Nevin Manimala

Mol Cancer. 2022 Sep 22;21(1):183. doi: 10.1186/s12943-022-01644-3.

ABSTRACT

BACKGROUND: Up to 80% of cases of prostate cancer present with multifocal independent tumour lesions leading to the concept of a field effect present in the normal prostate predisposing to cancer development. In the present study we applied Whole Genome DNA Sequencing (WGS) to a group of morphologically normal tissue (n = 51), including benign prostatic hyperplasia (BPH) and non-BPH samples, from men with and men without prostate cancer. We assess whether the observed genetic changes in morphologically normal tissue are linked to the development of cancer in the prostate.

RESULTS: Single nucleotide variants (P = 7.0 × 10^-03, Wilcoxon rank sum test) and small insertions and deletions (indels, P = 8.7 × 10^-06) were significantly higher in morphologically normal samples, including BPH, from men with prostate cancer compared to those without. The presence of subclonal expansions under selective pressure, supported by a high level of mutations, were significantly associated with samples from men with prostate cancer (P = 0.035, Fisher exact test). The clonal cell fraction of normal clones was always higher than the proportion of the prostate estimated as epithelial (P = 5.94 × 10^-05, paired Wilcoxon signed rank test) which, along with analysis of primary fibroblasts prepared from BPH specimens, suggests a stromal origin. Constructed phylogenies revealed lineages associated with benign tissue that were completely distinct from adjacent tumour clones, but a common lineage between BPH and non-BPH morphologically normal tissues was often observed. Compared to tumours, normal samples have significantly less single nucleotide variants (P = 3.72 × 10^-09, paired Wilcoxon signed rank test), have very few rearrangements and a complete lack of copy number alterations.

CONCLUSIONS: Cells within regions of morphologically normal tissue (both BPH and non-BPH) can expand under selective pressure by mechanisms that are distinct from those occurring in adjacent cancer, but that are allied to the presence of cancer. Expansions, which are probably stromal in origin, are characterised by lack of recurrent driver mutations, by almost complete absence of structural variants/copy number alterations, and mutational processes similar to malignant tissue. Our findings have implications for treatment (focal therapy) and early detection approaches.

PMID:36131292 | DOI:10.1186/s12943-022-01644-3

BMC Health Serv Res. 2022 Sep 21;22(1):1184. doi: 10.1186/s12913-022-08573-3.

ABSTRACT

INTRODUCTION: Prevalence of cancer patients is dramatically increasing. We aimed at quantifying the oncology workload generated by each new cancer patient in the two years following first consultation.

METHODS: In this record-based retrospective study, we retrieved data of all newly diagnosed patients treated at the Oncology Department of Udine Academic Hospital between 01.01.2012 and 31.12.2017. We calculated mean number and standard deviation of the activity type generated by each new cancer patient during the following 2 years.

RESULTS: Seven thousand four hundred fifty-two cancer patients generated a total of 85,338 clinical episodes. The two-years mean number of oncology episodes generated was 11.31 (i.e., for every 1,000 new cancer patients, 11,310 oncology activities are generated overall in the following two-year lapse). Patients with advanced disease generated the highest workload (24.3; SD 18.8) with a statistically significant difference compared to adjuvant and follow-up patients (p < 0.001). The workload generated in the period 0-6 and 0-12 months was significantly higher than in the following months (p < 0.001) and it was also higher for patients initially designated to treatment (p < 0.001).

CONCLUSION: This is the first study reporting on the mean oncology workload generated during the 2 years following first consultation. Workload is the highest for patient with advanced disease, especially in the first months and in patients in active treatment. A detailed analysis of workloads in oncology is feasible and could be crucial for planning a sustainable framework for cancer care in the next future.

PMID:36131286 | DOI:10.1186/s12913-022-08573-3

BMC Med Inform Decis Mak. 2022 Sep 21;22(1):246. doi: 10.1186/s12911-022-01983-7.

