Nevin Manimala

Nephron. 2021 Jul 5:1-7. doi: 10.1159/000516984. Online ahead of print.

ABSTRACT

Membranous nephropathy (MN) is an immune-mediated glomerular disease that can lead to nephrotic syndrome and progressive kidney function loss. The cyclic steroid-cyclophosphamide regimen (the modified Ponticelli protocol) and the monoclonal anti-CD20 antibody rituximab have been advocated as effective therapies to improve renal outcomes, but a direct comparison of these treatments had never been carried out in a prospective study. Subject of Review: Scolari et al. [J Am Soc Nephrol. 2021;32:972-82] recently reported the results of a pilot randomized controlled trial (RI-CYCLO) designed to provide direct estimates of the effect of rituximab (1 g × 2) compared to the cyclic steroid-cyclophosphamide regimen in 74 patients with MN. The proportion of patients with complete remission at 12 months was higher in the cyclic regimen arm than that of rituximab (32 and 16%, respectively), but the difference was not statistically significant in intention-to-treat analyses. Interestingly, differences in the cumulative incidence of complete and partial remissions between treatment arms progressively reduced over the follow-up and became virtually nonexistent from 24 months (>80% in both groups). The frequency of serious and nonserious adverse events was similar between the 2 treatment arms. Infusion reactions and drug discontinuation were more common with rituximab, while infections and leukopenia were more frequently observed with the cyclic regimen. The risk of cancer was similar in the 2 allocation groups, but the limited follow-up length did not allow to draw definitive conclusions. Independent of treatment allocation, 18% of patients experienced at least 1 relapse after achieving complete or partial remission. Second Opinion: Notwithstanding the intrinsic limitations of a pilot study, the RI-CYCLO trial represents an important milestone in the treatment of MN. Findings from this study support the hypothesis that the cyclic regimen and rituximab may have comparable efficacy in inducing disease remission over the long term. Considering its potentially better-albeit not yet formally proven-long-term safety profile, rituximab could be considered as a first-line therapy for most patients with MN. Several questions remain to be addressed, including rituximab ideal dose and its efficacy in patients with a significant reduction in glomerular filtration rate. In light of RI-CYCLO results, a large-scale trial to assess rituximab noninferiority to the cyclic regimen would require the enrollment of thousands of patients, and it would be probably unfeasible within a reasonable time frame. In our opinion, resources should be allocated to provide an answer to the pressing matter of treatment nonresponse and intolerance, which may be addressed in the near future with novel therapeutic strategies.

PMID:34225270 | DOI:10.1159/000516984

Phys Med Biol. 2021 Jul 5. doi: 10.1088/1361-6560/ac1157. Online ahead of print.

ABSTRACT

Healthcare professionals have been increasingly viewing medical images and videos in their routine clinical practice, and this in a wide variety of environments. Both the perception and interpretation of medical visual information, across all branches of practice or medical specialties (e.g., diagnostic, therapeutic, or surgical medicine), career stages, and practice settings (e.g., emergency care), appear to be critical for patient care. However, medical images and videos are not self-explanatory and, therefore, need to be interpreted by humans, i.e., medical experts. In addition, various types of degradations and artifacts may appear during image acquisition or processing, and consequently affect medical imaging data. Such distortions tend to impact viewers’ quality of experience, as well as their clinical practice. It is accordingly essential to better understand how medical experts perceive the quality of visual content. Thankfully, progress has been made in the recent literature towards such understanding. In this article, we present an up-to-date state of the art of relatively recent (i.e., not older than ten years old) existing studies on the subjective quality assessment of medical images and videos, as well as research works using task-based approaches. Furthermore, we discuss the merits and drawbacks of the methodologies used, and we provide recommendations about experimental designs and statistical processes to evaluate the perception of medical images and videos for future studies, which could then be used to optimise the visual experience of image readers in real clinical practice. Finally, we tackle the issue of the lack of available annotated medical image and video quality databases, which appear to be indispensable for the development of new dedicated objective metrics.

PMID:34225264 | DOI:10.1088/1361-6560/ac1157

Eur J Radiol. 2021 Jun 24;141:109827. doi: 10.1016/j.ejrad.2021.109827. Online ahead of print.

ABSTRACT

PURPOSE: In this case-control study, we evaluated different quantitative parameters derived from routine multi-detector computed tomography (MDCT) scans with respect to their ability to predict incident osteoporotic vertebral fractures of the thoracolumbar spine.

