Nevin Manimala

Clin Biomech (Bristol, Avon). 2021 Apr 27;85:105364. doi: 10.1016/j.clinbiomech.2021.105364. Online ahead of print.

ABSTRACT

BACKGROUND: Pes planovalgus is common in children with cerebral palsy. Although severity influences treatment, there still lacks standard clinical measurements to objectively quantify pes planovalgus in this population. The comparison of pedobarographic data and radiographic measurements to clinical evaluation has not been reported in this population.

METHODS: 395 feet were identified from a population of ambulatory pediatric patients with cerebral palsy. Each patient initially underwent clinical evaluation by an experienced physical therapist who classified feet as: 136 controls, 116 mild, 100 moderate, and 43 severe pes planovalgus. Quantitative measurements were then calculated from antero-posterior and lateral radiographs of the foot. Pedobarographic analysis included the arch index, center of pressure index, and a newly defined medial index.

FINDINGS: A multivariate analysis was performed on the radiographic and pedobarographic measurements collected. It identified seven variables that improved objective classification of pes planovalgus severity when utilized together. These include the foot progression angle, initial contact force, arch index, medial index, antero-posterior talonavicular coverage, lateral calcaneal pitch and lateral Meary’s angle. While the lateral calcaneal pitch angle statistically differed amongst all severity classes, no pedobarographic value statistically differed between all severity classes.

INTERPRETATION: Overall, the combination of radiographic and pedobarographic measurements provides valuable information for objectively classifying severity of pes planovalgus in children with cerebral palsy by utilizing these values together rather than independently. In a clinical setting, radiographs and pedobarographic data may be obtained to enhance assessment of severity and guide treatment.

PMID:33940478 | DOI:10.1016/j.clinbiomech.2021.105364

Eur J Obstet Gynecol Reprod Biol. 2021 Apr 24;261:144-147. doi: 10.1016/j.ejogrb.2021.04.031. Online ahead of print.

ABSTRACT

Randomized controlled trials (RCTs) are a cornerstone for the assessment of the effectiveness of interventions. Appropriate randomization, design, sample size, statistical analyses, and conduct that reduces the risk of bias, enhance the chance they will deliver true research findings. The credibility of RCTs is difficult to assess without objective evidence of compliance with Good Clinical Practice standards. Remarkably, no mechanisms are in place both in the initial peer review process and during meta-analysis to assess these, and little guidance on how to assess data where research integrity cannot be confirmed (e.g. where data originated from a setting without established infrastructure or an era preceding current standards). We describe the case of the use of antenatal steroids. When these drugs are used in early preterm birth, their benefits outweigh the harms. However, later in pregnancy, and specifically at term, this balance is less clear. We describe that the four randomised clinical trials that inform clinical practice through the Cochrane meta-analysis, for various reasons, lack clear governance which makes it difficult to verify provenance and reliability of the data. We conclude that transparency and assessment of data credibility need to be inbuilt both at the time of publication and at the time of meta-analysis. This will drive up standards and encourage appropriate interpretation of results and the context from which they were derived.

PMID:33940424 | DOI:10.1016/j.ejogrb.2021.04.031

Sci Total Environ. 2021 Apr 26;785:147324. doi: 10.1016/j.scitotenv.2021.147324. Online ahead of print.

