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.

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.

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).

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.

Utilizing the sublingual form of squalene in COVID-19 patients: a randomized clinical trial.

In this study, the efficacy of sublingual squalene in decreasing the mortality rate among patients with COVID-19 was investigated. Squalene was extracted from pumpkin seed oil with a novel method. Then, the microemulsion form of squalene was prepared for sublingual usage. In the clinical study, among 850 admitted patients, 602 eligible COVID-19 patients were divided in two groups of control (N = 301) and cases (N = 301) between Nov 2021 and Jan 2022. Groups were statistically the same in terms of age, sex, BMI, lymphocyte count on 1st admission day, hypertension, chronic kidney disease, chronic respiratory disease, immunosuppressive disease, and required standard treatments. The treatment group received five drops of sublingual squalene every 4 h for 5 days plus standard treatment, while the control group received only standard treatment. Patients were followed up for 30 days after discharge from the hospital. The sublingual form of squalene in the microemulsion form was associated with a significant decrease in the mortality rate (p < 0.001), in which 285 (94.7%) cases were alive after one month while 245 (81.4%) controls were alive after 1 month of discharge from the hospital. In addition, squalene appears to be effective in preventing re-hospitalization due to COVID-19 (p < 0.001), with 141 of controls (46.8%) versus 58 cases (19.3%). This study suggests sublingual squalene in the microemulsion as an effective drug for reducing mortality and re-hospitalization rates in COVID-19 patients.Trial Registration Number: IRCT20200927048848N3.

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.

Outcomes of early treatment of radial dysplasia.

Purpose: Radial dysplasia, also termed radial club hand is an abnormality along the longitudinal axis of the hand characterized by hypoplasia or aplasia of radial structures. Surgery that centralize the wrist on the distal end of the ulna gives quite good results in terms of anatomical recovery but affecting range of motion of the wrist and fingers, limbs length. We conducted this study to evaluate the outcome of serial casting followed by centralization at our institution. Materials and methods: We conducted a prospective study involving 20 pediatric patients with 25 limbs affected by Bayne Types III and IV radial dysplasia, with an average follow-up period of 4.2 years. Each limb underwent progressive soft tissue stretching via serial casting, followed by centralization. Clinical and radio-graphic data were collected at surgery and during follow-up assessments. Results: The study achieved an average correction of 60° in radial deviation, with a decrease in wrist range of motion from 79° to 28° over the follow-up period. Finger mobility showed increased stiffness. Ulnar length recovery reached 57% of the normal contra-lateral side. Final results, based on the Bayne and Klug criteria, revealed that 24 out of 25 hands (96%) exhibited good or satisfactory outcomes. Conclusion: Early intervention employing gradual corrective casting followed by centralization is an effective treatment for radial dysplasia in children, consistently resulting in good or satisfactory outcomes. However, this approach entails a trade-off with reduced wrist and finger range of motion and potential implications for limb growth.

Searching for a "Window of Opportunity" in the Treatment of Vulvar Lichen Sclerosus: Evidence for Therapeutic Benefits of an Early Corticosteroid Treatment.

INTRODUCTION: Vulvar lichen sclerosus (VLS) is characterized by progressive anatomical changes which become increasingly severe and irreversible. The objective of this study was to investigate if a "window of opportunity" exists in VLS, i.e., to assess if an early treatment may prevent disease progression and facilitate clearance of symptoms and/or signs. METHODS: This retrospective, cohort study included VLS patients treated for the first time with a topical corticosteroid, namely with mometasone furoate 0.1% ointment, for 12 weeks (2016-2021). Scoring of subjective symptoms (global subjective score, GSS, and dyspareunia) and clinical features (global objective score [GOS] and sclerosis-scarring-atrophy) was performed at baseline (T0) and at the control visit (T1). We assessed if the achievement of clearance in GSS, GOS, sclerosis-scarring-atrophy, or dyspareunia depended on the time elapsed between VLS onset and treatment initiation. RESULTS: Among the 168 patients (59.2 ± 13.2 years) included, the median time between VLS onset and first treatment was 14.0 months. At T1, 48.8% of patients achieved clearance of GSS, 28% of GOS and 11.9% of both GSS and GOS, 57.9% of dyspareunia, and 19.2% of sclerosis-scarring-atrophy. The logistic regression model showed that each 10-month increase in treatment initiation adversely affected the clearance of GSS while starting treatment within 6 months of disease onset was significantly associated with clearance of GOS and sclerosis-scarring-atrophy. CONCLUSION: Early treatment is crucial in determining a complete healing of VLS-related symptoms and signs, especially of tissue sclerosis-scarring-atrophy, which appear poorly responsive, or even unresponsive, after the earliest stages of the disease. Thus our findings provide evidence for a "window of opportunity" in VLS treatment.

