Tag: statistics

J Chem Theory Comput. 2022 Aug 24. doi: 10.1021/acs.jctc.2c00248. Online ahead of print.

ABSTRACT

Molecular assembly processes are generally driven by thermodynamic properties in solutions. Atomistic modeling can be very helpful in designing and understanding complex systems, except that bulk solvent is very inefficient to treat explicitly as discrete molecules. In this work, we develop and assess two multiscale solvation models for computing solvation thermodynamic properties. The new SLIC/CDC model combines continuum solvent electrostatics based on the solvent layer interface condition (SLIC) with new statistical thermodynamic models for hydrogen bonding and nonpolar modes: cavity formation, dispersion interactions, combinatorial mixing (CDC). Given the structures of 500 solutes, the SLIC/CDC model predicts Gibbs energies of solvation in water with an average accuracy better than 1 kcal/mol, when compared to experimental measurements, and better than 0.8 kcal/mol, when compared to explicit-solvent molecular dynamics simulations. The individual SLIC/CDC energy mode values agree quantitatively with those computed from explicit-solvent molecular dynamics. The previously published SLIC/SASA multiscale model combines the SLIC continuum electrostatic model with the solvent-accessible surface area (SASA) nonpolar energy mode. With our new, improved parametrization method, the SLIC/SASA model now predicts Gibbs energies of solvation with better than 1.4 kcal/mol average accuracy in aqueous systems, compared to experimental and explicit-solvent molecular dynamics, and better than 1.6 kcal/mol average accuracy in ionic liquids, compared to explicit-solvent molecular dynamics. Both models predict solvation entropies, and are the first implicit-solvation models capable of predicting solvation heat capacities.

PMID:36001344 | DOI:10.1021/acs.jctc.2c00248

JAMA Netw Open. 2022 Aug 1;5(8):e2228083. doi: 10.1001/jamanetworkopen.2022.28083.

ABSTRACT

IMPORTANCE: Brain metastasis (BrM) in gastroesophageal adenocarcinoma (GEA) is a rare and poorly understood phenomenon associated with poor prognosis.

OBJECTIVES: To examine the clinical and genomic features of patients with BrM from GEA and evaluate factors associated with survival.

DESIGN, SETTING, AND PARTICIPANTS: In this single-institution retrospective cohort study, 68 patients with BrM from GEA diagnosed between January 1, 2008, and December 31, 2020, were identified via review of billing codes and imaging reports from the electronic medical record with follow-up through November 3, 2021. Genomic data were derived from the Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets clinical sequencing platform.

EXPOSURES: Treatment with BrM resection and/or radiotherapy.

MAIN OUTCOMES AND MEASURES: Overall survival after BrM diagnosis.

RESULTS: Sixty-eight patients (median age at diagnosis, 57.4 years [IQR, 49.8-66.4 years]; 59 [86.8%] male; 55 [85.9%] White) participated in the study. A total of 57 (83.8%) had primary tumors in the distal esophagus or gastroesophageal junction. Median time from initial diagnosis to BrM diagnosis was 16.9 months (IQR, 8.5-27.7 months). Median survival from BrM diagnosis was 8.7 months (95% CI, 5.5-11.5 months). Overall survival was 35% (95% CI, 25%-48%) at 1 year and 24% (95% CI, 16%-37%) at 2 years. In a multivariable analysis, an Eastern Cooperative Oncology Group performance status of 2 or greater (hazard ratio [HR], 4.66; 95% CI, 1.47-14.70; P = .009) and lack of surgical or radiotherapeutic intervention (HR, 7.71; 95% CI, 2.01-29.60; P = .003) were associated with increased risk of all-cause mortality, whereas 3 or more extracranial sites of disease (HR, 1.85; 95% CI, 0.64-5.29; P = .25) and 4 or more BrMs (HR, 2.15; 95% CI, 0.93-4.98; P = .07) were not statistically significant. A total of 31 patients (45.6%) had ERBB2 (formerly HER2 or HER2/neu)-positive tumors, and alterations in ERBB2 were enriched in BrM relative to primary tumors (8 [47.1%] vs 7 [20.6%], P = .05), as were alterations in PTPRT (7 [41.2%] vs 4 [11.8%], P = .03).