METHODS: 16 patients who received baseline and follow-up contrast-enhanced MDCT and were diagnosed with an incident osteoporotic vertebral fracture at follow-up, and 16 age-, sex-, and follow-up-time-matched controls were included in the study. Vertebrae were labelled and segmented using a fully automated pipeline. Volumetric bone mineral density (vBMD), finite element analysis (FEA)-based failure load (FL) and failure displacement (FD), as well as 24 texture features were extracted from L1 – L3 and averaged. Odds ratios (OR) with 95% confidence intervals (CI), expressed per standard deviation decrease, receiver operating characteristic (ROC) area under the curve (AUC), as well as logistic regression models, including all analyzed parameters as independent variables, were used to assess the prediction of incident vertebral fractures.

RESULTS: The texture feature Correlation (AUC = 0.754, p = 0.014; OR = 2.76, CI = 1.16-6.58) and vBMD (AUC = 0.750, p = 0.016; OR = 2.67, CI = 1.12-6.37) classified incident vertebral fractures best, while the best FEA-based parameter FL showed an AUC = 0.719 (p = 0.035). Correlation was the only significant predictor of incident fractures in the logistic regression analysis of all parameters (p = 0.022).

CONCLUSION: MDCT-derived FEA parameters and texture features, averaged from L1 – L3, showed only a moderate, but no statistically significant improvement of incident vertebral fracture prediction beyond BMD, supporting the hypothesis that vertebral-specific parameters may be superior for fracture risk assessment.

PMID:34225250 | DOI:10.1016/j.ejrad.2021.109827

Chemosphere. 2021 Jul 1;284:131400. doi: 10.1016/j.chemosphere.2021.131400. Online ahead of print.

ABSTRACT

We investigated particle size distribution and heavy metal concentrations in surface sediments of streams and lakes in the Seomjin River Basin by comparison with Sediment Quality Guidelines (SQGs). Origins were identified using statistical and geochemical approaches. Sand was prevalent in mean particle size of surface sediments (except lakes). Mean concentrations of Pb, Zn, Cd, and Hg were similar for the Seomjin and Boseong rivers, while those of Cu, As, Cr, and Ni were approximately 1.5-2.0 times higher in the Boseong. SQGs revealed no serious pollution in the basin’s site concentrations, although As and Ni levels in the Boseong had some potential for benthos toxicity. Correlation and principal component/factor analysis showed that concentrations of Cu, As, Cr, and Ni were dominant from geological origins rather than anthropogenic. The reducible fraction bound to Fe and Mn-oxides was prevalent in Pb, while the water- and acid-soluble fractions were easily exchangeable or bound to high Cd carbonates. The fraction bound to the highest lattice in residual prevailed in Zn, Cu, Cr, and Ni, accounting for 64%, 65%, 87%, and 86%, respectively. Similarly, results indicated geological origins. Risk assessment to benthos based on labile fractions (F1 + F2 + F3) were Cd (72%) < Pb (66%) < Zn (36%) ≈ Cu (35%) < Ni (14%) ≈ Cr (13%). While Cd and Pb showed the highest risk, their concentrations were relatively lower. However, Cr and Ni showed the highest concentrations but low risk levels, suggesting their pollution is unlikely to have adverse effects on benthos.

PMID:34225114 | DOI:10.1016/j.chemosphere.2021.131400

Depress Anxiety. 2021 Jul 5. doi: 10.1002/da.23191. Online ahead of print.

ABSTRACT

BACKGROUND: Patients with specific phobia (SP) show altered brain activation when confronted with phobia-specific stimuli. It is unclear whether this pathogenic activation pattern generalizes to other emotional stimuli. This study addresses this question by employing a well-powered sample while implementing an established paradigm using nonspecific aversive facial stimuli.

METHODS: N = 111 patients with SP, spider subtype, and N = 111 healthy controls (HCs) performed a supraliminal emotional face-matching paradigm contrasting aversive faces versus shapes in a 3-T magnetic resonance imaging scanner. We performed region of interest (ROI) analyses for the amygdala, the insula, and the anterior cingulate cortex using univariate as well as machine-learning-based multivariate statistics based on this data. Additionally, we investigated functional connectivity by means of psychophysiological interaction (PPI).

RESULTS: Although the presentation of emotional faces showed significant activation in all three ROIs across both groups, no group differences emerged in all ROIs. Across both groups and in the HC > SP contrast, PPI analyses showed significant task-related connectivity of brain areas typically linked to higher-order emotion processing with the amygdala. The machine learning approach based on whole-brain activity patterns could significantly differentiate the groups with 73% balanced accuracy.

