trial.

BACKGROUND: For some common cancers, survival is lower in the UK than in comparable high-income countries. AIM: To assess the effectiveness of a targeted postal intervention (to promote awareness of cancer symptoms and earlier help seeking) on patient consultation rates. DESIGN AND SETTING: A two-arm randomised controlled trial was carried out on patients aged 50-84 years registered at 23 general practices in rural and urban areas of Greater London, Greater Manchester, and the North East of England. METHOD: Patients who had not had a consultation at their general practice in the previous 12 months and had at least two other risk factors for late presentation with cancer were randomised to intervention and control arms. The intervention consisted of a posted letter and leaflet. Primary outcome was the number of consultations at the practice with patients randomised to each arm in the 6 months subsequent to posting the intervention. All patients with outcome data were included in the intention-to-treat analyses. RESULTS: In total, 1513 patients were individually randomised to the intervention (n = 783) and control (n = 730) arms between Nov 2016 - May 2017; outcome data were available for 749 and 705 patients, respectively, with a statistically significantly higher rate of consultation in the intervention arm compared with the control arm: 436 versus 335 consultations (relative risk 1.40, 95% confidence interval = 1.11 to 1.77, P = 0.004). There was, however, no difference in the numbers of patients consulting. CONCLUSION: Targeted interventions of this nature can change behaviour; there is a need to develop interventions that can be more effective at engaging patients with primary care. This study demonstrates that targeted interventions promoting both awareness of possible cancer symptoms and earlier health seeking, can change behaviour. There is a need to develop and test interventions that can be more effective at engaging the most at-risk patients.

Adult Hip and Knee Reconstruction Education during the COVID-19 Pandemic.

BACKGROUND: The COVID-19 pandemic caused an abrupt disruption in residency and fellowship training, with most in-person teaching ceasing in March 2020. The AAHKS (American Association of Hip and Knee Surgeons) Board of Directors quickly initiated an online lecture series named the Fellows Online COVID-19 AAHKS Learning initiative. The purpose of this study is to illustrate the impact that this educational platform had on residents and adult hip and knee reconstruction fellows. METHODS: Between March 31, 2020 and June 25, 2020 an online educational platform was simultaneously developed and delivered. Adult hip and knee reconstruction fellows and residents were invited to participate in the free, live, online education sessions. Faculty from well-respected institutions from around the United States volunteered their time to host the initiative, choosing topics to present, ranging from hip (13 lectures) and knee (9 lectures), to practice management/miscellaneous (12 lectures). Attendee registrations were tracked via the online platform and the maximum number of attendees per session was recorded. A survey was administered to attendees for feedback. RESULTS: Thirty-four, 1-hour virtual lectures were delivered in real time by 79 different faculty members from 20 different institutions. A total of 4746 registrations for the 34 lectures were received, with 2768 registrants (58.3%) attending. The average attendance was 81 viewers per session (range 21-143), with attendance peaking mid-April 2020. A survey administered to lecture participants showed that 104/109 (95.4%) attended live lectures and 93/109 (85.3%) watched recorded sessions. About 92.5% of attendees responded that they wanted the lectures to continue after clinical responsibilities resumed. CONCLUSION: Amid a pandemic with cessation of in-person training, AAHKS delivered a robust virtual training alternative, exposing residents and fellows to a variety of renowned faculty and topics. Attendance with the program was very high, along with continued interest to continue this initiative. These worldwide lectures may lead to future opportunities in virtual residency and fellowship education.

Quantifying the impact of pre-existing conditions on the stage of oesophagogastric cancer at diagnosis: a primary care cohort study using electronic medical records.

