The influence of muscle strength on the gait profile score (GPS) across different patients

BACKGROUND Muscle strength greatly influences gait kinematics. The question was whether this association is similar in different diseases. METHODS Data from instrumented gait analysis of 716 patients were retrospectively assessed. The effect of muscle strength on gait deviations, namely the gait profile score (GPS) was evaluated by means of generalised least square models. This was executed for seven different patient groups. The groups were formed according to the type of disease: orthopaedic/neurologic, uni-/bilateral affection, and flaccid/spastic muscles. RESULTS Muscle strength had a negative effect on GPS values, which did not significantly differ amongst the different patient groups. However, an offset of the GPS regression line was found, which was mostly dependent on the basic disease. Surprisingly, spastic patients, who have reduced strength and additionally spasticity in clinical examination, and flaccid neurologic patients showed the same offset. Patients with additional lack of trunk control (Tetraplegia) showed the largest offset. CONCLUSION Gait kinematics grossly depend on muscle strength. This was seen in patients with very different pathologies. Nevertheless, optimal correction of biomechanics and muscle strength may still not lead to a normal gait, especially in that of neurologic patients. The basic disease itself has an additional effect on gait deviations expressed as a GPS-offset of the linear regression line.

Prediction of 1-year mortality in patients with acute coronary syndromes undergoing percutaneous coronary intervention: validation of the logistic clinical SYNTAX (Synergy Between Percutaneous Coronary Interventions With Taxus and Cardiac Surgery) score

OBJECTIVES This study sought to validate the Logistic Clinical SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) score in patients with non-ST-segment elevation acute coronary syndromes (ACS), in order to further legitimize its clinical application. BACKGROUND The Logistic Clinical SYNTAX score allows for an individualized prediction of 1-year mortality in patients undergoing contemporary percutaneous coronary intervention. It is composed of a "Core" Model (anatomical SYNTAX score, age, creatinine clearance, and left ventricular ejection fraction), and "Extended" Model (composed of an additional 6 clinical variables), and has previously been cross validated in 7 contemporary stent trials (>6,000 patients). METHODS One-year all-cause death was analyzed in 2,627 patients undergoing percutaneous coronary intervention from the ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) trial. Mortality predictions from the Core and Extended Models were studied with respect to discrimination, that is, separation of those with and without 1-year all-cause death (assessed by the concordance [C] statistic), and calibration, that is, agreement between observed and predicted outcomes (assessed with validation plots). Decision curve analyses, which weight the harms (false positives) against benefits (true positives) of using a risk score to make mortality predictions, were undertaken to assess clinical usefulness. RESULTS In the ACUITY trial, the median SYNTAX score was 9.0 (interquartile range 5.0 to 16.0); approximately 40% of patients had 3-vessel disease, 29% diabetes, and 85% underwent drug-eluting stent implantation. Validation plots confirmed agreement between observed and predicted mortality. The Core and Extended Models demonstrated substantial improvements in the discriminative ability for 1-year all-cause death compared with the anatomical SYNTAX score in isolation (C-statistics: SYNTAX score: 0.64, 95% confidence interval [CI]: 0.56 to 0.71; Core Model: 0.74, 95% CI: 0.66 to 0.79; Extended Model: 0.77, 95% CI: 0.70 to 0.83). Decision curve analyses confirmed the increasing ability to correctly identify patients who would die at 1 year with the Extended Model versus the Core Model versus the anatomical SYNTAX score, over a wide range of thresholds for mortality risk predictions. CONCLUSIONS Compared to the anatomical SYNTAX score alone, the Core and Extended Models of the Logistic Clinical SYNTAX score more accurately predicted individual 1-year mortality in patients presenting with non-ST-segment elevation acute coronary syndromes undergoing percutaneous coronary intervention. These findings support the clinical application of the Logistic Clinical SYNTAX score.

