Novel Irritable Bowel Syndrome Subgroups are Reproducible in the Global Adult Population.

BACKGROUND & AIMS: Current classification systems for irritable bowel syndrome (IBS) based on bowel habit do not consider psychological impact. We validated a classification model in a UK population with confirmed IBS, using latent class analysis, incorporating psychological factors. We applied this model in the Rome Foundation Global Epidemiological Survey (RFGES), assessing impact of IBS on the individual and the health care system, and examining reproducibility. METHODS: We applied our model to 2195 individuals in the RFGES with Rome IV-defined IBS. As described previously, we identified 7 clusters, based on gastrointestinal symptom severity and psychological burden. We assessed demographics, health care-seeking, symptom severity, and quality of life in each. We also used the RFGES to derive a new model, examining whether the broader concepts of our original model were replicated, in terms of breakdown and characteristics of identified clusters. RESULTS: All 7 clusters were identified. Those in clusters with highest psychological burden, and particularly cluster 6 with high overall gastrointestinal symptom severity, were more often female, exhibited higher levels of health care-seeking, were more likely to have undergone previous abdominal surgeries, and had higher symptom severity and lower quality of life (P < .001 for trend for all). When deriving a new model, the best solution consisted of 10 clusters, although at least 2 seemed to be duplicates, and almost all mapped on to the previous clusters. CONCLUSIONS: Even in the community, our original clusters derived from patients with physician-confirmed IBS identified groups of individuals with significantly higher rates of health care-seeking and abdominal surgery, more severe symptoms, and impairments in quality of life.

Demographic and clinical characteristics associated with advanced stage colorectal cancer: a registry-based cohort study in Saudi Arabia.

BACKGROUND: In Saudi Arabia, approximately one-third of colorectal cancer (CRC) patients are diagnosed at an advanced stage. Late diagnosis is often associated with a worse prognosis. Understanding the risk factors for late-stage presentation of CRC is crucial for developing targeted interventions enabling earlier detection and improved patient outcomes. METHODS: We conducted a retrospective cohort study on 17,541 CRC patients from the Saudi Cancer Registry (1997-2017). We defined distant CRCs as late-stage and localized and regional CRCs as early-stage. To assess risk factors for late-stage CRC, we first used multivariable logistic regression, then developed a decision tree to segment regions by late-stage CRC risk, and finally used stratified logistic regression models to examine geographical and sex variations in risk factors. RESULTS: Of all cases, 29% had a late-stage diagnosis, and 71% had early-stage CRC. Young (< 50 years) and unmarried women had an increased risk of late-stage CRC, overall and in some regions. Regional risk variations by sex were observed. Sex-related differences in late-stage rectosigmoid cancer risk were observed in specific regions but not in the overall population. Patients diagnosed after 2001 had increased risks of late-stage presentation. CONCLUSION: Our study identified risk factors for late-stage CRC that can guide targeted early detection efforts. Further research is warranted to fully understand these relationships and develop and evaluate effective prevention strategies.

Supporting Pain Self-Management in Patients With Cancer: App Development Based on a Theoretical and Evidence-Driven Approach.

BACKGROUND: To inform the development of an intervention, it is essential to have a well-developed theoretical understanding of how an intervention causes change, as stated in the UK Medical Research Council guidelines for developing complex interventions. Theoretical foundations are often ignored in the development of mobile health apps intended to support pain self-management for patients with cancer. OBJECTIVE: This study aims to systematically set a theory- and evidence-driven design for a pain self-management app and specify the app's active features. METHODS: The Behavior Change Wheel (BCW) framework, a step-by-step theoretical approach to the development of interventions, was adopted to achieve the aim of this study. This started by understanding and identifying sources of behavior that could be targeted to support better pain management. Ultimately, the application of the BCW framework guided the identification of the active contents of the app, which were characterized using the Behavior Change Technique Taxonomy version 1. RESULTS: The theoretical analysis revealed that patients may have deficits in their capability, opportunity, and motivation that prevent them from performing pain self-management. The app needs to use education, persuasion, training, and enablement intervention functions because, based on the analysis, they were found the most likely to address the specified factors. Eighteen behavior change techniques were selected to describe precisely how the intervention functions can be presented to induce the desired change regarding the intervention context. In other words, they were selected to form the active contents of the app, potentially reducing barriers and serving to support patients in the self-management of pain while using the app. CONCLUSIONS: This study fully reports the design and development of a pain self-management app underpinned by theory and evidence and intended for patients with cancer. It provides a model example of the BCW framework application for health app development. The work presented in this study is the first systematic theory- and evidence-driven design for a pain app for patients with cancer. This systematic approach can support clarity in evaluating the intervention's underlying mechanisms and support future replication.

