Category: Statistics

Int J Stroke. 2024 Jun 18:17474930241264686. doi: 10.1177/17474930241264686. Online ahead of print.

ABSTRACT

BACKGROUND: Stroke prevention is a pressing global health priority, with reducing elevated lipids recognized as a key strategy. East Asians, constituting over 1.6 billion individuals and the largest racial group worldwide, are a key demographic in this effort. Yet, the effectiveness of lipid-lowering therapies for stroke prevention in this population remains uncertain.

AIMS AND METHODS: We conducted a systematic review and meta-analysis of large-scale randomized controlled trials (RCTs) with at least 3 years of follow-up to evaluate the long-term impact of lipid-lowering therapies on stroke incidence in East Asians. We systematically searched four electronic databases up to January 11, 2024. The association was quantified using relative risk (RR) with a 95% confidence interval (CI), and between-study heterogeneity was evaluated using the I2 statistic. Additionally, we utilized the Cochrane Risk of Bias Tool to assess the risk of bias in each included RCT and applied the GRADE approach to evaluate the certainty of the evidence.

RESULTS: This study incorporated data from 9 large-scale RCTs involving 54,354 participants. Our findings of overall analyses revealed that lipid-lowering therapies did not significantly affect the long-term incidence of all strokes (9 RCTs; 54,354 participants; RR, 0.98 [95% CI, 0.87-1.10]; P = 0.75), ischemic stroke (7 RCTs; 52,059 participants; RR, 0.91 [95% CI, 0.79-1.04]; P = 0.16), or hemorrhage stroke (7 RCTs; 52,059 participants; RR, 1.24 [95% CI, 0.97-1.59]; P = 0.09) in East Asians. Notably, there was no evidence of heterogeneity or publication bias, and the quality of evidence assessed using GRADE methodologies was rated as high. Sensitivity analyses confirmed the robustness of our results, with no single study significantly affecting the overall findings. Furthermore, subgroup analyses consistently supported the conclusions, further bolstering the reliability of our study.

CONCLUSIONS: Lipid-lowering therapies did not demonstrate any beneficial effects on long-term stroke prevention among East Asians.

PMID:38888036 | DOI:10.1177/17474930241264686

Oral Dis. 2024 Jun 18. doi: 10.1111/odi.15042. Online ahead of print.

ABSTRACT

OBJECTIVE: To analyze trends of antibiotic consumption and expenditure in Chinese stomatology hospitals between 2014 and 2018 with a longitudinal study design, and show the impacts of the comprehensive policy on dental antibiotic use in China.

SUBJECT AND METHODS: Consumption was quantified as the number of daily defined doses (DDDs) and expenditure as the procurement costs, using medical institutions’ drug procurement data from the Chinese Monitoring Network for Rational Use of Drugs. Descriptive statistics was employed and the compound annual growth rate (CAGR) was calculated to show the average annual growth rate.

RESULTS: Between 2014 and 2018, overall antibiotic consumption increased from 842.6 thousand DDDs to 1376.7 thousand DDDs (p < 0.001) and expenditure increased from 11.6 million RMB to 20.9 million RMB (p < 0.001), where other β-lactam antibacterials accounted for the largest proportion of total consumption (37.1%-50.1%) and expenditure (52.9%-66.6%), and also increase the largest (CAGR = 18.4%, p < 0.001). The proportion of oral antibiotics was nearly 9 times of parenteral antibiotics in consumption (CAGR = 0.3%, p = 0.023) and only 2 times in expenditure (CAGR = -1.7%, p = 0.112). The non-restricted group accounted for more than 90% of consumption (CAGR = 0.6%, p < 0.001). In 2018, oral first-generation cephalosporins (22.8%), oral imidazole derivatives (22.3%), and oral second-generation cephalosporins (19.2%) were the most frequently used antibiotic classification, while parenteral second-generation cephalosporins were top one (19.8%) for expenditure. At chemical substance levels, the consumption of oral cefradine ranked top one (21.4%) and parenteral cefuroxime accounted for the largest proportion of expenditure (14.5%) in 2018. Oral cefradine, oral metronidazole, and oral cefaclor were the top three frequently consumed antibiotics throughout the five years.

