Greater Statistical Power Research Articles

Rotating-Hinge Total Knee Arthroplasty: Clinical and Radiographic Results from a Medium-Term, Multi-Center Study in a Latin American Population

Background: Hinged prostheses are a good choice in the setting of complex knee arthroplasty. Nevertheless, the results could be different in the Latin-American people. Methods: A retrospective follow-up was performed. Seventy-six patients underwent pTKA using hinged prosthesis from 2012 to 2017. Survival analysis was performed with the Kaplan-Meier method. Functional results were assessed using Oxford Knee Score (OKS), OKS-APQ (Activity and Participation Questionnaire) and KOOS-12. Radiologic assessment was performed at each follow-up. In all the surgeries the rotating-hinge prosthesis solved the cases of complex knee surgery. Results: Seventy-six patients underwent pTKA using hinged prosthesis from 2012 to 2017. Survival analysis was performed with the Kaplan-Meier method. Functional results were assessed using Oxford Knee Score (OKS), OKS-APQ (Activity and Participation Questionnaire) and KOOS-12. Radiologic assessment was performed at each follow-up. In all the surgeries the rotating-hinge prosthesis solved the cases of complex knee surgery. Hinge prostheses for complex knee arthroplasty in Latin-American people have a 10-year survivorship of 90.8% which is within the range of 51% to 92.5%, shown in a recent literature review of non-Latin American world population. Conclusions: Rotating Hinge prostheses are a good option for patients with major deformities, grade 3 ligament instability, neurological sequalae that compromises the knee joint and severe bone loss. The Latin-American population shows a similar behavior in terms of survivorship in comparison with the literature from the rest of the world. However, comparative studies with greater statistical power are needed to show more accurate conclusions. Level of Evidence: Level III

A Retrospective Analysis of the Association of Obesity with Anthracycline and Trastuzumab-Induced Cardiotoxicity in the Treatment of Breast Cancer and Lymphoma

IntroductionBackground: Trastuzumab and anthracyclines are mainstays of chemotherapy in breast cancer and lymphoma patients. We aimed to assess the relationship between obesity and the risk of developing chemotherapy-associated cardiotoxicity.Material and methodsA retrospective chart review was conducted of all patients who received trastuzumab or anthracyclines at our tertiary care center. Bivariate analyses were conducted to determine the association between demographic and clinical variables with cardiotoxicity status. Two multivariate logistic regression models were generated to assess whether BMI was independently associated with cardiotoxicity.ResultsOf the 368 patients receiving either trastuzumab or anthracyclines, 16 patients developed cardiotoxicity. Demographically, age, race, BMI, BSA, and weight did not differ between the patients who developed cardiotoxicity and those who did not. The mean dose of anthracycline and trastuzumab did not differ between the patients who developed cardiotoxicity and those who did not. Obesity was not found to increase the odds of developing cardiotoxicity and was slightly protective. A non-significant decrease in the odds of developing cardiotoxicity was found for every one-unit increase in BMI. In a multivariable model using BMI as a continuous predictor and controlling for BMI, age, hypertension, chemotherapy type and coronary artery disease, the only significant predictor of cardiotoxicity was a previous history of arrhythmia.ConclusionsObesity was not a significant risk factor for patients developing cardiotoxicity from trastuzumab or anthracycline based chemotherapy and may be a protective factor for cardiotoxicity. Additional studies with greater statistical power are needed to further evaluate this effect and independently evaluate obesity as a risk factor for cardiotoxicity.

Trial Design with Win Statistics for Multiple Time-to-Event Endpoints with Hierarchy

The conventional approach to the analysis of composite endpoints is time-to-first event analysis. However, this approach has been criticized because it ignores the differences in clinical severity and may end up emphasizing the less severe time-to-event. To overcome this limitation, win statistics (win ratio, win odds, or net benefit) have become popular in analysis of hierarchical time to event endpoints. However, design of randomized clinical trials using the win statistics is lagging behind. In this article, we derive formulas for the win statistics and probability of ties under specific assumptions that can be useful in practice. We also address two design issues: the selection of meaningful and justifiable design parameters and power calculations, when the win statistics method is the primary analysis method for multiple time-to-event endpoints for a pre-specified hierarchy. Finally, we identify patterns where the win statistics approach would have greater statistical power than time-to-first event analysis. Several examples are used to illustrate the usefulness of the formula-based power calculations.

