Number Of Clinical Risk Factors Research Articles

Erratum to: High fracture probability predicts fractures in a 4-year follow-up in women from the RAC-OST-POL study

In 770 postmenopausal women, the fracture incidence during a 4-year follow-up was analyzed in relation to the fracture probability (FRAX risk assessment tool) and risk (Garvan risk calculator) predicted at baseline. Incident fractures occurred in 62 subjects with a higher prevalence in high-risk subgroups. Prior fracture, rheumatoid arthritis, femoral neck T-score and falls increased independent of fracture incidence. The aim of the study was to analyze the incidence of fractures during a 4-year follow-up in relation to the baseline fracture probability and risk. Enrolled in the study were 770 postmenopausal women with a mean age of 65.7 ± 7.3 years. Bone mineral density (BMD) at the proximal femur, clinical data, and fracture probability using the FRAX tool and risk using the Garvan calculator were determined. Each subject was asked yearly by phone call about the incidence of fracture during the follow-up period. Of the 770 women, 62 had a fracture during follow-up, and 46 had a major fracture. At baseline, BMD was significantly lower, and fracture probability and fracture risk were significantly higher in women who had a fracture. Among women with a major fracture, the percentage with a high baseline fracture probability (>10 %) was significantly higher than among those without a fracture (p < 0.01). Fracture incidence during follow-up was significantly higher among women with a high baseline fracture probability (12.7 % vs. 5.2 %) and a high fracture risk (9.2 vs. 5.3 %) so that the “fracture-free survival” curves were significantly different (p < 0.05). The number of clinical risk factors noted at baseline was significantly associated with fracture incidence (chi-squared = 20.82, p < 0.01). Prior fracture, rheumatoid arthritis, and femoral neck T-score were identified as significant risk factors for major fractures (for any fractures, the influence of falls was also significant). During follow-up, fracture incidence was predicted by baseline fracture probability (FRAX risk assessment tool) and risk (Garvan risk calculator). A number of clinical risk factors and a prior fracture, rheumatoid arthritis, femoral neck T-score, and falls increased independent of fracture incidence.

High fracture probability predicts fractures in a 4-year follow-up in women from the RAC-OST-POL study.

In 770 postmenopausal women, the fracture incidence during a 4-year follow-up was analyzed in relation to the fracture probability (FRAX risk assessment tool) and risk (Garvan risk calculator) predicted at baseline. Incident fractures occurred in 62 subjects with a higher prevalence in high-risk subgroups. Prior fracture, rheumatoid arthritis, femoral neck T-score and falls increased independent of fracture incidence. The aim of the study was to analyze the incidence of fractures during a 4-year follow-up in relation to the baseline fracture probability and risk. Enrolled in the study were 770 postmenopausal women with a mean age of 65.7 ± 7.3 years. Bone mineral density (BMD) at the proximal femur, clinical data, and fracture probability using the FRAX tool and risk using the Garvan calculator were determined. Each subject was asked yearly by phone call about the incidence of fracture during the follow-up period. Of the 770 women, 62 had a fracture during follow-up, and 46 had a major fracture. At baseline, BMD was significantly lower, and fracture probability and fracture risk were significantly higher in women who had a fracture. Among women with a major fracture, the percentage with a high baseline fracture probability (>10 %) was significantly higher than among those without a fracture (p < 0.01). Fracture incidence during follow-up was significantly higher among women with a high baseline fracture probability (12.7 % vs. 5.2 %) and a high fracture risk (9.2 vs. 5.3 %) so that the "fracture-free survival" curves were significantly different (p < 0.05). The number of clinical risk factors noted at baseline was significantly associated with fracture incidence (chi-squared = 20.82, p < 0.01). Prior fracture, rheumatoid arthritis, and femoral neck T-score were identified as significant risk factors for major fractures (for any fractures, the influence of falls was also significant). During follow-up, fracture incidence was predicted by baseline fracture probability (FRAX risk assessment tool) and risk (Garvan risk calculator). A number of clinical risk factors and a prior fracture, rheumatoid arthritis, femoral neck T-score, and falls were independently associated with an increased incidence of fractures. [Corrected]

Mortality and outcomes in very elderly patients 90 years of age or older admitted to the ICU.

