Objectives:
To assess the impact of timing of natalizumab cessation/redosing on long-term maternal and infant outcomes in 72 out of the original 74 pregnancies of the Italian Pregnancy Dataset in ...multiple sclerosis (MS).
Methods:
Maternal outcomes in patients who received natalizumab until conception and restarted the drug within 1 month after delivery (“treatment approach,” (TA)) and patients who stopped natalizumab before conception and/or restarted the drug later than 1 month after delivery (“conservative approach,” (CA)) were compared through multivariable Cox regression analyses. Pediatric outcomes were assessed through a semi-structured questionnaire.
Results:
After a mean follow-up of 6.1 years, CA (hazard ratio (HR) = 4.1, 95% CI 1.6–10.6, p = 0.003) was the only predictor of relapse occurrence. Worsening on the Expanded Disability Status Scale (EDSS) was associated with higher annualized relapse-rate during the follow-up (HR = 3.3, 95% CI 1.4–7.9 p = 0.007). We found no major development abnormalities in children.
Discussion:
Our data confirm that TA reduces the risk of disease activity; we did not observe an increase in major development abnormalities in the child.
This study examined the prevalence of Axis I and II psychopathology and its relationship with quality of life in candidates for bariatric surgery.
Consecutive obese subjects (N = 282) with a body ...mass index (BMI) of 30 kg/m(2) or more received a thorough psychiatric assessment including the Structured Clinical Interviews for DSM-IV Axis I and II Disorders; the Hamilton Rating Scale for Depression; the Bulimic Investigatory Test, Edinburgh; and the short-form Quality of Life Enjoyment and Satisfaction Questionnaire. Subjects were recruited between November 2001 and March 2006.
The overall prevalence of lifetime Axis I disorders in the sample was 37.6%. Mood disorders were the most common diagnoses (22.0%). Anxiety disorders and eating disorders were found in 18.1% and 12.8% of the sample, respectively. Alcohol or substance use disorders were uncommon. The percentage of subjects meeting criteria for at least 1 lifetime Axis I disorder did not vary by BMI class or gender. The prevalence of current Axis I disorders was 20.9% (N = 59). Fifty-five subjects (19.5%) met criteria for at least 1 Axis II disorder. Cluster C disorders, including avoidant, dependent, and obsessive-compulsive personality disorders, comprised virtually all the disorders in the sample (N = 53, 18.8%). Quality of life was poor, unrelated with gender or BMI, and significantly more impaired in individuals with comorbid Axis I and II disorders compared with those without disorders (p = .035).
About one fifth of the sample presented with a current Axis I disorder, and the same percentage had a personality disorder. Although obesity surgery is not contraindicated based on psychiatric disorders, adequate preoperative treatment should be provided to individuals in need of psychiatric support to improve the postoperative outcome and reduce the risk of complications.
Results from case‐control and prospective studies suggest a moderate positive association between obesity and height and differentiated thyroid carcinoma (TC). Little is known on the relationship ...between other measures of adiposity and differentiated TC risk. Here, we present the results of a study on body size and risk of differentiated TC based on a large European prospective study (EPIC). During follow‐up, 508 incident cases of differentiated TC were identified in women, and 58 in men. 78% of cases were papillary TC. Cox proportional hazard models were used to estimate hazard ratios (HRs). In women, differentiated TC risk was significantly associated with body mass index (BMI, kg/m2) (HR highest vs lowest quintile = 1.41, 95% CI: 1.03–1.94); height (HR = 1.61; 95% CI: 1.18–2.20); HR highest vs lowest tertile waist (HR = 1.34, 95% CI: 1.00–1.79) and waist‐to‐hip ratio (HR = 1.42, 95% CI: 1.05–1.91). The association with BMI was somewhat stronger in women below age 50. Corresponding associations for papillary TC were similar to those for all differentiated TC. In men the only body size factors significantly associated with differentiated TC were height (non linear), and leg length (HR highest vs. lowest tertile = 3.03, 95% CI: 1.30–7.07). Our study lends further support to the presence of a moderate positive association between differentiated TC risk and overweight and obesity in women. The risk increase among taller individuals of both sexes suggests that some genetic characteristics or early environmental exposures may also be implicated in the etiology of differentiated TC.
Geo-hydrological risk reduction is a key issue for local governments in Italy. In this context, a collaboration was undertaken between multiple actors in the La Spezia municipality aimed at: (i) ...monitoring building characteristics, using specific and valuable indicators, and (ii) increasing the knowledge of geo-hydrological hazards across residents and local land planners (iii) implementing local emergency civil protection plan. An extensive mobile data collection was carried out through apps specifically developed for Android and IOS mobile devices. The digital forms were differentiated on the basis of the potential hazard: one of 46 fields and one of 125 fields designed for buildings respectively located in flood prone areas and in medium to very high landslide susceptibility areas. The digital version of the forms was designed using the Open Data Kit (ODK) and GISCloud client-server approach. All the collected data, including geospatial locations and images, were automatically sent to a central server, stored and organized in a database. Geospatial data-analysis and maps resulted useful in evaluating possible impacts to exposed buildings to potential geo-hydrological processes. The proposed public participation method for data-gathering increased the knowledge across residents providing a better understanding of the urban systems, of the buildings condition and their relation respect to the geo-hydrological risk. The method can be considered as part of the decision support systems for civil protection purposes to better planning geo-hydrological mitigation measures. The application of mobile technology for data collection can be effectively used when local government resources are limited.