BACKGROUND: Pre-existing conditions interfere with cancer diagnosis by offering diagnostic alternatives, competing for clinical attention or through patient surveillance. OBJECTIVE: To investigate associations between oesophagogastric cancer stage and pre-existing conditions. METHODS: Retrospective cohort study using Clinical Practice Research Datalink (CPRD) data, with English cancer registry linkage. Participants aged ≥40 years had consulted primary care in the year before their incident diagnosis of oesophagogastric cancer in 01/01/2010-31/12/2015. CPRD records pre-diagnosis were searched for codes denoting clinical features of oesophagogastric cancer and for pre-existing conditions, including those providing plausible diagnostic alternatives for those features. Logistic regression analysed associations between stage and multimorbidity (≥2 conditions; reference category: no multimorbidity) and having 'diagnostic alternative(s)', controlling for age, sex, deprivation and cancer site. RESULTS: Of 2444 participants provided, 695 (28%) were excluded for missing stage, leaving 1749 for analysis (1265/1749, 72.3% had advanced-stage disease). Multimorbidity was associated with stage [odds ratio 0.63, 95% confidence interval (CI) 0.47-0.85, P = 0.002], with moderate evidence of an interaction term with sex (1.76, 1.08-2.86, P = 0.024). There was no association between alternative explanations and stage (odds ratio 1.18, 95% CI 0.87-1.60, P = 0.278). CONCLUSIONS: In men, multimorbidity is associated with a reduced chance of advanced-stage oesophagogastric cancer, to levels seen collectively for women.

Diagnosing cancer is complicated by existing medical conditions. Diagnosis may be delayed if conditions explain cancer symptoms, or dominate appointments. Diagnosis may be quicker if conditions increase doctor­patient contact. We studied the association between existing illness and stage (early or advanced) of diagnosis with cancer of the stomach or gullet. We studied the primary-care records of patients aged ≥40 years, diagnosed in 01/01/2010­31/12/2015, and got stage from English cancer registry data. We searched the primary-care records for cancer symptoms (e.g. difficulty swallowing), and for 27 conditions that were common or explained cancer symptoms (e.g. difficulty swallowing following a stroke). We analysed cancer stage, looking at age, sex, multimorbidity (two or more conditions) and explanations for symptoms. We studied 1749 patients, of whom 1265 (72.3%) had advanced-stage cancer. The chance of advanced stage was similar in women with (71%, 95% CI 66­75%) or without (69%, 62­76%) multimorbidity. It was lower for men with (70%, 67­74%) than without (79%, 75­83%) multimorbidity. Stage of cancer was not affected by having explanations for cancer symptoms. In summary, for men, multimorbidity is associated with a reduced chance of advanced-stage cancer of the stomach or gullet to levels seen collectively for women.

Economic evaluation of GPs' direct access to computed tomography for identification of brain tumours.

BACKGROUND: When GPs suspect a brain tumour, a referral for specialist assessment and subsequent brain imaging is generally the first option. NICE has recommended that GPs have rapid direct access to brain imaging for adults with progressive sub-acute loss of central nervous function; however, no studies have evaluated the cost-effectiveness. METHODS: We developed a cost-effectiveness model based on data from one region of the UK with direct access computed tomography (DACT), routine data from GP records and the literature, to explore whether unrestricted DACT for patients with suspected brain tumour might be more cost-effective than criteria-based DACT or no DACT. RESULTS: Although criteria-based DACT allows some patients without brain tumour to avoid imaging, our model suggests this may increase costs of diagnosis due to non-specific risk criteria and high costs of diagnosing or 'ruling out' brain tumours by other pathways. For patients diagnosed with tumours, differences in outcomes between the three diagnostic strategies are small. CONCLUSIONS: Unrestricted DACT may reduce diagnostic costs; however, the evidence is not strong and further controlled studies are required. Criteria-based access to CT for GPs might reduce demand for DACT, but imperfect sensitivity and specificity of current risk stratification mean that it will not necessarily be cost-effective.

Cancer diagnostic tools to aid decision-making in primary care: mixed-methods systematic reviews and cost-effectiveness analysis.

