Early Treatment of Nevus of Ota in Children is More Effective and Beneficial to Mental Health: Observation on the Efficacy of Q-Switched Ruby Laser in Treating 159 Cases of Nevus of Ota in Children.

Background and Objective: Nevus of Ota (NO), also known as "brownish-blue nevus of the palate of the eye", is a benign dermal pigmentation that increases skin disease. The Q-switched ruby laser is a classic treatment for nevus of Ota in children, but the optimal age for treatment is still controversial. The aim of this study was to investigate the treatment effect of Q-switched ruby laser in children with nevus of Ota at different ages and the effect on psychological health status. Materials and Methods: Children with nevus of Ota treated with Q-switched ruby laser in the Department of Dermatology of the Second Affiliated Hospital of Wenzhou Medical University from June 2015 to June 2019 were retrospectively analysed. And the mental health status was assessed using the CDI scale. Results: In the preschool children group (0-7 year age), the significant efficacy rates was 93.1%, the average number of treatments was 3.6, and the overall incidence of adverse reactions was 4.7%. The significant efficacy rates in the school-age children group (7-14 year age) was 90.3%, the average number of treatments was 5.1, and the overall incidence of adverse reactions was 13.7%. The mean post-treatment CDI score in the preschool children group was 10.8, and 9.7% of children exceeding 19 points. The mean pre-treatment CDI score in the school-age children group was 17.3, and 24.6% of children exceeding 19 points. The mean post-treatment CDI score was 13.6 and 15.1% of children exceeded 19 points. The chi-square test for the significant efficacy rate of the two groups showed P>0.05, which was not statistically significant. The significant efficacy rate of the preschool group and that of the school-age children group. The t-test for the number of treatments in the two groups showed P<0.05, which was statistically significant. Adverse reactions in the two groups showed a statistically significant P<0.05. The mean CDI scores and the percentage of depressed individuals in the school-age children group were significantly lower after treatment than before treatment (p<0.05). Conclusion: Q-switched ruby laser is safe and effective in treating nevus of Ota in children. Early treatment can reduce the number of treatments and the incidence of adverse reactions. In addition, early treatment can reduce children's depression, which is beneficial to mental health.

Comparing the Pre-writing Skills of Diplegic Cerebral Palsy Children to Those of Normal Children.

INTRODUCTION: The pencil grasp and drawing patterns are specific to different age levels. So, if one knows a certain pattern for that particular age, it will guide the intervention plan for children with cerebral palsy (CP). The chances of improvement in diplegic CP are possible with the help of early intervention; therefore, early intervention is only possible if one knows the areas of delay and the age at which the intervention should be started. MATERIAL AND METHODS: It was a cross-sectional, case-control study. A total of 60 children were selected for the study, of which 30 (50%) were normal and 30 (50%) had diplegic cerebral palsy. A convenient sampling method is used for evaluation. RESULTS: The t-value for pencil grasp between the two groups, i.e., normal and CP diplegic, was 3.515 (P=0.001), revealing a significant difference in the grasp pattern of the two groups. Similarly, the t-value for drawing patterns between the two groups, i.e., normal and CP diplegic, was 5.796 (P = 0.001). A significant difference was found in the drawing patterns of both groups. CONCLUSION: Our study found that diplegic CP children performed lower on the Erhardt Developmental Prehension Assessment (EDPA) and showed larger variation in the pencil grasp and drawing than the normal children.

Hydroxyurea in sickle cell disease and invasive bacterial infections: a case-control study.

Hydroxyurea decreases painful events among children with sickle cell disease but could increase the risk of infections in treated patients through leucopenia. We performed a case-control study, comparing hydroxyurea treatment for sickle cell disease in cases with an invasive bacterial infection and in controls without infection. No difference was found.

Proportion of early treatment seeking for sexually transmitted infections and associated factors among patients attending youth friendly service in Bahir Dar City health centers, Northwest, Ethiopia.

