Tag: statistics

Drug Saf. 2024 Jun 29. doi: 10.1007/s40264-024-01456-y. Online ahead of print.

ABSTRACT

BACKGROUND: Seasonal influenza is prevented through annual vaccination, especially in children and older adults. These vaccines are annually updated based on World Health Organization recommendations and require continuous safety monitoring.

OBJECTIVE: We assessed the frequency and severity of adverse events within 7 days of administering GSK’s inactivated quadrivalent seasonal influenza vaccine (IIV4) in Belgium, Germany, and Spain during the 2022/2023 influenza season.

METHODS: In this enhanced safety surveillance study, adults who received GSK’s IIV4 and parents/guardians/legally acceptable representatives of vaccinated children (aged 6 months-17 years) were invited to complete adverse drug reaction cards reporting adverse events within 7 days post-vaccination.

RESULTS: In total, 1332 participants (53.6% female) received at least one dose of GSK’s IIV4, including 43 children who received two doses. Overall, 97.8% of adverse drug reaction cards were completed and returned in the study. All participants in Belgium were adults, while 54.7% and 7.4% in Spain and Germany, respectively, were pediatric participants aged 6 months-17 years. After Dose 1, across all age groups, 49.8% of participants reported at least one adverse event. The most common adverse events (cumulative frequency >5%) following Dose 1 were injection-site pain (37.6%), fatigue (15.0%), headache (13.2%), injection-site swelling (9.3%), myalgia (7.6%), and injection-site erythema (7.4%). Across all countries, adverse events were most common in adults aged 18-65 years (59.7%), followed by those aged 3-17 years (47.0%), >65 years (35.7%), and 6-35 months (23.5%). After Dose 2, 18.6% of participants reported at least one adverse event, with general disorders and administration site conditions again being the most frequent.

CONCLUSIONS: Across all age and risk groups for serious disease, no serious adverse events related to GSK’s IIV4 were reported within 7 days post-vaccination. This study supports and confirms the acceptable safety profile of GSK’s IIV4 across all recommended age groups.

CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov number: not applicable.

PMID:38949714 | DOI:10.1007/s40264-024-01456-y

Methods Mol Biol. 2024;2833:65-77. doi: 10.1007/978-1-0716-3981-8_8.

ABSTRACT

Pyrazinamide (PZA) is a key component of chemotherapy for the treatment of drug-susceptible tuberculosis (TB) and is likely to continue to be included in new drug combinations. Potentiation of PZA could be used to reduce the emergence of resistance, shorten treatment times, and lead to a reduction in the quantity of PZA consumed by patients, thereby reducing the toxic effects. Acidified medium is required for the activity of PZA against Mycobacterium tuberculosis. In vitro assessments of pyrazinamide activity are often avoided because of the lack of standardization, which has led to a lack of effective in vitro tools for assessing and/or enhancing PZA activity.We have developed and optimized a novel, robust, and reproducible, microtiter plate assay, that centers around acidity levels that are low enough for PZA activity. The assay can be applied to the evaluation of novel compounds for the identification of potentiators that enhance PZA activity. In this assay, potentiation of PZA is demonstrated to be statistically significant with the addition of rifampicin (RIF), which can, therefore, be used as a positive control. Conversely, norfloxacin demonstrates no potentiating activity with PZA and can be used as a negative control. The method, and the associated considerations, described here, can be adapted in the search for potentiators of other antimicrobials.

PMID:38949702 | DOI:10.1007/978-1-0716-3981-8_8

Environ Monit Assess. 2024 Jun 29;196(7):677. doi: 10.1007/s10661-024-12833-6.

ABSTRACT

We assessed the hydrochemistry of 15 watersheds in the Halton Region, southern Ontario, in high resolution (n > 500 samples across n > 40 streams) to characterize water quality dynamics and governing controls on major and trace element concentrations in this rapidly urbanizing region. In 2022, major water quality parameters were generally in line with historic monitoring data yet significantly different across catchments, e.g., in specific conductance, turbidity, phosphate and chloride, and trace element concentrations. Distinct hydrochemical signatures were observed between urban and rural creeks, with urban stream sections and sites near the river mouths close to Lake Ontario having consistently higher chloride (up to 700 mg/L) and occasional enrichment in nutrients levels (up to 8 and 20 mg/L phosphate and nitrate, respectively). Particularly upper reaches exhibited hydrochemical signatures that were reflective of the catchment surface lithologies, for instance through higher dissolved Ca to Mg ratios. Unlike for chloride and phosphate, provincial water quality guidelines for trace elements and heavy metals were seldom surpassed (on < 10 occasions for copper, zinc, cadmium, and uranium). Concentrations of other trace elements (e.g., platinum group elements or rare earth elements) were expectedly low (< 0.3 µg/L) but showed spatiotemporal concentration patterns and concentration-discharge dynamics different from those of the major water quality parameters. Our results help improve the understanding of surface water conditions within Halton’s regional Natural Heritage Systems and demonstrate how enhanced environmental monitoring can deliver actionable information for watershed decision-making.

