Category: Statistics

Environ Sci Technol. 2023 Jul 12. doi: 10.1021/acs.est.2c09264. Online ahead of print.

ABSTRACT

Particulate matter air pollution is a leading cause of global mortality, particularly in Asia and Africa. Addressing the high and wide-ranging air pollution levels requires ambient monitoring, but many low- and middle-income countries (LMICs) remain scarcely monitored. To address these data gaps, recent studies have utilized low-cost sensors. These sensors have varied performance, and little literature exists about sensor intercomparison in Africa. By colocating 2 QuantAQ Modulair-PM, 2 PurpleAir PA-II SD, and 16 Clarity Node-S Generation II monitors with a reference-grade Teledyne monitor in Accra, Ghana, we present the first intercomparisons of different brands of low-cost sensors in Africa, demonstrating that each type of low-cost sensor PM_2.5 is strongly correlated with reference PM_2.5, but biased high for ambient mixture of sources found in Accra. When compared to a reference monitor, the QuantAQ Modulair-PM has the lowest mean absolute error at 3.04 μg/m³, followed by PurpleAir PA-II (4.54 μg/m³) and Clarity Node-S (13.68 μg/m³). We also compare the usage of 4 statistical or machine learning models (Multiple Linear Regression, Random Forest, Gaussian Mixture Regression, and XGBoost) to correct low-cost sensors data, and find that XGBoost performs the best in testing (R²: 0.97, 0.94, 0.96; mean absolute error: 0.56, 0.80, and 0.68 μg/m³ for PurpleAir PA-II, Clarity Node-S, and Modulair-PM, respectively), but tree-based models do not perform well when correcting data outside the range of the colocation training. Therefore, we used Gaussian Mixture Regression to correct data from the network of 17 Clarity Node-S monitors deployed around Accra, Ghana, from 2018 to 2021. We find that the network daily average PM_2.5 concentration in Accra is 23.4 μg/m³, which is 1.6 times the World Health Organization Daily PM_2.5 guideline of 15 μg/m³. While this level is lower than those seen in some larger African cities (such as Kinshasa, Democratic Republic of the Congo), mitigation strategies should be developed soon to prevent further impairment to air quality as Accra, and Ghana as a whole, rapidly grow.

PMID:37437161 | DOI:10.1021/acs.est.2c09264

N Engl J Med. 2023 Jul 13;389(2):118-126. doi: 10.1056/NEJMoa2213329.

ABSTRACT

BACKGROUND: Craniopharyngiomas, primary brain tumors of the pituitary-hypothalamic axis, can cause clinically significant sequelae. Treatment with the use of surgery, radiation, or both is often associated with substantial morbidity related to vision loss, neuroendocrine dysfunction, and memory loss. Genotyping has shown that more than 90% of papillary craniopharyngiomas carry BRAF V600E mutations, but data are lacking with regard to the safety and efficacy of BRAF-MEK inhibition in patients with papillary craniopharyngiomas who have not undergone previous radiation therapy.

METHODS: Eligible patients who had papillary craniopharyngiomas that tested positive for BRAF mutations, had not undergone radiation therapy previously, and had measurable disease received the BRAF-MEK inhibitor combination vemurafenib-cobimetinib in 28-day cycles. The primary end point of this single-group, phase 2 study was objective response at 4 months as determined with the use of centrally determined volumetric data.

RESULTS: Of the 16 patients in the study, 15 (94%; 95% confidence interval [CI], 70 to 100) had a durable objective partial response or better to therapy. The median reduction in the volume of the tumor was 91% (range, 68 to 99). The median follow-up was 22 months (95% CI, 19 to 30) and the median number of treatment cycles was 8. Progression-free survival was 87% (95% CI, 57 to 98) at 12 months and 58% (95% CI, 10 to 89) at 24 months. Three patients had disease progression during follow-up after therapy had been discontinued; none have died. The sole patient who did not have a response stopped treatment after 8 days owing to toxic effects. Grade 3 adverse events that were at least possibly related to treatment occurred in 12 patients, including rash in 6 patients. In 2 patients, grade 4 adverse events (hyperglycemia in 1 patient and increased creatine kinase levels in 1 patient) were reported; 3 patients discontinued treatment owing to adverse events.

