Comparative effectiveness and cost-effectiveness of natalizumab and fingolimod in rapidly evolving severe relapsing-remitting multiple sclerosis in the United Kingdom.

AIM: To evaluate the real-world comparative effectiveness and the cost-effectiveness, from a UK National Health Service perspective, of natalizumab versus fingolimod in patients with rapidly evolving severe relapsing-remitting multiple sclerosis (RES-RRMS). METHODS: Real-world data from the MSBase Registry were obtained for patients with RES-RRMS who were previously either naive to disease-modifying therapies or had been treated with interferon-based therapies, glatiramer acetate, dimethyl fumarate, or teriflunomide (collectively known as BRACETD). Matched cohorts were selected by 3-way multinomial propensity score matching, and the annualized relapse rate (ARR) and 6-month-confirmed disability worsening (CDW6M) and improvement (CDI6M) were compared between treatment groups. Comparative effectiveness results were used in a cost-effectiveness model comparing natalizumab and fingolimod, using an established Markov structure over a lifetime horizon with health states based on the Expanded Disability Status Scale. Additional model data sources included the UK MS Survey 2015, published literature, and publicly available sources. RESULTS: In the comparative effectiveness analysis, we found a significantly lower ARR for patients starting natalizumab compared with fingolimod (rate ratio [RR] = 0.65; 95% confidence interval [CI], 0.57-0.73) or BRACETD (RR = 0.46; 95% CI, 0.42-0.53). Similarly, CDI6M was higher for patients starting natalizumab compared with fingolimod (hazard ratio [HR] = 1.25; 95% CI, 1.01-1.55) and BRACETD (HR = 1.46; 95% CI, 1.16-1.85). In patients starting fingolimod, we found a lower ARR (RR = 0.72; 95% CI, 0.65-0.80) compared with starting BRACETD, but no difference in CDI6M (HR = 1.17; 95% CI, 0.91-1.50). Differences in CDW6M were not found between the treatment groups. In the base-case cost-effectiveness analysis, natalizumab dominated fingolimod (0.302 higher quality-adjusted life-years [QALYs] and £17,141 lower predicted lifetime costs). Similar cost-effectiveness results were observed across sensitivity analyses. CONCLUSIONS: This MSBase Registry analysis suggests that natalizumab improves clinical outcomes when compared with fingolimod, which translates to higher QALYs and lower costs in UK patients with RES-RRMS.

There are several medications used to treat people with relapsing remitting multiple sclerosis, such as interferon-based therapies (Betaferon/Betaseron (US), Rebif, Avonex, Extavia), glatiramer acetate (Copaxone), teriflunomide (Aubagio), and dimethyl fumarate (Tecfidera), collectively named BRACETD. Other treatments for multiple sclerosis (MS) have a narrower use, such as natalizumab (Tysabri) or fingolimod (Gilenya), among others.This study objective was to assess how well natalizumab and fingolimod helped treating MS (clinical effectiveness) and subsequently estimate what the cost of these treatments is in comparison to the benefit they bring to people with rapidly evolving severe MS that use them in the United Kingdom (UK) (cost-effectiveness).We used an international disease registry (MSBase), which collects clinical data from people with MS in various centers around the world to compare the effectiveness of natalizumab, fingolimod and BRACETD treatments. We used a technique called propensity score matching to obtain results from comparable patient groups. People treated with natalizumab had better disease control, namely with fewer relapses and higher improvement on their disability level, than patients on fingolimod or BRACETD. Conversely, there were no differences between each group of people on a measure called disability worsening.Based on these clinical results, we built an economic model that simulates the lifetime costs and consequences of treating people with MS with natalizumab in comparison with fingolimod. We found that using natalizumab was less costly and was more effective compared to using fingolimod in UK patients.

Repair of radiation-induced rectovaginal fistula with rectal stricture by a combined Tuttle, Turnbull-Cutait and Singapore flap approach.

Radiation-induced rectovaginal fistula (RI-RVF) with associated rectal stricture represents a challenging problem in management. The aim of the present technical note is to describe a surgical technique aimed at minimizing disease recurrence by avoiding radiated tissue in the reconstruction: 1. Tuttle longitudinal incision of posterior vaginal wall with sharp excision of proximally located fistula; 2. Resection of strictured rectum via a combined transvaginal/laparotomy access, reconstruction with Turnbull-Cutait colon pull-through, and delayed handsewn coloanal anastomosis with loop ileostomy; 3. Bridge closure of the posterior vaginal wall by the interposition of a Singapore flap. This approach resulted in a favorable outcome at the 1-year follow-up in one patient with a medical history of gynecological carcinoma status after hystero-salpingo-oophorectomy followed by adjuvant radiation.

Robotic-Assisted Surgery Training (RAST): Assessment of Surgeon Console Ergonomic Skills.