CONCLUSIONS: Despite the potential antibiotic overuse, the comprehensive antibiotic stewardship regulations of China got a satisfactory and better performance in dental practices. More effort is needed to establish more explicit guidelines to improve antibiotic stewardship, such as priority recommending amoxicillin and its derivatives for endodontic infections.

PMID:38888035 | DOI:10.1111/odi.15042

Khirurgiia (Mosk). 2024;(6):28-35. doi: 10.17116/hirurgia202406128.

ABSTRACT

OBJECTIVE: To demonstrate clinical features and outcomes in patients with cavitary lung lesions and COVID-19 associated pneumonia.

MATERIAL AND METHODS: A retrospective analysis of electronic medical records of 8261 patients with COVID-19 was performed. We selected 40 patients meeting the inclusion criteria. Sex, age, hospital-stay, lung tissue lesion, comorbidities, treatment, methods of respiratory support, complications and outcomes were evaluated.

RESULTS: Cavitary lung lesions were more common in men (67.5%). Age of patients ranged from 28 to 88 (mean 64.9±13.7) years. Hospital-stay in patients with cavitary lung lesions was 9-58 (median 27.5) days. There were 18 complications in 14 (35%) patients. Pneumothorax, isolated pneumomediastinum, pleural empyema, hemoptysis and sigmoid colon perforation were considered as complications of cavitary lung lesions. Nine (22.5%) patients died (5 of them with complications). Three patients died after surgical treatment. Long-term results were analyzed in 8 (25.8%) patients. Patients were followed-up for 3 months after discharge. Shrinkage of lesions occurred after 7-60 (mean 23) days, and complete obliteration of cavities came after 32 (range 14-90) days.

CONCLUSION: Cavitary lung lesions are a rare complication of COVID-19 pneumonia. There was no significant correlation of complications with age, sex, therapy, volume of lung lesions and non-invasive ventilation (NIV). Despite more common fatal outcomes in older patients undergoing NIV, the last one was prescribed exclusively due to disease progression and respiratory failure. Further research on this problem is necessary to identify possible risk factors of cavitary lung lesions.

PMID:38888016 | DOI:10.17116/hirurgia202406128

Vet Dermatol. 2024 Jun 18. doi: 10.1111/vde.13276. Online ahead of print.

ABSTRACT

BACKGROUND: Limited information exists about the correlation between clinical history and positive serum (SAT) and intradermal allergen test (IDAT) results in atopic dogs.

OBJECTIVES: To evaluate the correlation between clinical history and SAT/IDAT results in atopic dogs.

ANIMALS: Twenty-nine client-owned dogs with nonseasonal atopic dermatitis with or without seasonal exacerbation were enrolled.

MATERIALS AND METHODS: IDAT, SAT (immunoglobulin (Ig)M antibody capture enzyme-linked immunosorbent assay [MacELISA] with bromelain CCD inhibitor) and clinical information collected in a questionnaire regarding seasonal variations in pruritus affecting the dogs were performed on the same day. Two independent investigators (Inv A and Inv B) recorded IDAT results.

RESULTS: The kappa coefficients agreement for positive IDAT scores between Inv A and B was substantial. The agreement between IDAT and SAT results at different ELISA absorbance units (EAU) cut-offs (>79 and ≥300) was slight and fair for both investigators, respectively. A higher agreement was observed between IDAT and SAT (≥300 EAU) than between IDAT and SAT (>79 EAU) with the exception of mite and flea allergens. There was a statistically significant association between clinical history and positive IDAT results for seasonal allergens (Inv A and Inv B, p = 0.016). There was no significance between positive SAT results and clinical history. Five (IDAT) and 12 of 13 (SAT) atopic dogs without clinical seasonal exacerbation showed positive results for seasonal allergens.

