Category: Statistics

Science. 2024 Jun 21;384(6702):eadf1329. doi: 10.1126/science.adf1329. Epub 2024 Jun 21.

ABSTRACT

Persistent inflammation driven by cytokines such as type-one interferon (IFN-I) can cause immunosuppression. We show that administration of the Janus kinase 1 (JAK1) inhibitor itacitinib after anti-PD-1 (programmed cell death protein 1) immunotherapy improves immune function and antitumor responses in mice and results in high response rates (67%) in a phase 2 clinical trial for metastatic non-small cell lung cancer. Patients who failed to respond to initial anti-PD-1 immunotherapy but responded after addition of itacitinib had multiple features of poor immune function to anti-PD-1 alone that improved after JAK inhibition. Itacitinib promoted CD8 T cell plasticity and therapeutic responses of exhausted and effector memory-like T cell clonotypes. Patients with persistent inflammation refractory to itacitinib showed progressive CD8 T cell terminal differentiation and progressive disease. Thus, JAK inhibition may improve the efficacy of anti-PD-1 immunotherapy by pivoting T cell differentiation dynamics.

PMID:38900877 | DOI:10.1126/science.adf1329

J Bone Joint Surg Am. 2024 Jun 20. doi: 10.2106/JBJS.24.00368. Online ahead of print.

ABSTRACT

Today, well-designed randomized clinical trials (RCTs) are considered the pinnacle of clinical research, and they inform many practices in orthopaedics. When designing these studies, researchers conduct a power analysis, which allows researchers to strike a balance between (1) enrolling enough patients to detect a clinically important treatment effect (i.e., researchers can be confident that the effect is unlikely due to chance) and (2) cost, time, and risk to patients, which come with enrolling an excessive number of patients. Because researchers will have a desire to conduct resource-efficient RCTs and protect patients from harm, many studies report a p value that is close to the threshold for significance. The concept of the fragility index (FI) was introduced as a simple way to interpret RCT findings, but it does not account for RCT design. The adoption of the FI conflicts with researchers’ goals of designing efficient RCTs that conserve resources and limit ineffective or harmful treatments to patients. The use of the FI may reflect many clinicians’ lack of familiarity with interpreting p values beyond “significant” or “nonsignificant.” Instead of inventing new metrics to convey the same information provided by the p value, greater emphasis should be placed on educating clinicians on how to interpret p values and, more broadly, statistics, when reading scientific studies.

PMID:38900863 | DOI:10.2106/JBJS.24.00368

Health Informatics J. 2024 Apr-Jun;30(2):14604582241260607. doi: 10.1177/14604582241260607.

ABSTRACT

Background: Wearables have the potential to transform healthcare by enabling early detection and monitoring of chronic diseases. This study aimed to assess wearables’ acceptance, usage, and reasons for non-use. Methods: Anonymous questionnaires were used to collect data in Germany on wearable ownership, usage behaviour, acceptance of health monitoring, and willingness to share data. Results: Out of 643 respondents, 550 participants provided wearable acceptance data. The average age was 36.6 years, with 51.3% female and 39.6% residing in rural areas. Overall, 33.8% reported wearing a wearable, primarily smartwatches or fitness wristbands. Men (63.3%) and women (57.8%) expressed willingness to wear a sensor for health monitoring, and 61.5% were open to sharing data with healthcare providers. Concerns included data security, privacy, and perceived lack of need. Conclusion: The study highlights the acceptance and potential of wearables, particularly for health monitoring and data sharing with healthcare providers. Addressing data security and privacy concerns could enhance the adoption of innovative wearables, such as implants, for early detection and monitoring of chronic diseases.

PMID:38900846 | DOI:10.1177/14604582241260607

PLoS One. 2024 Jun 20;19(6):e0304482. doi: 10.1371/journal.pone.0304482. eCollection 2024.

