Temporal Trends in Surgical Resection Rates and Biologic Prescribing in Crohn's Disease: A Population-based Cohort Study.

BACKGROUND: The use of biologic therapy for Crohn's disease [CD] continues to evolve, however, the effect of this on the requirement for surgery remains unclear. We assessed changes in biologic prescription and surgery over time in a population-based cohort. METHODS: We performed a retrospective cohort study of all 1753 patients diagnosed with CD in Lothian, Scotland, between January 1, 2000 and December 31, 2017, reviewing the electronic health record of each patient to identify all CD-related surgery and biologic prescription. Cumulative probability and hazard ratios for surgery and biologic prescription from diagnosis were calculated and compared using the log-rank test and Cox regression analysis stratified by year of diagnosis into cohorts. RESULTS: The 5-year cumulative risk of surgery was 20.4% in cohort 1 [2000-2004],18.3% in cohort 2 [2005-2008], 14.7% in cohort 3 [2009-2013], and 13.0% in cohort 4 [2014-2017] p <0.001. The 5-year cumulative risk of biologic prescription was 5.7% in cohort 1, 12.2% in cohort 2, 22.0% in cohort 3, and 44.9% in cohort 4 p <0.001. CONCLUSIONS: The increased and earlier use of biologic therapy in CD patients corresponded with a decreasing requirement for surgery over time within our cohort. This could mean that adopting a top-down or accelerated step-up treatment strategy may be effective at reducing the requirement for surgery in newly diagnosed CD.

Towards precision dosing of vancomycin in critically ill patients: an evaluation of the predictive performance of pharmacometric models in ICU patients.

OBJECTIVES: Vancomycin dose recommendations depend on population pharmacokinetic models. These models have not been adequately assessed in critically ill patients, who exhibit large pharmacokinetic variability. This study evaluated model predictive performance in intensive care unit (ICU) patients and identified factors influencing model performance. METHODS: Retrospective data from ICU adult patients administered vancomycin were used to evaluate model performance to predict serum concentrations a priori (no observed concentrations included) or with Bayesian forecasting (using concentration data). Predictive performance was determined using relative bias (rBias, bias) and relative root mean squared error (rRMSE, precision). Models were considered clinically acceptable if rBias was between ±20% and 95% confidence intervals included zero. Models were compared with rRMSE; no threshold was used. The influence of clinical factors on model performance was assessed with multiple linear regression. RESULTS: Data from 82 patients were used to evaluate 12 vancomycin models. The Goti model was the only clinically acceptable model with both a priori (rBias 3.4%) and Bayesian forecasting (rBias 1.5%) approaches. Bayesian forecasting was superior to a priori prediction, improving with the use of more recent concentrations. Four models were clinically acceptable with Bayesian forecasting. Renal replacement therapy status (p < 0.001) and sex (p = 0.007) significantly influenced the performance of the Goti model. CONCLUSIONS: The Goti, Llopis and Roberts models are clinically appropriate to inform vancomycin dosing in critically ill patients. Implementing the Goti model in dose prediction software could streamline dosing across both ICU and non-ICU patients, considering it is also the most accurate model in non-ICU patients.

Age and sex-related decline of muscle strength across the adult lifespan: a scoping review of aggregated data.

Muscle strength is sex-related and declines with advancing age; yet, a comprehensive comparative evaluation of age-related strength loss in human females and males has not been undertaken. To do so, segmented piecewise regression analysis was performed on aggregated data from studies published from 1990 to 2018 and are available in CINAHL, EMBASE, MEDLINE, and PsycINFO databases. The search identified 5613 articles that were reviewed for physical assessment results stratified by sex and age. Maximal isometric and isokinetic 60°·s-1 knee extension (KE) and knee flexion (KF) contractions from 57 studies and 15 283 subjects (N = 7918 females) had sufficient data reported on females and males for meaningful statistical evaluation to be undertaken. The analysis revealed that isometric KE and KF strength undergo similar rapid declines in both sexes late in the sixth decade of life. Yet, there is an abrupt age-related decline in KE 60°·s-1 peak torque earlier in females (aged 41.8 years) than males (aged 66.7 years). In the assessment of KF peak torque, an age-related acceleration in strength loss was only identified in males (aged 49.3 years). The results suggest that age-related isometric strength loss is similar between sexes while the characteristics of KE and KF peak torque decline are sex-related, which likely explains the differential rate of age-related functional decline. Novelty Inclusion of muscle strength and torque of KE and KF data from >15 000 subjects. Isometric KE and KF strength loss are similar between sexes. Isokinetic 60°·s-1 KE torque decline accelerates 25 years earlier in females and female age-related KF peak torque decline does not accelerate with age.

