Tag: statistics

Comp Med. 2021 Mar 11. doi: 10.30802/AALAS-CM-20-000089. Online ahead of print.

ABSTRACT

CT (computerized tomography) is a necessary imaging modality for cancer staging and disease monitoring. Rodent models of cancer are commonly studied prior to human clinical trials, but CT in rodents can be difficult due to their small size and constant movement, which necessitates general anesthesia. Because microCT equipment is not always available, clinical CT may be a viable alternative. Limitations of microCT and clinical CT include biosecurity, anesthesia to limit image distortion due to motion, and cost. To address several of these constraints, we created a 3D-printed apparatus that accommodated simultaneous imaging of as many as 9 rats under gas anesthesia. Rats were anesthetized in series and placed in a 3 × 3 arrangement. To assess differences in attenuation between individual chambers and rows or columns in the device, we first imaged a standardized phantom plug as a control. We hypothesized that attenuation of specific rat organs would not be affected regardless of the location or position in the 3D-printed device. Four organs-liver, kidney, femur, and brain-were evaluated in 9 rats. For both the phantom and kidneys, statistically significant, but clinically negligible, effects on attenuation were noted between rows but not between columns. We attribute this finding to the absence of a top layer of the apparatus, which thus created asymmetric attenuation and beam hardening through the device. This apparatus allowed us to successfully image 9 rats simultaneously in a clinical CT machine, with negligible effects on attenuation. Planned improvements in this apparatus include completely enclosed versions for biosecure imaging.

PMID:33706858 | DOI:10.30802/AALAS-CM-20-000089

Euro Surveill. 2021 Mar;26(10). doi: 10.2807/1560-7917.ES.2021.26.10.2100130.

ABSTRACT

We show that the SARS-CoV-2 B.1.1.7 lineage is highly disseminated in Portugal, with the odds of B.1.1.7 proportion increasing at an estimated 89% (95% confidence interval: 83-95%) per week until week 3 2021. RT-PCR spike gene target late detection (SGTL) can constitute a useful surrogate to track B.1.1.7 spread, besides the spike gene target failure (SGTF) proxy. SGTL/SGTF samples were associated with statistically significant higher viral loads, but not with substantial shift in age distribution compared to non-SGTF/SGTL cases.

PMID:33706862 | DOI:10.2807/1560-7917.ES.2021.26.10.2100130

Eur J Intern Med. 2021 Mar 8:S0953-6205(21)00048-0. doi: 10.1016/j.ejim.2021.02.011. Online ahead of print.

ABSTRACT

BACKGROUND: Growth-differentiation factor-15 (GDF-15) has recently been described as a potential biomarker for predicting risk of mortality and cardiovascular events in patients with atrial fibrillation (AF) but requires validation in clinical practice.

METHODS: The study population consisted of 362 patients (mean age: 71 years, 37% women) with non-valvular AF included in a prospective cohort study. Relationship of GDF-15 with all-cause mortality and major adverse cardiac events (MACE) was analyzed using Cox regression. Survival analysis stratified by GDF-15 was based on national death records, while MACE was recorded at personal follow-up. Further, we evaluated the recently developed GDF-15 based prognostic score towards prediction of all-cause mortality (ABC-death score).

RESULTS: Over a median observation period of 4.3 years, 81 (23.3%) patients died, and over a median personal follow-up of 316 days 47 MACE occurred. GDF-15 was independently associated with all-cause mortality (adjusted HR per double increase 2.33, 95%CI 1.74-3.13) and MACE (adjusted HR per double increase 2.33, 95%CI 1.60-3.39). GDF-15 levels, measured at follow-up, were similarly associated with mortality, and longitudinal measurements of GDF-15 did not significantly differ. Six-year survival probability of patients above vs. below the median GDF-15 level was 44% (95%CI 34-57) and 84% (95%CI 76-93), respectively. The ABC-death score revealed a C-statistic of 0.80.

CONCLUSION: GDF-15 predicts risk of all-cause mortality and MACE in patients with non-valvular AF. Further, the ABC-death score showed good predictive accuracy in a “real-world” cohort. Therefore, introduction of GDF-15 into clinical practice would enhance risk prediction of morbidity and mortality in AF patients.