ABSTRACT

Despite the growing interest in energy-efficient homes (EEHs), there is still a lack of evidence regarding whether the mechanical ventilation system of an EEH positively or negatively impacts indoor air quality (IAQ) and the health and wellbeing of occupants. This study aimed to evaluate the IAQ level and daily health symptoms of adults and children living in EEHs compared to conventional buildings over the course of one year. A two-way mixed analysis of variance was conducted to compare the level of IAQ between the two housing types. A binomial generalized linear mixed model (GLMM) and generalized additive mixed model was developed to investigate the association between IAQ and daily risks of symptoms. Differences in the daily prevalence of symptoms between the two housing types were assessed using a Poisson GLMM model. Overall, the indoor concentrations of particulate matter (PM₁₀ and PM_2.5), carbon dioxide (CO₂), and volatile organic compounds (VOCs) were lower in EEH after controlling for seasonality. The indoor temperature and relative humidity level were relatively constant in the EEH. We also found that an increased level of indoor air quality parameters, particularly CO_2, which is closely related to the indoor ventilation rate, was associated with the daily risk of eye fatigue, allergic rhinitis, and atopic dermatitis symptoms. Considering that EEH effectively reduced indoor air pollutants and IAQ improvement was associated with a reduction in the risk of individual symptoms, the IAQ improvement of EEH may have positively impacted occupants’ health. Symptoms such as eye fatigue and skin dryness, which have been reported in previous studies as potential side effects of mechanical ventilation, were reported in this study; however, they were not found to be statistically significantly different from those reported in the conventional building.

PMID:33940416 | DOI:10.1016/j.scitotenv.2021.147324

Sci Total Environ. 2021 Apr 16;785:147134. doi: 10.1016/j.scitotenv.2021.147134. Online ahead of print.

ABSTRACT

To evaluate the evolution of river water quality in a changing environment, measuring the objective water quality is critical for understanding the rules of river water pollution. Based on the sample entropy theory and a nonlinear statistical method, this study aims to identify the spatiotemporal dynamics of water quality and its complexity in the Yangtze River basin using time series data, to separate the contributions of human activity and climate change to water quality, and to establish a data-driven risk assessment framework for the spatial (potential risk) and temporal (direct risk) aspects of water pollution. The results demonstrate that the spatiotemporal dynamics of water quality and sample entropy in each monitoring section are closely related to the characteristics of the corresponding location. The water quality of the main stream is superior, and its complexity is less than that of the tributaries. Cascade reservoir operation and vegetation status, agricultural production, and rainfall patterns exert great influences in the upper, middle, and lower reaches, respectively. Dam construction, urban agglomeration development, and interactions between river and lake are also influencing factors. An attributional analysis found that climate change and human activities negatively contributed to the evolution of NH₃-N concentration in most of the monitored sections, and the average relative contribution rates of human activities to changes in water quality in the main and tributary streams were -55.46% and -48.49%, respectively. In addition, the construction of data-driven risk assessment framework can efficiently and accurately assess the potential and direct water pollution risks of rivers.

PMID:33940408 | DOI:10.1016/j.scitotenv.2021.147134

Environ Int. 2021 Apr 30;155:106603. doi: 10.1016/j.envint.2021.106603. Online ahead of print.

ABSTRACT

Filtering respiratory protection devices (FRPD) are mandatory for workers to wear in the Portuguese waste-sorting industry. Previous results regarding microbial contamination found on FRPD interior layer raised the question of whether microbial contamination from the exhalation valve would also have cytotoxicity effects. Since the FRPD exhalation valves are very close to workers’ nose and mouth, they represent a source of exposure to bioburden by inhalation. This study aimed to evaluate the cytotoxicity of the microbial contamination present in the FRPD exhalation valves. For this purpose, the cytotoxicity effects were determined through the MTT assay in two different cell lines (human A549 epithelial lung cells, and swine kidney cells) and compared with previous results obtained with FRPD interior layers. The contamination present in the FRPD exhalation valves presented some cytotoxicity on epithelial lung cells, suggesting the inhalation route as a potential route of exposure through the use of FRPD in the waste-sorting industry. Half-maximal (50%) inhibitory concentration (IC50) values were lower for FRPD interior layer than exhalation valves in lung cells, with overall cytotoxicity lower in exhalation valves when compared to interior layer (z = -4.455, p = 0.000). Higher bacterial counts in TSA were correlated with lower IC50 values, thus, higher cytotoxicity effect in lung cells. No statistically significant differences were detected among different workplaces.

PMID:33940392 | DOI:10.1016/j.envint.2021.106603

Mar Pollut Bull. 2021 Apr 30;168:112428. doi: 10.1016/j.marpolbul.2021.112428. Online ahead of print.