ABSTRACT

BACKGROUND: Optimal COVID-19 management is still undefined. In this complicated scenario, the construction of a computational model capable of extracting information from electronic medical records, correlating signs, symptoms and medical prescriptions, could improve patient management/prognosis.

METHODS: The aim of this study is to investigate the correlation between drug prescriptions and outcome in patients with COVID-19. We extracted data from 3674 medical records of hospitalized patients: drug prescriptions, outcome, and demographics. The outcome evaluated was hospital outcome. We applied correlation analysis using a Logistic Regression algorithm for machine learning with Lasso and Matthews correlation coefficient.

RESULTS: We found correlations between drugs and patient outcomes (death/discharged alive). Anticoagulants, used very frequently during all phases of the disease, were associated with good prognosis only after the first week of symptoms. Antibiotics very frequently prescribed, especially early, were not correlated with outcome, suggesting that bacterial infections may not be important in determining prognosis. There were no differences between age groups.

CONCLUSIONS: In conclusion, we achieved an important result in the area of Artificial Intelligence, as we were able to establish a correlation between concrete variables in a real and extremely complex environment of clinical data from COVID-19. Our results are an initial and promising contribution in decision-making and real-time environments to support resource management and forecasting prognosis of patients with COVID-19.

PMID:36131274 | DOI:10.1186/s12911-022-01983-7

BMC Public Health. 2022 Sep 21;22(1):1790. doi: 10.1186/s12889-022-14161-1.

ABSTRACT

BACKGROUND: Sufficient sleep is important to an individual’s health and well-being, but also for school achievement among adolescents. This study investigates the associations between sleepiness, sleep deficits, and school achievements among adolescents.

METHODS: This trend study involved a representative sample of Norwegian adolescents based on the “Trends in International Mathematics and Science Study” (TIMSS), N = 4499 (2015) and N = 4685 (2019) and their teachers. The students were 9th graders from a Norwegian compulsory secondary school. The survey included questions on students’ sleepiness as students reported in 2019 and sleep deficits among students that limited teaching in class as their teachers reported in 2015 and 2019. Regression, triangulation, and mediation analyses were used. Mplus was used to perform the statistical analyses.

RESULTS: The results revealed significant negative associations between sleep deficits and school achievements, adjusted for gender, socioeconomic status (SES), and minority status among Norwegian 9th graders. These results were found for both mathematics and science achievements in 2015 and 2019. Sleepiness that the students reported was negatively associated with school achievements in 2019. Trend and mediation analyses showed that sleep deficits explained 18 and 11% of the decrease in mathematics and science achievements, respectively, from 2015 to 2019.

CONCLUSIONS: Sleep deficits were associated with school achievements in mathematics and science among Norwegian 9th graders. Mediation analyses revealed that sleep deficits explained a significant part of the decline in academic achievements. Insufficient sleep may have negative public health implications and influence adolescents’ academic achievements and competences, and should therefore be discussed in both the educational and health systems.

PMID:36131267 | DOI:10.1186/s12889-022-14161-1

BMC Psychiatry. 2022 Sep 21;22(1):622. doi: 10.1186/s12888-022-04262-x.

ABSTRACT

BACKGROUND: The symptoms and outcomes of depressed mood are considered severe social issues among Korean adolescents. However, it is difficult to detect depressed mood and evaluate the factors associated with suicide among such individuals. Identifying the risk factors of depressed mood would allow for improved perspectives for interventions. Therefore, in this study, we investigated the association between sedentary behavior and the prevalence of depressed mood.

METHODS: From 2014 to 2020, the Korea Youth Risk Behavior Survey (KYRBS), which is a web-based self-report survey, was used for analysis. A total of 366,405 individuals participated in this study. Sedentary behavior was divided into 3 groups based on the duration of sedentary behavior: low sedentary time group (LS, 25 percentile), middle sedentary time group (MS, from 25 to 75 percentile, reference), and high sedentary time group (HS, above 75 percentile). Further, sedentary behavior is divided into 4 subgroups based on weekdays or weekends and owing to studying or non-studying. The chi-square test and multivariate logistic regression were used in this study.

