Tag: statistics

Pharm Stat. 2021 Dec 21. doi: 10.1002/pst.2187. Online ahead of print.

ABSTRACT

New technologies for novel biomarkers have transformed the field of precision medicine. However, in applications such as liquid biopsy for early tumor detection, the misclassification rates of next generation sequencing and other technologies have become an unavoidable feature of biomarker development. Because initial experiments are usually confined to specific technology choices and application settings, a statistical method that can project the performance metrics of other scenarios with different misclassification rates would be very helpful for planning further biomarker development and future trials. In this article, we describe an approach based on an extended version of simulation extrapolation (SIMEX) to project the performance of biomarkers measured with varying misclassification rates due to different technological or application settings when experimental results are only available from one specific setting. Through simulation studies for logistic regression and proportional hazards models, we show that our proposed method can be used to project the biomarker performance with good precision when switching from one to anther technology or application setting. Similar to the original SIMEX model, the proposed method can be implemented with existing software in a straightforward manner. A data analysis example is also presented using a lung cancer data set and performance metrics for two gene panel based biomarkers. Results demonstrate that it is feasible to infer the potential implications of using a range of technologies or application scenarios for biomarkers with limited human trial data.

PMID:34935280 | DOI:10.1002/pst.2187

Int J Rheum Dis. 2021 Dec 21. doi: 10.1111/1756-185X.14268. Online ahead of print.

ABSTRACT

AIM: Predicting radiographic progression is vital for assessing the prognosis of patients with radiographic axial spondyloarthritis, and C-reactive protein (CRP) may be a valuable biomarker for this purpose. This study aimed to investigate the relationship between changes in the CRP level and spinal radiographic progression in patients with radiographic axial spondyloarthritis who were initially treated with non-biologics.

METHODS: Patients with radiographic axial spondyloarthritis who were followed up for 18 years at a single center and initially treated with nonsteroidal anti-inflammatory drugs and/or conventional disease-modifying antirheumatic drugs for 3 months were included. Patients with a CRP level of <0.8 mg/dL or 50% of the baseline CRP at 3 months were assigned to the controlled CRP group (n = 351), and the remaining patients were assigned to the uncontrolled CRP group (n = 452). A generalized estimating equation was used to analyze the differences in the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) between the 2 groups.

RESULTS: The increase in the mSASSS was slower in the controlled CRP group than in the uncontrolled CRP group (interaction term β = -.499, 95% confidence interval -0.699 to -0.300).

CONCLUSION: Controlled CRP achieved in response to initial treatment with non-biologic agents for 3 months was significantly associated with a slower rate of spinal radiographic change in patients with radiographic axial spondyloarthritis. The CRP level at 3 months after initial non-biologic treatment is a good predictor of radiographic progression.

PMID:34935282 | DOI:10.1111/1756-185X.14268

J Obstet Gynaecol Res. 2021 Dec 21. doi: 10.1111/jog.15136. Online ahead of print.

ABSTRACT

AIM: The study aimed at investigating pregnancy complications, birth outcomes, and postnatal child development in pregnancies of women with inflammatory bowel diseases (IBDs).

METHODS: This is an uncontrolled retrospective single-center study between 2014 and 2019. It is a mixed-method cross-sectional study using data from (1) electronic patient records and (2) questionnaires and copies of mothers’ and children’s health booklets. Disease activity and IBD medications were analyzed and related to pregnancy complications, birth outcomes, and postnatal child development using mixed models for statistical analyses.

RESULTS: Fifty live births from 46 patients were included. Disease activity anytime during pregnancy occurred in 56%. Biologics were applied in ca. 25% of pregnancies, mostly only through the second trimester. Pregnancies of mothers with active disease were slightly shorter than those of mothers with inactive disease (37.4 weeks vs. 38.9 weeks). Adverse pregnancy outcomes were reported in 28% of the live births, including small for gestational age in 6%, low birth weight in 18%, and preterm birth in 20%. Postnatal developmental abnormalities and health problems were reported in 26.8% of the children. Mixed model analyses failed to reveal significant associations between IBD activity and IBD medications during pregnancy and pregnancy complications, perinatal birth outcomes, and postnatal child development.