Recommendations for the use of ultrasound in rheumatoid arthritis: literature review and SONAR score experience

Ultrasound (US) has become a useful tool in the detection of early disease, differential diagnosis, guidance of treatment decisions and treatment monitoring of rheumatoid arthritis (RA). In 2008, the Swiss Sonography in Arthritis and Rheumatism (SONAR) group was established to promote the use of US in inflammatory arthritis in clinical practice. A scoring system was developed and taught to a large number of Swiss rheumatologists who already contributed to the Swiss Clinical Quality Management (SCQM) database, a national patient register. This paper intends to give a Swiss consensus about best clinical practice recommendations for the use of US in RA on the basis of the current literature knowledge and experience with the Swiss SONAR score. Literature research was performed to collect data on current evidence. The results were discussed among specialists of the Swiss university centres and private practice, following a structured procedure. Musculoskelatal US was found to be very helpful in establishing the diagnosis and monitoring the evolution of RA, and to be a reliable tool if used by experienced examiners. It influences treatment decisions such as continuing, intensifying or stepping down therapy. The definite modalities of integrating US into the diagnosis and monitoring of RA treatments will be defined within a few years. There are, however, strong arguments to use US findings as of today in daily clinical care. Some practical recommendations about the use of US in RA, focusing on the diagnosis and the use of the SONAR score, are proposed.

Health care index score and risk of death following tuberculosis diagnosis in HIV-positive patients

OBJECTIVES: To assess health care utilisation for patients co-infected with TB and HIV (TB-HIV), and to develop a weighted health care index (HCI) score based on commonly used interventions and compare it with patient outcome. METHODS: A total of 1061 HIV patients diagnosed with TB in four regions, Central/Northern, Southern and Eastern Europe and Argentina, between January 2004 and December 2006 were enrolled in the TB-HIV study. A weighted HCI score (range 0–5), based on independent prognostic factors identified in multivariable Cox models and the final score, included performance of TB drug susceptibility testing (DST), an initial TB regimen containing a rifamycin, isoniazid and pyrazinamide, and start of combination antiretroviral treatment (cART). RESULTS: The mean HCI score was highest in Central/Northern Europe (3.2, 95%CI 3.1–3.3) and lowest in Eastern Europe (1.6, 95%CI 1.5–1.7). The cumulative probability of death 1 year after TB diagnosis decreased from 39% (95%CI 31–48) among patients with an HCI score of 0, to 9% (95%CI 6–13) among those with a score of ≥4. In an adjusted Cox model, a 1-unit increase in the HCI score was associated with 27% reduced mortality (relative hazard 0.73, 95%CI 0.64–0.84). CONCLUSIONS: Our results suggest that DST, standard anti-tuberculosis treatment and early cART may improve outcome for TB-HIV patients. The proposed HCI score provides a tool for future research and monitoring of the management of TB-HIV patients. The highest HCI score may serve as a benchmark to assess TB-HIV management, encouraging continuous health care improvement.

A reliable risk score for stage IV esophagogastric cancer

BACKGROUND The role of surgery for patients with metastatic esophagogastric adenocarcinoma (EGC) is not defined. The purpose of this study was to define selection criteria for patients who may benefit from resection following systemic chemotherapy. METHODS From 1987 to 2007, 160 patients presenting with synchronous metastatic EGC (cT3/4 cNany cM0/1 finally pM1) were treated with chemotherapy followed by resection of the primary tumor and metastases. Clinical and histopathological data, site and number of metastases were analyzed. A prognostic score was established and validated in a second cohort from another academic center (n = 32). RESULTS The median survival (MS) in cohort 1 was 13.6 months. Significant prognostic factors were grading (p = 0.046), ypT- (p = 0.001), ypN- (p = 0.011) and R-category (p = 0.015), lymphangiosis (p = 0.021), clinical (p = 0.004) and histopathological response (p = 0.006), but not localization or number of metastases. The addition of grading (G1/2:0 points; G3/4:1 points), clinical response (responder: 0; nonresponder: 1) and R-category (complete:0; R1:1; R2:2) defines two groups of patients with significantly different survival (p = 0.001) [low risk group (Score 0/1), n = 22: MS 35.3 months, 3-year-survival 47.6%); high risk group (Score 2/3/4) n = 126: MS 12.0 months, 3-year-survival 14.2%]. The score showed a strong trend in the validation cohort (p = 0.063) [low risk group (MS not reached, 3-year-survival 57.1%); high risk group (MS 19.9 months, 3-year-survival 6.7%)]. CONCLUSION We observed long-term survival after resection of metastatic EGC. A simple clinical score may help to identify a subgroup of patients with a high chance of benefit from resection. However, the accurate estimation of achieving a complete resection, which is an integral element of the score, remains challenging.