BACKGROUND: Sexually transmitted infection is a common public health issue of youths and is characteristically transmitted through sexual intercourse. Even though early treatment for sexually transmitted infection is very important to reduce further complications and economic burden, studies to identify the proportion and the possible factor of early treatment seeking is rare in Ethiopia. OBJECTIVE: To assess the proportion of early treatment seeking for sexually transmitted infections and associated factors among patients attending youth friendly service in Bahir Dar city health centers, northwest, Ethiopia 2023. METHOD: Institutional based Cross-sectional study was used among 407 participants from April 25 to May 24 /2023. A systematic random sampling technique was used to select the participants. An interview-administered questionnaire was used for data collection, whereas Epi-data version 4.6.0.2 and the statistical package for statistical science version 23 were used for data entry and analysis respectively. A frequency table and bar chart were used for descriptive analysis. Multiple binary logistic regression was employed to identify the factors at p-value of <0.05. The necessary assumption of the model was also checked by the Hosmer and Lemishow test. RESULTS: The response rate of this study was 391 (96.1%) and the proportion of early treatment for sexually transmitted infection was 108 (27.6%, 95%CI; 23-32). Good knowledge about sexually transmitted infection (AOR=1.98, 95CI%; 1.13-3.47) know about their HIV status (AOR=1.95, 95%CI; 1.13-3.36), perceive severity of sexually transmitted infection (AOR=11.23, 95%CI; 6.15-20.45), and not fear the stigma about being infected with sexually transmitted infection (AOR=2.29, 95%CI; 1.32-3.96) were the significantly associated factors for early treatment of sexually transmitted infection. CONCLUSION AND RECOMMENDATION: The proportion of early treatment for sexually transmitted infection in Bahir Dar city was low. Knowledge about STIs, testing/ knowing HIV status, perception of the severity about sexually transmitted infection, and fear of stigma about sexually transmitted infection were the statistically significant factors for early treatment of sexually transmitted infection. So the government better give attention to health education and other health promotion activities to increase the knowledge of youths about sexually transmitted infection and to change their perception of sexually transmitted infection.

Safety and Early Outcomes of Cochlear Implantation of Nucleus Devices in Infants: A Multi-Centre Study.

This multi-center study examined the safety and effectiveness of cochlear implantation of children between 9 and 11 months of age. The intended impact was to support practice regarding candidacy assessment and prognostic counseling of pediatric cochlear implant candidates. Data in the clinical chart of children implanted at 9-11 months of age with Cochlear Ltd devices at five cochlear implant centers in the United States and Canada were included in analyses. The study included data from two cohorts implanted with one or two Nucleus devices during the periods of January 1, 2012-December 31, 2017 (Cohort 1, n = 83) or between January 1, 2018 and May 15, 2020 (Cohort 2, n = 50). Major adverse events (requiring another procedure/hospitalization) and minor adverse events (managed with medication alone or underwent an expected course of treatment that did not require surgery or hospitalization) out to 2 years post-implant were monitored and outcomes measured by audiometric thresholds and parent-reports on the IT-MAIS and LittlEARS questionnaires were collected. Results revealed 60 adverse events in 41 children and 227 ears implanted (26%) of which 14 major events occurred in 11 children; all were transitory and resolved. Improved hearing with cochlear implant use was shown in all outcome measures. Findings reveal that the procedure is safe for infants and that they show clear benefits of cochlear implantation including increased audibility and hearing development.

Case report: Virtual reality-based arm and leg cycling combined with transcutaneous electrical spinal cord stimulation for early treatment of a cervical spinal cord injured patient.