CONCLUSION: Despite a tendency of shorter pregnancies in patients with active IBD and lower birth weight and birth size in patients with IBD-related therapy during pregnancy, disease activity and medications did not significantly influence pregnancy, birth, and developmental outcomes.

PMID:34935257 | DOI:10.1111/jog.15136

Eur J Oral Sci. 2021 Dec 22. doi: 10.1111/eos.12838. Online ahead of print.

ABSTRACT

The aim of this study was to evaluate the effect of saliva contamination on bond strength to dentin with an etch-and-rinse and a self-etch adhesive system. For each of these adhesive systems, the dentin surface of 24 human molars were allocated to one of four groups representing different saliva contamination scenarios. Saliva was applied at different stages in the bonding process, and was investigated to be remedied by water rinsing and/or air drying. Uncontaminated tooth surfaces were used as controls. Bonding procedures were performed according to the manufacturer’s instructions, and a polymer-based composite was placed. The bond strength was measured by a micro-tensile test. Except for the etch-and-rinse approach having contamination with saliva after etching, followed by air drying, all salivary contamination regimens resulted in a substantial number of specimens not surviving the test, and the bond strength value of these was therefore set to 0 MPa for the purposes of the statistical analysis. Water rinsing after etching and salivary contamination did significantly reduce the bond strength. Contamination after priming showed the lowest bond strength. For the self-etch approach, saliva contamination before the adhesive procedure, followed by air drying, significantly reduced the bond strength, while contamination followed by water rinsing or air drying did not statistically significantly reduce the strength.

PMID:34935213 | DOI:10.1111/eos.12838

Respirology. 2021 Dec 21. doi: 10.1111/resp.14194. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: Idiopathic pulmonary fibrosis (IPF) is one of the most common forms of interstitial lung diseases. While studies have been conducted in other countries to determine the epidemiological burden of IPF, there is limited information in Australia. Our study aimed to address this gap and generate the first estimates for the mortality, incidence and prevalence of IPF in Australia.

METHODS: Estimates were generated by utilizing the novel Mortality Incidence Analysis Model (MIAMOD) method and software based on the illness-death model. Data inputs included population estimates and mortality data from the Australian Bureau of Statistics (ABS) for the period 1997-2015 and participant data from the Australian IPF Registry (AIPFR). Projections were estimated for a 10-year period up to 2025.

RESULTS: Overall crude and age-standardized estimates for mortality were 5.9 and 6.3 per 100,000 population; incidence, 10.4 and 11.2 per 100,000 population; and prevalence, 32.6 and 35.1 per 100,000 population. Crude and age-standardized mortality, incidence and prevalence increased over the study period; however, they demonstrated a decreasing trend over the projected period. Persons older than 70 years constituted 9% of the population; however, they accounted for approximately 82%-83% of all deaths, incident and prevalent cases. All estimates were higher in males than in females.

CONCLUSION: Our study provides the first estimates for incidence, prevalence and mortality of IPF in Australia. By reporting national estimates for IPF, our study addresses an information gap important for policy, planning and to help optimize the allocation of resources for the management of patients with IPF.

PMID:34935240 | DOI:10.1111/resp.14194

Br J Clin Pharmacol. 2021 Dec 22. doi: 10.1111/bcp.15192. Online ahead of print.

ABSTRACT

AIM: With growing evidence on the protective effect of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) in coronavirus disease 2019 (Covid-19), we aimed to thoroughly investigate the association between the use of major classes of antihypertensive medications and Covid-19 outcomes in comparison with the use of ACEIs and ARBs.

METHODS: We conducted a population-based study in patients with pre-existing hypertension in the UK Biobank with data from the first two SARS-CoV-2 waves prior population-based vaccination. Multivariable logistic regression analysis was performed adjusting for a wide range of confounders.