CONCLUSIONS AND RELEVANCE: This study suggests that that a notable proportion of patients with BrM from GEA achieve survival exceeding 1 and 2 years from BrM diagnosis, a more favorable prognosis than previously reported. Good performance status and treatment with combination surgery and radiotherapy were associated with the best outcomes. ERBB2 positivity and amplification as well as PTPRT alterations were enriched in BrM tissue compared with primary tumors; therefore, further study should be pursued to identify whether these variables represent genomic risk factors for BrM development.

PMID:36001319 | DOI:10.1001/jamanetworkopen.2022.28083

JAMA Netw Open. 2022 Aug 1;5(8):e2228093. doi: 10.1001/jamanetworkopen.2022.28093.

ABSTRACT

IMPORTANCE: Hypertensive disorders of pregnancy are leading causes of morbidity and mortality among pregnant individuals as well as newborns, with increasing incidence during the past decade. Understanding the individual associations of advancing age of pregnant individuals at delivery, more recent delivery year (period), and more recent birth year of pregnant individuals (cohort) with adverse trends in hypertensive disorders of pregnancy could help guide public health efforts to improve the health of pregnant individuals.

OBJECTIVE: To clarify the independent associations of delivery year and birth year of pregnant individuals, independent of age of pregnant individuals, with incident rates of hypertensive disorders of pregnancy.

DESIGN, SETTING, AND PARTICIPANTS: This serial cross-sectional study of 38 141 561 nulliparous individuals aged 15 to 44 years with a singleton, live birth used 1995-2019 natality data from the National Vital Statistics System.

EXPOSURES: Year of delivery (period) and birth year (cohort) of pregnant individuals.

MAIN OUTCOMES AND MEASURES: Rates of incident hypertensive disorders of pregnancy, defined as gestational hypertension, preeclampsia, or eclampsia, recorded on birth certificates. Generalized linear mixed models were used to calculate adjusted rate ratios (aRRs) comparing the incidence of hypertensive disorders of pregnancy in each delivery period (adjusted for age and cohort) and birth cohort (adjusted for age and period) with the baseline group as the reference for each. Analyses were additionally stratified by the self-reported racial and ethnic group of pregnant individuals.

RESULTS: Of 38 141 561 individuals, 20.2% were Hispanic, 0.8% were non-Hispanic American Indian or Alaska Native, 6.5% were non-Hispanic Asian or Pacific Islander, 13.9% were non-Hispanic Black, and 57.8% were non-Hispanic White. Among pregnant individuals who delivered in 2015 to 2019 compared with 1995 to 1999, the aRR for the incidence of hypertensive disorders of pregnancy was 1.59 (95% CI, 1.57-1.62), adjusted for age and cohort. Among pregnant individuals born in 1996 to 2004 compared with 1951 to 1959, the aRR for the incidence of hypertensive disorders of pregnancy was 2.61 (95% CI, 2.41-2.84), adjusted for age and period. The incidence was higher among self-identified non-Hispanic Black individuals in each birth cohort, with similar relative changes for period (aRR, 1.76 [95% CI, 1.70-1.81]) and cohort (aRR, 3.26 [95% CI, 2.72-3.91]) compared with non-Hispanic White individuals (period: aRR, 1.60 [95% CI, 1.57-1.63]; cohort: aRR, 2.53 [95% CI, 2.26-2.83]).

CONCLUSIONS AND RELEVANCE: This cross-sectional study suggests that more recent birth cohorts of pregnant individuals have experienced a doubling of rates of hypertensive disorders of pregnancy, even after adjustment for age and delivery period. Substantial racial and ethnic disparities persisted across generations.

PMID:36001318 | DOI:10.1001/jamanetworkopen.2022.28093

JAMA Netw Open. 2022 Aug 1;5(8):e2228544. doi: 10.1001/jamanetworkopen.2022.28544.

ABSTRACT

IMPORTANCE: Although numerous studies have shown an association between alcohol consumption and cancer, how changes in drinking behavior increase or decrease the incidence of cancer is not well understood.

OBJECTIVE: To investigate the association between the reduction, cessation, or increase of alcohol consumption and the development of alcohol-related cancers and all cancers.