Spinal cord injury is a condition affecting the central nervous system, causing different levels of dysfunction below the point of nerve damage. A 50-year-old woman suffered a neck injury as a result of a car accident. After undergoing posterior cervical C3-C6 internal fixation with titanium plates on one side and C7 lamina decompression, the patient, who had been diagnosed with C3-C7 cervical disk herniation and spinal stenosis causing persistent compression of the spinal cord, was transferred to the rehabilitation department. After implementing the combined therapy of Virtual Reality-based arm and leg cycling along with transcutaneous electrical stimulation of the spinal cord, the patients experienced a notable enhancement in both sensory and motor abilities as per the ASIA scores. The patient's anxiety and depression were reduced as measured by the Hamilton Anxiety and Hamilton Depression Tests. As evaluated by the SCIM-III, the patient's self-reliance and capacity to carry out everyday tasks showed ongoing enhancement, leading to the restoration of their functionality. Hence, the use of Virtual Reality-based arm and leg cycling along with transcutaneous electrical spinal cord stimulation has potential to positively impact function in patients with spinal cord injury. However, as this is a case report, the small number of patients and the fact that the intervention was initiated early after the injury, we were unable to separate the recovery due to the intervention from the natural recovery that is known to occur in the initial weeks and months after SCI. Therefore, further randomized controlled trials with a large sample size is necessary.

Effects of Removable Functional Appliances on the Dentoalveolar Unit in Growing Patients.

Background and Objectives: The objective of this retrospective controlled study is to compare class II growing patients who underwent treatment with two different functional appliances: the Fraenkel regulator (FR-2), utilized as the control group, and the elastodontic device "Cranium Occluded Postural Multifunctional Harmonizers" (AMCOP), utilized as the test group. Materials and Methods: The study sample consisted of 52 patients with class II division I malocclusion (30 males, 22 females, mean age 8.6 ± 1.4 years) who were treated with the two different types of appliances: Group 1 (n = 27, mean age 8 [7.00, 9.00] years, 12 females, 15 males) received treatment with AMCOP, while Group 2 (n = 25, mean age 9.2 years [8.20, 10.00], 10 females, 15 males) received treatment with FR-2. The mean treatment duration for Group 1 was 28.00 [21.50, 38.00] months, while for Group 2 it was 23.70 [17.80, 27.40] months. Cephalometric analyses were performed on lateral cephalograms taken before treatment (T1) and after treatment (T2). Results: Significant intragroup differences were observed over time in Group 1 for 1^/PP. Similarly, significant intragroup differences were observed over time in Group 2 for SNB, ANB, and IMPA. Conclusions: Both treatment modalities resulted in the correction of class II malocclusion with dentoalveolar compensation, although the treatment duration with AMCOP tended to be longer on average.

Analysis of prefabricated myofunctional appliances with different overjet and bumper designs: a three-dimensional finite element analysis.

BACKGROUND: Prefabricated myofunctional appliance can guide tooth eruption, improve dentition alignment, correct myofunctional disorders and harmful oral habits. However, its application to skeletal discrepancy may result in unsatisfactory tooth inclination. This study aimed to construct a novel appliance with overjet design to avoid this side effect and investigated its shape and mechanical changes under occlusion using three-dimensional finite element method. METHODS: We established three samples of prefabricated myofunctional appliances. The first one was edge to edge without overjet, and the outer shield of both jaws were flattened. The second one was 3 mm overjet with stepped the outer shield. The last one was 3 mm overjet, and the outer shield of both jaws were flatted, which meant the front wall of lower jaw was strengthened with bumper, termed as lower bumper. A complete dentition model was applied to the study. 150 N occlusal force was applied to each type of appliance and the deformation displacement and the changes in stress was recorded. RESULTS: The deformation was significant in the incisors regions, especially in the vertical and lateral dimensions. The maximum displacements of 3 mm overjet with step shield group were 7.08 mm (vertical), 3.99 mm (lateral), and 2.90 mm (sagittal), while it decreased to 3.92 mm(vertical), 1.94 mm (lateral), and 1.55 mm (sagittal) in overjet with bumper group. Moreover, the upper molar regions exhibited higher vertical and sagittal displacement in 3 mm overjet with step shield group, which were 3.03 mm (vertical) and 1.99 mm (sagittal), and the bumper design could decrease the maximum displacement to 1.72 mm (vertical) and 0.72 mm (sagittal). In addition, the Von Mises stress of appliances was analyzed, and results indicated that 3 mm overjet with step shield generated higher stress than other groups, with the maximum Von Mises stress was 0.9387 MP, which were 0.5858 and 0.5657 MP in edge to edge group and 3 mm overjet with lower bumper group, respectively. CONCLUSION: The prefabricated myofunctional appliances may cause deformation during occlusion. Compared to step shield group, the application of lower bumper exhibited better resistance to occlusal force.