RESULTS: The use of either beta-blockers (BBs), calcium-channel blockers (CCBs), or diuretics was associated with a higher risk of Covid-19 hospitalization compared to ACEI use (adjusted OR (95%CI): 1.66 [1.43-1.93]) and ARB use (1.53 [1.30-1.81]). The risk of 28-day mortality among Covid-19 patients was also increased among users of BBs, CCBs or diuretics when compared to ACEI users (1.74 [1.30-2.33]) but not when compared to ARB users (1.26 [0.93-1.71]). The association between BB, CCB or diuretics use (compared to ACEI use) and 28-day mortality among hospitalized Covid-19 patients narrowly missed statistical significance (1.47 [0.99-2.18]) but it was statistically significant when the analysis was restricted to patients hospitalized during the second SARS-CoV-2 wave (1.80 [1.15-2.83]).

CONCLUSION: Our results suggest protective effects of inhibition of the renin-angiotensin-aldosterone system on Covid-19 hospitalization and mortality, particularly with ACEI, among patients with pharmaceutically treated hypertension. If confirmed by randomized controlled trials, this finding could have high clinical relevance for treating hypertension during the SARS-CoV-2 pandemic.

PMID:34935181 | DOI:10.1111/bcp.15192

J Clin Lab Anal. 2021 Dec 21:e24145. doi: 10.1002/jcla.24145. Online ahead of print.

ABSTRACT

BACKGROUND: The role of CD59 and fluorescently labeled aerolysin (FLAER) in acute myeloid leukemia (AML) remains unclear and requires further investigation. To explore the relationship between CD59, FLAER, and AML, we investigated CD59 and FLAER expression in AML and analyzed their relationship with clinical characteristics of AML patients.

METHODS: We employed flow cytometry (FCM) to analyze CD59 and FLAER expression in 161 AML patients at Tianjin Medical University General Hospital and evaluated its association with sex, white blood cell (WBC) count, platelet (PLT) count, thrombin time (TT), prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), D-Dimer(D-D), and lactate dehydrogenase (LDH), followed by analyzing its connection with disease progression and complete remission (CR).

RESULTS: CD59 and FLAER deficiencies were identified in AML patients. Compared with CR group, non-CR group patients revealed more CD59 and FLAER deficiency. Compared with non-acute promyelocytic leukemia (M3) group, M3 group patients had more CD59 and FLAER deficiency. CD59^– level in primordial cells of M3 patients was positively correlated with primordial cell ratio (r = 0.660, p = 0.003). Additionally, we discovered that the decline in CD59 and FLAER levels might be linked to higher D-D and LDH in AML patients. The difference was statistically significant (p < 0.05).

CONCLUSIONS: We demonstrated that the decline in CD59 and FLAER levels was associated with leukemia cell proliferation and abnormal coagulation function in AML, suggesting that they could serve as a predictor of AML coagulation dysfunction, particularly in M3.

PMID:34935195 | DOI:10.1002/jcla.24145

J Adv Nurs. 2021 Dec 21. doi: 10.1111/jan.15138. Online ahead of print.

ABSTRACT

AIM: To analyse the effects of active video games on physical function in independent community-dwelling older adults.

DESIGN: Systematic review and meta-analysis of randomized controlled trials.

DATA SOURCES: The CINAHL, LILACS, Medline, Proquest and Scopus databases were consulted, with no restriction by year of publication.

REVIEW METHODS: Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. The meta-analysis was performed using RevMan software.

RESULTS: The analysis included 22 randomized controlled trials with a total of 1208 participants (all ≥55 years old). In our meta-analyses, the effects produced by playing the active video games (mean differences) were statistically significant for the variables Gait speed and Timed up-and-go. The differences between the control and experimental groups were not significant in the following tests: 6-minute walk, 30-second chair stand, balance (measured with the Berg Balance Scale), cadence, grip strength, knee extension strength, 8-Foot Up-and-Go or velocity.

CONCLUSIONS: Physical exercise from participation in active video games has beneficial effects on two clinical parameters (Gait speed and Timed up-and-go) in independent community-dwelling older adults. However, the effects on other parameters do not differ from those obtained with conventional exercise training. Therefore, the clinical significance of these benefits is limited.