P-012 Euploid and good-quality blastocysts using testicular sperm from men with high sperm DNA fragmentation (SDF), oligozoospermia, and previous failed ICSI with ejaculated sperm

Abstract Study question Are euploid rate and blastocyst quality improved when testicular sperm is used in patients with elevated SDF and poor semen parameters or/and previous ICSI failure? Summary answer The use of testicular spermatozoa in non-azoospermic males does preserve blastocyst ploidy while favoring the proportion of good-quality embryos available for the couple. What is known already Sperm extracted from the testicle has been proposed as a strategy to improve reproductive outcomes in couples with elevated DNA fragmentation in the ejaculate and with severe male infertility or previous ICSI failure. Different studies and meta-analyses show to increase pregnancy and live birth rates, and one of the reasons could be the lower genetic damage of spermatozoa retrieved from the testicle. However, there is little information on the effect on the quality of the embryos generated and their ploidy since the use of testicular sperm tends to have a higher rate of aneuploidy. Study design, size, duration This is a prospective, blinded, randomized, and controlled trial conducted in a private university-affiliated IVF center between October 2020 and June 2023. In each patient (n = 6), oocytes were randomly microinjected by sperm from the testis (T-ICSI) or ejaculate (E-ICSI) assigned in a 1:1 ratio. All males had an SDF>30% (measured by Sperm Chromatin dispersion (SCD) test), severe oligozoospermia, and/or a previous ICSI failure. Participants/materials, setting, methods Males underwent testicular sperm extraction (TESE) to obtain spermatozoa, which were frozen along with an ejaculated semen sample obtained previously on the same day. Women were <38 years old with good ovarian reserve (antral follicle count>10). SDF level was compared between both sources. The primary outcome was the euploid rate (among a total number of biopsied embryos). Secondary outcomes were fertilization rate, blastocyst rate, good-quality blastocyst rate, and ongoing pregnancy rate per embryo transfer (ET). Main results and the role of chance Mean ejaculated SDF was 44.83±16.6 (IC95% 27.5 -62.2), while mean women age was 31.8±2.9 (28.76-34.9). An average of 14.5±5.8 metaphase II oocytes were microinjected per patient. A total of 87 oocytes were randomized to the T-ICSI group (n = 45) or E-ICSI group (n = 42). There was a 14% difference between the SDF of testicular (44.7% (31.3-58.0) and ejaculated sperm (58.5% (37.6-79.4) (p = 0.2). The fertilization rate was slightly lower in the T-ICSI group (53.3% (38.1-68.1) compared to the E-ICSI group (61.9 (61.8-76.0) (p = 0.6). A total of 21 embryos reached the blastocyst stage, being the blastocyst arrival rate per correctly fertilized oocyte 41.7% (10/24) (22.8-63.1) for T-ICSI and 42.3% (11/26) (24.0-62.8) for E-ICSI (p = 1.0). Of them, a higher proportion of good-quality blastocysts was found in the T-ICSI (29.2% (13.4-51.6)) group than in the E-ICSI (19.2% (7.3-40.0)) group, although the difference was not statistically significant. In addition, the euploidy rate was comparable between the T-ICSI (60% (27.4-86.3)) and E-ICSI (63.6% (31.6-87.6)) groups (p = 1.0). Seven embryos were transferred in 6 ET, three in each study group. Only one of the ET in the E-ICSI group resulted in pregnancy (33.3% (1.8-87.5), while the three transfers in the T-ICSI group resulted in an ongoing pregnancy (100% (31.0-100)) (p = 1.0). Limitations, reasons for caution Despite being a randomized controlled trial, the number of subjects recruited is small; it is necessary to increase the number of cases to obtain results with greater statistical power. TESE is a technique that is not risk-free, so its performance should be evaluated in terms of its cost-benefit for patients. Wider implications of the findings The use of less genome-damaged testicular spermatozoa in non-azoospermic males seems to be a reliable strategy for couples with high ejaculated SDF and severe oligospermia and/or previous ICSI failures. However, although we have found an improvement, remains to be statistically confirmed with more cases. Trial registration number NCT04795440

Using Alternative Definitions of Controls to Increase Statistical Power in GWAS.

