Reduction In Progression Research Articles

Multifocal Optics for Myopia Control.

The rising prevalence of myopia among children and adolescents necessitates effective interventions to mitigate long-term risks, such as retinal detachment and macular degeneration. Traditional approaches like undercorrection with single-vision lenses have proven ineffective. Recent research underscores the significance of peripheral vision in managing myopia progression. While hyperopic defocus in the peripheral retina may encourage axial elongation, multifocal lenses designed to induce peripheral myopic defocus can potentially curb this elongation. Randomized controlled trials (RCTs) have demonstrated that spectacle lenses with peripheral modifications, such as highly aspherical lenslets (HAL) or defocus incorporated multiple segments (DIMS), reduce myopia progression and axial elongation over 2 years. Similarly, multifocal contact lenses, especially those with high-add power (+ 2.50 D), have shown comparable reductions over 3 years. Safety is a critical consideration in myopia control. Multifocal spectacle lenses with peripheral plus designs are generally well tolerated, with only transient side effects, like dizziness and blurred vision. Soft multifocal contact lenses also exhibit a favorable safety profile, with low rates of serious adverse events. Thorough monitoring and reporting in these studies are essential to provide assurance about the safety of these interventions for children. Future research should aim to include more diverse populations in order to ensure the generalizability of findings across various demographic groups. Additionally, real-world data would offer valuable insights into the performance of these treatments in everyday scenarios. Observational studies, less influenced by industry sponsorship, could further validate these findings. Lastly, the clinical significance of the observed effects should be critically assessed to confirm that the reported benefits lead to meaningful reductions in myopia progression.

Summary of Research: Dapagliflozin Utilization in Chronic Kidney Disease and Its Real-World Effectiveness Among Patients with Lower Levels of Albuminuria in the USA and Japan.

This is a summary of the original article 'Dapagliflozin Utilization in Chronic Kidney Disease and Its Real-World Effectiveness Among Patients with Lower Levels of Albuminuria in the USA and Japan'. The slowing down of kidney function decline is important for managing chronic kidney disease (CKD) and preventing its complications. Clinical trials of dapagliflozin, a sodium-glucose cotransporter-2 inhibitor (SGLT-2i), have shown reductions in disease progression and death in patients with CKD and elevated levels of albuminuria. This summary of research provides an overview of a previously published article that aimed to find out whether dapagliflozin is also effective in patients with lower levels of albuminuria [urinary albumin-to-creatinine ratio (UACR) below 200mg/g]. Starting dapagliflozin was associated with slower kidney function decline in patients with CKD and UACR below 200mg/g compared with not starting. This effect was also observed in a subgroup analysis of patients without type 2 diabetes. These results suggest that the established benefits of SGLT-2is may extend to patients with lower levels of albuminuria.

Colchicine and/or Naltrexone for Hospitalized COVID-19 Patients Not Requiring High Levels of Ventilatory Support (COLTREXONE): A Prospective, Randomized, Open-Label Trial.

We assessed the efficacy and safety of colchicine and low-dose naltrexone (LDN), alone and in combination, in preventing progression to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In this prospective, randomized, open-label trial, colchicine and LDN were compared to standard of care (SOC) in patients hospitalized with SARS-CoV-2 not requiring high levels of ventilatory support. Patients were randomly assigned to colchicine alone, LDN alone, colchicine/LDN in combination, or SOC. The primary outcome was time to disease recovery. Secondary outcomes included total time hospitalized,study enrollment, level of care, oxygen support, and adverse events. One-hundred and thirty-seven patients were randomized (Nc = 34, Nc+ldn = 33, Nldn = 35, Nsoc = 35). Eighty-four patients (61%) achieved disease recovery by day 5. There was no significant difference in the proportion of patients who experienced the primary efficacy outcome among those who received colchicine, LDN, or between the four study arms.Patients receiving colchicine had a shorter length of enrollment but not a significant reduction in the length of stay. Diarrhea was the most common adverse reaction. In adults hospitalized with SARS-CoV-2 not requiring high-level ventilatory support, colchicine and LDN, alone and in combination, were not associated with significant reductions in progression to severe disease.

Inconsistent Associations Between Risk Factor Profiles and Adjuvant Radiation Therapy (ART) Treatment in Patients with Cutaneous Squamous Cell Carcinoma and Utility of the 40-Gene Expression Profile to Refine ART Guidance.