ABSTRACT

Plastic production and pollution of the environment with plastic items is rising rapidly and outpacing current mitigation measures. Success of mitigation actions can only be determined if progress can be measured reliably through incorporation of specific, measurable targets. Here we evaluate temporal changes in the amount and composition of plastic in boluses from Flesh-footed Shearwaters during 2002-2020 and assess their suitability for measuring progress against national and international commitments to reduce plastic pollution. Plastic in the shearwater boluses showed a generally decreasing pattern from 2002 to 2015 and increasing again to 2020. The colour and type of plastics in boluses was comparable to items recovered from live and necropsied birds, but a much smaller sample size (~35 boluses/year) was required to detect changes in plastic number and mass over time. We therefore suggest shearwater boluses are a low-effort, high-statistical power monitoring tool for quantifying progress against environmental policies in Australia.

PMID:33940375 | DOI:10.1016/j.marpolbul.2021.112428

J Environ Manage. 2021 Apr 30;291:112656. doi: 10.1016/j.jenvman.2021.112656. Online ahead of print.

ABSTRACT

Ecotourism in national parks of developing countries is increasingly recognised as a promising option to achieve sustainable development goals, regardless, might imply various paradoxical managerial challenges. This paper, therefore, seeks to contribute a methodological framework utilising ES-based social landscape metrics (SLM) to address the potential barriers in managing ecotourism-integrated multi-functional national parks. We present a mixed-method case study in Vietnam’s Tram Chim National Park (TCNP), conducted via semi-structural interviews and PGIS with tourists and locals. Multiple key informants, i.e. TCNP’s authorities were also interviewed to provide their managerial insights and assist in verifying the PGIS results obtained from the tourists and locals. Via the quantified and mapped SLMs, the study reveals the differences between tourists and locals in terms of how and where they perceive and appreciate the intangible values of TCNP. Through spatial statistics, we reported important spatial correlations (i) between different categories of Ecosystem Services (ES) and (ii) between ES richness and diversity on different TCNP’s land covers. As a contribution to the decision-making outlook, we remarked potential areas to expand of ecotourism activities based on the spatial hot and cold spots. This study concludes by highlighting opportunities for future research in expanding on socio-geographical assessments of ES, especially in the fields of ecotourism.

PMID:33940358 | DOI:10.1016/j.jenvman.2021.112656

ESMO Open. 2021 Apr 30;6(3):100145. doi: 10.1016/j.esmoop.2021.100145. Online ahead of print.

ABSTRACT

On 21 January 2021, the European Commission amended the marketing authorisation granted for pembrolizumab to include the first-line treatment of microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) metastatic colorectal cancer (mCRC) in adults. The recommended dose of pembrolizumab was either 200 mg every 3 weeks or 400 mg every 6 weeks by intravenous infusion. Pembrolizumab was evaluated in a phase III, open-label, multicentre, randomised trial versus standard of care (SOC: FOLFOX6/FOLFIRI alone or in combination with bevacizumab/cetuximab) as first-line treatment of locally confirmed mismatch repair-deficient or microsatellite instability-high stage IV CRC. Subjects randomised to the SOC arm had the option to crossover and receive pembrolizumab once disease progressed. Both progression-free survival (PFS) and overall survival were primary endpoints. Pembrolizumab showed a statistically significant improvement in PFS compared with SOC, with a hazard ratio of 0.60 [95% confidence interval (CI): 0.45-0.80], P = 0.0002. Median PFS was 16.5 (95% CI: 5.4-32.4) versus 8.2 (95% CI: 6.1-10.2) months for the pembrolizumab versus SOC arms, respectively. The most frequent adverse events in patients receiving pembrolizumab were diarrhoea, fatigue, pruritus, nausea, increased aspartate aminotransferase, rash, arthralgia, and hypothyroidism. Having reviewed the data submitted, the European Medicines Agency’s (EMA’s) Committee for Medicinal Products for Human Use (CHMP) considered that the benefit-risk balance was positive. This is the first time the CHMP has issued an opinion for a target population defined by DNA repair deficiency biomarkers. The aim of this manuscript is to summarise the scientific review of the application leading to regulatory approval in the European Union.