BACKGROUND: Tools based on diagnostic prediction models are available to help general practitioners diagnose cancer. It is unclear whether or not tools expedite diagnosis or affect patient quality of life and/or survival. OBJECTIVES: The objectives were to evaluate the evidence on the validation, clinical effectiveness, cost-effectiveness, and availability and use of cancer diagnostic tools in primary care. METHODS: Two systematic reviews were conducted to examine the clinical effectiveness (review 1) and the development, validation and accuracy (review 2) of diagnostic prediction models for aiding general practitioners in cancer diagnosis. Bibliographic searches were conducted on MEDLINE, MEDLINE In-Process, EMBASE, Cochrane Library and Web of Science) in May 2017, with updated searches conducted in November 2018. A decision-analytic model explored the tools' clinical effectiveness and cost-effectiveness in colorectal cancer. The model compared patient outcomes and costs between strategies that included the use of the tools and those that did not, using the NHS perspective. We surveyed 4600 general practitioners in randomly selected UK practices to determine the proportions of general practices and general practitioners with access to, and using, cancer decision support tools. Association between access to these tools and practice-level cancer diagnostic indicators was explored. RESULTS: Systematic review 1 - five studies, of different design and quality, reporting on three diagnostic tools, were included. We found no evidence that using the tools was associated with better outcomes. Systematic review 2 - 43 studies were included, reporting on prediction models, in various stages of development, for 14 cancer sites (including multiple cancers). Most studies relate to QCancer® (ClinRisk Ltd, Leeds, UK) and risk assessment tools. DECISION MODEL: In the absence of studies reporting their clinical outcomes, QCancer and risk assessment tools were evaluated against faecal immunochemical testing. A linked data approach was used, which translates diagnostic accuracy into time to diagnosis and treatment, and stage at diagnosis. Given the current lack of evidence, the model showed that the cost-effectiveness of diagnostic tools in colorectal cancer relies on demonstrating patient survival benefits. Sensitivity of faecal immunochemical testing and specificity of QCancer and risk assessment tools in a low-risk population were the key uncertain parameters. SURVEY: Practitioner- and practice-level response rates were 10.3% (476/4600) and 23.3% (227/975), respectively. Cancer decision support tools were available in 83 out of 227 practices (36.6%, 95% confidence interval 30.3% to 43.1%), and were likely to be used in 38 out of 227 practices (16.7%, 95% confidence interval 12.1% to 22.2%). The mean 2-week-wait referral rate did not differ between practices that do and practices that do not have access to QCancer or risk assessment tools (mean difference of 1.8 referrals per 100,000 referrals, 95% confidence interval -6.7 to 10.3 referrals per 100,000 referrals). LIMITATIONS: There is little good-quality evidence on the clinical effectiveness and cost-effectiveness of diagnostic tools. Many diagnostic prediction models are limited by a lack of external validation. There are limited data on current UK practice and clinical outcomes of diagnostic strategies, and there is no evidence on the quality-of-life outcomes of diagnostic results. The survey was limited by low response rates. CONCLUSION: The evidence base on the tools is limited. Research on how general practitioners interact with the tools may help to identify barriers to implementation and uptake, and the potential for clinical effectiveness. FUTURE WORK: Continued model validation is recommended, especially for risk assessment tools. Assessment of the tools' impact on time to diagnosis and treatment, stage at diagnosis, and health outcomes is also recommended, as is further work to understand how tools are used in general practitioner consultations. STUDY REGISTRATION: This study is registered as PROSPERO CRD42017068373 and CRD42017068375. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology programme and will be published in full in Health Technology Assessment; Vol. 24, No. 66. See the NIHR Journals Library website for further project information.

