Pregnant women with mild COVID-19 followed in community setting by telemedicine, and factors associated with unfavorable outcome.

OBJECTIVES: Few is known on pregnant women with mild COVID-19 managed in a community setting with a telemedicine solution, including their outcomes. The objective of this study is to evaluate the adverse fetal outcomes and hospitalization rates of pregnant COVID-19 outpatients who were monitored with the Covidom© telemedicine solution. METHODS: A nested study was conducted on pregnant outpatients with confirmed COVID-19, who were managed with Covidom© between March and November 2020. The patients were required to complete a standard medical questionnaire on co-morbidities and symptoms at inclusion, and were then monitored daily for 30 days after symptom onset. Adverse fetal outcome was defined as a composite of preterm birth, low birthweight, or stillbirth, and was collected retrospectively through phone contact with a standardized questionnaire. RESULTS: The study included 714 pregnant women, with a median age of 32.0 [29.0-35.0] and a median BMI of 23.8 [21.3-27.0]. The main comorbidities observed were smoking (53%), hypertension (19%). The most common symptoms were asthenia (45.6%), cough (40.3%) and headache (25.7%), as well as anosmia (28.4%) and agueusia (32.3%). Adverse fetal outcomes occurred in 64 (9%) cases, including 38 (5%) preterm births, 33 (5%) low birthweights, and 6 (1%) stillbirths. Hospitalization occurred in 102 (14%) cases and was associated with adverse fetal outcomes (OR 2.4, 95% CI 1.3-4.4). CONCLUSIONS: Our study suggests that adverse fetal outcomes are rare in pregnant women with mild COVID-19 who are monitored at home with telemedicine. However, hospitalization for COVID-19 and pregnancy-induced hypertension are associated with a higher risk of adverse fetal outcome.

A functional link between lariat debranching enzyme and the intron-binding complex is defective in non-photosensitive trichothiodystrophy.

The pre-mRNA life cycle requires intron processing; yet, how intron-processing defects influence splicing and gene expression is unclear. Here, we find that TTDN1/MPLKIP, which is encoded by a gene implicated in non-photosensitive trichothiodystrophy (NP-TTD), functionally links intron lariat processing to spliceosomal function. The conserved TTDN1 C-terminal region directly binds lariat debranching enzyme DBR1, whereas its N-terminal intrinsically disordered region (IDR) binds the intron-binding complex (IBC). TTDN1 loss, or a mutated IDR, causes significant intron lariat accumulation, as well as splicing and gene expression defects, mirroring phenotypes observed in NP-TTD patient cells. A Ttdn1-deficient mouse model recapitulates intron-processing defects and certain neurodevelopmental phenotypes seen in NP-TTD. Fusing DBR1 to the TTDN1 IDR is sufficient to recruit DBR1 to the IBC and circumvents the functional requirement for TTDN1. Collectively, our findings link RNA lariat processing with splicing outcomes by revealing the molecular function of TTDN1.

The emerging clinical role of wearables: factors for successful implementation in healthcare.

Wearable technologies promise to redefine assessment of health behaviors, yet their clinical implementation remains a challenge. To address this gap, two of the NIH's Big Data to Knowledge Centers of Excellence organized a workshop on potential clinical applications of wearables. A workgroup comprised of 14 stakeholders from diverse backgrounds (hospital administration, clinical medicine, academia, insurance, and the commercial device industry) discussed two successful digital health interventions that involve wearables to identify common features responsible for their success. Seven features were identified including: a clearly defined problem, integration into a system of healthcare delivery, technology support, personalized experience, focus on end-user experience, alignment with reimbursement models, and inclusion of clinician champions. Health providers and systems keen to establish new models of care inclusive of wearables may consider these features during program design. A better understanding of these features is necessary to guide future clinical applications of wearable technology.

Real World Home Blood Pressure Variability in Over 56,000 Individuals With Nearly 17 Million Measurements.

BACKGROUND: Using the data from 56,365 individuals, from 185 countries, and a Nokia Health Wireless blood pressure (BP) monitor, we investigated real-world characteristics of BP variability (BPV). METHODS: All included individuals self-measured and uploaded their BP using Bluetooth at least 20 times over a period of ≥1 month at a frequency and duration of their choosing. In total, 16,904,844 BP measurements were analyzed, with a median of 146 measurements per person (interquartile range [IQR] 73-321) over a median of 14 months (IQR 7-31). SD, coefficient of variation, maximum BP, and maximum minus minimum BP difference were all calculated as measures of BPV. RESULTS: BPV showed a distinct pattern, influenced by season of year, day of week, and time of day. BPV index was higher in females compared with males (P < 0.001) and increased with age (P < 0.001). Compared to the weekend, the weekday BPV index was significantly higher, and this finding was more prominent in females (P = 0.001). In multivariate analysis, BPV index were significantly associated with age, gender, geographic location, and mean BP values. CONCLUSION: Using the largest BP data set we are aware of, with the benefits and limitations of real-world measurement, we could show the pattern of BPV and provide reference values that may be helpful in understanding the nature of BPV as self-measurement at home becomes more common, and help guide individualized management.

