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Hannover, Germany

Lee J.,Floating Hospital for Children at Tufts Medical Center | Dammann O.,Floating Hospital for Children at Tufts Medical Center | Dammann O.,Hannover Medical School | Dammann O.,Neuroepidemiology Unit
Seminars in Fetal and Neonatal Medicine | Year: 2012

The major known risk factors for retinopathy of prematurity (ROP) are extremely low gestational age, exposure to high levels of oxygen early after birth (phase I) and relatively lower oxygen levels later (phase II). In this review, we summarize recent data suggesting that exposure to perinatal infection/inflammation is associated with an increased risk for ROP. Part of this effect might be due to direct exposure of the developing retina to circulating products of infection and/or inflammation. Another potential mechanism that deserves exploration is that inflammation and/or oxidative stress can modify the known increased risk of oxygen-associated ROP. Taken together, accumulating evidence suggests that prenatal, perinatal, and postnatal systemic inflammation contribute to a 'pre-phase', sensitizing the pre-ROP retina for subsequent insults, setting the stage for what are now called phase I and phase II of ROP pathogenesis. Strategies targeting inflammatory responses might help reduce the risk for ROP in extremely low gestational age newborns. © 2011 Elsevier Ltd.

Filippini G.,Neuroepidemiology Unit
The Cochrane database of systematic reviews | Year: 2013

Different therapeutic strategies are available for treatment of multiple sclerosis (MS) including immunosuppressants, immunomodulators, and monoclonal antibodies. Their relative effectiveness in the prevention of relapse or disability progression is unclear due to the mitoxantrone (median OR versus placebo 0.43, 95% CrI 0.20 to 0.87), glatiramer acetate (median OR versus placebo 0.48, 95% CrI 0.38 to 0.75), IFNß-1b (Betaseron) (median OR versus placebo 0.48, 95% CrI 0.29 to 0.78). However, our confidence was moderate for direct comparison of mitoxantrone and IFNB-1b vs placebo and very low for direct comparison of glatiramer vs placebo. The relapse outcome for RRMS at three years' follow-up was not reported by any of the included trials.Disability progression was based on surrogate markers in the majority of included studies and was unavailable for RRMS beyond two to three years. The pairwise meta-analysis suggested, with moderate quality evidence, that natalizumab and IFNß-1a (Rebif) probably decreased the odds of the participants with RRMS having disability progression at two years' follow-up, with an absolute reduction of 14% and 10%, respectively, compared to placebo. Natalizumab and IFNß-1b (Betaseron) were significantly more effective (OR 0.62, 95% CI 0.49 to 0.78; OR 0.35, 95% CI 0.17 to 0.70, respectively) than IFNß-1a (Avonex) in reducing the number of the participants with RRMS who had progression at two years' follow-up, and confidence in this result was graded as moderate. From the network meta-analyses, mitoxantrone appeared to be the most effective agent in decreasing the odds of the participants with RRMS having progression at two years' follow-up, but our confidence was very low for direct comparison of mitoxantrone vs placebo. Both pairwise and network meta-analysis revealed that none of the individual agents included in this review were effective in preventing disability progression over two or three years in patients with progressive MS.There was not a dose-effect relationship for any of the included treatments with the exception of mitoxantrone. Our review should provide some guidance to clinicians and patients. On the basis of high quality evidence, natalizumab and IFNß-1a (Rebif) are superior to all other treatments for preventing clinical relapses in RRMS in the short-term (24 months) compared to placebo. Moderate quality evidence supports a protective effect of natalizumab and IFNß-1a (Rebif) against disability progression in RRMS in the short-term compared to placebo. These treatments are associated with long-term serious adverse events and their benefit-risk balance might be unfavourable. IFNß-1b (Betaseron) and mitoxantrone probably decreased the odds of the participants with RRMS having relapses, compared with placebo (moderate quality of evidence). The benefit-risk balance with azathioprine is uncertain, however this agent might be effective in decreasing the odds of the participants with RRMS having relapses and disability progression over 24 to 36 months, compared with placebo. The lack of convincing efficacy data shows that IFNß-1a (Avonex), intravenous immunoglobulins, cyclophosphamide and long-term steroids have an unfavourable benefit-risk balance in RRMS. None of the included treatments are effective in decreasing disability progression in patients with progressive MS. It is important to consider that the clinical effects of all these treatments beyond two years are uncertain, a relevant point for a disease of 30 to 40 years duration. Direct head-to-head comparison(s) between natalizumab and IFNß-1a (Rebif) or between azathioprine and IFNß-1a (Rebif) should be top priority on the research agenda and follow-up of the trial cohorts should be mandatory.