We evaluated the clinical characteristics and factors associated with mortality in very elderly patients ≥ 90 y of age admitted to the ICU. We evaluated age-specific rates of admission and mortality in 16,935 subjects ≥ 18 y old and retrospectively analyzed the clinical data of 155 (0.92%) subjects ≥ 90 y old admitted to the ICU from January 2003 to July 2012. The clinical mortality index was defined as the ICU mortality rate associated with clinical risk factors including poor nutrition, do not resuscitate (DNR) order, pneumonia, chronic renal failure, cancer, mechanical ventilation, use of a vasopressor, and admission from a ward. The mortality rate of ICU subjects ≥ 90 y of age was 32.3%. A Cox's regression hazard model revealed that high glucose (P = .006), poor nutrition (P = .001), high Simplified Acute Physiology Scoring II scores (P < .001), DNR order (P = .002), and vasopressor treatment (P = .03) were independent predictive factors of mortality in subjects ≥ 90 y of age admitted to the ICU. An increasing number of clinical risk factors was associated with progressively higher mortality rates. All subjects with more than 5 risk factors died. The very elderly subjects (≥ 90 y) admitted to the ICU had a higher mortality rate compared with subjects of other ages. High Simplified Acute Physiology Scoring II scores, poor nutritional status, high glucose, use of vasopressors, and DNR orders should be considered as important predictors of mortality in very elderly ICU patients. The level of ICU treatment should be carefully considered in very elderly patients presenting with 5 or more risk factors.

AB1081 Results of A Walk-In Bone and Joint Screening CAMPAIGN to AID in the Diagnosis of Rheumatic Diseases

BackgroundRheumatic diseases are underdiagnosed in the Middle East. Screening and awareness campaigns can be used in conjunction with peripheral ultrasound machines used to screen for low bone mass are a...

Effect Of Cumulative Adverse Clinical Risk Factors On Patients With Multiple Myeloma Undergoing First GCSF Apheresis