Associations with Non-Persistence with Intra-Vitreal Therapy for Neovascular Age-Related Macular Degeneration at 24 Months.

AIMS: The aim of the study was to investigate non-persistence with treatment for neovascular age-related macular degeneration (NvAMD) before day 720 (24 months) after initiation, explore associations with baseline characteristics and variation between sites. METHODS: Anonymised demographic and clinical data were extracted from electronic medical records at treating National Health Service (NHS) Trusts for NvAMD eyes starting intra-vitreal therapy from 2017 to 2018. Time to non-persistence with treatment, defined as no recorded attendance for either monitoring or treatment for a period ≥6 months, was visualised with a Kaplan-Meier survival plot. Associations with treatment non-persistence were investigated using a Cox proportional hazards model. RESULTS: Analysis included 7,970 eyes of 7,112 patients treated at 13 NHS trusts. Censoring deaths and those eyes in which treatment was stopped permanently, the Kaplan-Meier analyses demonstrated survival figures of 77.7% for persistence with treatment to day 360 and 71.8% to day 720. Hazard ratios for non-persistence with treatment were reduced at 10 sites, relative to the reference, with first-treated eye status and with baseline acuity worse than or equal to LogMAR 1.0. Hazard ratios increased with younger age, in the presence of other ocular co-morbidities and with baseline acuity better than or equal to LogMAR 0.5. After an episode of non-persistence, visual acuity decreased by at least 0.1 and 0.3 LogMAR in 39% and 18% of eyes, respectively. CONCLUSIONS: Non-persistence with treatment was common, especially in the first year of treatment, and was often associated with a decrease in visual acuity. Treatment site, baseline visual acuity, and age were the strongest predictors of treatment non-persistence before day 720. Understanding and addressing reasons for non-persistence are important to ensure that effective but expensive treatments are used cost-effectively and to maintain acuity. Variation in non-persistence between sites, even after adjustment for other variables, suggests that local factors in treatment provision may be particularly important.

Blood loss and transfusion risk in intramedullary nailing for subtrochanteric fractures.

BACKGROUND: The incidence of hip fractures and subtrochanteric fractures in particular is increasing, along with the globally expanding aging population. Intramedullary nailing remains the 'gold standard' of their treatment. Blood loss can be a result of the original trauma, but also secondary to the subsequent surgical insult, especially during the reaming of the intramedullary canal. OBJECTIVES: The aim of our study was to report on the blood loss and incidence of blood transfusion in patients presenting with a subtrochanteric fracture treated with intramedullary nailing. Most importantly, we aim to identify factors associated with the need for transfusion within the first 48 h post-operatively. METHODS: Following institutional board approval, 431 consecutive patients (131 males; age: 79.03 years old, SD 13.68 years) presenting in a Level 1 Trauma Centre with a subtrochanteric fracture treated with an intramedullary nail were retrospectively identified, over an 8-year period. Exclusion criteria included patients with high energy injuries, pathological fractures, primary operations at other institutions and patients lost to follow-up. To identify risk factors leading to increased risk of transfusion, we first compared patients requiring intra-operative transfusion or transfusion during the first 48 h post-operatively against those who did not require transfusion. This was then followed by multivariate regression analysis adjusted for confounding factors to identify the most important risk factors associated with need for transfusion within the first 48 h post-operatively. RESULTS: Incidence of blood transfusion was 6.0% pre-operatively, compared to 62.7% post-operatively. A total of 230 patients (52.3%) required either intra-operative transfusion or transfusion during the first 48 h following surgery. Patients having a transfusion within the first 48 h post-operatively had a higher incidence of escalation in their care (p = 0.050), LOS (p = 0.015), 30-day (p = 0.033) and one-year mortality (p = 0.004). Multivariate regression analysis adjusted for confounding factors identified that the most important association of a need for transfusion within the first 48 post-operative hours was a pre-operative Hb <100 g/L (OR 6.64); a nail/canal ratio <70% (OR 3.92), followed by need for open reduction (OR 2.66). Fracture involving the lesser trochanter was also implicated with an increased risk (OR 2.08). Additionally, pre-operative moderate/severe renal impairment (OR 4.56), as well as hypoalbuminaemia on admission (OR 2.10) were biochemical predictors of an increased risk of transfusion. Most importantly, the need for transfusion was associated with an increase in 30-day mortality (OR 12.07). CONCLUSION: Several patient, fracture and surgery related factors are implicated with an increased risk for transfusion within the first 48-h post-operatively. Early identification, and where possible correction of these factors can potentially reduce blood loss and risk of transfusion, along with all the associated sequelae and mortality risk. LEVEL OF EVIDENCE: III.