In the UK, people with cancer tend to die sooner than people with cancer in other European countries. This may be because their cancers are caught at a later stage, perhaps after they have spread. Spotting cancer earlier in people, and testing them sooner, may extend people's lives. Researchers have developed 'diagnostic tools', which give the probability of having cancer, based on a patient's symptoms, blood test results and other information. The tools help family doctors decide who needs further testing for possible cancer, including cancers of the digestive, urinary and reproductive systems, and in the blood. We do not know how many family doctors have these tools, or how well the tools work. We systematically reviewed published studies about how these tools were developed, how good and accurate they are, and what effects their use has on patients. We found that many tools have been developed, but there is little evidence that they improve the quality or length of life. We sent surveys to family doctors all over the UK asking if they had the tools at their practice and if they used them. Based on the replies we received, we estimate that the tools are in about one in three practices. They are likely to be used in about half of the practices where they are available. For practices in England only, we looked for, but did not find, any association between using the tools and the number of urgent appointments made for cancer testing. We used a computer model to show what might happen if family doctors used the tools for patients who have symptoms of bowel cancer. In our model, if general practitioners used the tools, patients would need fewer appointments before they were referred to a specialist. This should reduce the time to diagnosis and treatment, compared with not using the tools. However, there is very little evidence as to whether or not this is indeed the case. Therefore, at the moment, we cannot say whether or not the use of such tools by general practitioners is better for patients and the NHS. More research is needed on what effect these tools have on patients, especially as to whether or not quality and length of life are improved.

Does a "July Effect" Exist for Fellowship Training in Total Hip and Knee Arthroplasty?

BACKGROUND: The hypothetical association between health-care errors and the transition of the medical academic year has been termed the "July effect." Data supporting its existence are conflicting, particularly in orthopedic surgery, and prior studies have inappropriately grouped fellows with resident trainees. No studies to date have examined whether a training initiation effect exists among surgical fellows in adult reconstructive orthopedics. METHODS: This is a level IV retrospective cohort study reviewing 15,650 primary hip and knee arthroplasties performed from 2006 to 2016 at a single institution. Forty arthroplasty fellows were trained during this 10-year period. Primary outcome measures included intraoperative complications, additional procedures, revisions, and nonoperative complications within 90 days of surgery. These complication rates were analyzed by quarter of academic year and by temporal progression through three-month fellowship rotations. RESULTS: There were no differences in intraoperative complication, revision, or nonoperative complication rates between any academic quarter. There was a single statistically lower rate of additional procedures in the third quarter (1.2%) than in the fourth quarter (1.8%, P = .04). The most common complication in this subset was wound dehiscence for patients undergoing hip arthroplasty and stiffness for patients undergoing knee arthroplasty. There was no difference in complication rates during the first, second, or third month as fellows progressed through a single rotation. CONCLUSION: This study does not support the existence of a training-initiation effect among fellows in adult hip and knee reconstruction. Graduated autonomy can be safely employed in a fellowship program without negatively impacting patient outcomes, ensuring the continued high-caliber training of future surgeons.

Development of an intervention to expedite cancer diagnosis through primary care: a protocol.

BACKGROUND: GPs can play an important role in achieving earlier cancer diagnosis to improve patient outcomes, for example through prompt use of the urgent suspected cancer referral pathway. Barriers to early diagnosis include individual practitioner variation in knowledge, attitudes, beliefs, professional expectations, and norms. AIM: This programme of work (Wales Interventions and Cancer Knowledge about Early Diagnosis [WICKED]) will develop a behaviour change intervention to expedite diagnosis through primary care and contribute to improved cancer outcomes. DESIGN & SETTING: Non-experimental mixed-method study with GPs and primary care practice teams from Wales. METHOD: Four work packages will inform the development of the behaviour change intervention. Work package 1 will identify relevant evidence-based interventions (systematic review of reviews) and will determine why interventions do or do not work, for whom, and in what circumstances (realist review). Work package 2 will assess cancer knowledge, attitudes, and behaviour of GPs, as well as primary care teams' perspectives on cancer referral and investigation (GP survey, discrete choice experiment [DCE], interviews, and focus groups). Work package 3 will synthesise findings from earlier work packages using the behaviour change wheel as an overarching theoretical framework to guide intervention development. Work package 4 will test the feasibility and acceptability of the intervention, and determine methods for measuring costs and effects of subsequent behaviour change in a randomised feasibility trial. RESULTS: The findings will inform the design of a future effectiveness trial, with concurrent economic evaluation, aimed at earlier diagnosis. CONCLUSION: This comprehensive, evidence-based programme will develop a complex GP behaviour change intervention to expedite the diagnosis of symptomatic cancer, and may be applicable to countries with similar healthcare systems.

