The CoronaVirus Disease 19 (COVID-19) pandemic is a threat of particular concern for people affected by chronic immune-mediated diseases, such as multiple sclerosis (MS), who are often treated with ...immunomodulatory and immunosuppressive drugs, which may increase the risk of infections in general. At the beginning of the COVID-19 pandemic, empirical guidelines on how to manage treatments for immune-mediated diseases, including MS, were released. Subsequently, the first clinical pictures and data sets have been published, describing the outcomes of COVID-19 in patients with MS treated with immunomodulatory and immunosuppressive drugs. Here we will review available information on how infections by human coronaviruses affect the immune system in untreated subjects and in patients affected by MS treated with drugs which modulate the immune system.
To evaluate the efficacy of a myopia control spectacle lens (DIMS) at slowing the progression of myopia in a population of European children in comparison with 0.01% atropine and combined DIMS and ...atropine.
The study was a non-randomised experimenter-masked prospective controlled observational study of individuals aged 6-18 years with progressing myopia but no ocular pathology. Participants were allocated, according to patient/parent choice, to receive 0.01% atropine eyedrops, DIMS (Hoya® MiyoSmart®) spectacles, combined atropine+DIMS or single vision spectacle lenses (control group). The key outcome variables, cycloplegic autorefraction spherical equivalent refraction (SER) and axial length (AL), were measured at baseline and after three, six, and 12 months.
Of the 146 participants (mean age 10.3y ±3.2), 53 received atropine, 30 DIMS spectacles, 31 atropine+DIMS, and 32 single vision control spectacles. Generalized linear mixed model analysis revealed for SER, whilst controlling for age and SER at baseline, at each stage all treatment groups had significantly reduced progression compared with the control group (p<0.016). For AL, whilst controlling for baseline age and AL, at 6 and 12 months all treatment groups had significantly less progression than the control group (p<0.005). For SER only, in pairwise comparisons at 12 months the atropine+DIMS group had significantly reduced progression compared with the DIMS only and Atropine only groups (p<0.001).
In a European population, DIMS and atropine are effective at reducing myopia progression and axial elongation in progressing myopia and are most successful at reducing myopia progression when used in combination.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background:
Randomized clinical trials (RCTs) in progressive multiple sclerosis (MS) often revealed non-significant treatment effects on disability progression.
Objectives:
To investigate whether the ...failure to detect a significant benefit from treatment may be motivated by a delay in treatment effect, possibly related to baseline characteristics.
Methods:
We re-analyzed data from two RCTs testing interferon-beta and glatiramer-acetate versus placebo in progressive MS with no significant effect on EDSS progression. We first designed a time-dependent Cox model with no treatment effect up to time = t0, and constant hazard ratio (HR) after time = t0. We selected the best-fitting t0 from 0 (standard Cox model) to 2.5 years. Furthermore, we modeled the delay as a function of baseline EDSS and fitted the resulting Cox model to the merged dataset.
Results:
The time-dependent Cox model revealed a significant benefit of treatment delayed by t0 = 2.5 years for the SPECTRIMS study (HR = 0.65 (0.43–0.98), p = 0.041), and delayed by t0 = 2 years for the PROMISE study (HR = 0.65, (0.42–0.99), p = 0.044). In the merged dataset, the HR for the EDSS-dependent delayed effect was 0.68 (0.56, 0.82), p < 0.001.
Conclusion:
The assumption of a delayed treatment effect improved the fit to the data of the two examined RCTs, uncovering a significant, although shifted, benefit of treatment.
Anxiety and depression may frequently affect patients with asthma. However, the findings of several studies are partially conflicting and conducted in selected cohorts.
To investigate the effect of ...anxiety and depression in a group of outpatients with asthma.