Statistical methods for measuring trends in colorectal cancer incidence in registries: A systematic review.

Background: Monitoring cancer trends in a population is essential for tracking the disease's burden, allocating resources, and informing public health policies. This review describes variations in commonly employed methods to estimate colorectal cancer (CRC) incidence trends. Methods: We performed a systematic literature search in four databases to identify population-based studies reporting CRC incidence trends, published between January 2010 and May 2020. We extracted and described data on methods to estimate trends and assess model validity, and the software used. Results: This review included 145 articles based on studies conducted in five continents. The majority (93%) presented visual summaries of trends combined with absolute, relative, or annual change estimates. Fourteen (10%) articles exclusively calculated the relative change in incidence over a given time interval, presented as the percentage of change in rates. Joinpoint regression analysis was the most commonly used method for assessing incidence trends (n= 65, 45%), providing estimates of the annual percentage change (APC) in rates. Nineteen (13%) studies performed Poisson regression and 18 (12%) linear regression analysis. Age-period-cohort modeling- a type of generalized linear models- was conducted in 18 (12%) studies. Thirty-nine (37%) of the studies modeling incidence trends (n=104, 72%) indicated the method used to evaluate model fitness. The joinpoint program (52%) was the statistical software most commonly used. Conclusion: This review identified variation in the calculation of CRC incidence trends and inadequate reporting of model fit statistics. Our findings highlight the need for increasing clarity and transparency in reporting methods to facilitate interpretation, reproduction, and comparison with findings from previous studies.

Subtrochanteric femoral fractures and intramedullary nailing complications: a comparison of two implants.

INTRODUCTION: Intramedullary (IM) nails are considered the 'gold' standard treatment for subtrochanteric femoral fractures. The incidence and risk factors for re-operation in subtrochanteric fractures remain unclear. Furthermore, no studies have compared the outcomes of different nailing systems used to treat subtrochanteric fractures in the same study population. AIMS/OBJECTIVES: Our study aimed to (i) investigate the cumulative incidence and factors associated with an increased risk of re-operation in subtrochanteric fractures treated with a long intramedullary (IM) nail, (ii) compare the outcomes of subtrochanteric fractures treated with long Affixus and Gamma nails, and (iii) establish whether the addition of a proximal anti-rotation screw in the Affixus nail confers any clinical benefit. METHODS: A retrospective review of all adult patients admitted to a level 1 trauma centre with a subtrochanteric femur fracture treated with a long cephalomedullary IM nail over an 8-year period was conducted. Exclusion criteria were primary surgery performed at another institution, prophylactic nailing because of tumours, incomplete fractures, and patients who were lost to follow-up or died before fracture healing. Data variables were assessed for normality prior to determining the use of either parametric or non-parametric tests. Logistic regression analysis was performed to identify potential factors associated with re-operation. For the comparison between the two nail types, patients were matched into two groups of 119 each by age (10-year intervals), gender and mechanism of injury (low energy, high energy and pathological fractures). A p-value < 0.05 was considered significant. The Kaplan-Meier nail survival curve was used to demonstrate the survival of each nail. Data were analysed using the statistical package R (R version 3.6.0). RESULTS: A total of 309 subtrochanteric fractures were treated with a distally locked long IM nail (re-operation rate: 22.33%) over an 8-year period. Logistic regression identified six factors associated with an increased risk of re-operation, including age < 75 years old, use of a long Gamma nail, pre-injury coxa-vara femoral neck shaft angles, an immediate post-operative reduction angle of > 10° varus, deep wound infection and non-union. Following matching, we compared the two long cephalomedullary nailing systems used (Gamma versus Affixus nail). The only differences identified from the unadjusted analysis were a higher overall incidence of nail failure in Gamma nails due to any cause, re-operation, and impingement of the nail tip distally against the anterior femoral cortex. When we corrected for covariates, no significant differences remained evident between the two nails. From the Kaplan-Meier nail survival curves, however, the Affixus nail demonstrated better survivorship up to 5 years post-implantation in terms of nail failure and re-operation for all causes. Finally, the addition of a proximal anti-rotation screw in the Affixus nail did not seem to confer any benefit. CONCLUSION: We reported a 22.3% re-operation rate in our cohort of subtrochanteric fractures treated with a long IM nail. We have identified six risk factors associated with re-operation: age < 75 years old, pre-injury femoral neck shaft angle, choice of nail, varus reduction angle, fracture-related infection and non-union. The addition of a proximal anti-rotation screw in the Affixus nail did not confer any benefit.