PMID:38949676 | DOI:10.1007/s10661-024-12833-6

J Youth Adolesc. 2024 Jun 29. doi: 10.1007/s10964-024-02039-x. Online ahead of print.

ABSTRACT

Schools in the United States are increasingly offering ethnic studies classes, which focus on exploring students’ ethnic-racial identities (ERI) and critical analysis of systemic racism, to their diverse student bodies, yet scant research exists on their effectiveness for students of different ethnic-racial backgrounds in multiracial classrooms. A policy change to require all high school students in one school district to take an ethnic studies class facilitated a natural experiment for comparing the effects of quasi-random assignment to an ethnic studies class (treatment) relative to a traditional social studies class (control; e.g., U.S. Government, Human Geography). Student surveys and school administrative data were used to compare students’ ERI development, well-being, and academic outcomes across ethnic studies and control classes. Participants (N = 535 9th graders; 66.1% ethnic studies) had diverse ethnic-racial (33.5% non-Latine White, 29.5% Black, 21.1% Latine, 10.7% biracial, 2.8% Asian, 2.2% Native American) and gender identities (44.7% female, 7.1% non-binary). Ethnic studies students reported marginally higher ERI exploration and resolution than controls, and sensitivity analyses showed a statistically significant effect on ERI among participants with complete midpoint surveys. Higher resolution was associated with better psychological well-being for all students and higher attendance for White students. Students with low middle school grades (GPA < 2.0) had better high school grades in core subjects when enrolled in ethnic studies than the control class. Overall, the results of this natural experiment provide preliminary support for ethnic studies classes as a method for promoting ERI development, well-being, attendance, and academic achievement for students from diverse ethnic-racial backgrounds.

PMID:38949674 | DOI:10.1007/s10964-024-02039-x

Glob Health Action. 2024 Dec 31;17(1):2371184. doi: 10.1080/16549716.2024.2371184. Epub 2024 Jul 1.

ABSTRACT

BACKGROUND: The COVID-19 pandemic prompted varied policy responses globally, with Latin America facing unique challenges. A detailed examination of these policies’ impacts on health systems is crucial, particularly in Bolivia, where information about policy implementation and outcomes is limited.

OBJECTIVE: To describe the COVID-19 testing trends and evaluate the effects of quarantine measures on these trends in Cochabamba, Bolivia.

METHODS: Utilizing COVID-19 testing data from the Cochabamba Department Health Service for the 2020-2022 period. Stratified testing rates in the health system sectors were first estimated followed by an interrupted time series analysis using a quasi-Poisson regression model for assessing the quarantine effects on the mitigation of cases during surge periods.

RESULTS: The public sector reported the larger percentage of tests (65%), followed by the private sector (23%) with almost double as many tests as the public-social security sector (11%). In the time series analysis, a correlation between the implementation of quarantine policies and a decrease in the slope of positive rates of COVID-19 cases was observed compared to periods without or with reduced quarantine policies.

CONCLUSION: This research underscores the local health system disparities and the effectiveness of stringent quarantine measures in curbing COVID-19 transmission in the Cochabamba region. The findings stress the importance of the measures’ intensity and duration, providing valuable lessons for Bolivia and beyond. As the global community learns from the pandemic, these insights are critical for shaping resilient and effective health policy responses.

PMID:38949664 | DOI:10.1080/16549716.2024.2371184

J Nerv Ment Dis. 2024 Jul 1;212(7):398-402. doi: 10.1097/NMD.0000000000001778.

ABSTRACT

The DSM-III symptomatic criteria for major depression (MD) were derived from those proposed by Feighner and colleagues in 1972, which closely resembled those published by Cassidy in 1957. I here present a counter-factual history in which Feighner carefully read a key reference in Cassidy, a large 1953 follow-up study by Campbell of depressed patients with detailed tables of depressive signs and symptoms. In this alternative timeline, the Feighner criteria for MD were modified by Campbell’s results, which then changed DSM-III and subsequent MD criteria sets. The historical pathway to the current DSM MD criteria was contingent on a range of historical events and could easily have been different. This story is not meant to criticize DSM MD criteria that perform well. Rather, it suggests that these criteria represent a useful but fallible set of symptoms/signs that index but do not constitute MD and therefore are not to be reified.

PMID:38949660 | DOI:10.1097/NMD.0000000000001778

J Nerv Ment Dis. 2024 Jul 1;212(7):392-397. doi: 10.1097/NMD.0000000000001777.