DESIGN, SETTING, AND PARTICIPANTS: This population-based cohort study analyzed adult beneficiaries in the Korean National Health Insurance Service. Participants (aged ≥40 years) included those who underwent a national health screening in both 2009 and 2011 and had available data on their drinking status. Data were analyzed from April 16 to July 6, 2020.

EXPOSURES: Alcohol consumption level, which was self-reported by participants in health screening questionnaires, was categorized into none (0 g/d), mild (<15 g/d), moderate (15-29.9 g/d), and heavy (≥30 g/d) drinking. Based on changes in alcohol consumption level from 2009 to 2011, participants were categorized into the following groups: nondrinker, sustainer, increaser, quitter, and reducer.

MAIN OUTCOMES AND MEASURES: The primary outcome was newly diagnosed alcohol-related cancers (including cancers of the head and neck, esophagus, colorectum, liver, larynx, and female breast), and the secondary outcome was all newly diagnosed cancers (except for thyroid cancer).

RESULTS: Among the 4 513 746 participants (mean [SD] age, 53.6 [9.6] years; 2 324 172 [51.5%] men), the incidence rate of cancer was 7.7 per 1000 person-years during a median (IQR) follow-up of 6.4 (6.1-6.6) years. Compared with the sustainer groups at each drinking level, the increaser groups had a higher risk of alcohol-related cancers and all cancers. The increased alcohol-related cancer incidence was associated with dose; those who changed from nondrinking to mild (adjusted hazard ratio [aHR], 1.03; 95% CI, 1.00-1.06), moderate (aHR, 1.10; 95% CI, 1.02-1.18), or heavy (aHR, 1.34; 95% CI, 1.23-1.45) drinking levels had an associated higher risk than those who did not drink. Those with mild drinking levels who quit drinking had a lower risk of alcohol-related cancer (aHR, 0.96; 95% CI, 0.92-0.99) than those who sustained their drinking levels. Those with moderate (aHR, 1.07; 95% CI, 1.03-1.12) or heavy (aHR, 1.07; 95% CI, 1.02-1.12) drinking levels who quit drinking had a higher all cancer incidence than those who sustained their levels, but when quitting was sustained, this increase in risk disappeared. Compared with sustained heavy drinking, reduced heavy drinking levels to moderate levels (alcohol-related cancer: aHR, 0.91 [95% CI, 0.86-0.97]; all cancers: aHR, 0.96 [95% CI, 0.92-0.99]) or mild levels (alcohol-related cancer: aHR, 0.92 [95% CI, 0.86-0.98]; all cancers: aHR, 0.92 [95% CI, 0.89-0.96]) were associated with decreased cancer risk.

CONCLUSIONS AND RELEVANCE: Results of this study showed that increased alcohol consumption was associated with higher risks for alcohol-related and all cancers, whereas sustained quitting and reduced drinking were associated with lower risks of alcohol-related and all cancers. Alcohol cessation and reduction should be reinforced for the prevention of cancer.

PMID:36001313 | DOI:10.1001/jamanetworkopen.2022.28544

Pediatr Emerg Care. 2022 Aug 23. doi: 10.1097/PEC.0000000000002833. Online ahead of print.

ABSTRACT

OBJECTIVES: Removal of nasal foreign bodies in children should be completed as few numbers of times as possible to reduce the burden on the child. This study aimed to reveal the characteristics of pediatric nasal foreign body cases that required multiple removal procedure and to investigate the appropriate removal method for each shape of foreign body.

METHODS: We retrospectively reviewed patients who visited a pediatric emergency department because of nasal foreign body from November 1, 2018, to October 31, 2020. We compared the characteristics of patients, foreign bodies, and treatment between the success and failure groups in the first removal procedure. Moreover, we described the detail of patients in the failure group. We also showed final successful removal methods according to the shape of the foreign bodies.

RESULTS: We included 104 children in our analysis. Between the success and failure groups in the first removal procedure, there was no statistically significant difference in the characteristics of patients and foreign bodies but a significant difference in the removal method (P < 0.001). In the failure groups, the most frequent number of times required for removal is 2 and the most common methods in the first removal procedure was the parent’s kiss, most of which were performed on spherical foreign bodies in younger children, Finally, only 7 cases (6.7%) failed to remove the foreign body. According to the shape of the foreign bodies, the percentage of forceps and clamps used for successful removal was high in every shape.

