Early treatment of high‐risk COVID‐19 patients may prevent disease progression. However, there are limited data to support treatment of hospitalized or fully vaccinated patients with mild‐to‐moderate ...disease. In this retrospective cohort study, we studied the effect of early use of sotrovimab and remdesivir in high‐risk hospitalized COVID‐19 patients. We included PCR‐confirmed COVID‐19 patients admitted to the National Centre for Infectious Diseases who presented within the first 5 days of illness, and who were not requiring oxygen or ICU care at presentation. Sotrovimab‐ and remdesivir‐treated groups were compared with control (no early treatment). A multiple propensity‐score adjusted multivariable regression analysis was conducted with a composite primary endpoint of in‐hospital deterioration (oxygen requirement, ICU admission, or mortality). Of 1118 patients, 841 were in the control group, 106 in the sotrovimab group and 169 in the remdesivir group. The median age was 63 years (IQR 46–74 years) and 505 (45.2%) were female. In unvaccinated patients, both remdesivir and sotrovimab treatment were protective (adjusted odds ratio aOR 0.19, 95% CI 0.064–0.60 and 0.18 95% CI 0.066–0.47), respectively. Contrarily, among the vaccinated patients there was no significant treatment effect with early remdesivir treatment (aOR 2.51, 95% CI 0.83–7.57, p = 0.10). Remdesivir and sotrovimab treatment, given early in the disease course to unvaccinated high‐risk patients, was effective in reducing the risk of in‐hospital deterioration and severe disease. This effect was not seen in fully vaccinated patients, which may be due to a small sample size or residual confounding.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may induce several vascular endothelial-dependent systemic complications, and sulodexide has pleiotropic actions on the vascular ...endothelium, which may prove beneficial. We aimed to assess the effect of sulodexide when used within 3 days of coronavirus disease 2019 (COVID-19) clinical onset. We conducted a randomized placebo-controlled outpatient trial. To be included, patients must have been at high risk for severe clinical progression. Participants received sulodexide (oral 1,000 LRU/d) or placebo for 21 days. The primary endpoint was the need for hospital care. Also assessed were patients' need for supplemental oxygen as well as D-dimer and C-reactive protein (CRP) levels, thromboembolic events, major bleeding, and mortality. A total of 243 patients were included in the per-protocol analysis from June 5 to August 30, 2020. Of these, 124 received sulodexide and 119 received a placebo. Only 17.7% of the patients in the sulodexide group required hospitalization, compared with 29.4% in the placebo group (
p
= 0.03). This benefit persisted in the intention-to-treat analysis (15% in sulodexide group vs. 24% with placebo
p
= 0.04). With sulodexide, fewer patients required supplemental oxygen (30 vs. 42%
p
= 0.05). After 2 weeks, fewer patients had D-dimer levels >500 ng/dL (22 vs. 47%
p
< 0.01), and patients also had lower mean CRP levels (12.5 vs. 17.8 mg/dL
p
< 0.01). There were no between-group differences in thromboembolic events, major bleeding, or mortality. Treatment of COVID-19 patients with sulodexide, when provided within 3 days of clinical onset, improved their clinical outcomes. Although the results should be confirmed, sulodexide could be valuable in an outpatient setting.
Background:
The optimal timing of treatment starts for achieving the best control on the long-term disability accumulation in multiple sclerosis (MS) is still to be defined.
Objective:
The aim of ...this study was to estimate the optimal time to start disease-modifying therapies (DMTs) to prevent the long-term disability accumulation in MS, using a pooled dataset from the Big Multiple Sclerosis Data (BMSD) network.
Methods:
Multivariable Cox regression models adjusted for the time to first treatment start from disease onset (in quintiles) were used. To mitigate the impact of potential biases, a set of pairwise propensity score (PS)-matched analyses were performed. The first quintile, including patients treated within 1.2 years from onset, was used as reference.
Results:
A cohort of 11,871 patients (median follow-up after treatment start: 13.2 years) was analyzed. A 3- and 12-month confirmed disability worsening event and irreversible Expanded Disability Status Scale (EDSS) 4.0 and 6.0 scores were reached by 7062 (59.5%), 4138 (34.9%), 3209 (31.1%), and 1909 (16.5%) patients, respectively. The risk of reaching all the disability outcomes was significantly lower (p < 0.0004) for the first quintile patients’ group.