With the new treatments for multiple myeloma (MM), increasing numbers of patients fail to mobilize sufficient peripheral blood stem cells (PBSC) for autologous stem cell transplant (ASCT). Multiple studies have identified clinical and laboratory factors, such as age, number of lines of chemotherapy, radiation exposure, bone marrow involvement, and low PLT count as risks for poor mobilization. However, there are fewer studies that analyze only the effect of multiple clinical risk factors on mobilization outcomes. We retrospectively analyzed 259 MM patients who underwent first apheresis after GCSF mobilization between December 2000 and December 2012. Clinical risk factors analyzed include age, number of lines of chemotherapy, number of cycles of chemotherapy, number of doses of cyclophosphamide, number of doses of lenalidomide, and prior external beam radiation. The standard dose of GCSF was 10 mcg/kg/day, however the exact dose for a significant number of patients was not known. Patients were assessed as to whether optimal (≥8x106 CD34+ cells/kg) or minimal (≥4x106 CD34+ cells/kg) number of stem cells for two ASCTs were collected. The median age of the entire cohort was 59.7 years (27.9-76.0). Overall 10.8% and 32.6% failed to collect the minimal and optimal number of stem cells after one round of apheresis. Of the twenty patients who underwent a second round of apheresis, 9 (45%) collected minimal and 7 (35%) collected optimal total number of stem cells, with an overall failure rate of 4.6% and 29.8%, respectively. The effect of the number of clinical risk factors on the mobilization failure during first apheresis is summarized in Table 1. For each additional clinical risk factor, the likelihood of collecting the minimal and optimal number of CD34+ cells is reduced by 34% (CI=0.484-0.893, p=0.0072) and 32% (CI=0.538–0.860, p=0.0013) respectively. On univariate analysis, all risk factors were analyzed as continuous variables, except for prior radiation which was analyzed as a categorical variable. Prior lenalidomide exposure (odds ratio=0.502, CI=0.297–0.845, p=0.0096), and prior radiation therapy (odds ratio=0.502, CI=0.293–0.861, p=0.0123) had the greatest negative predictive value. Of the 38 patients who were exposed to lenalomide (median 4 cycles; range 1-24 cycles), 13% and 42% failed to collect minimal and optimal number of stem cells in the first apheresis cycle, respectively. An association was seen between number of days required to collect target number of stem cells and number of risk factors (p≤0.001). Median number of days required to collect target number of stem cells for 0, 1 or 2+ clinical risk factors was 2, 2, and 4 days, respectively. When the effect of clinical risk factors were analyzed according to number of CD34+ cells/kg collected on each day of apheresis, statistically significant differences in collection efficiency were seen on the first 3 days of apheresis (Figure 1). In summary, clinical characteristics of patients with MM can potentially be used to predict mobilization failure. The presence of 2 or greater clinical risk factors adversely affect the ability to successfully collect the target stem cell dose. These risk factors may help in identifying high-risk MM patients who may benefit from alternative mobilization regimens that can be tested in prospective clinical trials.Number of Clinical Risk Factors012+N1128561% Patients not collecting optimal # of cells on 1st apheresis cycle23.231.850.895% CI15.8-32.122.1-42.833.7-63.9p-value0.19710.0003% Patients not collecting minimal # of cells on 1st apheresis cycle5.411.818.095% CI2.0-11.35.8-20.69.4-30.0p-value0.11950.0096Median number of days of collection224Range1-81-91-10p-value0.4233&lt;0.0001 Disclosures: No relevant conflicts of interest to declare.

New horizons in fracture risk assessment

Fracture is the clinical outcome of concern in osteoporosis, a disease variably defined over the last 30 years, mostly in terms of bone mineral density (BMD). However, an 'osseocentric' view of the condition may have hampered our understanding of how best to identify patients at the greatest risk of fragility fracture. More recently, the identification of a number of clinical risk factors for fragility fracture and the creation of fracture risk assessment tools, such as FRAX®, QFracture and Garvan have helped in a move towards clinically useful definitions, using the common currency of 10-year major osteoporotic and 10-year hip fracture risks. However, there are a large number of available fracture risk assessment tools and there remain few validation studies comparing their performance. The National Institute for Health and Clinical Excellence has recently advocated the use of these methods in case finding and studies are underway in their clinical application. It seems likely that the operational definition of osteoporosis must now include fracture risk, which will never replace fracture incidence as a measure of clinical efficacy but may be used in future studies to define patient groups likely to benefit from intervention. We still need to understand more about the performance of these tools, particularly in the context of specific patient groups, such as those with vertebral osteoporosis, the frail, those who fall and patients with secondary osteoporosis.

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EndoPredict improves the prognostic classification derived from common clinical guidelines in ER-positive, HER2-negative early breast cancer

BackgroundIn early estrogen receptor (ER)-positive/HER2-negative breast cancer, the decision to administer chemotherapy is largely based on prognostic criteria. The combined molecular/clinical EndoPredict test (EPclin) has been validated to accurately assess prognosis in this population. In this study, the clinical relevance of EPclin in relation to well-established clinical guidelines is assessed.Patients and methodsWe assigned risk groups to 1702 ER-positive/HER2-negative postmenopausal women from two large phase III trials treated only with endocrine therapy. Prognosis was assigned according to National Comprehensive Cancer Center Network-, German S3-, St Gallen guidelines and the EPclin. Prognostic groups were compared using the Kaplan–Meier survival analysis.ResultsAfter 10 years, absolute risk reductions (ARR) between the high- and low-risk groups ranged from 6.9% to 11.2% if assigned according to guidelines. It was at 18.7% for EPclin. EPclin reassigned 58%–61% of women classified as high-/intermediate-risk (according to clinical guidelines) to low risk. Women reclassified to low risk showed a 5% rate of distant metastasis at 10 years.ConclusionThe EPclin score is able to predict favorable prognosis in a majority of patients that clinical guidelines would assign to intermediate or high risk. EPclin may reduce the indications for chemotherapy in ER-positive postmenopausal women with a limited number of clinical risk factors.

