Tag: statistics

Thorac Cancer. 2022 Oct 24. doi: 10.1111/1759-7714.14694. Online ahead of print.

ABSTRACT

BACKGROUND: The present study aimed to evaluate the performance of several machine learning (ML) algorithms in predicting 1-year afatinib continuation and 2-year survival after afatinib initiation and to identify the differences in survival outcomes between ML-classified strata.

METHODS: Data that were also used in the RESET study were retrospectively collected from 16 hospitals in South Korea. A stratified random sampling method was applied to split the data into training and test sets (70:30 split ratio). Clinical information, such as age, sex, tumor stage, smoking, performance status, metastasis, type of metastasis, dose adjustment, and pathologic information on EGFR mutations were inputted. Training was performed using eight ML algorithms: logistic regression, decision tree, deep neural network, random forest, support vector machine, boosting, bagging, and the naïve Bayes classifier. The model performance was assessed based on sensitivity, specificity, and accuracy. Area under the receiver operator characteristic curve (AUC) was calculated and compared between the ML models using DeLong’s test. A Kaplan-Meier (KM) curve was used to visualize the identified strata obtained from the ML models.

RESULTS: No significant differences in the input variables were observed between the training and test datasets. The best-performing models were support vector machine in predicting 1-year afatinib continuation (AUC 0.626) and decision tree in 2-year survival after afatinib start (AUC 0.644), although the performances of the ML models were comparable and did not display any predictive roles. KM analysis and log-rank test revealed significant differences between the strata identified from the ML model (p < 0.001) in terms of both time-on-treatment (TOT) and overall survival (OS).

CONCLUSION: The performances of ML models in our study found no discernible roles in predicting afatinib-related outcomes, although the identified strata revealed different TOT and OS in the KM analysis. This implies the strength of ML in predicting the survival outcome, as well as the limitation of electronic medical record-based variables in ML algorithms. Careful consideration of variable inclusion is likely to improve the general model performance.

PMID:36278315 | DOI:10.1111/1759-7714.14694

Int J Clin Pharmacol Ther. 2022 Oct 24. doi: 10.5414/CP204257. Online ahead of print.

ABSTRACT

OBJECTIVE: Theracurmin, which contains the curcumin composition, CR-033P, has been demonstrated to be highly bioavailable. To compare the pharmacokinetics of the three compositions, CR-033P, CR-043P using modified starch as an alternative to the dispersant gum ghatti used in the CR-033P, and TS-P1 containing the newly developed amorphous curcumin, a randomized double-blind crossover study (3-way, 3-period) was conducted.

MATERIALS AND METHODS: A single dose of the curcumin capsules (TS-P1 45 mg, CR-033P 90 mg, and CR-043P 90 mg) was administered to healthy adult participants. Blood sampling was performed 24 hours after capsule administration, and the plasma concentration of total curcumin was determined using high-performance liquid chromatography coupled with tandem mass spectrometry.

RESULTS: TS-P1 and CR-043P tended to have a slightly lower area under the concentration time curve (AUC) _0-24h than CR-033P, while TS-P1 displayed bioequivalence to CR-043P. Further, TS-P1 displayed bioequivalence to CR-033P in terms of AUC_0-12h, while that of CR-043P tended to be lower than that of CR-033P. TS-P1 had a higher AUC_0-12h than CR-043P. A statistically significant difference (p < 0.001) was found between the preparations in terms of C_max. TS-P1 tended to have a higher C_max than CR-033P, CR-043P tended to have a slightly lower C_max than CR-033P, and TS-P1 tended to have a higher C_max than CR-043P.

CONCLUSION: The newly developed TS-P1 composition seemed to display similar curcumin systemic exposure except for a higher plasma concentration than the CR-033P composition. Further, only a few significant differences were found between CR-043P and CR-033P.

PMID:36278294 | DOI:10.5414/CP204257

Int J Health Serv. 2022 Oct 22:207314221134038. doi: 10.1177/00207314221134038. Online ahead of print.

