Tag: statistics

Stat Med. 2021 Aug 25. doi: 10.1002/sim.9175. Online ahead of print.

ABSTRACT

In clinical trials, sample size re-estimation is often conducted at interim. The purpose is to determine whether the study will achieve study objectives if the observed treatment effect at interim preserves till end of the study. A traditional approach is to conduct a conditional power analysis for sample size only based on observed treatment effect. This approach, however, does not take into consideration the variabilities of (i) the observed (estimate) treatment effect and (ii) the observed (estimate) variability associated with the treatment effect. Thus, the resultant re-estimated sample sizes may not be robust and hence may not be reliable. In this article, a couple of methods are proposed, namely, adjusted effect size (AES) approach and iterated expectation/variance (IEV) approach, which can account for the variability associated with the observed responses at interim. The proposed methods provide interval estimates of sample size required for the intended trial, which is useful for making critical go/no go decision. Statistical properties of the proposed methods are evaluated in terms of controlling of type I error rate and statistical power. The results show that traditional approach performs poorly in controlling type I error inflation, whereas IEV approach has the best performance in most cases. Additionally, all re-estimation approaches can keep the statistical power over 80 % ; especially, IEV approach’s statistical power, using adjusted significance level, is over 95 % . However, IEV approach may lead to a greater increment in sample size when detecting a smaller effect size. In general, IEV approach is effective when effect size is large; otherwise, AES approach is more suitable for controlling type I error rate and keep power over 80 % with a more reasonable re-estimated sample size.

PMID:34433225 | DOI:10.1002/sim.9175

Appl Immunohistochem Mol Morphol. 2021 Aug 24. doi: 10.1097/PAI.0000000000000968. Online ahead of print.

ABSTRACT

Pulmonary lymphangioleiomyomatosis (LAM) is a rare cystic lung disease affecting predominantly young women. Classified as a low-grade malignant soft tissue neoplasm from the family of perivascular epithelioid cell (PEC) tumors or PEComas, it is characterized by a proliferation of abnormal smooth muscle-like cells (LAM cells), coexpressing myogenic and melanocytic markers, with HMB45 as the gold-standard immunohistochemical diagnostic marker. Cathepsin K, a papain-like cysteine protease with high matrix degrading activity, is commonly used in the pathologic diagnosis of other PEComa tumors, but there are few data regarding its expression in pulmonary LAM. This study compares the sensitivity of cathepsin K with that of HMB45 as immunohistochemical diagnostic markers for pulmonary LAM. Twenty-one (n=21) specimens of pulmonary LAM were retrieved from the archives of the Department of Pathology of the Cleveland Clinic. All cases were evaluated for protein expression of HMB45 and cathepsin K, on consecutive sections of formalin-fixed, paraffin-embedded tissue. The intensity and the total area of the immunostaining were quantified using an Aperio Scan Scope and analyzed with imaging software (Spectrum). Statistical analysis was performed using GraphPad software. The probability of a positive stained lesion on a transbronchial biopsy for each antibody was calculated. The percentage of LAM cells expressing cathepsin K was significantly higher than for HMB45 and overall expression was statistically significantly higher (P=0.0116). Our findings conclude that cathepsin K is a significantly more sensitive immunohistochemical marker than HMB45 in diagnosing pulmonary LAM.

PMID:34433182 | DOI:10.1097/PAI.0000000000000968

Z Geburtshilfe Neonatol. 2021 Aug 25. doi: 10.1055/a-1579-1338. Online ahead of print.

ABSTRACT

BACKGROUND: Following the discovery that fetal DNA originates from the trophoblastic cells of the placenta, the contribution of the cell-free DNA test in placenta-related obstetric complications has begun to be investigated. Compared to uncomplicated pregnancies, higher fetal fractions were detected in placenta accreta spectrum and placenta previa, which are among placenta-related obstetric complications. However, this data applies only to advanced gestational weeks.

