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Pentosan polysulfate sodium (Elmiron) maculopathy: a genetic perspective

Retina. 2023 Mar 28. doi: 10.1097/IAE.0000000000003794. Online ahead of print.

ABSTRACT

PURPOSE: To assess genetic associations for pentosan polysufate sodium maculopathy.

METHODS: Genetic testing for inherited retinal dystrophy (IRD) genes using exome testing and for 14 age-related macular degeneration (AMD) associated single nucleotide polymorphisms (SNP) using panel testing were performed. Additionally, full-field electroretinograms (ffERG) were obtained to identify any cone-rod dystrophy.

RESULTS: Eleven out of fifteen patients were female, with a mean age of 69 (range 46-85). IRD exome testing in five patients revealed six pathogenic variants but failed to confirm IRD in any patient genetically. FfERG performed in 12 patients demonstrated only non-specific a- and b-wave abnormalities in 11 cases and was normal in one case. For AMD SNPs, CFH rs3766405 (p=0.003) and CETP (p=0.027) were found to be statistically significantly associated with pentosan polysulfate maculopathy phenotype compared to the control population.

CONCLUSION: Pentosan polysulfate maculopathy is not associated with Mendelian IRD genes. However, several AMD risk alleles were identified to be associated with maculopathy compared to their frequency in the normal population. This suggests a role for genes in disease pathology, particularly the alternative complement pathway. These findings would benefit from further investigation to understand the risk of developing maculopathy in taking pentosan polysulfate.

PMID:36996461 | DOI:10.1097/IAE.0000000000003794

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Complement Inhibition for Geographic Atrophy: Review of Salient Functional Outcomes and Perspective

Retina. 2023 Mar 28. doi: 10.1097/IAE.0000000000003796. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate available rationale and outcomes of randomized trial results for complement inhibition for geographic atrophy.

METHODS: Data from recently completed randomized trials of complement inhibition, particularly for pegcetacoplan and avacincaptad pegol, were evaluated for both the outcome, area of autofluorescence loss, and functional vision tests.

RESULTS: Pegcetacoplan 2 mg showed statistically significant reduction in expansion of area of autofluorescence loss with monthly, but not every-other-month dosing, in a 12-month phase 2 trial. Nearly 40% of patients recruited for the monthly arm did not complete the trial. In two parallel phase 3 studies there was a statistically significant reduction in the area of atrophy in one but not both studies. Data released at 24 months follow-up showed statistically significant reduction in area of autofluorescence detected atrophy in both studies compared with sham. Patients did not show functional difference in best corrected visual acuity, maximum reading speed, Functional Reading Independence Index, and mean microperimetry threshold sensitivities in the treatment versus sham arms. Avacincaptad pegol was evaluated in 2 randomized pivotal studies and showed a statistically significant reduction in expansion of autofluorescence loss at 12 months. Patients in the treatment arms did not show any difference as compared with sham in best corrected visual acuity or low luminance visual acuity, the only functional outcomes mentioned. Both drugs increased the risk of macular neovascularization.

CONCLUSIONS: Both avacincaptad pegol and pegcetacoplan show significant differences compared with sham in autofluorescence imaging but no benefit in visual function at 12 and 24 months, respectively.

PMID:36996460 | DOI:10.1097/IAE.0000000000003796

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Joint Attention-Based Occupational Therapy Intervention in Preschoolers With Autism Spectrum Disorder: A Randomized Controlled Trial

Am J Occup Ther. 2023 Mar 1;77(2):7702205090. doi: 10.5014/ajot.2023.050177.

ABSTRACT

IMPORTANCE: A viable occupational therapy program based on joint attention is needed to ensure that children with autism spectrum disorder (ASD) lead lives in which they interact socially.

OBJECTIVE: To explore the benefit of a joint attention-based occupational therapy program offered simultaneously with the usual special education program (USEP) compared with USEP alone.

DESIGN: Randomized controlled study, including pre-, post-, and follow-up testing.

SETTING: Special education and rehabilitation center.

PARTICIPANTS: Twenty children with ASD in the study group, M = 4.80 yr (SD = 0.78 yr), and the control group, M = 5.10 yr (SD = 0.73 yr), were included.

INTERVENTION: All children received USEP (2 sessions/wk for 12 wk). Joint attention-based occupational therapy was applied to the study group in addition to USEP (3 sessions/wk for 12 wk).

OUTCOMES AND MEASURES: The Social Communication Questionnaire (SCQ), Autism Behavior Checklist (ABC), and Motor-Free Visual Perception Test-4 (MVPT-4) were implemented.