Genome-wide association studies (GWAS) are often underpowered due to small effect sizes of common single nucleotide polymorphisms (SNPs) on phenotypes and extreme multiple testing thresholds. The most common approach for increasing statistical power is to increase sample size. We propose an alternative strategy of redefining case-control outcomes into ordinal case-subthreshold-asymptomatic variables. While maintaining the clinical case threshold, we subdivide controls into two groups: individuals who are symptomatic but do not meet the clinical criteria for diagnosis (subthreshold) and individuals who are effectively asymptomatic. We conducted a simulation study to examine the impact of effect size, minor allele frequency, population prevalence, and the prevalence of the subthreshold group on statistical power to detect genetic associations in three scenarios: a standard case-control, an ordinal, and a case-asymptomatic control analysis. Our results suggest the ordinal model consistently provides the greatest statistical power while the case-control model the least. Power in the case-asymptomatic control model reflects the case-control or ordinal model depending on the population prevalence and size of the subthreshold category. We then analyzed a major depression phenotype from the UK Biobank to corroborate our simulation results. Overall, the ordinal model improves statistical power in GWAS consistent with increasing the sample size by approximately 10%.

Platelet-Rich Plasma Therapy for Chronic Low Back Pain with Neuropathic Component in a Pain Medicine Clinic in Mexico: Retrospective Study

Introduction: Low back pain is a common problem affecting millions worldwide. Even after surgical treatment some patients do not improve; others suffer from persistent radiculopathy. We define Complex Chronic Low Back Pain (CCLBP) as any low back pain that has lasted for at least three months and has at least two triggering pain mechanisms. Objective: To describe our experience with platelet-rich plasma (PRP) therapy in managing CCLBP with a neuropathic component Methods: Quantitative, retrospective analysis from 57 medical records of patients treated with PRP for CCLBP. We used IBM-SPSS 21 to obtain descriptive statistics, Chi-square, Student T and Odds-Ratio. Results: The mean age of our sample was 59.8 (±14.4) years, with 6.51 (±8.7) years of pain and a follow-up of 9 (±12.2) months. 33.3% had lumbar surgery, 29.8% had lumbar trauma, 31.6% used a walking aid, 56.7% had MODIC changes on MRI, and 42% of them received intraosseous-PRP technic. 84.2% reported severe pain (VAS 8-10). The results showed that 96.5% of patients experienced some improvement after PRP treatment. Additionally, 10.5% experienced pain suppression. No significant differences in age, lumbar trauma, lumbar surgery, diseases, or the use of walking aids between patients who benefited from PRP treatment and those who did not. VAS after treatment shows significance (p<0.01) with 5.36±2.6 points. Subjects with less than five years of radicular pain had an improvement greater than 3 points on VAS (OR 7.38, IC95% 1.72-31.7). Conclusion: Autologous platelet-rich plasma injections for chronic low back pain with a neuropathic component are an effective alternative to address CCLBP’s current challenge. New studies with greater statistical power are necessary to make a statement of efficacy, but with the data obtained, it seems a promising option.
 Keywords: Platelet-Rich Plasma, Low Back Pain, Radiculopathy, Intraosseous

Using multivariate pattern analysis to increase effect sizes for event-related potential analyses.