AIM: To investigate the possible predictive value of fetal fraction in cell-free DNA tests in pregnancies with placenta previa and placenta accreta spectrum in early gestational ages.

MATERIALS AND METHODS: This study was conducted in women who were screened via cell-free DNA tests for common aneuploidies in the first and second trimester and subsequently diagnosed with placenta previa or placenta accreta spectrum. After the diagnosis was confirmed with a C-section, fetal fractions were retrospectively compared to a control group with a history of an uncomplicated C-section who were also previously screened by cell-free DNA test.

RESULTS: The median and interquartile range (IQR) of fetal fractions for placenta previa (n=19), placenta accreta spectrum (n=7), and control groups (n=85) were 8.1 (6-10), 6.8 (6.7-10.7), and 7.1 (4.7-9.65), respectively. No statistically significant difference was observed among the three groups in terms of fetal fractions (p=0.587).

CONCLUSIONS: According to our data, we did not observe any relationship between placental invasion abnormalities vs. control group or placenta previa vs. control group using the fetal fractions of the cell-free DNA test. Furthermore, we could not confirm a predictive role and/or any additional clinical contribution. We believe that future studies focusing on placental mRNA might be more helpful than cell-free fetal DNA testing.

PMID:34433209 | DOI:10.1055/a-1579-1338

Mult Scler Relat Disord. 2021 Aug 19;55:103219. doi: 10.1016/j.msard.2021.103219. Online ahead of print.

ABSTRACT

Background Multiple sclerosis (MS) is an autoimmune and neurodegenerative disease of the central nervous system in which disease activity can be monitored with some biomarkers. The aim of our study was to investigate serum Glial Fibrillary Acidic Protein (GFAP) and Neurofilament Light Chain (NFL) in relapsing-remitting MS (RRMS) patients after the aerobic exercise. Methods A total of 38 participants with RRMS (Expanded Disability Status Scale: 1.0 – 4.5) were randomized to a study group (3 × /week for 8 weeks at 60 – 70 % of maximal aerobic capacity (VO_2max) + home exercises) and a control group (were given home exercises programme 3 times a week for 8 week). Serum NFL and GFAP levels were analyzed using enzyme-linked immunosorbent analysis method before and at the end of 8 weeks. Results: NFL and GFAP levels were statistically lower in the study group at the end of the study than before the study. In the control group, no significant changes were observed in serum NFL and GFAP levels. ΔNFL levels were significantly higher in the study group than control group. Conclusion It was shown, for the first time that serum GFAP and NFL levels (%10 and % 32, respectively) in RRMS patients decreased after aerobic exercise. Our study is important in terms of investigating the effects of aerobic exercise in individuals with RRMS and elucidating the underlying measurable biomarkers. The significant reduction of NFL and GFAP, which have an important role in the pathology associated with nervous system damage in MS, with aerobic exercise may be promising in understanding the regulation of disease activity in MS patients.

PMID:34433118 | DOI:10.1016/j.msard.2021.103219

Cardiorenal Med. 2021;11(4):174-183. doi: 10.1159/000517123. Epub 2021 Aug 10.

ABSTRACT

INTRODUCTION: Patients with chronic kidney disease experience high rates of cardiovascular mortality and morbidity. When kidney disease progresses to the need for dialysis, sudden cardiac death (SCD) accounts for 25-35% of all cardiovascular deaths. The objective was to determine if rare genetic variants known to be associated with cardiovascular death in the general population are associated with SCD in patients undergoing hemodialysis.

METHODS: We performed a case-control study comparing 126 (37 African American [AfAn] and 89 European ancestry [EA]) SCD subjects and 107 controls (34 AfAn and 73 EA), matched for age, sex, self-reported race, dialysis duration (<2, 2-5 and >5 years), and the presence or absence of diabetes mellitus. To target the coding regions of genes previously reported to be associated with 15 inherited cardiac conditions (ICCs), we used the TruSight Cardio Kit (Illumina, San Diego, CA, USA) to capture the genetic regions of interest. In all, the kit targets 572-kb regions that include the protein-coding regions and 40-bp 5′ and 3′ end-flanking regions of 174 genes associated with the 15 ICCs. Using the sequence data, burden tests were conducted to identify genes with an increased number of variants among SCD cases compared to matched controls.