COVID-19 mortality paradox (United States vs Africa): Mass vaccination vs early treatment.

The coronavirus disease 2019 (COVID-19) mortality rate in 55 African countries is almost 4.5 times lower than in the coronavirus disease 2019 (COVID-19) despite Africa having over 4.2 times more people. This mortality paradox is also evident when comparing Nigeria, a heavily populated, poorly vaccinated and weakly mandated country to Israel, a small, highly vaccinated and strictly mandated country. Nigeria has almost 4 times lower COVID mortality than Israel. In this Field of Vision perspective, I explain how this paradox has evolved drawing upon my academic, clinical and social experience. Since April 2020, I've developed and been using the Egyptian immune-modulatory Kelleni's protocol to manage COVID-19 patients including pediatric, geriatric, pregnant, immune-compromised and other individuals suffering from multiple comorbidities. It's unfortunate that severe acute respiratory syndrome coronavirus 2 is still evolving accompanied by more deaths. However in Africa, we've been able to live without anxiety or mandates throughout the pandemic because we trust science and adopted early treatment using safe, and effective repurposed drugs that have saved the majority of COVID-19 patients. This article represents an African and Egyptian tale of honor.

Long-term skeletodental changes with early and late treatment using modified C-palatal plates in hyperdivergent Class II adolescents.

OBJECTIVES: To compare skeletodental changes between early and late treatment groups using modified C-palatal plates (MCPP) and long-term retention outcomes in hyperdivergent Class II adolescents. MATERIALS AND METHODS: Seventy-one hyperdivergent Class II patients were divided into four groups according to treatment modality and treatment timing: group 1, early treatment with MCPP (n = 16; 9.9 ± 0.9 years); group 2, late treatment with MCPP (n = 19; 12.3 ± 0.8 years); group 3, early treatment with headgear (HG; n = 18; 9.6 ± 0.8 years); and group 4, late treatment with HG (n = 18; 12.1 ± 1.2 years). Lateral cephalograms were taken and skeletal and dental variables were measured. For statistical analysis, paired t-tests, independent t-tests, and multiple regression were performed. RESULTS: The early MCPP group showed a more significant decrease in mandibular plane angle than the late MCPP group did, and vertical control was more efficient in the early group than in the late group. In the MCPP groups, both FMA and SN-GoGn were increased with late treatment but decreased with early treatment, and the difference was statistically significant (P < .01). The early-treatment MCPP group had a significant decrease in SN-GoGn of 0.6° compared with an increase of 1.7° in the early treatment HG group (P < .01). Posttreatment stability of both the early and late MCPP groups was maintained in long-term retention. CONCLUSIONS: Early MCPP showed more significant vertical control than late MCPP. However, there was no difference in long-term stability between early and late groups.

Effects of eruption guidance appliance in the early treatment of Class III malocclusion.

OBJECTIVES: To evaluate the dentoskeletal effects and effectiveness of the eruption guidance appliance in Class III patients in the mixed dentition. MATERIALS AND METHODS: The experimental group comprised 22 patients with Class III malocclusion and anterior cross-bite (12 males, 10 females, mean age 7.63 ± 0.96 years) treated with the eruption guidance appliance over a mean period of 1.72 ± 0.48 years. The control group comprised 22 untreated subjects (12 males, 10 females, mean age 7.21 ± 0.60 years) with Class III malocclusion. Lateral cephalometric radiographs were obtained at pretreatment (T1) and posttreatment (T2). Intergroup comparisons were performed with Mann-Whitney and t-tests (P < .05). RESULTS: In the experimental and control groups, the anteroposterior relationship between the maxilla and mandible (ANB angle) remained stable during the treatment period (T1 to T2). The mandibular plane angle decreased in the experimental group and increased in the control group. In the experimental group, the lower anterior face height increase and maxillary molar vertical development were significantly smaller compared to controls. Positive overjet was achieved in 54% of the experimental group. CONCLUSIONS: The eruption guidance appliance produced no change in the skeletal anteroposterior relationship. The anterior cross-bite/edge-to-edge relationship was corrected in only about half of the treated subjects.