CONCLUSIONS: In this small, single-group study involving patients with papillary craniopharyngiomas, 15 of 16 patients had a partial response or better to the BRAF-MEK inhibitor combination vemurafenib-cobimetinib. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT03224767.).

PMID:37437144 | DOI:10.1056/NEJMoa2213329

Int J Surg Pathol. 2023 Jul 12:10668969231185090. doi: 10.1177/10668969231185090. Online ahead of print.

ABSTRACT

Introduction. Pathology plays a major role in the management of patients. Specimen delivery to a pathology laboratory is the first step in the process. Sending materials to the pathology laboratory should be included as part of residency training. The aim of this study was to determine the level of knowledge and daily practice of residents who send materials to pathology laboratory. Methods. A 34-item questionnaire asking questions about biopsy/resection and cytology material handling and transportation was answered by 154 residents. Likert scaling and multiple-choice questions with a single answer were used to evaluate the responses. Their daily routines and levels of knowledge were statistically analyzed. Results. The mean age of the respondents was 29.1 ± 3.04 (range: 24-42 years), and 63% of the residents were male. The residents of the university hospital claimed that the clinical information they had learned about transferring material to the pathology laboratory was “sufficient” or “very sufficient” (statistically significant, P = .04). Correct answers about the process of sending biopsy/resection materials of experienced residents were statistically higher, while there was no statistical significance for questions about cytology materials (P = .005, P = .24, respectively). Conclusion. The pathway to correct diagnosis builds on an understanding of the significance of pathology material. In residency training, knowledge about delivering biopsy/resection material to pathology laboratory is mostly acquired through experience. Experienced residents seem to be less familiar with cytology materials. Clinicopathological meetings may solve the main problems, but both clinics and pathology departments need to emphasize this process.

PMID:37437129 | DOI:10.1177/10668969231185090

J Palliat Med. 2023 Jul 12. doi: 10.1089/jpm.2022.0544. Online ahead of print.

ABSTRACT

Background: Integrating palliative care in the management of patients with lung cancer improves quality of life, patient satisfaction, and overall survival. However, few patients receive timely palliative care consultation. The Lung Diagnostic Assessment Program (LDAP) in Southeastern Ontario is a multidisciplinary rapid assessment clinic that expedites the diagnosis and management of patients with suspected lung cancer. Objectives: We sought to increase the percentage of LDAP patients with stage IV lung cancer receiving palliative care consultation within three months of diagnosis. Design: We integrated a palliative care specialist in LDAP to facilitate in-person, same-visit consultation for patients with a new lung cancer diagnosis. Setting/Subjects: Five hundred fifty patients in a Canadian academic center (154 initial baseline, 104 COVID baseline, 292 post-palliative care integration). Measurements: Baseline data were established using retrospective chart review (February-June 2020 and December 2020-March 2021 due to COVID-19 pandemic). Data were collected prospectively to assess improvement (March-August 2021). Statistical Process Control charts assessed for special cause variation; chi-square tests assessed for differences between groups. Results: The percentage of patients with stage IV lung cancer seen by palliative care within three months increased from 21.8% (12/55) during early-COVID baseline to 49.2% (32/65) after palliative care integration (p < 0.006). Palliative care integration in LDAP reduced mean time from referral to consultation from 24.8 to 12.3 days, including same-day consultation for 15/32 (46.8%) patients with stage IV disease. Conclusions: Integrating palliative care specialists into LDAP improved the timeliness of palliative care assessment for patients with stage IV lung cancer.

PMID:37437122 | DOI:10.1089/jpm.2022.0544

Genetics. 2023 Jul 12:iyad127. doi: 10.1093/genetics/iyad127. Online ahead of print.

