Category: Nevin Manimala

BMJ Open. 2023 Apr 24;13(4):e071350. doi: 10.1136/bmjopen-2022-071350.

ABSTRACT

INTRODUCTION: Multidrug chemoimmunotherapy with rituximab, high-dose methotrexate, procarbazine and vincristine (R-MPV) is a standard therapy for younger patients with primary central nervous system lymphoma (PCNSL); however, prospective data regarding its use in elderly patients are lacking. This multi-institutional, non-randomised, phase II trial will assess the efficacy and safety of R-MPV and high-dose cytarabine (HD-AraC) for geriatric patients with newly diagnosed PCNSL.

METHODS AND ANALYSIS: Forty-five elderly patients will be included. If R-MPV does not achieve complete response, the patients will undergo reduced-dose, whole-brain radiotherapy comprising 23.4 Gy/13 fractions, followed by local boost radiotherapy comprising 21.6 Gy/12 fractions. After achieving complete response using R-MPV with or without radiotherapy, the patients will undergo two courses of HD-AraC. All patients will undergo baseline geriatric 8 (G8) assessment before HD-AraC and after three, five and seven R-MPV courses. Patients with screening scores of ≥14 points that decrease to <14 points during subsequent treatment, or those with screening scores <14 points that decrease from the baseline during subsequent treatment are considered unfit for R-MPV/HD-AraC. The primary endpoint is overall survival, and the secondary endpoints are progression-free survival, treatment failure-free survival and frequency of adverse events. The results will guide a later phase III trial and provide information about the utility of a geriatric assessment for defining chemotherapy ineligibility.

ETHICS AND DISSEMINATION: This study complies with the latest Declaration of Helsinki. Written informed consent will be obtained. All participants can quit the study without penalty or impact on treatment. The protocol for the study, statistical analysis plan and informed consent form have been approved by the Certified Review Board at Hiroshima University (CRB6180006) (approval number: CRB2018-0011). The study is ongoing within nine tertiary and two secondary hospitals in Japan. The findings of this trial will be disseminated through national and international presentations and peer-reviewed publications.

TRIAL REGISTRATION: jRCTs061180093.

PMID:37094899 | DOI:10.1136/bmjopen-2022-071350

BMJ Open. 2023 Apr 24;13(4):e069850. doi: 10.1136/bmjopen-2022-069850.

ABSTRACT

OBJECTIVES: Personality differences between doctors and patients can affect treatment outcomes. We examine these trait disparities, as well as differences across medical specialities.

DESIGN: Retrospective, observational statistical analysis of secondary data.

SETTING: Data from two data sets that are nationally representative of doctors and the general population in Australia.

PARTICIPANTS: We include 23 358 individuals from a representative survey of the general Australian population (with subgroups of 18 705 patients, 1261 highly educated individuals and 5814 working in caring professions) as well as 19 351 doctors from a representative survey of doctors in Australia (with subgroups of 5844 general practitioners, 1776 person-oriented specialists and 3245 technique-oriented specialists).

MAIN OUTCOME MEASURES: Big Five personality traits and locus of control. Measures are standardised by gender, age and being born overseas and weighted to be representative of their population.

RESULTS: Doctors are significantly more agreeable (a: standardised score -0.12, 95% CIs -0.18 to -0.06), conscientious (c: -0.27 to -0.33 to -0.20), extroverted (e: 0.11, 0.04 to 0.17) and neurotic (n: 0.14, CI 0.08 to 0.20) than the general population (a: -0.38 to -0.42 to -0.34, c: -0.96 to -1.00 to -0.91, e: -0.22 to -0.26 to -0.19, n: -1.01 to -1.03 to -0.98) or patients (a: -0.77 to -0.85 to -0.69, c: -1.27 to -1.36 to -1.19, e: -0.24 to -0.31 to -0.18, n: -0.71 to -0.76 to -0.66). Patients (-0.03 to -0.10 to 0.05) are more open than doctors (-0.30 to -0.36 to -0.23). Doctors have a significantly more external locus of control (0.06, 0.00 to 0.13) than the general population (-0.10 to -0.13 to -0.06) but do not differ from patients (-0.04 to -0.11 to 0.03). There are minor differences in personality traits among doctors with different specialities.

CONCLUSIONS: Several personality traits differ between doctors, the population and patients. Awareness about differences can improve doctor-patient communication and allow patients to understand and comply with treatment recommendations.

PMID:37094898 | DOI:10.1136/bmjopen-2022-069850

BMJ Open. 2023 Apr 24;13(4):e064159. doi: 10.1136/bmjopen-2022-064159.

ABSTRACT

OBJECTIVES: Evaluate the experiences and perceptions of patients participating in a simulated clinical trial and identify ways to enhance future patient-centric trial designs.

DESIGN: International, multicentre, non-interventional, virtual clinical trial visits with patient debriefs and advisory boards.

SETTING: Virtual clinic visits and accompanying advisory boards.

