Tag: statistics

Med Phys. 2023 Jul 31. doi: 10.1002/mp.16655. Online ahead of print.

ABSTRACT

BACKGROUND: Alzheimer’s disease (AD) is a heterogeneous, multifactorial neurodegenerative disorder characterized by three neurobiological factors beta-amyloid, pathologic tau, and neurodegeneration. There are no effective treatments for AD at a late stage, urging for early detection and prevention. However, existing statistical inference approaches in neuroimaging studies of AD subtype identification do not take into account the pathological domain knowledge, which could lead to ill-posed results that are sometimes inconsistent with the essential neurological principles.

PURPOSE: Integrating systems biology modeling with machine learning, the study aims to assist clinical AD prognosis by providing a subpopulation classification in accordance with essential biological principles, neurological patterns, and cognitive symptoms.

METHODS: We propose a novel pathology steered stratification network (PSSN) that incorporates established domain knowledge in AD pathology through a reaction-diffusion model, where we consider non-linear interactions between major biomarkers and diffusion along the brain structural network. Trained on longitudinal multimodal neuroimaging data, the biological model predicts long-term evolution trajectories that capture individual characteristic progression pattern, filling in the gaps between sparse imaging data available. A deep predictive neural network is then built to exploit spatiotemporal dynamics, link neurological examinations with clinical profiles, and generate subtype assignment probability on an individual basis. We further identify an evolutionary disease graph to quantify subtype transition probabilities through extensive simulations.

RESULTS: Our stratification achieves superior performance in both inter-cluster heterogeneity and intra-cluster homogeneity of various clinical scores. Applying our approach to enriched samples of aging populations, we identify six subtypes spanning AD spectrum, where each subtype exhibits a distinctive biomarker pattern that is consistent with its clinical outcome.

CONCLUSIONS: The proposed PSSN (i) reduces neuroimage data to low-dimensional feature vectors, (ii) combines AT[N]-Net based on real pathological pathways, (iii) predicts long-term biomarker trajectories, and (iv) stratifies subjects into fine-grained subtypes with distinct neurological underpinnings. PSSN provides insights into pre-symptomatic diagnosis and practical guidance on clinical treatments, which may be further generalized to other neurodegenerative diseases.

PMID:37522278 | DOI:10.1002/mp.16655

Chemistry. 2023 Jul 31:e202302154. doi: 10.1002/chem.202302154. Online ahead of print.

ABSTRACT

Boosted by the emerging need for highly integrated gas sensors in IoT ecosystems, electronic noses (e-noses) are gaining interest for the detection of specific molecules over a background of interfering gases. The sensing of nitrogen dioxide (NO2) is particularly relevant for applications in environmental monitoring and precision medicine. Here we present an easy and efficient functionalization procedure to covalently modify graphene layers, taking advantage of diazonium chemistry. Separate graphene layers were functionalised with one of three different aryl rings 4-nitrophenyl, 4-carboxyphenyl, and 4-bromophenyl). The distinct mod(ified graphene layers were assembled with a pristine layer into an e-nose for NO2 discrimination. A remarkable sensitivity to NO2 is demonstrated through exposures to gaseous solutions with NO2 concentrations in the 1-10 ppm range at room temperature. Then, the discrimination capability of the sensor array is tested by carrying out exposures to several interfering gases and analyzing the data through multivariate statistical analysis. This analysis shows that the e-nose can discriminate NO2 among all the interfering gases in a two-dimensional principal component analysis space. Finally, the e-nose is trained to accurately recognize NO2 contributions with a linear discriminant analysis approach, thus providing a metric for discrimination assessment with a prediction accuracy above 95%.

PMID:37522257 | DOI:10.1002/chem.202302154

Alzheimers Dement. 2023 Jul 31. doi: 10.1002/alz.13419. Online ahead of print.

ABSTRACT

BACKGROUND: Delirium, a common syndrome with heterogeneous etiologies and clinical presentations, is associated with poor long-term outcomes. Recording and analyzing all delirium equally could be hindering the field’s understanding of pathophysiology and identification of targeted treatments. Current delirium subtyping methods reflect clinically evident features but likely do not account for underlying biology.

METHODS: The Delirium Subtyping Initiative (DSI) held three sessions with an international panel of 25 experts.