Early treatment with fluvoxamine, bromhexine, cyproheptadine, and niclosamide to prevent clinical deterioration in patients with symptomatic COVID-19: a randomized clinical trial.

Background: Repurposed drugs with host-directed antiviral and immunomodulatory properties have shown promise in the treatment of COVID-19, but few trials have studied combinations of these agents. The aim of this trial was to assess the effectiveness of affordable, widely available, repurposed drugs used in combination for treatment of COVID-19, which may be particularly relevant to low-resource countries. Methods: We conducted an open-label, randomized, outpatient, controlled trial in Thailand from October 1, 2021, to June 21, 2022, to assess whether early treatment within 48-h of symptoms onset with combinations of fluvoxamine, bromhexine, cyproheptadine, and niclosamide, given to adults with confirmed mild SARS-CoV-2 infection, can prevent 28-day clinical deterioration compared to standard care. Participants were randomly assigned to receive treatment with fluvoxamine alone, fluvoxamine + bromhexine, fluvoxamine + cyproheptadine, niclosamide + bromhexine, or standard care. The primary outcome measured was clinical deterioration within 9, 14, or 28 days using a 6-point ordinal scale. This trial is registered with ClinicalTrials.gov (NCT05087381). Findings: Among 1900 recruited, a total of 995 participants completed the trial. No participants had clinical deterioration by day 9, 14, or 28 days among those treated with fluvoxamine plus bromhexine (0%), fluvoxamine plus cyproheptadine (0%), or niclosamide plus bromhexine (0%). Nine participants (5.6%) in the fluvoxamine arm had clinical deterioration by day 28, requiring low-flow oxygen. In contrast, most standard care arm participants had clinical deterioration by 9, 14, and 28 days. By day 9, 32.7% (110) of patients in the standard care arm had been hospitalized without requiring supplemental oxygen but needing ongoing medical care. By day 28, this percentage increased to 37.5% (21). Additionally, 20.8% (70) of patients in the standard care arm required low-flow oxygen by day 9, and 12.5% (16) needed non-invasive or mechanical ventilation by day 28. All treated groups significantly differed from the standard care group by days 9, 14, and 28 (p < 0.0001). Also, by day 28, the three 2-drug treatments were significantly better than the fluvoxamine arm (p < 0.0001). No deaths occurred in any study group. Compared to standard care, participants treated with the combination agents had significantly decreased viral loads as early as day 3 of treatment (p < 0.0001), decreased levels of serum cytokines interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1ß) as early as day 5 of treatment, and interleukin-8 (IL-8) by day 7 of treatment (p < 0.0001) and lower incidence of post-acute sequelae of COVID-19 (PASC) symptoms (p < 0.0001). 23 serious adverse events occurred in the standard care arm, while only 1 serious adverse event was reported in the fluvoxamine arm, and zero serious adverse events occurred in the other arms. Interpretation: Early treatment with these combinations among outpatients diagnosed with COVID-19 was associated with lower likelihood of clinical deterioration, and with significant and rapid reduction in the viral load and serum cytokines, and with lower burden of PASC symptoms. When started very soon after symptom onset, these repurposed drugs have high potential to prevent clinical deterioration and death in vaccinated and unvaccinated COVID-19 patients. Funding: Ped Thai Su Phai (Thai Ducks Fighting Danger) social giver group.