PMID:33706979 | DOI:10.1016/j.ejim.2021.02.011

Genome Med. 2021 Mar 11;13(1):42. doi: 10.1186/s13073-021-00845-7.

ABSTRACT

BACKGROUND: Contemporary deep learning approaches show cutting-edge performance in a variety of complex prediction tasks. Nonetheless, the application of deep learning in healthcare remains limited since deep learning methods are often considered as non-interpretable black-box models. However, the machine learning community made recent elaborations on interpretability methods explaining data point-specific decisions of deep learning techniques. We believe that such explanations can assist the need in personalized precision medicine decisions via explaining patient-specific predictions.

METHODS: Layer-wise Relevance Propagation (LRP) is a technique to explain decisions of deep learning methods. It is widely used to interpret Convolutional Neural Networks (CNNs) applied on image data. Recently, CNNs started to extend towards non-Euclidean domains like graphs. Molecular networks are commonly represented as graphs detailing interactions between molecules. Gene expression data can be assigned to the vertices of these graphs. In other words, gene expression data can be structured by utilizing molecular network information as prior knowledge. Graph-CNNs can be applied to structured gene expression data, for example, to predict metastatic events in breast cancer. Therefore, there is a need for explanations showing which part of a molecular network is relevant for predicting an event, e.g., distant metastasis in cancer, for each individual patient.

RESULTS: We extended the procedure of LRP to make it available for Graph-CNN and tested its applicability on a large breast cancer dataset. We present Graph Layer-wise Relevance Propagation (GLRP) as a new method to explain the decisions made by Graph-CNNs. We demonstrate a sanity check of the developed GLRP on a hand-written digits dataset and then apply the method on gene expression data. We show that GLRP provides patient-specific molecular subnetworks that largely agree with clinical knowledge and identify common as well as novel, and potentially druggable, drivers of tumor progression.

CONCLUSIONS: The developed method could be potentially highly useful on interpreting classification results in the context of different omics data and prior knowledge molecular networks on the individual patient level, as for example in precision medicine approaches or a molecular tumor board.

PMID:33706810 | DOI:10.1186/s13073-021-00845-7

Eur J Med Res. 2021 Mar 12;26(1):24. doi: 10.1186/s40001-021-00491-0.

ABSTRACT

BACKGROUND: The incidence of post-traumatic osteoarthritis (PTOA) after anterior cruciate ligament reconstruction (ACLR) is high, but there is still a lack of intra-operative preventive measures. This study aimed to evaluate the effect of different irrigating solutions continuous irrigation on intra-articular inflammation and cartilage degeneration.

METHODS: 66 New Zealand rabbits were randomly divided into normal (N) group, no treatment (NT) group, sodium chloride (NaCl) group, magnesium sulfate (MgSO₄) group, and calcium chloride (CaCl₂) group. The right knee joint of the experimental group was utilized to construct the model of PTOA, and the left side was utilized as the normal control group. At different time points postoperatively, the blood concentration of hemoglobin and Mg2 + , the synovial fluid concentration of IL-1 β, TNF-α, tartrate-resistant acid phosphatase-5b (TRAP-5b), and Type II Collagen, the gene expression of IL-1 β and MMP-3, and the protein expression of TRPV5 and CaM were detected. Pearson’s linear correlation was employed to identify the possible relationship between the expression of TRAP-5b and the expression of IL-1β, IL-6, TNF-α, and Type II collagen. The hematoxylin and eosin staining (HE), Masson’s trichrome staining, and Alcian blue staining were performed at postoperative 35 days. Osteoarthritis Scoring (OA score) comprised categories including Alcian blue staining, cartilage histology, the cellular density of cartilage, degree of cell disintegration, and formation of chondrocyte cluster were blindly scored by trained researchers at postoperative 35 days.

