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Nevin Manimala Statistics

Clinical use of the mRNA urinary biomarker SelectMDx test for prostate cancer

Prostate Cancer Prostatic Dis. 2022 Jul 9. doi: 10.1038/s41391-022-00562-1. Online ahead of print.

ABSTRACT

BACKGROUND: Molecular biomarker tests are developed as diagnostic tools for prostate cancer (PCa) diagnosis. The SelectMDx (MDxHealth, Nijmegen, The Netherlands) test is a urinary-based biomarker test intended to be used to predict presence of high-grade PCa upon biopsy in men with elevated serum prostate-specific antigen (PSA) levels. Previous validation of the SelectMDx test revealed that 53% of the unnecessary biopsies (biopsies indicating no- or GG1 PCa) could be avoided using the SelectMDx test as a decision-tool to select men for prostate biopsy. The objective of this study is to examine the use of the commercially available SelectMDx test under routine, real-life practice.

METHODS: Men that underwent a SelectMDx test between May 2019 and December 2020 and that were originating from countries that perform the SelectMDx test on a regular basis were included in this study, resulting in 5157 cases from 10 European countries. Clinical parameters, urinary RNA scores, and test outcomes were compared between PSA groups, age groups, countries, and the validation cohort (described previously [4]) using the Mann-Whitney U test, Chi-Square test, Benjamini-Hochberg and Kruskal-Wallis tests.

RESULTS: 40.72% of the cases received a negative SelectMDx result. The test is also used in patients outside the intended-use population (PSA < 3 and >10 ng/mL). Clinical parameters (age, PSA density, DRE outcome) varied between patient population from individual countries and the validation cohort, resulting in differences in the potential number of saved biopsies using the test.

CONCLUSIONS: The potential number of reduced biopsies in clinical use was 40,72% using the SelectMDx test, assuming a negative SelectMDx test resulted in the decision not to biopsy the patient. This is higher compared to the validation cohort, which is explained by differences in patient population.

PMID:35810263 | DOI:10.1038/s41391-022-00562-1

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Nevin Manimala Statistics

Positive effects of training curriculum using the example of the interdisciplinary intensive care unit

Med Klin Intensivmed Notfmed. 2022 Jul 9. doi: 10.1007/s00063-022-00938-0. Online ahead of print.

ABSTRACT

The training of new medical colleagues in hospitals is due to various aspects such as for instance staff shortages and time pressure often very challenging for everyone involved. Using the example of the interdisciplinary intensive care unit, the positive effects of a structured training curriculum have been scientifically proven in regular employee surveys. There was a statistically significant increase in satisfaction in the quality of induction (p < 0.0001), quality of training (p < 0.0001), preparation for night shifts in the intensive care unit (p < 0.0001) and an improvement in general satisfaction in the clinic (p < 0.003) can also be shown. For these reasons, such curriculum contributes to increasing the quality of care and patient safety as well as the safety of medical staff in the medical work.

PMID:35810250 | DOI:10.1007/s00063-022-00938-0

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Nevin Manimala Statistics

Neonatal abstinence syndrome: Effectiveness of targeted umbilical cord drug screening

J Perinatol. 2022 Jul 9. doi: 10.1038/s41372-022-01457-8. Online ahead of print.

ABSTRACT

OBJECTIVE: This study sought to determine if targeted drug screening of newborns was effective in identifying a positive drug test result.

STUDY DESIGN: This was a retrospective cross-sectional study. A total of 340 infants met criteria for drug screening. Sensitivity and specificity were used to evaluate each of the potential risk factors in terms of their ability to predict a positive drug test result. Two-sample t-tests were used to compare differences in Finnegan scores between babies with a positive drug test result and those with a negative one.

RESULT: The risk factor with the highest sensitivity was maternal history of drug use. The difference in the Finnegan scores between groups was statistically significant.

CONCLUSION: The risk factors associated with this study were not very sensitive. The only way to identify all infants at risk of NAS is to standardize the screening process and apply to all infants.

PMID:35810246 | DOI:10.1038/s41372-022-01457-8

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Nevin Manimala Statistics

Does Residual Cancer Burden Predict Local Recurrence After Neoadjuvant Chemotherapy?

Ann Surg Oncol. 2022 Jul 9. doi: 10.1245/s10434-022-12038-6. Online ahead of print.

ABSTRACT

BACKGROUND: The extent of residual disease after neoadjuvant chemotherapy (NAC) can be quantified by the Residual Cancer Burden (RCB), a prognostic tool used to estimate survival outcomes in breast cancer. This study investigated the association between RCB and locoregional recurrence (LRR).