Real-world Effectiveness and Safety of Vedolizumab for the Treatment of Inflammatory Bowel Disease: The Scottish Vedolizumab Cohort.

BACKGROUND & AIMS: Vedolizumab is an anti-a4b7 monoclonal antibody that is licensed for the treatment of moderate to severe Crohn's disease and ulcerative colitis. The aims of this study were to establish the real-world effectiveness and safety of vedolizumab for the treatment of inflammatory bowel disease. METHODS: This was a retrospective study involving seven NHS health boards in Scotland between June 2015 and November 2017. Inclusion criteria included: a diagnosis of ulcerative colitis or Crohn's disease with objective evidence of active inflammation at baseline (Harvey-Bradshaw Index[HBI] ≥5/Partial Mayo ≥2 plus C-reactive protein [CRP] >5 mg/L or faecal calprotectin ≥250 µg/g or inflammation on endoscopy/magnetic resonance imaging [MRI]); completion of induction; and at least one clinical follow-up by 12 months. Kaplan-Meier survival analysis was used to establish 12-month cumulative rates of clinical remission, mucosal healing, and deep remission [clinical remission plus mucosal healing]. Rates of serious adverse events were described quantitatively. RESULTS: Our cohort consisted of 180 patients with ulcerative colitis and 260 with Crohn's disease. Combined median follow-up was 52 weeks (interquartile range [IQR] 26-52 weeks). In ulcerative colitis, 12-month cumulative rates of clinical remission, mucosal healing, and deep remission were 57.4%, 47.3%, and 38.5%, respectively. In Crohn's disease, 12-month cumulative rates of clinical remission, mucosal healing, and deep remission were 58.4%, 38.9%, and 28.3% respectively. The serious adverse event rate was 15.6 per 100 patient-years of follow-up. CONCLUSIONS: Vedolizumab is a safe and effective treatment for achieving both clinical remission and mucosal healing in ulcerative colitis and Crohn's disease.

Faecal Calprotectin and Magnetic Resonance Enterography in Ileal Crohn's Disease: Correlations Between Disease Activity and Long-Term Follow-Up.

BACKGROUND AND AIMS: Magnetic resonance enterography [MRE] is the gold standard for assessing ileal inflammation in Crohn's disease [CD]. The aim of the present study was to correlate faecal calprotectin [FC] to MRE via a simple score in an exclusive ileal cohort with long-term follow-up for association with time to surgery or biologic therapy. METHODS: In total, 150 MRE studies with matched FC [±30 days] were identified from the Edinburgh FC Register [2008-12; n = 18138]. Scans were re-read blinded to clinical data, independently, by two expert gastrointestinal radiologists, to generate a simple MRE score [range 0-10] from assessment of the worst intestinal segment plus total disease extent. RESULTS: In total, 119 MRE scans were evaluated from 104 patients with ileal CD [L1 or L3 with panproctocolectomy]. Receiver operating characteristic analysis showed an area under the curve of 0.77 [0.67-0.87, p < 0.0001] for FC and MRE score >1, with an optimal cut-off of 145 µg/g for severe inflammation on MRE with 69.3% [57.6-79.5] sensitivity and 71.4% [53.7-85.4] specificity. Long-term follow-up over a median [interquartile range] of 2086 days [1786-2353] revealed FC ≥ 145 µg/g was associated with reduced biologic-free survival until 3 years following MRE, whereas MRE score [severe vs absent] was associated with reduced surgery- and biologic-free survival throughout follow-up. Backwards stepwise logistic regression revealed that length of ileal disease (odds ratio [OR] 3.8, 1.1-13.2, p = 0.034) and increased bowel wall thickness at MRE [OR 4.2, 1.6-10.7, p < 0.0001] or female sex [OR 5.2, 1.5-18.7, p = 0.011] increased the risk of biologic use or surgery, respectively. CONCLUSIONS: FC correlates well with MRE assessment of ileal CD with MRE parameters associated with long-term biologic- and surgery-free remission.

Chromatic techniques for in vivo monitoring jaundice in neonate tissues.