Skeletal and dental effects of function-generating bite appliance compared to rapid palatal expander and untreated controls.

INTRODUCTION: Maxillary expansion is a fundamental interceptive orthodontic treatment, which can be achieved through either a rapid expansion protocol or functional devices. However, no data exist about the efficacy of functional devices in achieving skeletal expansion. Therefore, the aim of this study was to compare the effects of the rapid palatal expander (RPE) and the function-generating bite type M (FGB-M) on the transversal dimension of the maxilla, and on the maxillary and mandibular dental arch width. METHODS: One hundred eighty-one skeletal Class I patients, aged between 6 and 12 years and with a cervical vertebral maturation stage II or III, with maxillary transversal deficiency were retrospectively enrolled; among these 55 were treated with FGB-M, 73 were treated with RPE and 51 were untreated subjects retrieved from historical databases. The pre-treatment (T0) and post-treatment (T1) frontal cephalograms were retrieved, and the maxillary and mandibular widths, and the distance between upper and lower first molars were measured. T1-T0 interval was of 17.3 months (RPE), 24.6 months (FGB-M) and 18.2 months (controls). RESULTS: The statistical analysis showed that there were no statistically significant differences between the RPE and FGB-M groups regarding skeletal and dental expansion, while the untreated control group differed significantly from the other two groups. CONCLUSION: The comparison between patients treated with RPE and FGB-M showed that there were no statistically significant differences between the RPE and FGB-M groups regarding the amount of skeletal expansion and dental arch width, suggesting that both appliances can be used to achieve similar results.

Initial development of an 'Orthodontic Care Index' involving treatment need,-complexity and-priority.

BACKGROUND/OBJECTIVES: The aim of this study was to develop an evidence-based scoring system for prioritizing limited orthodontic resources based on orthodontic treatment need (OTN), orthodontic treatment complexity (OTC), and orthodontic treatment priority (OTP), which is not merely a scoring system for malocclusion but also a comprehensive classification of orthodontic issues incorporating patient- and treatment-related factors, called Orthodontic Care Index (OCI). MATERIALS AND METHODS: The development of the OCI involved eight phases, starting with a systematic literature review to identify all possible parameters involved in determining OTN, OTC, and OTP. An eight-member orthodontic specialist panel then evaluated and scored the significance of each parameter, resulting in a parameter-score list. Subsequently, a retrospective convenience sample of 61 patients was scored with the parameter-score list, and using the same convenience sample a gold standard was established through the expert opinion of a third orthodontic panel. Linear regression analysis was used to estimate weights of importance and construct a formula to calculate index scores. Lastly, the expert opinion was compared to the index scores, to determine the index performance. RESULTS: The preliminary index separately calculates OTN, OTC, and OTP for a patient as the weighted sum of his/her domain scores. The sensitivity of the index for predicting OTN, OTC, and OTP was high (98.1%, 82.9%, and 92.7% respectively), while the variability of each was relatively low (52.1%, 31.2%, and 52.6% respectively). CONCLUSIONS/IMPLICATIONS: The OCI shows promise as a guideline for prioritizing orthodontic care. It will be further refined and validated to enhance its performance and usefulness.

Clinical antiviral efficacy of favipiravir in early COVID-19 (PLATCOV): an open-label, randomised, controlled, adaptive platform trial.

In early symptomatic COVID-19 treatment, high dose oral favipiravir did not accelerate viral clearance. BACKGROUND: Favipiravir, an anti-influenza drug, has in vitro antiviral activity against SARS-CoV-2. Clinical trial evidence to date is inconclusive. Favipiravir has been recommended for the treatment of COVID-19 in some countries. METHODS: In a multicentre open-label, randomised, controlled, adaptive platform trial, low-risk adult patients with early symptomatic COVID-19 were randomised to one of ten treatment arms including high dose oral favipiravir (3.6g on day 0 followed by 1.6g daily to complete 7 days treatment) or no study drug. The primary outcome was the rate of viral clearance (derived under a linear mixed-effects model from the daily log10 viral densities in standardised duplicate oropharyngeal swab eluates taken daily over 8 days [18 swabs per patient]), assessed in a modified intention-to-treat population (mITT). The safety population included all patients who received at least one dose of the allocated intervention. This ongoing adaptive platform trial was registered at ClinicalTrials.gov (NCT05041907) on 13/09/2021. RESULTS: In the final analysis, the mITT population contained data from 114 patients randomised to favipiravir and 126 patients randomised concurrently to no study drug. Under the linear mixed-effects model fitted to all oropharyngeal viral density estimates in the first 8 days from randomisation (4,318 swabs), there was no difference in the rate of viral clearance between patients given favipiravir and patients receiving no study drug; a -1% (95% credible interval: -14 to 14%) difference. High dose favipiravir was well-tolerated. INTERPRETATION: Favipiravir does not accelerate viral clearance in early symptomatic COVID-19. The viral clearance rate estimated from quantitative measurements of oropharyngeal eluate viral densities assesses the antiviral efficacy of drugs in vivo with comparatively few studied patients.

