Category: Nevin Manimala

BMC Rheumatol. 2022 Oct 22;6(1):83. doi: 10.1186/s41927-022-00311-w.

ABSTRACT

BACKGROUND: Rheuma Tolerance for Cure (RTCure) is a five-year international collaboration between academia, industry and patients/members of the public. It focuses on developing approaches to predict the onset of rheumatoid arthritis (RA) and designing clinical trials to reduce the risk of disease development through immune-tolerising and other treatments. We conducted a mid-term evaluation of patient and public involvement (PPI) within the project.

METHODS: Two surveys on PPI were co-designed by the PPI Coordinator, Patient/Public Research Partners (PRPs) and a researcher. Both anonymous, electronic surveys were distributed to 61 researchers and 9 PRPs. Quantitative survey data were analysed using descriptive statistics and free text responses underwent inductive thematic analysis.

RESULTS: Researcher and Patient response rates were 33% and 78%, respectively. Quantitative Researcher Survey data highlighted that (i) responding researchers represented all seven Work Packages (WPs), (ii) 40% thought PRPs had made a large or extremely large contribution to their own WPs, (iii) 55% thought PPI has had a moderate or large impact on RTCure, (iv) 75% worked with PRPs in RTCure, and (v) 60% said PRPs had affected their research thinking. Quantitative PRP Survey data highlighted that (i) PRPs were most involved in four WPs, (ii) 43% thought they had made a minor contribution to their main WP, (iii) 57% thought PPI has had a small impact on RTCure, and (iv) 57% thought they received too little feedback on the outcome of their contribution to different tasks. Four main themes were identified in both surveys: ‘PRP contributions’, ‘Experiences of PPI’, ‘Impact of PPI on RTCure’, and ‘How PPI can be improved’. Two additional themes from the Researcher Survey were ‘Impact of PPI on researchers’ and ‘Influence on Future Projects’, and from the PRP Survey were ‘Impact of PPI on PRPs’ and ‘Engagement with PRPs’.

CONCLUSION: PPI seemed to have a significant impact on RTCure, however, PRPs were less aware. A focus on improving communication between PRPs and researchers (facilitated by the PPI Coordinator), and providing PPI training for researchers is likely to improve involvement. Complex legal agreements for PRPs should be avoided and careful attention paid to appropriate PRP compensation.

PMID:36273206 | DOI:10.1186/s41927-022-00311-w

Nat Commun. 2022 Oct 22;13(1):6302. doi: 10.1038/s41467-022-33580-7.

ABSTRACT

Viewing faces that are perceived as emotionally expressive evokes enhanced neural responses in multiple brain regions, a phenomenon thought to depend critically on the amygdala. This emotion-related modulation is evident even in primary visual cortex (V1), providing a potential neural substrate by which emotionally salient stimuli can affect perception. How does emotional valence information, computed in the amygdala, reach V1? Here we use high-resolution functional MRI to investigate the layer profile and retinotopic distribution of neural activity specific to emotional facial expressions. Across three experiments, human participants viewed centrally presented face stimuli varying in emotional expression and performed a gender judgment task. We found that facial valence sensitivity was evident only in superficial cortical layers and was not restricted to the retinotopic location of the stimuli, consistent with diffuse feedback-like projections from the amygdala. Together, our results provide a feedback mechanism by which the amygdala directly modulates activity at the earliest stage of visual processing.

PMID:36273204 | DOI:10.1038/s41467-022-33580-7

J Pharm Policy Pract. 2022 Oct 22;15(1):69. doi: 10.1186/s40545-022-00464-6.

ABSTRACT

BACKGROUND: Competitive tenders on pharmaceuticals are one of the most effective cost-containment instruments in healthcare systems. Its effectiveness has been demonstrated, among other things, in markets for generic medicine and biosimilars. In Denmark, an internationally unique model for competitive tenders on analogue substitutable pharmaceuticals has been developed and implemented for all public hospitals.

METHODS: We obtained data on all analogue competitive tenders carried out by the Danish Medicines Council from its foundation on January 1, 2017, to October 9, 2020. We calculated univariate descriptive statistics, pairwise correlations and made a multiple regression analysis on tender savings.

