Early treatment delays long-term disability accrual in RRMS: Results from the BMSD network

Background: The optimal timing of treatment starts for achieving the best control on the long-term disability accumulation in multiple sclerosis (MS) is still to be defined. Objective: The aim of this study was to estimate the optimal time to start disease-modifying therapies (DMTs) to prevent the long-term disability accumulation in MS, using a pooled dataset from the Big Multiple Sclerosis Data (BMSD) network. Methods: Multivariable Cox regression models adjusted for the time to first treatment start from disease onset (in quintiles) were used. To mitigate the impact of potential biases, a set of pairwise propensity score (PS)-matched analyses were performed. The first quintile, including patients treated within 1.2 years from onset, was used as reference. Results: A cohort of 11,871 patients (median follow-up after treatment start: 13.2 years) was analyzed. A 3- and 12-month confirmed disability worsening event and irreversible Expanded Disability Status Scale (EDSS) 4.0 and 6.0 scores were reached by 7062 (59.5%), 4138 (34.9%), 3209 (31.1%), and 1909 (16.5%) patients, respectively. The risk of reaching all the disability outcomes was significantly lower ( p < 0.0004) for the first quintile patients’ group. Conclusion: Real-world data from the BMSD demonstrate that DMTs should be commenced within 1.2 years from the disease onset to reduce the risk of disability accumulation over the long term.

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Importance of early treatment initiation in the clinical course of multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458516675039 ◽

2016 ◽

Vol 23 (9) ◽

pp. 1233-1240 ◽

Cited By ~ 48

Author(s):

Andrius Kavaliunas ◽

Ali Manouchehrinia ◽

Leszek Stawiarz ◽

Ryan Ramanujam ◽

Jonas Agholme ◽

...

Keyword(s):

Multiple Sclerosis ◽

Early Treatment ◽

Treatment Initiation ◽

Cox Regression ◽

Age At Onset ◽

Hazard Ratio ◽

Outcome Variable ◽

Treatment Start ◽

Disability Status

Objectives: The aim of this study was to identify factors influencing the long-term clinical progression of multiple sclerosis (MS). A special objective was to investigate whether early treatment decisions influence outcome. Methods: We included 639 patients diagnosed with MS from 2001 to 2007. The median follow-up time was 99 months (8.25 years). Cox regression models were applied to identify factors correlating with the outcome variable defined as time from treatment start to irreversible score 4 of the Expanded Disability Status Scale (EDSS). Results: Patients initiated on treatment later had a greater risk of reaching EDSS 4 (hazard ratio of 1.074 (95% confidence interval (CI), 1.048−1.101)), increased by 7.4% for every year of delay in treatment start after MS onset. Patients who started treatment after 3 years from MS onset reached the outcome sooner with hazard ratio of 2.64 (95% CI, 1.71−4.08) compared with the patients who started treatment within 1 year from MS onset. Baseline EDSS and age at onset were found to be predictive factors of disability progression. Conclusion: Early treatment initiation was associated with a better clinical outcome. In addition, we confirmed the well-established prognostic factors of late age at onset and early disability.

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Impact of Hybrid Operating Rooms on Long-Term Clinical Outcomes Following Fenestrated and Branched Endovascular Aortic Repair

Journal of Endovascular Therapy ◽

10.1177/1526602821996725 ◽

2021 ◽

pp. 152660282199672

Author(s):

Giovanni Tinelli ◽

Marie Bonnet ◽

Adrien Hertault ◽

Simona Sica ◽

Gian Luca Di Tanna ◽

...

Keyword(s):