RESULTS: Compared to the MS, which is the reference, male participants in both the LS and HS had experienced depressed mood (adjusted odds ratio (OR): 1.035, 95% CI = 1.003-1.068 in the LS, adjusted OR: 1.091, CI = 1.055-1.129 in the HS). Among females, only the HS was statistically significant (adjusted OR: 1.039, 95% CI = 1.011-1.069 in HS). Korean adolescents with longer sedentary durations during weekdays regardless of the cause of sedentary behavior are positively associated with depressed mood with suicidality in the HS for both genders.

CONCLUSION: This study found a positive association between the prevalence of depressed mood and sedentary behavior, and it focused on the cause and timing. Interventions targeting sedentary behavior could be effective in reducing depressed mood and suicidality among adolescents.

PMID:36131259 | DOI:10.1186/s12888-022-04262-x

BMC Urol. 2022 Sep 21;22(1):155. doi: 10.1186/s12894-022-01105-5.

ABSTRACT

INTRODUCTION: To examine the reduction of transverse rectal diameter and its effect on bladder dynamics in children with spinal dysraphism.

METHODS: We prospectively evaluated 61 consecutive children with spinal dysraphism, 25 (41%) boys and 36 (59%) girls, aged 4 to 16 years; mean age 9.3 ± 3.8 years, who received bowel management. All children underwent echosonographic measurement of transverse rectal diameter before and after starting bowel management. Also, all the patients had undergone urodynamic studies before and after starting bowel management, with no changes in their urological treatment.

RESULTS: Bowel management caused an decrease in transverse rectal diameter by 56 ± 7.2% (p < 0.001). In addition, a decrease was observed for maximal detrusor pressure by 27.8 ± 7.8% (p < 0.001), leak point pressure by 37.2 ± 4.4% (p < 0.001), and PVR by 36.7 ± 8.0 (p < 0.001). Maximum bladder capacity was significantly increased after bowel management in both non-adjusted (36.4 ± 14.8%; p < 0.001) and adjusted analysis for age (39.4 ± 14.3%, p < 0.001). Detrusor compliance was also increased by 89.2 ± 24.8% (p < 0.001). Female gender and % change of maximal detrusor pressure were significant predictors of transversal rectal diameter change in univariate as well as in multivariate analysis (OR = 10.548, 95% CI 2.309-48.180; p = 0.002 and OR = 1.121, 95% CI 1.009-1.245; p = 0.034).

CONCLUSIONS: Decrease in transverse rectal diameter may be useful for bladder function and urodynamic findings in children with spinal dysraphism. Therefore, decrease in transverse rectal diameter should be a supplement to standard urotherapy.

PMID:36131256 | DOI:10.1186/s12894-022-01105-5

BMC Cancer. 2022 Sep 21;22(1):1002. doi: 10.1186/s12885-022-10078-5.

ABSTRACT

BACKGROUND: Approximately 40% of hormone receptor positive/human epidermal receptor 2 negative (HR + /HER2-) metastatic breast cancer (mBC) patients harbor phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutations. However, associations between PIK3CA mutation status and clinical outcomes among patients with HR + /HER2- mBC have been heterogeneous across clinical trials. This meta-analysis was conducted to survey recently available trial data to assess the prognostic effects of PIK3CA among patients with HR + /HER2- mBC. METHODS: Randomized clinical trials reporting progression-free survival (PFS) or overall survival (OS) stratified by PIK3CA status in HR + /HER2- mBC were identified via systematic literature review. Trial arms receiving phosphatidylinositol 3-kinase (PI3K)-targeted therapies were excluded. Meta-regression analysis was used to estimate the association between PIK3CA status and PFS and OS among included studies.

