Background: Varus hindfoot deformity may increase the risk of chronic lateral ankle instability (CLAI). Our aim was to analyze hindfoot alignment (HFA) in patients with CLAI using weight-bearing cone beam computed tomography (WBCT) to assess this risk. Methods: This retrospective, comparative analysis was carried out using an existing WBCT database (Talas, CurveBeam LLC), including data sets for 370 consecutive feet (189 patients) obtained between July 2016 and October 2018 at a single institution. The software provided semiautomated measurement of HFA, given as foot ankle offset (FAO). Univariate analysis was conducted to compare feet with and without CLAI against sex, age, body mass index, and FAO. Significant variables were included in a multivariable logistic model with random effects to take into account correlation between feet of the same patient. Results: Forty-three feet had CLAI (34 patients). FAO ( P = .0009) was significant for CLAI by univariate analysis. Mean FAO was −2.2% ± 5.5% (varus) and + 2.6% ± 4.7% (valgus) with and without CLAI history, respectively. Multivariable logistic regression adjusted for sex and age demonstrated a 35% increased odds ratio (OR) of CLAI per 1% reduction in FAO value (varus) (adjusted OR=0.64, 95% confidence interval [CI]: 0.49-0.84; P = .001) and no significant effect of sex (adjusted OR=0.52; P = .617) or age (adjusted OR=0.94; P = .165) after adjustment for FAO. Conclusion: A positive relationship was found between varus HFA and the risk to have CLAI. Systematic recording of FAO measurements from WBCT images along with clinical data regarding CLAI history proved successful at quantifying the risk of CLAI. Level of Evidence: Level III, retrospective cohort study.

BackgroundTherapeutic options are limited in secondary progressive multiple sclerosis (SPMS). Open-label studies suggested efficacy of monthly IV cyclophosphamide (CPM) without induction for delaying progression but no randomized trial was conducted so far.ObjectiveTo compare CPM to methylprednisolone (MP) in SPMS.MethodsRandomized, double-blind clinical trial on two parallel groups. Patient with SPMS, with a documented worsening of the Expanded Disability Status Scale (EDSS) score during the last year and an EDSS score between 4·0 and 6·5 were recruited and received one intravenous infusion of treatment (CPM: 750 mg /m2 body surface area—MP: 1g) every four weeks for one year, and every eight weeks for the second year. The primary endpoint was the time to EDSS deterioration, when confirmed sixteen weeks later, analyzed using a Cox model.ResultsDue to recruitment difficulties, the study was terminated prematurely after 138 patients were included (CPM, n = 72; MP, n = 66). In the CPM group, 33 patients stopped treatment prematurely, mainly due to tolerability, compared with 22 in the MP group. Primary endpoint: the hazard ratio for EDSS deterioration in the CPM in comparison with the MP group was 0.61 [95% CI: 0·31–1·22](p = 0·16). According to the secondary multistate model analysis, patients in the CPM group were 2.2 times more likely ([1·14–4.29]; p = 0.02) to discontinue treatment than those in the MP group and 2.7 times less likely (HR = 0.37, 95% CI: 0.17–0.84; p = 0.02) to experience disability progression when they did not stop treatment prematurely. Safety profile was as expected.ConclusionAlthough the primary end-point was negative, secondary analysis suggested that CPM decreases the risk of progression in SPMS, but its use may be limited by low tolerability.Trial RegistrationClinicaltrials.gov NCT00241254

Varus hindfoot deformity may increase the risk of chronic ankle instability (CAI).Weightbearing CT (WBCT) semi-automated measurements and built-in databases may contribute to investigate the relationship between clinical and radiographic data. The objective of this study was to analyze hindfoot alignment (HA) in relation with CAI in a series of patients using these new tools. We hypothesized that there would be a positive correlation between a varus morphotype and a history of CAI. Methods: This is a Level 3 retrospective comparative study of a continuous series of 124 feet (63 patients) referred from July to December 2016. and subsequently assessed by WBCT (PedCAT®, CurveBeam LLC). The measurement software (Talas ®,Curvebeam LLC), gave HA as a value of Foot and Ankle Offset (FAO). This measures the offset between the center of the ankle joint and the median line of the foot joining the centers of the calcaneus and forefoot weight bearing surfaces. Data was prospectively saved in a database (CubeView®, CurveBeam, PA, USA). The definition of CAI was a history of at least 3 ankle sprains during a 6 months period. Exclusion criteria were medial instability and syndesmotic injuries (2 cases).A univariate analysis was conducted to study CAI against the following variables: gender (Fisher), BMI and FAO (Kurskal-Wallis). The significant variables were subsequently included in a multivariate logistic model. Results: Nineteen feet had CAI, in 12 patients. Gender (p=0.0467-the proportion of women for patients with CAI was 72.3%, compared to 33.3% without CAI) and FAO (p=0 .0002) were significant in the univariate analysis. The mean FAO was respectively-1.40 (SD: 5.50) and 3.56 (SD: 5.31) with and without a history of CAI. No significant difference of age or BMI was shown. After verification of log-linearity between odds of CAI and FAO, the multivariate logistic regression adjusted for gender demonstrated a 15% increase of odds of CAI per unit increase of varus (adjusted Odds Ratio (CI95%): 0.858 (0.771-0.943) p=0.003), and no more significant effect of gender after adjustment on FAO (Odds ratio (CI95%) Female versus Male: 0.548 (0.185-1.669) p=0.277). Conclusion: A positive linear relationship was found between Varus Hindfoot Alignment measured using a semi-automatic tool in WBCT and the odds ratio for Chronic Ankle Instability, thus confirming and quantifying previous findings. The recent development of semi-automatic measurements and prospective databases opens future perspectives for big data and multivariate analysis in foot and ankle pathology.

disease activity measured by adjusted mean SLEDAI (AMS), flares, and probability of organ damage progression are modelled separately for each health state and dynamically updated each cycle. Health state costs and utilities are based on multivariate regression analyses that increment payoffs for each cycle. Results: A new CEM framework was developed within a Markov model, which further allowed incorporation of AMS, flares and organ damage progression in SLE. Total costs and outcomes were similar to the previous CEM. ConClusions: This modelling study has simplified clinical assumptions of SLE to produce a Markov model that may be used by additional stakeholders due to its increased transparency and shorter run time. Study funded by GSK.

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