ABSTRACT

The study was set out to establish the potential for psychotherapy to effect improvements in patients with narcissistic personality disorder (NPD). Eight patients with NPD who improved in treatment were identified. Consensus clinician/investigator diagnostic scores from before and after the psychotherapies were retroactively established on the Diagnostic Interview for Narcissism (DIN) and the Diagnostic Statistic Manual for Psychiatric Disorders, 5th Edition (DSM-5) Personality Disorder Section II criteria. Psychosocial functioning (work or school, romantic relationships) before and after the psychotherapies was retroactively evaluated as well. At the completion of the therapies after 2.5 to 5 years, all patients had improved, no longer met DIN or DSM-5 criteria for NPD, and showed better psychosocial functioning. Symptomatic improvements were associated with large effect sizes. In conclusion, changes in NPD can occur in treatment after 2.5 to 5 years. Future research should identify patient characteristics, interventions, and common processes in such improved cases that could help with development of treatments.

PMID:38949659 | DOI:10.1097/NMD.0000000000001777

bioRxiv [Preprint]. 2024 Jun 18:2024.06.17.599426. doi: 10.1101/2024.06.17.599426.

ABSTRACT

Decades of neuroscience research has shown that macroscale brain dynamics can be reliably decomposed into a subset of large-scale functional networks, but the specific spatial topographies of these networks and the names used to describe them can vary across studies. Such discordance has hampered interpretation and convergence of research findings across the field. To address this problem, we have developed the Network Correspondence Toolbox (NCT) to permit researchers to examine and report spatial correspondence between their novel neuroimaging results and sixteen widely used functional brain atlases, consistent with recommended reporting standards developed by the Organization for Human Brain Mapping. The atlases included in the toolbox show some topographical convergence for specific networks, such as those labeled as default or visual. Network naming varies across atlases, particularly for networks spanning frontoparietal association cortices. For this reason, quantitative comparison with multiple atlases is recommended to benchmark novel neuroimaging findings. We provide several exemplar demonstrations using the Human Connectome Project task fMRI results and UK Biobank independent component analysis maps to illustrate how researchers can use the NCT to report their own findings through quantitative evaluation against multiple published atlases. The NCT provides a convenient means for computing Dice coefficients with spin test permutations to determine the magnitude and statistical significance of correspondence among user-defined maps and existing atlas labels. The NCT also includes functionality to incorporate additional atlases in the future. The adoption of the NCT will make it easier for network neuroscience researchers to report their findings in a standardized manner, thus aiding reproducibility and facilitating comparisons between studies to produce interdisciplinary insights.

PMID:38948881 | PMC:PMC11212927 | DOI:10.1101/2024.06.17.599426

bioRxiv [Preprint]. 2024 Jun 22:2024.06.18.599636. doi: 10.1101/2024.06.18.599636.

ABSTRACT

Functional connectivity (FC) is the degree of synchrony of time series between distinct, spatially separated brain regions. While traditional FC analysis assumes the temporal stationarity throughout a brain scan, there is growing recognition that connectivity can change over time and is not stationary, leading to the concept of dynamic FC (dFC). Resting-state functional magnetic resonance imaging (fMRI) can assess dFC using the sliding window method with the correlation analysis of fMRI signals. Accurate statistical inference of sliding window correlation must consider the autocorrelated nature of the time series. Currently, the dynamic consideration is mainly confined to the point estimation of sliding window correlations. Using in vivo resting-state fMRI data, we first demonstrate the non-stationarity in both the cross-correlation function (XCF) and the autocorrelation function (ACF). Then, we propose the variance estimation of the sliding window correlation considering the nonstationary of XCF and ACF. This approach provides a means to dynamically estimate confidence intervals in assessing dynamic connectivity. Using simulations, we compare the performance of the proposed method with other methods, showing the impact of dynamic ACF and XCF on connectivity inference. Accurate variance estimation can help in addressing the critical issue of false positivity and negativity.

PMID:38948863 | PMC:PMC11212997 | DOI:10.1101/2024.06.18.599636

bioRxiv [Preprint]. 2024 Jun 18:2024.06.18.599103. doi: 10.1101/2024.06.18.599103.

ABSTRACT

The role of dynamics in enzymatic function is a highly debated topic. Dihydrofolate reductase (DHFR), due to its universality and the depth with which it has been studied, is a model system in this debate. Myriad previous works have identified networks of residues in positions near to and remote from the active site that are involved in dynamics and others that are important for catalysis. For example, specific mutations on the Met20 loop in E. coli DHFR (N23PP/S148A) are known to disrupt millisecond-timescale motions and reduce catalytic activity. However, how and if networks of dynamically coupled residues influence the evolution of DHFR is still an unanswered question. In this study, we first identify, by statistical coupling analysis and molecular dynamic simulations, a network of coevolving residues, which possess increased correlated motions. We then go on to show that allosteric communication in this network is selectively knocked down in N23PP/S148A mutant E. coli DHFR. Finally, we identify two sites in the human DHFR sector which may accommodate the Met20 loop double proline mutation while preserving dynamics. These findings strongly implicate protein dynamics as a driving force for evolution.

PMID:38948820 | PMC:PMC11213021 | DOI:10.1101/2024.06.18.599103