Operating Room ◽

Clinical Outcomes ◽

Cox Regression ◽

Statistical Significance ◽

Aortic Aneurysms ◽

Study Patient ◽

Cox Regression Analysis ◽

Significant Difference ◽

The Impact

Purpose: Evaluate the impact of hybrid operating room (HOR) guidance on the long-term clinical outcomes following fenestrated and branched endovascular repair (F-BEVAR) for complex aortic aneurysms. Materials and Methods: Prospectively collected registry data were retrospectively analyzed to compare the procedural, short- and long-term outcomes of consecutive F-BEVAR performed from January 2010 to December 2014 under standard mobile C-arm versus hybrid room guidance in a high-volume aortic center. Results: A total of 262 consecutive patients, including 133 patients treated with a mobile C-arm equipped operating room and 129 with a HOR guidance, were enrolled in this study. Patient radiation exposure and contrast media volume were significantly reduced in the HOR group. Short-term clinical outcomes were improved despite higher case complexity in the HOR group, with no statistical significance. At a median follow-up of 63.3 months (Q1 33.4, Q3 75.9) in the C-arm group, and 44.9 months (Q1 25.1, Q3 53.5, p=0.53) in the HOR group, there was no statistically significant difference in terms of target vessel occlusion and limb occlusion. When the endograft involved 3 or more fenestrations and/or branches (complex F-BEVAR), graft instability (36% vs 25%, p=0.035), reintervention on target vessels (20% vs 11%, p=0.019) and total reintervention rates (24% vs 15%, p=0.032) were significantly reduced in the HOR group. The multivariable Cox regression analysis did not show statistically significant differences for long-term death and aortic-related death between the 2 groups. Conclusion: Our study suggests that better long-term clinical outcomes could be observed when performing complex F-BEVAR in the latest generation HOR.

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Chances and challenges of a long-term data repository in multiple sclerosis: 20th birthday of the German MS registry

Scientific Reports ◽

10.1038/s41598-021-92722-x ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Lisa-Marie Ohle ◽

David Ellenberger ◽

Peter Flachenecker ◽

Tim Friede ◽

Judith Haas ◽

...

Keyword(s):

Multiple Sclerosis ◽

Sociodemographic Factors ◽

Healthcare Research ◽

Structure Design ◽

Data Repository ◽

Research Projects ◽

Real World Data ◽

Data Repositories ◽

Term Data

AbstractIn 2001, the German Multiple Sclerosis Society, facing lack of data, founded the German MS Registry (GMSR) as a long-term data repository for MS healthcare research. By the establishment of a network of participating neurological centres of different healthcare sectors across Germany, GMSR provides observational real-world data on long-term disease progression, sociodemographic factors, treatment and the healthcare status of people with MS. This paper aims to illustrate the framework of the GMSR. Structure, design and data quality processes as well as collaborations of the GMSR are presented. The registry’s dataset, status and results are discussed. As of 08 January 2021, 187 centres from different healthcare sectors participate in the GMSR. Following its infrastructure and dataset specification upgrades in 2014, more than 196,000 visits have been recorded relating to more than 33,000 persons with MS (PwMS). The GMSR enables monitoring of PwMS in Germany, supports scientific research projects, and collaborates with national and international MS data repositories and initiatives. With its recent pharmacovigilance extension, it aligns with EMA recommendations and helps to ensure early detection of therapy-related safety signals.

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Long-term effectiveness in patients previously treated with cladribine tablets: a real-world analysis of the Italian multiple sclerosis registry (CLARINET-MS)

Therapeutic Advances in Neurological Disorders ◽

10.1177/1756286420922685 ◽

2020 ◽

Vol 13 ◽

pp. 175628642092268 ◽

Cited By ~ 1

Author(s):

Francesco Patti ◽

Andrea Visconti ◽

Antonio Capacchione ◽

Sanjeev Roy ◽

Maria Trojano ◽

...

Keyword(s):

Multiple Sclerosis ◽

Real World ◽

Event Analysis ◽

Treatment Change ◽

Real World Data ◽

Indirect Measure ◽

Disease Modifying Drugs ◽

Disease Modifying ◽

Using Data

Background: The CLARINET-MS study assessed the long-term effectiveness of cladribine tablets by following patients with multiple sclerosis (MS) in Italy, using data from the Italian MS Registry. Methods: Real-world data (RWD) from Italian MS patients who participated in cladribine tablets randomised clinical trials (RCTs; CLARITY, CLARITY Extension, ONWARD or ORACLE-MS) across 17 MS centres were obtained from the Italian MS Registry. RWD were collected during a set observation period, spanning from the last dose of cladribine tablets during the RCT (defined as baseline) to the last visit date in the registry, treatment switch to other disease-modifying drugs, date of last Expanded Disability Status Scale recording or date of the last relapse (whichever occurred last). Time-to-event analysis was completed using the Kaplan–Meier (KM) method. Median duration and associated 95% confidence intervals (CI) were estimated from the model. Results: Time span under observation in the Italian MS Registry was 1–137 (median 80.3) months. In the total Italian patient population ( n = 80), the KM estimates for the probability of being relapse-free at 12, 36 and 60 months after the last dose of cladribine tablets were 84.8%, 66.2% and 57.2%, respectively. The corresponding probability of being progression-free at 60 months after the last dose was 63.7%. The KM estimate for the probability of not initiating another disease-modifying treatment at 60 months after the last dose of cladribine tablets was 28.1%, and the median time-to-treatment change was 32.1 (95% CI 15.5–39.5) months. Conclusion: CLARINET-MS provides an indirect measure of the long-term effectiveness of cladribine tablets. Over half of MS patients analysed did not relapse or experience disability progression during 60 months of follow-up from the last dose, suggesting that cladribine tablets remain effective in years 3 and 4 after short courses at the beginning of years 1 and 2.