Treatment of maxillary hypoplasia with bone anchored maxillary protraction (BAMP) - A case report.

Early diagnosis and treatment is known to be beneficial in Class III malocclusions secondary to maxillary hypoplasia. However, success of treatment largely depends on the patient's compliance and thus, appropriate choice of treatment, appliance and the age for interception plays an important role. Bone anchored maxillary protraction is one such approach presented in this case report for a 13 years old boy who reported with the chief complaint of lower front teeth visibility during speech and smiling. On examination his molars were in Angle's Class III relation, anterior crossbite and deep bite with unerupted maxillary canines. Orthodontic treatment was begun for deep bite correction and for creating space for the maxillary canines, followed by surgical intervention for placement of bone anchored miniplates. Protraction was done for 14 months and the total treatment time was 20 months. Improvement in the patient's profile, aesthetics and function was achieved with well aligned arches.

Glucose tolerance and insulin resistance/sensitivity associate with retinal layer characteristics: the LIFE-Adult-Study.

AIMS/HYPOTHESIS: As the prevalence of insulin resistance and glucose intolerance is increasing throughout the world, diabetes-induced eye diseases are a global health burden. We aim to identify distinct optical bands which are closely related to insulin and glucose metabolism, using non-invasive, high-resolution spectral domain optical coherence tomography (SD-OCT) in a large, population-based dataset. METHODS: The LIFE-Adult-Study randomly selected 10,000 participants from the population registry of Leipzig, Germany. Cross-sectional, standardised phenotyping included the assessment of various metabolic risk markers and ocular imaging, such as SD-OCT-derived thicknesses of ten optical bands of the retina. Global and Early Treatment Diabetic Retinopathy Study (ETDRS) subfield-specific optical retinal layer thicknesses were investigated in 7384 healthy eyes of 7384 participants from the LIFE-Adult-Study stratified by normal glucose tolerance, prediabetes (impaired fasting glucose and/or impaired glucose tolerance and/or HbA1c 5.7-6.4% [39-47 mmol/mol]) and diabetes. The association of optical retinal band characteristics with different indices of glucose tolerance (e.g. fasting glucose, area under the glucose curve), insulin resistance (e.g. HOMA2-IR, triglyceride glucose index), or insulin sensitivity (e.g. estimated glucose disposal rate [eGDR], Stumvoll metabolic clearance rate) was determined using multivariable linear regression analyses for the individual markers adjusted for age, sex and refraction. Various sensitivity analyses were performed to validate the observed findings. RESULTS: In the study cohort, nine out of ten optical bands of the retina showed significant sex- and glucose tolerance-dependent differences in band thicknesses. Multivariable linear regression analyses revealed a significant, independent, and inverse association between markers of glucose intolerance and insulin resistance (e.g. HOMA2-IR) with the thickness of the optical bands representing the anatomical retinal outer nuclear layer (ONL, standardised ß=-0.096; p<0.001 for HOMA2-IR) and myoid zone (MZ; ß=-0.096; p<0.001 for HOMA2-IR) of the photoreceptors. Conversely, markers of insulin sensitivity (e.g. eGDR) positively and independently associated with ONL (ß=0.090; p<0.001 for eGDR) and MZ (ß=0.133; p<0.001 for eGDR) band thicknesses. These global associations were confirmed in ETDRS subfield-specific analyses. Sensitivity analyses further validated our findings when physical activity, neuroanatomical cell/tissue types and ETDRS subfield categories were investigated after stratifying the cohort by glucose homeostasis. CONCLUSIONS/INTERPRETATION: An impaired glucose homeostasis associates with a thinning of the optical bands of retinal ONL and photoreceptor MZ. Changes in ONL and MZ thicknesses might predict early metabolic retinal alterations in diabetes.

The quantitative parameters based on marrow metabolism derived from synthetic MRI: A pilot study of prognostic value in participants with newly diagnosed multiple myeloma.