RESULTS: The study group had a statistically and clinically significant improvement in SCQ, ABC, and MVPT-4 scores after the intervention (p < .001). The control group did not show statistically significant improvement in measurements (p > .05). The mean values of SCQ-Total, ABC-Total, and MVPT-4 variables measured at 3-mo follow-up were significantly different than preintervention (p < .05).

CONCLUSIONS AND RELEVANCE: Joint attention-based intervention, including a child-centered approach, can improve social communication, reduce ASD-related behaviors, and improve visual perception. What This Article Adds: This study emphasizes the importance of occupational therapy with a holistic perspective, based on joint attention, in terms of increasing the effectiveness of special education programs attended by children with ASD and reinforcing visual perception, communication, and positive behaviors in children with ASD.

PMID:36996457 | DOI:10.5014/ajot.2023.050177

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Food insecurity disparities and impact on academic and social experiences among college students at a large public university

J Am Coll Health. 2023 Mar 30:1-8. doi: 10.1080/07448481.2023.2194435. Online ahead of print.

ABSTRACT

Objective: This research seeks to understand food insecurity experiences among students at a large public university in the southern United States. Participants: Participants consented and completed an online survey disseminated on campus in April-May 2021 (N = 418). The participants sampled were predominantly undergraduate (78.2%), females (72.4%), who lived off campus (54.1%), and were racially/ethnically diverse. Methods: Descriptive statistics, multivariable logistic regression, and chi-squared tests were used to examine the differences and association between demographic characteristics and behaviors and food insecurity status. Results: About 32% students surveyed had experienced food insecurity in the last year, which resembles national trends. There were significant differences in students’ food insecurity status by race, sexual orientation, first-generation status, residential category, and main mode of transportation. Food insecurity impacted academic and socioeconomic student behaviors. Conclusions: This research has implications for improving the academic, physical, and psychological wellbeing of university students and should inform future programs and policies.

PMID:36996426 | DOI:10.1080/07448481.2023.2194435

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Approximate reciprocal relationship between two cause-specific hazard ratios in COVID-19 data with mutually exclusive events

Int J Biostat. 2023 Apr 3. doi: 10.1515/ijb-2022-0083. Online ahead of print.

ABSTRACT

COVID-19 survival data presents a special situation where not only the time-to-event period is short, but also the two events or outcome types, death and release from hospital, are mutually exclusive, leading to two cause-specific hazard ratios (csHR d and csHR r ). The eventual mortality/release outcome is also analyzed by logistic regression to obtain odds-ratio (OR). We have the following three empirical observations: (1) The magnitude of OR is an upper limit of the csHR d : |log(OR)| ≥ |log(csHR d )|. This relationship between OR and HR might be understood from the definition of the two quantities; (2) csHR d and csHR r point in opposite directions: log(csHR d ) ⋅ log(csHR r ) < 0; This relation is a direct consequence of the nature of the two events; and (3) there is a tendency for a reciprocal relation between csHR d and csHR r : csHR d ∼ 1/csHR r . Though an approximate reciprocal trend between the two hazard ratios is in indication that the same factor causing faster death also lead to slow recovery by a similar mechanism, and vice versa, a quantitative relation between csHR d and csHR r in this context is not obvious. These results may help future analyses of data from COVID-19 or other similar diseases, in particular if the deceased patients are lacking, whereas surviving patients are abundant.

PMID:36996414 | DOI:10.1515/ijb-2022-0083

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Trends in Incidence of Cancers Associated With Obesity and Other Modifiable Risk Factors Among Women, 2001-2018

Prev Chronic Dis. 2023 Mar 30;20:E21. doi: 10.5888/pcd20.220211.

ABSTRACT

We used data from the US Cancer Statistics database to determine trends in cancer incidence, stratified by age, race, and ethnicity, among women aged 20 years or older during an 18-year study period (2001-2018). We limited analysis to cancers associated with 5 modifiable risk factors: tobacco use, excess body fat, alcohol consumption, insufficient physical activity, and human papillomavirus infection. The incidence of cancers associated with obesity have risen, particularly among women aged 20 to 49 years (vs ≥50 y) and among Hispanic women. Strategies that address obesity rates in these populations may help decrease cancer risk.

PMID:36996404 | DOI:10.5888/pcd20.220211

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The value of percutaneous ultrasound-guided subacromial bursography in the diagnosis of rotator cuff tears

Med Ultrason. 2023 Mar 30;25(1):48-55. doi: 10.11152/mu-3913.