ABSTRACT

Many of the simple and low-cost child diarrhea morbidities interventions, such as adequate home care, access to health care services, and improved sanitation and hygiene practices, are far beyond the reach of many households in developing countries, and Namibia is not an exception to this. In this study, a quantitative cross-sectional study design using a multivariable log-binomial model was used to examine the effect of household demographic characteristics on diarrhea morbidity in children aged zero to 48 months using data collected from the 2013 Namibia Demographic and Health Survey. Household demographic characteristics such as household’s wealth index and main language spoken at home had lower risks on child diarrhea morbidity, while characteristics such as age of household head, toilet facilities shared with other households, current age of child, residency of the child, and child vaccination status had higher risks. The Namibian government, together with nongovernmental organizations, should make necessary vaccines interventions compulsory to prevent diarrheal diseases during the first few years of the child’s life and continuously enhance initiatives that invest in good sanitation and hygiene infrastructure within Rukwangali- and Lozi-speaking communities in the country.

PMID:36278288 | DOI:10.1177/00207314221134038

Korean J Intern Med. 2022 Oct 25. doi: 10.3904/kjim.2022.007. Online ahead of print.

ABSTRACT

BACKGROUND/AIMS: The concentration of serum ferritin, a storage form of iron, may be associated with carcinogenesis in various cancers. There are only limited studies on the relationship between serum ferritin levels and colorectal cancer (CRC) risk, especially in the Asian population. This study aimed to analyze the association between CRC incidence and serum ferritin levels.

METHODS: This was a national cohort study that used health checkup and insurance claims data of the Korean population. CRC incidence according to the serum ferritin level was analyzed during 2008-2018 in 17,116 participants.

RESULTS: The hazard ratio (HR) of CRC incidence decreased as serum ferritin levels increased (Q1: HR, 1.000 [95% confidence interval [CI], reference]; Q2: HR, 0.811 [95% CI, 0.558 to 1.178]; Q3: HR, 0.654 [95% CI, 0.442 to 0.968]; Q4: HR, 0.443 [95% CI, 0.285 to 0.687]; p = 0.0026). In subgroup analysis, 40 to 64 years of age, sex, body mass index of < 25 kg/ m2, presence of metabolic syndrome, absence of diabetes mellitus, and absence of anemia had HRs of < 0.5 (95% CI) in the highest quartiles compared with that in the lowest quartiles.

CONCLUSIONS: This study shows an inverse association between serum ferritin and CRC risk. Serum ferritin measurement can aid in identifying young adults requiring active CRC screening.

PMID:36278251 | DOI:10.3904/kjim.2022.007

J Agrar Chang. 2022 Oct;22(4):831-854. doi: 10.1111/joac.12497. Epub 2022 May 31.

ABSTRACT

Agricultural extensification refers to an expansive, low-input production strategy that is land rather than labour limited. Here, we present a robust method, using the archaeological proxies of cereal grain nitrogen isotope values and settlement size, to investigate the relationship between agricultural intensity and population size at Neolithic to Bronze/Iron Age settlement sites in northern Mesopotamia, the Aegean and south-west Germany. We conclude that urban form-in particular, density of occupation-as well as scale shaped the agroecological trajectories of early cities. Whereas high-density urbanism in northern Mesopotamia and the Aegean entailed radical agricultural extensification, lower density urbanism in south-west Germany afforded more intensive management of arable land. We relate these differing agricultural trajectories to long-term urban growth/collapse cycles in northern Mesopotamia and the Aegean, on the one hand, and to the volatility of early Iron Age elite power structures and urban centralization in south-west Germany, on the other.

PMID:36278250 | PMC:PMC9580239 | DOI:10.1111/joac.12497

Front Pharmacol. 2022 Oct 6;13:933519. doi: 10.3389/fphar.2022.933519. eCollection 2022.