RESULTS: Meeting participants suggest further characterization of delirium features to complement the existing Diagnostic and Statistical Manual of Mental Disorders Fifth Edition Text Revision diagnostic criteria. These should span the range of delirium-spectrum syndromes and be measured consistently across studies. Clinical features should be recorded in conjunction with biospecimen collection, where feasible, in a standardized way, to determine temporal associations of biology coincident with clinical fluctuations.

DISCUSSION: The DSI made recommendations spanning the breadth of delirium research including clinical features, study planning, data collection, and data analysis for characterization of candidate delirium subtypes.

HIGHLIGHTS: Delirium features must be clearly defined, standardized, and operationalized. Large datasets incorporating both clinical and biomarker variables should be analyzed together. Delirium screening should incorporate communication and reasoning.

PMID:37522255 | DOI:10.1002/alz.13419

J Cardiovasc Electrophysiol. 2023 Jul 31. doi: 10.1111/jce.16022. Online ahead of print.

ABSTRACT

AIMS: To investigate the association of cardiac resynchronization therapy (CRT) on outcomes among participants with and without a history of atrial fibrillation (AF).

METHODS: Individual-patient-data from four randomized trials investigating CRT-Defibrillators (COMPANION, MADIT-CRT, REVERSE) or CRT-Pacemakers (COMPANION, MIRACLE) were analyzed. Outcomes were time to a composite of heart failure hospitalization or all-cause mortality or to all-cause mortality alone. The association of CRT on outcomes for patients with and without a history of AF was assessed using a Bayesian-Weibull survival regression model adjusting for baseline characteristics.

RESULTS: Of 3964 patients included, 586 (14.8%) had a history of AF; 2245 (66%) were randomized to CRT. Overall, CRT reduced the risk of the primary composite endpoint (hazard ratio [HR]: 0.69, 95% credible interval [CI]: 0.56-0.81). The effect was similar (posterior probability of no interaction = 0.26) in patients with (HR: 0.78, 95% CI: 0.55-1.10) and without a history of AF (HR: 0.67, 95% CI: 0.55-0.80). In these four trials, CRT did not reduce mortality overall (HR: 0.82, 95% CI: 0.66-1.01) without evidence of interaction (posterior probability of no interaction = 0.14) for patients with (HR: 1.09, 95% CI: 0.70-1.74) or without a history of AF (HR: 0.70, 95% CI: 0.60-0.97).

CONCLUSION: The association of CRT on the composite endpoint or mortality was not statistically different for patients with or without a history of AF, but this could reflect inadequate power. Our results call for trials to confirm the benefit of CRT recipients with a history of AF.

PMID:37522254 | DOI:10.1111/jce.16022

Otolaryngol Head Neck Surg. 2023 Jul 31. doi: 10.1002/ohn.419. Online ahead of print.

ABSTRACT

OBJECTIVE: Determine the ideal head position to optimize visualization of the subglottis using flexible laryngoscopy.

STUDY DESIGN: Prospective cohort study.

SETTING: Outpatient multidisciplinary airway clinic at a tertiary care center.

METHODS: Patients presenting to a multidisciplinary airway clinic undergoing nasoendoscopic airway examination were enrolled. Three head positions were utilized to examine the subglottis during laryngoscopy: “sniffing,” chin tuck, and stooping positions. In-office reviewers and blinded clinician participants evaluated views of the airway based on Cormack-Lehane (CL) scale, airway grade (AG), and visual analog scale (VAS). Demographic data were obtained. Statistical analysis compared head positions and demographic data using Student’s t test, analysis of variance, and Tukey’s post hoc analysis.

RESULTS: One hundred patients participated. No statistical differences existed among in-clinic or blinded reviewers for the CL score in any head position (p = .35, .5, respectively). For both AG and VAS, flexed and stooping positions were rated higher than the sniffing positions by both in-clinic and blinded reviewers (p < .01 for all analyses), but there was no statistical difference between these two positions (p = .28, .18, respectively). There was an inverse correlation between age and scores for AG and VAS in the flexed position for both sets of reviewers (p = .02, <.01 respectively), and a higher body mass index was significantly associated with the need to perform tracheoscopy for full airway evaluation (p < .01).

CONCLUSION: Both flexion and stoop postures can be implemented by an experienced endoscopist in awake, transnasal flexible laryngoscopy to enhance visualization of the subglottic airway.

PMID:37522249 | DOI:10.1002/ohn.419

BJOG. 2023 Jul 31. doi: 10.1111/1471-0528.17620. Online ahead of print.