METHODS: The study reviewed 532 women with breast cancer who underwent NAC between 2010 and 2016. Relapse in the ipsilateral breast, skin/subcutis at the surgical site, chest wall, pectoralis, or regional lymph nodes defined an LRR. The LRR cumulative incidence (LRCI) was estimated using the Fine and Gray competing-risks model, with death and distant recurrence defined as competing events. The association of LRCI with prognostic variables was evaluated.

RESULTS: Overall, 5.5% of the patients experienced an LRR after a median follow-up period of 65 months. The 5-year LRCI rates by RCB were as follows: RCB-0 (0.9%), RCB-1 (3.2%), RCB-2 (6.0%), and RCB-3 (12.9%). In the univariable analysis, LRCI varied significantly by RCB (p = 0.010). The multivariable analysis showed a significant association of LRCI with increasing RCB, and the patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) phenotype were at lower risk for LRR than those with HER2+ and triple-negative cancers (p < 0.032). The patients with RCB-3 were at a higher risk for local relapse than those with RCB-0 (hazard ratio, 13.78; confidence interval, 2.25-84.45; p = 0.04). Type of operation (p = 0.04) and use of adjuvant radiation (p = 0.046) were statistically significant in the multivariable model.

CONCLUSIONS: The study results demonstrate a significant association between LRCI and increasing RCB, although distant recurrence is a substantial driver of disease outcomes. Future prospective studies should examine the role of RCB in clinical decisions regarding indications for adjuvant therapy.

PMID:35810226 | DOI:10.1245/s10434-022-12038-6

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Nevin Manimala Statistics

A convolutional neural network model for survival prediction based on prognosis-related cascaded Wx feature selection

Lab Invest. 2022 Jul 9. doi: 10.1038/s41374-022-00801-y. Online ahead of print.

ABSTRACT

Great advances in deep learning have provided effective solutions for prediction tasks in the biomedical field. However, accurate prognosis prediction using cancer genomics data remains challenging due to the severe overfitting problem caused by curse of dimensionality inherent to high-throughput sequencing data. Moreover, there are unique challenges to perform survival analysis, arising from the difficulty in utilizing censored samples whose events of interest are not observed. Convolutional neural network (CNN) models provide us the opportunity to extract meaningful hierarchical features to characterize cancer subtype and prognosis outcomes. On the other hand, feature selection can mitigate overfitting and reduce subsequent model training computation burden by screening out significant genes from redundant genes. To accomplish model simplification, we developed a concise and efficient survival analysis model, named CNN-Cox model, which combines a special CNN framework with prognosis-related feature selection cascaded Wx, with the advantage of less computation demand utilizing light training parameters. Experiment results show that CNN-Cox model achieved consistent higher C-index values and better survival prediction performance across seven cancer type datasets in The Cancer Genome Atlas cohort, including bladder carcinoma, head and neck squamous cell carcinoma, kidney renal cell carcinoma, brain low-grade glioma, lung adenocarcinoma (LUAD), lung squamous cell carcinoma, and skin cutaneous melanoma, compared with the existing state-of-the-art survival analysis methods. As an illustration of model interpretation, we examined potential prognostic gene signatures of LUAD dataset using the proposed CNN-Cox model. We conducted protein-protein interaction network analysis to identify potential prognostic genes and further analyzed the biological function of 13 hub genes, including ANLN, RACGAP1, KIF4A, KIF20A, KIF14, ASPM, CDK1, SPC25, NCAPG, MKI67, HJURP, EXO1, HMMR, whose high expression is significantly associated with poor survival of LUAD patients. These findings confirmed that CNN-Cox model is effective in extracting not only prognosis factors but also biologically meaningful gene features. The codes are available at the GitHub website: https://github.com/wangwangCCChen/CNN-Cox .

PMID:35810236 | DOI:10.1038/s41374-022-00801-y

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Nevin Manimala Statistics

Impact of Frailty on Short-Term Outcomes After Laparoscopic and Open Hepatectomy

World J Surg. 2022 Jul 9. doi: 10.1007/s00268-022-06648-0. Online ahead of print.

ABSTRACT

BACKGROUND: Although laparoscopic hepatectomy (LH) is associated with improved short-term outcomes compared to open hepatectomy (OH), it is unknown whether frail patients also benefit from LH. The aim of this study was to evaluate the impact of frailty on post-operative outcomes after LH and OH.

PATIENTS AND METHODS: Consecutive patients who underwent LH and OH between January 2011 and December 2018 were identified from a prospective database. Frailty was assessed using the modified Frailty Index (mFI), with patients scoring mFI ≥ 1 deemed to be frail.