IMPACT: Older adults usually perform little physical activity. In consequence, researchers have increasingly considered alternatives to traditional forms of exercise. One such is that provided by active video games, which can be a source of stimulation, encouraging adherence and motivation in exercise programmes. Our review shows that active video games can improve gait speed and mobility, but in other respects obtain no differences from conventional exercises. Further tailored randomized clinical trials should be undertaken with diverse populations of older adults to evaluate different physical function variables to determine the most appropriate training approach and its optimal design and duration.

PMID:34935178 | DOI:10.1111/jan.15138

Biom J. 2021 Dec 21. doi: 10.1002/bimj.202000169. Online ahead of print.

ABSTRACT

Randomized clinical trials in oncology typically utilize time-to-event endpoints such as progression-free survival or overall survival as their primary efficacy endpoints, and the most commonly used statistical test to analyze these endpoints is the log-rank test. The power of the log-rank test depends on the behavior of the hazard ratio of the treatment arm to the control arm. Under the assumption of proportional hazards, the log-rank test is asymptotically fully efficient. However, this proportionality assumption does not hold true if there is a delayed treatment effect. Cancer immunology has evolved over time and several cancer vaccines are available in the market for treating existing cancers. This includes sipuleucel-T for metastatic hormone-refractory prostate cancer, nivolumab for metastatic melanoma, and pembrolizumab for advanced nonsmall-cell lung cancer. As cancer vaccines require some time to elicit an immune response, a delayed treatment effect is observed, resulting in a violation of the proportional hazards assumption. Thus, the traditional log-rank test may not be optimal for testing immuno-oncology drugs in randomized clinical trials. Moreover, the new immuno-oncology compounds have been shown to be very effective in prolonging overall survival. Therefore, it is desirable to implement a group sequential design with the possibility of early stopping for overwhelming efficacy. In this paper, we investigate the max-combo test, which utilizes the maximum of two weighted log-rank statistics, as a robust alternative to the log-rank test. The new test is implemented for two-stage designs with possible early stopping at the interim analysis time point. Two classes of weights are investigated for the max-combo test: the Fleming and Harrington (1981) $G^{\rho ,\gamma }$ weights and the Magirr and Burman (2019) modest $\left({\tau }^{\ast }\right)$ weights.

PMID:34935177 | DOI:10.1002/bimj.202000169

Aliment Pharmacol Ther. 2021 Dec 22. doi: 10.1111/apt.16742. Online ahead of print.

ABSTRACT

BACKGROUND: The optimal choice of biological agents after failure of anti-tumour-necrosis-factor-(TNF)α agent in Crohn’s disease (CD) is yet to be defined.

AIMS: To assess the effectiveness and safety of ustekinumab compared to vedolizumab as second-line treatment in CD patients who failed anti-TNFα therapy.

METHODS: Retrospective analysis of clinical response and remission at 14 and 52 weeks to ustekinumab by physician global assessment (PGA). A propensity score-matched analysis with a cohort treated with vedolizumab was performed.

RESULTS: Of 282 patients (mean age 40 ± 15, F:M ratio 1.7:1) treated with ustekinumab, clinical response or remission was reached by 200/282 patients (70.9%) at 14 weeks, and 162/259 patients (62.5%) at 52 weeks. Overall, 74 adverse events occurred, of which 26 were labelled as serious (8.3 per 100 person-year). After exclusion of patients without prior anti-TNFα exposure and patients previously exposed to vedolizumab or ustekinumab, we analysed 275/282 patients (97.5%) on ustekinumab and 118/135 patients (87.4%) on vedolizumab. Propensity score analysis revealed that at 14 weeks, patients treated with ustekinumab were 38% (95% CI 25%-50%; P < 0.001) more likely to achieve clinical remission, while at 52 weeks, the difference of 9% (95% CI -15% to 33%; P = 0.462) was not significant.

CONCLUSIONS: Ustekinumab was effective and well tolerated in this real-world cohort. While ustekinumab proved more effective at 14-weeks, we found no statistically significant differences at 52 weeks compared to vedolizumab.

PMID:34935160 | DOI:10.1111/apt.16742