CONCLUSIONS AND CLINICAL RELEVANCE: The agreement between IDAT and SAT ≥300 EAU results was fair and the agreement between IDAT and SAT >79 EAU results was slight for all allergens. Only positive IDAT results significantly correlated with clinical history.

PMID:38887975 | DOI:10.1111/vde.13276

CNS Neurosci Ther. 2024 Jun;30(6):e14810. doi: 10.1111/cns.14810.

ABSTRACT

AIMS: To study the changes in cortical thickness and subcortical gray matter structures in children with complete spinal cord injury (CSCI), reveal the possible causes of dysfunction beyond sensory motor dysfunction after CSCI, and provide a possible neural basis for corresponding functional intervention training.

METHODS: Thirty-seven pediatric CSCI patients and 34 age-, gender-matched healthy children as healthy controls (HCs) were recruited. The 3D high-resolution T1-weighted structural images of all subjects were obtained using a 3.0 Tesla MRI system. Statistical differences between pediatric CSCI patients and HCs in cortical thickness and volumes of subcortical gray matter structures were evaluated. Then, correlation analyses were performed to analyze the correlation between the imaging indicators and clinical characteristics.

RESULTS: Compared with HCs, pediatric CSCI patients showed decreased cortical thickness in the right precentral gyrus, superior temporal gyrus, and posterior segment of the lateral sulcus, while increased cortical thickness in the right lingual gyrus and inferior occipital gyrus. The volume of the right thalamus in pediatric CSCI patients was significantly smaller than that in HCs. No significant correlation was found between the imaging indicators and the injury duration, sensory scores, and motor scores of pediatric CSCI patients.

CONCLUSIONS: These findings demonstrated that the brain structural reorganizations of pediatric CSCI occurred not only in sensory motor areas but also in cognitive and visual related brain regions, which may suggest that the visual processing, cognitive abnormalities, and related early intervention therapy also deserve greater attention beyond sensory motor rehabilitation training in pediatric CSCI patients.

PMID:38887969 | DOI:10.1111/cns.14810

Ann Clin Transl Neurol. 2024 Jun 18. doi: 10.1002/acn3.52128. Online ahead of print.

ABSTRACT

OBJECTIVE: High-risk types of diffuse gliomas in adults include isocitrate dehydrogenase (IDH) wild-type glioblastomas and grade 4 astrocytomas. Achieving noninvasive prediction of high-risk molecular subtypes of gliomas is important for personalized and precise diagnosis and treatment.

METHODS: We retrospectively collected data from 116 patients diagnosed with adult diffuse gliomas. Multiple high-risk molecular markers were tested, and various habitat models and whole-tumor models were constructed based on preoperative routine and diffusion kurtosis imaging (DKI) sequences to predict high-risk molecular subtypes of gliomas. Feature selection and model construction utilized Least absolute shrinkage and selection operator (LASSO) and support vector machine (SVM). Finally, the Wilcoxon rank-sum test was employed to explore the correlation between habitat quantitative features (intra-tumor heterogeneity score，ITH score) and heterogeneity, as well as high-risk molecular subtypes.

RESULTS: The results showed that the habitat analysis model based on DKI performed remarkably well (with AUC values reaching 0.977 and 0.902 in the training and test sets, respectively). The model’s performance was further enhanced when combined with clinical variables. (The AUC values were 0.994 and 0.920, respectively.) Additionally, we found a close correlation between ITH score and heterogeneity, with statistically significant differences observed between high-risk and non-high-risk molecular subtypes.

INTERPRETATION: The habitat model based on DKI is an ideal means for preoperatively predicting high-risk molecular subtypes of gliomas, holding significant value for noninvasively alerting malignant gliomas and those with malignant transformation potential.

