Category: Statistics

J Med Internet Res. 2022 Jun 1. doi: 10.2196/38443. Online ahead of print.

ABSTRACT

BACKGROUND: During the COVID-19 pandemic, there have been increased reports of racial biases against Asian Americans (AsAs) and Native Hawaiians and Pacific Islanders (NHPIs). However, the extent to which different AsA and NHPI groups perceive and/or experience first-hand or being a witness to such experiences) associated with COVID-19 has negatively affected people of their race has not received much attention.

OBJECTIVE: We used data from the COVID-19 Effects on the Mental and Physical Health of Asian Americans and Pacific Islanders Survey Study (COMPASS), a nationwide, multi-lingual, community-based survey to empirically examine racial bias beliefs on AsAs and NHPIs as related to the COVID-19 pandemic and the factors associated with these beliefs.

METHODS: COMPASS participants were AsA and NHPI adults who were able to speak English, Chinese (Cantonese or Mandarin), Korean, Samoan, or Vietnamese and who resided in the United States (US) during the time of the survey (October 2020-May 2021). Participants completed the survey online, by phone, or in-person. The Coronavirus Racial Bias Scale (CRBS) was used to assess COVID-19 related racial bias beliefs towards AsAs and NHPIs. Participants were asked to rate the degree to which they agree with 9 statements on a 5-point Likert scale (i.e., “1 strongly disagree” to “5 strongly agree”). Higher score indicated greater degree of agreement with coronavirus racial bias beliefs. Multivariable linear regression was used to examine associations of demographic, health, and COVID-19 related characteristics with perceived racial bias.

RESULTS: A total of 5,068 participants completed the survey (mean age=45.4 years old; range: 18-97). Overall, 74% agreed or strongly agreed to one or more of the COVID-19 racial bias beliefs in the past 6 months (during the COVID-19 pandemic). Across the 9 racial bias beliefs, participants scored on the average 2.59 (SD=0.96; range 1-5). Adjusted analyses revealed that compared to Asian Indians, those who are ethnic Chinese, Filipino, Hmong, Japanese, Korean, Vietnamese, and other/multi-cultural had significantly higher mean CRBS scores whereas no significant differences were found among NHPIs. Non-heterosexual participants had a statistically significant higher mean CRBS scores compared to heterosexual participants. Compared to participants who were 60 years or older, those who were younger (<30, 30-39, 40-49, and 50-59 years) had significantly higher mean CRBS scores. US born participants had significantly higher mean CRBS scores than those who were foreign-born, whereas those with limited English proficiency (relative to those reporting no limitation) had lower mean CRBS scores.

CONCLUSIONS: Many COMPASS participants reported racial bias beliefs due to the COVID-19 pandemic. Relevant sociodemographic contexts, pre-existing and COVID-specific factors across individual, community and society levels were associated with perceived racial bias of “being Asian” during the pandemic. Findings underscore the importance of addressing the burden of racial bias on AsA and NHPI communities among other COVID-19 related sequalae.

PMID:35658091 | DOI:10.2196/38443

Med Care. 2022 Jun 6. doi: 10.1097/MLR.0000000000001742. Online ahead of print.

ABSTRACT

BACKGROUND: Persons with multimorbidity (≥2 chronic conditions) face an increased risk of poor health outcomes, especially as they age. Psychosocial factors such as social isolation, chronic stress, housing insecurity, and financial insecurity have been shown to exacerbate these outcomes, but are not routinely assessed during the clinical encounter. Our objective was to extract these concepts from chart notes using natural language processing and predict their impact on health care utilization for patients with multimorbidity.

METHODS: A cohort study to predict the 1-year likelihood of hospitalizations and emergency department visits for patients 65+ with multimorbidity with and without psychosocial factors. Psychosocial factors were extracted from narrative notes; all other covariates were extracted from electronic health record data from a large academic medical center using validated algorithms and concept sets. Logistic regression was performed to predict the likelihood of hospitalization and emergency department visit in the next year.

