Category: Nevin Manimala

Ophthalmol Ther. 2022 Nov 30. doi: 10.1007/s40123-022-00611-x. Online ahead of print.

ABSTRACT

INTRODUCTION: Lenadogene nolparvovec is a promising novel gene therapy for patients with Leber hereditary optic neuropathy (LHON) carrying the m.11778G>A ND4 mutation (MT-ND4). A previous pooled analysis of phase 3 studies showed an improvement in visual acuity of patients injected with lenadogene nolparvovec compared to natural history. Here, we report updated results by incorporating data from the latest phase 3 trial REFLECT in the pool, increasing the number of treated patients from 76 to 174.

METHODS: The visual acuity of 174 MT-ND4-carrying patients with LHON injected in one or both eyes with lenadogene nolparvovec from four pooled phase 3 studies (REVERSE, RESCUE and their long-term extension trial RESTORE; and REFLECT trial) was compared to the spontaneous evolution of an external control group of 208 matched patients from 11 natural history studies.

RESULTS: Treated patients showed a clinically relevant and sustained improvement in their visual acuity when compared to natural history. Mean improvement versus natural history was – 0.30 logMAR (+ 15 ETDRS letters equivalent) at last observation (P < 0.01) with a maximal follow-up of 3.9 years after injection. Most treated eyes were on-chart as compared to less than half of natural history eyes at 48 months after vision loss (89.6% versus 48.1%; P < 0.01) and at last observation (76.1% versus 44.4%; P < 0.01). When we adjusted for covariates of interest (gender, age of onset, ethnicity, and duration of follow-up), the estimated mean gain was – 0.43 logMAR (+ 21.5 ETDRS letters equivalent) versus natural history at last observation (P < 0.0001). Treatment effect was consistent across all phase 3 clinical trials. Analyses from REFLECT suggest a larger treatment effect in patients receiving bilateral injection compared to unilateral injection.

CONCLUSION: The efficacy of lenadogene nolparvovec in improving visual acuity in MT-ND4 LHON was confirmed in a large cohort of patients, compared to the spontaneous natural history decline. Bilateral injection of gene therapy may offer added benefits over unilateral injection.

TRIAL REGISTRATION NUMBERS: NCT02652780 (REVERSE); NCT02652767 (RESCUE); NCT03406104 (RESTORE); NCT03293524 (REFLECT); NCT03295071 (REALITY).

PMID:36449262 | DOI:10.1007/s40123-022-00611-x

Jpn J Radiol. 2022 Nov 30. doi: 10.1007/s11604-022-01364-0. Online ahead of print.

ABSTRACT

PURPOSE: Amyloid light chain (AL) and transthyretin (ATTR) are the major subtypes of cardiac amyloidosis (CA). ^99mTc-pyrophosphate (PYP) scintigraphy is used to differentiate ATTR from other CA subtypes. We adapted the standardized uptake value (SUV) for ^99mTc-PYP and proposed two quantitative indices, amyloid deposition volume (AmyDV) and total amyloid uptake (TAU). This study aimed to evaluate the utility of these quantitative indices in differentiating ATTR from non-ATTRs.

MATERIALS AND METHODS: Before the SUV measurement, the Becquerel calibration factor (BCF) of ^99mTc was obtained by a phantom experiment. Thirty-two patients who had undergone hybrid SPECT/CT imaging 3 h after injection of ^99mTc-PYP (370 MBq) were studied. CT attenuation correction for image reconstruction was applied in all. We calculated SUV, AmyDV, and TAU using a quantitative analysis software program for bone SPECT (GI-BONE) and analyzed AmyDV using two methods: threshold method (set 40%); and constant value method (average SUV_max of ribs). We assessed the diagnostic ability of heart-to-contralateral lung (H/CL) ratio, SUV, AmyDV, and TAU to differentiate ATTR from non-ATTR using receiver operating characteristic (ROC) analysis.