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•The proposed technology allows the collection of several building characteristics to be used as vulnerability indicators.•The designed survey-forms are made available and accessible through a dedicated link.•The designed mobile application can be effective technology when local government resources are limited.•The proposed public participation method increases the knowledge across residents of geo-hydrological risks.•The outcomes constitute non-structural mitigation measures to manage geo-hydrological risk in both urban and rural context.
To assess fetal risk after pregnancy exposure to natalizumab in women with multiple sclerosis (MS), with a specific focus on spontaneous abortion (SA) and congenital anomalies (CA).
Data of all ...pregnancies occurring between 2009 and 2015 in patients with MS treated with natalizumab and referring to 19 participating sites were collected and compared with those of pregnancies in untreated patients and patients treated with injectable immunomodulatory agents. Rates of SA and CA were also compared with those reported in the Italian population. Multivariable logistic and linear regression models were performed.
A total of 92 pregnancies were tracked in 83 women. In the multivariable analysis, natalizumab exposure was associated with SA (odds ratio OR 3.9, 95% confidence interval CI 1.9-8.5,
< 0.001). However, the rate of SA (17.4%) was within the estimates for the general population, as well as the rate of major CA (3.7%). Moreover, exposure to natalizumab and interferon-β (IFN-β) was associated with lower length and weight of the babies (
< 0.001).
Our results showed that natalizumab exposure to up 12 weeks of gestation is associated with an increased risk of SA, although within the limits expected in the general population, whereas the risk of CA needs further investigation. Taking into account the high risk of disease reactivation after natalizumab suspension, pregnancy could be planned continuing natalizumab while strictly monitoring conception.
This study provides Class III evidence that in women with MS, natalizumab exposure increases the risk of spontaneous abortion as compared to IFN-β-exposed or untreated patients (OR 3.9, 95% CI 1.9-8.5).
Non-response to cardiac resynchronization therapy remains a significant problem in up to 30% of patients. Multisite stimulation has emerged as a way of potentially overcoming non-response. This may ...be achieved by the use of multiple leads placed within the coronary sinus and its tributaries (dual-vein pacing) or more recently by the use of multipolar (quadripolar) left ventricular pacing leads which can deliver pacing stimuli at multiple sites within the same vein. This review covers the role of multisite pacing including the interaction with the underlying pathophysiology, the current and planned studies, and the potential pitfalls of this technology.
We report the longest follow-up of clinical and biochemical features of two previously reported adult mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) patients treated with liver ...transplantation (LT), adding information on a third, recently transplanted, patient. All three patients overcame the early post-operative period and tolerated immunosuppressive therapy. Plasma nucleoside levels dramatically decreased, with evidence of clinical improvement of ambulation and neuropathy. Conversely, other features of MNGIE, as gastrointestinal dysmotility, low weight, ophthalmoparesis, and leukoencephalopathy were essentially unchanged. A similar picture characterized two patients treated with allogenic hematopoietic stem cell transplantation (AHSCT). In conclusion, LT promptly and stably normalizes nucleoside imbalance in MNGIE, stabilizing or improving some clinical parameters with marginal periprocedural mortality rate as compared to AHSCT. Nevertheless, restoring thymidine phosphorylase (TP) activity, achieved by both LT and AHSCT, does not allow a full clinical recovery, probably due to consolidated cellular damage and/or incomplete enzymatic tissue replacement.
To assess the risk of disease reactivation during pregnancy after natalizumab suspension in women with multiple sclerosis (MS).
Data of all pregnancies occurring between 2009 and 2015 in patients ...with MS treated with natalizumab and referring to 19 participating sites were collected and compared with those of pregnancies in untreated patients and patients treated with injectable immunomodulatory agents through a 2-factor repeated measures analysis. Predictors of disease activity were assessed through stepwise multivariable logistic regression models.
A total of 92 pregnancies were tracked in 83 women receiving natalizumab. Among these pregnancies, 74 in 70 women resulted in live births, with a postpartum follow-up of at least 1 year, and were compared with 350 previously published pregnancies. Relapse rate during and after pregnancy was higher in women treated with natalizumab (
< 0.001). In multivariable analysis, longer natalizumab washout period was the only predictor of relapse occurrence during pregnancy (
= 0.001). Relapses in the postpartum year were related to relapses during pregnancy (
= 0.019) and early reintroduction of disease-modifying drugs (DMD;
= 0.021). Disability progression occurred in 16.2% of patients and was reduced by early reintroduction of DMD (
= 0.024).
Taken as a whole, our findings indicate that the combination of avoiding natalizumab washout and the early resumption of DMD after delivery could be the best option in the perspective of maternal risk. This approach must take into account possible fetal risks that need to be discussed with the mother and require further investigation.
This study provides Class IV evidence that in women with MS, the risk of relapses during pregnancy is higher in those who had been using natalizumab as compared to those who had been using interferon-β or no treatment.
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