CONCLUSIONS: Patients suffering from SP are characterized by differences in the connectivity of the amygdala and areas typically linked to emotional processing in response to aversive facial stimuli (inferior parietal cortex, fusiform gyrus, middle cingulate, postcentral cortex, and insula). This might implicate a subtle difference in the processing of nonspecific emotional stimuli and warrants more research furthering our understanding of neurofunctional alteration in patients with SP.

PMID:34224655 | DOI:10.1002/da.23191

Clin Respir J. 2021 Jul 5. doi: 10.1111/crj.13417. Online ahead of print.

ABSTRACT

BACKGROUND: Co-existence of bronchiectasis with Chronic Obstructive Pulmonary Disease (COPD) may lead to the worsening of the functional parameters in exacerbations and may negatively affect the outcomes.

METHODS: This study is a retrospective cross-sectional study that aims to investigate the relationships between bronchiectasis with COPD exacerbation and all-cause of mortality. We retrospectively enrolled 122 cases hospitalized for COPD exacerbation from 2010 to 2016. Patients who underwent thoracic tomography in the previous year of the index exacerbation were included in the study. Patients who admitted to the intensive care unit, patients with infected bronchiectasis and, with conditions that mimic COPD exacerbation were excluded from the study. Demographic, clinical, and laboratory findings, comorbidities and the number of exacerbations in the previous year, the presence of bronchiectasis were recorded using hospital electronic registry. The radiological evaluation of bronchiectasis was made by the modified Reiff score (MRS).

RESULTS: Bronchiectasis was found in 66 (54%) of 122 patients included in the study. The mean age was 67.5±10.3 in the whole group, 108 (88.5%) of the patients were male and 14 (11.5%) were female. When patients were stratified according to the presence of bronchiectasis, no statistically significant difference was found in terms of comorbidity scores, respiratory functions, exacerbation parameters, laboratory values and all cause of mortality between the groups (p>0.05). There was no statistical relation between the presence of bronchiectasis and long-term survival (log-rank test p=0.83).

CONCLUSIONS: This study shows that patients with bronchiectasis did not cause a poor outcome in patients with COPD exacerbation.

PMID:34224649 | DOI:10.1111/crj.13417

Clin Respir J. 2021 Jul 5. doi: 10.1111/crj.13418. Online ahead of print.

ABSTRACT

INTRODUCTION: Asthma is prevalent among children and adolescents. Few studies have assessed the knowledge and perceptions of asthma among adolescents.

OBJECTIVES: This study assessed the knowledge and perception about asthma among secondary school students in an all-girls school in Nigeria.

METHODS: This cross-sectional study was conducted in a Nigerian secondary school in Enugu State (February 2020). In Senior Secondary School (SS1, SS2, SS3), students could be in one of three specialized classes: Sciences, Humanities, Business. A self-administered structured questionnaire was filled by conveniently sampled students in SS1 and SS2. Inferential statistics utilized the Pearson’s Chi-Square test and multiple linear regression with statistical significance set as P < 0.05.

RESULTS: Three hundred and eighty-eight (388) students participated in the study (mean age = 14.64 ± 0.93 years). Majority of the students were in Science class (n = 299; 77.1%). There was high awareness about asthma (n = 384; 99.0%). More than half of them had good asthma knowledge (n = 279; 71.9%); close to three-fifths had favourable perception of asthma (n = 222; 57.2%). More students in SS2 had good knowledge of asthma compared to those in SS1 (76.7% Vs. 67.2%; ꭓ² = 4.338; P = 0.037). More students in Science class had favourable perceptions about asthma compared to those in Humanities and Business class (60.5% Vs. 48.1% Vs. 25.0%; ꭓ² = 7.458; P = 0.024).

CONCLUSION: Majority of the students were aware about asthma and had good knowledge of the disease while close to three-fifths had favourable perceptions about asthma.

PMID:34224648 | DOI:10.1111/crj.13418

Genet Epidemiol. 2021 Jul 5. doi: 10.1002/gepi.22422. Online ahead of print.