PMID:38887966 | DOI:10.1002/acn3.52128

Genet Epidemiol. 2024 Jun 17. doi: 10.1002/gepi.22577. Online ahead of print.

ABSTRACT

Instrumental variable (IV) analysis has been widely applied in epidemiology to infer causal relationships using observational data. Genetic variants can also be viewed as valid IVs in Mendelian randomization and transcriptome-wide association studies. However, most multivariate IV approaches cannot scale to high-throughput experimental data. Here, we leverage the flexibility of our previous work, a hierarchical model that jointly analyzes marginal summary statistics (hJAM), to a scalable framework (SHA-JAM) that can be applied to a large number of intermediates and a large number of correlated genetic variants-situations often encountered in modern experiments leveraging omic technologies. SHA-JAM aims to estimate the conditional effect for high-dimensional risk factors on an outcome by incorporating estimates from association analyses of single-nucleotide polymorphism (SNP)-intermediate or SNP-gene expression as prior information in a hierarchical model. Results from extensive simulation studies demonstrate that SHA-JAM yields a higher area under the receiver operating characteristics curve (AUC), a lower mean-squared error of the estimates, and a much faster computation speed, compared to an existing approach for similar analyses. In two applied examples for prostate cancer, we investigated metabolite and transcriptome associations, respectively, using summary statistics from a GWAS for prostate cancer with more than 140,000 men and high dimensional publicly available summary data for metabolites and transcriptomes.

PMID:38887957 | DOI:10.1002/gepi.22577

Circ Cardiovasc Qual Outcomes. 2024 Jun 18:e010731. doi: 10.1161/CIRCOUTCOMES.123.010731. Online ahead of print.

ABSTRACT

BACKGROUND: Text messages may enhance physical activity levels in patients with cardiovascular disease, including those enrolled in cardiac rehabilitation. However, the independent and long-term effects of text messages remain uncertain.

METHODS: The VALENTINE study (Virtual Application-supported Environment to Increase Exercise) was a micro-randomized trial that delivered text messages through a smartwatch (Apple Watch or Fitbit Versa) to participants initiating cardiac rehabilitation. Participants were randomized 4× per day over 6-months to receive no text message or a message encouraging low-level physical activity. Text messages were tailored on contextual factors (eg, weather). Our primary outcome was step count 60 minutes following a text message, and we used a centered and weighted least squares mean method to estimate causal effects. Given potential measurement differences between devices determined a priori, data were assessed separately for Apple Watch and Fitbit Versa users over 3 time periods corresponding to the initiation (0-30 days), maintenance (31-120 days), and completion (121-182 days) of cardiac rehabilitation.

RESULTS: One hundred eight participants were included with 70 552 randomizations over 6 months; mean age was 59.5 (SD, 10.7) years with 36 (32.4%) female and 68 (63.0%) Apple Watch participants. For Apple Watch participants, text messages led to a trend in increased step count by 10% in the 60-minutes following a message during days 1 to 30 (95% CI, -1% to +20%), with no effect from days 31 to 120 (+1% [95% CI, -4% to +5%]), and a significant 6% increase during days 121 to 182 (95% CI, +0% to +11%). For Fitbit users, text messages significantly increased step count by 17% (95% CI, +7% to +28%) in the 60-minutes following a message in the first 30 days of the study with no effect subsequently.

CONCLUSIONS: In patients undergoing cardiac rehabilitation, contextually tailored text messages may increase physical activity, but this effect varies over time and by device.

REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04587882.

PMID:38887953 | DOI:10.1161/CIRCOUTCOMES.123.010731

Ann Surg. 2024 Jun 18. doi: 10.1097/SLA.0000000000006416. Online ahead of print.

ABSTRACT

OBJECTIVE: To assess the utility of tumor-intrinsic and cancer-associated fibroblast (CAF) subtypes of pancreatic ductal adenocarcinoma (PDAC) in predicting response to neoadjuvant therapy (NAT) and overall survival.