ABSTRACT

This study explains how the gap between theory and empirical research hinders scientific progress in the area of international political economy. To demonstrate this point, I use Chen’s Extended Dependence Theory, which challenges liberal peace theory but fails to provide supporting empirical evidence. Chen contends that it is not trade dependence between two states that fosters peace but a challenger’s trade relations with the defense-pact partners of the target. Although Chen criticizes liberal peace proponents whose primary concern is how to deter war, his empirical analysis is confined to how to decrease (fatal) militarized disputes short of war. I argue that for his theory to succeed, it must be validated against the most severe and intense form of conflict. Using statistical tests and substantive significance, I uncover no peace-building effect, with regards to war, attributable to Extended Dependence. It appears that the Extended Dependence variable exhibits a ceiling effect. Future research should explain why economic ties and security institutions fail to work together to lower the risk of the most destructive form of conflict.

PMID:38900838 | DOI:10.1371/journal.pone.0304482

PLoS One. 2024 Jun 20;19(6):e0305073. doi: 10.1371/journal.pone.0305073. eCollection 2024.

ABSTRACT

Stable isotope methods have been used to study protein metabolism in humans; however, there application in dogs has not been frequently explored. The present study compared the methods of precursor (13C-Leucine), end-products (15N-Glycine), and amino acid oxidation (13C-Phenylalanine) to determine the whole-body protein turnover rate in senior dogs. Six dogs (12.7 ± 2.6 years age, 13.6 ± 0.6 kg bodyweight) received a dry food diet for maintenance and were subjected to all the above-mentioned methods in succession. To establish 13C and 15N kinetics, according to different methodologies blood plasma, urine, and expired air were collected using a specifically designed mask. The volume of CO2 was determined using respirometry. The study included four methods viz. 13C-Leucine, 13C-Phenylalanine evaluated with expired air, 13C-Phenylalanine evaluated with urine, and 15N-Glycine, with six dogs (repetitions) per method. Data was subjected to variance analysis and means were compared using the Tukey test (P<0.05). In addition, the agreement between the methods was evaluated using Pearson correlation and Bland-Altman statistics. Protein synthesis (3.39 ± 0.33 g.kg-0,75. d-1), breakdown (3.26 ± 0.18 g.kg-0.75.d-1), and flux estimations were similar among the four methods of study (P>0.05). However, only 13C-Leucine and 13C-Phenylalanine (expired air) presented an elevated Pearson correlation and concordance. This suggested that caution should be applied while comparing the results with the other methodologies.

PMID:38900837 | DOI:10.1371/journal.pone.0305073

J Burn Care Res. 2024 Jun 20:irae109. doi: 10.1093/jbcr/irae109. Online ahead of print.

ABSTRACT

Vancomycin is a glycopeptide antibiotic that requires close therapeutic monitoring. Prolonged exposure to elevated concentrations increases risk for serious adverse effects such as nephrotoxicity. However, sub-therapeutic concentrations may lead to bacterial resistance and clinical failure or death. The most recent Infectious Diseases Society of America (IDSA) publication regarding therapeutic monitoring of vancomycin recommends utilizing area under the curve (AUC)-based monitoring to maximize clinical success. Despite the guideline recommendation for AUC-guided dosing, many institutions still use trough-only monitoring in their practices, including those caring for patients with acute burn injuries. Following burn injury, patients are at a higher risk for infections, multi-organ failure, and pharmacokinetic alterations. The primary objective of this multi-center retrospective study is to determine optimal therapeutic monitoring of vancomycin by comparing clinical success between AUC vs. trough-based monitoring in burn patients. MONITOR was a multicenter, retrospective study of patients with thermal or inhalation injury admitted to one of 13 burn centers from 1/1/17 to 8/31/22 who received vancomycin. Demographic and clinical course data, including acute kidney injury (AKI) incidence and clinical success were obtained. Patients were evaluated for clinical success and grouped according to method of monitoring and adjusting doses: AUC vs. trough-based monitoring. Clinical success was a composite definition and lack of meeting any 1 of 5 criteria: 1) persistent infection, 2) relapse, 3) antibiotic failure (clinical worsening), 4) AKI, 5) death. Five-hundred seventeen vancomycin courses were assessed from 485 patients. There was no difference in the rate of clinical success between AUC monitored and the trough-only monitored groups. Incidence of AKI was higher in the trough-only group; however, was not statistically significant after controlling for renal function on admission, past medical history of chronic kidney disease (CKD), and concomitant nephrotoxins.