ABSTRACT

Correlation among multiple phenotypes across related individuals may reflect some pattern of shared genetic architecture: individual genetic lociaffect multiple phenotypes (an effect known as pleiotropy), creating observable relationships between phenotypes. A natural hypothesis is that pleiotropic effects reflect a relatively small set of common “core” cellular processes: each genetic locus affects one or a few core processes, and these core processes in turn determine the observed phenotypes. Here, we propose a method to infer such structure in genotype-phenotype data. Our approach, sparse structure discovery (SSD) is based on a penalized matrix decomposition designed to identify latent structure that is low-dimensional (many fewer core processes than phenotypes and genetic loci), locus-sparse (each locus affects few core processes) and/or phenotype-sparse (each phenotype is influenced by few core processes). Our use of sparsity as a guide in the matrix decomposition is motivated by the results of a novel empirical test indicating evidence of sparse structure in several recent genotype-phenotype data sets. First, we use synthetic data to show that our SSD approach can accurately recover core processes if each genetic locus affects few core processes or if each phenotype is affected by few core processes. Next, we apply the method to three datasets spanning adaptive mutations in yeast, genotoxin robustness assay in human cell lines, and genetic loci identified from a yeast cross, and evaluate the biological plausibility of the core process identified. More generally, we propose sparsity as a guiding prior for resolving latent structure in empirical genotype-phenotype maps.

PMID:37437111 | DOI:10.1093/genetics/iyad127

J Child Adolesc Psychopharmacol. 2023 Jul 12. doi: 10.1089/cap.2022.0097. Online ahead of print.

ABSTRACT

Objective: Cariprazine is a dopamine D₃-preferring D₃/D₂ and serotonin 5-HT_1A receptor partial agonist approved to treat adults with schizophrenia and manic/mixed or depressive episodes associated with bipolar I disorder. This study, which is the first to evaluate cariprazine in pediatric patients with autism spectrum disorder (ASD) (including children 5-9 years of age) using an oral solution formulation, evaluated the safety, tolerability, pharmacokinetics (PK), and exploratory efficacy of cariprazine and its two major active metabolites, desmethyl cariprazine (DCAR) and didesmethyl cariprazine (DDCAR). Methods: This clinical pharmacology, open-label, multiple-dose study enrolled 25 pediatric patients from 5 to 17 years of age, who met the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria for ASD. All patients began treatment with cariprazine 0.5 mg once daily (QD) and underwent a titration over 7 days to maintenance doses of 1.5 or 3 mg QD for patients 13-17 years of age at Screening, 0.75 or 1.5 mg QD for patients 10-12 years of age at Screening, and 0.5 or 1.5 mg QD for patients 5-9 years of age at Screening. After 6 weeks total of dosing, there was a 6-week follow-up period. Study assessments included adverse events (AEs), safety parameters, noncompartmental PK parameters, and exploratory efficacy assessments, including the Aberrant Behavior Checklist-Irritability Subscale (ABC-I), Clinical Global Impressions (CGI-S), Caregiver Global Impressions (CgGI-S), Children’s Yale-Brown Obsessive Compulsiveness Scale Modified for ASD (CYBOCS-ASD), Social Responsiveness Scale (SRS), and Vineland Adaptive Behavior Scale (VABS-III). Results: All AEs were mild or moderate in severity. Most frequent treatment-emergent adverse events (TEAEs) were increased weight, increased alanine aminotransferase, increased appetite, dizziness, agitation, and nasal congestion. Increases in weight were not considered clinically meaningful. Two subjects reported extrapyramidal symptom-related TEAEs that resolved without leading to discontinuation. Dose-normalized exposures of all analytes were modestly higher in pediatric patients from 5 to 9 years of age when compared to older patients. Consistent with previous studies, at steady state, the rank of exposure in plasma was DDCAR > cariprazine > DCAR. There was numerical improvement on all exploratory endpoints (ABC-I, CGI-S, CgGI-S, CYBOCS-ASD, SRS, and VABS-III). Conclusions: PK of cariprazine and its metabolites were characterized in pediatric patients with ASD at doses up to 3 mg QD (13-17 years) and 1.5 mg QD (5-12 years). Caripazine treatment was generally well tolerated and results from this study will inform the selection of appropriate pediatric doses for subsequent studies.