National Comprehensive Cancer Network (NCCN) recommendations for adjuvant radiation therapy (ART) use are similar for High Risk and Very High Risk cutaneous squamous cell carcinoma (cSCC) with negative post-surgical margins. Although studies report reductions in disease progression following ART treatment, ART use is likely inconsistent when guided by available risk factors. This study evaluated the association of ART with clinical risk factors in ART-treated and untreated patients and showed the clinical utility of the 40-gene expression profile (40-GEP) for guiding ART. A multicenter study of 954 patients was conducted with institutional review board (IRB) approval. The 40-GEP test was performed using primary tumor tissue from patients with either a minimum of 3years of follow-up or a documented regional or distant metastasis. Unsupervised hierarchical cluster analysis identified patterns of clinical risk factors for ART-treated patients, then identified untreated patients with matching risk factor profiles. Results were cross-referenced to 40-GEP test results to determine utility of the test to guide ART. Analysis demonstrated inconsistent implementation of ART for eligible patients. Cluster analysis identified four patient profiles based on clusters of risk factors and, notably, matching profiles in ART-treated and untreated patients. Further, the analysis identified patients who received but could have deferred ART on the basis of 40-GEP test result and biologically low risk of metastasis, and untreated patients who likely would have benefitted from ART on the basis of their 40-GEP test result. ART guidance is not determined by the presence of specific clinicopathologic factors, with treated and untreated patients sharing the same risk factor profiles. cSCC risk determination based on NCCN recommendations for clinical factor assessment results in inconsistent use of ART. Including tumor biology-based prognostic information from the 40-GEP refines risk and identifies patients who are most appropriate and likely to benefit from ART, and those that can consider deferring ART.

C-reactive protein flare predicts response to checkpoint inhibitor treatment in melanoma.

The treatment of melanoma has been revolutionized by the use of immune checkpoint inhibition (ICI), but many patients do not benefit. Furthermore, immune-related adverse events may occur during therapy. A predictive biomarker is needed to reliably identify patients benefitting. In lung, renal cell and bladder cancer early C-reactive protein (CRP) kinetics were shown to be a predictive biomarker for ICI. Here, we investigate early CRP kinetics as predictive biomarker for ICI in melanoma patients. Two independent prospectively collected cohorts were analysed: Cohort 1 (n = 87) with advanced and Cohort 2 (n = 99) with completely resected melanoma. Patients were stratified by in the dynamics of CRP after ICI initiation: A doubling of baseline CRP within 30 days followed by at least a 30% drop within 3 months was classified as a CRP flare. If no doubling of CRP was reported, but a 30% drop within 3 months, patients were classified as CRP responders and all others as CRP non-responders. Analysed factors included clinical characteristics like S100B and LDH. Median follow-up was 1.5 and 1.7 years for Cohorts 1 and 2. In Cohort 1 CRP flare (n = 12), CRP responders (n = 43) and CRP non-responders (n = 32) with a progression-free survival (PFS) of 0.7, 0.6 and 0.2 years (p = 0.017) and an overall survival (OS) of 2.2, 1.5 and 1.0 years (p = 0.014), respectively. Multivariable Cox analysis showed an independent risk reduction of progression for CRP responders by 62% compared to CRP non-responders (p = 0.001). In Cohort 2 CRP flare (n = 13), CRP responders (n = 70) and CRP non-responders (n = 16) the log-rank analysis showed a significant difference between OS and recurrence-free survival (RFS) curves (p = 0.046 and p = 0.049). Early CRP kinetics could indicate a response to ICI with improved OS and RFS/PFS. CRP flare and CRP response indicating significantly improved outcomes compared to CRP non-responders.

Effect of lateral wedge insole on medial meniscus extrusion and its association with knee osteoarthritis progression.