ABSTRACT

AbstractPurpose To determine the feasibility and diagnostic value of percutaneous ultrasound-guided subacromial bursography (PUSB) in the diagnosis of rotator cuff tears.Methods Between July 2019 to October 2021, 78 patients who had suspected rotator cuff injury and who were admitted to the Second Affiliated Hospital of Xi’an Jiaotong University were selected, including 32 males and 46 females, aged 31-70 years (mean age 53.9±9.1 years), with a course of 1D-2 years. The MRI, US and PUSB images of patients were retrospectively analyzed to obtain the diagnostic and predictive indexes (sensitivity, specificity, positive predictive value,negative predictive value and accuracy) of these three methods for different rotator cuff tears types (full-thickness tears, partial-thickness tears and no tears of rotator cuff ). With the results of shoulder arthroscopy serving as the standard, PUSB results were compared with MRI and US results using the X2 -test (a=0.05, two-sided).Results In all 78 patients, the overall accuracy of MRI, US, and PUSB in diagnosing rotator cuff tears was 82.1% (64/78), 75.6% (59/78) and 96.2% (75/78), respectively (P < 0.001). Among 21 patients with full-thickness tears, the numbers of cases correctly diagnosed by MRI, US and PUSB were 19, 19 and 21, respectively. The sensitivity and specificity of MRI, US and PUSB in diagnosing full-thickness tears were 90.5%, 90.5%, 100% and 98.2%, 93.0%, 100%, respectively. The diagnostic accuracies of full-thickness rotator cuff tears were 90.5%, 90.5% and 100%, respectively, with no statistical difference (P = 0.344). Among 42 patients with partial-thickness tears, the numbers of patients whose cases were correctly diagnosed on MRI, US and PUSB were 32, 27 and 40, respectively. The sensitivity and specificity of MRI, US and PUSB in diagnosing partial-thickness tears were 76.2%, 64.3%, and 95.2% and 88.9%, 88.9%, and 97.2%, respectively. The diagnostic accuracies of partial-thickness rotator cuff tears were 76.2% (32/42), 64.3% (27/42) and 95.2% (40/42), respectively (P<0.05). Among the 15 patients without tears, the numbers of misdiagnosed cases by MRI, US and PUSB were 2, 2, and 1, respectively, and they were all misdiagnosed as partial-thickness tears. The sensitivity and specificity of MRI, US and PUSB in the diagnosis of complete rotator cuff were 86.7%, 86.7%, and 93.3% and 85.7%, 82.5% and 96.8%, respectively, and the accuracies in diagnosing no tears were 86.7% (13/15), 86.7% (13/15) and 87.5% (14/15), respectively (P = 0.997).Conclusions It is feasible to diagnose rotator cuff tears by PUSB, which can be used as an important supplement imaging method to evaluate rotator cuff tears.

PMID:36996393 | DOI:10.11152/mu-3913

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Measurable Residual Disease and Fusion Partner Independently Predict Survival and Relapse Risk in Childhood KMT2A-Rearranged Acute Myeloid Leukemia: A Study by the International Berlin-Frankfurt-Münster Study Group

J Clin Oncol. 2023 Mar 30:JCO2202120. doi: 10.1200/JCO.22.02120. Online ahead of print.

ABSTRACT

PURPOSE: A previous study by the International Berlin-Frankfurt-Münster Study Group (I-BFM-SG) on childhood KMT2A-rearranged (KMT2A-r) AML demonstrated the prognostic value of the fusion partner. This I-BFM-SG study investigated the value of flow cytometry-based measurable residual disease (flow-MRD) and evaluated the benefit of allogeneic stem-cell transplantation (allo-SCT) in first complete remission (CR1) in this disease.

METHODS: A total of 1,130 children with KMT2A-r AML, diagnosed between January 2005 and December 2016, were assigned to high-risk (n = 402; 35.6%) or non-high-risk (n = 728; 64.4%) fusion partner-based groups. Flow-MRD levels at both end of induction 1 (EOI1) and 2 (EOI2) were available for 456 patients and were considered negative (<0.1%) or positive (≥0.1%). End points were 5-year event-free survival (EFS), cumulative incidence of relapse (CIR), and overall survival (OS).

RESULTS: The high-risk group had inferior EFS (30.3% high risk v 54.0% non-high risk; P < .0001), CIR (59.7% v 35.2%; P < .0001), and OS (49.2% v 70.5%; P < .0001). EOI2 MRD negativity was associated with superior EFS (n = 413; 47.6% MRD negativity v n = 43; 16.3% MRD positivity; P < .0001) and OS (n = 413; 66.0% v n = 43; 27.9%; P < .0001), and showed a trend toward lower CIR (n = 392; 46.1% v n = 26; 65.4%; P = .016). Similar results were obtained for patients with EOI2 MRD negativity within both risk groups, except that within the non-high-risk group, CIR was comparable with that of patients with EOI2 MRD positivity. Allo-SCT in CR1 only reduced CIR (hazard ratio, 0.5 [95% CI, 0.4 to 0.8]; P = .00096) within the high-risk group but did not improve OS. In multivariable analyses, EOI2 MRD positivity and high-risk group were independently associated with inferior EFS, CIR, and OS.

