scholarly journals Long-term disability progression of pediatric-onset multiple sclerosis

Neurology ◽  
2019 ◽  
Vol 92 (24) ◽  
pp. e2764-e2773 ◽  
Author(s):  
Kyla A. McKay ◽  
Jan Hillert ◽  
Ali Manouchehrinia
Keyword(s):  
Multiple Sclerosis ◽  
Proportional Hazards ◽  
Clinical Information ◽  
Cox Proportional Hazards ◽  
Disability Progression ◽  
Kaplan Meier ◽  
Younger Age ◽  
Risk Of Progression ◽  
Pediatric Onset

ObjectiveTo evaluate long-term disability progression in pediatric-onset multiple sclerosis (POMS) and compare to adult-onset multiple sclerosis (AOMS).MethodsThis was a retrospective cohort study using prospectively collected clinical information from the Swedish MS Registry. Clinical features were compared and Kaplan-Meier and Cox proportional hazards regression were used to assess the risk of reaching sustained Expanded Disability Status Scale (EDSS) 3, 4, and 6 in POMS (multiple sclerosis [MS] onset <18 years) and AOMS (MS onset ≥18 years).ResultsA total of 12,482 persons were included; 549 (4.4%) were classified as POMS. The POMS cohort took longer to reach all 3 disability milestones from their MS onset, but did so at a younger age than the AOMS cohort. Primary progressive course (hazard ratio [HR] 4.63; 95% confidence interval [CI] 1.46–14.7), higher relapse rate in the first 5 years of disease (HR 5.35; 95% CI 3.37–8.49), and complete remission from the initial relapse (HR 0.41; 95% CI 0.18–0.94) were associated with an altered risk of progression to EDSS 4 among POMS cases. The same pattern emerged for the risk of reaching EDSS 3 and 6.ConclusionsPatients with pediatric-onset MS follow a distinctive clinical course, which should be considered in the treatment and management of the disease.

Inter-pregnancy interval and later pediatric cardiovascular health of the offspring – a population-based cohort study

2020 ◽  
pp. 1-5
Author(s):  
Majdi Imterat ◽  
Tamar Wainstock ◽  
Eyal Sheiner ◽  
Gali Pariente
Keyword(s):  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Population Based ◽  
Cox Proportional Hazards ◽  
Cardiovascular Morbidity ◽  
Cox Proportional Hazards Model ◽  
Hazards Model ◽  
Kaplan Meier ◽  
Inter Pregnancy Interval

Abstract Recent evidence suggests that a long inter-pregnancy interval (IPI: time interval between live birth and estimated time of conception of subsequent pregnancy) poses a risk for adverse short-term perinatal outcome. We aimed to study the effect of short (<6 months) and long (>60 months) IPI on long-term cardiovascular morbidity of the offspring. A population-based cohort study was performed in which all singleton live births in parturients with at least one previous birth were included. Hospitalizations of the offspring up to the age of 18 years involving cardiovascular diseases and according to IPI length were evaluated. Intermediate interval, between 6 and 60 months, was considered the reference. Kaplan–Meier survival curves were used to compare the cumulative morbidity incidence between the groups. Cox proportional hazards model was used to control for confounders. During the study period, 161,793 deliveries met the inclusion criteria. Of them, 14.1% (n = 22,851) occurred in parturient following a short IPI, 78.6% (n = 127,146) following an intermediate IPI, and 7.3% (n = 11,796) following a long IPI. Total hospitalizations of the offspring, involving cardiovascular morbidity, were comparable between the groups. The Kaplan–Meier survival curves demonstrated similar cumulative incidences of cardiovascular morbidity in all groups. In a Cox proportional hazards model, short and long IPI did not appear as independent risk factors for later pediatric cardiovascular morbidity of the offspring (adjusted HR 0.97, 95% CI 0.80–1.18; adjusted HR 1.01, 95% CI 0.83–1.37, for short and long IPI, respectively). In our population, extreme IPIs do not appear to impact long-term cardiovascular hospitalizations of offspring.

scholarly journals A Combined Prospective and Retrospective Comparison of Long-Term Functional Outcomes Suggests Delayed Loss of Ambulation and Pulmonary Decline with Long-Term Eteplirsen Treatment