RESULTS: Statistically significant differences in all quantitative indices were observed between ATTR and non-ATTR. The area under the curve of each quantitative index for discriminating between ATTR and non-ATTR were as follows: H/CL, 0.997; SUV_max, 0.953; SUV_mean (M1), 0.964; SUV_mean (M2), 0.969; AmyDV (M1), 0.875; AmyDV (M2), 0.974; and TAU, 0.974. The AmyDV (M2) had higher diagnostic ability than AmyDV (M1). Thus, TAU was calculated as AmyDV (M2) × SUV_mean (M2). In the ROC curve, SUV, AmyDV, and TAU had almost the same diagnostic ability as H/CL in distinguishing ATTR from non-ATTRs.

CONCLUSIONS: We propose two novel 3D-based quantitative parameters (AmyDV and TAU) that have almost equal ability to discriminate ATTR from non-ATTR.

PMID:36449252 | DOI:10.1007/s11604-022-01364-0

Environ Sci Pollut Res Int. 2022 Nov 30. doi: 10.1007/s11356-022-24376-9. Online ahead of print.

ABSTRACT

Over the years, the development of marine economy has been an important component of coastal cities’ total economic growth in China. Whether the coastal cities had paid enough attention to the coordination of marine economic development and ecological environment protection in the process of marine development activities needed to be evaluated accordingly. An index evaluation system for the coordination between marine ecological environment protection and marine economic development in coastal cities of China was established in this work by using the analytic hierarchy process. The statistical analysis results from 2006 to 2018 showed that much more attention had been paid on marine ecological environment protection since the year 2012 in China. The evaluated results showed that among all coastal provinces and cities, Shanghai and Shandong Provinces had the best coordination between marine economic development and marine ecological environment protection in the year 2016. Years of data showed that marine economic development and marine ecological environmental protection complement each other and promote each other. At the same time, the analysis results of this indicator evaluation system showed that marine ecological environment protection in China should further strengthen the protection by preventing and controlling marine pollution and carrying out ecological restoration.

PMID:36449239 | DOI:10.1007/s11356-022-24376-9

J Dent Educ. 2022 Nov 30. doi: 10.1002/jdd.13146. Online ahead of print.

ABSTRACT

OBJECTIVES: Oral and maxillofacial surgeons (OMS) treat adult and pediatric patients with obstructive sleep apnea (OSA). Objective 1 assessed sleep apnea-related education, knowledge, and professional behavior of OMS residents in the United States. Objective 2 was to compare the responses of junior versus senior residents and residents in single- versus dual-degree programs.

METHODS: OMS residents in the United States received a recruitment email with a link to an anonymous online survey; 81 residents responded. The survey included 20 questions to assess respondents’ OSA-related education, knowledge, attitudes, and professional behavior.

RESULTS: Respondents generally agreed that they had received OSA-related didactic-based education (5-point scale with “5” = agree strongly: mean = 3.62) and clinical training (mean = 3.75). Clinical and classroom educational gaps were identified in relation to treatment with oral appliances and hypoglossal nerve stimulation. The residents scored on average 10.38 out of 18 (58%) possible correct answer points for the knowledge questions. Findings about pediatric OSA suggest that only 43.8% of residents understand diagnostic criteria for pediatric OSA, with only 26.6% screening pediatric patients for OSA. A case analysis showed that only 1.5% of residents correctly identified an apnea-hypopnea index of 17 as moderate sleep apnea.

CONCLUSION(S): This survey found knowledge gaps in several areas that can be improved upon. It identifies deficiency in objective knowledge about OSA among OMS residents and a specific lack of clinical training and confidence with hypoglossal nerve stimulation and management of pediatric patients with OSA. Junior and senior residents and single- and dual-degree residents showed no statistically significant differences in any category except senior residents in regard to surgical management of OSA, particularly with maxillomandibular advancement.

PMID:36449210 | DOI:10.1002/jdd.13146

Ann Surg Oncol. 2022 Nov 30. doi: 10.1245/s10434-022-12869-3. Online ahead of print.