OBJECTIVE: A chromatic method is described for providing a preliminary indication of unacceptable bilirubin levels in a newly born baby in order to avoid the development of serious mental deficiencies. The aim was to investigate the reliability of a new chromatic approach using a novel template unit for a preliminary, non-invasive monitoring of the skin tissue of newly born babies with jaundice and its capability for use with different mobile phone cameras. APPROACH: A description of the monitoring system is given along with an explanation of the monitoring technique used. Preliminary tests have been performed on 48 different neonates each being addressed by one of six different mobile phone cameras, which were randomly available to the operating clinicians. MAIN RESULTS: The test results have a correlation (R 2) of 0.81, a sensitivity (Sn) of 0.97, a specificity (Sp) of 0.82, a positive predictive value (PPV) of 0.95 and a negative predictive value (NPV) of 0.9. SIGNIFICANCE: The significance of the results obtained is that they show the approach to have a high level of fail-safe reliability in indicating the bilirubin levels when compared with blood test results. The results also show that the approach can be used with a few different mobile phone cameras and that because of its non-invasive nature and its cost effectiveness, has the potential for remote use from a medical hospital to provide an immediate preliminary diagnosis.

Bilirubin concentration is positively associated with haemoglobin concentration and inversely associated with albumin to creatinine ratio among Indigenous Australians: eGFR Study.

Low serum bilirubin concentrations are reported to be strongly associated with cardio-metabolic disease, but this relationship has not been reported among Indigenous Australian people who are known to be at high risk for diabetes and chronic kidney disease (CKD). HYPOTHESIS: serum bilirubin will be negatively associated with markers of chronic disease, including CKD and anaemia among Indigenous Australians. METHOD: A cross-sectional analysis of 594 adult Aboriginal and Torres Strait Islander (TSI) people in good health or with diabetes and markers of CKD. Measures included urine albumin: creatinine ratio (ACR), estimated glomerular filtration rate (eGFR), haemoglobin (Hb) and glycated haemoglobin (HbA1c). Diabetes was defined by medical history, medications or HbA1c≥6.5% or ≥48mmol/mol. Anaemia was defined as Hb<130g/L or <120g/L in males and females respectively. A multivariate regression analysis examining factors independently associated with log-bilirubin was performed. RESULTS: Participants mean (SD) age was 45.1 (14.5) years, and included 62.5% females, 71.7% Aboriginal, 41.1% with diabetes, 16.7% with anaemia, 41% with ACR>3mg/mmol and 18.2% with eGFR<60mL/min/1.73m2. Median bilirubin concentration was lower in females than males (6 v 8µmol/L, p<0.001) and in Aboriginal than TSI participants (6 v 9.5µmol/L, p<0.001). Six factors explained 35% of the variance of log-bilirubin; Hb and cholesterol (both positively related) and ACR, triglycerides, Aboriginal ethnicity and female gender (all inversely related). CONCLUSION: Serum bilirubin concentrations were positively associated with Hb and total cholesterol, and inversely associated with ACR. Further research to determine reasons explaining lower bilirubin concentrations among Aboriginal compared with TSI participants are needed.

Physical activity levels of community-dwelling older adults are influenced by winter weather variables.

Winter weather conditions may negatively influence participation of older adults in daily physical activity (PA). OBJECTIVE: Assess the influence of winter meteorological variables, day-time peak ambient temperature, windchill, humidity, and snow accumulation on the ground to accelerometer measured PA values in older adults. METHODS: 50 community-dwelling older adults (77.4±4.7yrs; range 71-89; 12 females) living in Southwestern Ontario (Latitude 42.9°N Longitude 81.2° W) Canada, wore a waist-borne accelerometer during active waking hours (12h) for 7 consecutive days between February and April 2007. Hourly temperature, windchill, humidity, and snowfall accumulation were obtained from meteorological records and time locked to hourly accelerometer PA values. CONCLUSIONS: Regression analysis revealed significant relationships between time of day, ambient daytime high temperature and a humidity for participation in PA. Windchill temperature added no additional influence over PA acclamation already influenced by ambient day-time temperature and the observed variability in PA patterns relative to snow accumulation over the study period was too great to warrant its inclusion in the model. Most PA was completed in the morning hours and increased as the winter month's transitioned to spring (February through April). PRACTICE: An equation was developed to adjust for winter weather conditions using temperature, humidity and time of day. IMPLICATIONS: Accurate PA assessment during the winter months must account for the ambient daytime high temperatures, humidity, and time of day. These older adults were more physically active during the morning hours and became more active as the winter season transitioned to spring.

Stretch training induces unequal adaptation in muscle fascicles and thickness in medial and lateral gastrocnemii.