PMID:37437109 | DOI:10.1089/cap.2022.0097

PLoS One. 2023 Jul 12;18(7):e0288209. doi: 10.1371/journal.pone.0288209. eCollection 2023.

ABSTRACT

The use of mice as animal models in biomedical research allows the standardization of genetic background, housing conditions as well as experimental protocols, which all affect phenotypic variability. The phenotypic variability within the experimental unit determines the choice of the group size which is necessary for achieving valid and reproducible results. In this study, the variability of clinical chemical and hematological parameters which represent a comprehensive blood screen of laboratory mice, as well as of immunological parameters and behavioral tests was analyzed in data sets which have been submitted to the Mouse Phenome Database for mouse strains which are predominantly used in biomedical research. Most of the clinical chemical and hematological parameters-except of some parameters being known for their high variability-showed an average coefficient of variation (CV = standard deviation / mean) below 0.25. Most immunological parameters measured in blood samples had a CV between 0.2 and 0.4. The behavioral tests showed a CV between 0.4 and 0.6, or higher. In addition, a large range of the CV was found for most parameters/tests between and within the selected projects. This clearly demonstrates the appearance of unpredictable major interactions between genotype, environment and experiment regarding the variability of the parameters and tests analyzed.

PMID:37437097 | DOI:10.1371/journal.pone.0288209

Health Educ Res. 2023 Jul 11:cyad027. doi: 10.1093/her/cyad027. Online ahead of print.

ABSTRACT

This study compares the impact of pictorial health warning labels (HWLs) and their placements on waterpipe parts (device, tobacco and charcoal packages) on health communication outcomes between waterpipe smokers and nonsmokers in Lebanon. An online randomized crossover experimental study was conducted among young adults (n = 403, August 2021) who observed three conditions of HWLs: pictorial HWLs on the tobacco package, pictorial HWLs on all waterpipe’s parts and text-only HWL on the tobacco package in random order. Participants completed post-exposure assessments of health communication outcomes after each image. Using linear mixed models, we examined the differences in the effect of HWL conditions on several outcomes (i.e. warning reactions) between waterpipe smokers and nonsmokers, controlling for confounders (i.e. age, sex). Nonsmokers reported greater attention (β = 0.54 [95% confidence interval: 0.25-0.82]), cognitive elaboration (0.31 [0.05-0.58]) and social interaction (0.41 [0.18-0.65]) for pictorial HWLs on the tobacco packages than text-only compared with smokers. Pictorial HWLs on three parts versus one part elicited higher cognitive reactions and perceived message effectiveness in nonsmokers compared with waterpipe smokers. These findings provide valuable information for policymakers about the potential of implementing HWLs specific to waterpipes to prevent their use among young adults and limit tobacco-related morbidity and mortality in Lebanon.

PMID:37436823 | DOI:10.1093/her/cyad027

JMIR Res Protoc. 2023 Jul 12;12:e45712. doi: 10.2196/45712.

ABSTRACT

BACKGROUND: Pneumonia is a leading cause of death in patients with end-stage chronic kidney disease treated with dialysis. Current vaccination schedules recommend pneumococcal vaccination. However, this schedule disregards findings of rapid titer decline in adult hemodialysis patients after 12 months.

OBJECTIVE: The primary objective is to compare pneumonia rates between recently vaccinated patients and patients vaccinated more than 2 years ago. As an exploratory objective, antipneumococcal antibody titers in hemodialysis patients will be determined as a function. Factors influencing antibody kinetics will be identified.