Risk factors analysis of postsurgical gastroparesis syndrome and its impact on the survival of gastric cancer after subtotal gastrectomy

To investigate the risk factors of postsurgical gastroparesis syndrome (PGS) after subtotal gastrectomy in gastric cancer and the impact of PGS on prognosis. Clinical data of 422 patients who underwent subtotal gastrectomy for gastric cancer in the Central Hospital of Huzhou Sity from January 2004 to May 2010 were analyzed retrospectively. Risk factors of PGS were indentified and the recurrence-free survival was compared between the patients with and without PGS. PGS occurred in 42 patients (9.5%). Univariate analysis showed that: age over 65, combination of anxiety disorder, low-albuminemia in perioperative period, pyloric obstruction in preoperative period, high serume glucose level (≥ 11.2 mmol/L) in postoperative period, Billroth II (gastroenterostomy, operation time over 4 hours, using patient-controlled analgesia, or intravenous fluid over 3500 ml/d (all P<0.05) were prone to develop PGS. These might be potential clinical risk factors associated to PGS. Correlation analysis showed the number of clinical risk factors was positively correlated with the incidence of PGS (r=0.967, P<0.05). A total of 215 cases (50.9%) were followed up for 3-60 months. The mean recurrence-free survival time of patients with PGS was 26.1 months, which was shorter than that of those without PGS (33.4 months, P=0.029). Gastric cancer patients with the clinical risk factors mentioned above are prone to develop PGS after subtotal gastrectomy. PGS is associated with poor prognosis.

Goal-directed therapy in osteoporosis

Themanagement of osteoporosis is changing—for the better. Perhaps the most progressive recent step has been the assessment of fracture risk using clinical risk factors through tools such as the Fracture Risk Assessment Tool (FRAX). In addition to traditional intervention thresholds, such as those for osteoporosis defined by the WHO T-score or prior fracture, many guidelines now include recommendations for dual-energy X-ray absorptiometry (DXA) assessment or treatment for subgroups of patients identified to be at certain levels of fracture risk. In this regard, osteoporosis management is starting to follow risk-based strategies that have already been adopted in other disease areas, particularly in cardiovascular disease. In this issue’s Perspective article, Cummings and colleagues suggest that osteoporosis management should also embrace an additional strategy, that of goal-directed therapy. Although there is certainly merit in consideration and discussion of this proposal, the authors recognize that there are many challenges to be overcome. We would strongly argue that these challenges cannot be easily dismissed or glossed over in the desire to move forward—but we welcome the future discussions, debates, and most importantly, the research that will determine whether osteoporosis lends itself to goal-directed therapy. Themajor limitation in developing a goal-directed approach in osteoporosis is the choice of the parameter to define the goal. Cummings and colleagues imply that bone turnover markers (BTMs), bone mineral density (BMD), or fracture risk might be suitable parameters, but there remain many uncertainties and there is an ongoing debate about the optimal marker(s) of response in osteoporosis. Goal-directed therapy can only be considered when we are confident that we can accurately and consistently detect a therapeutic response and can demonstrate a strong correlation between that response and an improvement in clinical outcome. Such requirements are met in the fields of hypertension, hypercholesterolemia, diabetes, and critical care, in which treatment can be titrated to the desired level of effect. For example, in the treatment of hypercholesterolemia there is a strong relationship between the reduction in total cholesterol (TC) or low-density lipoprotein (LDL)-cholesterol (LDL-C) and mortality rates; in one meta-analysis, for every 1-mmol/L decrease in TC or LDL-C, there was a 24.5% or 28% reduction in coronary heart disease (CHD)-related mortality, respectively. Can we say the same about markers of response in osteoporosis? In the Perspective, a proposal is made that the goal could be a certain risk of fracture or level of BMD. It is certainly not unreasonable, given the availability of tools that calculate fracture risk, to consider a reduction to below a given threshold of risk as a goal for therapy. But how do we achieve this? The Perspective quite rightly draws attention to a number of unknowns about the interpretation of changes in risk factors during therapy. Other considerations are worth highlighting: a number of clinical risk factors can remain stable (eg, prior fracture status) or only progress in the direction of increased risk (eg, age, incident fracture in a fracture-naive patient). Others can move in the direction of lower risk, eg, stopping smoking or decreasing alcohol intake, though it is uncertain whether the expected risk reduction is actually achieved because there are no prospective studies to provide direct evidence of this. If such risk factors remain unchanged during therapy, then the only parameter in the risk models that can really show treatment-induced changes is BMD. So why not just propose a goal for BMD? As stated earlier, the role of BMD in monitoring therapeutic response remains controversial. In part, this reflects limitations in our ability to detect small within-person changes in BMD relative to the inherent measurement error. It also appears that the relationship between an increase in BMD and reduction in fracture risk in the setting of therapeutic response does not parallel the gradient of risk for BMD to predict fractures in untreated individuals. Many studies have shown that the relationship between change in BMD and fracture risk reduction is relatively weak COMMENTARY JBMR