RESULTS: The analyzed data included 3,219 patients from 33 study arms across 11 trials (PIK3CA mutated: 1,386, wild type: 1,833). PIK3CA mutation was associated with shorter median PFS (difference [95% CI] (months): -1.8 [-3.4, -0.1], I² = 35%) and shorter median OS (-8.4 [-13.4, -3.5], I² = 58%, N = 1,545). Findings were similar for PFS rates at 6 months (odds ratio [95% CI]: 0.74 [0.59, 0.94], I² = 42%, N = 3,160) and 12 months (0.76 [0.59, 0.99], I² = 42%, N = 2,468) and directionally consistent but not statistically significant at 18 months (N = 1,726).

CONCLUSIONS: Pooling evidence across multiple studies, PIK3CA mutation was associated with shorter PFS and OS. These findings suggest a negative prognostic value of PIK3CA mutations in patients with HR + /HER2- mBC.

PMID:36131248 | DOI:10.1186/s12885-022-10078-5

BMC Prim Care. 2022 Sep 21;23(1):245. doi: 10.1186/s12875-022-01851-3.

ABSTRACT

BACKGROUND: The COVID-19 pandemic caused widespread changes to healthcare, but few studies focus on ambulatory care during the early phase of the pandemic. We characterize veterans’ ambulatory care experience, specifically access and satisfaction, early in the pandemic.

METHODS: We employed a semi-structured telephone interview to capture quantitative and qualitative data from patients scheduled with a primary care provider between March 1 – June 30, 2020. Forty veterans were randomly identified at a single large urban Veterans Health Administration (VHA) medical center. The interview guide utilized 56 closed and open-ended questions to characterize veterans’ perceptions of access to and satisfaction with their primary care experience at VHA and non-VHA primary care sources. We also explored the context of veterans’ daily lives during the pandemic. We analyzed quantitative data using descriptive statistics and verbatim quotes using a matrix analysis.

RESULTS: Veterans reported completing more appointments (mean 2.6 (SD 2.2)) than scheduled (mean 2.3 (SD 2.2)) mostly due to same-day or urgent visits, with a shift to telephone (mean 2.1 (SD 2.2)) and video (mean 1.5 (SD 0.6)). Among those who reported decreased access to care early in the pandemic (n = 27 (67%)), 15 (56%) cited administrative barriers (“The phone would hang up on me”) and 9 (33%) reported a lack of provider availability (“They are not reaching out like they used to”). While most veterans (n = 31 (78%)) were highly satisfied with their VHA care (mean score 8.6 (SD 2.0 on a 0-10 scale), 9 (23%) reported a decrease in satisfaction since the pandemic. The six (15%) veterans who utilized non-VHA providers during the period of interest reported, on average, higher satisfaction ratings (mean 9.5 (SD 1.2)). Many veterans reported psychosocial effects such as the worsening of mental health (n = 6 (15%)), anxiety concerning the virus (n = 12 (30%)), and social isolation (n = 8 (20%), “I stay inside and away from people”).

CONCLUSIONS: While the number of encounters reported suggest adequate access and satisfaction, the comments regarding barriers to care suggest that enhanced approaches may be warranted to improve and sustain veteran perceptions of adequate access to and satisfaction with primary care during times of crisis.

PMID:36131246 | DOI:10.1186/s12875-022-01851-3

BMC Genomics. 2022 Sep 21;23(1):663. doi: 10.1186/s12864-022-08884-z.

ABSTRACT

BACKGROUND: There is a need to match characteristics of tobacco users with cessation treatments and risks of tobacco attributable diseases such as lung cancer. The rate in which the body metabolizes nicotine has proven an important predictor of these outcomes. Nicotine metabolism is primarily catalyzed by the enzyme cytochrone P450 (CYP2A6) and CYP2A6 activity can be measured as the ratio of two nicotine metabolites: trans-3′-hydroxycotinine to cotinine (NMR). Measurements of these metabolites are only possible in current tobacco users and vary by biofluid source, timing of collection, and protocols; unfortunately, this has limited their use in clinical practice. The NMR depends highly on genetic variation near CYP2A6 on chromosome 19 as well as ancestry, environmental, and other genetic factors. Thus, we aimed to develop prediction models of nicotine metabolism using genotypes and basic individual characteristics (age, gender, height, and weight).