RESULTS: Average annual saving on hospital pharmaceutical purchase prices was 44.1% ranging from 0.4% to 92.8% between therapeutic areas and areas of indication. There was a significant positive correlation between tender savings and the number of competitors participating in the tender, and a significant negative correlation between tender savings and the number of days since market authorization.

CONCLUSIONS: This study finds analogue tenders to be similar in effect and mechanism to competitive tenders in markets for generic medicine and biosimilars. It supports the increasing number of empirical findings that competitive tendering has a high potential to generate substantial savings on healthcare budgets.

PMID:36273196 | DOI:10.1186/s40545-022-00464-6

Trials. 2022 Oct 22;23(1):886. doi: 10.1186/s13063-022-06800-0.

ABSTRACT

BACKGROUND: Aboriginal Australians are known to suffer high levels of acquired brain injury (stroke and traumatic brain injury) yet experience significant barriers in accessing rehabilitation services. The aim of the Healing Right Way trial is to evaluate a culturally secure intervention for Aboriginal people with newly acquired brain injury to improve their rehabilitation experience and quality of life. Following publication of the trial protocol, this paper outlines the statistical analysis plan prior to locking the database. METHODS: The trial involves a stepped wedge design with four steps over 3 years. Participants were 108 adult Aboriginal Australians admitted to one of eight hospitals (four rural, four urban) in Western Australia within 6 weeks of onset of a new stroke or traumatic brain injury who consented to follow-up for 26 weeks. All hospital sites started in a control phase, with the intervention assigned to pairs of sites (one metropolitan, one rural) every 26 weeks until all sites received the intervention. The two-component intervention involves training in culturally safe care for hospital sites and enhanced support provided to participants by Aboriginal Brain Injury Coordinators during their hospital stay and after discharge. The primary outcome is quality of life as measured by the Euro QOL-5D-3L VAS. A mixed effects linear regression model will be used to assess the between-group difference at 26 weeks post-injury. The model will control for injury type and severity, age at recruitment and time since commencement of the trial, as fixed effects. Recruitment site and participant will be included as random effects. Secondary outcomes include measurements of function, independence, anxiety and depression, carer strain, allied health occasions of service received and hospital compliance with minimum processes of care based on clinical guidelines and best practice models of care.

DISCUSSION: The trial will provide the first data surrounding the effectiveness of an intervention package for Aboriginal people with brain injury and inform future planning of rehabilitation services for this population. The statistical analysis plan outlines the analyses to be undertaken.

TRIAL REGISTRATION: Australia New Zealand Clinical Trials Registry ACTRN12618000139279. Registered 30 January, 2018.

PMID:36273182 | DOI:10.1186/s13063-022-06800-0

Trials. 2022 Oct 22;23(1):889. doi: 10.1186/s13063-022-06796-7.

ABSTRACT

BACKGROUND: Randomised clinical trials with a factorial design may assess the effects of multiple interventions in the same population. Factorial trials are carried out under the assumption that the trial interventions have no interactions on outcomes. Here, we present a protocol for a simulation study investigating the consequences of different levels of interactions between the trial interventions on outcomes for the future 2×2×2 factorial designed randomised clinical Sedation, TEmperature, and Pressure after Cardiac Arrest and REsuscitation (STEPCARE) trial in comatose patients after out-of-hospital cardiac arrest.

METHODS: By simulating a multisite trial with 50 sites and 3278 participants, and a presumed six-month all-cause mortality of 60% in the control population, we will investigate the validity of the trial results with different levels of interaction effects on the outcome. The primary simulation outcome of the study is the risks of type-1 and type-2 errors in the simulated scenarios, i.e. at what level of interaction is the desired alpha and beta level exceeded. When keeping the overall risk of type-1 errors ≤ 5% and the risk of type-2 errors ≤ 10%, we will quantify the maximum interaction effect we can accept if the planned sample size is increased by 5% to take into account possible interaction between the trial interventions. Secondly, we will assess how interaction effects influence the minimal detectable difference we may confirm or reject to take into account 5% (small interaction effect), 10% (moderate), or 15% (large) positive interactions in simulations with no ‘true’ intervention effect (type-1 errors) and small (5%), moderate (10%), or large negative interactions (15%) in simulations with ‘true’ intervention effects (type-2 errors). Moreover, we will investigate how much the sample size must be increased to account for a small, moderate, or large interaction effects.