2021 ◽  
pp. 1-14 ◽  
Author(s):  
Olga Mitelman ◽  
Hoda Z. Abdel-Hamid ◽  
Barry J. Byrne ◽  
Anne M. Connolly ◽  
Peter Heydemann ◽  
...  
Keyword(s):  
Natural History ◽  
Repeated Measures ◽  
Proportional Hazards ◽  
Clinical Care ◽  
Standard Of Care ◽  
Cox Proportional Hazards ◽  
Kaplan Meier ◽  
Cox Proportional Hazards Models

Background: Studies 4658-201/202 (201/202) evaluated treatment effects of eteplirsen over 4 years in patients with Duchenne muscular dystrophy and confirmed exon-51 amenable genetic mutations. Chart review Study 4658-405 (405) further followed these patients while receiving eteplirsen during usual clinical care. Objective: To compare long-term clinical outcomes of eteplirsen-treated patients from Studies 201/202/405 with those of external controls. Methods: Median total follow-up time was approximately 6 years of eteplirsen treatment. Outcomes included loss of ambulation (LOA) and percent-predicted forced vital capacity (FVC%p). Time to LOA was compared between eteplirsen-treated patients and standard of care (SOC) external controls and was measured from eteplirsen initiation in 201/202 or, in the SOC group, from the first study visit. Comparisons were conducted using univariate Kaplan-Meier analyses and log-rank tests, and multivariate Cox proportional hazards models with regression adjustment for baseline characteristics. Annual change in FVC%p was compared between eteplirsen-treated patients and natural history study patients using linear mixed models with repeated measures. Results: Data were included from all 12 patients in Studies 201/202 and the 10 patients with available data from 405. Median age at LOA was 15.16 years. Eteplirsen-treated patients experienced a statistically significant longer median time to LOA by 2.09 years (5.09 vs. 3.00 years, p < 0.01) and significantly attenuated rates of pulmonary decline vs. natural history patients (FVC%p change: –3.3 vs. –6.0 percentage points annually, p < 0.0001). Conclusions: Study 405 highlights the functional benefits of eteplirsen on ambulatory and pulmonary function outcomes up to 7 years of follow-up in comparison to external controls.

scholarly journals Perinatal Outcome and Long-Term Gastrointestinal Morbidity of Offspring of Women with Celiac Disease

2019 ◽  
Vol 8 (11) ◽  
pp. 1924
Author(s):  
Abecassis ◽  
Wainstock ◽  
Sheiner ◽  
Pariente
Keyword(s):  
Risk Factor ◽  
Celiac Disease ◽  
Perinatal Outcome ◽  
Independent Risk Factor ◽  
Proportional Hazards ◽  
Perinatal Outcomes ◽  
Cox Proportional Hazards ◽  
Rank Test ◽  
Kaplan Meier

The aim of this study was to evaluate perinatal outcome and long-term offspring gastrointestinal morbidity of women with celiac disease. Perinatal outcomes, as well as long-term gastrointestinal morbidity of offspring of mothers with and without celiac disease were assessed. The study groups were followed until 18 years of age for gastrointestinal-related morbidity. For perinatal outcomes, generalized estimation equation (GEE) models were used. A Kaplan–Meier survival curve was used to compare cumulative incidence of long-term gastrointestinal morbidity, and Cox proportional hazards models were constructed to control for confounders. During the study period, 243,682 deliveries met the inclusion criteria, of which 212 (0.08%) were to mothers with celiac disease. Using GEE models, maternal celiac disease was noted as an independent risk factor for low birth weight and cesarean delivery. Offspring born to mothers with celiac disease had higher rates of gastrointestinal related morbidity (Kaplan–Meier log rank test P < 0.001). Using a Cox proportional hazards model, being born to a mother with celiac disease was found to be an independent risk factor for long-term gastrointestinal morbidity of the offspring. Pregnancy of women with celiac disease is independently associated with adverse perinatal outcome as well as higher risk for long-term gastrointestinal morbidity of offspring.