ABSTRACT

BACKGROUND: Prior studies of older cancer patients undergoing large operations have reported similar rates of complications to the general population but higher rates of mortality, suggesting higher rates of failure-to-rescue (FTR) with advanced age. Whether age is a marker for frailty, or an independent predictor of FTR, is not clear.

METHODS: The ACS-NSQIP database was queried from 2015-19 for patients undergoing surgery for gastrointestinal (GI) malignancy. Patients were divided into age-stratified cohorts: C1 (18-55), C2 (56-65), C3 (66-75), C4 (76-89). Adjusted odds ratios (aOR) were computed to assess the relationship of the FTR rate and age, while controlling for potential confounders. A second analysis was specified with all covariates converted to Z-scores, which generated scaled adjusted odds ratios (saOR) to determine the strongest predictor of FTR.

RESULTS: Multivariable analysis suggests that age is an independent predictor of FTR: C2:C1 aOR = 1.87 (p < 0.001); C3:C1 aOR = 3.33 (p < 0.001); C4:C1 aOR = 5.71 (p < 0.001). The scaled analysis demonstrated that age is the strongest predictor of FTR (saOR = 1.92, p < 0.001); a one standard deviation increase in age was associated with a 92% increased odds of FTR. The saOR for frailty (1.18, p < 0.001) and for number of comorbidities (1.10, p = 0.005) also were statistically significant.

CONCLUSIONS: Chronologic age was independently associated with increased FTR after surgery for GI malignancy and was the strongest predictor of FTR. These results suggest that chronologic age must be carefully considered when evaluating the fitness of a patient for GI cancer surgery.

PMID:36449206 | DOI:10.1245/s10434-022-12869-3

Cancer Treat Res. 2022;184:113-127. doi: 10.1007/978-3-031-04402-1_8.

ABSTRACT

Logistic regression is a statistical tool of paramount significance in the field of epidemiology¹ and ranks as one of the most frequently published multivariable analyses for designs involving a single binary dependent variable and one or more independent variables in the fields of public health^2,3 and medical⁴ research.

PMID:36449192 | DOI:10.1007/978-3-031-04402-1_8

Drugs R D. 2022 Nov 30. doi: 10.1007/s40268-022-00408-0. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: Systemic lupus erythematosus (SLE) is an autoimmune disease, with hydroxychloroquine being the main therapeutic agent for the treatment of SLE. This research explored the effects of hydroxychloroquine combined with low-dose aspirin on maternal and infant outcomes and cytokines of pregnant women with SLE.

METHODS: Ninety pregnant women with SLE were divided into the hydroxychloroquine (HCQ) group (45 cases) and the hydroxychloroquine combined with low-dose aspirin (HCQASP) group (45 cases) by random number table. Patients in the HCQ group were treated with oral administration of hydroxychloroquine, while patients in the HCQASP group were treated with low-dose aspirin based on oral administration of hydroxychloroquine. Pregnancy outcomes, fetal outcomes, and cytokine levels were statistically analyzed.

RESULTS: The HCQASP group had a significantly higher proportion of full-term pregnancies and a significantly lower proportion of hypertension, prematurity, and pregnancy loss than the HCQ group. Neonates in the HCQASP group also had significantly higher birth weights and Apgar scores and a significantly lower proportion of neonatal asphyxia than the HCQ group. After treatment, the HCQASP group had significantly higher interleukin (IL-2) and interferon (IFN)-γ levels and significantly lower IL-4 and IL-10 levels than the HCQ group.

CONCLUSION: Hydroxychloroquine combined with low-dose aspirin can effectively improve the pregnancy outcomes of pregnant women with SLE by affecting the levels of T helper (Th) 2 and Th1 cytokines.

PMID:36449182 | DOI:10.1007/s40268-022-00408-0

Pharmacoeconomics. 2022 Nov 30. doi: 10.1007/s40273-022-01218-7. Online ahead of print.

ABSTRACT

OBJECTIVES: The aim of this study was to estimate the relationship between EQ-5D-3L and EQ-5D-5L, in both directions, using a single model.