BACKGROUND: The value of SyMRI-derived parameters from lumbar marrow for predicting early treatment response and optimizing the risk stratification of the Revised International Staging System (R-ISS) in participants with multiple myeloma (MM) is unknown. METHODS: We prospectively enrolled participants with newly diagnosed MM before treatment. The SyMRI of lumbar marrow was used to calculate T1, T2, and PD values and the clinical features were collected. All participants were divided into good response (≥VGPR) and poor response (

Nirmatrelvir/ritonavir and remdesivir against symptomatic treatment in high-risk COVID-19 outpatients to prevent hospitalization or death during the Omicron era: a propensity score-matched study.

Background: Even though worldwide death rates from coronavirus disease 2019 (COVID-19) have decreased, the threat of disease progression and death for high-risk groups continues. Few direct comparisons between the available severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antivirals have been made. Objective: We aimed to compare two SARS-CoV-2 antivirals (nirmatrelvir/ritonavir and remdesivir) against all-cause hospitalization or death. Design: This is a propensity score-matched cohort study. Methods: We included all high-risk outpatients with COVID-19 in a tertiary referral center in Mexico City from 1 January 2022 to 31 July 2023. The primary outcome was all-cause hospitalization or death 28 days after symptom onset. The secondary outcome was COVID-19-associated hospitalization or death 28 days after symptom onset. Logistic regression analysis for characteristics associated with the primary outcome and a multi-group comparison with Kaplan-Meier survival estimates were performed. Results: Of 1566 patients analyzed, 783 did not receive antiviral treatment, 451 received remdesivir, and 332 received nirmatrelvir/ritonavir. The median age was 60 years (interquartile range: 46-72), 62.5% were female and 97.8% had at least one comorbidity. The use of nirmatrelvir/ritonavir was associated with an absolute risk reduction of 8.8% and a relative risk reduction of 90% for all-cause hospitalization or death. The use of remdesivir was associated with an absolute risk reduction of 6.4% and a relative risk reduction of 66% for all-cause hospitalization or death. In multivariable analysis, both antivirals reduced the odds of 28-day all-cause hospitalization or death [nirmatrelvir/ritonavir odds ratio (OR) 0.08 - 95% confidence interval (CI): 0.03-0.19, remdesivir OR 0.29 - 95% CI: 0.18-0.45]. Conclusion: In high-risk COVID-19 outpatients, early antiviral treatment with nirmatrelvir/ritonavir or remdesivir was associated with lower 28-day all-cause hospitalization or death.

Nirmatrelvir/ritonavir and remdesivir against symptomatic treatment in high-risk COVID-19 outpatients In this study, we included high-risk non-hospitalized patients with confirmed mild COVID-19. We compared those who received antiviral treatment (nirmatrelvir/ritonavir or remdesivir) against those who only received symptomatic treatment. The aim was to detect differences in hospitalization or death 28 days after symptom onset. We analyzed 1566 patients: 783 did not receive antiviral treatment, 451 received remdesivir, and 332 received nirmatrelvir/ritonavir. Most patients were female and over 60 years old. The most common comorbidities were chronic hypertension (44%), diabetes mellitus (26%), and autoimmune diseases (25%); systemic immunosuppression was registered in 35% of patients. Hospitalization or death 28 days after symptom onset occurred in 168 patients (136 in the symptomatic treatment group, 27 in the remdesivir group, and 5 in the nirmatrelvir/ritonavir group). Considering multiple variables like age, sex, comorbidities, and previous vaccination, both antivirals significantly reduced the odds of hospitalization or death (nirmatrelvir/ritonavir odds ratio 0.08, 95% confidence interval 0.03-0.19; remdesivir odds ratio 0.29, 95% confidence interval 0.18-0.45).

Early radiologic and metabolic tumour response assessment during combined chemo-radiotherapy for locally advanced NSCLC.