BACKGROUND: PDAC remains a deadly disease with limited treatment options, and both the tumor as well as the microenvironment play an important role in pathogenesis. Gene expression-based tumor-intrinsic subtypes (classical and basal-like) have been shown to predict outcomes, but tumor microenvironment subtypes are still evolving.

METHODS: RNA-sequencing was performed on 114 deidentified resected PDAC tumors. Clinical data were collected by retrospective chart review. Single sample classifiers (SSCs) were used to determine classical and basal-like subtypes as well as tumor-permissive permCAF and tumor-restraining restCAF subtypes. Survival was analyzed using log-rank test.

RESULTS: Patients who received NAT had an increase in overall survival (OS), with median survival of 27.9 months compared to 20.1 months for those who did not receive NAT, but the difference did not reach statistical significance (HR 0.64, P=0.076). Either tumor-intrinsic or CAF subtypes alone were associated with OS regardless of NAT or no NAT, and patients with classical or restCAF subtype had the best outcomes. When evaluated together, patients with classical-restCAF subtype had the best OS and basal-permCAF the worst OS (P<0.0001). NAT patients with classical-restCAF subtype demonstrated the longest OS compared to the other groups (P=0.00041).

CONCLUSIONS: CAF subtypes have an additive effect over tumor-intrinsic subtypes in predicting survival with or without neoadjuvant FOLFIRINOX in PDAC. Molecular subtyping of both tumor and CAF compartments of PDAC may be important steps in selecting first-line systemic therapy.

PMID:38887930 | DOI:10.1097/SLA.0000000000006416

Head Neck. 2024 Jun 18. doi: 10.1002/hed.27830. Online ahead of print.

ABSTRACT

BACKGROUND: To establish and validate a machine learning model using pretreatment multiparametric magnetic resonance imaging-based radiomics data with clinical data to predict radiation-induced temporal lobe injury (RTLI) in patients with nasopharyngeal carcinoma (NPC) after intensity-modulated radiotherapy (IMRT).

METHODS: Data from 230 patients with NPC who received IMRT (130 with RTLI and 130 without) were randomly divided into the training (n = 161) and validation cohort (n = 69) with a ratio of 7:3. Radiomics features were extracted from pretreatment apparent diffusion coefficient (ADC) map, T2-weighted imaging (T2WI), and CE-T1-weighted imaging (CE-T1WI). T-test, spearman rank correlation, and least absolute shrinkage and selection operator (LASSO) algorithm were employed to identify significant radiomics features. Clinical features were selected with univariate and multivariate analyses. Radiomics and clinical models were constructed using multiple machine learning classifiers, and a clinical-radiomics nomogram that combined clinical with radiomics features was developed. Receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) were drawn to compare and verify the predictive performances of the clinical model, radiomics model, and clinical-radiomics nomogram.

RESULTS: A total of 5064 radiomics features were extracted, from which 52 radiomics features were selected to construct the radiomics signature. The AUC of the radiomics signature based on multiparametric MRI was 0.980 in the training cohort and 0.969 in the validation cohort, outperforming the radiomics signature only based on T2WI and CE-T1WI (p < 0.05), which highlighted the significance of the DWI sequence in the prediction of temporal lobe injury. The area under the curve (AUC) of the clinical model was 0.895 in the training cohort and 0.905 in the validation cohort. The nomogram, which integrated radiomics and clinical features, demonstrated an impressive AUC value of 0.984 in the validation set; however, no statistically significant difference was observed compared to the radiomics model. The calibration curve and decision curve analysis of the nomogram demonstrated excellent predictive performance and clinical feasibility.

CONCLUSIONS: The clinical-radiomics nomogram, integrating clinical features with radiomics features derived from pretreatment multiparametric MRI, exhibits compelling predictive performance for RTLI in patients diagnosed with NPC.

PMID:38887926 | DOI:10.1002/hed.27830