CONCLUSIONS: There was a significant difference in the removal method between the success and failure groups in the first removal procedure, but finally, most foreign bodies were removed by emergency physicians. Therefore, further research is needed to determine the appropriate removal method for each patient and foreign body.

PMID:36001298 | DOI:10.1097/PEC.0000000000002833

Sports Med. 2022 Aug 24. doi: 10.1007/s40279-022-01752-6. Online ahead of print.

ABSTRACT

BACKGROUND: The measurement of physical fitness has a history that dates back nearly 200 years. Recently, there has been an increase in international research and surveillance on physical fitness creating a need for setting international priorities that could help guide future efforts.

OBJECTIVE: This study aimed to produce a list of the top 10 international priorities for research and surveillance on physical fitness among children and adolescents.

METHODS: Using a twin-panel Delphi method, two independent panels consisting of 46 international experts were identified (panel 1 = 28, panel 2 = 18). The panel participants were asked to list up to five priorities for research or surveillance (round 1), and then rated the items from their own panel on a 5-point Likert scale of importance (round 2). In round 3, experts were asked to rate the priorities identified by the other panel.

RESULTS: There was strong between-panel agreement (panel 1: r_s = 0.76, p < 0.01; panel 2: r_s = 0.77, p < 0.01) in the priorities identified. The list of the final top 10 priorities included (i) “conduct longitudinal studies to assess changes in fitness and associations with health”. This was followed by (ii) “use fitness surveillance to inform decision making”, and (iii) “implement regular and consistent international/national fitness surveys using common measures”.

CONCLUSIONS: The priorities identified in this study provide guidance for future international collaborations and research efforts on the physical fitness of children and adolescents over the next decade and beyond.

PMID:36001291 | DOI:10.1007/s40279-022-01752-6

Pharmacol Rep. 2022 Aug 24. doi: 10.1007/s43440-022-00408-6. Online ahead of print.

ABSTRACT

BACKGROUND: The real-world effectiveness of molnupiravir (MOL) during the dominance of Omicron SARS-CoV-2 lineage is urgently needed since the available data relate to the period of circulation of other viral variants. Therefore, this study assessed the efficacy of MOL in patients hospitalized for COVID-19 in a real-world clinical practice during the wave of Omicron infections.

METHODS: Among 11,822 patients hospitalized after 1 March 2020 and included in the SARSTer national database, 590 were treated between 1 January and 31 April 2022, a period of dominance of the Omicron SARS-CoV-2 variant. MOL was administered to 203 patients, whereas 387 did not receive any antiviral regimen. Both groups were similar in terms of sex, BMI and age allowing for direct comparisons.

RESULTS: Patients who did not receive antiviral therapy significantly more often required the use of Dexamethasone and Baricitinib. Treatment with MOL resulted in a statistically significant reduction in mortality during the 28-day follow-up (9.9 vs. 16.3%), which was particularly evident in the population of patients over 80 years of age treated in the first 5 days of the disease (14.6 vs. 35.2%). MOL therapy did not affect the frequency of the need for mechanical ventilation, but patients treated with MOL required oxygen supplementation less frequently than those without antivirals (31.7 vs. 49.2%). The time of hospitalization did not differ between groups.

CONCLUSIONS: The use of molnupiravir in patients hospitalized for COVID-19 during the dominance of Omicron variant reduced mortality. This effect is particularly evident in patients over 80 years of age.

PMID:36001284 | DOI:10.1007/s43440-022-00408-6

J Ultrasound. 2022 Aug 24. doi: 10.1007/s40477-022-00710-2. Online ahead of print.

ABSTRACT

AIMS: Current ultrasound (US) Doppler techniques cannot demonstrate the vascularization of the dermis. The purpose of this study was to investigate whether the new Superb Vascular Imaging (SMI) and Microvascular Flow (MV-Flow) techniques improve the detection of normal dermis vessels. SMI and MV-Flow were compared side-by-side to conventional power-Doppler (PD) imaging.

