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Nevin Manimala Statistics

What affects diagnostic and therapeutic times for cancer patients care?

Recenti Prog Med. 2023 Jun;114(6):362-367. doi: 10.1701/4042.40230.

ABSTRACT

INTRODUCTION: According with “Numbers of cancer in Italy. 2021” mortality is decreasing for both the genders (-10% for men, -8% for women) in Italy. However, this trend is not uniform and seems stable in the Southern regions. Analyses of oncological care in Campania Region highlighted some structural critical issues and delays, which did not guarantee an efficient and effective use of the available economic resources. So, the Campania region established in September 2016 the Campania oncological network (Roc) addressed to prevention, diagnosis, treatment and rehabilitation of tumours through the establishment of multidisciplinary oncological groups (Gom). In February 2020, the ValPeRoc project was launched with the aim of periodically and progressively evaluating the Roc’s performance both for the clinical services and for the economic aspects.

METHODS: In five Goms (colon, ovary, lung, prostate, bladder) active in some Roc hospitals, the pre-Gom time elapsing between the date of diagnosis and the date of the first Gom meeting and the Gom time elapsing between the date of the first Gom meeting and the date of the treatment decision were measured. Gom times longer than 28 days were defined as high. The risk of high Gom time was analyzed with a Bart-type machine learning algorithm, considering the set of regressors (features) available to classify patients.

RESULTS: The results on the test set (54 patients) report an accuracy of 0.68. The classification technique reported a good fit for colon Gom (93%) and an over-classification for lung Gom. The study of the marginal effects showed a higher risk for those who had a previous therapeutic act and for lung Gom.

CONCLUSIONS: Within the Goms took in consideration the proposed statistical technique showed that, depending on each Gom, correctly classified about 70% of individuals on risk of delaying permanence within the Roc. The ValPeRoc project evaluates Roc activity for the first time through a replicable analysis of patient pathway times from diagnosis to the act of treatment. Specifically, the times analyzed measure the quality of the regional health care system.

PMID:37229684 | DOI:10.1701/4042.40230

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Exposome: from definition to future challenges.

Recenti Prog Med. 2023 Jun;114(6):349-354. doi: 10.1701/4042.40227.

ABSTRACT

The exposome concept arises from the need to integrate different disciplines of public health and environmental sciences, mainly including environmental epidemiology, exposure science, and toxicology. The role of the exposome is to understand how the totality of an individual’s exposures throughout the lifetime can impact human health. The etiology of a health condition is rarely explained by a single exposure. Therefore, examining the human exposome as a whole becomes relevant to simultaneously consider multiple risk factors and more accurately estimate concurrent causes of different health outcomes. Generally, the exposome is explained through three domains: general external exposome, specific external exposome, and internal exposome. The general external exposome includes measurable population-level exposures such as air pollution or meteorological factors. The specific external exposome includes information on individual exposures, such as lifestyle factors, typically obtained from questionnaires. Meanwhile, the internal exposome encompasses multiple biological responses to external factors, detected through molecular and omics analyses. Additionally, in recent decades, the socio-exposome theory has emerged, where all exposures are studied as a phenomenon dependent on the interaction between socioeconomic factors that vary depending on the context, allowing the identification of mechanisms that lead to health inequalities. The considerable production of data in exposome studies has led researchers to face new methodological and statistical challenges, introducing various approaches to estimate the effect of the exposome on health. Among the most common are regression models (Exposome-Wide Association Study – ExWAS), dimensionality reduction and exposure grouping techniques, and machine learning methods. The significant conceptual and methodological innovation of the exposome for a more holistic evaluation of the risks associated with human health is continuously expanding and will require further investigations related to the application of information obtained from studies into prevention and public health policies.

PMID:37229681 | DOI:10.1701/4042.40227

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Benign incidental lesion of the calcaneus: the calcaneal vascular remnant

Acta Radiol. 2023 May 25:2841851231176266. doi: 10.1177/02841851231176266. Online ahead of print.

ABSTRACT

BACKGROUND: The calcaneal vascular remnant, first described by Fleming et al. in 2005, is a benign intramedullary lesion of the calcaneus with a vascular origin.