Cross-Sectional and longitudinal associations of objectively-measured physical activity on blood pressure: evaluation in 37 countries.

Background: We examined the cross-sectional and longitudinal associations of objectively-measured physical activity (step counts) and blood pressure (BP) among adults spanning 37 countries. Methods: Across 37 countries, we used data from a pool of 9238 adult owners of Withings' Pulse activity trackers, which measures steps taken each day, and Wireless Blood Pressure Monitor, which measures BP. Analyses were adjusted on age, sex, number of days where the tracker was worn, and number of BP measurements. Data was collected from 2009 to 2013. Results: Subjects had a mean ± standard deviation (SD) age of 51.6 ± 11.3 years and a body mass index (BMI) of 28.7±5.5 kg/m2. A 1-month increase of more than 3000 steps per day was associated with a decrease of systolic BP (SBP) and diastolic BP (DBP) among the obese (1.57mm Hg and 1.29 mm Hg respectively, both P<0.001) and the overweight population (0.79 mm Hg and 0.84 mm Hg respectively, both P≤0.001), but not in the normal weight population (P=0.60 and P=0.36 respectively). Conclusion: One-month increases in daily step counts was associated with a decrease of SBP and DBP in a large obese and overweight free living population.

Masitinib treatment in patients with progressive multiple sclerosis: a randomized pilot study.

BACKGROUND: Treatment options for patients suffering from progressive forms of multiple sclerosis (MS) remain inadequate. Mast cells actively participate in the pathogenesis of MS, in part because they release large amounts of various mediators that sustain the inflammatory network. Masitinib, a selective oral tyrosine kinase inhibitor, effectively inhibits the survival, migration and activity of mast cells. This exploratory study assessed the safety and clinical benefit of masitinib in the treatment of primary progressive MS (PPMS) or relapse-free secondary progressive MS (rfSPMS). METHODS: Multicenter, randomized, placebo-controlled, proof-of-concept trial. Masitinib was administered orally at 3 to 6 mg/kg/day for at least 12 months, with dose adjustment permitted in event of insufficient response with no toxicity. The primary response endpoint was the change relative to baseline in the multiple sclerosis functional composite score (MSFC). Clinical response was defined as an increase in MSFC score relative to baseline of > 100%. RESULTS: Thirty-five patients were randomized to receive masitinib (N = 27) or placebo (N = 8). Masitinib was relatively well tolerated with the most common adverse events being asthenia, rash, nausea, edema, and diarrhea. The overall frequency of adverse events was similar to the placebo group, however, a higher incidence of severe and serious events was associated with masitinib treatment. Masitinib appeared to have a positive effect on MS-related impairment for PPMS and rfSPMS patients, as evidenced by an improvement in MSFC scores relative to baseline, compared with a worsening MSFC score in patients receiving placebo; +103% ± 189 versus -60% ± 190 at month-12, respectively. This positive, albeit non-statistically significant response was observed as early as month-3 and sustained through to month-18, with similar trends seen in the PPMS and rfSPMS subpopulations. A total of 7/22 (32%) assessable masitinib patients reported clinical response following 12 months of treatment (according to the modified intent-to-treat population, observed cases) compared with none in the placebo group. The Expanded Disability Status Scale remained stable for both treatment groups. CONCLUSION: These data suggest that masitinib is of therapeutic benefit to PPMS and rfSPMS patients and could therefore represent an innovative avenue of treatment for this disease. This exploratory trial provides evidence that may support a larger placebo-controlled investigation.

Masitinib as an adjunct therapy for mild-to-moderate Alzheimer's disease: a randomised, placebo-controlled phase 2 trial.