OBJECTIVE: The aim of this study was to evaluate the responsiveness of postgraduate year (PGY) general surgery residents (GSRs) to surgeon console ergonomics within the robotic-assisted surgery training (RAST) program. DESIGN: This was a prospective educational study. GSRs were prepared with a pretraining educational video. Faculty provided one-on-one resident hands-on training and testing. Nine proficiency criteria (emergency stop & recover; left side pod adjustments; touchpad controls; footswitch panel; energy control pedals; camera control & focus; arm swap; master & finger clutch; dual console settings control) were assessed with a 5-point Likert-scale. Responsiveness was defined as change in performance over time. The robotic platform was Da Vinci Xi (Intuitive Surgical, Sunnyvale, CA). The Dundee ready educational environment measure (DREEM) inventory was used by GSRs to assess the educational environment. SETTING: Tertiary care academic teaching institution. PARTICIPANTS: A total of 22 GSRs: 4 PGY 1, 4 PGY 2, 4 PGY 3, 5 PGY 4, 5 PGY 5. RESULTS: From June 2022 to March 2023 the hands-on console time decreased at testing when compared to baseline: median 39.0 (range 37-41) vs 20.1 (range 19-22) minutes, respectively. There was no difference in mean hands-on testing scores stratified by PGY: 4.85±0.4 PGY1; 4.98 ± 0.3 PGY2; 4.86 ± 0.4 PGY3, 4.88 ± 0.2 PGY4, and 4.91 ± 0.1 PGY5 (ANOVA test; p = 0.095). The overall DREEM score was 167.1 ± 16.9 with CAC = 0.908 (excellent internal consistency). CONCLUSIONS: Training in ergonomics on the surgeon console impacted the responsiveness of the GSRs with 51% console time reduction. There were no differences in hands-on testing scores among PGYs. Perception of the educational environment by the GSRs was high.

Does the visceral fat area impact the histopathology specimen metrics after total mesorectal excision for distal rectal cancer?

BACKGROUND: The aim of this study was to evaluate whether the visceral fat area (VFA) has an impact on the histopathology specimen metrics of male patients undergoing robotic total mesorectal resection (rTME) for distal rectal cancer. METHODS: Prospectively collected data of patients undergoing rTME for resectable rectal cancer by five surgeons during a period of three years were extracted from the REgistry of Robotic SURgery for RECTal cancer (RESURRECT). VFA was measured in all patients at preoperative computed tomography. Distal rectal cancer was defined as <6cm from the anal verge. The histopathology metrics included circumferential resection margin (CRM) (in mm) and its involvement rate (if <1mm), distal resection margin (DRM), and quality of TME (complete, nearly-complete, incomplete). RESULTS: Of 839 patients who underwent rTME, 500 with distal rectal cancer were included. One hundred and six (21.2%) males with VFA>100cm2 were compared to 394 (78.8%) males or females with VFA≤100cm2. The mean CRM of males with VFA>100cm2 was not significantly different from its counterpart (6.6 ± 4.8 mm versus 7.1 ± 9.5mm; p=0.752). CRM involvement rates were 7.6% in both groups (p=1.000). The DRM was not significantly different: 1.8±1.9cm versus 1.8±2.6cm; p=0.996. The quality of TME did not significantly differ: complete TME 87.3% vs. 83.7%; nearly complete TME 8.9% vs. 12.8%; incomplete TME 3.8% vs. 3.6%. Complications and clinical outcomes did not significantly differ. CONCLUSION: This study did not find evidence to support that increased VFA would result in suboptimal histopathology specimen metrics when performing rTME in males with distal rectal cancer.

Quantitative and qualitative features of acute phase-adverse events following SARS-CoV-2 vaccination in a large sample of people with multiple sclerosis.

INTRODUCTION: Few data are available on adverse events (AE) associated to vaccines in persons with multiple sclerosis (pwMS). AIMS: to study the incidence of acute phase AE (AP-AE) related to SARS-CoV-2 mRNA vaccines in pwMS compared to a control group, and to analyze the association between AP-AE and disease modifying treatments (DMT). METHODS: This was a cross-sectional study on 438 PwMS and 481 age- and sex-matched subjects not affected by dysimmune diseases that underwent two doses of SARS-CoV-2 mRNA BNT162b2 vaccine (Pfizer/BioNtech). RESULTS: Two hundred and twenty five (51.4%) pwMS complained of ≥1 AP-AE after the first dose, 269 (61.4%) after the second dose. A logistic regression analysis revealed that only pwMS on Fingolimod and Ocrelizumab did not show a higher risk of developing AP-AE. The likelihood to present with ≥1 AP-AE, after correcting for age and sex, was significantly higher in pwMS than controls. CONCLUSIONS: This study reports qualitative and quantitative features of AP-AE associated with the first and second doses of SARS-CoV-2 vaccine in a large sample of pwMS. The only risk factor identified for developing AP-AE is female gender. AntiCD-20 monoclonal antibodies and S1P inhibitors are associated with a lower risk of AP-AE occurrence.