Socioeconomic status and disability progression in multiple sclerosis

Neurology ◽  
2019 ◽  
Vol 92 (13) ◽  
pp. e1497-e1506 ◽  
Author(s):  
Katharine E. Harding ◽  
Mark Wardle ◽  
Robert Carruthers ◽  
Neil Robertson ◽  
Feng Zhu ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Socioeconomic Status ◽  
Drug Exposure ◽  
Proportional Hazards ◽  
Meta Analysis ◽  
Random Effect ◽  
Cox Proportional Hazards ◽  
Disability Progression ◽  
Cox Proportional Hazards Models ◽  
Neighborhood Level

ObjectiveTo examine the association between socioeconomic status (SES) and disability outcomes and progression in multiple sclerosis (MS).MethodsHealth administrative and MS clinical data were linked for 2 cohorts of patients with MS in British Columbia (Canada) and South East Wales (UK). SES was measured at MS symptom onset (±3 years) based on neighborhood-level average income. The association between SES at MS onset and sustained and confirmed Expanded Disability Status Scale (EDSS) 6.0 and 4.0 and onset of secondary progression of MS (SPMS) were assessed using Cox proportional hazards models. EDSS scores were also examined via linear regression, using generalized estimating equations (GEE) with an exchangeable working correlation. Models were adjusted for onset age, sex, initial disease course, and disease-modifying drug exposure. Random effect models (meta-analysis) were used to combine results from the 2 cohorts.ResultsA total of 3,113 patients with MS were included (2,069 from Canada; 1,044 from Wales). A higher SES was associated with a lower hazard of reaching EDSS 6.0 (adjusted hazard ratio [aHR] 0.90, 95% confidence interval [CI] 0.89–0.91), EDSS 4.0 (aHR 0.93, 0.88–0.98), and SPMS (aHR 0.94, 0.88–0.99). The direction of findings was similar when all EDSS scores were included (GEE: β = −0.13, −0.18 to −0.08).ConclusionsLower neighborhood-level SES was associated with a higher risk of disability progression. Reasons for this association are likely to be complex but could include factors amenable to modification, such as lifestyle or comorbidity. Our findings are relevant for planning and development of MS services.

scholarly journals Long-term worsening of different body functions in persons with progressive multiple sclerosis

2020 ◽  
Vol 6 (4) ◽  
pp. 205521732096451
Author(s):  
Marco Kaufmann ◽  
Claude Vaney ◽  
Laura Barin ◽  
Xinglu Liu ◽  
Viktor von Wyl
Keyword(s):  
Multiple Sclerosis ◽  
Cox Regression ◽  
Inpatient Rehabilitation ◽  
Progressive Multiple Sclerosis ◽  
Advanced Stage ◽  
Disability Progression ◽  
Mobility Index ◽  
Kaplan Meier ◽  
Valid Predictor

Background It is unclear whether EDSS is responsive to disability worsening in advanced MS. Objective To explore the dynamics of disability worsening in persons with advanced-stage MS (EDSS ≥5.5) using three disability worsening definitions (EDSS, Rivermead Mobility Index (RMI), 9-Hole Peg Test (9-HPT)). Methods EDSS-, RMI- and 9-HPT-based disability worsening were assessed over a minimum of two years in a cohort of 286 persons with advanced MS attending inpatient rehabilitation using Kaplan-Meier Curves and multivariable Cox regression. Furthermore, the correspondence between EDSS-, RMI- and 9-HPT-based disability worsening was analyzed. Results Disability progression was observed in 49% (9-HPT), 52% (EDSS) and 53% (RMI), with 9-HPT-based worsening slightly lagging behind. The Multiple Sclerosis Severity Score (MSSS) was the only consistent factor predicting disability worsening based on all three definitions (EDSS: hazard ratio 1.48 [1.30;1.68]; RMI: 1.12 [0.99;1.27]; 9-HPT: 1.36 [1.18;1.57]). Correspondence between EDSS and the other definitions (9-HPT and RMI) was 44.3% and 55.7% at time of EDSS progression and 65.1% and 72.5% overall, respectively. Conclusion In persons with advanced-stage MS, half still developed disability worsening in different functional systems over a median of 6 years. MSSS seems a valid predictor for disability worsening in all three outcome measures in advanced MS.