Utility of Spine Bone Mineral Density in Fracture Prediction Within FRAX

Predicting individuals at risk for fracturing and modifying that risk are important in preventative health. Our aim was to quantify the impact of spine bone mineral density (BMD) on fracture risk prediction and determine the positive predictive value of fracture prediction using the lowest BMD value at the femoral neck, total hip, or lumbar spine. A retrospective cross-sectional analysis of 15,033 women was performed, assessing the contribution of age, body mass index, number of clinical risk factors, T-score, and osteoporosis category to the presence of fracture. In patients whose lumbar spine T-scores are 1 or 2 osteoporosis categories lower than femoral neck, there is an approximately 30% increased risk of fracture compared with the femoral neck alone. For patients younger than 60yr, the odds ratio of having a fracture based on the presence of lumbar spine osteoporosis was greater than that based on femoral neck osteoporosis. Osteoporosis at the total hip correlated best with the presence of fracture. When using FRAX, we recommend that the 10-yr fracture prediction be adjusted when lumbar spine T-score is 1–2 osteoporosis categories lower than the femoral neck T-score or when lumbar spine T-score is ≥1 standard deviation less than femoral neck T-score.

Cost-effectiveness of alendronate for the treatment of osteopenic postmenopausal women in Japan

Many postmenopausal women have osteopenia, a condition characterized by loss of bone mineral density (BMD) that is not as severe as in osteoporosis. The objective of this study was to estimate the cost-effectiveness of alendronate to prevent fractures in osteopenic postmenopausal women without a history of fracture in Japan. An individual simulation model was developed to predict lifetime costs and quality-adjusted life years (QALYs) of 5 years of preventive alendronate therapy versus no preventive therapy. The risk of hip and vertebral fracture associated with age and BMD was derived from epidemiologic studies in Japan. We ran the model with different combinations of age (65, 70, and 75 years), BMD (70%, 75%, and 80% of young adult mean [YAM]), and additional clinical risk factors. For 70-year-old women with a BMD of 70% of the YAM having one of the following risk factors: a family history of hip fracture, high alcohol intake, or current smoking, the incremental cost-effectiveness ratio (ICER) of alendronate was $92,937, $126,251, and $129,067 per QALY, respectively. These results were sensitive to age, BMD, and number of clinical risk factors. Probabilistic sensitivity analysis for the base case showed that in the presence of one, two, and three risk factors, alendronate was cost-effective in 0.2% to 2.6%, 13.1% to 56.1%, and 99.1% of the simulations, respectively, if society is willing to pay $50,000 per QALY. Additional analysis indicated that alendronate can be a good value in osteopenic women if the 10-year probability for a osteoporotic hip or vertebral fracture is more than 26.2%. Our results indicate that whether to treat osteopenia with alendronate should be determined on the basis of age, BMD, and number of clinical risk factors in terms of cost-effectiveness.