ABSTRACT

Objective: To investigate the efficacy of Integrative medicine (IM), compare with Western medicine (WM), in the treatment of rheumatoid arthritis (RA) in a cohort study. Methods: This is a cohort study with recruitment of RA patients from 10 hospitals in China. The primary outcome was change in disease activity score 28 (DAS28) during 4 follow-up visits. Generalized estimating equation (GEE) models that controlled for variables were used to investigate a time trend and assess group differences in the primary outcome and secondary outcomes after propensity score matching (PSM). Results: A total of 3195 patients with RA received IM (n = 1379, 43.2%) or WM (n = 1816, 56.8%). Following 1:1 propensity score matching, 1,331 eligible patients prescribed IM were compared to 1,331 matched patients prescribed WM. The GEE analysis with PSM showed that the IM was more beneficial to significantly decrease the levels of VAS, PGA and PhGA (VAS: odds ratio (OR), 0.76; 95% CI, 0.63-0.92; p = 0.004; PGA: OR, 0.76; 95% CI, 0.64-0.92; p = 0.007; and PhGA: OR, 0.77; 95% CI, 0.64, 0.93; p = 0.004), and reduce DAS28 (OR, 0.84; 95% CI, 0.73-0.98; p = 0.030) in the per-protocol population. Conclusion: This study suggests that compare to WM, IM has advantages in improving RA-related outcomes. However, the statistical significance might not reveal significant clinical difference. Further studies should be focused on specific treatment strategies and/or disease stages.

PMID:36278204 | PMC:PMC9582451 | DOI:10.3389/fphar.2022.933519

Nat Commun. 2022 Oct 23;13(1):6311. doi: 10.1038/s41467-022-34024-y.

ABSTRACT

Bromodomain and extraterminal (BET) proteins including BRD4 play important roles in oncogenesis and immune inflammation. Here we demonstrate that cancer cells with loss of the retinoblastoma (RB) tumor suppressor became resistant to small molecule bromodomain inhibitors of BET proteins. We find that RB binds to bromodomain-1 (BD1) of BRD4, but binding is impeded by CDK4/6-mediated RB phosphorylation at serine-249/threonine-252 (S249/T252). ChIP-seq analysis shows RB knockdown increases BRD4 occupancy at genomic loci of genes enriched in cancer-related pathways including the GPCR-GNBIL-CREB axis. S249/T252-phosphorylated RB positively correlates with GNBIL protein level in prostate cancer patient samples. BET inhibitor resistance in RB-deficient cells is abolished by co-administration of CREB inhibitor. Our study identifies RB protein as a bona fide intrinsic inhibitor of BRD4 and demonstrates that RB inactivation confers resistance to small molecule BET inhibitors, thereby revealing a regulatory hub that converges RB upstream signaling onto BRD4 functions in diseases such as cancer.

PMID:36274096 | DOI:10.1038/s41467-022-34024-y

Cancer Rep (Hoboken). 2022 Oct 23:e1722. doi: 10.1002/cnr2.1722. Online ahead of print.

ABSTRACT

BACKGROUND: In Iran, the delay in diagnosis and treatment of breast cancer results in low survival rates.

AIM: It is essential to characterize new therapeutic targets and prognostic breast cancer biomarkers. The rising evidence suggested that long non-coding RNAs (lncRNAs) expression levels are deregulated in human cancers and can use as biomarkers for the rapid diagnosis of breast cancer.

METHODS: In the present study, a quantitative real-time polymerase chain reaction (qRT-PCR) technique was used to measure 20 oncogenic and tumor suppressor lncRNAs expression levels in whole blood samples of female breast cancer patients and healthy women. Receiver operating characteristic curve (ROC) was used to assess the diagnostic value of each selected lncRNA as a biomarker.

RESULTS: The results revealed that some circulating lncRNAs (MEG3, NBAT1, NKILA, GAS5, EPB41L4A-AS2, Z38, and BC040587) were significantly down-regulated in breast cancer patients compared to healthy women. In contrast, other circulating lncRNAs (H19, SPRY4-IT1, XIST, UCA1, AC026904.1, CCAT1, CCAT2, ITGB2-AS, and AK058003) were significantly up-regulated in breast cancer patients compared to controls. It was shown that the expression levels of NKILA, and NBAT1 lncRNAs were related to tumor size, and BC040587 expression level related to age, node metastasis, tumor size, and grade (p < .05). The association between H19 and SPRY4-IT1 lncRNAs with HER-2 was confirmed statistically (p < .05). ROC curves illustrated that the blood levels of SPRY4-IT1, XIST, and H19 lncRNAs have excellent potential in discriminating breast cancer from the healthy controls, showing an AUC of 1.0 (95% CI 1.0-1.0, p = .00), 0.898 (95% CI 0.815-0.981, p = .00), and 0.848 (95% CI 0.701-0.995, p = .01), respectively.