Medial meniscus extrusion (MME) is associated with knee osteoarthritis (OA) progression because of increased loading stress in the medial compartment of the knee. Using a lateral wedge insole (LWI) decreases loading stress and immediately reduces MME. To investigate whether the wearing duration of LWI affects the midterm response to MME and is associated with knee OA progression. Cohort study. Twenty-three patients with knee OA who were conservatively treated with LWI were classified according to the duration of the LWI wear per day: less than 5 h (short-duration group) or over 5 h (long-duration group). MME was evaluated in the single-leg standing position by ultrasound. Knee OA progression and limb alignment were evaluated radiographically. These evaluations were performed thrice: at the initial office visit as a baseline without LWI (time 0), with LWI (LWI-time 0), and 1 year after intervention with LWI (LWI-1 year). In both groups, the MMEs at LWI time 0 were significantly decreased compared with those at time 0. In the long-duration group, this reduction in MME was maintained 1 year after the intervention compared with time 0 (time 0: 3.9 ± 0.9, LWI-1 year: 2.6 ± 1.1), but this improvement was not observed in the short-duration group (time 0: 3.8 ± 1.7, LWI-1 year: 3.6 ± 1.7). In addition, three of four patients demonstrated OA progression, and varus alignment had significantly progressed compared with that at time 0 in the short-duration group. However, the long-duration group showed OA progression only in one patient and maintained limb alignment. The duration of wearing LWI affects the midterm reduction of MME and knee OA progression while maintaining limb alignment.

Core decompression combined with platelet-rich plasma-augmented bone grafting for femur head necrosis: a systematic review and meta-analysis.

The clinical potential of biologic augmentation in core decompression and bone grafting for femoral head necrosis is widely acknowledged, with platelet-rich plasma (PRP) being a frequently employed biologic adjunct. However, its clinical application is not standardized, and high-level evidence is lacking. This study aimed to evaluate the efficacy and safety of core decompression and bone grafting combined with PRP for femur head necrosis. Several databases were systematically retrieved for randomized controlled trials comparing core decompression and bone grafting combined with or without PRP. A systematic review and meta-analysis were conducted following the PRISMA 2020 and AMSTAR 2 guidelines. The study is registered with PROSPERO under the code CRD42022361007, and it is also listed in the research registry under the identification number reviewregistry1537. Eleven studies with 642 participants (742 hips) were included. The pooled estimates revealed that when core decompression and bone grafting were combined with PRP, the Harris hip score (mean difference: 7.98; 95% CI: 5.77-10.20; P <0.001), visual analog scale (SMD: -0.68; 95% CI: -0.96 - -0.40; P <0.001) and the pain component of Harris hip score (SMD: 8.4; 95% CI: 4.12-12.68; P <0.001), and reduction of radiographic progression [risk ratio (RR): 0.40; 95% CI: 0.27-0.59; P <0.001] were superior to core decompression and bone grafting alone. Fewer patients with treatment failure (RR: 0.27; 95% CI: 0.14-0.52; P <0.001) and higher good-to-excellent results (RR: 1.48; 95% CI: 1.17-1.86; P <0.001) were observed in treatment groups than control groups. Meanwhile, the pooled analysis substantiated the superior safety profile of PRP (RR: 0.29; 95% CI: 0.11-0.77; P =0.01). The combination of core decompression and bone grafting with PRP is superior to the approach without PRP, demonstrating enhanced effectiveness in terms of function, pain relief, and radiographic progression. Additionally, it results in lower rates of treatment failure and adverse events. However, further high-quality RCTs are needed to evaluate their effectiveness due to methodological and implementation limitations observed in the existing evidence.

Digital Gait Measures Capture 1-Year Progression in Early-Stage Spinocerebellar Ataxia Type 2.

With disease-modifying drugs in reach for cerebellar ataxias, fine-grained digital health measures are highly warranted to complement clinical and patient-reported outcome measures in upcoming treatment trials and treatment monitoring. These measures need to demonstrate sensitivity to capture change, in particular in the early stages of the disease. Our aim is to unravel gait measures sensitive to longitudinal change in the-particularly trial-relevant-early stage of spinocerebellar ataxia type 2 (SCA2). We performed a multicenter longitudinal study with combined cross-sectional and 1-year interval longitudinal analysis in early-stage SCA2 participants (n = 23, including nine pre-ataxic expansion carriers; median, ATXN2 CAG repeat expansion 38 ± 2; median, Scale for the Assessment and Rating of Ataxia [SARA] score 4.8 ± 4.3). Gait was assessed using three wearable motion sensors during a 2-minute walk, with analyses focused on gait measures of spatio-temporal variability that have shown sensitivity to ataxia severity (eg, lateral step deviation). We found significant changes for gait measures between baseline and 1-year follow-up with large effect sizes (lateral step deviation P = 0.0001, effect size rprb = 0.78), whereas the SARA score showed no change (P = 0.67). Sample size estimation indicates a required cohort size of n = 43 to detect a 50% reduction in natural progression. Test-retest reliability and minimal detectable change analysis confirm the accuracy of detecting 50% of the identified 1-year change. Gait measures assessed by wearable sensors can capture natural progression in early-stage SCA2 within just 1 year-in contrast to a clinical ataxia outcome. Lateral step deviation represents a promising outcome measure for upcoming multicenter interventional trials, particularly in the early stages of cerebellar ataxia. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Comparison of the long-term effects of atropine in combination with Orthokeratology and defocus incorporated multiple segment lenses for myopia control in Chinese children and adolescents.