DISCUSSION: This protocol for a simulation study will inform the design of a 2×2×2 factorial randomised clinical trial of how potential interactions between the assessed interventions might affect conclusions. Protocolising this simulation study is important to ensure valid and unbiased results.

TRIAL REGISTRATION: Not relevant.

PMID:36273179 | DOI:10.1186/s13063-022-06796-7

J Ultrasound. 2022 Oct 22. doi: 10.1007/s40477-022-00735-7. Online ahead of print.

ABSTRACT

AIM: We aimed to evaluate the effectiveness of combining 2-dimensional shear wave elastography (2D-SWE) with ultrasonography (US) in diagnosing acute appendicitis in patients with suspected acute appendicitis.

METHODS: Clinical and laboratory findings, gray-scale US and 2D-SWE imaging features, operation information, and pathology results of 48 patients diagnosed with acute appendicitis who presented with right lower quadrant pain were prospectively evaluated. We compared the findings to the US and SWE imaging features of 79 asymptomatic patients.

RESULTS: Mean Alvarado score and appendix diameter were statistically significantly higher for acute appendicitis (p < 0.001). In patients with acute appendicitis, mesenteric lymphadenopathy and fat stranding were also more frequent (p < 0.001). The mean velocity and kPa values for appendix and mesenteric fat were statistically significantly higher in acute appendicitis (p < 0.001).

CONCLUSION: In the diagnosis of acute appendicitis, 2D-SWE increases the diagnostic performance of gray-scale US in the differentiation of inflamed and normal appendixes.

PMID:36273062 | DOI:10.1007/s40477-022-00735-7

Sci Rep. 2022 Oct 22;12(1):17791. doi: 10.1038/s41598-022-22723-x.

ABSTRACT

Xylanases are hydrolytic enzymes with a wide range of applications in several industries such as biofuels, paper and pulp, food, and feed. The objective of this study was to optimize the culture conditions and medium components for maximal xylanase production from a newly isolated Trichoderma harzianum strain using the Plackett-Burman Design (PBD) and Box Behnken Design (BBD) experimental strategies. Xylanase production was enhanced 4.16-fold to 153.80 U/ml by BBD compared to a preliminary one-factor-at-a-time (OFAT) activity of 37.01 U/ml and 2.24-fold compared to the PBD (68.70 U/ml). The optimal conditions for xylanase production were: 6 days of fermentation, incubation temperature of 70 °C, pH 5.0, agitation of 160 rpm, and 1.2% wheat bran and ammonium sulphate. The experimental design effectively provided conditions for the production of an acidic-thermostable enzyme with exciting potential for application in animal feed improvement. The acidic-thermostable xylanase was purified from the submerged culture and SDS-PAGE analysis revealed a molecular weight of 72 kDa. This protein had maximum xylanolytic activity at pH 6.0 and 65 °C and was stable for 4 h retaining > 70% activity and exhibited substrate specificity for beechwood xylan with a K_m of 5.56 mg/ml and V_max of 1052.63 µmol/min/mg. Enzyme activity was enhanced by Fe²⁺, Mg²⁺, and Zn²⁺. There was an absence of strong inhibitors of xylanase activity. Overall, these characteristics indicate the potential for at least two industrial applications.

PMID:36273028 | DOI:10.1038/s41598-022-22723-x

Sci Rep. 2022 Oct 22;12(1):17777. doi: 10.1038/s41598-022-22635-w.