This study compared adaptations in fascicle lengths, pennation angles, and muscle thickness of the lateral and medial gastrocnemii in response to 6 weeks of stretch training. The nondominant plantar flexors of 11 males were stretched five times per week for 6 weeks and compared with the contralateral leg and a nonstretched control group of 10 males. During stretch training, instantaneous electromyography was utilized to ensure passive muscle stretch. At baseline, week three, week six and 1 week after the conclusion of stretch training, ultrasound was used to measure fascicle lengths, pennation angles, muscle thickness of the lateral gastrocnemius and medial gastrocnemius, and Achilles tendon thickness and length. Plantar flexion torque was measured, and voluntary activation was assessed. Muscle thickness increased 5.6% after 6 weeks of stretch training (P=.009). The fascicles in the lateral gastrocnemius lengthened to a greater extent than the medial. Overall, fascicles lengthened 25% (P<.001) in the muscle tendon junction and 5.1% (P<.001) in the muscle belly. Pennation angles were unchanged in the medial gastrocnemius but decreased in the lateral gastrocnemius 7.1% (P=.02). There was no change in maximal voluntary contraction, voluntary activation, tendon length, or thickness. This study demonstrates that stretch training is a viable modality to alter muscle architecture of the human gastrocnemius through lengthening of muscle fascicles, decreasing pennation angles, and increasing muscle thickness, albeit adaptations are unequal between the lateral and medial heads.

EMG Functional tasks recordings determines frailty phenotypes in males and females.

BACKGROUND: Identification of frailty is essential to understanding and mitigating age-related physical impairments. Previous studies have indicated that frailty phenotype can be identified through electromyography (EMG) when collected over the course of an 8-h day. However, long duration recordings challenge both the clinician and the older adults but activities of daily living that are most sensitive to changes in frailty status are currently unknown. The purpose of this study was to determine if muscle activity recorded during specific task, or groups of tasks, could be used to correctly classify middle-aged, non-frail, pre-frail, and frail older adult pheonotypes. METHODS: Fifteen middle-aged (49 ± 5 years) and 76 older adults (77 ± 8 years) participated. Older adults were categorized as non-frail (n = 49), pre-frail (n = 20), or frail (n = 7) using self-selected normal gait speed and a modified frailty index score. Bursts and gaps in EMG of the biceps brachii, triceps brachii, vastus lateralis, and biceps femoris were measured bilaterally during nine different functional tasks. RESULTS: Relatively high levels of success for frailty group classification (near 90%) can be achieved from EMG. Bursts were more frequent and gaps fewer in frail compared with middle-aged and non-frail adults. The numbers of gaps and muscle quiescence in the upper limbs were particularly important. Changes in muscle activity offer predictive value in identifying frailty phenotype. Completing functional tasks (rising from the floor, toilet and chair) while undergoing EMG assessment can contribute to the identification of differences in frailty phenotype among older adults.

How is income generated by outpatient parenteral antibiotic treatment (OPAT) in the UK? Analysis of payment tariffs for cellulitis.

OBJECTIVES: We determined the available mechanisms to generate income from outpatient parenteral antimicrobial therapy (OPAT) in the UK and calculated the revenue generated from treatment of an episode of cellulitis. METHODS: Revenue was calculated for patients receiving treatment for cellulitis as an inpatient and for patients receiving OPAT by a series of different payment pathways. Selected established OPAT services in Northern Ireland, Scotland and Wales, where Payment-by-Results (PbR) does not operate, were contacted to determine individual national funding arrangements. RESULTS: In England, a traditional inpatient episode for uncomplicated cellulitis requiring 7 days of treatment generated £1361 of revenue, while OPAT generated revenue ranging from £773 to £2084 for the same length of treatment depending on the payment pathway used. Treatment using OPAT to avoid admission entirely generated £2084, inpatient admission followed by transfer to a virtual OPAT ward at day 2 generated £1361 and inpatient admission followed by discharge from hospital to OPAT at day 2 generated £773. In Northern Ireland, Scotland and Wales block contracts were used and no income was calculable for an individual episode of cellulitis. CONCLUSIONS: No single funding mechanism supports OPAT across the UK. In England, revenue generated by OPAT providers from treatment of cellulitis varied with the OPAT payment pathway used, but equalled or exceeded the income generated from equivalent inpatient care. Cost savings for OPAT and reuse of released inpatient beds will increase revenue further. A single OPAT tariff is proposed.

Precision high-value resistance scaling with a two-terminal cryogenic current comparator.