A multifactorial histopathologic score for the prediction of prognosis of resected esophageal adenocarcinomas after neoadjuvant chemotherapy

BACKGROUND For esophageal adenocarcinoma treated with neoadjuvant chemotherapy, postoperative staging classifications initially developed for non-pretreated tumors may not accurately predict prognosis. We tested whether a multifactorial TNM-based histopathologic prognostic score (PRSC), which additionally applies to tumor regression, may improve estimation of prognosis compared with the current Union for International Cancer Control/American Joint Committee on Cancer (UICC) staging system. PATIENTS AND METHODS We evaluated esophageal adenocarcinoma specimens following cis/oxaliplatin-based therapy from two separate centers (center 1: n = 280; and center 2: n = 80). For the PRSC, each factor was assigned a value from 1 to 2 (ypT0-2 = 1 point; ypT3-4 = 2 points; ypN0 = 1 point; ypN1-3 = 2 points; ≤50 % residual tumor/tumor bed = 1 point; >50 % residual tumor/tumor bed = 2 points). The three-tiered PRSC was based on the sum value of these factors (group A: 3; group B: 4-5; group C: 6) and was correlated with patients' overall survival (OS). RESULTS The PRSC groups showed significant differences with respect to OS (p < 0.0001; hazard ratio [HR] 2.2 [95 % CI 1.7-2.8]), which could also be demonstrated in both cohorts separately (center 1 p < 0.0001; HR 2.48 [95 % CI 1.8-3.3] and center 2 p = 0.015; HR 1.7 [95 % CI 1.1-2.6]). Moreover, the PRSC showed a more accurate prognostic discrimination than the current UICC staging system (p < 0.0001; HR 1.15 [95 % CI 1.1-1.2]), and assessment of two goodness-of-fit criteria (Akaike Information Criterion and Schwarz Bayesian Information Criterion) clearly supported the superiority of PRSC over the UICC staging. CONCLUSION The proposed PRSC clearly identifies three subgroups with different outcomes and may be more helpful for guiding further therapeutic decisions than the UICC staging system.

Effects of zoledronate versus placebo on spine bone mineral density and microarchitecture assessed by the trabecular bone score in postmenopausal women with osteoporosis: a three-year study

The trabecular bone score (TBS) is an index of bone microarchitectural texture calculated from anteroposterior dual-energy X-ray absorptiometry (DXA) scans of the lumbar spine (LS) that predicts fracture risk, independent of bone mineral density (BMD). The aim of this study was to compare the effects of yearly intravenous zoledronate (ZOL) versus placebo (PLB) on LS BMD and TBS in postmenopausal women with osteoporosis. Changes in TBS were assessed in the subset of 107 patients recruited at the Department of Osteoporosis of the University Hospital of Berne, Switzerland, who were included in the HORIZON trial. All subjects received adequate calcium and vitamin D3. In these patients randomly assigned to either ZOL (n = 54) or PLB (n = 53) for 3 years, BMD was measured by DXA and TBS assessed by TBS iNsight (v1.9) at baseline and 6, 12, 24, and 36 months after treatment initiation. Baseline characteristics (mean ± SD) were similar between groups in terms of age, 76.8 ± 5.0 years; body mass index (BMI), 24.5 ± 3.6 kg/m(2) ; TBS, 1.178 ± 0.1 but for LS T-score (ZOL-2.9 ± 1.5 versus PLB-2.1 ± 1.5). Changes in LS BMD were significantly greater with ZOL than with PLB at all time points (p < 0.0001 for all), reaching +9.58% versus +1.38% at month 36. Change in TBS was significantly greater with ZOL than with PLB as of month 24, reaching +1.41 versus-0.49% at month 36; p = 0.031, respectively. LS BMD and TBS were weakly correlated (r = 0.20) and there were no correlations between changes in BMD and TBS from baseline at any visit. In postmenopausal women with osteoporosis, once-yearly intravenous ZOL therapy significantly increased LS BMD relative to PLB over 3 years and TBS as of 2 years.