RESULTS: There was no statistical difference (P > 0.05) in the hemoglobin concentration between different groups. The concentration of serum Mg²⁺ in the MgSO₄ group was higher than that of the other three groups (P < 0.05) on the same day of operation, then gradually decreased. The expression of IL-1 β, IL-6, and TRAP-5b in synovial fluid increased 5 days after the operation, decreased at 15 days, and then increased again with time in the NT group, NaCl group, and NT group and NaCl group. At 35 days after the operation, the expression of IL-1 β, IL-6, TRAP-5b, and type II collagen in the MgSO₄ group were lower than that in the other three groups (except group N) (P < 0.05).The correlation analysis results showed that the TRAP-5b levels correlated positively with IL-1 β, IL-6, TNF-α, and type II collagen concentrations. The histological examination revealed that the surface smoothness of cartilage, the morphology of chondrocytes, the arrangement of collagen fibers, and the density of proteoglycan in the MgSO₄ group were better than those in other experimental groups. At 35 days postoperatively, the gene expression of IL-1 β and MMP-3 and the protein expression of CaM and TRPV5 in synovium in the MgSO₄ group was lower than that in the NaCl group and CaCl₂ group.

CONCLUSION: Intra-operative irrigation with magnesium sulfate solution can inhibit the inflammatory factors and the expression of TRPV5, which can also reduce collagen loss and delay cartilage degeneration. Therefore, the use of magnesium sulfate in intra-operative irrigation may be an ideal choice to prevent PTOA.

PMID:33706812 | DOI:10.1186/s40001-021-00491-0

Behav Cogn Psychother. 2021 Mar 12:1-13. doi: 10.1017/S1352465821000114. Online ahead of print.

ABSTRACT

BACKGROUND: This was a multi-site evaluation of psycho-educational transdiagnostic seminars (TDS) as a pre-treatment intervention to enhance the effectiveness and utilisation of high-intensity cognitive behavioural therapy (CBT).

AIMS: To evaluate the effectiveness of TDS combined with high-intensity CBT (TDS+CBT) versus a matched sample receiving CBT only. Second, to determine the consistency of results across participating services which employed CBT+TDS. Finally, to determine the acceptability of TDS across patients with different psychological disorders.

METHOD: 106 patients across three services voluntarily attended TDS while on a waiting list for CBT (TDS+CBT). Individual and pooled service pre-post treatment effect sizes were calculated using measures of depression, anxiety and functional impairment. Effectiveness and completion rates for TDS+CBT were compared with a propensity score matched sample from an archival dataset of cases who received high-intensity CBT only.

RESULTS: Pre-post treatment effect sizes for TDS+CBT were comparable to the matched sample. Recovery rates were greater for the group receiving TDS; however, this was not statistically significant. Greater improvements were observed during the waiting-list period for patients who had received TDS for depression (d = 0.49 compared with d = 0.07) and anxiety (d = 0.36 compared with d = 0.04).

CONCLUSIONS: Overall, this new evidence found a trend for TDS improving symptoms while awaiting CBT across three separate IAPT services. The effectiveness of TDS now warrants further exploration through an appropriately sized randomised control trial.

PMID:33706847 | DOI:10.1017/S1352465821000114

Zhonghua Shao Shang Za Zhi. 2021 Mar 3;37(3):1-5. doi: 10.3760/cma.j.cn501120-20200304-00121. Online ahead of print.