RESULTS: We identified four multiethnic studies with nicotine metabolites and DNA samples. We constructed a 263 marker panel from filtering genome-wide association scans of the NMR in each study. We then applied seven machine learning techniques to train models of nicotine metabolism on the largest and most ancestrally diverse dataset (N=2239). The models were then validated using the other three studies (total N=1415). Using cross-validation, we found the correlations between the observed and predicted NMR ranged from 0.69 to 0.97 depending on the model. When predictions were averaged in an ensemble model, the correlation was 0.81. The ensemble model generalizes well in the validation studies across ancestries, despite differences in the measurements of NMR between studies, with correlations of: 0.52 for African ancestry, 0.61 for Asian ancestry, and 0.46 for European ancestry. The most influential predictors of NMR identified in more than two models were rs56113850, rs11878604, and 21 other genetic variants near CYP2A6 as well as age and ancestry.

CONCLUSIONS: We have developed an ensemble of seven models for predicting the NMR across ancestries from genotypes and age, gender and BMI. These models were validated using three datasets and associate with nicotine dosages. The knowledge of how an individual metabolizes nicotine could be used to help select the optimal path to reducing or quitting tobacco use, as well as, evaluating risks of tobacco use.

PMID:36131240 | DOI:10.1186/s12864-022-08884-z

Spine Deform. 2022 Sep 21. doi: 10.1007/s43390-022-00586-6. Online ahead of print.

ABSTRACT

PURPOSE: To compare direct costs of index and revision operations of thoracic posterior spinal instrumented fusion (TPSIF) and thoracic anterior spinal tethering (TAST) for adolescent idiopathic thoracic scoliosis in children.

METHODS: Children (ages 11-18 years) who underwent TPSIF and TAST (2/2013-9/2019) were reviewed. Follow-up < 2 years and cervical instrumentation and/or instrumentation of a lumbar level at L3 or below were exclusion criteria. Patient demographics, radiographic curve magnitude, index operations and postoperative data, as well as indications for revisions/readmissions were collected. Direct costs were identified and compared for index and revision operations during follow-up.

RESULTS: One hundred and four patients were included (TPSIF: 78; TAST: 25). TAST procedures were performed in children significantly younger and for smaller curve magnitudes. They had significantly fewer levels instrumented, shorter operating room (OR) times, and less estimated blood loss (EBL). After operation, a significantly higher percentage of TAST were admitted to ICU. Hospital length of stay (LOS) was similar between groups. Index operations’ average direct costs were significantly higher for TAST than TPSIF ($52,947 v. $46,641; p = 0.02). Major cost drivers for both groups were implants, OR services, post-anesthesia care unit (PACU), and room/board. Revisions following TAST were more frequent than for TPSIF (36 v. 11.5%). Majority of TPSIF revisions were for junctional deformity. Curve progression and overcorrection were most common reason for TAST revisions. Average direct costs for revisions/readmissions were similar between groups (TPSIF: $28,485 v. TAST: $27,590; p = 0.46).

CONCLUSIONS: Index operations’ average direct costs were statistically similar between TPSIF and TAST for adolescent idiopathic scoliosis. Major cost drivers were implants, OR services, PACU, and room/board. TAST index operations’ direct costs and associated direct costs for implants and room/board were significantly higher, while their anesthesia and OR services were significantly lower than TPSIF. TAST revisions were for overcorrection and curve progression, while TPSIF revisions were most commonly for junctional deformity. Overall average direct costs for revisions were similar despite revision rates being higher for TAST.

LEVEL OF EVIDENCE: III.

PMID:36131225 | DOI:10.1007/s43390-022-00586-6