ABSTRACT

OBJECTIVE: To identify vaginal morphology and position factors associated with prolapse recurrence following vaginal surgery.

DESIGN: Secondary analysis of magnetic resonance images (MRI) of the Defining Mechanisms of Anterior Vaginal Wall Descent cross-sectional study.

SETTING: Eight clinical sites in the US Pelvic Floor Disorders Network.

POPULATION OR SAMPLE: Women who underwent vaginal mesh hysteropexy (hysteropexy) with sacrospinous fixation or vaginal hysterectomy with uterosacral ligament suspension (hysterectomy) for uterovaginal prolapse between April 2013 and February 2015.

METHODS: The MRI (rest, strain) obtained 30-42 months after surgery, or earlier for participants with recurrence who desired reoperation before 30 months, were analysed. MRI-based prolapse recurrence was defined as prolapse beyond the hymen at strain on MRI. Vaginal segmentations (at rest) were used to create three-dimensional models placed in a morphometry algorithm to quantify and compare vaginal morphology (angulation, dimensions) and position.

MAIN OUTCOME MEASURES: Vaginal angulation (upper, lower and upper-lower vaginal angles in the sagittal and coronal plane), dimensions (length, maximum transverse width, surface area, volume) and position (apex, mid-vagina) at rest.

RESULTS: Of the 82 women analysed, 12/41 (29%) in the hysteropexy group and 22/41 (54%) in the hysterectomy group had prolapse recurrence. After hysteropexy, women with recurrence had a more laterally deviated upper vagina (p = 0.02) at rest than women with successful surgery. After hysterectomy, women with recurrence had a more inferiorly (lower) positioned vaginal apex (p = 0.01) and mid-vagina (p = 0.01) at rest than women with successful surgery.

CONCLUSIONS: Vaginal angulation and position were associated with prolapse recurrence and suggestive of vaginal support mechanisms related to surgical technique and potential unaddressed anatomical defects. Future prospective studies in women before and after prolapse surgery may distinguish these two factors.

PMID:37522240 | DOI:10.1111/1471-0528.17620

Technol Health Care. 2023 Jul 20. doi: 10.3233/THC-220732. Online ahead of print.

ABSTRACT

BACKGROUND: Recurrent acute pancreatitis is a common acute abdominal disease in surgery.

OBJECTIVE: To evaluate the radiographic features of pancreatic computed tomography (CT) imaging in the diagnosis of acute and chronic pancreatitis.

METHODS: 48 pancreatitis patients who met the criteria were selected in this retrospective study from 2010 to 2019. Each diagnosis was evaluated as functional abdominal pain, recurrent acute pancreatitis, or chronic pancreatitis. All clinical data were collected from the patient’s medical records. 54 radiological features were extracted from each region of interest in outline the pancreas and divided into five categories: first order statistics, the gray level co-occurrence matrix (GLCM), the gray level run-length matrix (GLRLM), the neighborhood gray level difference matrix (NGTDM), and morphological features by the MATLAB program.

RESULTS: Of the 48 patients, 16 had functional abdominal pain (33.3%), 18 had recurrent acute pancreatitis (37.5%), and 14 had chronic pancreatitis (29.2%). In the univariate analysis, nine radiological features, eight GLCM features and one NGTDM feature were significantly different between groups. Nine radiological characteristics had important reference values with AUC values ranging from 0.73-0.91.

CONCLUSION: Nine radiographic features of CT imaging demonstrate good evaluation efficiency in the diagnosis of pancreatitis and can distinguish patients with functional abdominal pain, recurrent acute pancreatitis, and chronic pancreatitis.

PMID:37522229 | DOI:10.3233/THC-220732

J Alzheimers Dis. 2023 Jul 26. doi: 10.3233/JAD-230159. Online ahead of print.

ABSTRACT

BACKGROUND: A connection between plasma levels of haptoglobin (Hp) and Alzheimer’s disease (AD) has been shown in several observational studies. It is debatable, nonetheless, how the two are related causally.

OBJECTIVE: To establish the causal relationship between Hp and AD using a two-sample Mendelian randomization (MR) study.

METHODS: From the extensive genome-wide association studies and FinnGen dataset, summaries and statistics pertaining to AD were gathered. We investigated the possibility of a causal link between Hp and AD using a two-sample MR study. Inverse variance weighting was used as the primary analytical technique, and it was supported by the joint application of complementary analyses and fixed effects meta-analysis to combine results from various sources.