PMID:33940347 | DOI:10.1016/j.esmoop.2021.100145

ESMO Open. 2021 Apr 30;6(3):100124. doi: 10.1016/j.esmoop.2021.100124. Online ahead of print.

ABSTRACT

BACKGROUND: The role of tumor mutational burden (TMB) is still debated for selecting advanced non-oncogene addicted non-small-cell lung cancer (NSCLC) patients who might benefit from immune checkpoint inhibitors (ICIs). Of note, TMB failed to predict a benefit in overall survival (OS) among such patients.

MATERIALS AND METHODS: The purpose of this meta-analysis was to compare efficacy outcomes among first-line immune-oncology (IO) agents versus standard platinum-based chemotherapy (CT) within two subgroups (TMB-low and TMB-high on either tissue or blood). We collected hazard ratios (HRs) to evaluate the association for progression-free survival (PFS) and OS, with the relative 95% confidence intervals (CIs). Risk ratios (RRs) were used as an association measure for objective response rate (ORR).

RESULTS: Eight different cohorts of five randomized controlled phase III studies (3848 patients) were analyzed. In TMB-high patients, IO agents were associated with improved ORR (RRs 1.37, 95% CI 1.13-1.66), PFS (HR 0.69, 95% CI 0.61-0.79) and OS (HR 0.67, 95% CI 0.59-0.77) when compared with CT, thus suggesting a possible predictive role of high TMB for IO regimens. In TMB-low patients, the IO strategy did not lead to any significant benefit in survival and activity, whereas the pooled results of both ORR and PFS were intriguingly associated with a statistical significance in favor of CT.

CONCLUSIONS: This meta-analysis resulted in a proven benefit in OS in favor of IO agents in the TMB-high population. Although more prospective data are warranted, we postulated the hypothesis that monitoring TMB, in addition to the existing programmed death-ligand 1 (PD-L1) expression level, could represent the preferable option for future clinical research in the first-line management of advanced non-oncogene addicted NSCLC patients.

PMID:33940346 | DOI:10.1016/j.esmoop.2021.100124

Arch Endocrinol Metab. 2021 Apr 29:2359-3997000000367. doi: 10.20945/2359-3997000000367. Online ahead of print.

ABSTRACT

OBJECTIVE: To determine sonographic features of malignancy in partially cystic thyroid nodules and assess the diagnostic efficacy of these features for differentiating between benign and malignant lesions in the nodules with indeterminate cytology.

METHODS: From January 2016 to December 2017, a total of 91 patients with 94 partially cystic thyroid nodules who had undergone ultrasound-guided fine-needle aspiration biopsy and thyroid surgery in our hospital were included in this study. The sonographic features of the thyroid nodules were analyzed to identify the predictive features of malignancy and assess the diagnostic efficacy of these features.

RESULTS: The features of hypoechogenicity, microcalcification, composition, and an eccentric solid component with an acute angle had statistically significant associations with malignant nodule (p<005) by univariable analysis. Binary logistic regression analysis showed that microcalcification and hypoechogenicity were significantly associated with malignancy. Using the combination of microcalcification, hypoechogenicity, and a solid component comprising of greater than or equal to 50% of the total volume, the diagnostic sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were 97.6%, 32.7%, 53.9%, and 94.4%, respectively. In these nodules with indeterminate cytology, this combination also exhibited a high sensitivity of 92.3% and an NPV of 83.3%.

CONCLUSION: This study demonstrated that microcalcification and hypoechogenicity were independently associated with malignancy in partially cystic thyroid nodules. The combination of microcalcification, hypoechogenicity, and a solid portion that is greater than or equal to 50% of the total volume will help guide clinical decisions in mixed cystic solid nodules.

PMID:33939910 | DOI:10.20945/2359-3997000000367