Multivariate pattern analysis (MVPA) approaches can be applied to the topographic distribution of event-related potential (ERP) signals to "decode" subtly different stimulus classes, such as different faces or different orientations. These approaches are extremely sensitive, and it seems possible that they could also be used to increase effect sizes and statistical power in traditional paradigms that ask whether an ERP component differs in amplitude across conditions. To assess this possibility, we leveraged the open-source ERP CORE data set and compared the effect sizes resulting from conventional univariate analyses of mean amplitude with two MVPA approaches (support vector machine decoding and the cross-validated Mahalanobis distance, both of which are easy to compute using open-source software). We assessed these approaches across seven widely studied ERP components (N170, N400, N2pc, P3b, lateral readiness potential, error related negativity, and mismatch negativity). Across all components, we found that multivariate approaches yielded effect sizes that were as large or larger than the effect sizes produced by univariate approaches. These results indicate that researchers could obtain larger effect sizes, and therefore greater statistical power, by using multivariate analysis of topographic voltage patterns instead of traditional univariate analyses in many ERP studies.

Melanoma Brain Metastases: Immunotherapy or Targeted Therapy? A Systematic Review and Meta-Analyses

Background. Brain metastases are one of the leading causes of death in melanoma patients. This systematic review and meta-analysis aimed to look at the variables that affect melanoma patients’ intracranial treatment responses to immunotherapy and targeted therapy. Methods. A systematic search of PubMed and Scopus up to December 2023 was conducted to identify trials investigating treatment response of melanoma brain metastasis. This meta-analysis presents summary estimates (SEs) of treatment response and odd ratios (ORs) for the comparison between symptomatic and asymptomatic metastases. Generalised linear mixed models were used for the SE of the proportion of clinical responses and 95% CIs are reported. We investigated between-study heterogeneity using meta-regression. Results. We included 19 independent clinical trials for a total of 1074 patients with brain metastases. The SE of the overall response was 36% 95%CI [27%; 47%], I2 = 84%, similar to the SE for symptomatic metastases: SE = 29% 95%CI [16%; 47%], I2 = 80%. A significantly higher response of symptomatic metastases was observed between patients who had previously received immunotherapy compared to those who had not (47% vs. 9%, p-value = 0.001). The SE was greater for asymptomatic metastases (38% 95%CI [29%; 49%], I2 = 80%), and among these, patients that received the combo-immunotherapy importantly responded more than those who had received monotherapy (45% vs. 26.1%, p-value = 0.002). The major limit of our analysis is the absence of data about the specific intracranial response separately in asymptomatic and symptomatic patients in seven studies. Conclusions. This study shows the importance of starting immunotherapy as early as possible in asymptomatic patients. Randomised trials with greater statistical power are needed to find the best strategies for symptomatic and asymptomatic brain metastases.

Real-world evidence of Pressure-Enabled Drug Delivery for trans-arterial chemoembolization and radioembolization among patients with hepatocellular carcinoma and liver metastases

Objectives Pressure-Enabled Drug Delivery (PEDD), a method using pressure to advance catheter-delivered drug distribution, can improve treatment for hepatocellular carcinoma (HCC) and liver metastases, but real-world evidence is limited. We compared baseline patient characteristics, clinical complexity, and post-procedure healthcare resource utilization (HRUs) and clinical complications for PEDD and non-PEDD procedures. Methods This study used a retrospective, longitudinal, cohort design of claims data from Clarivate’s Real World Data Repository, which includes 98% of US payers with over 300 million unique patients from all US states. We identified patients with a trans-arterial chemoembolization (TACE) or trans-arterial radioembolization (TARE) from 1 January 2019 to 31 December 2022. Subsamples grouped patients with HCC receiving a TARE procedure at their first embolization and patients with metastatic colorectal cancer (CRC) that received a TARE procedure. We reported descriptive comparisons of our full sample of patients with HCC and liver metastases receiving PEDD versus non-PEDD procedures. We then conducted a matching-adjusted comparison of HRUs and clinical complications for PEDD and non-PEDD patients among our subsamples (HCC receiving a TARE procedure at their first embolization and patients with metastatic CRC that received a TARE procedure). Matching was based on baseline demographic and clinical characteristics using coarsened exact matching and propensity-score matching. HRUs included inpatient, outpatient, and emergency department visits. Clinical complications included ascites, cholecystitis, fatigue, gastric ulcer, gastritis, jaundice, LFT increase, lymphopenia, portal hypertension, and post-embolization syndrome. Results PEDD procedures were used on patients with worse baseline disease burdens: baseline Charlson comorbidity index (mean of 6.5 vs. 5.8), any prior clinical complication related to underlying disease (33.7 vs. 31.0%), and prior systemic therapy (22.1% vs. 16.2%). PEDD patients had a greater number of procedural codes indicative of technical complexity for TACE (PEDD mean = 226.3; non-PEDD mean = 134.5; p value <.01) and TARE (PEDD mean = 205.56; non-PEDD mean = 94.8; p value <0.01). Matching-adjusted analyses of patients with HCC and CRC demonstrated comparable HRU and clinical complications for PEDD and non-PEDD procedures post-index. Conclusion Despite higher baseline disease burden and complexity, post-procedure HRU and clinical complications for PEDD patients were similar to non-PEDD patients. The complex baseline clinical profile may reflect selection of challenging cases for PEDD use. Future studies should validate the benefits observed with PEDD embolization in larger samples with greater statistical power.

