Category: Statistics

Cardiol Young. 2023 Jan 10:1-6. doi: 10.1017/S1047951122004140. Online ahead of print.

ABSTRACT

BACKGROUND: While most children with multisystem inflammatory syndrome in children have rapid recovery of cardiac dysfunction, little is known about the long-term outcomes regarding exercise capacity. We aimed to compare the exercise capacity among patients with multisystem inflammatory syndrome in children versus viral/idiopathic myocarditis at 3-6 months after initial diagnosis.

METHODS: We performed a retrospective cohort study among patients with multisystem inflammatory syndrome in children in June 2020 to May 2021 and patients with viral/idiopathic myocarditis in August 2014 to January 2020. Data from cardiopulmonary exercise test as well as echocardiographic and laboratory data were obtained. Inclusion criteria included diagnosis of multisystem inflammatory syndrome in children or viral/idiopathic myocarditis, exercise test performed within 3-6 months of hospital discharge, and maximal effort on cardiopulmonary exercise test as determined by respiratory exchange ratio >1.10.

RESULTS: Thirty-one patients with multisystem inflammatory syndrome in children and 25 with viral/idiopathic myocarditis were included. The mean percent predicted peak VO2 was 90.84% for multisystem inflammatory syndrome in children patients and 91.08% for those with viral/idiopathic myocarditis (p-value 0.955). There were no statistically significant differences between the groups with regard to percent predicted maximal heart rate, metabolic equivalents, percent predicted peak VO2, percent predicted anerobic threshold, or percent predicted O2 pulse. There was a statistically significant correlation between lowest ejection fraction during hospitalisation and peak VO2 among viral/idiopathic myocarditis patients (r: 0.62, p-value 0.01) but not multisystem inflammatory syndrome in children patients (r: 0.1, p-value 0.6).

CONCLUSIONS: Patients with multisystem inflammatory syndrome in children and viral myocarditis appear to, on average, have normal exercise capacity around 3-6 months following hospital discharge. For patients with viral/idiopathic myocarditis, those with worse ejection fraction during hospitalisation had lower peak VO2 on cardiopulmonary exercise test.

PMID:36624558 | DOI:10.1017/S1047951122004140

Stat Med. 2023 Jan 9. doi: 10.1002/sim.9647. Online ahead of print.

ABSTRACT

We propose a joint modeling approach to investigating the effects of social-psychological factors on the onset of depression. The proposed model comprises two components. The first one is a confirmatory factor analysis model that summarizes latent factors through multiple correlated observed variables. The second one is a logistic regression model that investigates the effects of observed and latent influence factors on the occurrence of depression. We develop a hybrid procedure based on the borrow-strength estimation procedure and the weighted score function to estimate the model parameters. The asymptotic properties of the proposed estimators are established. Simulation studies demonstrate that the method we proposed performs well. An application to a study concerning the social-psychological factors of depression is provided.

PMID:36624549 | DOI:10.1002/sim.9647

Exp Hematol Oncol. 2023 Jan 9;12(1):2. doi: 10.1186/s40164-022-00362-2.

ABSTRACT

Hemophagocytic lymphohistiocytosis (HLH) is a potentially fatal inflammatory clinical condition, in which an exaggerated immune response is ineffectively regulated. Although etoposide-containing regimens are generally recommended for children with HLH, the exact role of etoposide in the adult setting remains unclear. We performed a systematic review of the literature on the use of etoposide in adults with HLH. All articles written in English on the use of etoposide in adults with HLH available from seven databases and published on or before July 2021 were analyzed. Thirteen studies were found to be relevant to the search results. Ten of these studies report a statistical analysis on the effect of etoposide, of which five found etoposide-containing regimens superior to non-etoposide-containing regimens. Seven studies provided sufficient data to be included in the meta-analysis. For these data, the estimated logit relative risk of etoposide on survival was 1.06 (95% confidence interval: 0.92-1.21, standard error: 2.06). The pooled data of the meta-analysis did thus not support a beneficial effect of etoposide. It should be taken into account that the presented results are highly susceptible to bias and that the effect of etoposide differs between HLH-triggers. Although the meta-analysis does not support the effect of etoposide, we do not recommend abandoning etoposide as treatment modality. The limitations of the meta-analysis, together with several individual articles confirming the benefit of etoposide, justify etoposide for select cases in adults with HLH such as refractory or severe disease with (threatening) multiorgan failure.

PMID:36624539 | DOI:10.1186/s40164-022-00362-2

Crit Care. 2023 Jan 9;27(1):8. doi: 10.1186/s13054-022-04292-7.