PURPOSE: To determine the prevalence and magnetic resonance imaging (MRI) characteristics of incidental calcaneal vascular remnant on routine ankle MRI.

MATERIAL AND METHODS: We retrospectively reviewed 457 ankle MRI scans for the presence of calcaneal vascular remnant. MRI was considered positive when a focal cyst-like area was seen on a T2-weighted sequence, and a low signal intensity was identified on a T1-weighted image beneath the calcaneal sulcus. Patients with calcaneal vascular remnants were further evaluated for age, gender, right or left foot location, size, and lesion characteristics.

RESULTS: The prevalence of incidental calcaneal vascular remnant was 21.7% on our consecutive ankle MR examinations. The average lesion size was 5.5 mm. No statistically significant difference was noted in the frequency of lesion detection between gender, age, and side of the lesions (P > 0.05). Multilobulated lesions were detected predominantly in women (P = 0.013) and classic type lesions were detected predominantly in men (P = 0.036).

CONCLUSION: This report is the first to determine the prevalence and MRI characteristics of calcaneal vascular remnants. Detecting and reporting this lesion on routine MRI is essential to avoid confusion with other pathologic entities.

PMID:37229665 | DOI:10.1177/02841851231176266

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Nevin Manimala Statistics

Improved use of faecal immunochemical tests for haemoglobin in the Scottish bowel screening programme

J Med Screen. 2023 May 25:9691413231175611. doi: 10.1177/09691413231175611. Online ahead of print.

ABSTRACT

OBJECTIVES: This study aimed to develop a risk-scoring model in the Scottish Bowel Screening Programme incorporating faecal haemoglobin concentration with other risk factors for colorectal cancer.

METHODS: Data were collected for all individuals invited to participate in the Scottish Bowel Screening Programme between November 2017 and March 2018 including faecal haemoglobin concentration, age, sex, National Health Service Board, socioeconomic status, and screening history. Linkage with The Scottish Cancer Registry identified all screening participants diagnosed with colorectal cancer. Logistic regression was performed to identify which factors demonstrated significant association with colorectal cancer and could be used in the development of a risk-scoring model.

RESULTS: Of 232,076 screening participants, 427 had colorectal cancer: 286 diagnosed following a screening colonoscopy and 141 arising after a negative screening test result giving an interval cancer proportion of 33.0%. Only faecal haemoglobin concentration and age showed a statistically significant association with colorectal cancer. Interval cancer proportion increased with age and was higher in women (38.1%) than men (27.5%). If positivity in women were mirrored in men at each age quintile interval cancer proportion would still have remained higher in women (33.2%). Moreover, an additional 1201 colonoscopies would be required to detect 11 colorectal cancers.

CONCLUSIONS: Development of a risk scoring model using early data from the Scottish Bowel Screening Programme was not feasible due to most variables showing insignificant association with colorectal cancer. Tailoring the faecal haemoglobin concentration threshold according to age could help to diminish some of the disparity in interval cancer proportion between women and men. Strategies to achieve sex equality using faecal haemoglobin concentration thresholds depend considerably on which variable is selected for equivalency and this requires further exploration.

PMID:37229658 | DOI:10.1177/09691413231175611

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Fragment Merging Using a Graph Database Samples Different Catalogue Space than Similarity Search

J Chem Inf Model. 2023 May 25. doi: 10.1021/acs.jcim.3c00276. Online ahead of print.

ABSTRACT

Fragment merging is a promising approach to progressing fragments directly to on-scale potency: each designed compound incorporates the structural motifs of overlapping fragments in a way that ensures compounds recapitulate multiple high-quality interactions. Searching commercial catalogues provides one useful way to quickly and cheaply identify such merges and circumvents the challenge of synthetic accessibility, provided they can be readily identified. Here, we demonstrate that the Fragment Network, a graph database that provides a novel way to explore the chemical space surrounding fragment hits, is well-suited to this challenge. We use an iteration of the database containing >120 million catalogue compounds to find fragment merges for four crystallographic screening campaigns and contrast the results with a traditional fingerprint-based similarity search. The two approaches identify complementary sets of merges that recapitulate the observed fragment-protein interactions but lie in different regions of chemical space. We further show our methodology is an effective route to achieving on-scale potency by retrospective analyses for two different targets; in analyses of public COVID Moonshot and Mycobacterium tuberculosis EthR inhibitors, potential inhibitors with micromolar IC50 values were identified. This work demonstrates the use of the Fragment Network to increase the yield of fragment merges beyond that of a classical catalogue search.