This cross-sectional, real-life study included 263 patients (109 males; mean age, 39.2 years) with asthma. Clinical examination, lung function, fractional exhaled nitric oxide measurement, Asthma Control Test (ACT) score, asthma control grade, perception of symptoms by visual analog scale, and Hospital Anxiety and Depression Scale (HADS) questionnaires were evaluated.
Globally, 97 patients (36.9%) had anxiety, and 29 (11%) had depression. Of these patients, 71 had combined anxiety and depression. Anxiety and depression were associated with poor asthma control (P =.007 and .02, respectively). Patients with depression had higher body mass indexes (P =.002). Anxiety and depression were associated with lower ACT scores (P < .001 for both). The scores on the anxiety and depression subscales of HADS were moderately related (r = 0.57).
The present real-life study indicates that anxiety and depression are common and relevant comorbidities in asthmatic outpatients and are associated with uncontrolled asthma and lower ACT scores. Thus, assessment of comorbid mental disorders should be performed in common practice.
Background:
Distinctive differences in multiple sclerosis (MS) have been observed by race and ethnicity. We aim to (1) assess how often race and ethnicity were reported in clinical trials registered ...on ClinicalTrials.gov, (2) evaluate whether the population was diverse enough, and (3) compare with publications.
Methods:
We included phase 3 clinical trials registered with results on ClinicalTrials.gov between 2007 and 2023. When race and/or ethnicity were reported, we searched for the corresponding publications.
Results:
Out of the 99 included studies, 56% reported race and/or ethnicity, of which only 26% of those primarily completed before 2017. Studies reporting race or ethnicity contributed to a total of 33,891 participants, mainly enrolled in Eastern Europe. Most were White (93%), and the median percentage of White participants was 93% (interquartile range (IQR) = 86%–98%), compared to 3% for Black (IQR = 1%–12%) and 0.2% for Asian (IQR = 0%–1%). Four trials omitted race and ethnicity in publications and even when information was reported, some discrepancies in terminology were identified and categories with fewer participants were often collapsed.
Conclusion:
More efforts should be done to improve transparency, accuracy, and representativeness, in publications and at a design phase, by addressing social determinants of health that historically limit the enrollment of underrepresented population.
Background. Cow’s milk allergy (CMA) is the most common food allergy in early childhood. Children with CMA require a precise and punctual diagnosis. Oral food challenge (OFC) is the gold-standard ...procedure for diagnosing allergies, but it is laborious and requires a particular setting. The aim of the study was to identify the cutoff value of serum allergen-specific IgE values able to predict a positive response to OFC. Methods. Children with suspected CMA performed OFC with cow’s milk (CM) or derivatives. Total IgE and specific IgE to raw CM, α-lactalbumin, β-lactoglobulin, and casein were measured. Results. Seventy-two children performed OFC, and 30 (41.6%) had a positive response. The significant predictive factors were sensitization to raw CM extract (p=0.03), α-lactalbumin (p=0.013), β-lactoglobulin (p=0.09), and casein (p=0.019). The cutoff was, respectively: 5.13 kUA/L for raw CM, 1.47 for α-lactalbumin, 1.35 for β-lactoglobulin, and 4.87 for casein. Conclusions. This study allowed us to define a set of cutoff values for CM protein-specific IgE. However, these cutoffs should be interpreted not as a diagnostic tool for CMA but only predictive of response to OFC in a specific territory. Thus, the practical message may be that a value above the cutoff allows a good approximation to identify children to be started on OFC.
Background:
Patients with multiple sclerosis (pwMS) treated with anti-CD20 or fingolimod showed a reduced humoral response to SARS-CoV-2 vaccines.
Objective:
In this study we aimed to monitor the ...risk of breakthrough SARS-CoV-2 infection in pwMS on different disease-modifying therapies (DMTs).
Methods:
Data on the number of vaccinated patients and the number of patients with a breakthrough infection were retrospectively collected in 27 Italian MS centers. We estimated the rate of breakthrough infections and of infection requiring hospitalization per DMT.