RESULTS: In all, 76,479 patients were eligible; the majority were White (89%), 54% were female, with mean age 73. Those with psychosocial factors were older, had higher baseline utilization, and more chronic illnesses. The 4 psychosocial factors all independently predicted future utilization (odds ratio=1.27-2.77, C-statistic=0.63). Accounting for demographics, specific conditions, and previous utilization, 3 of 4 of the extracted factors remained predictive (odds ratio=1.13-1.86) for future utilization. Compared with models with no psychosocial factors, they had improved discrimination. Individual predictions were mixed, with social isolation predicting depression and morbidity; stress predicting atherosclerotic cardiovascular disease onset; and housing insecurity predicting substance use disorder morbidity.

DISCUSSION: Psychosocial factors are known to have adverse health impacts, but are rarely measured; using natural language processing, we extracted factors that identified a higher risk segment of older adults with multimorbidity. Combining these extraction techniques with other measures of social determinants may help catalyze population health efforts to address psychosocial factors to mitigate their health impacts.

PMID:35658116 | DOI:10.1097/MLR.0000000000001742

Colorectal Dis. 2022 Jun 3. doi: 10.1111/codi.16194. Online ahead of print.

ABSTRACT

AIM: There are discrepancies in the guidelines on preparation for colorectal surgery. While intravenous antibiotics (IV) are usually administered, the use of mechanical bowel preparation (MBP) and/or oral antibiotics (OA) is controversial. A recent network meta-analysis (NMA) demonstrated that the addition of OA reduced incisional surgical site infections (iSSIs) by more than 50%. We aimed to perform a NMA including only the highest quality randomized clinical trials (RCTs) in order to determine the ranking of different treatment strategies and assess these RCTs for methodological problems that may affect the conclusions of the NMAs.

METHOD: A NMA was performed according to PRISMA guidelines. RCTs of adult patients undergoing elective colorectal surgery with appropriate antibiotic cover and with at least 250 participants recruited, clear definition of endpoints and duration of follow-up extending beyond discharge from hospital were included. The search included Medline, Embase, Cochrane and SCOPUS databases. Primary outcomes were iSSI and anastomotic leak (AL). Statistical analysis was performed in Stata v.15.1 using frequentist routines.

RESULTS: Ten RCTs including 5107 patients were identified. Treatments compared IV (2218 patients), IV + OA (460 patients), MBP + IV (1405 patients), MBP + IV + OA (538 patients) and OA (486 patients). The likelihood of iSSI was significantly lower for IV + OA (rank 1) and MBP + IVA + OA (rank 2), reducing iSSIs by more than 50%. There were no differences between treatments for AL. Methodological issues included differences in definition, assessment and frequency of primary endpoint infections and the limited number of participants included in some treatment options.

CONCLUSION: While this NMA supports the addition of OA to IV to reduce iSSI it also highlights unanswered questions and the need for well-designed pragmatic RCTs.

PMID:35658069 | DOI:10.1111/codi.16194

PLoS One. 2022 Jun 3;17(6):e0269460. doi: 10.1371/journal.pone.0269460. eCollection 2022.

ABSTRACT

Evidence-Based Practice (EBP) is a cost-effective approach for improving the quality of clinical care and implementing only well-tested evidence. Health professions, especially physiotherapy, must embrace EBP principles. This paper presents normative data from the Spanish physiotherapist population using the Health-Sciences Evidence-Based Practice questionnaire and explores EBP clusters/profiles of professionals in practice. An intentional sample of 419 practicing physiotherapists was recruited from the Spanish Professional Council of Physiotherapy. Participants completed a cross-sectional online survey with 60 Likert items (scale 1-10) measuring 5 dimensions: 1) Beliefs and attitudes, 2) Results from literature, 3) Professional practice, 4) Assessment of results, and 5) Barriers and Facilitators. The protocol also included sociodemographic, training, and practice-related contrast variables. Normative data were estimated and tabulated for each dimension and then a K-means clustering procedure was implemented using the contrast variables. Results for normative data showed, in descending order, the following 50th percentile values for the five EBP factors: Beliefs and attitudes (8.25), Professional practice (8.00), Assessment of results (7.42), Results from literature (6.71), and EBP Barriers and Facilitators (5.17); all expressed on a scale of 1 to 10. Academic degree, EBP training level, and work time shared in healthcare activity, research, or teaching activity were all statistically significant for discriminating EBP dimension scores. Finally, six different clusters showed that when EBP level is low, the scores in all dimensions are equally low, and vice-versa. The EBP dimensions “Beliefs and attitudes”, “Professional practice”, and “Evaluation of results” obtained better normative scores overall than “Search for bibliographic evidence and its inclusion in practice” and especially “Perception of EBP barriers”, which had the worst score. Normative data are useful for comparing individual scores and the reference population, and information about clusters will enable appropriate global EBP intervention programs to be designed and implemented.