PMID:38900835 | DOI:10.1093/jbcr/irae109

PLoS One. 2024 Jun 20;19(6):e0304885. doi: 10.1371/journal.pone.0304885. eCollection 2024.

ABSTRACT

Same-sex sexual behaviour (SSSB) occurs in most animal clades, but published reports are largely concentrated in a few taxa. Thus, there remains a paucity of published reports for most mammalian species. We conducted a cross-sectional expert survey to better understand the underlying reasons for the lack of publications on this topic. Most respondents researched Primates (83.6%, N = 61), while the rest studied Carnivora (6.9%, N = 5), Rodentia (4.1%, N = 3), Artiodactyla (2.7%, N = 2), and Proboscidea (2.7%, N = 2). Most respondents (76.7%, N = 56) had observed SSSB in their study species, but only 48.2% (N = 27) collected data on SSSB, and few (18.5%, N = 5) had published papers on SSSB. Of the unique species identified as engaging in SSSB in the survey, 38.6% (N = 17) have no existing reports of SSSB to the knowledge of the authors. In both the survey questions and freeform responses, most respondents indicated that their lack of data collection or publication on SSSB was because the behaviours were rare, or because it was not a research priority of their lab. No respondents reported discomfort or sociopolitical concerns at their university or field site as a reason for why they did not collect data or publish on SSSB. Multiple logistic regressions were performed to assess whether taxa studied, education level, or identification within the LGBTQ+ community predicted observing, collecting data on, or publishing on SSSB, but none of these variables were significant predictors. These results provide preliminary evidence that SSSB occurs more frequently than what is available in the published record and suggest that this may be due to a publishing bias against anecdotal evidence.

PMID:38900815 | DOI:10.1371/journal.pone.0304885

PLoS One. 2024 Jun 20;19(6):e0304030. doi: 10.1371/journal.pone.0304030. eCollection 2024.

ABSTRACT

We overview of our whole room indirect calorimeter (WRIC), demonstrate validity and reliability of our WRIC, and explore a novel application of Bayesian hierarchical modeling to assess responses to small carbohydrate loads. To assess WRIC validity seven gas infusion studies were performed using a gas blender and profiles designed to mimic resting and postprandial metabolic events. Sixteen participants underwent fasting and postprandial measurements, during which they consumed a 75-kcal drink containing sucrose, dextrose, or fructose in a crossover design. Linear mixed effects models were used to compare resting and postprandial metabolic rate (MR) and carbohydrate oxidation. Postprandial carbohydrate oxidation trajectories for each participant and condition were modeled using Bayesian Hierarchical Modeling. Mean total error in infusions were 1.27 ± 0.67% and 0.42 ± 0.70% for VO2 and VCO2 respectively, indicating a high level of validity. Mean resting MR was similar across conditions ([Formula: see text] = 1.05 ± 0.03 kcal/min, p = 0.82, ICC: 0.91). While MR increased similarly among all conditions (~13%, p = 0.29), postprandial carbohydrate oxidation parameters were significantly lower for dextrose compared with sucrose or fructose. We provide evidence validating our WRIC and a novel application of statistical methods useful for research using WRIC.

PMID:38900814 | DOI:10.1371/journal.pone.0304030

PLoS One. 2024 Jun 20;19(6):e0304948. doi: 10.1371/journal.pone.0304948. eCollection 2024.