CONCLUSION: EOI2 flow-MRD is an independent prognostic factor and should be included as risk stratification factor in childhood KMT2A-r AML. Treatment approaches other than allo-SCT in CR1 are needed to improve prognosis.

PMID:36996387 | DOI:10.1200/JCO.22.02120

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Randomized Phase III Study of Enzalutamide Compared With Enzalutamide Plus Abiraterone for Metastatic Castration-Resistant Prostate Cancer (Alliance A031201 Trial)

J Clin Oncol. 2023 Mar 30:JCO2202394. doi: 10.1200/JCO.22.02394. Online ahead of print.

ABSTRACT

PURPOSE: Enzalutamide and abiraterone both target androgen receptor signaling but via different mechanisms. The mechanism of action of one drug may counteract the resistance pathways of the other. We sought to determine whether the addition of abiraterone acetate and prednisone (AAP) to enzalutamide prolongs overall survival (OS) in patients with metastatic castration-resistant prostate cancer (mCRPC) in the first-line setting.

PATIENTS AND METHODS: Men with untreated mCRPC were randomly assigned (1:1) to receive first-line enzalutamide with or without AAP. The primary end point was OS. Toxicity, prostate-specific antigen declines, pharmacokinetics, and radiographic progression-free survival (rPFS) were also examined. Data were analyzed using an intent-to-treat approach. The Kaplan-Meier estimate and the stratified log-rank statistic were used to compare OS between treatments.

RESULTS: In total, 1,311 patients were randomly assigned: 657 to enzalutamide and 654 to enzalutamide plus AAP. OS was not statistically different between the two arms (median, 32.7 [95% CI, 30.5 to 35.4] months for enzalutamide v 34.2 [95% CI, 31.4 to 37.3] months for enzalutamide and AAP; hazard ratio [HR], 0.89; one-sided P = .03; boundary nominal significance level = .02). rPFS was longer in the combination arm (median rPFS, 21.3 [95% CI, 19.4 to 22.9] months for enzalutamide v 24.3 [95% CI, 22.3 to 26.7] months for enzalutamide and AAP; HR, 0.86; two-sided P = .02). However, pharmacokinetic clearance of abiraterone was 2.2- to 2.9-fold higher when administered with enzalutamide, compared with clearance values for abiraterone alone.

CONCLUSION: The addition of AAP to enzalutamide for first-line treatment of mCRPC was not associated with a statistically significant benefit in OS. Drug-drug interactions between the two agents resulting in increased abiraterone clearance may partly account for this result, although these interactions did not prevent the combination regimen from having more nonhematologic toxicity.

PMID:36996380 | DOI:10.1200/JCO.22.02394

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Assessing muscle strength of persons with transfemoral amputation with and without a prosthesis: A cross-sectional study

Prosthet Orthot Int. 2023 Mar 30. doi: 10.1097/PXR.0000000000000228. Online ahead of print.

ABSTRACT

BACKGROUND: There is a gap in the research about the influence of wearing or not wearing a prosthesis for muscle strength assessment in transfemoral amputees (TFA) and how it is associated with functional mobility.

OBJECTIVES: The aim of this study was to compare the muscle isometric strength of the residual limb with and without the prosthesis in people with TFA and to analyze associations between muscle strength and functional mobility.

STUDY DESIGN: Cross-sectional study.

METHODS: 20 subjects with TFA were included. A handheld dynamometer was used for the assessment of residual limb muscle strength. Functional mobility was assessed with the Timed Up and Go test. The Wilcoxon rank sum test with the rank biserial correlation effect size were used.

RESULTS: There were statistically significant differences when testing isometric strength of the residual limb with and without the prosthesis (flexion [p = 0.007], extension [p < 0.001], and abduction [p = 0.003]). There was association between functional mobility and flexion and abduction strength with the prosthesis (p = 0.005, p = 0.01).

CONCLUSIONS: Measurements of muscle strength of the residual limb were different when assessed with and without the prosthesis. Isometric strength of the residual limb in abduction and flexion using the prosthesis were correlated with functional mobility.

PMID:36996310 | DOI:10.1097/PXR.0000000000000228