ABSTRACT

BACKGROUND: Generalised convulsive status epilepticus (GCSE) is a medical emergency. Guidelines recommend a stepwise strategy of benzodiazepines followed by a second-line anti-seizure medicine (ASM). However, GCSE is uncontrolled in 20-40% patients and is associated with protracted hospitalisation, disability, and mortality. The objective was to determine whether valproic acid (VPA) as complementary treatment to the stepwise strategy improves the outcomes of patients with de novo established GCSE.

METHODS: This was a multicentre, double-blind, randomised controlled trial in 244 adults admitted to intensive care units for GCSE in 16 French hospitals between 2013 and 2018. Patients received standard care of benzodiazepine and a second-line ASM (except VPA). Intervention patients received a 30 mg/kg VPA loading dose, then a 1 mg/kg/h 12 h infusion, whilst the placebo group received an identical intravenous administration of 0.9% saline as a bolus and continuous infusion. Primary outcome was proportion of patients discharged from hospital by day 15. The secondary outcomes were seizure control, adverse events, and cognition at day 90.

RESULTS: A total of 126 (52%) and 118 (48%) patients were included in the VPA and placebo groups. 224 (93%) and 227 (93%) received a first-line and a second-line ASM before VPA or placebo infusion. There was no between-group difference for patients hospital-discharged at day 15 [VPA, 77 (61%) versus placebo, 72 (61%), adjusted relative risk 1.04; 95% confidence interval (0.89-1.19); p = 0.58]. There were no between-group differences for secondary outcomes.

CONCLUSIONS: VPA added to the recommended strategy for adult GCSE is well tolerated but did not increase the proportion of patients hospital-discharged by day 15.

TRIAL REGISTRATION NO: NCT01791868 (ClinicalTrials.gov registry), registered: 15 February 2012.

PMID:36624526 | DOI:10.1186/s13054-022-04292-7

J Transl Med. 2023 Jan 9;21(1):12. doi: 10.1186/s12967-022-03760-6.

ABSTRACT

BACKGROUND/AIMS: Nonobese metabolic dysfunction-associated fatty liver disease (MAFLD) is paradoxically associated with improved metabolic and pathological features at diagnosis but similar cardiovascular diseases (CVD) prognosis to obese MAFLD. We aimed to utilize the metabolomics to identify the potential metabolite profiles accounting for this phenomenon.

METHODS: This prospective multicenter cross-sectional study was conducted in China enrolling derivation and validation cohorts. Liquid chromatography coupled with mass spectrometry and gas chromatography-mass spectrometry were applied to perform a metabolomics measurement.

RESULTS: The study involved 120 MAFLD patients and 60 non-MAFLD controls in the derivation cohort. Controls were divided into two groups according to the presence of carotid atherosclerosis (CAS). The MAFLD group was further divided into nonobese MAFLD with/without CAS groups and obese MAFLD with/without CAS groups. Fifty-six metabolites were statistically significant for discriminating the six groups. Among the top 10 metabolites related to CAS in nonobese MAFLD, only phosphatidylethanolamine (PE 20:2/16:0), phosphatidylglycerol (PG 18:0/20:4) and de novo lipogenesis (16:0/18:2n-6) achieved significant areas under the ROC curve (AUCs, 0.67, p = 0.03; 0.79, p = 0.02; 0.63, p = 0.03, respectively). The combination of these three metabolites and liver stiffness achieved a significantly higher AUC (0.92, p < 0.01). In obese MAFLD patients, cystine was found to be significant with an AUC of 0.69 (p = 0.015), followed by sphingomyelin (SM 16:1/18:1) (0.71, p = 0.004) and de novo lipogenesis (16:0/18:2n-6) (0.73, p = 0.004). The combination of these three metabolites, liver fat content and age attained a significantly higher AUC of 0.91 (p < 0.001). The AUCs of these metabolites remained highly significant in the independent validation cohorts involving 200 MAFLD patients and 90 controls.

CONCLUSIONS: Diagnostic models combining different metabolites according to BMI categories could raise the accuracy of identifying subclinical CAS. Trial registration The study protocol was approved by the local ethics committee and all the participants have provided written informed consent (Approval number: [2014] No. 112, registered at the Chinese Clinical Trial Registry, ChiCTR-ChiCTR2000034197).

PMID:36624524 | DOI:10.1186/s12967-022-03760-6

Diagn Progn Res. 2023 Jan 10;7(1):1. doi: 10.1186/s41512-022-00138-6.

ABSTRACT

BACKGROUND: Simple blood tests can play an important role in identifying patients for cancer investigation. The current evidence base is limited almost entirely to tests used in isolation. However, recent evidence suggests combining multiple types of blood tests and investigating trends in blood test results over time could be more useful to select patients for further cancer investigation. Such trends could increase cancer yield and reduce unnecessary referrals. We aim to explore whether trends in blood test results are more useful than symptoms or single blood test results in selecting primary care patients for cancer investigation. We aim to develop clinical prediction models that incorporate trends in blood tests to identify the risk of cancer.