Can the CHOP-INTEND be used as An Outcome Measure in the First Months of Age? Implications for Clinical Trials and Real World Data.

BACKGROUND: The CHOP-INTEND is an established outcome measure used to assess motor function in young and weak SMA patients previously validated in type I infants older than 3 months. OBJECTIVE: The aim of our study was to assess the maturation of the CHOP-INTEND scores in a group of healthy infants, establishing which items of the scale can be reliably used in individuals younger than 3 months. METHODS: This is a prospective observational study. The whole cohort was divided into 5 age groups. Each of the 16 CHOP-INTEND items was analyzed looking at the frequency distribution of the scores in each age subgroup. An item was considered developmentally appropriate when > 85% of the infants achieved a full score. RESULTS: our study includes 61 assessments collected < 2 weeks, 25 at 2-4 weeks, 20 at 5-8 weeks, 25 at 9-12 weeks and 20 at 13-17 weeks. Eight of the 16 items were developmentally appropriate already in the first week and another by the end of the first month. The remaining 7 items had more variable responses in the first three months and full scores were consistently achieved only after the third month. CONCLUSIONS: Our findings suggest that the CHOP-INTEND can be used before the age of 3 months, but the results should be interpreted with caution, considering which items are developmentally appropriate at the time of testing. This will also help to establish whether the changes observed following early treatments are a sign of efficacy or at least partly reflect maturational aspects.

Autonomic nervous modulation: early treatment for pulmonary artery hypertension.

Pulmonary artery hypertension (PAH) is a chronic vascular disease defined by the elevation of pulmonary vascular resistance and mean pulmonary artery pressure, which arises due to pulmonary vascular remodelling. Prior research has already established a link between the autonomic nervous system (ANS) and PAH. Therefore, the rebalancing of the ANS offers a promising approach for the treatment of PAH. The process of rebalancing involves two key aspects: inhibiting an overactive sympathetic nervous system and fortifying the impaired parasympathetic nervous system through pharmacological or interventional procedures. However, the understanding of the precise mechanisms involved in neuromodulation, whether achieved through medication or intervention, remains insufficient. This limited understanding hinders our ability to determine the appropriate timing and scope of such treatment. This review aims to integrate the findings from clinical and mechanistic studies on ANS rebalancing as a treatment approach for PAH, with the ultimate goal of identifying a path to enhance the safety and efficacy of neuromodulation therapy and improve the prognosis of PAH.

Congenital scrub typhus: a case report and literature review.

Background: This study aimed to analyze the clinical course of a newborn with congenital scrub typhus caused by vertical transmission and explore early diagnosis and treatment strategies. The clinical data of the neonate were retrospectively analyzed and the related literature was reviewed. Case presentation: The newborn was a full-term one, with a good Apgar score at birth. The neonate had apnea at 3 h of life, requiring NICU care and IV antibiotics (piperacillin) for suspected sepsis. An examination revealed hepatosplenomegaly. Blood tests revealed anemia and thrombocytopenia and a chest x-ray showed patchy inflammation. On the second day of life, he developed a fever. On the third day of life, he required mechanical ventilation because his condition worsened after he presented with dyspnea, hypotension, depressed sensorium, and other signs of sepsis. Importantly, the neonate's mother had a history of scrub typhus at 31+ weeks of gestation. While the blood culture result was still pending, high-throughput sequencing of blood and cerebrospinal fluid was performed. To address the suspected scrub typhus infection, oral azithromycin dry suspension was added to the treatment regimen. High-throughput sequencing results on the 5th day of life confirmed a significant presence of 16SrRNA sequences in the blood, suggesting an Orientia tsutsugamushi infection. The neonate steadily recovered and was discharged 16 days after hospitalization. The neonate was followed up for 9 months, and the outcome was favorable with normal growth and development. Conclusions: This article reports a case of congenital Orientia tsutsugamushi infection, a rare condition caused by vertical transmission. Our review of the literature, combined with the presented case, brings the total number of documented congenital scrub typhus cases caused by vertical transmission to eight. Regrettably, one patient from this group unexpectedly died on the 10th day of hospitalization, resulting in a mortality rate of 12.5% (1/8). The special transmission mode and clinical manifestations of this disease will serve as an alert to doctors for timely diagnosis and treatment. Because of the non-specific clinical manifestations of congenital scrub typhus, limited understanding, low index of suspicion among clinicians, and a lack of diagnostic facilities, scrub typhus is seriously underdiagnosed in pregnant women, fetuses, and neonates.