Do patients' and referral centers' characteristics influence multiple sclerosis phenotypes? Results from the Italian multiple sclerosis and related disorders register.

BACKGROUND: Multiple sclerosis (MS) is characterized by phenotypical heterogeneity, partly resulting from demographic and environmental risk factors. Socio-economic factors and the characteristics of local MS facilities might also play a part. METHODS: This study included patients with a confirmed MS diagnosis enrolled in the Italian MS and Related Disorders Register in 2000-2021. Patients at first visit were classified as having a clinically isolated syndrome (CIS), relapsing-remitting (RR), primary progressive (PP), progressive-relapsing (PR), or secondary progressive MS (SP). Demographic and clinical characteristics were analyzed, with centers' characteristics, geographic macro-areas, and Deprivation Index. We computed the odds ratios (OR) for CIS, PP/PR, and SP phenotypes, compared to the RR, using multivariate, multinomial, mixed effects logistic regression models. RESULTS: In all 35,243 patients from 106 centers were included. The OR of presenting more advanced MS phenotypes than the RR phenotype at first visit significantly diminished in relation to calendar period. Females were at a significantly lower risk of a PP/PR or SP phenotype. Older age was associated with CIS, PP/PR, and SP. The risk of a longer interval between disease onset and first visit was lower for the CIS phenotype, but higher for PP/PR and SP. The probability of SP at first visit was greater in the South of Italy. DISCUSSION: Differences in the phenotype of MS patients first seen in Italian centers can be only partly explained by differences in the centers' characteristics. The demographic and socio-economic characteristics of MS patients seem to be the main determinants of the phenotypes at first referral.

Multiple sclerosis epidemiological trends in Italy highlight the environmental risk factors.

Italy is definitely a high-risk country for multiple sclerosis (MS). Over the last 50 years, several epidemiological studies, including longitudinal surveys, have disclosed that MS incidence and prevalence in Italy mainland and Islands (Sardinia and Sicily) have progressively increased, picturing a semi-parabolic curve. Based on the comprehensive scrutiny of 58 papers, we conclude that the latitude risk gradient does not fit to the Italian map of MS. The genetic heterogeneity of the Italian ethnicities, that likely forms the basis of MS predisposition, does not account for the dramatic increase of MS incidence and prevalence observed in Italy over the last half century that, rather, seems better explained by the effect of environmental factors.

Efficacy of levetiracetam on upper limb movement in multiple sclerosis patients with cerebellar signs: a multicenter double-blind, placebo-controlled, crossover study.

BACKGROUND AND PURPOSE: The literature provides contrasting results on the efficacy of levetiracetam (LEV) in multiple sclerosis (MS) patients with cerebellar signs. It was sought to evaluate the efficacy of LEV on upper limb movement in MS patients. METHODS: In this multicenter double-blind placebo-controlled crossover study, MS patients with prevalently cerebellar signs were randomly allocated into two groups: LEV followed by placebo (group 1) or placebo followed by LEV (group 2). Clinical assessments were performed by a blinded physician at T0 (day 1), T1 (day 22), T2 (2-week wash-out period, day 35) and T3 (day 56). The primary outcome was dexterity in the arm with greater deficit, assessed by the nine-hole peg test (9HPT). Secondary clinical outcomes included responders on the 9HPT (∆9HPT >20%), tremor activity of the daily living questionnaire and self-defined upper limb impairment, through a numeric rating scale. Kinematic evaluation was performed using a digitizing tablet, providing data on normalized jerk, aiming error and centripetal acceleration. RESULTS: Forty-eight subjects (45.2 ± 10.4 years) were randomly allocated into two groups (n = 24 each). 9HPT significantly improved in the LEV phase in both groups (P < 0.001). The LEV treatment phase led to a significant improvement (P < 0.01) of all clinical outcomes in group 1 and in dexterity in group 2. No significant changes were reported during both placebo phases in the two groups. Considering the kinematic analysis, only normalized jerk significantly improved after treatment with LEV (T0-T1) in group 1. CONCLUSIONS: Levetiracetam treatment seems to be effective in improving upper limb dexterity in MS patients with cerebellar signs.

Right hemicolectomy - from laparoscopic facilitated technique to robotic intracorporeal anastomosis.

Several different operative techniques have been applied in minimally invasive right colectomy. Data reported in literature confirm the advantages of laparoscopic approach, however, there is no sure evidence of which one is the best. The pure laparoscopic technique with intracorporeal anastomosis seems to show some advantages compared to the other laparoscopic and open procedures, although for the price of technical difficulty and a longer operating time.