Microstructural Parameters of Bone Evaluated Using HR-pQCT Correlate with the DXA-Derived Cortical Index and the Trabecular Bone Score in a Cohort of Randomly Selected Premenopausal Women.

BACKGROUND Areal bone mineral density is predictive for fracture risk. Microstructural bone parameters evaluated at the appendicular skeleton by high-resolution peripheral quantitative computed tomography (HR-pQCT) display differences between healthy patients and fracture patients. With the simple geometry of the cortex at the distal tibial diaphysis, a cortical index of the tibia combining material and mechanical properties correlated highly with bone strength ex vivo. The trabecular bone score derived from the scan of the lumbar spine by dual-energy X-ray absorptiometry (DXA) correlated ex vivo with the micro architectural parameters. It is unknown if these microstructural correlations could be made in healthy premenopausal women. METHODS Randomly selected women between 20-40 years of age were examined by DXA and HR-pQCT at the standard regions of interest and at customized sub regions to focus on cortical and trabecular parameters of strength separately. For cortical strength, at the distal tibia the volumetric cortical index was calculated directly from HR-pQCT and the areal cortical index was derived from the DXA scan using a Canny threshold-based tool. For trabecular strength, the trabecular bone score was calculated based on the DXA scan of the lumbar spine and was compared with the corresponding parameters derived from the HR-pQCT measurements at radius and tibia. RESULTS Seventy-two healthy women were included (average age 33.8 years, average BMI 23.2 kg/m(2)). The areal cortical index correlated highly with the volumetric cortical index at the distal tibia (R  =  0.798). The trabecular bone score correlated moderately with the microstructural parameters of the trabecular bone. CONCLUSION This study in randomly selected premenopausal women demonstrated that microstructural parameters of the bone evaluated by HR-pQCT correlated with the DXA derived parameters of skeletal regions containing predominantly cortical or cancellous bone. Whether these indexes are suitable for better predictions of the fracture risk deserves further investigation.

Coronary artery disease severity and aortic stenosis: clinical outcomes according to SYNTAX score in patients undergoing transcatheter aortic valve implantation.

AIM The aim of this study was to evaluate whether coronary artery disease (CAD) severity exerts a gradient of risk in patients with aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI). METHODS AND RESULTS A total of 445 patients with severe AS undergoing TAVI were included into a prospective registry between 2007 and 2012. The preoperative SYNTAX score (SS) was determined from baseline coronary angiograms. In case of revascularization prior to TAVI, residual SS (rSS) was also determined. Clinical outcomes were compared between patients without CAD (n = 158), patients with low SS (0-22, n = 207), and patients with high SS (SS >22, n = 80). The pre-specified primary endpoint was the composite of cardiovascular death, stroke, or myocardial infarction (MI). At 1 year, CAD severity was associated with higher rates of the primary endpoint (no CAD: 12.5%, low SS: 16.1%, high SS: 29.6%; P = 0.016). This was driven by differences in cardiovascular mortality (no CAD: 8.6%, low SS: 13.6%, high SS: 20.4%; P = 0.029), whereas the risk of stroke (no CAD: 5.1%, low SS: 3.3%, high SS: 6.7%; P = 0.79) and MI (no CAD: 1.5%, low SS: 1.1%, high SS: 4.0%; P = 0.54) was similar across the three groups. Patients with high SS received less complete revascularization as indicated by a higher rSS (21.2 ± 12.0 vs. 4.0 ± 4.4, P < 0.001) compared with patients with low SS. High rSS tertile (>14) was associated with higher rates of the primary endpoint at 1 year (no CAD: 12.5%, low rSS: 16.5%, high rSS: 26.3%, P = 0.043). CONCLUSIONS Severity of CAD appears to be associated with impaired clinical outcomes at 1 year after TAVI. Patients with SS >22 receive less complete revascularization and have a higher risk of cardiovascular death, stroke, or MI than patients without CAD or low SS.