ABSTRACT

The trajectory of the body centre of mass (BCoM) during locomotion differs through speeds, gaits and pathological states; statistical methods are needed to compare it among different conditions. Here, ten participants walked on treadmill at 1.1 and 1.4 m/s; BCoM trajectories were obtained through stereophotogrammetry and expressed as Fourier series. Trajectories were compared among speeds using (i) zero-dimensional (0D) linear and circular tests for difference on amplitudes and phases of Fourier series harmonic, (ii) one-dimensional statistical parametric mapping (1D-SPM) t-tests on the anteroposterior, mediolateral and vertical axial components of the BCoM trajectory and (iii) 1D-SPM Hotelling’s T² test on the three-dimensional BCoM trajectory. Increasing speed increased the amplitude and decreased the phase of the fundamental (2nd) vertical harmonic. Coherently, the BCoM vertical trajectory featured greater displacement and a forward-shift, combined with greater displacement along the anteroposterior axis. Hotelling’s T² 1D-SPM on the whole trajectory featured supra-threshold clusters at the transition between double and single support, and mid of the single support. 0D and 1D test yielded coherent and complementary results: 1D-SPM Hotelling’s T² is suitable to compare whole three-dimensional BCoM trajectories; however, when researchers hypothesize that conditions may impact specific harmonics or axial components, 0D or 1D-SPM t-tests are recommended.

PMID:36273024 | DOI:10.1038/s41598-022-22635-w

Sci Rep. 2022 Oct 22;12(1):17798. doi: 10.1038/s41598-022-22900-y.

ABSTRACT

Geometries of the 3-methyl-1-phenyl-4-(phenyldiazenyl)-1H-pyrazol-5-amine azo-dye compound and its tautomer were optimized using B3LYP and M06-2X functionals in coupling with TZVP and 6-311 + G(d,p) basis sets. The ¹H- and ¹³C-NMR chemical shifts of all species were predicted using 13 density functional theory (DFT) approaches in coupling with TZVP and 6-311 + G(d,p) basis sets at the different optimized geometries by applying the using GIAO method using the eight geometries. The selected functionals are characterized by having different amount of Hartree-Fock exchange. The selected DFT methods were B3LYP, M06-2X, BP86, B97XD, TPSSTPSS, PBE1PBE, CAM-B3LYP, wB97XD, LSDA, HSEH1PBE, PW91PW91, LC-WPBE, and B3PW91. The results obtained were compared with the available experimental data using different statistical descriptors such as root mean square error (RMSE) and maximum absolute error (MAE). Results revealed that the prediction of the ¹H-NMR chemical shifts has more significant dependence on the applied geometry than that of the prediction of the ¹³C-NMR chemical shifts. Among all the examined functionals, B97D and TPSSTPSS functionals were found to be the most accurate ones, while the M06-2X functional is the least accurate one. Results also revealed that the prediction of NMR chemical shifts using TZVP basis sets results is more accurate results than 6-311 + G(2d,p) basis set.

PMID:36273019 | DOI:10.1038/s41598-022-22900-y

Sci Rep. 2022 Oct 22;12(1):17742. doi: 10.1038/s41598-022-20058-1.

ABSTRACT

Anthropometric markers are the most important aspect of a child’s health assessment. Using large-scale nationally representative data from the National Family Health Survey (NFHS-4), 2015-2016, this study aimed to investigate the relationship between children born to women with high-risk fertility behaviours and children’s health outcomes. The sample consisted of 2,55,726 children of currently married women aged 15-49 years in India. The key explanatory variable, high-risk fertility behaviour was defined by women’s age at birth (below 18 or above 34 years), birth interval (less than 24 months), and higher birth orders (four and above). The key outcome variables for assessing child health outcomes were stunting, wasting, and underweight in children aged 0-59 months. We used descriptive statistics, Pearson’s chi-square test and logistic regression models to analyse the objectives. Approximately 33% of children were born with any single high-risk condition in the last 5 years in India. The bivariate analysis showed that all three components of child health, stunting, wasting, and underweight, were higher among children born to women with high-risk fertility behaviour. The findings from the multivariable analysis suggest that children born with a high risk fertility behaviour were suffering from stunting (AOR = 1.30; 95% CI 1.27-1.33) and underweight (AOR = 1.23; 95% CI 1.20-1.27). In addition, children born to women of multiple high-risk categories had higher odds of stunting (AOR = 1.53; 95% CI 1.46-1.59) and underweight (AOR = 1.38; 95% CI 1.32-1.44) as compared to children born to women with no risk. Our findings highlight an urgent need for effective legislation to prevent child marriage that would be helpful in increasing the maternal age at birth. The government should also focus on the interventions in health education and improvement of reproductive healthcare to promote optimal birth spacing.

PMID:36273013 | DOI:10.1038/s41598-022-20058-1