Subset scanning for multi-trait analysis using GWAS summary statistics.

Multi-trait analysis has been shown to have greater statistical power than single-trait analysis. Most of the existing multi-trait analysis methods only work with a limited number of traits and usually prioritize high statistical power over identifying relevant traits, which heavily rely on domain knowledge. To handle diseases and traits with obscure etiology, we developed TraitScan, a powerful and fast algorithm that identifies potential pleiotropic traits from a moderate or large number of traits (e.g. dozens to thousands) and tests the association between one genetic variant and the selected traits. TraitScan can handle either individual-level or summary-level GWAS data. We evaluated TraitScan using extensive simulations and found that it outperformed existing methods in terms of both testing power and trait selection when sparsity was low or modest. We then applied it to search for traits associated with Ewing Sarcoma, a rare bone tumor with peak onset in adolescence, among 754 traits in UK Biobank. Our analysis revealed a few promising traits worthy of further investigation, highlighting the use of TraitScan for more effective multi-trait analysis as biobanks emerge. We also extended TraitScan to search and test association with a polygenic risk score and genetically imputed gene expression. Our algorithm is implemented in an R package "TraitScan" available at https://github.com/RuiCao34/TraitScan.

Applied Physical Activity Epidemiology: Relationship of Physical Activity and Exercise Exposures with Health Outcomes.

There is consistent, strong evidence that both physical activity and exercise lowers risk of many diseases, yet the way physical activity and exercise are measured varies substantially. Physical activity epidemiologists use observational designs (such as cohort or case-control studies) to examine the relationship of physical activity exposures and outcomes including mortality, or disease-specific such as incident type 2 diabetes mellitus, cancer, cardiovascular disease, anxiety, or depression. These same observational designs can be used to examine the associations of prevalent disease in reducing symptom burden in those who are physically active compared to those who are not, specifically examining anxiety and depression. There is great statistical power and often large sample sizes in physical activity epidemiologic studies with valid and reliable assessment tools but known limitations such as measurement error or social desirability bias. Overall, physical activity epidemiology can be a useful tool to understand the influence of exercise and physical activity on risk of disease. In this chapter, we will explore the strength, consistency, and sources of evidence primarily using a physical activity epidemiology lens.

Polygenic scores of subcortical brain volumes as possible modulators of treatment response in depression