A systematic review of methods to estimate colorectal cancer incidence using population-based cancer registries.

BACKGROUND: Epidemiological studies of incidence play an essential role in quantifying disease burden, resource planning, and informing public health policies. A variety of measures for estimating cancer incidence have been used. Appropriate reporting of incidence calculations is essential to enable clear interpretation. This review uses colorectal cancer (CRC) as an exemplar to summarize and describe variation in commonly employed incidence measures and evaluate the quality of reporting incidence methods. METHODS: We searched four databases for CRC incidence studies published between January 2010 and May 2020. Two independent reviewers screened all titles and abstracts. Eligible studies were population-based cancer registry studies evaluating CRC incidence. We extracted data on study characteristics and author-defined criteria for assessing the quality of reporting incidence. We used descriptive statistics to summarize the information. RESULTS: This review retrieved 165 relevant articles. The age-standardized incidence rate (ASR) (80%) was the most commonly reported incidence measure, and the 2000 U.S. standard population the most commonly used reference population (39%). Slightly more than half (54%) of the studies reported CRC incidence stratified by anatomical site. The quality of reporting incidence methods was suboptimal. Of all included studies: 45 (27%) failed to report the classification system used to define CRC; 63 (38%) did not report CRC codes; and only 20 (12%) documented excluding certain CRC cases from the numerator. Concerning the denominator estimation: 61% of studies failed to state the source of population data; 24 (15%) indicated census years; 10 (6%) reported the method used to estimate yearly population counts; and only 5 (3%) explicitly explained the population size estimation procedure to calculate the overall average incidence rate. Thirty-three (20%) studies reported the confidence interval for incidence, and only 7 (4%) documented methods for dealing with missing data. CONCLUSION: This review identified variations in incidence calculation and inadequate reporting of methods. We outlined recommendations to optimize incidence estimation and reporting practices. There is a need to establish clear guidelines for incidence reporting to facilitate assessment of the validity and interpretation of reported incidence.

Impact of introducing procalcitonin testing on antibiotic usage in acute NHS hospitals during the first wave of COVID-19 in the UK: a controlled interrupted time series analysis of organization-level data.

BACKGROUND: Blood biomarkers have the potential to help identify COVID-19 patients with bacterial coinfection in whom antibiotics are indicated. During the COVID-19 pandemic, procalcitonin testing was widely introduced at hospitals in the UK to guide antibiotic prescribing. We have determined the impact of this on hospital-level antibiotic consumption. METHODS: We conducted a retrospective, controlled interrupted time series analysis of organization-level data describing antibiotic dispensing, hospital activity and procalcitonin testing for acute hospitals/hospital trusts in England and Wales during the first wave of COVID-19 (24 February to 5 July 2020). RESULTS: In the main analysis of 105 hospitals in England, introduction of procalcitonin testing in emergency departments/acute medical admission units was associated with a statistically significant decrease in total antibiotic use of -1.08 (95% CI: -1.81 to -0.36) DDDs of antibiotic per admission per week per trust. This effect was then lost at a rate of 0.05 (95% CI: 0.02-0.08) DDDs per admission per week. Similar results were found specifically for first-line antibiotics for community-acquired pneumonia and for COVID-19 admissions rather than all admissions. Introduction of procalcitonin in the ICU setting was not associated with any significant change in antibiotic use. CONCLUSIONS: At hospitals where procalcitonin testing was introduced in emergency departments/acute medical units this was associated with an initial, but unsustained, reduction in antibiotic use. Further research should establish the patient-level impact of procalcitonin testing in this population and understand its potential for clinical effectiveness.