PMID:35658062 | DOI:10.1371/journal.pone.0269460

PLoS One. 2022 Jun 3;17(6):e0269491. doi: 10.1371/journal.pone.0269491. eCollection 2022.

ABSTRACT

BACKGROUND: Neuronal dysfunction plays an important role in the high prevalence of HIV-associated neurocognitive disorders (HAND) in people with HIV (PWH). Transcranial direct current stimulation (tDCS)-with its capability to improve neuronal function-may have the potential to serve as an alternative therapeutic approach for HAND. Brain imaging and neurobehavioral studies provide converging evidence that injury to the anterior cingulate cortex (ACC) is highly prevalent and contributes to HAND in PWH, suggesting that ACC may serve as a potential neuromodulation target for HAND. Here we conducted a randomized, double-blind, placebo-controlled, partial crossover pilot study to test the safety, tolerability, and potential efficacy of anodal tDCS over cingulate cortex in adults with HIV, with a focus on the dorsal ACC (dACC).

METHODS: Eleven PWH (47-69 years old, 2 females, 100% African Americans, disease duration 16-36 years) participated in the study, which had two phases, Phase 1 and Phase 2. During Phase 1, participants were randomized to receive ten sessions of sham (n = 4) or cingulate tDCS (n = 7) over the course of 2-3 weeks. Treatment assignments were unknown to the participants and the technicians. Neuropsychology and MRI data were collected from four additional study visits to assess treatment effects, including one baseline visit (BL, prior to treatment) and three follow-up visits (FU1, FU2, and FU3, approximately 1 week, 3 weeks, and 3 months after treatment, respectively). Treatment assignment was unblinded after FU3. Participants in the sham group repeated the study with open-label cingulate tDCS during Phase 2. Statistical analysis was limited to data from Phase 1.

RESULTS: Compared to sham tDCS, cingulate tDCS led to a decrease in Perseverative Errors in Wisconsin Card Sorting Test (WCST), but not Non-Perseverative Errors, as well as a decrease in the ratio score of Trail Making Test-Part B (TMT-B) to TMT-Part A (TMT-A). Seed-to-voxel analysis with resting state functional MRI data revealed an increase in functional connectivity between the bilateral dACC and a cluster in the right dorsal striatum after cingulate tDCS. There were no differences in self-reported discomfort ratings between sham and cingulate tDCS.

CONCLUSIONS: Cingulate tDCS is safe and well-tolerated in PWH, and may have the potential to improve cognitive performance and brain function. A future study with a larger sample is warranted.

PMID:35658059 | DOI:10.1371/journal.pone.0269491

PLoS One. 2022 Jun 3;17(6):e0269247. doi: 10.1371/journal.pone.0269247. eCollection 2022.

ABSTRACT

INTRODUCTION: Severe COVID-19 constitutes a form of viral sepsis. Part of the specific pathophysiological pattern of this condition is the occurrence of cardiovascular events. These include pulmonary embolism, arrhythmias and cardiomyopathy as manifestations of extra-pulmonary organ dysfunction. Hitherto, the prognostic impact of these cardiovascular events and their predisposing risk factors remains unclear. This study aims to explore this question in two cohorts of viral sepsis-COVID-19 and influenza-in order to identify new theragnostic strategies to improve the short- and long-term outcome of these two diseases.