PMID:37229647 | DOI:10.1021/acs.jcim.3c00276

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Dimension reduction in higher-order contagious phenomena

Chaos. 2023 May 1;33(5):053117. doi: 10.1063/5.0152959.

ABSTRACT

We investigate epidemic spreading in a deterministic susceptible-infected-susceptible model on uncorrelated heterogeneous networks with higher-order interactions. We provide a recipe for the construction of one-dimensional reduced model (resilience function) of the N-dimensional susceptible-infected-susceptible dynamics in the presence of higher-order interactions. Utilizing this reduction process, we are able to capture the microscopic and macroscopic behavior of infectious networks. We find that the microscopic state of nodes (fraction of stable healthy individual of each node) inversely scales with their degree, and it becomes diminished due to the presence of higher-order interactions. In this case, we analytically obtain that the macroscopic state of the system (fraction of infectious or healthy population) undergoes abrupt transition. Additionally, we quantify the network’s resilience, i.e., how the topological changes affect the stable infected population. Finally, we provide an alternative framework of dimension reduction based on the spectral analysis of the network, which can identify the critical onset of the disease in the presence or absence of higher-order interactions. Both reduction methods can be extended for a large class of dynamical models.

PMID:37229635 | DOI:10.1063/5.0152959

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Normal range of intraoperative three-dimensionally derived right ventricular free-wall strain in coronary artery bypass surgery patients

Echocardiography. 2023 May 25. doi: 10.1111/echo.15624. Online ahead of print.

ABSTRACT

BACKGROUND: Data on intraoperative three-dimensionally derived right ventricular free-wall strain (3D-RV FWS) is sparse.

OBJECTIVES: We sought to evaluate the normal range of intraoperative 3D-RV FWS in patients scheduled for coronary artery bypass graft (CABG) surgery and compared to conventional echocardiographic parameters. Prospective observational study.

METHODS: A total of 150 patients with preserved left and right ventricular (RV) function and sinus rhythm, without significant heart valve disease or pulmonary hypertension undergoing isolated on-pump CABG surgery, with an uneventful, complication-free intraoperative course. 3D-RV FWS analysis and conventional echocardiographic assessment of RV function were performed intraoperatively in anesthetized and ventilated patients using transesophageal echocardiography (TEE). TomTec 4D RV-Function 2.0 software for assessment of 3D-RV FWS and three-dimensional right ventricular ejection fraction (3D-RV EF). Philips QLAB 10.8 was used to evaluate tissue velocity of the tricuspid annulus (RV S´), tricuspid annular systolic excursion (TAPSE), and RV fractional area change (FAC). All echocardiographic measurements were performed under stable hemodynamic conditions and predefined fluid management without any vasoactive support or pacing. The prospective observational study was performed in a single university hospital setting.

RESULTS: Assessment of 3D-RV FWS was feasible in 95% of patients. No included patient experienced any serious perioperative complication. In our group of patients, median values with interquartile range (IQR) for 3D-RV FWS and 3D-RV EF were -25.2 (IQR -29.9 to -21.8) and 46.3% (IQR 41.0%-50.1%), respectively. RV FAC, RV S´, and TAPSE accounted for 39.7% (IQR 34.5%-44.4%), 14.8 cm/s (IQR 11.8-19.0 cm/s), and 22 mm (IQR 20-25 mm). The normal range (2.5% to 97.5% percentile) for 3D-RV FWS was -37.1 to -12.8. There was no relevant correlation of 3D-RV FWS to postoperative outcome in this group of CABG patients.