RESULTS: Of 1826 patients, 34.7% (N = 634) were frail and 18.6% (N = 340) were elderly (≥ 75 years). Frail patients had significantly higher 90-day mortality (6.6% vs. 2.9%, p < 0.001) and post-operative complications (36.3% vs. 26.1%, p < 0.001) than those who were not frail, effects that were independent of patient age on multivariate analysis. For those undergoing minor resections, the benefits of LH vs. OH were similar for frail and non-frail patients. Length of hospital stay was 53% longer in OH (vs. LH) in frail patients, compared to 58% longer in the subgroup of non-frail patients.

CONCLUSIONS: Frailty is independently associated with inferior post-operative outcomes in patients undergoing hepatectomy. However, the benefits of laparoscopic (compared to open) hepatectomy are similar for frail and non-frail patients. Frailty should not be a contraindication to laparoscopic minor hepatectomy in carefully selected patients.

PMID:35810214 | DOI:10.1007/s00268-022-06648-0

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Nevin Manimala Statistics

Cartilage thickness and bone shape variations as a function of sex, height, body mass, and age in young adult knees

Sci Rep. 2022 Jul 9;12(1):11707. doi: 10.1038/s41598-022-15585-w.

ABSTRACT

The functional relationship between bone and cartilage is modulated by mechanical factors. Scarce data exist on the relationship between bone shape and the spatial distribution of cartilage thickness. The aim of the study was to characterise the coupled variation in knee bone morphology and cartilage thickness distributions in knees with healthy cartilage and investigate this relationship as a function of sex, height, body mass, and age. MR images of 51 knees from young adults (28.4 ± 4.1 years) were obtained from a previous study and used to train a statistical shape model of the femur, tibia, and patella and their cartilages. Five multiple linear regression models were fitted to characterise morphology as a function of sex, height, body mass, and age. A logistic regression classifier was fitted to characterise morphological differences between males and females, and tenfold cross-validation was performed to evaluate the models’ performance. Our results showed that cartilage thickness and its distribution were coupled to bone morphology. The first five shape modes captured over 90% of the variance and described coupled changes to the bone and spatial distribution of cartilage thickness. Mode 1 (size) was correlated to sex (p < 0.001) and height (p < 0.0001). Mode 2 (aspect ratio) was also correlated to sex (p = 0.006) and height (p = 0.017). Mode 4 (condylar depth) was correlated to sex only (p = 0.024). A logistic regression model trained on modes 1, 2, and 4 could classify sex with an accuracy of 92.2% (95% CI [81.1%, 97.8%]). No other modes were influenced by sex, height, body mass, or age. This study demonstrated the coupled relationship between bone and cartilage, showing that cartilage is thicker with increased bone size, diaphysis size, and decreased femoral skew. Our results show that sex and height influence bone shape and the spatial distribution of cartilage thickness in a healthy young adult population, but body mass and age do not.

PMID:35810204 | DOI:10.1038/s41598-022-15585-w

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Nevin Manimala Statistics

Identifying socio-ecological drivers of common cold in Bhutan: a national surveillance data analysis

Sci Rep. 2022 Jul 9;12(1):11716. doi: 10.1038/s41598-022-16069-7.

ABSTRACT

The common cold is a leading cause of morbidity and contributes significantly to the health costs in Bhutan. The study utilized multivariate Zero-inflated Poisson regression in a Bayesian framework to identify climatic variability and spatial and temporal patterns of the common cold in Bhutan. There were 2,480,509 notifications of common cold between 2010 and 2018. Children aged < 15 years were twice (95% credible interval [CrI] 2.2, 2.5) as likely to get common cold than adults, and males were 12.4% (95 CrI 5.5%, 18.7%) less likely to get common cold than females. A 10 mm increase in rainfall lagged one month, and each 1 °C increase of maximum temperature was associated with a 5.1% (95% CrI 4.2%, 6.1%) and 2.6% (95% CrI 2.3%, 2.8%) increase in the risk of cold respectively. An increase in elevation of 100 m and 1% increase in relative humidity lagged three months were associated with a decrease in risk of common cold by 0.1% (95% CrI 0.1%, 0.2%) and 0.3% (95% CrI 0.2%, 0.3%) respectively. Seasonality and spatial heterogeneity can partly be explained by the association of common cold to climatic variables. There was statistically significant residual clustering after accounting for covariates. The finding highlights the influence of climatic variables on common cold and suggests that prioritizing control strategies for acute respiratory infection program to subdistricts and times of the year when climatic variables are associated with common cold may be an effective strategy.

PMID:35810192 | DOI:10.1038/s41598-022-16069-7

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Nevin Manimala Statistics

Association between cord blood metabolites in tryptophan pathway and childhood risk of autism spectrum disorder and attention-deficit hyperactivity disorder

Transl Psychiatry. 2022 Jul 9;12(1):270. doi: 10.1038/s41398-022-01992-0.