Epidemiological Data on Osteoporosis in Women From the RAC-OST-POL Study

In the RAC-OST-POL study, epidemiological data were presented concerning osteoporosis in 625 women older than 55yr coming from the District of Raciborz in Poland. The mean age was 66.4±7.8yr. All the women fulfilled a questionnaire, gathering data on clinical risk factors of osteoporosis. Femoral neck (FN) and total hip (TH) were measured. The mean value of bone mineral density for FN was 0.862±0.129g/cm2, T-score −1.25±0.92, and Z-score 0.039±0.78, whereas the respective values for TH were 0.945±0.149g/cm2, −0.47±1.19, and 0.52±0.98. T-score for FN below −2.5 was noted in 59 women (9.5%) and for TH in 23 women (3.7%). One hundred seventy six women reported prior osteoporotic fracture(s) (28.2%). Falls were the most common clinical risk factor. The number of clinical risk factors was significantly higher in subjects with fracture history than in those without fracture records. The only first-line antiresorptive medications, used in the therapy for osteoporosis, included alendronate—42 subjects (6.7%). Estrogen therapy was prescribed in 135 women and 7 were treated with calcitonin. Calcium was administered in 94 patients and vitamin D in 84 women. In all the women on therapy, Z-score values were significantly lower than in untreated women. Concluding, the results of our epidemiological study demonstrate low treatment rate in women with history of low trauma fracture. Effective strategies are needed for prevention, especially in regard to falls, and management of this disease, in particular for improvement of the treatment rates in affected women with prior fracture, in general.

Comparison of Exercise Treadmill Testing With Cardiac Computed Tomography Angiography Among Patients Presenting to the Emergency Room With Chest Pain

Background— The aims of our study were to (1) examine how data from exercise treadmill testing (ETT) can identify patients who have coronary plaque or stenosis, using CT angiography (CTA) as the reference standard, and (2) identify patient characteristics that may be used in selecting ETT versus CTA. Methods and Results— The Rule Out Myocardial Infarction Using Computer-Assisted Tomography (ROMICAT) trial was an observational cohort study of acute chest pain patients presenting to the emergency department with normal initial troponin and a nonischemic ECG. Univariate and multivariable analyses were performed to assess the relationship of baseline clinical data and ETT parameters with coronary plaque and stenosis on CTA. Of the 220 patients who had ETT (mean age, 51 years; 63% men), 21 (10%) had positive results. A positive ETT had a sensitivity of 30% and specificity of 93% to detect &gt;50% stenosis. The sensitivity increased to 83% after excluding uninterpretable segments and evaluating the ability to detect a &gt;70% stenosis. Predictors of plaque included older age, male sex, diabetes, hypertension, hyperlipidemia, lower functional capacity, and a lower Duke Treadmill Score. Both a positive ETT and a low Duke Treadmill Score were significant univariate and multivariable predictors of stenosis &gt;50% on CTA Whereas the prevalence of stenosis by CTA was greater among patients with more risk factors, coronary stenosis was not present among men &lt;40 years old or women &lt;50 years old or individuals who achieved at least 13 metabolic equivalents on ETT. Conclusions— Among low- to intermediate-risk patients with acute chest pain, a positive ETT has a limited sensitivity but high specificity for the detection of &gt;50% stenosis by CTA. Although patients with a high number of clinical risk factors are more likely to have obstructive coronary artery disease, those who are young or who would be expected to have a very high exercise capacity are unlikely to have coronary stenosis and therefore may benefit from initial ETT testing instead of CTA.