CONCLUSION: We present distribution values for intraoperative 3D-RV FWS and conventional parameters of RV function assessment in a healthy on-pump CABG patient population without serious perioperative complications. We observed no correlations of these parameters with any of the outcome parameters considered. Therefore, we consider these values to be intraoperative TEE-assessed normal values, which can be expected in on-pump CABG patients.

PMID:37229579 | DOI:10.1111/echo.15624

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Does the SORG Machine-learning Algorithm for Extremity Metastases Generalize to a Contemporary Cohort of Patients? Temporal Validation From 2016 to 2020

Clin Orthop Relat Res. 2023 May 25. doi: 10.1097/CORR.0000000000002698. Online ahead of print.

ABSTRACT

BACKGROUND: The ability to predict survival accurately in patients with osseous metastatic disease of the extremities is vital for patient counseling and guiding surgical intervention. We, the Skeletal Oncology Research Group (SORG), previously developed a machine-learning algorithm (MLA) based on data from 1999 to 2016 to predict 90-day and 1-year survival of surgically treated patients with extremity bone metastasis. As treatment regimens for oncology patients continue to evolve, this SORG MLA-driven probability calculator requires temporal reassessment of its accuracy.

QUESTION/PURPOSE: Does the SORG-MLA accurately predict 90-day and 1-year survival in patients who receive surgical treatment for a metastatic long-bone lesion in a more recent cohort of patients treated between 2016 and 2020?

METHODS: Between 2017 and 2021, we identified 674 patients 18 years and older through the ICD codes for secondary malignant neoplasm of bone and bone marrow and CPT codes for completed pathologic fractures or prophylactic treatment of an impending fracture. We excluded 40% (268 of 674) of patients, including 18% (118) who did not receive surgery; 11% (72) who had metastases in places other than the long bones of the extremities; 3% (23) who received treatment other than intramedullary nailing, endoprosthetic reconstruction, or dynamic hip screw; 3% (23) who underwent revision surgery, 3% (17) in whom there was no tumor, and 2% (15) who were lost to follow-up within 1 year. Temporal validation was performed using data on 406 patients treated surgically for bony metastatic disease of the extremities from 2016 to 2020 at the same two institutions where the MLA was developed. Variables used to predict survival in the SORG algorithm included perioperative laboratory values, tumor characteristics, and general demographics. To assess the models’ discrimination, we computed the c-statistic, commonly referred to as the area under the receiver operating characteristic (AUC) curve for binary classification. This value ranged from 0.5 (representing chance-level performance) to 1.0 (indicating excellent discrimination) Generally, an AUC of 0.75 is considered high enough for use in clinical practice. To evaluate the agreement between predicted and observed outcomes, a calibration plot was used, and the calibration slope and intercept were calculated. Perfect calibration would result in a slope of 1 and intercept of 0. For overall performance, the Brier score and null-model Brier score were determined. The Brier score can range from 0 (representing perfect prediction) to 1 (indicating the poorest prediction). Proper interpretation of the Brier score necessitates a comparison with the null-model Brier score, which represents the score for an algorithm that predicts a probability equal to the population prevalence of the outcome for each patient. Finally, a decision curve analysis was conducted to compare the potential net benefit of the algorithm with other decision-support methods, such as treating all or none of the patients. Overall, 90-day and 1-year mortality were lower in the temporal validation cohort than in the development cohort (90 day: 23% versus 28%; p < 0.001, and 1 year: 51% versus 59%; p<0.001).

RESULTS: Overall survival of the patients in the validation cohort improved from 28% mortality at the 90-day timepoint in the cohort on which the model was trained to 23%, and 59% mortality at the 1-year timepoint to 51%. The AUC was 0.78 (95% CI 0.72 to 0.82) for 90-day survival and 0.75 (95% CI 0.70 to 0.79) for 1-year survival, indicating the model could distinguish the two outcomes reasonably. For the 90-day model, the calibration slope was 0.71 (95% CI 0.53 to 0.89), and the intercept was -0.66 (95% CI -0.94 to -0.39), suggesting the predicted risks were overly extreme, and that in general, the risk of the observed outcome was overestimated. For the 1-year model, the calibration slope was 0.73 (95% CI 0.56 to 0.91) and the intercept was -0.67 (95% CI -0.90 to -0.43). With respect to overall performance, the model’s Brier scores for the 90-day and 1-year models were 0.16 and 0.22. These scores were higher than the Brier scores of internal validation of the development study (0.13 and 0.14) models, indicating the models’ performance has declined over time.