Maternal Hypothyroidism during Pregnancy and the Risk for Infectious Morbidity of the Offspring

2019 ◽  
Vol 37 (03) ◽  
pp. 291-295 ◽  
Author(s):  
Ofer Beharier ◽  
Asnat Walfisch ◽  
Tamar Wainstock ◽  
Irit Szaingurten-Solodkin ◽  
Daniela Landau ◽  
...  
Keyword(s):  
Animal Studies ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Infectious Morbidity ◽  
Hazards Model ◽  
Kaplan Meier ◽  
Increased Risk

Abstract Objective Animal studies indicate a possible intrauterine immunological imprinting in pregnancies complicated by hypothyroidism. We aimed to evaluate whether exposure to maternal hypothyroidism during pregnancy increases the risk of long-term infectious morbidity of the offspring. Study Design A retrospective cohort study compared the long-term risk of hospitalization associated with infectious morbidity in children exposed and unexposed in utero to maternal hypothyroidism. Outcome measures included infectious diagnoses obtained during any hospitalization of the offspring (up to the age of 18 years). Results The study included 224,950 deliveries. Of them, 1.1% (n = 2,481) were diagnosed with maternal hypothyroidism. Children exposed to maternal hypothyroidism had a significantly higher rate of hospitalizations related to infectious morbidity (13.2 vs. 11.2% for control; odds ratio: 1.2; 95% confidence interval: 1.08–1.36; p = 0.002). Specifically, incidences of ear, nose, and throat; respiratory; and ophthalmic infections were significantly higher among the exposed group. The Kaplan–Meier curve indicated that children exposed to maternal hypothyroidism had higher cumulative rates of long-term infectious morbidity. In the Cox proportional hazards model, maternal hypothyroidism remained independently associated with an increased risk of infectious morbidity in the offspring while adjusting for confounders. Conclusion Maternal hypothyroidism during pregnancy is associated with significant pediatric infectious morbidity of the offspring.

scholarly journals THE PROGNOSTIC SIGNIFICANCE OF CD3+, CD68+, CD20+ INTERSTITIAL CELLS IN PATIENTS WITH KIDNEY ALLOGRAFT GLOMERULITIS

2018 ◽  
Vol 22 (6) ◽  
pp. 47-55
Author(s):  
V. A. Dobronravov ◽  
A. O. Mukhametdinova ◽  
M. S. Khrabrova ◽  
A. Nabokow ◽  
H. -J. Gröne ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Cox Regression ◽  
Prognostic Significance ◽  
Cox Proportional Hazards ◽  
Cox Regression Analysis ◽  
Kaplan Meier ◽  
Long Term Prognosis ◽  
The Impact ◽  
The Relationship

THE OBJECTIVEof the study was to assess the impact of the count of interstitial CD3+, CD68+ and CD20+ cells on long-term prognosis of renal allograft (RA).PATIENTS AND METHODS.86 RA recipients with biopsy-proven according to the Banff 2013- 2017 criteria glomerulitis were enrolled in this retrospective study. The patients were subdivided into the following groups: 1) isolated glomerulitis with negative donor-specific antibodies (DSA) at the biopsy (n=53); 2) glomerulitis with positive DSA (n=22); 3) glomerulitis with undetermined DSA (n=11). Quantitative assay of interstitial positive cells was performed after immunohistochemical staining for CD68+, CD3+, CD20+. The Kaplan-Meier method and Cox proportional hazards regression model were used for the analysis of the relationship between interstitial CD3+, CD68+, CD20+ cells and risk of RA loss.RESULTS.CD68+ and CD3+ cells prevailed in interstitium in RA glomerulitis. CD20+ infiltrates were found in 60% of cases. CD20+ cells tended to form infiltrates, in 9 cases these infiltrates reached large sizes (≥ 50 CD20+ lymphocytes) and formed nodular structures. There was no difference in the count of interstitial CD3+ and CD68+ cells and in the presence of CD20+ infiltrates between DSA subgroups. Interstitial CD68+ ≥ 5 cells per field of view (FOV) (x400) and CD3+ ≥ 8 cells per FOV (x400), as well as the presence of large CD20+ infiltrates were associated with a lower RA survival (plog-rank < 0,05). Interstitial CD68+ (≥ 5 cells/FOV), CD3 + (≥ 8 cells/FOV) and the presence of large CD20+ interstitial infiltrates were independently associated with the risk of RA loss in the multivariable Cox regression analysis adjusted for DSA, cold and warm ischemia time (p < 0.05). CONCLUSION. Grade of interstitial infiltration by CD68+, CD3+ and CD20+ cells in RA glomerulitis could be independent predictor of RA loss.

scholarly journals Long term follow-up of pediatric-onset Evans syndrome: broad immunopathological manifestations and high treatment burden

Haematologica ◽  
2021 ◽  
Author(s):  
Thomas Pincez ◽  
Helder Fernandes ◽  
Thierry Leblanc ◽  
Gérard Michel ◽  
Vincent Barlogis ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Second Line ◽  
Treatment Burden ◽  
Evans Syndrome ◽  
Subsequent Increase ◽  
Wide Range ◽  
Pediatric Onset