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Optimal Timing of Introduction of Complementary feeding: Protocol for a systematic review and meta-analysis

10.21203/rs.3.rs-290067/v1 ◽

2021 ◽

Author(s):

Zahra A. Padhani ◽

Rehana A. Salam ◽

Zohra S. Lassi ◽

Faareha Siddiqui ◽

Emily C. Keats ◽

...

Keyword(s):

Systematic Review ◽

Randomized Trials ◽

Complementary Feeding ◽

Optimal Time ◽

Optimal Timing ◽

Case Control Studies ◽

Poor Growth ◽

Developmental Potential ◽

Early Introduction ◽

The Impact

Abstract Background: The complementary feeding (CF) period accompanies a critical window of vulnerability. During this time, failure to consume adequate energy, protein, vitamins and minerals is a significant concern and can lead to poor growth outcomes, increased susceptibility to infections, allergies, and diseases, and lower developmental potential. It is therefore of utmost importance to determine the most optimal time to start CF. The objective of this review is to assess the impact of early and late of introduction of CF on infant health, nutrition and developmental outcomes.Methods: We will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We will search MEDLINE, Embase, CINAHL, CENTRAL, Web of Science, and other databases and key organizational websites using terms related to complementary feeding and infants. We will also search clinicaltrials.gov for ongoing trials. We will include experimental (randomized trials (individually or cluster) and quasi-randomized trials) and observational studies with a concurrent comparison group (cohort (prospective and retrospective), controlled before-after studies and nested case control studies). We will only include studies that enroll infants, living in low, middle- or high-income countries. Outcomes will be assessed for the following two comparisons:1. Early introduction of CF (before 5 months of age) compared to introduction at 5 to 6.9 months of age2. Late introduction of CF (after 7 months) compared to introduction at 5 to 6.9 months of age All the included studies will be screened on Covidence software and analyzed on Review Manager (version 5.4.1) software.Discussion: There are inconsistencies in the existing recommendations for the introduction of CF, as the recommended age for introducing CF ranges between four and six months of age in various international guidelines. It is imperative to evaluate of consequences of both early and late introduction of complementary foods since optimal timing of introduction may have potential beneficial short- and long-term health effects. Systematic review registration: PROSPERO CRD42020218517

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Do patient and proxy agree? Long-term changes in multiple sclerosis physical impact and walking ability on patient-reported outcome scales

Multiple Sclerosis Journal ◽

10.1177/1352458514529173 ◽

2014 ◽

Vol 20 (12) ◽

pp. 1616-1623 ◽

Cited By ~ 4

Author(s):

Judith M Sonder ◽

Lisanne J Balk ◽

Libertje VAE Bosma ◽

Chris H Polman ◽

Bernard MJ Uitdehaag

Keyword(s):

Multiple Sclerosis ◽

Patient Reported Outcome ◽

Study Data ◽

Walking Ability ◽

Impact Scale ◽

Patient Reported ◽

Proxy Responses ◽

Physical Impact ◽

The Impact

Background: Patient-reported outcome scales (PROs) are useful in monitoring changes in multiple sclerosis (MS) over time. Although these scales are reliable and valid measures in longitudinal studies in MS patients, it is unknown what the impact is when obtaining longitudinal data from proxies. Objective: The objective of this paper is to compare longitudinal changes in patient and proxy responses on PROs assessing physical impact of MS and walking ability. Methods: In a prospective observational study, data on the Multiple Sclerosis Impact Scale (MSIS-29 physical) and Multiple Sclerosis Walking Scale (MSWS-12) were obtained from 137 patient-proxy couples at baseline and at two-year follow-up. Demographic and disease-related variables explaining agreement or disagreement between patients and proxies were investigated using linear regression analyses. Results: Full agreement was found in 56% (MSIS) and 62% (MSWS) of the patient-proxy couples. Complete disagreement was very rare for both scales (2% MSIS, 5% MSWS). When patients were more positive than proxies, a higher age, longer disease duration, longer patient-proxy relationship and increased levels of depression, anxiety and caregiver burden in proxies were observed. Conclusion: In the majority of the patient-proxy couples there was agreement. Proxies can serve as a valuable source of information, but caution remains essential when using scores from proxies.