The aim of this study was to evaluate the efficacy of Orthokeratology (Ortho-K), defocus incorporated multiple segment (DIMS) lens, combined Ortho-K/atropine, and combined DIMS/atropine for myopia control in children. A retrospective study included 167 myopic children aged 6-14 years with a spherical equivalent refraction (SER) of -0.75 to -4.00 diopter treated with Ortho-K (OK, n = 41), combined Ortho-K/atropine (OKA, n = 43), DIMS (n = 41), or combined DIMS/atropine (DIMSA, n = 42). Axial length (AL) was measured at baseline and at 3, 6, 9 and 12 months. Axial elongation over time and between groups were analysed. After 12 months, the AL change was 0.20 ± 0.12 mm, 0.12 ± 0.14 mm, 0.22 ± 0.14 mm, and 0.15 ± 0.15 mm in the OK, OKA, DIMS, and DIMSA, respectively. There was no significant difference in AL change between OK and DIMS. OKA and DIMSA significantly slowed axial elongation compared to OK and DIMS monotherapy. After stratification by age, in the subgroup aged 6-10 years, there was significant difference in AL change between OKA and DIMS (p = 0.013), and no difference between other groups, while in the subgroup aged 10-14 years, the difference between OKA and DIMS became insignificant (p = 0.237), and the difference between OK and OKA, OK and DIMSA, DIMS and DIMSA became significant. Ortho-K and DIMS lenses show similar reductions in myopia progression among children with low initial myopia. Atropine can significantly improve the efficacy of myopia control of both Ortho-K and DIMS lenses, and this add-on effect is better in older children.

Two-Year Results of 0.01% Atropine Eye Drops and 0.1% Loading Dose for Myopia Progression Reduction in Danish Children: A Placebo-Controlled, Randomized Clinical Trial.

We investigated the two-year safety and efficacy of 0.1% loading dose and 0.01% low-dose atropine eye drops in Danish children for reduction in myopia progression in an investigator-initiated, placebo-controlled, double-masked, randomized clinical trial. Ninety-seven six- to twelve-year old myopic participants were randomized to 0.1% loading dose for six months and then 0.01% for eighteen months (loading dose group, N = 33), 0.01% for two years (0.01% group, N = 32) or placebo for two years (placebo, N = 32). Axial length (AL) and spherical equivalent refraction (SER) were primary outcomes. Secondary outcomes included adverse events and reactions, choroidal thickness, and other ocular biometrical measures. Outcomes were measured from baseline and at six-month intervals. Individual eyes nested by participant ID were analyzed with linear-mixed model analysis. Data were analyzed with intention-to-treat. Mean AL was 0.08 mm less (95% confidence interval (CI): -0.01; 0.17, p-value = 0.08) in the 0.1% loading dose and 0.10 mm less (95% CI: 0.01; 0.19, p-value = 0.02) in the 0.01% group after two years of treatment compared to placebo. Mean SER progression was 0.12 D (95% CI: -0.10; 0.33) less in the loading dose and 0.26 D (95% CI: 0.04; 0.48) less in the 0.01% groups after two years of treatment compared to placebo (p-value = 0.30 and 0.02, respectively). In total, 17 adverse events were reported in the second-year follow-up, and all were rated as mild. Adjusting for iris color did not affect treatment effect estimates. Intra-ocular pressure increased over two years comparably between all groups but remained within normal limits. Two-year treatment with 0.01% low-dose atropine eye drops is a safe and moderately efficacious intervention in Danish children for reducing myopia progression.

The impact of sodium-glucose cotransporter-2 inhibitors on outcome of patients with diabetes mellitus and colorectal cancer.