Multicentre validation of the Geneva Risk Score for hospitalised medical patients at risk of venous thromboembolism. Explicit ASsessment of Thromboembolic RIsk and Prophylaxis for Medical PATients in SwitzErland (ESTIMATE).

There is a need to validate risk assessment tools for hospitalised medical patients at risk of venous thromboembolism (VTE). We investigated whether a predefined cut-off of the Geneva Risk Score, as compared to the Padua Prediction Score, accurately distinguishes low-risk from high-risk patients regardless of the use of thromboprophylaxis. In the multicentre, prospective Explicit ASsessment of Thromboembolic RIsk and Prophylaxis for Medical PATients in SwitzErland (ESTIMATE) cohort study, 1,478 hospitalised medical patients were enrolled of whom 637 (43%) did not receive thromboprophylaxis. The primary endpoint was symptomatic VTE or VTE-related death at 90 days. The study is registered at ClinicalTrials.gov, number NCT01277536. According to the Geneva Risk Score, the cumulative rate of the primary endpoint was 3.2% (95% confidence interval [CI] 2.2-4.6%) in 962 high-risk vs 0.6% (95% CI 0.2-1.9%) in 516 low-risk patients (p=0.002); among patients without prophylaxis, this rate was 3.5% vs 0.8% (p=0.029), respectively. In comparison, the Padua Prediction Score yielded a cumulative rate of the primary endpoint of 3.5% (95% CI 2.3-5.3%) in 714 high-risk vs 1.1% (95% CI 0.6-2.3%) in 764 low-risk patients (p=0.002); among patients without prophylaxis, this rate was 3.2% vs 1.5% (p=0.130), respectively. Negative likelihood ratio was 0.28 (95% CI 0.10-0.83) for the Geneva Risk Score and 0.51 (95% CI 0.28-0.93) for the Padua Prediction Score. In conclusion, among hospitalised medical patients, the Geneva Risk Score predicted VTE and VTE-related mortality and compared favourably with the Padua Prediction Score, particularly for its accuracy to identify low-risk patients who do not require thromboprophylaxis.

Serum calcification propensity predicts all-cause mortality in predialysis CKD

Medial arterial calcification is accelerated in patients with CKD and strongly associated with increased arterial rigidity and cardiovascular mortality. Recently, a novel in vitro blood test that provides an overall measure of calcification propensity by monitoring the maturation time (T50) of calciprotein particles in serum was described. We used this test to measure serum T50 in a prospective cohort of 184 patients with stages 3 and 4 CKD, with a median of 5.3 years of follow-up. At baseline, the major determinants of serum calcification propensity included higher serum phosphate, ionized calcium, increased bone osteoclastic activity, and lower free fetuin-A, plasma pyrophosphate, and albumin concentrations, which accounted for 49% of the variation in this parameter. Increased serum calcification propensity at baseline independently associated with aortic pulse wave velocity in the complete cohort and progressive aortic stiffening over 30 months in a subgroup of 93 patients. After adjustment for demographic, renal, cardiovascular, and biochemical covariates, including serum phosphate, risk of death among patients in the lowest T50 tertile was more than two times the risk among patients in the highest T50 tertile (adjusted hazard ratio, 2.2; 95% confidence interval, 1.1 to 5.4; P=0.04). This effect was lost, however, after additional adjustment for aortic stiffness, suggesting a shared causal pathway. Longitudinally, serum calcification propensity measurements remained temporally stable (intraclass correlation=0.81). These results suggest that serum T50 may be helpful as a biomarker in designing methods to improve defenses against vascular calcification.