PARTICIPANTS: Nine patients with palmoplantar pustulosis for simulated trial visits; 14 patients and patient representatives for advisory boards.

MAIN OUTCOME MEASURES: Qualitative responses to trial documentation, visit schedule and logistics, and trial design were collected during patient debriefs. Results were discussed at two virtual advisory board meetings.

RESULTS: Patients identified key barriers to participation and potential difficulties encountered when attending trial visits and completing assessments. They also proposed recommendations to overcome these challenges. Patients recognised the need for comprehensive informed consent forms, but recommended use of non-technical language, brevity and additional support to aid understanding. Other trial documentations should be relevant to the disease and include known efficacy and safety of the study drug. Patients were concerned about receiving placebo, stopping existing medications and being unable to receive the study drug after trial completion; therefore, patients and physicians recommended an open-label extension following trial completion. Trial visits were too numerous (n=20) and too long (3-4 hours each); patients recommended improvements to the design to make best use of their time and reduce unnecessary waiting. They also requested financial and logistical support. Patients expressed a desire for study outcomes that matter to them, related to their ability to undertake normal daily activities and not be a burden to others.

CONCLUSIONS: Simulated trials are an innovative method for assessing trial design and acceptance from a patient-centric perspective, enabling specific improvements to be made prior to trial initiation. Incorporation of recommendations from simulated trials could enhance trial recruitment and retention, and optimise trial outcomes and data quality.

PMID:37094891 | DOI:10.1136/bmjopen-2022-064159

BMJ Open. 2023 Apr 24;13(4):e069226. doi: 10.1136/bmjopen-2022-069226.

ABSTRACT

OBJECTIVE: To examine the prevalence and predictors of self-reported sexually transmitted infections (SR-STIs) among adolescent girls and young women in Mali.

DESIGN: We performed a cross-sectional analysis of data from the Demographic and Health Survey of Mali, which was conducted in 2018. A weighted sample of 2105 adolescent girls and young women aged 15-24 was included. Percentages were used to summarise the results of the prevalence of SR-STIs. We used a multilevel binary logistic regression analysis to examine the predictors of SR-STIs. The results were presented using an adjusted odds ratio (aOR) with 95% confidence interval (CI). Statistical significance was set at p<0.05.

SETTING: Mali.

PARTICIPANTS: Adolescent girls (15-19 years) and young women (20-24 years).

OUTCOME MEASURE: SR-STIs.

RESULTS: The prevalence of SR-STIs among the adolescent girls and young women was 14.1% (95% CI=12.3 to 16.2). Adolescent girls and young women who had ever tested for HIV, those with one parity, those with multiparity, those with two or more sexual partners, those residing in urban areas, and those exposed to mass media were more likely to self-report STIs. However, those residing in Sikasso and Kidal regions were less likely to report STIs.

CONCLUSION: Our study has shown that SR-STIs are prevalent among adolescent girls and young women in Mali. Health authorities in Mali and other stakeholders should formulate and implement policies and programmes that increase health education among adolescent girls and young women and encourage free and easy access to STI prevention and treatment services.

PMID:37094889 | DOI:10.1136/bmjopen-2022-069226

Eur J Hosp Pharm. 2023 Apr 24:ejhpharm-2022-003594. doi: 10.1136/ejhpharm-2022-003594. Online ahead of print.

ABSTRACT

OBJECTIVES: Interleukin-17 (IL-17) contributes to the pathogenesis of psoriasis. Secukinumab, ixekizumab, and brodalumab are monoclonal antibodies anti-IL-17 antibodies, approved for the treatment of moderate/severe plaque psoriasis.The aim of the study was to describe the effectiveness and safety of anti-IL-17 agents in moderate/severe plaque psoriasis in clinical practice. We also analysed anti-IL-17 therapies’ survival, dose adjustment, and clinical patients’ factors associated with their effectiveness and safety.

METHODS: A retrospective, longitudinal study was conducted at a tertiary hospital. We included patients with moderate/severe psoriasis treated with anti-IL-17 agents. The effectiveness was evaluated with Psoriasis Area and Severity Index (PASI) score and safety through the adverse drug reactions (ADRs) collected.

RESULTS: 38 patients were studied (median age=47.4 years, 71.0% male). The mean number of biological therapies that patients received was 2.6, and anti-IL-17 therapy was the first biological therapy for 36.8% of patients. The median years in treatment were 2.5 (95% CI 1.95 to 2.98) for secukinumab, 1.2 (95% CI 0.36 to 1.47) for ixekizumab, and 0.7 (IQR 0.71) for brodalumab. The median PASI score after 6 months of treatment was 0 (IQR 0) and 85.3% of patients achieved a PASI of 90 (84.0% with secukinumab, 87.5% with ixekizumab, and 100% with brodalumab). Dose adjustment was associated with the line of treatment (p=0.034 for naïve patients), age (p=0.044 for younger patients), and concomitant pathologies (p=0.015 without more diseases).24 patients suffered from ADRs, mainly infections of the upper respiratory tract, and there were no statistically significant differences between the three therapies.