CONCLUSION: The SORG MLA to predict survival after surgical treatment of extremity metastatic disease showed decreased performance on temporal validation. Moreover, in patients undergoing innovative immunotherapy, the possibility of mortality risk was overestimated in varying severity. Clinicians should be aware of this overestimation and discount the prediction of the SORG MLA according to their own experience with this patient population. Generally, these results show that temporal reassessment of these MLA-driven probability calculators is of paramount importance because the predictive performance may decline over time as treatment regimens evolve. The SORG-MLA is available as a freely accessible internet application at https://sorg-apps.shinyapps.io/extremitymetssurvival/.Level of Evidence Level III, prognostic study.

PMID:37229565 | DOI:10.1097/CORR.0000000000002698

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Student Use and Perceptions of Embedded Formative Assessments in a Basic Science Veterinary Program

J Vet Med Educ. 2023 May 25:e20230011. doi: 10.3138/jvme-2023-0011. Online ahead of print.

ABSTRACT

This work describes the implementation of online timed closed-book formative assessments across several modules of a first-year undergraduate veterinary program. This process does not require significant time investment since it can be implemented into existing programs of study. Students were surveyed on how they used these formative assessments for learning and overall, were overwhelmingly positive about the opportunity to practice and receive feedback on their performance. Quantitative statistics on preferences as well as qualitative thematic analysis of open free-text questions reveal clear preferences in how they choose to engage with the assessments for learning, as well as how they prefer assessments to be administered. Students were positive about the online nature of the exams and prefer formative assessments to be distributed across the teaching semesters without any time restrictions, allowing them to be completed as and when they choose. Immediate feedback in the form of model answers is the students’ preference, although some value signposting to relevant resources for further research. Furthermore, students report that they want more questions and tests to complement their learning, and overwhelming rely on guided and structured activities for learning and revision which will need to be balanced with opportunities to develop critical thinking and independent learning skills when studying in a professional course, given students are not likely to default into such behavior. This work models a process many curriculum designers have, and continue to undergo in higher education as online, hybrid, and blended approaches to teaching have received renewed interest.

PMID:37229550 | DOI:10.3138/jvme-2023-0011

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Growth Mindset in Veterinary Educators: An International Survey

J Vet Med Educ. 2023 May 25:e20220128. doi: 10.3138/jvme-2022-0128. Online ahead of print.

ABSTRACT

Carol Dweck’s mindset theory describes whether an individual believes that attributes, like intelligence or morality, can be honed (growth mindset) or are innate (fixed mindset). An educator’s mindset impacts their approach to teaching, students’ learning, participation in faculty development, and wellbeing. Mindset can affect faculty members’ openness to curricular change, making the study of veterinary educator mindset timely and salient, as competency-based education is spurring curricular change worldwide. The purpose of this study was to examine the mindsets of veterinary educators internationally. A survey, consisting of demographic questions and mindset items (based on previously published scales), was distributed electronically to veterinary educators internationally, at universities where English is the primary instruction medium. Mindset was evaluated for the following traits: intelligence, clinical reasoning, compassion, and morality. Scale validation, descriptive statistics, and associations to demographic variables were evaluated. Four hundred and forty-six complete surveys were received. Overall, the study population demonstrated predominantly growth mindsets for all traits, higher than population averages, with some variation by trait. There was a small effect on years teaching towards growth mindset. No other associations were found. Veterinary educators internationally who participated in this study demonstrated higher rates of growth mindset than the general population. In other fields, a growth mindset in educators has had implications for faculty wellbeing, teaching and assessment practices, participation in faculty development, and openness to curricular change. Further research is needed in veterinary education to evaluate the implications of these high rates of growth mindset.

PMID:37229549 | DOI:10.3138/jvme-2022-0128