METHODS: By using US, 50 healthy volunteers were evaluated at level of five body areas: forehead, forearm, palm, buttock, and thigh. Two off-site operators evaluated the images to assess the difference between SMI and PD imaging and between MV-Flow and PD imaging in terms of dermis flow amount. A 0-3 scoring system was adopted.

RESULTS: SMI scored grade 0 in 0% of body areas, grade 1 in 58%, grade 2 in 33%, and grade 3 in 9%. In comparison with SMI, PD scored grade 0 in 38% of body areas, grade 1 in 56%, grade 2 in 6%, and grade 3 in 0%. MV-Flow scored grade 0 in 0% of body areas, grade 1 in 52%, grade 2 in 43%, and grade 3 in 6%. Comparted to MV-Flow, PD scored grade 0 in 53% of body areas, grade 1 in 34%, grade 2 in 13%, and grade 3 in 0%. The difference in terms of sensitivity was statistically significant for all the body areas investigated.

CONCLUSIONS: We found both SMI and MV-Flow to be superior to PD imaging and capable to demonstrate normal vascularization of the dermis.

PMID:36001281 | DOI:10.1007/s40477-022-00710-2

Breast Cancer. 2022 Aug 24. doi: 10.1007/s12282-022-01396-4. Online ahead of print.

ABSTRACT

BACKGROUND: It remains unclear whether original full-field digital mammograms (DMs) can be replaced with synthesized mammograms in both screening and diagnostic settings. To compare reader performance of artificial intelligence computer-aided detection synthesized mammograms (AI CAD SMs) with that of DM alone or in combination with digital breast tomosynthesis (DBT) images in an experimental setting.

METHODS: We compared the performance of multireader (n = 4) and reading multicase (n = 388), in 84 cancers, 83 biopsy-proven benign lesions, and 221 normal or benign cases with negative results after 1-year follow-up. Each reading was independently interpreted with four reading modes: DM, AI CAD SM, DM + DBT, and AI CAD SM + DBT. The accuracy of probability of malignancy (POM) and five-category ratings were evaluated using areas under the receiver operating characteristic curve (AUC) in the random-reader analysis.

RESULTS: The mean AUC values based on POM for DM, AI CAD SM, DM + DBT, and AI CAD SM + DBT were 0.871, 0.902, 0.895, and 0.909, respectively. The mean AUC of AI CAD SM was significantly higher (P = 0.002) than that of DM. For calcification lesions, the sensitivity of SM and DM did not differ significantly (P = 0.204). The mean AUC for AI CAD SM + DBT was higher than that of DM + DBT (P = 0.082). ROC curves based on the five-category ratings showed similar proximity of the overall performance levels.

CONCLUSIONS: AI CAD SM alone was superior to DM alone. Also, AI CAD SM + DBT was superior to DM + DBT but not statistically significant.

PMID:36001270 | DOI:10.1007/s12282-022-01396-4

Int Urol Nephrol. 2022 Aug 24. doi: 10.1007/s11255-022-03342-x. Online ahead of print.

ABSTRACT

PURPOSE: Detrusor pressure-volume relationship evaluation by urodynamics provides useful clinical information; however, it is invasive, and requires specific installations. An alternative technique proposed by our research group is the electrical bioimpedance (BI) which is an easily performed and non-invasive method. In this work, we assess the relationship between BI and detrusor bladder pressure in adults with neurogenic lower urinary tract dysfunction.

METHODS: A prospective observational study was conducted. 20 patients (11 females and 9 male) previously diagnosed with neurogenic bladder were included. All participants underwent simultaneously a urodynamic evaluation (UDS) and BI determination, and both examination signals were recorded and subjected to Shapiro-Wilks statistical test. A correlational statistical test was used to compare the pressure parameters (detrusor, vesical and abdominal) with their respective BI determinations. Subsequently, a linear regression test was performed to evaluate the concordance between BI and their respective pressure values.

RESULTS: From the 20 correlations, between detrusor bladder pressure (PDET) and abdominal bioimpedance determinations (ZABD), obtained for all participants, 16 evidenced significant results over 90% (p < 0.05).

CONCLUSIONS: A significantly high correlation between abdominal bioimpedance determinations and the detrusor bladder pressures was evidenced. These results should be confirmed in a larger group of participants.

PMID:36001269 | DOI:10.1007/s11255-022-03342-x