We describe a cryogenic two-terminal high-resistance bridge and its application in precision resistance scaling from the quantized Hall resistance (QHR) at RH = RK/2 = 12 906.4035 Ω to decade resistance standards with values between 1 MΩ and 1 GΩ. The design minimizes lead resistance errors with multiterminal connections to the QHR device. A single variable voltage source and resistive ratio windings are utilized to achieve excellent dynamic stability, which is not readily obtained in low-current measurements with conventional cryogenic current comparators (CCCs). Prototypes of this bridge have been verified by a successful international comparison of high-resistance scaling using two-terminal CCCs in the national metrology institutes of Argentina, Mexico, and the United States.

A portable system for identifying urinary tract infection in primary care using a PC-based chromatic technique.

An approach is described for monitoring urine samples using a portable system based on chromatic techniques and for predicting urinary tract infection (UTI) from the results. The system uses a webcam-computer combination with the screen of a computer visual display unit as a tuneable illumination source. It is shown that the system can operate in a robust manner under ambient lighting conditions and with potential for use as a point of care test in primary care. The present approach combines information on urine liquid concentration and turbidity. Its performance in an exploratory study is compared with microbiological culture of 200 urine samples, of which 79 had bacterial growth >10(5) colony forming unit/millilitre (cfu ml(-1)) indicative of UTI. It is shown that both sensitivity and negative predictive value of 0.92 could be achieved.

Systematic review: The use of thiopurines or anti-TNF in post-operative Crohn's disease maintenance--progress and prospects.

BACKGROUND: Post-operative recurrence of Crohn's disease is an important management challenge, with 2-year recurrence rates defined by clinical, endoscopic and radiological parameters of up to 77%, 64% and 49%. Clinical and severe endoscopic recurrence vary widely in controlled trials from 13% to 36% and 22% to 56% with thiopurine treatment or 0% and 9% with infliximab treatment respectively at 1 year. AIMS: To provide a review of the evidence for thiopurine or anti-TNF use in post-operative Crohn's disease, and to assess the ability to identify those patients at highest risk of recurrent disease. METHODS: A literature search was undertaken using Medline, Embase and Cochrane databases to identify studies using search terms 'thiopurine', 'azathioprine', 'mercaptopurine', 'Infliximab', 'adalimumab', 'Anti-TNF', 'Crohn's disease', 'post-operative' and 'recurrence'. RESULTS: Trials to examine this important area have proved difficult to execute, with recruitment and retention of patients posing major challenges to randomised clinical trials. There have been four RCTs of 433 patients of thiopurine therapy (with three meta-analyses of these data), and one of anti-TNF therapy involving 24 patients. Overall the efficacy data for thiopurine use in this setting are inconclusive, and other than smoking, there are no consistent predictors of post-operative relapse. CONCLUSIONS: At present, evidence for routine use of thiopurine treatment in post-operative Crohn's disease is heterogeneous and unconvincing. Stratification by risk of relapse emerges as a key challenge in post-operative management that needs to be addressed, using clinical parameters and emerging biomarkers. The evidence for prophylactic anti-TNF use is limited though promising, with its routine use guided by early assessment of relapse.

Performance of formulas for estimating glomerular filtration rate in Indigenous Australians with and without Type 2 diabetes: the eGFR Study.

AIMS: It has been proposed that the Chronic Kidney Disease Epidemiology Collaboration formula estimates glomerular filtration rate more accurately than the Modification of Diet in Renal Disease formula. With the very high incidence of diabetes and end-stage kidney disease in Indigenous Australians, accurate estimation of glomerular filtration rate is vital in early detection of kidney disease. We aimed to assess the performance of the Chronic Kidney Disease Epidemiology Collaboration, Modification of Diet in Renal Disease and Cockcroft-Gault formulas in Indigenous Australians with and without diabetes. METHODS: Indigenous Australians with (n = 224) or without (n = 340) Type 2 diabetes had a reference glomerular filtration rate measure using plasma disappearance of iohexol (measured glomerular filtration rate) over 4 h. Serum creatinine was measured by an enzymatic method. Performance was assessed by bias (measured glomerular filtration rate - estimated glomerular filtration rate) and accuracy (percentage of estimated glomerular filtration rate within 30% of measured glomerular filtration rate). RESULTS: The median measured glomerular filtration rate (interquartile range) in participants with or without diabetes was 97 (68-119) and 108 (90-122) ml min(-1)  1.73 m(-2) , respectively. The Chronic Kidney Disease Epidemiology Collaboration formula had smaller bias and greater accuracy than the Modification of Diet in Renal Disease and Cockcroft-Gault formulas overall, for participants both with and without diabetes. However, for estimated glomerular filtration rate > 90 ml min(-1)  1.73 m(-2) , the Chronic Kidney Disease Epidemiology Collaboration formula had greater bias in participants with diabetes, underestimating measured glomerular filtration rate by 7.4 vs. 1.0 ml min(-1)  1.73 m(-2) in those without diabetes. The Chronic Kidney Disease Epidemiology Collaboration formula was less accurate across the whole range of estimated glomerular filtration rates in participants with vs. those without diabetes (87.1% vs. 93.3%). CONCLUSIONS: The Chronic Kidney Disease Epidemiology Collaboration formula outperforms the Modification of Diet in Renal Disease and Cockcroft-Gault formulas overall in Indigenous Australians with and without diabetes. However, the Chronic Kidney Disease Epidemiology Collaboration formula has greater bias in people with diabetes compared with those without diabetes, especially in those with normal renal function.