Farinotti M.,Neuroepidemiology Unit
Cochrane database of systematic reviews (Online) | Year: 2012

Clinical and experimental data suggest that certain dietary regimens, particularly those including polyunsaturated fatty acids (PUFAs) and vitamins, might improve outcomes in people with multiple sclerosis (MS). Diets and dietary supplements are much used by people with MS in the belief that they might improve disease outcomes and overcome the effectiveness limits of conventional treatments.This is an update of the Cochrane review "Dietary intervention for multiple sclerosis" (first published on The Cochrane Library 2007, Issue 1). To answer MS patients' questions regarding the efficacy and safety of dietary regimens for MS. Can changes in dietary habits be an effective intervention for MS patients? Are the potential side effects of these interventions known, and have they been measured? Are potential interactions between dietary interventions and other curative or symptomatic treatments known and have they been studied? We searched the Cochrane Multiple Sclerosis and Rare Diseases of the Central Nervous System Group Specialised Register (November 2011), CENTRAL (The Cochrane Library 2011, Issue 4), MEDLINE (PubMed) (1966 to November 2011), EMBASE (embase.com) (1974 to November 2011) and reference lists of papers found. All controlled trials (randomised controlled trials (RCTs) and controlled clinical trials (CCTs)) on a specific dietary intervention, diet plan or dietary supplementation, except for vitamin D supplementation, compared to no dietary modification or placebo were eligible. Two review authors independently selected articles, assessed trial quality and extracted data. Data were entered and analysed in RevMan.Dichotomous data were summarised as relative risks (RR) with 95% confidence intervals (95% CI) using a random-effects model in the presence of heterogeneity (I2 > 60%). Continuous data were analysed using weighted mean differences, determined by the difference between the pre- and post-intervention changes in the treatment and control groups. Six RCTs that investigated PUFAs emerged from the search strategy, accounting for 794 randomised patients.PUFAs did not have a significant effect on disease progression at 24 months. Omega-6 fatty acids (11 to 23 g/day linoleic acid) didn't show any benefit in 144 MS patients (RR 1.04, 95% CI 0.66 to 1.63). Linoleic acid (2.9 to 3.4 g/day) had no benefit in 65 chronic progressive MS patients (RR 0.78, 95% CI 0.43 to 1.42). Omega-3 fatty acids had no benefit in 292 relapsing remitting MS patients (RR 0.82, 95% CI 0.65 to 1.03, P = 0.08).Slight potential benefits in relapse outcomes were associated with omega-6 fatty acids in some studies, however these findings were limited by the reduced validity of the endpoints. No judgements about safety or patient-reported outcomes were possible. In general, trial quality was poor.No studies on vitamin supplementation and allergen-free diets were analysed as none met the eligibility criteria, mainly due to lack of clinical outcomes. PUFAs seem to have no major effect on the main clinical outcome in MS (disease progression), but they may tend to reduce the frequency of relapses over two years. However, the data that are available are insufficient to assess a real benefit or harm from PUFA supplementation because of their uncertain quality.Evidence on the possible benefits and risks of vitamin supplementation and antioxidant supplements in MS is lacking. More research is required to assess the effectiveness of dietary interventions in MS.

Milo R.,Barzilai Medical Center | Kahana E.,Barzilai Medical Center | Kahana E.,Neuroepidemiology Unit
Autoimmunity Reviews | Year: 2010

Multiple sclerosis (MS) is a chronic immune-mediated demyelinating disease of the central nervous system characterized by relapses and remissions. The risk of acquiring this complex disease is associated with exposure to environmental factors in genetically susceptible individuals. The epidemiology of MS has been extensively studied. We review the geographic epidemiology of the disease, the influence of immigration, age at immigration, clustering and epidemics. Various presumptive risk factors are discussed such as ultraviolet radiation, vitamin D, Epstein-Barr virus and infectious mononucleosis, other infectious agents and non-infectious factors. Two different hypotheses, the hygiene hypothesis and the prevalence hypothesis, were proposed to explain these environmental risk factors for MS. The epidemiological data, combined with pathological and immunological data, may contribute to the debate whether MS is an autoimmune disease, a latent or persistent viral disease, or a neurodegenerative disease. © 2009 Elsevier B.V. All rights reserved.

Dammann O.,Tufts University | Dammann O.,Floating Hospital for Children at Tufts Medical Center | Dammann O.,Hannover Medical School | Leviton A.,Neuroepidemiology Unit
Pediatric Research | Year: 2014

Exposure to perinatal infection and inflammation is associated with an increased risk for neonatal brain damage and developmental disabilities. In this integrated mechanism review, we discuss evidence in support of the contention that the preterm newborn is capable of intermittent or sustained systemic inflammation (ISSI), which appears to contribute more to adverse neurodevelopmental outcomes in preterm infants than does shorter duration inflammation. Copyright © 2014 International Pediatric Research Foundation, Inc.

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