METHODS AND ANALYSIS: In this prospective multi-centre cohort study, clinical assessment will take place during the acute and post-acute phase of sepsis and be complemented by molecular laboratory analyses. Specifically, echocardiography and cardiovascular risk factor documentation will be performed during the first two weeks after sepsis onset. Aside from routine haematological and biochemical laboratory tests, molecular phenotyping will comprise analyses of the metabolome, lipidome and immune status. The primary endpoint of this study is the difference in 3-month mortality of patients with and without septic cardiomyopathy in COVID-19 sepsis. Patients will be followed up until 6 months after onset of sepsis via telephone interviews and questionnaires. The results will be compared with a cohort of patients with influenza sepsis as well as previous cohorts of patients with bacterial sepsis and healthy controls.

ETHICS AND DISSEMINATION: Approval was obtained from the Ethics Committee of the Friedrich Schiller University Jena (2020-2052-BO). The results will be published in peer-reviewed journals and presented at appropriate conferences.

TRIAL REGISTRATION: DRKS00024162.

PMID:35658058 | DOI:10.1371/journal.pone.0269247

PLoS Comput Biol. 2022 Jun 3;18(6):e1010177. doi: 10.1371/journal.pcbi.1010177. Online ahead of print.

ABSTRACT

Engineered microbial cells present a sustainable alternative to fossil-based synthesis of chemicals and fuels. Cellular synthesis routes are readily assembled and introduced into microbial strains using state-of-the-art synthetic biology tools. However, the optimization of the strains required to reach industrially feasible production levels is far less efficient. It typically relies on trial-and-error leading into high uncertainty in total duration and cost. New techniques that can cope with the complexity and limited mechanistic knowledge of the cellular regulation are called for guiding the strain optimization. In this paper, we put forward a multi-agent reinforcement learning (MARL) approach that learns from experiments to tune the metabolic enzyme levels so that the production is improved. Our method is model-free and does not assume prior knowledge of the microbe’s metabolic network or its regulation. The multi-agent approach is well-suited to make use of parallel experiments such as multi-well plates commonly used for screening microbial strains. We demonstrate the method’s capabilities using the genome-scale kinetic model of Escherichia coli, k-ecoli457, as a surrogate for an in vivo cell behaviour in cultivation experiments. We investigate the method’s performance relevant for practical applicability in strain engineering i.e. the speed of convergence towards the optimum response, noise tolerance, and the statistical stability of the solutions found. We further evaluate the proposed MARL approach in improving L-tryptophan production by yeast Saccharomyces cerevisiae, using publicly available experimental data on the performance of a combinatorial strain library. Overall, our results show that multi-agent reinforcement learning is a promising approach for guiding the strain optimization beyond mechanistic knowledge, with the goal of faster and more reliably obtaining industrially attractive production levels.

PMID:35658018 | DOI:10.1371/journal.pcbi.1010177

PLoS One. 2022 Jun 3;17(6):e0269556. doi: 10.1371/journal.pone.0269556. eCollection 2022.

ABSTRACT

Due to greater environmental awareness, domestic laundry habits are changing, and antimicrobial control by chemical methods has become an essential factor to compensate for the use of lower temperatures during washing machine cycles. Disinfectants added to laundry detergents are a preventive strategy to reduce the transmission of bacteria, fungi, and viruses in the home, correct aesthetic damage (e.g., spotting, discolouration, and staining), and control the microbial contamination that leads to malodour. In Europe, disinfectants are regulated by the EU Biocidal Products Regulation (No. 528/2012), which stipulates that antimicrobial efficacy must be evaluated according to standardized methods. Current European standards for laundry sanitization only apply to clinical settings (EN 16616: 2015) and are restricted to the main wash cycle. Therefore, there is a gap in the EU standards regarding the testing of product efficacy in household laundering. With the aim of addressing this gap, an international ring trial was organized to evaluate the robustness of a new method (prEN 17658) designed to test the efficacy of antimicrobial laundry products in a domestic setting. The seven participating laboratories were equipped with 5 different laboratory-scale devices to simulate the washing process, and they evaluated 7 microbial parameters for 2 experimental conditions and 3 levels of active substance. The analysis of data according to ISO 5725-2 and ISO 13528 demonstrated that the method was robust. All reproducibility standard deviation values were between 0.00 and 1.40 and the relative standard deviation indicates satisfactory reproducibility. Values of logarithmic reduction ranged from less than 2 log10 for tests with water to more than 5 log10 when disinfectants were added. The evidence generated by the ring trial was presented in a proposal for a standardized method under CEN/TC 216, in which the SOP used in the ring trial is referred to as the prEN 17658 phase 2 step 2 test method covering chemothermal textile disinfection in domestic settings.