The impact of health literacy on diagnosis and outcomes of symptomatic cancer by ethnicity: a systematic review protocol.

BACKGROUND: Ethnic minorities in multi-ethnic societies like the UK and USA have poorer outcomes for some cancer types when compared with the majority. The causes of ethnic inequalities in cancer outcomes are complex and not fully understood. In particular, the potential role of health literacy on symptomatic presentation and diagnostic interval (the period between first consultation within primary care and definitive diagnosis of cancer) by ethnicity is unknown. Given the increasing need for shared decision-making and patient involvement in the diagnostic process, understanding the potential impact of the differences in health literacy may help redress ethnic inequality in cancer outcomes. The present study aims to critically examine the evidence in this area. METHODS: Seven electronic databases will be searched using keywords and controlled vocabulary related to ethnicity, health literacy, cancer diagnosis and cancer outcomes. Citations and bibliography searches of included studies will be performed to identify relevant studies that have cited eligible articles. Authors of included studies will be contacted to identify unpublished studies. Eligible studies will be restricted to primary cancers. Study quality will be evaluated in using the Critical Appraisal Skills Programme (CASP) checklists. A descriptive summary of selected studies will be presented, and the synthesis will follow a narrative framework. DISCUSSION: This systematic review will summarise the evidence regarding ethnic inequality in health literacy and how this impacts on diagnosis and outcomes of cancer. The review will identify possible areas for future research, and inform clinical practice and interventions to reduce ethnic inequalities in cancer diagnosis and outcomes.

Sex and BMI Alter the Benefits and Risks of Sulfonylureas and Thiazolidinediones in Type 2 Diabetes: A Framework for Evaluating Stratification Using Routine Clinical and Individual Trial Data.

OBJECTIVE: The choice of therapy for type 2 diabetes after metformin is guided by overall estimates of glycemic response and side effects seen in large cohorts. A stratified approach to therapy would aim to improve on this by identifying subgroups of patients whose glycemic response or risk of side effects differs markedly. We assessed whether simple clinical characteristics could identify patients with differing glycemic response and side effects with sulfonylureas and thiazolidinediones. RESEARCH DESIGN AND METHODS: We studied 22,379 patients starting sulfonylurea or thiazolidinedione therapy in the U.K. Clinical Practice Research Datalink (CPRD) to identify features associated with increased 1-year HbA1c fall with one therapy class and reduced fall with the second. We then assessed whether prespecified patient subgroups defined by the differential clinical factors showed differing 5-year glycemic response and side effects with sulfonylureas and thiazolidinediones using individual randomized trial data from ADOPT (A Diabetes Outcome Progression Trial) (first-line therapy, n = 2,725) and RECORD (Rosiglitazone Evaluated for Cardiovascular Outcomes and Regulation of Glycemia in Diabetes) (second-line therapy, n = 2,222). Further replication was conducted using routine clinical data from GoDARTS (Genetics of Diabetes Audit and Research in Tayside Scotland) (n = 1,977). RESULTS: In CPRD, male sex and lower BMI were associated with greater glycemic response with sulfonylureas and a lesser response with thiazolidinediones (both P < 0.001). In ADOPT and RECORD, nonobese males had a greater overall HbA1c reduction with sulfonylureas than with thiazolidinediones (P < 0.001); in contrast, obese females had a greater HbA1c reduction with thiazolidinediones than with sulfonylureas (P < 0.001). Weight gain and edema risk with thiazolidinediones were greatest in obese females; however, hypoglycemia risk with sulfonylureas was similar across all subgroups. CONCLUSIONS: Patient subgroups defined by sex and BMI have different patterns of benefits and risks on thiazolidinedione and sulfonylurea therapy. Subgroup-specific estimates can inform discussion about the choice of therapy after metformin for an individual patient. Our approach using routine and shared trial data provides a framework for future stratification research in type 2 diabetes.