Patients with type 2 diabetes mellitus (T2DM) have a higher risk of colorectal cancer (CRC), and those with diagnosed CRC have a poorer prognosis compared with individuals with normal glucose levels. The inhibition of sodium-glucose cotransporter 2 (SGLT2) channels has been associated with a reduction in tumor proliferation in preclinical studies. We aimed to investigate the impact of sodium-glucose cotransporter 2 inhibitors (SGLT2i) on the outcome of T2DM patients with colorectal cancer. We performed a retrospective cohort study comprising adult patients with T2DM and colorectal adenocarcinoma. SGLT2i recipients were matched to non-SGLT2i recipients in a 1:1 ratio based on age, sex, and cancer stage. The primary outcome was overall survival (OS) and progression-free survival (PFS), and the secondary outcomes were previously reported serious adverse events associated with SGLT2i. We identified 1347 patients with T2DM and colorectal adenocarcinoma, from which 92 patients in the SGLT2i cohort were matched to the non-SGLT2i cohort. Compared to non-SGLT2i recipients, SGLT2i recipients had a higher rate of 5-year OS (86.2% [95% CI: 72.0-93.5] vs 62.3% [95% CI: 50.9-71.8], P=0.013) and 5-year PFS (76.6% [95% CI: 60.7-86.7] vs 57.0% [95% CI: 46.2-66.4], P=0.021). In Cox proportional hazard analyses, SGLT2i were associated with a 50-70% reduction in all-cause mortality and disease progression. SGLT2i were not associated with an increased risk of serious adverse events. SGLT2i were associated with a higher rate of survival in T2DM patients with colorectal cancer.

Real‐world implementation of DPYD and UGT1A1 pharmacogenetic testing in a community‐based cancer center

AbstractWe set out to demonstrate the feasibility of pharmacogenetic testing of DPYD and UGT1A1 and explore the clinical benefits in a community‐based cancer center. We conducted a retrospective review of 280 patients who underwent pharmacogenetic testing between November 2020 and May 2023. The primary end points included the percentage of patients with results prior to chemotherapy initiation, percentage of DPYD‐ and UGT1A1‐guided interventions implemented before chemotherapy initiation, and the turnaround time (TAT) for the pharmacogenetics results. Exploratory end points included a comparison of unplanned hospitalizations and treatment interruptions among (1) DPD phenotypes in patients who received fluoropyrimidines and (2) UGT1A1 phenotypes in patients who received irinotecan ± fluoropyrimidines. We evaluated cancer progression among patients who received DPYD‐guided dose reductions in the curative setting. More than 75% of patients had results prior to initiation of chemotherapy and 61.5% of the actionable interventions were implemented before chemotherapy, with a median TAT of 7 calendar days (IQR 5–8 calendar days). A non‐significant higher percentage of unplanned hospitalizations and treatment interruptions occurred among patients with normal DPYD compared with patients with DPYD‐guided dose reductions. A non‐significant higher frequency of treatment interruptions and dose reductions were observed in UGT1A1 intermediate metabolizer (IM) compared with UGT1A1 normal metabolizer (NM). None of the patients who received DPYD‐guided dose reductions in the curative setting experienced progression after a median follow‐up of 342 days. The real‐world evidence generated from this study demonstrates the feasibility of pre‐chemotherapy pharmacogenetic testing of DPYD and UGT1A1 in a community‐based cancer center.

Treatment of Rapid Progression of Myopia: Topical Atropine 0.05% and MF60 Contact Lenses.

This retrospective study evaluates the effectiveness of combining 0.05% atropine with MF60 contact lenses in managing rapid myopia progression in children over one year. The study involved three groups: the treatment group (TG) with 15 children (53% male, average age 12.9 ± 1.04), the MF group (MF) with 12 children (50% male, average age 12.8 ± 0.8) using only MF60 lenses, and the control group (CG) with 14 children (43% male, average age 12.1 ± 0.76). Baseline myopia and axial length (AL) were similar across groups, with the TG, MF, and CG showing -4.02 ± 0.70 D, -4.18 ± 0.89 D, -3.86 ± 0.99 D, and 24.72 ± 0.73 mm, 24.98 ± 0.70 mm, 24.59 ± 1.02 mm, respectively. Prior to the study, all groups exhibited significant myopia and AL progression, with no previous myopia control management. The treatment involved daily 0.05% atropine instillation, the use of MF60 lenses and increased outdoor activity. Biannual cycloplegic refraction and slit lamp evaluations confirmed no adverse reactions. After one year, the TG showed a significant reduction in myopia and AL progression (-0.43 ± 0.46 D, p < 0.01; 0.22 ± 0.23 mm, p < 0.01), whereas the CG showed minimal change (-1.30 ± 0.43 D, p = 0.36; 0.65 ± 0.35 mm, p = 0.533). The MF group also exhibited a notable decrease (-0.74 ± 0.45 D, p < 0.01; 0.36 ± 0.23 mm). Increased outdoor activity during the treatment year did not significantly impact myopia control, suggesting its limited additional effect in this cohort. The study concludes that the combination of 0.05% atropine and peripheral defocus soft contact lenses effectively controls myopia progression in children.