Should Radiation Exposure be an Issue of Concern in Children With Multiple Trauma?

OBJECTIVE: The aims of this study were 3-fold: first, establish the level of radiation exposure experienced by the pediatric trauma patients; second, model the level of risk of developing fatal carcinogenesis; and third, test whether pattern of injury was predictive of the level of exposure. SUMMARY BACKGROUND DATA: There are certain conditions that cause children to be exposed to increased radiation, that is, scoliosis, where level of radiation exposure is known. The extent that children are exposed to radiation in the context of multiple traumas remains unclear. METHODS: Patients below the age of 16 years and with an Injury Severity Score (ISS) ≥10, treated by a Major Trauma Center for the period January 2008 to December 2018 were identified. The following data were extracted for the year following the patient's injury: number, doses, and type of radiological examination.The sex and age of the patient was taken into account in the calculation of the risk of developing a carcinogenesis. RESULTS: The median radiation dose of the 425 patients identified in the 12 months following injury, through both CT and radiographs, was 24.3 mSv. Modeling the predictive value of pattern of injury and other relevant clinical values, ISS was proportionately predictive of cumulative dose received. CONCLUSION: A proportion of younger polytrauma patients were exposed to high levels of radiation that in turn mean an increased risk of carcinogenesis. However, the ISS, age, injury pattern, and length of hospital stay are predictive of both risks, enabling monitoring and patient advisement of the risks.

Development and Validation of a Post-Operative Non-Union Risk Score for Subtrochanteric Femur Fractures.

BACKGROUND: Our objective was to develop and validate a predictive model for non-union following a subtrochanteric fracture of the femur. METHODS: Following institutional board approval, 316 consecutive patients presenting to our institution (84 non-unions) who fulfilled the inclusion criteria were retrospectively identified. To identify potential unadjusted associations with progression to non-union, simple logistic regression models were used, followed by a revised adjusted model of multiple logistic regression. RESULTS: Having established the risk factors for non-union, the coefficients were used to produce a risk score for predicting non-union. To identify the high-risk patients in the early post-operative period, self-dynamisation was excluded. The revised scoring system was the sum of the following: diabetes (6); deep wound infection (35); simple or severe comminution (13); presence of an atypical fracture (14); lateral cortex gap size ≥5 mm (11), varus malreduction (5-10 degrees) (9); varus malreduction (>10 degrees) (20). On the ROC (receiver operating characteristic) curve, the area under the curve (0.790) demonstrated very good discriminatory capability of the scoring system, with good calibration (Hosmer-Lemeshow test; p = 0.291). Moreover, 5-fold cross validation confirmed good fit of the model and internal validity (accuracy 0.806; Kappa 0.416). The cut-point determined by Youden's formula was calculated as 18. CONCLUSION: This study demonstrates that the risk of non-union can be reliably estimated in patients presenting with a subtrochanteric fracture, from the immediate post-operative period. The resulting non-union risk score can be used not only to identify the high-risk patients early, offering them appropriate consultation and in some cases surgical intervention, but also informs surgeons of the modifiable surgery related factors that contribute to this risk.

Can CRP Levels Predict Infection in Presumptive Aseptic Long Bone Non-Unions? A Prospective Cohort Study.

Nonunion remains a major complication of the management of long bone fractures. The primary aim of the present study was to investigate whether raised levels of C-reactive protein (CRP) and white blood cell count (WBC), in the absence of clinical signs, are correlated with positive intraoperative tissue cultures in presumptive aseptic long-bone nonunions. Infection was classified as positive if any significant growth of microorganisms was observed from bone/tissue samples sent from the theater at the time of revision surgery. Preoperatively all patients were investigated with full blood count, white blood count differential as well as C-reactive protein (CRP). A total of 105 consecutive patients (59 males) were included in the study, with an average age of 46.76 years (range 16-92 years) at the time of nonunion diagnosis. The vast majority were femoral (56) and tibial (37) nonunions. The median time from the index surgical procedure to the time of nonunion diagnosis was 10 months (range 9 months to 10 years). Positive cultures revealed a mixed growth of microorganisms, with coagulase-negative Staphylococcus (56.4%) being the most prevalent microorganism, followed by Staphylococcusaureus (20.5%). Pseudomonas, Methicillin-Resistant Staphylococcus aureus (MRSA), coliforms and micrococcus were present in the remainder of the cases (23.1%). Overall, the risk of infection with normal CRP levels (<10 mg/L) was 21/80 = 0.26. Elevated CRP levels (≥10 mg/L) increased the risk of infection to 0.72. The relative risk given a positive CRP test was RR = 0.72/0.26 = 2.74. Overall, the WBC count was found to be an unreliable marker to predict infection. Solid union was achieved in all cases after an average of 6.5 months (3-24 months) from revision surgery. In patients with presumed aseptic long bone nonunion and normal CRP levels, the risk of underlying low-grade indolent infection can be as high as 26%. Patients should be made aware of this finding, which can complicate their treatment course and outcomes.