Validation of the DRAGON score in 12 stroke centers in anterior and posterior circulation

BACKGROUND AND PURPOSE The DRAGON score predicts functional outcome in the hyperacute phase of intravenous thrombolysis treatment of ischemic stroke patients. We aimed to validate the score in a large multicenter cohort in anterior and posterior circulation. METHODS Prospectively collected data of consecutive ischemic stroke patients who received intravenous thrombolysis in 12 stroke centers were merged (n=5471). We excluded patients lacking data necessary to calculate the score and patients with missing 3-month modified Rankin scale scores. The final cohort comprised 4519 eligible patients. We assessed the performance of the DRAGON score with area under the receiver operating characteristic curve in the whole cohort for both good (modified Rankin scale score, 0-2) and miserable (modified Rankin scale score, 5-6) outcomes. RESULTS Area under the receiver operating characteristic curve was 0.84 (0.82-0.85) for miserable outcome and 0.82 (0.80-0.83) for good outcome. Proportions of patients with good outcome were 96%, 93%, 78%, and 0% for 0 to 1, 2, 3, and 8 to 10 score points, respectively. Proportions of patients with miserable outcome were 0%, 2%, 4%, 89%, and 97% for 0 to 1, 2, 3, 8, and 9 to 10 points, respectively. When tested separately for anterior and posterior circulation, there was no difference in performance (P=0.55); areas under the receiver operating characteristic curve were 0.84 (0.83-0.86) and 0.82 (0.78-0.87), respectively. No sex-related difference in performance was observed (P=0.25). CONCLUSIONS The DRAGON score showed very good performance in the large merged cohort in both anterior and posterior circulation strokes. The DRAGON score provides rapid estimation of patient prognosis and supports clinical decision-making in the hyperacute phase of stroke care (eg, when invasive add-on strategies are considered).

The MI SYNTAX score for risk stratification in patients undergoing primary percutaneous coronary intervention for treatment of acute myocardial infarction: A substudy of the COMFORTABLE AMI trial.

BACKGROUND To investigate the performance of the MI Sxscore in a multicentre randomised trial of patients undergoing primary percutaneous coronary intervention (PPCI). METHODS AND RESULTS The MI Sxscore was prospectively determined among 1132 STEMI patients enrolled into the COMFORTABLE AMI trial, which randomised patients to treatment with bare-metal (BMS) or biolimus-eluting (BES) stents. Patient- (death, myocardial infarction, any revascularisation) and device-oriented (cardiac death, target-vessel MI, target lesion revascularisation) major adverse cardiac events (MACEs) were compared across MI Sxscore tertiles and according to stent type. The median MI SXscore was 14 (IQR: 9-21). Patients were divided into tertiles of Sxscorelow (≤10), Sxscoreintermediate (11-18) and Sxscorehigh (≥19). At 1year, patient-oriented MACE occurred in 15% of the Sxscorehigh, 9% of the Sxscoreintermediate and 5% of the Sxscorelow tertiles (p<0.001), whereas device-oriented MACE occurred in 8% of the Sxscorehigh, 6% of the Sxscoreintermediate and 4% of the Sxscorelow tertiles (p=0.03). Addition of the MI Sxscore to the TIMI risk score improved prediction of patient- (c-statistic value increase from 0.63 to 0.69) and device-oriented MACEs (c-statistic value increase from 0.65 to 0.70). Differences in the risk for device-oriented MACE between BMS and BES were evident among Sxscorehigh (13% vs. 4% HR 0.33 (0.15-0.74), p=0.007 rather than those in Sxscorelow: 4% vs. 3% HR 0.68 (0.24-1.97), p=0.48) tertiles. CONCLUSIONS The MI Sxscore allows risk stratification of patient- and device-oriented MACEs among patients undergoing PPCI. The addition of the MI Sxscore to the TIMI risk score is of incremental prognostic value among patients undergoing PPCI for treatment of STEMI.