Assessing Longitudinal Treatment Efficacies and Alterations in Molecular Markers Associated with Glutamatergic Signaling and Immune Checkpoint Inhibitors in a Spontaneous Melanoma Mouse Model

Previous work done by our laboratory described the use of an immunocompetent spontaneous melanoma-prone mouse model, TGS (TG-3/SKH-1), to evaluate treatment outcomes using inhibitors of glutamatergic signaling and immune checkpoint for 18 weeks. We showed a significant therapeutic efficacy with a notable sex-biased response in male mice. In this follow-up 18-week study, the dose of the glutamatergic signaling inhibitor was increased (from 1.7 mg/kg to 25 mg/kg), which resulted in improved responses in female mice but not male mice. The greatest reduction in tumor progression was observed in male mice treated with single-agent troriluzole and anti-PD-1. Furthermore, a randomly selected group of mice was removed from treatment after 18 weeks and maintained for up to an additional 48 weeks demonstrating the utility of the TGS mouse model to perform a ≥1-year preclinical therapeutic study in a physiologically relevant tumor-host environment. Digital spatial imaging analyses were performed in tumors and tumor microenvironments across treatment modalities using antibody panels for immune cell types and immune cell activation. The results suggest that immune cell populations and cytotoxic activities of T cells play critical roles in treatment responses in these mice. Examination of a group of molecular protein markers based on the proposed mechanisms of action of inhibitors of glutamatergic signaling and immune checkpoint showed that alterations in expression levels of xCT, γ-H2AX, EAAT2, PD-L1, and PD-1 are likely associated with the loss of treatment responses. These results suggest the importance of tracking changes in molecular markers associated with the mechanism of action of therapeutics over the course of a longitudinal preclinical therapeutic study in spatial and temporal manners.

The relationship between knee flexion excursion and mechanical stress during gait in medial knee osteoarthritis

BackgroundA decrease in knee flexion excursion during the loading response may affect not only quadriceps muscle weakness, pain, and inflammatory symptoms, but also lead to physical function decline and activity limitation. The aim of this investigation was to clarify the relationship between knee flexion excursion during the loading response and mechanical stress on the knee joint, muscle strength, pain, and physical function in patients with knee osteoarthritis. MethodsTwenty patients diagnosed with medial knee osteoarthritis. The participants walked along a 10 m corridor in the laboratory at a comfortable pace. The kinematic and kinetic data were collected using a 3D motion analysis system. We employed to control for gait speed and age while examining the relationship between knee flexion excursion during the loading response and mechanical stress on the knee joint, muscle strength, pain, and physical function. FindingsKnee flexion excursion showed a significant positive correlation with the peak and angular impulse of knee flexion moment. In the partial correlation coefficients controlling for age and gait speed, significant negative correlations were found between knee flexion excursion and knee adduction moment angular impulse. InterpretationIt can be inferred that gait with reduced knee flexion movement during the loading response in patients with knee osteoarthritis may result in increased mechanical stress on the knee joint in the frontal plane. Exercise interventions aimed at increasing knee flexion excursion may result in a reduction in disease progression.

Red light instruments for myopia exceed safety limits.