ABSTRACT

The X-chromosome is often excluded from genome-wide association studies because of analytical challenges. Some of the problems, such as the random, skewed, or no X-inactivation model uncertainty, have been investigated. Other considerations have received little to no attention, such as the value in considering nonadditive and gene-sex interaction effects, and the inferential consequence of choosing different baseline alleles (i.e., the reference vs. the alternative allele). Here we propose a unified and flexible regression-based association test for X-chromosomal variants. We provide theoretical justifications for its robustness in the presence of various model uncertainties, as well as for its improved power when compared with the existing approaches under certain scenarios. For completeness, we also revisit the autosomes and show that the proposed framework leads to a more robust approach than the standard method. Finally, we provide supporting evidence by revisiting several published association studies. Supporting Information for this article are available online.

PMID:34224641 | DOI:10.1002/gepi.22422

Neurourol Urodyn. 2021 Jul 5. doi: 10.1002/nau.24740. Online ahead of print.

ABSTRACT

AIM: To compare the efficacy of the treatment with transcutaneous perineal electrostimulation versus intracavitary electrostimulation to reduce the frequency of urinary incontinence after radical prostatectomy and the impact on the quality of life (QoL).

METHODS: This single-blind equivalence-randomized controlled trial equally (1:1) randomly allocated men with urinary incontinence post radical prostatectomy into surface electrodes perineal group (intervention group, IG) and intra-anal probe group (control group, CG). Outcomes included changes in the 24h-Pad Test (main variable), and ICIQ-SF (International Consultation on Incontinence Questionnaire Short-Form), SF-12 (Short Form Health Survey), and I-QOL (incontinence quality of life questionnaire) questionnaires. Clinical data were collected at baseline, 6 and 10 weeks. For the comparisons between variables, χ² test and Student’s t test were used. Equivalence was analyzed by estimating the mean change (90% confidence interval) of urinary incontinence based on the Pad Test. The analysis was performed for the per-protocol and the intention-to-treat populations. Statistical significance level was set at p < 0.05.

RESULTS: Seventy patients were included, mean age 62.8 (SD 9.4) years. Mean baseline 24h-Pad Test was 328.3 g (SD 426.1) and a significant decrease (p < 0.001) in the grams of urine loss at 5 weeks (159.1 g in the IG and 121.7 g in the CG), and at 10 weeks of treatment (248.5 g in the IG and 235.8 g in the CG) was observed. However, the final difference in the grams of urine loss between both treatments showed the absence of statistical significance (p = 0.874). In both groups, the ICIQ-SF, I-QOL, and SF-12 questionnaires revealed a significant improvement in QoL.

CONCLUSION: Surface and intra-anal electrostimulation treatments reduced significantly losses of urine, but differences in grams of urine loss throughout the therapy between groups were not significant, suggesting that the efficacy of the two treatments is not statistically different. Nonetheless, the improvement observed in both groups was statistically significant and clinically relevant.

PMID:34224598 | DOI:10.1002/nau.24740

Am J Hematol. 2021 Jul 5. doi: 10.1002/ajh.26286. Online ahead of print.

ABSTRACT

Several controlled studies have evidenced good efficacy and short- and mid-term safety profiles for hydroxyurea (HU), which has become the cornerstone for prevention of sickle-cell disease (SCD)-related vaso-occlusive crises. However, there are few large-scale reports on its long-term use and certain caregivers and patients have concerns about its safety. Following the licensing of HU in Europe for children and adults with severe forms of SCD, ESCORT-HU was designed as a Phase IV observational cohort study. It included 1,906 participants, of whom 55% were adults. The most common hemoglobin (Hb) genotypes were HbSS (84.7%) and HbSβ+ (7.0%). The median duration of follow-up was 45 months, for a total of 7,309 patient-years of observation. The dose of HU after one year was 20.6 mg/kg/d for children and 16.3 mg/kg/d for adults. There was a statistically significant decrease in the number of vaso-occlusive episodes lasting > 48 hours, acute chest syndrome episodes, hospitalizations, and the percentage of patients requiring blood transfusions within the first 12 months relative to the year before enrolment. Neutropenia and thrombocytopenia were the most commonly reported adverse effects. No new HU toxicity was identified. Overall, 125 pregnancies were reported in 101 women and no malformations were observed in the neonates. There were 12 pregnancies for partners of male patients treated with HU. One case of fatal myelodysplastic syndrome was reported, for which a causal association with HU could not be excluded. This cohort study of patients with SCD highlights the positive benefit-to-risk ratio of HU in children and adults. This article is protected by copyright. All rights reserved.

PMID:34224583 | DOI:10.1002/ajh.26286