A significant proportion of patients with major depressive disorder (MDD) do not experience remission after one or more pharmacological treatments. Research has explored brain structural measures, particularly hippocampal volume, as potential predictors of treatment response, as well as genetic factors.This study investigated the association of polygenic scores (PGSs) for seven subcortical brain volumes (including the hippocampus, nucleus accumbens, amygdala, and caudate nucleus) with treatment non-response and non-remission in MDD.Patients with MDD were recruited in the context of five clinical studies, including a total of 3637 individuals. PGSs were estimated using a Bayesian framework and continuous shrinkage priors (PRS-CS-auto) after standard genotype quality control and imputation. Logistic regressions were performed between PGSs and non-response or non-remission in each sample, adjusting for age, sex, baseline symptom severity, recruitment sites, and population stratification. Results were meta-analysed across samples, using a random-effect model.No association was significant in the meta-analysis after Bonferroni correction. The top finding was found for the caudate volume PGS and non-remission (OR = 1.09, 95% CI = 1.01–1.19, p = 0.036), with no evidence of heterogeneity. Leave-one-out sensitivity analyses showed that this result was influenced by the two largest samples in the meta-analysis.This result should be considered as preliminary as it did not reach the Bonferroni-adjusted significance threshold. Future studies with greater statistical power may enhance the predictive performance of PGSs and contribute to the identification of polygenic predictors of treatment outcomes in MDD, contributing to precision psychiatry.

Comparative efficacy of a combination of undenatured type II collagen, Boswellic acids, methylsulfonylmethane, vitamins C and D3 and a combination of chondroitin sulfate and glucosamine hydrochloride in the treatment of primary osteoarthritis of the knee joint

To evaluate the efficacy of Artneo (AN) in comparison with a combination of glucosamine hydrochloride and chondroitin sulfate (GC) in patients with osteoarthritis (OA) of the knee joint (KJ). 70 patients with stages I-III of primary knee OA were randomized into 2 groups. Participants in the 1st (n=35) took AN 1 caps/day, in the 2nd (n=35) GC according to the standard regimen. After 7, 30, 90, 180 days, the Lequesne index (severity of OA), pain when moving according to VAS, WOMAC score were assessed, after 1, 3, 6 months - quality of life SF-36 and morning stiffness, after 6 months - MRI with T2 mapping, laboratory safety indicators. Over the course of 6 months of use, an improvement in the WOMAC index and a decrease in pain were observed without intergroup differences, and a greater decrease in stiffness in the AN group. After 3 months, the severity of OA decreased from moderate to mild in the AN group and was significantly lower compared to the GC group; quality of life (physical component of SF-36) was higher in the AN group. After 6 months, there was an improvement in cartilage ultrastructure (T2 relaxation time) in both groups and a more pronounced reduction of the synovitis area (MRI) in the AN group (2.95 and 1.37 times in the AN and GC group, respectively). There were no clinically significant adverse reactions observed in both groups. The use of AN in patients with stage I-III primary knee OA was not inferior in efficacy to the combination of GC. Further studies with greater statistical power (sample size) and follow-up period are warranted including in real clinical practice.

Can Clean Delivery Kits Prevent Infections? Lessons from Traditional Birth Attendants in Nigeria.

In resource-poor settings, perinatal infections contribute significantly to maternal and neonatal deaths, and the use of clean delivery kits (CDKs) has been proposed as a tool to reduce the risk of infection-related deaths. This study aims to assess the acceptability and effectiveness of CDKs in preventing infections in deliveries attended by traditional birth attendants (TBAs) in Abeokuta, Nigeria. The study was a cluster-randomized trial with 67 birth centres/clusters, 453 births/mothers, and 457 babies randomized to intervention or control arms; intervention involved supplementation of delivery with JANMA CDKs. Interviews were conducted at the birth homes, and the primary outcomes were neonatal infection and puerperal fever. The association between infection and perinatal risk factors was tested using the Chi-square and Fisher's exact tests. CDKs were well accepted by TBAs. The incidence of puerperal fever and neonatal infection was 1.1% and 11.2%, respectively. Concurrent infection was found in 1 (0.22%) of the mother-neonate pair. There was no significant association between any of the sociodemographic factors and infection for both mothers and neonates. PROM and prolonged labour were significantly associated with puerperal infection. All mothers with puerperal fever were from the control group. Compared to the control group, the relative risk of puerperal infection and neonatal infection in the intervention group was 0.08 (0.004 -1.35, p = 0.079) and 0.64 (0.37 to 1.1, p = 0.10), respectively. CDKs hold promising results in attenuating maternal infections in resource-poor settings. Larger studies with greater statistical power are required to establish statistically reliable information.