What predicts mortality in the elderly patient presenting as a trauma call? A report from a Major Trauma Centre.

PURPOSE: Within the UK there is a continued expansion of the population over the age of 65, this currently accounts for 17.8% of the British population. We review the impact that centralization of Major Trauma has had, as well as analysing for significant predictors of poor outcome. METHOD: All patients presenting to Leeds Major Trauma Centre as a 'Major Trauma' who were equal to or over the age of 65 were included in this study. Prospectively collected data from the Trauma Audit Research Network (TARN) was collated to include the above data set from the 1st April 2012 - 1st April 2016. The 1st April 2012 represents the commencement of the Major Trauma Network within Yorkshire. To allow more quantative assessment of patients' co-morbidities, they were coded as per Charlson Co-morbidity Index for analysis. RESULTS: 1167 patients presented within the above timeframe. Mean age was 79.5 (range 65-103.5). Mean ISS was 14.8 of the entire cohort. Mortality was 12.9% of the entire cohort. The leading mechanisms of injury were from low energy falls <2m-59.89%, Fall >2m-23.05% and Road Traffic Collision - 16.45%. CONCLUSION: Mortality rates since the commencement of the Major Trauma Network within this age group have reduced. This is likely secondary to centralization of major trauma. Variables found to be statistically significant with increased mortality were increasing age, head injury, presence of Chronic Lung Disease, presence of metastases, decreased GCS and increased ISS.

Bedside breath tests in children with abdominal pain: a prospective pilot feasibility study.

BACKGROUND: There is no definitive method of accurately diagnosing appendicitis before surgery. We evaluated the feasibility of collecting breath samples in children with abdominal pain and gathered preliminary data on the accuracy of breath tests. METHODS: We conducted a prospective pilot study at a large tertiary referral paediatric hospital in the UK. We recruited 50 participants with suspected appendicitis, aged between 5 and 15 years. Five had primary diagnosis of appendicitis. The primary outcome was the number of breath samples collected. We also measured the number of samples processed within 2 h and had CO2 ≥ 3.5%. Usability was assessed by patient-reported pain pre- and post-sampling and user-reported sampling difficulty. Logistic regression analysis was used to predict appendicitis and evaluated using the area under the receiver operator characteristic curve (AUROC). RESULTS: Samples were collected from all participants. Of the 45 samples, 36 were processed within 2 h. Of the 49 samples, 19 had %CO2 ≥ 3.5%. No difference in patient-reported pain was observed (p = 0.24). Sampling difficulty was associated with patient age (p = 0.004). The logistic regression model had AUROC = 0.86. CONCLUSIONS: Breath tests are feasible and acceptable to patients presenting with abdominal pain in clinical settings. We demonstrated adequate data collection with no evidence of harm to patients. The AUROC was better than a random classifier; more specific sensors are likely to improve diagnostic performance. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03248102. Registered 14 Aug 2017.

Defective Proliferation and Osteogenic Potential with Altered Immunoregulatory phenotype of Native Bone marrow-Multipotential Stromal Cells in Atrophic Fracture Non-Union.