Atrial fibrillation and hyperthyroidism: relation between transoesophageal markers of a thrombogenic milieu and clinical risk factors for thromboembolism

Hyperthyroidism is a questionable risk factor for thromboembolism among patients with atrial fibrillation. To correlate clinical risk factors for thromboembolism from a group of patients with atrial fibrillation related to hyperthyroidism with transoesophageal echocardiography (TOE) markers of a thrombogenic milieu. Clinical risk factors for thromboembolism, thyroid hormonal status, time since diagnosis of hyperthyroidism and TOE markers of a thrombogenic milieu were assessed in consecutive patients with atrial fibrillation related to hyperthyroidism. The following TOE parameters were assessed to define the presence of thrombogenic milieu: dense spontaneous echo contrast, thrombi or left atrial appendage blood flow velocities <0·20 m/s. Clinical risk factors for thromboembolism were based on CHADS(2) (Cardiac failure, Hypertension, Age, Diabetes and Stroke) classification. This study included 31 consecutive patients aged between 18 and 65 years with atrial fibrillation related to hyperthyroidism scheduled for TOE. Thrombogenic milieu was present in 14 of 31 (45·2%) patients. The thyroid status could not predict the presence of a thrombogenic milieu. Despite low CHADS(2) score of 0/1, 6 of 13 (46·1%) patients had a thrombogenic milieu, whereas 10 of 18 (55·6%) patients with score ≥2 had none. The probability of having a thrombogenic milieu did not correlate with the number of clinical risk factors. Among patients younger than 65 years of age with atrial fibrillation related to hyperthyroidism, there is no association between clinical risk factors with TOE markers of a thrombogenic milieu. TOE adds useful information that may affect antithrombotic therapy guided by clinical risk classification.

Validity of the 6 min walk test in prediction of the anaerobic threshold before major non-cardiac surgery

For perioperative risk stratification, a robust, practical test could be used where cardiopulmonary exercise testing (CPET) is unavailable. The aim of this study was to assess the utility of the 6 min walk test (6MWT) distance to discriminate between low and high anaerobic threshold (AT) in patients awaiting major non-cardiac surgery. In 110 participants, we obtained oxygen consumption at the AT from CPET and recorded the distance walked (in m) during a 6MWT. Receiver operating characteristic (ROC) curve analysis was used to derive two different cut-points for 6MWT distance in predicting an AT of <11 ml O(2) kg(-1) min(-1); one using the highest sum of sensitivity and specificity (conventional method) and the other adopting a 2:1 weighting in favour of sensitivity. In addition, using a novel linear regression-based technique, we obtained lower and upper cut-points for 6MWT distance that are predictive of an AT that is likely to be (P≥0.75) <11 or >11 ml O(2) kg(-1) min(-1). The ROC curve analysis revealed an area under the curve of 0.85 (95% confidence interval, 0.77-0.91). The optimum cut-points were <440 m (conventional method) and <502 m (sensitivity-weighted approach). The regression-based lower and upper 6MWT distance cut-points were <427 and >563 m, respectively. Patients walking >563 m in the 6MWT do not routinely require CPET; those walking <427 m should be referred for further evaluation. In situations of 'clinical uncertainty' (≥427 but ≤563 m), the number of clinical risk factors and magnitude of surgery should be incorporated into the decision-making process. The 6MWT is a useful clinical tool to screen and risk stratify patients in departments where CPET is unavailable.

Postoperative recurrent luminal Crohnʼs Disease: A systematic review

Despite improved immunosuppressive therapy, surgical resection is still often required for uncontrolled inflammatory disease and the stenosing and perforating complications of Crohn's disease. However, surgery is not curative. A majority of patients develop disease recurrence at or above the anastomosis. Subclinical endoscopically identifiable recurrence precedes the development of clinical symptoms; identification and treatment of early mucosal recurrence may therefore prevent clinical recurrence. Therapy to achieve mucosal healing should now be the focus of postoperative therapy. A number of clinical risk factors for the development of earlier postoperative recurrence have been identified, and reasonable evidence is now available regarding the efficacy of drug therapies in preventing recurrence. This evidence now needs to be incorporated into prospective treatment strategies.