Board Diversity and Corporate Sustainability Performance: Do CEO Power and Firm Environmental Sensitivity Matter?

The study assesses whether CEO power and firm environmental sensitivity matter to board diversity (i.e., board cultural (BCD) and board gender (BGD) diversity) and corporate sustainability performance nexus. Australian S&amp;P/ASX300′s firm data for a period of ten years (2011–2020) were used in the study’s analysis. Although board diversity positively influences ESG performance, the presence of powerful CEOs and when firms operate in environmentally sensitive industries weaken the board diversity and sustainability performance nexus. Additionally, the study found that although board diversity is essential, the effect of BGD has a greater statistical power on sustainability than BCD, affirming the present focus on BGD.

Evaluation of pragmatic oxygenation measurement as a proxy for Covid-19 severity

Choosing optimal outcome measures maximizes statistical power, accelerates discovery and improves reliability in early-phase trials. We devised and evaluated a modification to a pragmatic measure of oxygenation function, the S/F ratio. Because of the ceiling effect in oxyhaemoglobin saturation, S/F ratio ceases to reflect pulmonary oxygenation function at high {S}_{p}{O}_{2} values. We found that the correlation of S/F with the reference standard ({P}_{a}{O}_{2}/{F}_{I}{O}_{2} ratio) improves substantially when excluding {S}_{p}{O}_{2} > 0.94 and refer to this measure as S/{F}_{94}. Using observational data from 39,765 hospitalised COVID-19 patients, we demonstrate that S/{F}_{94} is predictive of mortality, and compare the sample sizes required for trials using four different outcome measures. We show that a significant difference in outcome could be detected with the smallest sample size using S/{F}_{94}. We demonstrate that S/{F}_{94} is an effective intermediate outcome measure in COVID-19. It is a non-invasive measurement, representative of disease severity and provides greater statistical power.

Prevalence and predictors of QTc prolongation in patients seen in a clozapine clinic in a real-world setting in Australia

BackgroundMany antipsychotic drugs have been associated with QTc prolongation, which is a risk factor for sudden death. We studied the prevalence and predictors of QTc prolongation in treatment-resistant schizophrenia patients who were receiving clozapine in a real-world setting. MethodsData were extracted from the records of all schizophrenia patients aged 18–65 years, enrolled in a clozapine clinic in metropolitan Australia during October 2020 to April 2022, for whom ECG data were available. ResultsThere were 104 eligible patients. The mean age of the sample was 42 years. The sample was 56 % male. About a third of patients were receiving antipsychotic and antidepressant drugs in addition to clozapine. The mean (standard deviation) QTc was 437.0 (24.8) ms in men and 445.8 (28.5) ms in women. QTc prolongation was present in 36.5 % of the sample. In univariate analysis, higher heart rate and higher clozapine levels were significantly associated with QTc prolongation; in multivariable logistic regression analysis, nonsignificant statistical trends were observed for male sex, higher heart rate, and higher serum clozapine level. ConclusionsQTc prolongation may be common in schizophrenia patients who receive clozapine in real world settings; this is a matter of much concern. Potential predictors of QTc prolongation need to be identified and these predictors and their interactions require to be explored in studies with greater statistical power.

Comparative effectiveness and drug survival of biosimilar infliximab CPT-13 vs. reference infliximab in inflammatory bowel disease: A retrospective cohort study