Clinical and cost-effectiveness of progressive exercise compared with best practice advice, with or without corticosteroid injection, for the treatment of rotator cuff disorders: protocol for a 2x2 factorial randomised controlled trial (the GRASP trial).

INTRODUCTION: Shoulder pain is very common, with around 70% of cases due to disorders of the rotator cuff. Despite widespread provision of physiotherapy, there is uncertainty about which type of exercise and delivery mechanisms are associated with best outcomes. There is also uncertainty around the long-term benefits and harms of corticosteroid injection therapy, which is often used in addition to physiotherapy. The Getting it Right: Addressing Shoulder Pain trial will assess the clinical and cost-effectiveness of individually tailored, progressive exercise compared with best practice advice, with or without corticosteroid injection, in adults with a rotator cuff disorder. METHODS AND ANALYSIS: We are conducting a large multicentre randomised controlled trial (2×2 factorial design). We will recruit adults ≥18 years with a new episode of shoulder pain attributable to a rotator cuff disorder as per British Elbow and Shoulder Society guidelines, not currently receiving physiotherapy or being considered for surgery, from at least eight UK National Health Service primary care-based musculoskeletal and related physiotherapy services. Participants (n=704) will be randomised (centralised computer-generated 1:1:1:1 allocation ratio) to one of four interventions: (1) progressive exercise (≤6 physiotherapy sessions); (2) best practice advice (one physiotherapy session); (3) corticosteroid injection then progressive exercise (≤6 sessions) or (4) corticosteroid injection then best practice advice (one session). The primary outcome is the mean difference in Shoulder Pain and Disability Index (SPADI) total score at 12 months. Secondary outcomes are: pain and function SPADI subdomains; health-related quality of life (Five-Level version of the EuroQol EQ-5D-5L); sleep disturbance; return to activity; global impression of change; health resource use; out-of-pocket expenses; work disability. A parallel within-trial economic evaluation will be conducted. The primary analysis will be intention to treat. ETHICS AND DISSEMINATION: Research Ethics Committee approval (REC: 16/SC/0508) has been obtained. Results of the main trial and secondary outcomes will be submitted for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ISRCTN16539266; EudraCT number: 2016-002991-28.

Language from police body camera footage shows racial disparities in officer respect.

Using footage from body-worn cameras, we analyze the respectfulness of police officer language toward white and black community members during routine traffic stops. We develop computational linguistic methods that extract levels of respect automatically from transcripts, informed by a thin-slicing study of participant ratings of officer utterances. We find that officers speak with consistently less respect toward black versus white community members, even after controlling for the race of the officer, the severity of the infraction, the location of the stop, and the outcome of the stop. Such disparities in common, everyday interactions between police and the communities they serve have important implications for procedural justice and the building of police-community trust.

The Role of Ultrasound Compared to Biopsy of Temporal Arteries in the Diagnosis and Treatment of Giant Cell Arteritis (TABUL): a diagnostic accuracy and cost-effectiveness study.