Results:
19,641 vaccinated pwMS were included in the database. After a median follow-up of 8 months, we observed 137 breakthrough infections. Compared with other DMTs, the rate of breakthrough infections was significantly higher on ocrelizumab (0.57% vs 2.00%, risk ratio (RR) = 3.55, 95% CI = 2.74–4.58, p < 0.001) and fingolimod (0.58% vs 1.62%, RR = 2.65, 95% CI = 1.75–4.00, p < 0.001), while there were no significant differences in any other DMT group. In the ocrelizumab group the hospitalization rate was 16.7% versus 19.4% in the pre-vaccination era (RR = 0.86, p = 0.74) and it was 3.9% in all the other DMT groups versus 11.9% in the pre-vaccination period (RR = 0.33, p = 0.02).
Conclusions:
The risk of breakthrough SARS-CoV-2 infections is higher in patients treated with ocrelizumab and fingolimod, and the rate of severe infections was significantly reduced in all the DMTs excluding ocrelizumab.
Handwriting deteriorates proportionally to the writer's cognitive state. Such knowledge is of special importance in the case of a contested will, where dementia of the testator is claimed, but ...medical records are often insufficient to decide what the testator's cognitive state really was. By contrast, if the will is handwritten, handwriting analysis allows us to gauge the testator's cognitive state at the precise moment when he/she was writing the will. However, quantitative methods are needed to precisely evaluate whether the writer's cognitive state was normal or not. We aim to provide a test that quantifies handwriting deterioration to gauge a writer's cognitive state.
We consecutively enrolled patients who came for the evaluation of cognitive impairment at the Outpatient Clinic for Cognitive Impairment of the Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics and Maternal and Child Sciences (DINOGMI) of the University of Genoa, Italy. Additionally, we enrolled their caregivers. We asked them to write a short text by hand, and we administered the Mini Mental State Examination (MMSE). Then, we investigated which handwriting parameters correlated with cognitive state as gauged by the MMSE.
Our study found that a single score, which we called the
nitive
mpairment
hrough h
ndwri
ing (
) score, reliably allows us to predict the writer's cognitive state.
The COGITAT score may be a valuable tool to gage the cognitive state of the author of a manuscript. This score may be especially useful in contested handwritten wills, where clinical examination of the writer is precluded.
Background. Type-2 inflammation commonly marks asthma in childhood. Also, gut and lung dysbiosis is detectable in patients with asthma. Strain-related probiotic supplementation may restore a ...physiological immune response, dampen airway inflammation, and repair dysbiosis. Therefore, the probiotics in pediatric asthma management (PROPAM) study is aimed at demonstrating that Ligilactobacillus salivarius LS01 (DSM 22775) and Bifidobacterium breve B632 (DSM 24706) mixture could reduce asthma exacerbations in children, followed in a primary care setting. Methods. The study was randomized, placebo-controlled, and double-blind. It involved 11 Italian primary care pediatricians. The probiotic mixture (containing Ligilactobacillus salivarius LS01 1×109 live cells and Bifidobacterium breve B632 1×109 live cells) or placebo was taken twice daily (1 sachet in the morning and 1 in the evening) for eight weeks and subsequently once daily for a further eight weeks. Outcomes included number, severity, and duration of asthma exacerbations, intensity of maintenance and as need treatments, and safety. Results. The per-protocol population included 422 children (mean age seven years, 240 males and 182 females). The probiotic mixture significantly reduced the number of asthmatic exacerbations (OR=3.17). In addition, the number of children with two exacerbations was less than a third in the active group (OR=3.65). Conclusions. This PROPAM study demonstrated that probiotic strains Ligilactobacillus salivarius LS01 (DSM 22775) and Bifidobacterium breve B632 (DSM 24706) were safe and significantly reduced by more than a third the frequency of asthma exacerbations. At present, the first-line treatment of asthma is still drug-based, but specific strains of probiotics may be auxiliary remedies.