Low-level red light (LLRL) therapy has recently emerged as a myopia treatment in children, with several studies reporting significant reduction in axial elongation and myopia progression. The goal of this study was to characterise the output and determine the thermal and photochemical maximum permissible exposure (MPE) of LLRL devices for myopia control. Two LLRL devices, a Sky-n1201a and a Future Vision, were examined. Optical power measurements were made using an integrating sphere radiometer through a 7-mm diameter aperture, in accordance with ANSI Z136.1-2014, sections 3.2.3-3.2.4. Retinal spot sizes of the devices were obtained using a model eye and high-resolution beam profiler. Corneal irradiance, retinal irradiance and MPE were calculated for an eye positioned at the oculars of each device. Both devices were confirmed to be Class 1 laser products. Findings showed that the Sky-n1201a delivers laser light as a point source with a 654-nm wavelength, 0.2 mW power (Ø 7 mm aperture, 10-cm distance), 1.17 mW/cm2 corneal irradiance and 7.2 W/cm2 retinal irradiance (Ø 2 mm pupil). The MPE for photochemical damage is 0.55-7.0 s for 2-7 mm pupils and for thermal damage is 0.41-10 s for 4.25-7 mm pupils. Future Vision delivers the laser as an extended source subtending 0.75 × 0.325°. It has a 652-nm wavelength, 0.06 mW power (Ø 7 mm aperture, 10 cm distance), 0.624 mW/cm2 corneal irradiance and 0.08 W/cm2 retinal irradiance (Ø 2 mm pupil). MPE for photochemical damage is 50-625 s for 2-7 mm pupils. For both of the LLRL devices evaluated here, 3 min of continuous viewing approached or surpassed the MPE, putting the retina at risk of photochemical and thermal damage. Clinicians should be cautious with the use of LLRL therapy for myopia in children until safety standards can be confirmed.

7‐methylxanthine for myopia control in Denmark – Clinical results 2003–2023

In 2009, the Danish Medicines Agency authorized the use of pharmacy‐compounded 7‐methylxanthine (7‐MX) tablets for treatment of progressive myopia in children. 7‐MX has since been prescribed to more than 1200 individuals with no reports of adverse effects. A high compliance rate has demonstrated that the concept of using an oral pharmaceutical to control myopia progression is feasible. Analysis with the use of linear mixed models of longitudinal data from 711 children aged 7–14 years and with less than 10 diopters (D) of myopia at baseline has shown that myopia progression and axial eye growth is linearly associated with the average daily dose of 7‐MX taken during the observation period. Linear regression of data from 350 children aged 7–10 years at baseline who completed 3 years of follow‐up suggest that the absolute reduction of myopia progression and axial growth over 3 years associated with taking 400 mg three times daily is approximately 1.2 D and 0.35 mm, regardless of baseline myopia. Linear regression of data from 157 children aged 7–10 years at baseline who completed 5 years of follow‐up suggest that the absolute reduction of myopia progression and axial growth over 5 years associated with taking 400 mg three times daily is approximately 1.8 D and 0.62 mm.Thus, the efficacy of 7‐MX does not seem to decrease with duration of treatment. Negative eye growth (eye shortening) of 0.05 mm or more in children taking an average daily dose of 640 mg or more occurs in 1% of children aged 6–9, 3% of children aged 10–13, and 8% of children aged 14–15 at baseline. The largest eye shortening found was in a 6‐year‐old child with an initial myopia of −7.125/−7.75 diopters (D) and axial length of 26.07/26.29 mm who took an average dose of 1152 mg 7‐MX per day. After 1 year, the myopia was reduced to −5.5/−5.75 D and the axial length reduced to 25.77/25.94 mm. 7‐MX does not seem to induce thickening of the choroid and may therefore work by another mechanism than other myopia control interventions. Preliminary data suggest that the effects of 7‐MX and other myopia control methods are additive. In conclusion, based on 20 years of clinical experience in Denmark, 7‐MX shows promise as a non‐toxic, side‐effect free, oral myopia control pharmaceutical, suitable for use as a supplement when myopia progression cannot be completely arrested by monotherapy with low‐dose atropine or an optical device.

Oral glutamine dipeptide or oral glutamine free amino acid reduces burned injury progression in rats.

This study was carried out to evaluate the effect of Glutamine, as a dipeptide or a free amino acid form, on the progression of burn injuries in rats. Thirty male Wistar rats were burned with a comb metal plate heated in boiling water (98 °C) for three minutes, creating four rectangular full-thickness burn areas separated by three unburned interspaces (zone of stasis) in both dorsum sides. The animals were randomized into three groups (n=10): saline solution (G1-Control) and treated groups that orally received Glutamine as dipeptide (G2-Dip) or free amino acid (G3-FreeAA). Two and seven days after burn injury, lesions were photographed for unburned interspaces necrosis evolution assessment. Seven days after injury, glutathione seric was measured and histopathological analysis was performed. By photographs, there was a significant reduction in necrosis progression in G3-Free-AA between days two and seven. Histopathological analysis at day 7 showed a significantly higher stasis zone without necrosis and a higher number of fibroblasts in G2-Dip and G3-FreeAA compared with G1-Control. Also, glutathione serum dosage was higher in G2-Dip. The plasmatic glutathione levels were higher in the G2-Dip than the G1-Control, and there was a trend to higher levels in G3-FreeAA. The reduction in histological lesions, greater production of fibroblasts, and greater amounts of glutathione may have benefited the evolution of burn necrosis, which showed greater preservation of interspaces.