ABSTRACT

Objective: To explore the effect of autologous skin paste on repairing wound of medium-thickness skin donor site. Methods: The prospective randomized controlled research method was applied. From October 2018 to December 2019, 18 patients with flame burn or hydrothermal scald, met the inclusion criteria were admitted to Jinhua Hospital Affiliated to Zhejiang University School of Medicine, including 15 males and 3 females, aged (45±6) years, and the wounds were repaired with medium-thickness skin grafts. The wound area after medium-thickness skin grafting was (121±33) cm2. The wound of donor site of medium-thickness skin graft in each patient was divided into 2 wounds in equal area and included into autologous skin paste group and conventional treatment group with random number table, with 18 wounds in each group.The wounds in autologous skin paste group were repaired with skin paste prepared with remaining skin fragments after autologous medium-thickness skin grafting, and the wounds in conventional treatment group were repaired with petroleum jelly gauze and sterile gauze. On 3, 7, 14, 21 d after operation, the wound healing in 2 groups was observed, and the wound healing rate was calculated. The wound healing time in 2 groups was recorded. Occurrences of subcutaneous effusion and infection on 3, 7, 14, 21 d after operation and wound rupture in 3 months after operation were observed. In 6 months after operation, the Vancouver scar scale (VSS) was used to evaluate the scar formation of wounds in 2 groups. Data were statistically analyzed with analysis of variance for repeated measurement, chi-square test, and group t test. Results: The wounds in 2 groups did not heal on 3 and 7 d after operation. The wound healing rate in autologous skin paste group was (29.8±2.5)% and (95.6±4.7)% on 14 and 21 d after operation, which were significantly higher than (25.8±2.9)% and (82.6±8.9)% in conventional treatment group (t=4.3, 5.6, P<0.01). The wound healing time in autologous skin paste group was (21.8±1.4) d, which was significantly shorter than (25.6±2.0) d in conventional treatment group (t=6.24, P<0.01). On 3, 7, 14, 21 d after operation, there were no complications such as subcutaneous effusion and infection in wounds of 2 groups. In 3 months after operation, ulceration occurred in wounds of 2 patients in autologous skin paste group, which was significantly less than 12 patients in conventional treatment group (χ2=11.688, P＜0.01). The wounds with ulceration healed after dressing change. In 6 months after operation, the VSS score of wounds in autologous skin paste group was (9.1±1.1) points, which was significantly lower than (11.3±1.2) points in conventional treatment group (t=-5.75, P＜0.01). Conclusion: The remaining fragments after autologous medium-thickness skin grafting are prepared into skin paste to repair wound of donor site of medium-thickness skin graft can shorten wound healing time, improve wound healing quality, reduce degree of scar hyperplasia, which has a good clinical effect.

PMID:33706433 | DOI:10.3760/cma.j.cn501120-20200304-00121

Zhonghua Xin Xue Guan Bing Za Zhi. 2021 Mar 24;49(3):236-241. doi: 10.3760/cma.j.cn112148-20200526-00431. Online ahead of print.

ABSTRACT

Objective: To investigate the impact of different levels of systolic blood pressure on all-cause, cardiovascular and cerebrovascular mortality in patients with nonvalvular atrial fibrillation (AF). Methods: This is a prospective cohort study. Patients with AF or atrial flutter diagnosed by 12 lead electrocardiogram during physical examination of Kailuan Group employees from July 2006 to December 2017 or previously diagnosed with AF in an inpatient setting at a level 2A hospital or above were eligible for the study. Baseline clinical characteristics including age, gender, systolic blood pressure were collected. According to the level of systolic blood pressure, patients were divided into systolic blood pressure<120 mmHg (1 mmHg=0.133 kPa)group, 120 mmHg ≤ systolic blood pressure<140 mmHg group, and systolic blood pressure ≥140 mmHg group. The time of first diagnosis with AF was defined as the start of follow-up and the final follow-up ended at December 2018. Primary endpoint was all-cause death. Related information was obtained through the social security system or inpatient medical records. The cause of death was defined according to the International Classification of Diseases disease (ICD-10) codes by professional medical stuffs. Multifactorial Cox proportional risk model was used to analyze the relative risk ratios for the occurrence of death in different systolic blood pressure level groups. The relationship between systolic blood pressure levels and mortality in the patients with AF was analyzed by using natural spline function curves. Results: A total of 1 721 patients with AF were enrolled (average age=(67.0±9.0) years), patients were followed up for (6.3±3.8) years. 544 out of 1 721 patients with AF died during the follow-up period (31.61%). The cumulative incidence rate of all-cause mortality, cardiovascular and cerebrovascular death was 26.13%, 25.59%, 36.96% and 14.86%, 11.87%, 19.76% respectively in the systolic blood pressure<120 mmHg, 120 mmHg ≤ systolic blood pressure<140 mmHg and systolic blood pressure ≥140 mmHg groups. The cumulative incidence rate of all-cause, cardiovascular and cerebrovascular death was significantly higher in the group with systolic blood pressure ≥140 mmHg than in 120 mmHg ≤ systolic blood pressure<140 mmHg group (P<0.05). Compared with 120 mmHg ≤ systolic blood pressure<140 mmHg group, multivariable Cox proportional hazards regression models showed that the HRs (95%CI) for all-cause, cardiovascular and cerebrovascular death were 1.47 (1.20 to 1.79) and 1.69 (1.27 to 2.26) for the group with systolic blood pressure ≥ 140 mmHg (P<0.05). In contrast, the HRs (95%CI) for all-cause, cardiovascular and cerebrovascular death in the systolic blood pressure<120 mmHg group were 0.99 (0.73-1.35) and 1.24 (0.82-1.89), respectively, with no statistically significant differences between the two groups (P>0.05). The natural spline curve showed that there was a “U” relationship between systolic blood pressure levels and all cause death and cardiovascular and cerebrovascular death in this patient cohort. Systolic blood pressure greater than or less than 123 mmHg was associated with increased risk of death of AF patients in this cohort. Conclusion: Compared with systolic blood pressure<120 mmHg and systolic blood pressure≥140 mmHg group, the risk of all-cause and cardiovascular and cerebrovascular death is the lowest in AF patients with 120 mmHg ≤ systolic blood pressure<140 mmHg in this cohort.