PMID:35658049 | DOI:10.1371/journal.pone.0269556

PLoS Biol. 2022 Jun 3;20(6):e3001626. doi: 10.1371/journal.pbio.3001626. eCollection 2022 Jun.

ABSTRACT

The evolution of cooperation in cellular groups is threatened by lineages of cheaters that proliferate at the expense of the group. These cell lineages occur within microbial communities, and multicellular organisms in the form of tumours and cancer. In contrast to an earlier study, here we show how the evolution of pleiotropic genetic architectures-which link the expression of cooperative and private traits-can protect against cheater lineages and allow cooperation to evolve. We develop an age-structured model of cellular groups and show that cooperation breaks down more slowly within groups that tie expression to a private trait than in groups that do not. We then show that this results in group selection for pleiotropy, which strongly promotes cooperation by limiting the emergence of cheater lineages. These results predict that pleiotropy will rapidly evolve, so long as groups persist long enough for cheater lineages to threaten cooperation. Our results hold when pleiotropic links can be undermined by mutations, when pleiotropy is itself costly, and in mixed-genotype groups such as those that occur in microbes. Finally, we consider features of multicellular organisms-a germ line and delayed reproductive maturity-and show that pleiotropy is again predicted to be important for maintaining cooperation. The study of cancer in multicellular organisms provides the best evidence for pleiotropic constraints, where abberant cell proliferation is linked to apoptosis, senescence, and terminal differentiation. Alongside development from a single cell, we propose that the evolution of pleiotropic constraints has been critical for cooperation in many cellular groups.

PMID:35658016 | DOI:10.1371/journal.pbio.3001626

J Clin Oncol. 2022 Jun 3:JCO2200912. doi: 10.1200/JCO.22.00912. Online ahead of print.

ABSTRACT

PURPOSE: Resistance to immune checkpoint inhibition (ICI) in advanced non-small-cell lung cancer (NSCLC) represents a major unmet need. Combining ICI with vascular endothelial growth factor (VEGF)/VEGF receptor inhibition has yielded promising results in multiple tumor types.

METHODS: In this randomized phase II Lung-MAP nonmatch substudy (S1800A), patients ineligible for a biomarker-matched substudy with NSCLC previously treated with ICI and platinum-based chemotherapy and progressive disease at least 84 days after initiation of ICI were randomly assigned to receive ramucirumab plus pembrolizumab (RP) or investigator’s choice standard of care (SOC: docetaxel/ramucirumab, docetaxel, gemcitabine, and pemetrexed). With a goal of 130 eligible patients, the primary objective was to compare overall survival (OS) using a one-sided 10% level using the better of a standard log-rank (SLR) and weighted log-rank (WLR; G[rho = 0, gamma = 1]) test. Secondary end points included objective response, duration of response, investigator-assessed progression-free survival, and toxicity.

RESULTS: Of 166 patients enrolled, 136 were eligible (69 RP; 67 SOC). OS was significantly improved with RP (hazard ratio [80% CI]: 0.69 [0.51 to 0.92]; SLR one-sided P = .05; WLR one-sided P = .15). The median (80% CI) OS was 14.5 (13.9 to 16.1) months for RP and 11.6 (9.9 to 13.0) months for SOC. OS benefit for RP was seen in most subgroups. Investigator-assessed progression-free survival (hazard ratio [80% CI]: 0.86 [0.66 to 1.14]; one-sided SLR, P = .25 and .14 for WLR) and response rates (22% RP v 28% SOC, one-sided P = .19) were similar between arms. Grade ≥ 3 treatment-related adverse events occurred in 42% of patients in the RP group and 60% on SOC.

CONCLUSION: This randomized phase II trial demonstrated significantly improved OS with RP compared with SOC in patients with advanced NSCLC previously treated with ICI and chemotherapy. The safety was consistent with known toxicities of both drugs. These data warrant further evaluation.

PMID:35658002 | DOI:10.1200/JCO.22.00912