INTRODUCTION: Neuroinflammation is thought to be important in Alzheimer's disease pathogenesis. Mast cells are a key component of the inflammatory network and participate in the regulation of the blood-brain barrier's permeability. Masitinib, a selective oral tyrosine kinase inhibitor, effectively inhibits the survival, migration and activity of mast cells. As the brain is rich in mast cells, the therapeutic potential of masitinib as an adjunct therapy to standard care was investigated. METHODS: A randomised, placebo-controlled, phase 2 study was performed in patients with mild-to-moderate Alzheimer's disease, receiving masitinib as an adjunct to cholinesterase inhibitor and/or memantine. Patients were randomly assigned to receive masitinib (n = 26) (starting dose of 3 or 6 mg/kg/day) or placebo (n = 8), administered twice daily for 24 weeks. The primary endpoint was change from baseline in the Alzheimer's Disease Assessment Scale - cognitive subscale (ADAS-Cog) to assess cognitive function and the related patient response rate. RESULTS: The rate of clinically relevant cognitive decline according to the ADAS-Cog response (increase >4 points) after 12 and 24 weeks was significantly lower with masitinib adjunctive treatment compared with placebo (6% vs. 50% for both time points; P = 0.040 and P = 0.046, respectively). Moreover, whilst the placebo treatment arm showed worsening mean ADAS-Cog, Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory, and Mini-Mental State Examination scores, the masitinib treatment arm reported improvements, with statistical significance between treatment arms at week 12 and/or week 24 (respectively, P = 0.016 and 0.030; P = 0.035 and 0.128; and P = 0.047 and 0.031). The mean treatment effect according to change in ADAS-Cog score relative to baseline at weeks 12 and 24 was 6.8 and 7.6, respectively. Adverse events occurred more frequently with masitinib treatment (65% vs. 38% of patients); however, the majority of events were of mild or moderate intensity and transitory. Severe adverse events occurred at a similar frequency in the masitinib and placebo arms (15% vs. 13% of patients, respectively). Masitinib-associated events included gastrointestinal disorders, oedema, and rash. CONCLUSIONS: Masitinib administered as add-on therapy to standard care during 24 weeks was associated with slower cognitive decline in Alzheimer's disease, with an acceptable tolerance profile. Masitinib may therefore represent an innovative avenue of treatment in Alzheimer's disease. This trial provides evidence that may support a larger placebo-controlled investigation. TRIAL REGISTRATION: Clinicaltrials.gov NCT00976118.

Microbial fuel cell enables phosphate recovery from digested sewage sludge as struvite.

Orthophosphate was mobilized from iron phosphate (FePO(4)) contained in digested sewage sludge by microbial fuel cell power. FePO(4) was reduced through electrons and protons obtained from metabolic activity of Escherichia coli. The process yielded up to 82% or 600 mg/l. Optical emission spectroscopy was used for phosphate dosage. (31)P NMR showed a singlet at δ(p)=3.72 ppm indicating that orthophosphate (H(3)PO(4), HPO(4)(-), HPO(4)(2-) and PO(4)(3-)) was recovered. The phosphate containing supernatant solution was reacted with stoichiometric amounts of MgCl(2) and NH(4)OH to precipitate struvite (MgNH(4)PO(4)·6H(2)O). The crystalline fertilizer was analyzed by scanning electron microscopy comprising elemental analysis, revealing a composition accuracy of ∼ 90% and the absence of any toxic metals such as As, Cd, Pb, or Cr. The phosphate extraction is also a means to reduce the volume of digested sewage sludge while increasing the heat of combustion. This study represents a concept for sustainable decentralized phosphate recycling.

Coping strategy and anxiety evolution in multiple sclerosis patients initiating interferon-beta treatment.

This study (ACSEPT) aimed to assess anxiety evolution according to coping strategy in patients with multiple sclerosis (MS) during their first months of treatment with interferon (IFN)-beta1a. Recently diagnosed relapsing-remitting MS (RRMS) patients (n = 255) were included and received standardized information on MS. At inclusion, the preferred coping mode was determined using the Coping Inventory for Stressful Situations (CISS). Anxiety and depression were assessed at inclusion and after 3 months using the Spielberger State-Trait Anxiety Inventory and the Beck Depression Inventory, respectively. At inclusion, the preferred coping strategy was task-oriented for most patients (53%), 51% were considered as anxious, and the mean Beck depression score was low. Emotion-oriented patients were more anxious and more depressed than the 2 other coping groups (task- and avoidance-oriented). During the first 3 months of IFN treatment, the anxiety level slightly decreased in the total population, more intensively in the emotion-oriented group, and there were no clinically significant changes in the Beck depression score. Anxiety and depression remained stable or decreased during the first 3 months of IFN treatment, depending on coping strategy. Identifying these coping strategies during therapy initiation may allow customized support and improve treatment adherence.

Can amnesic patients learn without awareness? New evidence comparing deterministic and probabilistic sequence learning.

Can associative learning take place without awareness? We explore this issue in a sequence learning paradigm with amnesic and control participants, who were simply asked to react to one of four possible stimuli on each trial. Unknown to them, successive stimuli occurred in a sequence. We manipulated the extent to which stimuli followed the sequence in a deterministic manner (noiseless condition) or only probabilistically so (noisy condition). Through this paradigm, we aimed at addressing two central issues: first, we asked whether sequence learning takes place in either condition with amnesic patients. Second, we asked whether this learning takes place without awareness. To answer this second question, participants were asked to perform a subsequent sequence generation task under inclusion and exclusion conditions, as well as a recognition task. Reaction times results show that amnesic patients learned the sequence only in the deterministic condition. However, they failed to be able to reproduce the sequence in the generation task. In contrast, we found learning for both sequence structures in control participants, but only control participants exposed to a deterministic sequence were successful in performing the generation task, thus suggesting that the acquired knowledge can be used consciously in this condition. Neither amnesic nor control participants showed correct old/new judgments in the recognition task. The results strengthen the claim that implicit learning is at least partly spared in amnesia, and the role of contextual information available for learning is discussed.