PMID:33706457 | DOI:10.3760/cma.j.cn112148-20200526-00431

Zhonghua Shao Shang Za Zhi. 2021 Mar 3;37(3):1-8. doi: 10.3760/cma.j.cn501120-20200120-00030. Online ahead of print.

ABSTRACT

Objective: To observe the functional changes of skeletal muscle in severely burned rats, and investigate the possible effects and mechanisms of Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) pathway inhibitors on skeletal muscle function. Methods: The experiment research method was applied. One hundred and twenty male Wistar rats of 8-weeks-old were divided into sham injury group, simple burn group, and burn+JAK/STAT3 inhibitor group according to the random number table, with 40 rats in each group. Rats in simple burn group and burn+JAK/STAT3 inhibitor group were inflicted with 50% total body surface area full-thickness scald in back and abdomen, and rats in sham injury group were sham injured. Rats in burn+JAK/STAT3 inhibitor group were intraperitoneally injected with JAK/STAT3 inhibitor ruxolitinib. On post injury day (PID) 0, 1, 4, 7, and 14, 8 rats in each group were used to measure the specific force generated by extensor digitorum longus in optimal length stimulated with pulse frequency of 20, 40, 60, 80, 100, 120, 140, 160 Hz using a multichannel electrophysiological instrument, and specific force in fatigue period of extensor digitorum longus in optimal length stimulated with pulse frequency of 50 Hz for 0, 10, 20, 30, 60, 120, 180, 240, 300 s. On PID 0, 1, 4, 7, and 14, carbonyl compound content of extensor digitorum longus was determined by ultraviolet spectrophotometry, and ATP content of extensor digitorum longus was determined by micrometry. Data were statistically analyzed with analysis of variance for factorial design, Bonferroni test, and t test. Results: (1) Compared with sham injury group, specific forces of extensor digitorum longus of rats in simple burn group were significantly decreased after stimulated with all the pulse frequency on PID 0, 1, 7, and all the pulse frequency except for 20 Hz on PID 4, and pulse frequency of 20 and 40 Hz on PID 14 (P<0.05 or P<0.01). Compared with simple burn group, specific forces of extensor digitorum longus of rats in burn+JAK/STAT3 inhibitor group were significantly increased after stimulated with all pulse frequency except for 20 Hz on PID 1 and all the pulse frequency on PID 4, 7, and 14 (P<0.05 or P<0.01). (2) Compared with sham injury group, specific forces of extensor digitorum longus of rats in simple burn group were significantly decreased in fatigue period at all the stimulation time points except for 240 s on PID 7 (P<0.05 or P<0.01). Compared with simple burn group, specific forces of extensor digitorum longus of rats in burn+JAK/STAT3 inhibitor group were significantly increased in fatigue period at all stimulation time points except for 240 s on PID 4, and all stimulation time points on PID 7 and 14 (P<0.05 or P<0.01). (3) The carbonyl compound content of extensor digitorum longus of rats in simple burn group on PID 0, 1, 4, 7, and 14 was (0.651±0.155), (0.739±0.194), (0.618±0.086), (0.813±0.162), (0.615±0.115) nmol/mg, which were significantly higher than (0.196±0.0190, (0.156±0.004), (0.169±0.023) (0.156±0.027), (0.175±0.008) nmol/mg of rats in simple burn group (t=7.219, 6.491, 10.938, 9.182, 11.589, P<0.01) and (0.538±0.069), (0.369±0.059), (0.273±0.061), (0.334±0.109), (0.318±0.101) nmol/mg of rats in burn+JAK/STAT3 inhibitor group (t=2.446, 4.689, 8.355, 5.754, 6.097, P<0.05 or P<0.01). (4) The ATP content in extensor digitorum longus of rats in simple burn group on PID 1, 4, 7, and 14 was significantly lower than that in sham injury group (t=7.159, 7.591, 7.473, 4.026, P<0.01) and burn+JAK/STAT3 inhibitor group (t=2.295, 2.575, 2.453, 2.997, P<0.05). Conclusions: After severe burn, the specific force of extensor digitorum longus in rat decreased significantly after stimulated with different pulse frequencies, and the extensor digitorum longus in rat was prone to fatigue. Blocking the JAK/STAT3 signaling pathway could reduce the oxidative stress of muscle protein and increase ATP content, thereby reducing the muscle strength decline caused by burn and improving the muscle strength decline during fatigue.