RESULTS: Genetically determined Hp was causally associated with AD [odds ratio (OR), 1.05; 95% confidence interval (CI), 1.02 to 1.09; p = 8.96×10-4]; Inverse variance-weighted estimates coming from different data sources were combined in a meta-analysis with consistent findings (OR, 1.03; 95% CI, 1.01 to 1.05; p = 2.00×10-3). The outcomes of the inverse MR analysis showed that AD had no appreciable causal impact on Hp.

CONCLUSION: The present MR analysis shows that higher plasma Hp leads to an increased risk of AD. Strategies for plasma Hp testing may open up new doors for the early diagnosis and prevention of AD.

PMID:37522206 | DOI:10.3233/JAD-230159

Ir J Psychol Med. 2023 Jul 31:1-13. doi: 10.1017/ipm.2023.35. Online ahead of print.

ABSTRACT

OBJECTIVES: Despite a substantial epidemiological literature on the incidence of psychotic disorders in Ireland, no systematic review has previously been undertaken. Such evidence can help inform understanding of need for psychosis care.

METHODS: We conducted a prospectively registered systematic review (PROSPERO: CRD42021245891) following PRISMA guidelines. We searched four databases (Medline, PsycInfo, Web of Science, Embase) for papers containing incidence data on non-organic psychotic disorders, in people 16-64 years, published between 1950 and 2021 in the general adult population. We conducted duplicate screening, risk of bias assessments, and extracted data to a standardised template. We undertook a narrative synthesis for each major diagnostic outcome. Random effects meta-analyses were conducted for comparisons with ≥5 incidence rates.

RESULTS: Our search yielded 1975 non-duplicate citations, of which 23 met inclusion criteria, containing incidence data ascertained between 1974 and 2016 (median study quality: 5/8; interquartile range: 4-6). Incidence of all psychotic disorders (N = 4 studies) varied from 22.0 (95%CI: 17.3-28.0) in Dublin to 34.1 per 100,000 person-years (95%CI: 31.0-37.5) in Cavan and Monaghan. The pooled incidence of schizophrenia (N = 6 studies, N = 8 settings) was 20.0 per 100,000 person-years, though with imprecision around this estimate (95%CI: 10.6-37.5; I²: 97.6%). Higher rates of most outcomes were observed in men. There was consistent evidence of raised rates in more deprived and fragmented social environments, but no clear pattern by rural-urban status.

CONCLUSIONS: Patterns of incidence of psychotic disorders in Ireland are broadly consistent with the wider literature from the Global North. Findings could help identify populations at higher risk of psychosis in Ireland.

PMID:37522189 | DOI:10.1017/ipm.2023.35

J Am Heart Assoc. 2023 Jul 31:e029190. doi: 10.1161/JAHA.122.029190. Online ahead of print.

ABSTRACT

Background Epidemiologic studies have identified risk factors associated with pulmonary hypertension and right heart failure, but causative drivers of pulmonary hypertension and right heart adaptation are not well known. We sought to leverage unbiased genetic approaches to determine clinical conditions that share genetic architecture with pulmonary pressure and right ventricular dysfunction. Methods and Results We leveraged Vanderbilt University’s deidentified electronic health records and DNA biobank to identify 14 861 subjects of European ancestry who underwent at least 1 echocardiogram with available estimates of pulmonary pressure and right ventricular function. Analyses of the study were performed between 2020 and 2022. The final analytical sample included 14 861 participants (mean [SD] age, 63 [15] years and mean [SD] body mass index, 29 [7] kg/m²). An unbiased phenome-wide association study identified diabetes as the most statistically significant clinical International Classifications of Diseases, Ninth Revision (ICD-9) code associated with polygenic risk for increased pulmonary pressure. We validated this finding further by finding significant associations between genetic risk for diabetes and a related condition, obesity, with pulmonary pressure estimate. We then used 2-sample univariable Mendelian randomization and multivariable Mendelian randomization to show that diabetes, but not obesity, was independently associated with genetic risk for increased pulmonary pressure and decreased right ventricle load stress. Conclusions Our findings show that genetic risk for diabetes is the only significant independent causative driver of genetic risk for increased pulmonary pressure and decreased right ventricle load stress. These findings suggest that therapies targeting genetic risk for diabetes may also potentially be beneficial in treating pulmonary hypertension and right heart dysfunction.

PMID:37522172 | DOI:10.1161/JAHA.122.029190