BackgroundStudies have investigated the efficacy and safety of switching to the biosimilar infliximab (CT-P13) in patients with inflammatory bowel disease (IBD). However, there is limited research directly comparing the effectiveness, drug survival, and pharmacokinetic profiles of the reference infliximab (IFX) and CT-P13 in real clinical settings. ObjectiveTo compare the effectiveness and drug survival of CPT-13 and reference IFX at weeks 26 and 52, and to determine the pharmacokinetic profiles and safety profile in real-world settings. MethodsA retrospective observational cohort analysis was conducted at a single center. The study compared the proportion of patients achieving clinical remission and experiencing poor clinical outcomes at weeks 26 and 52. The drug survival rate of CT-P13 and reference infliximab was also assessed during the follow-up period. ResultsA total of 153 patients were included in the study, 39.2% receiving CPT-13 and 60.8% reference IFX. At week 26, clinical remission rates were 66.7% (CPT-13: 74.4% vs. reference IFX: 62.3%, p=0.178), and at week 52, they were 64% (CPT-13: 85.4% vs. reference IFX: 63.0%, p=0.012). Subgroup analysis with therapeutic drug monitoring (TDM) found no significant differences at week 26 (CPT-13: 74.4% vs. reference IFX: 58.8%, p=0.235) or at week 52 (CPT-13: 85.4% vs. reference IFX: 68.8%, p=0.153). ConclusionOur study demonstrates comparable efficacy, drug survival, pharmacokinetic profiles, and incidence of immunogenicity between both drugs in a real clinical setting. Further studies with greater statistical power are needed to validate these findings.

Cuantificación absoluta de la captación miocárdica de 99mTc-DPD en pacientes con amiloidosis cardiaca por depósitos de transtiretina (ATTR)

PurposeTo determine the diagnostic contribution of the absolute quantification of the myocardial deposit of 99mTc-DPD in patients with cardiac amyloidosis due to transthyretin deposits (ATTR). Materials and methodsSPECT/CT was performed on 41 patients with positive scintigraphic results for ATTR cardiac amyloidosis. The patients were divided into two groups (Perugini grades2 and3) and the SUVmax at the level of the bone and both ventricles and the percentage of dose calculated in these areas were calculated. Student's t-test was used to compare results and the area under the curve (AUC) was calculated to assess differential efficacy and establish discriminatory cut-off points between both groups of patients. ResultsStatistically significant differences were observed in all the study variables, with the exception of SUVmax bone. The differences with the greatest statistical power were observed in the variables SUVmaxRV and the percentage of dose in both ventricles (P<.001). The cut-off point obtained for the variable SUVmaxLV was 8.620 (sensitivity 87.9% and specificity 100%; AUC: 0.966), while that of the variable SUVmaxRV was 6.195 (sensitivity 81.8% and specificity 100%; AUC: 0.955). ConclusionsThe absolute quantification of myocardial uptake of 99mTc-DPD in the SPECT/CT images of patients with suspected cardiac amyloidosis due to transthyretin deposits represents a new diagnostic tool that allows an adequate classification of patients, according to the visual grading scale of Perugini.

Lympho-hematopoietic malignancies risk after exposure to low dose ionizing radiation during cardiac catheterization in childhood.

Pediatric patients with congenital heart disease (CHD) often undergo low dose ionizing radiation (LDIR) from cardiac catheterization (CC) for the diagnosis and/or treatment of their disease. Although radiation doses from a single CC are usually low, less is known about the long-term radiation associated cancer risks. We aimed to assess the risk of lympho-hematopoietic malignancies in pediatric CHD patients diagnosed or treated with CC. A French cohort of 17,104 children free of cancer who had undergone a first CC from 01/01/2000 to 31/12/2013, before the age of 16 was set up. The follow-up started at the date of the first recorded CC until the exit date, i.e., the date of death, the date of first cancer diagnosis, the date of the 18th birthday, or the 31/12/2015, whichever occurred first. Poisson regression was used to estimate the LDIR associated cancer risk. The median follow-up was 5.9 years, with 110,335 person-years. There were 22,227 CC procedures, yielding an individual active bone marrow (ABM) mean cumulative dose of 3.0 milligray (mGy). Thirty-eight incident lympho-hematopoietic malignancies were observed. When adjusting for attained age, gender and predisposing factors to cancer status, no increased risk was observed for lympho-hematopoietic malignancies RR/mGy = 1.00 (95% CI: 0.88; 1.10). In summary, the risk of lympho-hematopoietic malignancies and lymphoma was not associated to LDIR in pediatric patients with CHD who undergo CC. Further epidemiological studies with greater statistical power are needed to improve the assessment of the dose-risk relationship.