Conclusion:
Real-world data from the BMSD demonstrate that DMTs should be commenced within 1.2 years from the disease onset to reduce the risk of disability accumulation over the long term.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
The early treatment of Class II/1 malocclusion is influenced by factors such as the severity of the anomaly, the time of initiation of orthodontic treatment, patient cooperation, treatment steps and ...the type of orthodontic appliance used. Early treatments act on growth by reducing skeletal discrepancies, correcting occlusal relationships, normalizing functions and allowing the sagittal growth potential of the mandible to be expressed. Functional appliances for the correction of mandibular retrognathism are effective if they are applied during the pubertal growth stage, when the effectiveness is maximum, but we must always keep in mind that the result of early treatment with functional appliances is the patient’s individual response to the type of treatment used.
Impairments across multiple domains are a disabling consequence of multiple sclerosis (MS). Originating from preventive medical strategies, the “time matters”-perspective has become a focal point ...when treating MS. In particular, early detection of physical and cognitive deficits, along with deficits in patient-reported outcomes seems crucial to further optimize both pharmacological and non-pharmacological MS treatment strategies. Therefore, this topical review investigates the level of impairments across multiple domains (physical function, cognitive function, and patient-reported outcomes) in the early stage of MS (⩽5 years since diagnosis, including clinically isolated syndrome (CIS)), when compared to matched healthy controls. Even at early disease stages, studies show impairments corresponding to 8%–34% and small-to-large numerical effect sizes (0.35–2.85) in MS/CIS patients across domains. This evidence call for early screening programs along with early interventions targeting the multiple impaired domains. This further highlights the importance of preventive initiatives preserving and/or restoring physical and cognitive reserve capacity if possible.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
In orthodontic treatment, the combination of an activator with a headgear is commonly used in treatment of the hyperdivergent Class II malocclusion. However, the distribution of stresses transmitted ...to the maxilla by these appliances has been little studied. This study aimed to compare the biomechanical effects of stresses transmitted to the maxilla and teeth by a Teuscher activator (TA) for different lines of action of extraoral force, using finite element analysis.
A tridimensional finite element model of the maxilla and teeth was created based on the true geometry of a human skull. The (TA) and the face bow were designed in 3D computer-aided design and fixed in the maxilla model. To study the effects of mechanical stress transmitted to the maxilla in the treatment of hyperdivergent Class II malocclusion with (TA) combined with extraoral forces, five different finite element models were used, considering the centers of resistance of the maxilla and dentition.
The results showed that stresses increased progressively when the force line of action moved in posteroanterior direction. Von Mises equivalent stress was lower in Model 1 (0°) than in Model 5 (60°). In Models 1 (0°) and 2 (15°), molars suffered greater distal displacement and incisors showed extrusion. In Model 3 (30°), the force line of action promoted a distal displacement of molars and incisors. In Models 4 (45°) and 5 (60°), the whole maxillary anterior sector showed counterclockwise displacement.
Different force lines of action influence the intensity and distribution of orthodontic and orthopedic forces in the maxilla. The extraoral force's line of action used in Model 3 (30°) is the most compatible with the objectives of the hyperdivergent Class II malocclusion treatment in growing patients.
Class II, Headgear, Early treatment, FEA.
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The coronavirus disease 2019 (COVID-19) epidemic has been almost controlled in China under a series of policies, including “early diagnosis and early treatment”. This study aimed to ...explore the association between early treatment with Qingfei Paidu decoction (QFPDD) and favorable clinical outcomes. In this retrospective multicenter study, we included 782 patients (males, 56 %; median age 46) with confirmed COVID-19 from 54 hospitals in nine provinces of China, who were divided into four groups according to the treatment initiation time from the first date of onset of symptoms to the date of starting treatment with QFPDD. The primary outcome was time to recovery; days of viral shedding, duration of hospital stay, and course of the disease were also analyzed. Compared with treatment initiated after 3 weeks, early treatment with QFPDD after less than 1 week, 1-2 weeks, or 2-3 weeks had a higher likelihood of recovery, with adjusted hazard ratio (HR) (95 % confidence interval CI) of 3.81 (2.65–5.48), 2.63 (1.86-3.73), and 1.92 (1.34-2.75), respectively. The median course of the disease decreased from 34 days to 24 days, 21 days, and 18 days when treatment was administered early by a week (P < 0.0001). Treatment within a week was related to a decrease by 1-4 days in the median duration of hospital stay compared with late treatment (P<0.0001). In conclusion, early treatment with QFPDD may serve as an effective strategy in controlling the epidemic, as early treatment with QFPDD was associated with favorable outcomes, including faster recovery, shorter time to viral shedding, and a shorter duration of hospital stay. However, further multicenter, prospective studies with a larger sample size should be conducted to confirm the benefits of early treatment with QFPDD.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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