CONCLUSIONS: Anti-IL-17 agents constitute an effective treatment for patients with moderate/severe plaque psoriasis and for longer. Dose reductions were associated with fewer lines of treatment, younger patients and absence of concomitant pathologies. ADR were minor and similar among the anti-IL-17.

PMID:37094886 | DOI:10.1136/ejhpharm-2022-003594

J Med Entomol. 2023 Apr 24:tjad032. doi: 10.1093/jme/tjad032. Online ahead of print.

ABSTRACT

Triatoma costalimai and Triatoma jatai are related species, which occur in sympatry in Paranã, Tocantins, Brazil, in rocky outcrops and in peridomicile and intradomicile environments. This study compared morphologic and morphometric aspects of the eggs of these species using optical microscopy (OM) and scanning electron microscopy (SEM). Operculum cells (OP) and egg body (EB) were drawn and photographed, their surfaces were measured, and spots were quantified. Statistical analyses were performed using ANOVA and t-tests. OM showed an egg exochorium with spots in T. costalimai and a predominance of short lines in T. jatai. We found significant differences in egg length and width, which were larger in T. costalimai. SEM analysis showed that the operculum of both species had cells with straight and/or rounded rims, with a smooth aspect, random spots, and predominantly pentagonal shape. In the EB, hexagonal cells were predominant, with indices exceeding 60% in both species. Triatoma costalimai cells were flat, with a discrete definition of the rims, whereas T. jatai cells were smooth with well-defined rims. Statistical tests showed significant differences for EB, where T. costalimai cells were larger and have more spots than T. jatai. The eggs can thus be differentiated, thereby contributing to integrative taxonomy.

PMID:37094884 | DOI:10.1093/jme/tjad032

BMJ. 2023 Apr 24;381:e073725. doi: 10.1136/bmj-2022-073725.

NO ABSTRACT

PMID:37094878 | DOI:10.1136/bmj-2022-073725

Proc Natl Acad Sci U S A. 2023 May 2;120(18):e2217090120. doi: 10.1073/pnas.2217090120. Epub 2023 Apr 24.

ABSTRACT

We present the first observations of seismic waves propagating through the core of Mars. These observations, made using seismic data collected by the InSight geophysical mission, have allowed us to construct the first seismically constrained models for the elastic properties of Mars’ core. We observe core-transiting seismic phase SKS from two farside seismic events detected on Mars and measure the travel times of SKS relative to mantle traversing body waves. SKS travels through the core as a compressional wave, providing information about bulk modulus and density. We perform probabilistic inversions using the core-sensitive relative travel times together with gross geophysical data and travel times from other, more proximal, seismic events to seek the equation of state parameters that best describe the liquid iron-alloy core. Our inversions provide constraints on the velocities in Mars’ core and are used to develop the first seismically based estimates of its composition. We show that models informed by our SKS data favor a somewhat smaller (median core radius = 1,780 to 1,810 km) and denser (core density = 6.2 to 6.3 g/cm³) core compared to previous estimates, with a P-wave velocity of 4.9 to 5.0 km/s at the core-mantle boundary, with the composition and structure of the mantle as a dominant source of uncertainty. We infer from our models that Mars’ core contains a median of 20 to 22 wt% light alloying elements when we consider sulfur, oxygen, carbon, and hydrogen. These data can be used to inform models of planetary accretion, composition, and evolution.

PMID:37094138 | DOI:10.1073/pnas.2217090120

Proc Natl Acad Sci U S A. 2023 May 2;120(18):e2216507120. doi: 10.1073/pnas.2216507120. Epub 2023 Apr 24.

ABSTRACT

The number of noisy images required for molecular reconstruction in single-particle cryoelectron microscopy (cryo-EM) is governed by the autocorrelations of the observed, randomly oriented, noisy projection images. In this work, we consider the effect of imposing sparsity priors on the molecule. We use techniques from signal processing, optimization, and applied algebraic geometry to obtain theoretical and computational contributions for this challenging nonlinear inverse problem with sparsity constraints. We prove that molecular structures modeled as sums of Gaussians are uniquely determined by the second-order autocorrelation of their projection images, implying that the sample complexity is proportional to the square of the variance of the noise. This theory improves upon the nonsparse case, where the third-order autocorrelation is required for uniformly oriented particle images and the sample complexity scales with the cube of the noise variance. Furthermore, we build a computational framework to reconstruct molecular structures which are sparse in the wavelet basis. This method combines the sparse representation for the molecule with projection-based techniques used for phase retrieval in X-ray crystallography.

PMID:37094135 | DOI:10.1073/pnas.2216507120

Proc Natl Acad Sci U S A. 2023 May 2;120(18):e2303890120. doi: 10.1073/pnas.2303890120. Epub 2023 Apr 24.

NO ABSTRACT

PMID:37094115 | DOI:10.1073/pnas.2303890120