ABSTRACT

INTRODUCTION: Cigarette smoking is a persistent public health problem as it is a risk factor for many diseases. Previous studies on the role of illegal drug use in cigarette smoking have yielded disparate and inconclusive results, hindering the development of effective intervention strategies to address this issue. Therefore, this systematic review and meta-analysis aimed to estimate the pooled prevalence of cigarette smoking and its associated factors, with a specific focus on the influence of illegal drug use among students in Ethiopia.

METHODS: We conducted a comprehensive search of international databases, including PubMed, Cochrane Library, Science Direct, CINAHL, African Journals Online, HINARI, Global Health, and Google and Google Scholar. Grey literature was also identified from various university digital libraries. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA) guidelines. Due to the high heterogeneity among the included studies (I2 = 98.6%; p-value <0.001), we employed a random-effects model with a 95% confidence interval (CI) to estimate the pooled effect using STATA 14 software. The publication bias was assessed using a statistical Egger regression test.

RESULTS: A total of 22 studies involving 18,144 students met the eligibility criteria for this systematic review and meta-analysis. The pooled prevalence of lifetime and current cigarette smoking among students in Ethiopia was 13.8% (95% CI: 9.90-17.82) and 9.61% (95% CI: 7.19-12.03), respectively. Students who used illegal drugs were twenty-three times more likely to smoke cigarettes compared to their counterparts (OR = 23.57, 95% CI: 10.87-51.1). Living in urban settings (OR = 2.9; 95% CI: 1.15-7.28) and the habit of alcohol consumption (OR = 4.79; 95% CI: 1.57-14.64) were also identified as factors associated with cigarette smoking.

CONCLUSIONS: We found that more than one in eight students in Ethiopia have engaged in lifetime cigarette smoking. Notably, students who used illegal drugs exhibited a significantly higher likelihood of cigarette smoking. In light of these findings, it is imperative to implement comprehensive public health interventions that target illegal drug use, cigarette smoking, and alcohol consumption, with a particular emphasis on urban residents.

PMID:38900812 | DOI:10.1371/journal.pone.0304948

PLOS Glob Public Health. 2024 Jun 20;4(6):e0003365. doi: 10.1371/journal.pgph.0003365. eCollection 2024.

ABSTRACT

Core outcome set (COS) development and use enhances comparability of research findings. It may also enhance the translation of research into practice and reduce research waste. However, there is limited involvement of stakeholders from low- and middle-income countries (LMICs) in COS development and use. In this study, we explored the experiences of researchers in COS development projects who included stakeholders from LMICs. Online survey conducted in English of 70 COS developers from HICs who had included LMIC stakeholders in the process of developing a COS, published before the end of 2019. Respondents were identified from the COMET database and sent a link to the survey via a personalised email. Quantitative data were analysed using simple descriptive statistics. Qualitative data analysis was based on qualitative content analysis. There were 37 respondents yielding a 53% overall response rate. Analysis was limited to the responses related to 29 COS developed in the years 2015 to 2019, to reduce the potential for recall bias for earlier COS. Most respondents 20/29 (69%) were researchers. Determining ‘what to measure’ was reported as the most common stage of inclusion of LMIC stakeholders. Respondents cited (24/29, 83%) their ongoing collaborations with LMIC stakeholders such as clinicians or researchers as their main rationale for including LMICs stakeholders and reported that translation of the Delphi into languages other than English may be useful to enhance wider stakeholder participation. Involvement of LMIC stakeholders only in the later stages of COS development, lack of adequate resources to support their involvement, and lack of networks and contacts were thought to limit fuller participation of stakeholders from LMICs. To improve the involvement of LMIC stakeholders in COS development and use, COS developers need to raise awareness on the utility of COS. The need for and feasibility of translation into multiple languages warrants further discussion.

PMID:38900810 | DOI:10.1371/journal.pgph.0003365