CONCLUSION: In conclusion, the expression levels of circulating H19 and SPRY4-IT1 lncRNAs in breast cancer patients could consider as the prognostic biomarkers and therapeutic targets in breast cancer, because of their excellent power in discriminating breast cancer from healthy individuals and the significant correlation of H19, and SPRY4-IT1 lncRNAs with clinicopathological traits. We also suggest the possible application of BC040587 lncRNA as a diagnostic and prognostic indicator to assess tumor progression in case of verification in larger patients’ cohorts.

PMID:36274054 | DOI:10.1002/cnr2.1722

Enferm Infecc Microbiol Clin (Engl Ed). 2022 Oct 20:S2529-993X(22)00198-8. doi: 10.1016/j.eimce.2022.03.014. Online ahead of print.

ABSTRACT

INTRODUCTION: Congenital citomegalovirus (CMVc) infection is more common in children exposed to HIV during pregnancy, with reported rates in pre-ART era from 2 to 7%. The use of combined antiretroviral treatment (ARTc) could be a determining factor in reducing this risk of CMV transmission. The aim of this study was to describe the epidemiology of CMVc infection in newborns of HIV-infected mothers at Hospital Universitario 12 de Octubre, Madrid, Spain, from 2000 to 2017.

MATERIAL AND METHODS: An observational and retrospective study was carried out. Epidemiological and clinical variables were collected. Statistical analysis was performed with the SPSS 24.0 computer program.

RESULTS: 288 mother-infant pairs were included in the study. We observed a CMVc rate of 2.1% (95% CI 0.9-4.9).

CONCLUSIONS: The rate of CMVc in HIV-exposed children observed was lower than that reported in pre-ARTc era but seems higher than those described in general population.

PMID:36274043 | DOI:10.1016/j.eimce.2022.03.014

J Med Imaging Radiat Sci. 2022 Oct 20:S1939-8654(22)00374-5. doi: 10.1016/j.jmir.2022.09.023. Online ahead of print.

ABSTRACT

INTRODUCTION: Undetected femoroacetabular impingement (FAI), caused by asphericity of the femoral head, has been implicated as a leading cause of hip osteoarthritis in later stages. Two known types of impingement of the femur head with the acetabulum include the cam-type and pincer type, and the alpha angle and triangular index are indices applied in determining the presence of FAI in a hip radiograph.

OBJECTIVE: To determine the normal range and upper limit of normal of the alpha angle and triangular index of an African population using non-pathological hip radiographs.

MATERIALS AND METHODS: Hip radiographs of 104 subjects reported to be normal were retrospectively studied. The images were reassessed jointly by three radiographers and afterwards by three consultant radiologists. The alpha angle and triangular index of selected radiographs were measured with appropriate electronic callipers. Values obtained were correlated with the age and gender of the patients.

RESULTS: The mean ± SD of the alpha angle for the population studied was 46.70 ± 12.34⁰ with a range of 33.30⁰-96.82⁰ (males: 45.09 ± 12.03⁰, females: 47.32 ± 12.37⁰), and the upper limit of normal obtained was 79.16⁰. The mean triangular index was 1.71±1.38 with a range of 0.03-5.98 (males: 1.77 ± 1.39, females: 1.65 ± 1.36), 4.12 being the upper limit of normal. There was no statistically significant difference between measurements of both indices with age and gender. However, there was excellent agreement between and within raters for both measurements (alpha angle: 0.992; triangular index: 0.924).

CONCLUSION: The upper limits of normal for the alpha angle and triangular index of the studied population are 79.16⁰ and 4.12. Age and gender were independent of the values measured, and the measurements demonstrated excellent inter-rater and intra-rater agreement. A normal range is thus provided, with upper limits beyond which a possible femoroacetabular impingement may be diagnosed.

PMID:36274033 | DOI:10.1016/j.jmir.2022.09.023