Pediatric-onset Evans syndrome (pES) is defined by both immune thrombocytopenic purpura (ITP) and autoimmune hemolytic anemia (AIHA) before the age of 18 years. There have been no comprehensive long-term studies of this rare disease, which can be associated to various immunopathological manifestations (IMs). We report outcomes of the 151 patients with pES and more than 5 years of follow-up from the nationwide French prospective OBS’CEREVANCE cohort. Median age at final follow-up was 18.5 (6.8–50.0) years and the median follow-up period was 11.3 (5.1–38.0) years. At 10 years, ITP and AIHA were in sustained complete remission in 54.5% and 78.4% of patients, respectively. The frequency and number of clinical and biological IMs increased with age: at 20 years old, 74% had at least one clinical cIM. A wide range of cIMs occurred, mainly lymphoproliferation, dermatological, gastrointestinal/hepatic and pneumological IMs. The number of cIMs was associated with a subsequent increase in the number of second-line treatments received (other than steroids and immunoglobulins; hazard ratio, 1.4; 95% confidence interval, 1.15–1.60; p = 0.0002, Cox proportional hazards method). Survival at 15 years after diagnosis was 84%. Death occurred at a median age of 18 (1.7–31.5) years, and the most frequent cause was infection. The number of second-line treatments and severe/recurrent infections were independently associated with mortality. In conclusion, longterm outcomes of pES showed remission of cytopenias but frequent IMs linked to high secondline treatment burden. Mortality was associated to drugs and/or underlying immunodeficiencies, and adolescents-young adults are a high-risk subgroup.

Stereotactic Radiosurgery for Neurofibromatosis 2—Associated Vestibular Schwannomas

Neurosurgery ◽  
2013 ◽  
Vol 74 (3) ◽  
pp. 292-301 ◽  
Author(s):  
Grant W. Mallory ◽  
Bruce E. Pollock ◽  
Robert L. Foote ◽  
Matthew L. Carlson ◽  
Colin L. Driscoll ◽  
...  
Keyword(s):  
Tumor Volume ◽  
Proportional Hazards ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Nerve Function ◽  
Facial Nerve Function ◽  
Free Survival ◽  
Kaplan Meier

Abstract BACKGROUND: Management of neurofibromatosis type 2 (NF2)—associated vestibular schwannomas (VSs) remains controversial. Stereotactic radiosurgery (SRS) with conventional dosing is less effective for NF2-related VS compared with sporadic lesions. OBJECTIVE: To evaluate optimal SRS dose parameters for NF2-related VS and to report long-term outcomes. METHODS: A prospective database was reviewed and outcome measures, including radiographic progression, American Academy of Otolaryngology—Head and Neck Surgery hearing class, and facial nerve function, were analyzed. Progression-free survival was estimated with Kaplan-Meier methods. Associations between tumor progression and radiosurgical treatment parameters, tumor volume, and patient age were explored with the use of Cox proportional hazards regression. RESULTS: Between 1990 and 2010, 26 patients with 32 NF2-related VSs underwent SRS. Median marginal dose and tumor volume were 14 Gy and 2.7 cm3, respectively. Twenty-seven tumors (84%) showed no growth (median follow-up, 7.6 years). Kaplan-Meier estimates for 5- and 10-year progression-free survival were 85% and 80%, respectively. Cox proportional hazards demonstrated a significant inverse association between higher marginal doses and tumor progression (hazard ratio, 0.49; 95% confidence interval, 0.17-0.92; P = .02). Audiometric data were available in 30 ears, with 12 having class A/B hearing before SRS. Only 3 maintained serviceable hearing at the last follow-up. Four underwent cochlear implantation. Initially, 3 achieved open-set speech recognition, although only 1 experienced long-term benefit. Facial nerve function remained stable in 50% of cases. CONCLUSION: Higher marginal doses than commonly prescribed for sporadic VS were associated with improved tumor control in patients with NF2. Hearing outcomes were poor even when contemporary reduced marginal doses were used. However, SRS allows an anatomically preserved cochlear nerve and may permit hearing rehabilitation with cochlear implantation. Further consideration should be given to optimum dosing to achieve long-term control while maximizing functional outcomes.

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