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Indirect costs associated with ulcerative colitis: a systematic literature review of real-world data

BMC Gastroenterology ◽

10.1186/s12876-019-1095-9 ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 1

Author(s):

Joelle Constantin ◽

Petar Atanasov ◽

Daniel Wirth ◽

Andras Borsi

Keyword(s):

Ulcerative Colitis ◽

Sick Leave ◽

Indirect Costs ◽

Cochrane Library ◽

Real World Data ◽

Eligibility Criteria ◽

Productivity Costs ◽

Productivity Losses ◽

The Impact

Abstract Background The economic burden of ulcerative colitis (UC), specifically related to indirect costs, is not extensively documented. Understanding and quantifying it is required by health care decision makers. Aim To assess the impact of indirect costs of UC in observation studies. Method A systematic literature search was conducted in MEDLINE®, Embase® and Cochrane Library to capture all relevant publications reporting outcomes on absenteeism, presenteeism and productivity losses in moderate to severe UC. Eligibility criteria for inclusion into the review were established using a predefined PICOS scheme. All costs were adjusted to 2017 currency values (USD dollars, $). Results In total, 18 studies reporting data on indirect costs were included in the analysis. Absenteeism costs were classified into three categories: sick leave, short-term and long-term disability. Most of the studies captured absenteeism costs related specifically to sick leave, which was experienced on average by 10 to 24% patients with UC. Only three studies captured presenteeism costs, as these are difficult to measure, however costs ranged from 1602 $ to 2947 $ per patient year. The proportion of indirect costs accounted for 35% of total UC costs (Total UC costs were defined as the sum of healthcare costs, productivity costs and out-of-pocket costs). Discussion A limited number of studies were identified describing the indirect costs in patients with moderate to severe UC. Insufficient data on different components of costs allowed a limited analysis on the impact of indirect costs in patients with UC. Further studies are needed to gain an understanding of the influence of UC on patients’ functional abilities.

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VP08 Real-World Data Use In Health Technology Assessments: A Comparison Of Five Health Technology Assessment Agencies

International Journal of Technology Assessment in Health Care ◽

10.1017/s0266462317003051 ◽

2017 ◽

Vol 33 (S1) ◽

pp. 149-150

Author(s):

Amr Makady ◽

Ard van Veelen ◽

Anthonius de Boer ◽

Hans Hillege ◽

Olaf Klunger ◽

...

Keyword(s):

Health Technology Assessment ◽

Technology Assessment ◽

Real World ◽

Relative Effectiveness ◽

Internal Validity ◽

Health Technology ◽

Real World Data ◽

World Data ◽

The Impact

INTRODUCTION:Reimbursement decisions are usually based on evidence from randomized controlled trials (RCT) with high internal validity but lower external validity. Real-World Data (RWD) may provide complimentary evidence for relative effectiveness assessments (REA's) and cost-effectiveness assessments (CEA's) of treatments. This study explores to which extent RWD is incorporated in REA's and CEA's of drugs used to treat metastatic melanoma (MM) by five Health Technology Assessment (HTA) agencies.METHODS:Dossiers for MM drugs published between 1 January 2011 and 31 December 2016 were retrieved for HTA agencies in five countries: the United Kingdom (NICE), Scotland (SMC), France (HAS), Germany (IQWiG) and the Netherlands (ZIN). A standardized data-extraction form was used to extract data on RWD mentioned in the assessment and its impact on appraisal (for example, positive, negative, neutral or unknown) for both REA and CEA.RESULTS:In total, fourty-nine dossiers were retrieved: NICE = 10, SMC = 13, IQWiG = 16, HAS = 8 and ZIN = 2. Nine dossiers (18.4 percent) included RWD in REA's for several parameters: to describe effectiveness (n = 5) and/or the safety (n = 2) of the drug, and/or the prevalence of MM (n = 4). CEA's were included in 25/49 dossiers (IQWiG and HAS did not perform CEA's). Of the twenty-five CEA's, twenty (80 percent) included RWD to extrapolate long-term effectiveness (n = 19), and/or identify costs associated with treatments (n = 7). When RWD was included in REA's (n = 9), its impact on the appraisal was negative (n = 4), neutral (n = 2), unknown (n = 1) or was not discussed in the appraisal (n = 2). When RWD was included in CEA's (n = 11), its impact on the appraisal varied between positive (n = 2), negative (n = 5) and unknown (n = 4).CONCLUSIONS:Generally, RWD is more often included in CEA's than REA's (80 percent versus 18.4 percent, respectively). When included, RWD was mostly used to describe the effectiveness of the drug (REA) or to predict long-term effectiveness (CEA). The impact of RWD on the appraisal varied greatly within both REA's and CEA's.