Bone marrow-Multipotential stromal cells (BM-MSCs) are increasingly used to treat complicated fracture healing e.g., non-union. Though, the quality of these autologous cells is not well characterized. We aimed to evaluate bone healing-related capacities of non-union BM-MSCs. Iliac crest-BM was aspirated from long-bone fracture patients with normal healing (U) or non-united (NU). Uncultured (native) CD271highCD45low cells or passage-zero cultured BM-MSCs were analyzed for gene expression levels, and functional assays were conducted using culture-expanded BM-MSCs. Blood samples were analyzed for serum cytokine levels. Uncultured NU-CD271highCD45low cells significantly expressed fewer transcripts of growth factor receptors, EGFR, FGFR1, and FGRF2 than U cells. Significant fewer transcripts of alkaline phosphatase (ALPL), osteocalcin (BGLAP), osteonectin (SPARC) and osteopontin (SPP1) were detected in NU-CD271highCD45low cells. Additionally, immunoregulation-related markers were differentially expressed between NU- and U-CD271highCD45low cells. Interestingly, passage-zero NU BM-MSCs showed low expression of immunosuppressive mediators. However, culture-expanded NU and U BM-MSCs exhibited comparable proliferation, osteogenesis, and immunosuppression. Serum cytokine levels were found similar for NU and U groups. Collectively, native NU-BM-MSCs seemed to have low proliferative and osteogenic capacities; therefore, enhancing their quality should be considered for regenerative therapies. Further research on distorted immunoregulatory molecules expression in BM-MSCs could potentially benefit the prediction of complicated fracture healing.

Patient and implant survival following intraoperative periprosthetic femoral fractures during primary total hip arthroplasty: an analysis from the national joint registry for England, Wales, Northern Ireland and the Isle of Man.

AIMS: We compared implant and patient survival following intraoperative periprosthetic femoral fractures (IOPFFs) during primary total hip arthroplasty (THA) with matched controls. PATIENTS AND METHODS: This retrospective cohort study compared 4831 hips with IOPFF and 48 154 propensity score matched primary THAs without IOPFF implanted between 2004 and 2016, which had been recorded on a national joint registry. Implant and patient survival rates were compared between groups using Cox regression. RESULTS: Ten-year stem survival was worse in the IOPFF group (p < 0.001). Risk of revision for aseptic loosening increased 7.2-fold following shaft fracture and almost 2.8-fold after trochanteric fracture (p < 0.001). Risk of periprosthetic fracture of the femur revision increased 4.3-fold following calcar-crack and 3.6-fold after trochanteric fracture (p < 0.01). Risk of instability revision was 3.6-fold after trochanteric fracture and 2.4-fold after calcar crack (p < 0.001). Risk of 90-day mortality following IOPFF without revision was 1.7-fold and 4.0-fold after IOPFF with early revision surgery versus uncomplicated THA (p < 0.001). CONCLUSION: IOPFF increases risk of stem revision and mortality up to ten years following surgery. The risk of revision depends on IOPFF subtype and mortality risk increases with subsequent revision surgery. Surgeons should carefully diagnose and treat IOPFF to minimize fracture progression and implant failure. Cite this article: Bone Joint J 2019;101-B:1199-1208.

Risk Factors for Intraoperative Periprosthetic Femoral Fractures During Primary Total Hip Arthroplasty. An Analysis From the National Joint Registry for England and Wales and the Isle of Man.

BACKGROUND: The aim of this study is to estimate risk factors for intraoperative periprosthetic femoral fractures (IOPFF) and each anatomic subtype (calcar crack, trochanteric fracture, femoral shaft fracture) during primary total hip arthroplasty. METHODS: This retrospective cohort study included 793,823 primary total hip arthroplasties between 2004 and 2016. Multivariable regression modeling was used to estimate relative risk of patient, surgical, and implant factors for any IOPFF and for all anatomic subtypes of IOPFF. Clinically important interactions were assessed using multivariable regression. RESULTS: Patient factors significantly increasing the risk of fracture were female gender, American Society of Anesthesiologists grade 3 to 5, and preoperative diagnosis including avascular necrosis of the hip, previous trauma, inflammatory disease, pediatric disease, and previous infection. Overall risk of IOPFF associated with age was greatest in patients below 50 years and above 80 years. Risk of any fracture reduced with computer-guided surgery and in non-National Health Service hospitals. Nonposterior approaches increased the risk of shaft and trochanteric fracture only. Cementless implants significantly increased the risk of only calcar cracks and shaft fractures and not trochanteric fractures. CONCLUSION: Fracture risk increases in patients younger than 50 and older than 80 years, females, American Society of Anesthesiologists grade 3 to 5, and indications other than primary osteoarthritis. Large cumulative reduction in IOPFF risk may occur with use of cemented implants, posterior approach, and computer-guided surgery. LEVEL OF EVIDENCE: Level 3b (cohort study).

Towards UK poSt Arthroplasty Follow-up rEcommendations (UK SAFE): protocol for an evaluation of the requirements for arthroplasty follow-up, and the production of consensus-based recommendations.