METHODS: An online survey containing both variants of EQ-5D, with randomised ordering, was administered to a large UK sample in 2020. A joint statistical model of the ten EQ-5D responses (five at 5L, five at 3L), using a multi-equation ordinal regression framework was estimated. The joint model ensures mappings in either direction are fully consistent with the information in the sample and satisfy Bayes’ rule. Three extensions enhance model flexibility: a copula specification allows differing degrees of correlation between the 3L and 5L responses at the upper and lower extremes of health; a normal mixture residual distribution gives flexibility in the distributional form of responses; and a common factor captures correlations in responses across the five dimensions.

RESULTS: Almost 50,000 responses were received. Thirty-five percent of respondents reported an existing medical condition. Ninety percent of possible 3L and 43% of possible 5L health states were observed. The preferred model specification includes age, sex and the responses to the EQ-5D instrument. Close alignment to the observed data was observed both in within-sample and out-of-sample comparisons.

CONCLUSION: The results from this study provide a means of translating evidence to or from EQ-5D-3L to or from 5L based on a large-scale UK population survey with randomised ordering. Mapping can be performed either using descriptive system responses, individual utility scores or summary statistics.

PMID:36449173 | DOI:10.1007/s40273-022-01218-7

J Racial Ethn Health Disparities. 2022 Nov 30. doi: 10.1007/s40615-022-01477-2. Online ahead of print.

ABSTRACT

PURPOSE: This study explores whether nativity differences in health care and sociodemographic factors help to account for nativity differences in low birth weight (LBW) when comparing US-born Black women (USBW) to Black Immigrant women (BIW).

METHODS: Bivariate analyses and multinomial nested logit (MNL) models were performed using the National Survey of Family Growth (NSFG) dataset.

RESULTS: Statistically significant nativity differences between USBW and BIW were found across variables of LBW (p = .009), marital status (p < .001), education level (p < .001), receiving public assistance (p < .001), health care coverage (p < .001), age (p < .001), and poverty level income (p < .001). Results from the MNL models indicated that BIW were 91% less likely to have a LBW baby (p < .001). When accounting for other sociodemographic and health care related variables differing by nativity, although a statistically significant, narrowing gap between BIW and USBW was observed (OR = .12, p < .001), BIW were still less likely to have a LBW baby.

CONCLUSIONS: Differences between USBW and BIW across sociodemographic variables and health care related factors related to adverse pregnancy outcomes were observed in this study. Controlling for the factors attenuated nativity differences but did not eliminate the differences on LBW. Future research should continue to explore this relationship.

PMID:36449128 | DOI:10.1007/s40615-022-01477-2

Environ Geochem Health. 2022 Nov 30. doi: 10.1007/s10653-022-01441-3. Online ahead of print.

ABSTRACT

The dramatic upsurge of artisanal and small-scale gold mining (ASGM) activities in Ghana has resulted in environmental degradation, water pollution and human exposure to mercury-the main hazardous element used in gold extraction. This study evaluated the degree of human exposure to mercury based on the concentrations found in the air and soil samples taken at a resolution of 1 km² across Konongo, a historic mining town in Ghana’s Ashanti Region. The highest atmospheric mercury concentration was 193 ng/m³, which is much higher than the levels the European Union and Japan allowed, which are 10 ng/m³ and 40 ng/m³, respectively. The concentration in the soil was 3.6 mg Hg/kg, which is around ten times higher than the background concentration in nature. Additionally, the soil concentrations were higher above the worrisome levels of soil contamination in agricultural land (4 mg/kg) and industrial areas (16 mg/kg), respectively. Soils are extremely contaminated with mercury at sites artisanal mining activities take place. The concentrations of mercury in the air and soils were significantly higher (p < 0.5) at locations of prominent mining activities compared to areas not close to mining sites. The inhabitants of the Konongo community are therefore exposed to mercury, most likely emitted from artisanal mining activities. A non-carcinogenic risk is posed to the people by inhaling mercury vapour through the air and vapourisation from the soil. Children are exposed to a higher risk than adults as they receive higher daily doses of mercury than adults.

PMID:36449127 | DOI:10.1007/s10653-022-01441-3