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Examining the optimal timing for closed-loop auditory stimulation of slow-wave sleep in young and older adults

SLEEP ◽

10.1093/sleep/zsz315 ◽

2019 ◽

Vol 43 (6) ◽

Cited By ~ 5

Author(s):

Miguel Navarrete ◽

Jules Schneider ◽

Hong-Viet V Ngo ◽

Mario Valderrama ◽

Alexander J Casson ◽

...

Keyword(s):

Slow Wave ◽

Closed Loop ◽

Slow Wave Sleep ◽

Auditory Stimulation ◽

Optimal Time ◽

Optimal Timing ◽

Experimental Conditions ◽

Young Subjects ◽

The Impact ◽

Specific Phase

Abstract Study Objectives Closed-loop auditory stimulation (CLAS) is a method for enhancing slow oscillations (SOs) through the presentation of auditory clicks during sleep. CLAS boosts SOs amplitude and sleep spindle power, but the optimal timing for click delivery remains unclear. Here, we determine the optimal time to present auditory clicks to maximize the enhancement of SO amplitude and spindle likelihood. Methods We examined the main factors predicting SO amplitude and sleep spindles in a dataset of 21 young and 17 older subjects. The participants received CLAS during slow-wave-sleep in two experimental conditions: sham and auditory stimulation. Post-stimulus SOs and spindles were evaluated according to the click phase on the SOs and compared between and within conditions. Results We revealed that auditory clicks applied anywhere on the positive portion of the SO increased SO amplitudes and spindle likelihood, although the interval of opportunity was shorter in the older group. For both groups, analyses showed that the optimal timing for click delivery is close to the SO peak phase. Click phase on the SO wave was the main factor determining the impact of auditory stimulation on spindle likelihood for young subjects, whereas for older participants, the temporal lag since the last spindle was a better predictor of spindle likelihood. Conclusions Our data suggest that CLAS can more effectively boost SOs during specific phase windows, and these differ between young and older participants. It is possible that this is due to the fluctuation of sensory inputs modulated by the thalamocortical networks during the SO.

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124Impact of intimal tracking for recanalization of CTO lesions on long-term clinical outcomes

European Heart Journal ◽

10.1093/eurheartj/ehz747.0040 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

S Kano ◽

K Nasu ◽

M Habara ◽

T Shimura ◽

M Yamamoto ◽

...

Keyword(s):

Clinical Outcomes ◽

Cox Regression ◽

Target Lesion ◽

Hazard Ratio ◽

Rank Test ◽

Total Occlusion ◽

Significant Difference ◽

The Impact

Abstract Background For recanalization of coronary chronic total occlusion (CTO) lesions, subintimal guidewire tracking in both antegrade and retrograde approaches are commonly used. Purpose This study aimed to assess the impact of subintimal tracking on long-term clinical outcomes after recanalization of CTO lesions. Methods Between January 2009 and December 2016, 474 CTO lesions (434patients) were successfully recanalized in our center. After guidewire crossing in a CTO lesion, those lesions were divided into intimal tracking group (84.6%, n=401) and subintimal tracking group (15.4%, n=73) according to intravascular ultrasound (IVUS) findings. Long-term clinical outcomes including death, target lesion revascularization (TLR), target vessel revascularization (TVR) were compared between the two groups. In addition, the rate of re-occlusion after successful revascularization was also evaluated. Results The median follow-up period was 4.7 years (interquartile range, 2.8–6.1). There was no significant difference of the rate of cardiac death between the two groups (intimal tracking vs. subintimal tracking: 7.0% vs. 4.1%; hazard ratio, 0.61; 95% confidence interval [CI], 0.19 to 2.00; p=0.41), TLR (14.3% vs. 16.2%; hazard ratio, 1.34; 95% CI, 0.71 to 2.53; p=0.37), and TVR (17.5% vs. 20.3%; hazard ratio, 1.27; 95% CI, 0.72 to 2.23; p=0.42). However, the rate of re-occlusion was significantly higher in the subintimal tracking group than intimal tracking group at 3-years re-occlusion (4.2% vs. 14.5%; log-rank test, p=0.002, Figure). In the multivariate COX regression, subintimal guidewire tracking was an independent predictor of re-occlusion after CTO recanalization (HR: 5.40; 95% CI: 2.11–13.80; p<0.001). Figure 1 Conclusions Subintimal guidewire tracking for recanalization of coronary CTO was associated with significantly higher incidence of target lesion re-occlusion during long-term follow-up period.

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