Background: The role of early treatment response for patients with locally advanced non-small cell lung cancer (LA-NSCLC) treated with concurrent chemo-radiotherapy (cCRT) is unclear. The study aims to investigate the predictive value of response to induction chemotherapy (iCX) and the correlation with pattern of failure (PoF). Materials and methods: Patients with LA-NSCLC treated with cCRT were included for analyses (n = 276). Target delineations were registered from radiotherapy planning PET/CT to diagnostic PET/CT, in between which patients received iCX. Volume, sphericity, and SUVpeak were extracted from each scan. First site of failure was categorised as loco-regional (LR), distant (DM), or simultaneous LR+M (LR+M). Fine and Gray models for PoF were performed: a baseline model (including performance status (PS), stage, and histology), an image model for squamous cell carcinoma (SCC), and an image model for non-SCC. Parameters included PS, volume (VOL) of tumour, VOL of lymph nodes, ΔVOL, sphericity, SUVpeak, ΔSUVpeak, and oligometastatic disease. Results: Median follow-up was 7.6 years. SCC had higher sub-distribution hazard ratio (sHR) for LRF (sHR = 2.771 [1.577:4.87], p < 0.01) and decreased sHR for DM (sHR = 0.247 [0.125:0.485], p  <  0.01). For both image models, high diagnostic SUVpeak increased risk of LRF (sHR = 1.059 [1.05:1.106], p < 0.01 for SCC, sHR = 1.12 [1.03:1.21], p < 0.01 for non-SCC). Patients with SCC and less decrease in VOL had higher sHR for DM (sHR = 1.025[1.001:1.048] pr. % increase, p = 0.038). Conclusion: Poor response in disease volume was correlated with higher sHR of DM for SCC, no other clear correlation of response and PoF was observed. Histology significantly correlated with PoF with SCC prone to LRF and non-SCC prone to DM as first site of failure. High SUVpeak at diagnosis increased the risk of LRF for both histologies.

The Importance of Early Treatment of Inherited Neuromuscular Conditions.

There has been tremendous progress in treatment of neuromuscular diseases over the last 20 years, which has transformed the natural history of these severely debilitating conditions. Although the factors that determine the response to therapy are many and in some instance remain to be fully elucidated, early treatment clearly has a major impact on patient outcomes across a number of inherited neuromuscular conditions. To improve patient care and outcomes, clinicians should be aware of neuromuscular conditions that require prompt treatment initiation. This review describes data that underscore the importance of early treatment of children with inherited neuromuscular conditions with an emphasis on data resulting from newborn screening efforts.

Efficacy of sotrovimab on omicron BA.2, BA.4 and BA.5 subvariants of sars-cov-2 vs. other early therapies: a systematic review and meta-analysis of literature data.

Background: The aim of this meta-analysis was to ascertain whether sotrovimab was effective in reducing COVID-19 related hospitalization and mortality also in Omicron BA.2, BA.4 and BA.5 subvariants compared to other antivirals effective in index period. Methods: A systematic review and meta-analysis of Randomized Controlled Trials (RCTs) and observational studies comparing the efficacy of early treatment with sotrovimab compared to other early treatment effective in index period, antivirals or monoclonal antibodies (mAbs), in patients with COVID-19 during BA.2, BA.4, BA.5 waves, conducted in accordance with PRISMA guidelines. We searched MEDLINE, Google Scholar and the Cochrane Library. Mortality and hospitalization were defined as outcomes. Results: Four studies were included, allowing a meta-analysis of 8,041 patients. Meta-analysis showed no statistical difference between groups in hospitalization and mortality. Precisely, the RR of mortality showed no difference in the sotrovimab group compared to treatment with other drugs (OR 0.38, 95% CI 0.10-1.49, p<0.166). As regards the rate of hospitalization, no significant difference resulted between the patients treated with sotrovimab and those with other drugs (OR 1.66, 95% CI 0.41-6.66, p=0.477). Interpretation: In conclusion, this meta-analysis showed no significant difference between sotrovimab or other antivirals in reducing COVID-19 evolution in patients with a high risk of progression, considering both hospitalization and mortality.