How Do Community Physical and Occupational Therapists Classify Frailty? A pilot Study.

BACKGROUND: Frailty is a complex geriatric syndrome that is often difficult to diagnose, especially by healthcare professionals working in the community. Objectives, Measurements: This study examined how physical and occupational therapists classified community-dwelling clients using categories of 'nonfrail', 'prefrail' or 'frail' as compared to measurements of established frailty criteria from the Cardiovascular Health Study frailty index (CHSfi). RESULTS: Results indicate that community therapists underestimate frailty in comparison to the CHSfi. Therapists' classification of frailty suggested their perceptions of frailty may not only relate to client's functional capacity, but the context in which the client receives care. CONCLUSION: A multi-dimensional approach is required to capture all aspects of frailty across the healthcare continuum that accounts for how the client thrives within their personal environment.

Impact of antibiotic treatment for pulmonary exacerbations on bacterial diversity in cystic fibrosis.

BACKGROUND: A diverse array of bacterial species is present in the CF airways, in addition to those recognised as clinically important. Here, we investigated the relative impact of antibiotics, used predominantly to target Pseudomonas aeruginosa during acute exacerbations, on other non-pseudomonal species. METHODS: The relative abundance of viable P. aeruginosa and non-pseudomonal species was determined in sputa from 12 adult CF subjects 21, 14, and 7 days prior to antibiotics, day 3 of treatment, the final day of treatment, and 10-14 days afterwards, by T-RFLP profiling. RESULTS: Overall, relative P. aeruginosa abundance increased during antibiotic therapy compared to other bacterial species; mean abundance pre-antibiotic 51.0±36.0% increasing to 71.3±30.4% during antibiotic (ANOVA: F(1,54)=5.16; P<0.027). Further, the number of non-pseudomonal species detected fell; pre-antibiotic 6.0±3.3 decreasing to 3.7±3.3 during treatment (ANOVA: F(1,66)=5.11; P<0.027). CONCLUSIONS: Antibiotic treatment directed at P. aeruginosa has an additional significant impact on non-pseudomonal, co-colonising species.

Audit of acute Charcot's disease in the UK: the CDUK study.

AIMS/HYPOTHESIS: We studied factors associated with the development and resolution of acute Charcot foot using a web-based observational study. METHODS: Clinicians managing cases of acute Charcot foot in the UK and Ireland between June 2005 and February 2007 were invited to register anonymised details on a secure website. RESULTS: A total of 288 cases (age 57.0 ± 11.3 years [mean ± SD]; 71.2% male) were registered from 76 centres. Of these, 36% of patients recalled an episode of relevant trauma in the preceding 6 months, while 12% had had surgery to the affected foot. In 101 (35%) cases, ulceration was present at registration and 20% of these had osteomyelitis. Non-removable off-loading devices were used at presentation in 35.4% of cases, with removable off-loading used in 50%. Data on resolution were available for 219 patients. The median time to resolution was 9 months in patients whose initial management included the use of non-removable off-loading, compared with 12 months in the remainder (p = 0.001). Bisphosphonates were administered intravenously in 25.4% and orally in 19.4% of cases. The median time to resolution in patients who received bisphosphonates was 12 months and was longer than in those who did not (10 months, p = 0.005). CONCLUSIONS/INTERPRETATION: The median time to resolution was longer than in earlier series. Although limited by being observational and non-randomised, these data suggest that the use of non-removable off-loading at presentation may shorten the time to resolution. They provide no evidence to indicate that the use of bisphosphonates is beneficial.