INTRODUCTION: Hip and knee arthroplasties have revolutionised the management of degenerative joint diseases and, due to an ageing population, are becoming increasingly common. Follow-up of joint prostheses is to identify problems in symptomatic or asymptomatic patients due to infection, osteolysis, bone loss or potential periprosthetic fracture, enabling timely intervention to prevent catastrophic failure at a later date. Early revision is usually more straight-forward surgically and less traumatic for the patient. However, routine long-term follow-up is costly and requires considerable clinical time. Therefore, some centres in the UK have curtailed this aspect of primary hip and knee arthroplasty services, doing so without an evidence base that such disinvestment is clinically or cost-effective. METHODS: Given the timeline from joint replacement to revision, conducting a randomised controlled trial (RCT) to determine potential consequences of disinvestment in hip and knee arthroplasty follow-up is not feasible. Furthermore, the low revision rates of modern prostheses, less than 10% at 10 years, would necessitate thousands of patients to adequately power such a study. The huge variation in follow-up practice across the UK also limits the generalisability of an RCT. This study will therefore use a mixed-methods approach to examine the requirements for arthroplasty follow-up and produce evidence-based and consensus-based recommendations as to how, when and on whom follow-up should be conducted. Four interconnected work packages will be completed: (1) a systematic literature review; (2a) analysis of routinely collected National Health Service data from five national data sets to understand when and which patients present for revision surgery; (2b) prospective data regarding how patients currently present for revision surgery; (3) economic modelling to simulate long-term costs and quality-adjusted life years associated with different follow-up care models and (4) a Delphi-consensus process, involving all stakeholders, to develop a policy document which includes a stratification algorithm to determine appropriate follow-up care for an individual patient. ETHICS AND DISSEMINATION: Favourable ethical opinion has been obtained for WP2a (RO-HES) (220520) and WP2B (220316) from the National Research Ethics Committee. Following advice from the Confidentiality Advisory Group (17/CAG/0122), data controllers for the data sets used in WP2a (RO-HES) - NHS Digital and The Phoenix Partnership - confirmed that Section 251 support was not required as no identifiable data was flowing into or out of these parties. Application for approval of WP2a (RO-HES) from the Independent Group Advising on the Release of Data (IGARD) at NHS Digital is in progress (DARS-NIC-147997). Section 251 support (17/CAG/0030) and NHS Digital approval (DARS-NIC-172121-G0Z1H-v0.11) have been obtained for WP2a (NJR-HES-PROMS). ISAC (11_050MnA2R2) approval has been obtained for WP2a (CPRD-HES).

PROMs for Pain in Adult Cancer Patients: A Systematic Review of Measurement Properties.

CONTEXT: Pain is one of the most devastating symptoms for cancer patients. One third of patients who experience pain do not receive effective treatment. A key barrier to effective pain management is lack of routine measurement and monitoring of pain. Patient-reported outcome measures (PROMs) are recommended for measuring cancer pain. However, evidence to guide the selection of the most appropriate measure to identify and monitor cancer pain is limited. A systematic review of measurement properties of PROMs for pain in cancer patients is needed to identify the best validated measure for adoption to an electronic platform. OBJECTIVES: To systematically review measurement properties of PROMs used for adult cancer patients to measure pain and, as a secondary goal, to investigate the evidence of validated mobile health (mHealth) applications used to measure pain (registration number: CRD42017065575). METHODS: Medline, Embase, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) were systematically searched in March 2018 for studies examining measurement properties for PROMs for pain in adult cancer patients. The methodological quality of the studies and their results were appraised using the Consensus-based Standards for the Selection of Health Measurement Instruments (COSMIN) checklist and specific measurement properties criteria, respectively. RESULTS: Sixteen studies evaluating 8 instruments were included. No studies using a PROM in an mHealth application were identified. The methodological quality of the measurement properties ranged between poor and fair. No instrument showed strong positive evidence for all the evaluated measurement properties. Based on the available evidence, the Brief Pain Inventory-Short Form (BPI-SF) had the strongest evidence to support its selection for the measurement of cancer pain. CONCLUSION: The BPI-SF was the best performing measure across all properties evaluated through COSMIN. Better quality validation studies of PROMs for cancer pain are needed to explore the full range of measurement properties. Utilizing mHealth applications to measure pain in cancer patients is an innovative approach worthy of further investigation.