Construction of a FRAX® model for the assessment of fracture probability in Canada and implications for treatment

We describe the creation of a FRAX® model for the assessment of fracture probability in Canadian men and women, calibrated from national hip fracture and mortality data. This FRAX tool was used to examine possible thresholds for therapeutic intervention in Canada in two large complementary cohorts of women and men. To evaluate a Canadian World Health Organization (WHO) fracture risk assessment (FRAX®) tool for computing 10-year probabilities of osteoporotic fracture. Fracture probabilities were computed from national hip fracture data (2005) and death hazards (2004) for Canada. Probabilities took account of age, sex, clinical risk factors (CRFs), and femoral neck bone mineral density (BMD). Treatment implications were studied in two large cohorts of individuals age 50years and older: the population-based Canadian Multicentre Osteoporosis Study (4,778 women and 1,919 men) and the clinically referred Manitoba BMD Cohort (36,730 women and 2,873 men). Fracture probabilities increased with age, decreasing femoral neck T-score, and number of CRFs. Among women, 10.1-11.3% would be designated high risk based upon 10-year major osteoporotic fracture probability exceeding 20%. A much larger proportion would be designated high risk based upon 10-year hip fracture probability exceeding 3% (25.7-28.0%) or osteoporotic BMD (27.1-30.9%), and relatively few from prior hip or clinical spine fracture (1.6-4.2%). One or more criteria for intervention were met by 29.2-34.0% of women excluding hip fracture probability (35.3-41.0% including hip fracture probability). Lower intervention rates were seen among CaMos (Canadian Multicentre Osteoporosis Study) men (6.8-12.9%), but in clinically referred men from the Manitoba BMD Cohort, one or more criteria for high risk were seen for 26.4% excluding hip fracture probability (42.4% including hip fracture probability). The FRAX tool can be used to identify intervention thresholds in Canada. The FRAX model supports a shift from a dual X-ray absorptiometry (DXA)-based intervention strategy, towards a strategy based on fracture probability for a major osteoporotic fracture.

¿Qué es el FRAX?: pros y contras

FRAX is a tool that is available online to calculate the risk of fracture from a number of clinical risk factors, whether bone mineral density is known or not. Due to the quality of the data used in its calculation and the methodology employed, FRAX is now probably the preferred method for determining fracture risk. However, this tool has certain limitations and the physician's clinical judgment remains critical, especially for the assessment of risk factors not included in the algorithm such as lumbar bone mineral density or frequency of falls. The wide acceptance and use of FRAX could identify people at high risk of osteoporotic fracture, who are suitable for early intervention and are so far overlooked. Equally, FRAX could help to reduce the number of unnecessary treatments in patients with a low fracture risk. Another potential use of FRAX would be its use in identifying patients with indications for bone densitometry.

Assessment of Individual Fracture Risk: FRAX and Beyond

The World Health Organization fracture risk assessment tool (FRAX) and the Garvan fracture risk calculator are both widely available tools for individualized fracture risk prediction in daily practice. The FRAX model is implemented in several guidelines and most widely used at present. However, clinicians should take into account the differences between the models, especially with regard to the effect of the number of falls, number and clustering of previous fractures, and the number of clinical risk factors on the outcome of predicted fracture risk. Further development will be needed for optimal integration of bone- and fall-related risks, clustering of fractures, and dosing of risk factors to validate the models in different populations and to validate the ability to select patients who will achieve fracture risk reduction with anti-osteoporosis therapy. FRAX may be used as the primary model, and in patients with recurrent fractures and falls the use of the Garvan model may be of additional value.