ABSTRACT

Alterations in tryptophan and serotonin have been implicated in various mental disorders; but studies are limited on child neurodevelopmental disabilities such as autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD). This prospective cohort study examined the associations between levels of tryptophan and select metabolites (5-methoxytryptophol (5-MTX), 5-hydroxytryptophan (5-HTP), serotonin, N-acetyltrytophan) in cord plasma (collected at birth) and physician-diagnosed ASD, ADHD and other developmental disabilities (DD) in childhood. The study sample (n = 996) derived from the Boston Birth Cohort, which included 326 neurotypical children, 87 ASD, 269 ADHD, and 314 other DD children (mutually exclusive). These participants were enrolled at birth and followed-up prospectively (from October 1, 1998 to June 30, 2018) at the Boston Medical Center. Higher levels of cord 5-MTX was associated with a lower risk of ASD (aOR: 0.56, 95% CI: 0.41, 0.77) and ADHD (aOR: 0.79, 95% CI: 0.65, 0.96) per Z-score increase, after adjusting for potential confounders. Similarly, children with cord 5-MTX ≥ 25th percentile (vs. <25th percentile) had a reduction in ASD (aOR: 0.27, 95% CI: 0.14, 0.49) and ADHD risks (aOR: 0.45, 95% CI: 0.29, 0.70). In contrast, higher levels of cord tryptophan, 5-HTP and N-acetyltryptophan were associated with higher risk of ADHD, with aOR: 1.25, 95% CI: 1.03, 1.51; aOR: 1.32, 95% CI: 1.08, 1.61; and aOR: 1.27, 95% CI: 1.05, 1.53, respectively, but not with ASD and other DD. Cord serotonin was not associated with ASD, ADHD, and other DD. Most findings remained statistically significant in the sensitivity and subgroup analyses.

PMID:35810183 | DOI:10.1038/s41398-022-01992-0

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Nevin Manimala Statistics

Evaluation of water quality index and geochemical characteristics of surfacewater from Tawang India

Sci Rep. 2022 Jul 9;12(1):11698. doi: 10.1038/s41598-022-14760-3.

ABSTRACT

In this study,the water samples were collected from 31 sites of Tawang, Arunachal Pradesh, India (North-Eastern Himalaya), during the winter season to check the suitability of water for drinking and irrigation purposes.The study scientifically demonstrates the estimation of Water quality index (WQI) andhydrogeochemical characteristics of surface water samples by utilizing multivariate statistical methods. The main water quality parameters considered for this study were TDS, conductivity, salinity, pH, hardness, cations and anions. WQI was calculated in order to find out the deviation in the water quality parameters particularly with respect to BIS permissible limits.The major influencing factors responsible for the variation in these parameters were derived by using Principal component analysis (PCA) and Correlation matrix.To check the suitability of water for drinking purpose, hydrogeochemical facies and rock water interaction was derived by using well established methods such as Piper Plot (determine water type), WQI (Quality monitoring), and saturation index (for mineral dissolution). The results revealed that the silicate weathering was the main ionic source in comparison to carbonate weathering which is due to the higher dissolution capacity of silicate minerals.The results of the scattered plot between (Ca2+ + Mg2+)-(HCO3– + SO42-) versus (Na+ + K+)-Cl- (meq/L) highlighted thation exchange occurs between Mg2+ and Ca2+ofsurface water with Na+ and K+of rock /soil. This means that calcium ion was getting adsorbed, and sodium ion was getting released. The Ca2+-Mg2+-HCO3-, Na+-HCO3-and Na+-Cl- type of surface water suggested permanent and temporary hardness respectively in the studied region. The dominant cations of this study were Na+ and Ca2+ while the dominant anions were HCO3– and SO42-. In order to check the suitability of water sources for irrigation, parameters like, Magnesium hazard (MH), Total hardness (TH), Permeability Index (PI), Kelly Index (KI), Sodium adsorption rate (SAR), Sodium percentage (Na%), and Residual sodium carbonate (RSC) were determined. The results showed that 93% of the samples had PI score < 75, which indicates the suitability of the water for irrigation. Also the WQI calculation showed an average WQI value of 82.49, amongst which 61% samples were in the range of 0-50 being considered as good for drinking, while 39% were catageorised as unsuitable for drinking showing a value of > 50. Hence the above findings reveal that geogenic activities play a major role in influencing the water quality of Tawang region. Hence suitable water treatment technologies or methods might be used to eliminate thenon desirable elements and minerals present in surface water.

PMID:35810170 | DOI:10.1038/s41598-022-14760-3