METHODS: Within this prospective multicenter study, we aim to compare 2 strata of vaccinated patients: those recently vaccinated and those vaccinated more than 2 years ago. A total of 792 patients will be enrolled. Twelve partner sites (within the German Centre for Infection Research [DZIF]) with allocated dialysis practices participate in this study. All dialysis patients who are vaccinated against pneumococcal infection in accordance with Robert Koch Institute guidelines prior to enrollment will be eligible. Data on baseline demographics, vaccination history, and underlying disease will be assessed. Pneumococcal antibody titers will be determined at baseline and every 3 months for 2 years. DZIF clinical trial units coordinate titer assessment schedules and actively follow-up on study patients for 2-5 years after enrollment, including validation of end points of hospitalization, pneumonia, and death.

RESULTS: The study has enrolled 792 patients and the last follow-up has been completed. Currently, the statistical and laboratory analyses are ongoing.

CONCLUSIONS: Results will increase physician adherence to current recommendations. Establishing a framework for the efficient evaluation of guideline recommendations through a combination of routine and study data will inform the evidence base for future guidelines.

TRIAL REGISTRATION: ClinicalTrials.gov NCT03350425; https://clinicaltrials.gov/ct2/show/NCT03350425.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/45712.

PMID:37436797 | DOI:10.2196/45712

JMIR Res Protoc. 2023 Jul 12;12:e48666. doi: 10.2196/48666.

ABSTRACT

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a progressive condition associated with physical and cognitive impairments contributing to difficulty in performing activities of daily living (ADLs) that require dual tasking (eg, walking and talking). Despite evidence showing that cognitive decline occurs among patients with COPD and may contribute to functional limitations and decreased health-related quality of life (HRQL), pulmonary rehabilitation continues to focus mainly on physical training (ie, aerobic and strength exercises). An integrated cognitive and physical training program compared to physical training alone may be more effective in increasing dual-tasking ability among people living with COPD, leading to greater improvements in performance of ADLs and HRQL.

OBJECTIVE: The aims of this study are to evaluate the feasibility of an 8-week randomized controlled trial of home-based, cognitive-physical training versus physical training for patients with moderate to severe COPD and derive preliminary estimates of cognitive-physical training intervention efficacy on measures of physical and cognitive function, dual task performance, ADLs, and HRQL.

METHODS: A total of 24 participants with moderate to severe COPD will be recruited and randomized into cognitive-physical training or physical training. All participants will be prescribed an individualized home physical exercise program comprising 5 days of moderate-intensity aerobic exercise (30-50 minutes/session) and 2 days of whole-body strength training per week. The cognitive-physical training group will also perform cognitive training for approximately 60 minutes, 5 days per week via the BrainHQ platform (Posit Science Corporation). Participants will meet once weekly with an exercise professional (via videoconference) who will provide support by reviewing the progression of their training and addressing any queries. Feasibility will be assessed through the recruitment rate, program adherence, satisfaction, attrition, and safety. The intervention efficacy regarding dual task performance, physical function, ADLs, and HRQL will be evaluated at baseline and at 4 and 8 weeks. Descriptive statistics will be used to summarize intervention feasibility. Paired 2-tailed t tests and 2-tailed t tests will be used to compare the changes in the outcome measures over the 8-week study period within and between the 2 randomized groups, respectively.

RESULTS: Enrollment started in January 2022. It is estimated that the enrollment period will be 24 months long, with data collection to be completed by December 2023.

CONCLUSIONS: A supervised home-based cognitive-physical training program may be an accessible intervention to improve dual-tasking ability in people living with COPD. Evaluating the feasibility and effect estimates is a critical first step to inform future clinical trials evaluating this approach and its effects on physical and cognitive function, ADL performance, and HRQL.

TRIAL REGISTRATION: ClinicalTrials.gov NCT05140226; https://clinicaltrials.gov/ct2/show/NCT05140226.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/48666.

PMID:37436794 | DOI:10.2196/48666