Impact of Engagement with Outcome Sustainability using a Fluid Multidisciplinary Preventive Cardiology Center: Protocol and Methods

IntroductionIntensive lifestyle interventions ameliorate cardiometabolic risk factors in the short term, however this effect decreases in subsequent years. The Center for Clinical Cardiovascular Health at Mount Sinai Heart (the “Center”) was built to apply interdisciplinary preventive care, lifestyle medicine, and guideline-directed medical therapy in one physical location. We posit that patient engagement within a fluid multidisciplinary preventive cardiology center is associated with increased guideline-directed medical therapy and lower rates of cardiometabolic based chronic disease (CMBCD) development and progression compared with published data. We also seek to determine a correlation between engagement scores and patient response/sustainability. MethodsPatient visits to the Center are tracked since March 1, 2017. This data will be curated according to variables that indicate specific coordinates of CMBCD at the initial visit. This classification will allow determination of the “dominant” or “target” metabolic driver, which is the driver at the most advanced stage at baseline for each patient. Logistic regression was used to analyze health care utilization and initial driver stage with odds of sustainability. Factor analysis was used to analyze the main variables associated with intervention response and sustainability. ConclusionsEarly management of cardiometabolic disease requires understanding and utilization of a three-dimensional approach. Dimension 1: CMBCD drivers exist along a pathophysiological continuum rather than as a dichotomous (absent/present) state. Dimension 2: key mechanistic drivers include adiposity, dysglycemia, hypertension, and dyslipidemia. Dimension 3: ascertaining structural/social determinants of health portends improved individualized sustainability. Increased patient engagement scores are also associated with both short-term and long-term reduction of CMBCD disease progression.

A composite endpoint using version 3 of the Alzheimers’ Disease Research Centers’ neuropsychological test battery

AbstractBackgroundVersion 3 of the Uniform Data Set (UDS) has been collected by the National Alzheimer’s Coordinating Center (NACC) since 2015, which contains neuropsychological test scores on multiple domains. However, its potential utility as prevention trial outcomes needs to be examined, in comparison with other previously validated outcomes.MethodThe analytical sample was extracted from the December 2022 data freeze from NACC, which includes baseline and follow‐up visits from participants who were cognitively normal during initial visits. Standardized z‐scores for each cognitive domain (attention/working memory, episodic memory, semantic memory/language, executive function, visuospatial function) were calculated. Linear mixed effects models with random intercepts and slopes were used for studying longitudinal changes comparing participants who progressed to MCI or AD (decline subgroup) and those who remained cognitively normal for up to 4 years of follow‐up (stable subgroup), controlling for baseline age, sex, race, education and APOE‐e4 carrier status. We then constructed an approximate effect size weighted average of domain‐specific scores as a global composite measure, obtain effect size estimates using the mini‐mental state examination (MMSE), the Montreal Cognitive Assessment (MoCA) and the composite measure as outcomes, and perform sample size calculations using the following assumptions: a significance level of 5%, 80% power, an equal proportion randomized in a hypothesized intervention and a placebo control arms, in which the intervention group has a 10% to 30% reduction of progression to MCI during the study period, each participant has a baseline visit and up to four annual follow‐up visits, a dropout rate of 10% per year.ResultThe estimated difference of the annualized rate of change in z‐scores between the decline and stable subgroups ranged from 0.028 (attention) to 0.105 (executive function) standardized units for the domain‐specific scores, and 0.068 standard deviation units for the composite score. The composite score requires a smaller sample size for detecting the same level of reduction in progression compared to MoCA and MMSE.ConclusionUsing a global composite score of UDS version 3 neuropsychological tests as a prevention trial outcome would result in about 30‐50% reduction of sample size needed compared to MMSE and MoCA.