PMID:33706427 | DOI:10.3760/cma.j.cn501120-20200120-00030

Zhonghua Shao Shang Za Zhi. 2021 Mar 3;37(3):1-6. doi: 10.3760/cma.j.cn501120-20200210-00048. Online ahead of print.

ABSTRACT

Objective: To explore the effects of stepwise acute pain management on acute pain and post-traumatic stress disorder (PTSD) in burn children. Method: From November 2018 to December 2019, 196 burn children who were admitted to the Department of Burns of West China Hospital of Sichuan University and met the inclusion criteria were enrolled in the prospective randomized controlled study. The patients were divided into traditional pain management group (97 patients, 51 males and 46 females, aged 1 to 6 years) and stepped pain management group (96 patients, 55 males and 41 females, aged 1 to 6 years) according to the random number table. Children in traditional pain management group were treated with traditional acute pain care, while the children in stepped pain management group were treated with stepped acute pain management (moderate pain was treated with oral administration of acetaminophen sustained-release dry suspension, and severe pain was treated with morphine intravenous injection) after admission. The revised COMFORT behavior scale was applied to compare the resting pain levels of children in the two groups within 3 days after burn (1, 9, and 17 o’clock per day).The adverse reactions of patients in the stepped pain management group during the treatment period were recorded. The occurrence of PTSD one month after injury was evaluated in both groups by the PTSD alternative algorithm. Data were statistically analyzed with independent sample t test, Bonferroni correction, analysis of variance for repeated measurement, chi-square test, Wilcoxon rank sum test, and Fisher’s exact probability test. Results: The pain scores of children in stepped pain management group were lower than traditional pain management group at 1, 9, and 17 o’clock on post injury day (PID) 1, 1, 9, and 17 o’clock on PID 2, and 1, 9, and 17 o’clock on PID 3 (t=2.71, 3.44, 4.05, 4.18, 4.08, 4.19, 4.25, 3.69, 3.71, P＜0.05 or P＜0.01). The pain scores of children in both groups showed a decreasing trend over time. Of the 96 children in stepped pain management group, 84 children were treated with oral administration of acetaminophen sustained-release dry suspension, and 12 children were treated with morphine intravenous injection. No adverse reactions occurred during the treatment period. The incidence of PTSD of children in stepped pain management group was 3.12% (3/96), which was significantly lower than 14.43% (14/97) in traditional pain management group, P＜0.05. Conclusions: The stepped acute pain management can relieve the acute pain and reduce the incidence of PTSD in burn children.

PMID:33706428 | DOI:10.3760/cma.j.cn501120-20200210-00048