BACKGROUND: Giant cell arteritis (GCA) is a relatively common form of primary systemic vasculitis, which, if left untreated, can lead to permanent sight loss. We compared ultrasound as an alternative diagnostic test with temporal artery biopsy, which may be negative in 9-61% of true cases. OBJECTIVE: To compare the clinical effectiveness and cost-effectiveness of ultrasound with biopsy in diagnosing patients with suspected GCA. DESIGN: Prospective multicentre cohort study. SETTING: Secondary care. PARTICIPANTS: A total of 381 patients referred with newly suspected GCA. MAIN OUTCOME MEASURES: Sensitivity, specificity and cost-effectiveness of ultrasound compared with biopsy or ultrasound combined with biopsy for diagnosing GCA and interobserver reliability in interpreting scan or biopsy findings. RESULTS: We developed and implemented an ultrasound training programme for diagnosing suspected GCA. We recruited 430 patients with suspected GCA. We analysed 381 patients who underwent both ultrasound and biopsy within 10 days of starting treatment for suspected GCA and who attended a follow-up assessment (median age 71.1 years; 72% female). The sensitivity of biopsy was 39% [95% confidence interval (CI) 33% to 46%], which was significantly lower than previously reported and inferior to ultrasound (54%, 95% CI 48% to 60%); the specificity of biopsy (100%, 95% CI 97% to 100%) was superior to ultrasound (81%, 95% CI 73% to 88%). If we scanned all suspected patients and performed biopsies only on negative cases, sensitivity increased to 65% and specificity was maintained at 81%, reducing the need for biopsies by 43%. Strategies combining clinical judgement (clinician's assessment at 2 weeks) with the tests showed sensitivity and specificity of 91% and 81%, respectively, for biopsy and 93% and 77%, respectively, for ultrasound; cost-effectiveness (incremental net monetary benefit) was £485 per patient in favour of ultrasound with both cost savings and a small health gain. Inter-rater analysis revealed moderate agreement among sonographers (intraclass correlation coefficient 0.61, 95% CI 0.48 to 0.75), similar to pathologists (0.62, 95% CI 0.49 to 0.76). LIMITATIONS: There is no independent gold standard diagnosis for GCA. The reference diagnosis used to determine accuracy was based on classification criteria for GCA that include clinical features at presentation and biopsy results. CONCLUSION: We have demonstrated the feasibility of providing training in ultrasound for the diagnosis of GCA. Our results indicate better sensitivity but poorer specificity of ultrasound compared with biopsy and suggest some scope for reducing the role of biopsy. The moderate interobserver agreement for both ultrasound and biopsy indicates scope for improving assessment and reporting of test results and challenges the assumption that a positive biopsy always represents GCA. FUTURE WORK: Further research should address the issue of an independent reference diagnosis, standards for interpreting and reporting test results and the evaluation of ultrasound training, and should also explore the acceptability of these new diagnostic strategies in GCA. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Public health interventions to protect against falsified medicines: a systematic review of international, national and local policies.

BACKGROUND: Falsified medicines are deliberately fraudulent drugs that pose a direct risk to patient health and undermine healthcare systems, causing global morbidity and mortality. OBJECTIVE: To produce an overview of anti-falsifying public health interventions deployed at international, national and local scales in low and middle income countries (LMIC). DATA SOURCES: We conducted a systematic search of the PubMed, Web of Science, Embase and Cochrane Central Register of Controlled Trials databases for healthcare or pharmaceutical policies relevant to reducing the burden of falsified medicines in LMIC. RESULTS: Our initial search identified 660 unique studies, of which 203 met title/abstract inclusion criteria and were categorised according to their primary focus: international; national; local pharmacy; internet pharmacy; drug analysis tools. Eighty-four were included in the qualitative synthesis, along with 108 articles and website links retrieved through secondary searches. DISCUSSION: On the international stage, we discuss the need for accessible pharmacovigilance (PV) global reporting systems, international leadership and funding incorporating multiple stakeholders (healthcare, pharmaceutical, law enforcement) and multilateral trade agreements that emphasise public health. On the national level, we explore the importance of establishing adequate medicine regulatory authorities and PV capacity, with drug screening along the supply chain. This requires interdepartmental coordination, drug certification and criminal justice legislation and enforcement that recognise the severity of medicine falsification. Local healthcare professionals can receive training on medicine quality assessments, drug registration and pharmacological testing equipment. Finally, we discuss novel technologies for drug analysis which allow rapid identification of fake medicines in low-resource settings. Innovative point-of-purchase systems like mobile phone verification allow consumers to check the authenticity of their medicines. CONCLUSIONS: Combining anti-falsifying strategies targeting different levels of the pharmaceutical supply chain provides multiple barriers of protection from falsified medicines. This requires the political will to drive policy implementation; otherwise, people around the world remain at risk.