METHODS: Primary care electronic health record data from the English Clinical Practice Research Datalink Aurum primary care database will be accessed and linked to cancer registrations and secondary care datasets. Using a cohort study design, we will describe patterns in blood testing (aim 1) and explore associations between covariates and trends in blood tests with cancer using mixed-effects, Cox, and dynamic models (aim 2). To build the predictive models for the risk of cancer, we will use dynamic risk modelling (such as multivariate joint modelling) and machine learning, incorporating simultaneous trends in multiple blood tests, together with other covariates (aim 3). Model performance will be assessed using various performance measures, including c-statistic and calibration plots.

DISCUSSION: These models will form decision rules to help general practitioners find patients who need a referral for further investigation of cancer. This could increase cancer yield, reduce unnecessary referrals, and give more patients the opportunity for treatment and improved outcomes.

PMID:36624489 | DOI:10.1186/s41512-022-00138-6

BMC Surg. 2023 Jan 9;23(1):4. doi: 10.1186/s12893-022-01899-z.

ABSTRACT

BACKGROUND: Computer Assisted Design and Computer Assisted Manufacturing (CAD/CAM) have revolutionized oncologic surgery of the head and neck. A multitude of benefits of this technique has been described, but there are only few reports of donor site comorbidity following CAD/CAM surgery.

METHODS: This study investigated comorbidity of the hip following deep circumflex iliac artery (DCIA) graft raising using CAD/CAM techniques. A cross-sectional examination was performed to determine range of motion, muscle strength and nerve disturbances. Furthermore, correlations between graft volume and skin incision length with postoperative donor site morbidity were assessed using Spearman’s rank correlation, linear regression and analysis of variance (ANOVA).

RESULTS: Fifteen patients with a mean graft volume of 21.2 ± 5.7 cm³ and a mean incision length of 228.0 ± 30.0 mm were included. Patients reported of noticeable physical limitations in daily life activities (12.3 ± 11.9 weeks) and athletic activities (38.4 ± 40.0 weeks in mean) following surgery. Graft volume significantly correlated with the duration of the use of walking aids (R = 0.57; p = 0.033) and impairment in daily life activities (R = 0.65; p = 0.012). The length of the scar of the donor-site showed a statistically significant association with postoperative iliohypogastric nerve deficits (F = 4.4, p = 0.037). Patients with anaesthaesia of a peripheral cutaneous nerve had a larger mean scar length (280 ± 30.0 mm) than subjects with hypaesthesia (245 ± 10.1 mm) or no complaints (216 ± 27.7 mm).

CONCLUSIONS: Despite sophisticated planning options in modern CAD/CAM surgery, comorbidity of the donor site following iliac graft harvesting is still a problem. This study is the first to investigate comorbidity after DCIA graft raising in a patient group treated exclusively with CAD/CAM techniques. The results indicate that a minimal invasive approach in terms of small graft volumes and small skin incisions could help to reduce postoperative symptomatology. Trial registration Retrospectively registered at the German Clinical Trials Register (DRKS-ID: DRKS00029066); registration date: 23/05/2022.

PMID:36624485 | DOI:10.1186/s12893-022-01899-z

J Transl Med. 2023 Jan 9;21(1):11. doi: 10.1186/s12967-022-03819-4.

ABSTRACT

BACKGROUND: Radiotherapy (RT) is the standard treatment for nasopharyngeal carcinoma (NPC). However, due to individual differences in radiosensitivity, biomarkers are needed to tailored radiotherapy to cancer patients. However, comprehensive genome-wide radiogenomic studies on them are still lacking. The aim of this study was to identify genetic variants associated with radiotherapy response in patients with NPC.

METHODS: This was a large‑scale genome-wide association analysis (GWAS) including a total of 981 patients. 319 individuals in the discovery stage were genotyped for 688,783 SNPs using whole genome-wide screening microarray. Significant loci were further genotyped using MassARRAY system and TaqMan SNP assays in the validation stages of 847 patients. This study used logistic regression analysis and multiple bioinformatics tools such as PLINK, LocusZoom, LDBlockShow, GTEx, Pancan-meQTL and FUMA to examine genetic variants associated with radiotherapy efficacy in NPC.

RESULTS: After genome-wide level analysis, 19 SNPs entered the validation stage (P < 1 × 10^{– 6}), and rs11130424 ultimately showed statistical significance among these SNPs. The efficacy was better in minor allele carriers of rs11130424 than in major allele carriers. Further stratified analysis showed that the association existed in patients in the EBV-positive, smoking, and late-stage (III and IV) subgroups and in patients who underwent both concurrent chemoradiotherapy and induction/adjuvant chemotherapy.

CONCLUSION: Our study showed that rs11130424 in the CACNA2D3 gene was associated with sensitivity to radiotherapy in NPC patients.

TRIAL REGISTRATION NUMBER: Effect of genetic polymorphism on nasopharyngeal carcinoma chemoradiotherapy reaction, ChiCTR-OPC-14005257, Registered 18 September 2014, http://www.chictr.org.cn/showproj.aspx?proj=9546 .

PMID:36624463 | DOI:10.1186/s12967-022-03819-4

Virol J. 2023 Jan 9;20(1):4. doi: 10.1186/s12985-023-01962-y.

ABSTRACT

BACKGROUND: Under the pressure of non-pharmaceutical interventions (NPIs) targeting severe acute respiratory syndrome coronavirus 2, the prevalence of human adenovirus (HAdV) was monitored before and after NPIs launched on Jan 24, 2020 in pediatric patients in Beijing, China.

METHODS: Respiratory samples collected from children hospitalized with acute respiratory infections from Jan 2015 to Dec 2021 were screened by direct immunofluorescence test or capillary electrophoresis-based multiplex PCR assay. The hexon, penton base, and fiber genes were amplified from HAdV positive specimens, then sequenced. For HAdV typing, phylogenetic trees were built by MEGA X. Then clinical data of HAdV positive cases were collected. All data were evaluated using SPSS Statistics 22.0 software.

RESULTS: A total of 16,097 children were enrolled and 466 (2.89%, 466/16,097) were HAdV-positive. The positive rates of HAdV varied, ranging from 4.39% (151/3,438) in 2018 to1.25% (26/2,081) in 2021, dropped from 3.19% (428/13,408) to 1.41% (38/2,689) from before to after NPIs launched (P < 0.001). There were 350 cases typed into nine types of species B, C, or E and 34 recorded as undetermined. Among them, HAdV-B3 (51.56%, 198/384) was the most prevalent types from 2015 to 2017, and HAdV-B7 (29.17%, 112/384) co-circulated with HAdV-B3 from 2018 to 2019. After NPIs launched, HAdV-B3 and B7 decreased sharply with HAdV-B7 undetected in 2021, while HAdV-C1 became the dominant one and the undetermined were more.

CONCLUSIONS: The endemic pattern of HAdV changed in Beijing because of the NPIs launched for COVID-19. Especially, the dominant types changed from HAdV-B to HAdV-C.

PMID:36624458 | DOI:10.1186/s12985-023-01962-y

World J Emerg Surg. 2023 Jan 9;18(1):3. doi: 10.1186/s13017-023-00474-y.

ABSTRACT

BACKGROUND: Colorectal cancer presents as emergencies in 20% of the cases. Emergency resection is associated with high postoperative morbidity and mortality. The specialization of the operating team in the emergency settings differs from the elective setting, which may have an impact on outcome. The aim of this study was to evaluate short- and long-term outcomes following emergent colon cancer surgery depending on sub-specialization of the operating team.

METHODS: This is a retrospective population study based on data from the Swedish Colorectal Cancer Registry (SCRCR). In total, 656 patients undergoing emergent surgery for colon cancer between 2011 and 2016 were included. The cohort was divided in groups according to specialization of the operating team: (1) colorectal team (CRT); (2) emergency surgical team (EST); (3) general surgical team (GST). The impact of specialization on short- and long-term outcomes was analyzed.

RESULTS: No statistically significant difference in 5-year overall survival (CRT 48.3%; EST 45.7%; GST 42.5%; p = 0.60) or 3-year recurrence-free survival (CRT 80.7%; EST 84.1%; GST 77.7%21.1%; p = 0.44) was noted between the groups. Neither was any significant difference in 30-day mortality (4.4%; 8.1%; 5.5%, p = 0.20), 90-day mortality (8.8; 11.9; 7.9%, p = 0.37) or postoperative complication rate (35.5%, 35.9 30.7, p = 0.52) noted between the groups. Multivariate analysis adjusted for case-mix showed no difference in hazard ratios for long-term survival or postoperative complications. The rate of permanent stoma after 3 years was higher in the EST group compared to the CRT and GST groups (34.5% vs. 24.3% and 23.9%, respectively; p < 0.0.5).

CONCLUSION: Surgical sub-specialization did not significantly affect postoperative complication rate, nor short- or long-term survival after emergent operation for colon cancer. Patients operated by emergency surgical teams were more likely to have a permanent stoma after 3 years.

PMID:36624451 | DOI:10.1186/s13017-023-00474-y