RESULTS: Eleven genes were associated with SCD, but after correction for multiple testing, none of the 174 genes were identified as having more variants in the SCD cases than the matched controls, including previously identified genes. Secondary burden tests grouping variants based on diseases and gene function did not produce statistically significant associations.

DISCUSSION/CONCLUSIONS: We found no associations between genes known to be associated with ICCs and SCD in our sample of patients undergoing hemodialysis. This suggests that genetic causes are unlikely to be a major pathogenic factor in SCD in hemodialysis patients, although our sample size limits definitive conclusions.

PMID:34433165 | DOI:10.1159/000517123

Cardiorenal Med. 2021;11(4):193-199. doi: 10.1159/000517884. Epub 2021 Aug 12.

ABSTRACT

INTRODUCTION: Several clinical studies and meta-analyses have demonstrated lower incidence of adverse renal and cardiovascular outcomes associated with the use of iso-osmolar contrast media (IOCM) than low-osmolar contrast media (LOCM) in patients with variable risk profiles undergoing intra-arterial interventional procedures. However, the association of contrast-type and major adverse renal and cardiovascular events (MARCE) has not been studied via comprehensive and robust real-world data analyses in patients with comorbid conditions considered at risk for post-procedural acute kidney injury (AKI). The objective of this study was therefore to retrospectively assess the MARCE rates comparing IOCM with LOCM in at-risk patients receiving iodinated intra-arterial contrast media using a real-world inpatient data source.

METHODS: Patients who underwent a diagnostic or treatment procedure with intra-arterial IOCM or LOCM administration were identified using the Premier Healthcare Database. Patient subgroups including those with diabetes, heart failure, chronic kidney disease (CKD) stages 1-4, CKD 3-4, or diagnosis of chronic total occlusion (CTO) were formed. Subgroups with combinations of diabetes and CKD 3-4 with and without CTO were also investigated. We compared the primary endpoint of MARCE (composite of AKI, AKI requiring dialysis, acute myocardial infarction, stroke/transient ischemic attack, stent occlusion/thrombosis, or death) after IOCM versus LOCM administration via adjusted multivariable regression analyses.

RESULTS: A total of 536,013 inpatient visits met the primary inclusion and exclusion criteria (IOCM = 133,192; LOCM = 402,821). After multivariable modeling, the use of IOCM was associated with a significantly lower incidence of MARCE than LOCM in patients with CKD 1-4, CKD 3-4, diabetes, or heart failure, with greatest absolute risk reduction (ARR) of 2.4% (p < 0.0001) in CKD 3-4 patients (relative risk reduction [RRR] = 13.8%, number needed to treat [NNT] = 43). Additionally, ARR associated with IOCM increased to 3.5% (p < 0.0001) in patients with combined comorbidities of diabetes and CKD 3-4 (RRR = 19.1%, NNT = 29). Statistically significant risk reduction was also found for the use of IOCM among patients who underwent revascularization for CTO (ARR = 1.6% [p < 0.0001], RRR = 22.3%, NNT = 62).

CONCLUSION: Intra-arterial administration using IOCM in at-risk patients is associated with lower rates of MARCE than the use of LOCM. This difference is especially apparent in patients with a combination of CKD 3-4 and diabetes and in patients with CTO, providing real-world data validation with meaningful NNT in favor of IOCM.

PMID:34433166 | DOI:10.1159/000517884

Water Res. 2021 Aug 12;203:117543. doi: 10.1016/j.watres.2021.117543. Online ahead of print.

ABSTRACT

According to the European Directives (UE) 2020/2184 and 2009/54/EC, which establishes the sanitary criteria for water intended for human consumption in Europe, water suitable for human consumption must be free of the bacterial indicators Escherichia coli, Clostridium perfringens and Enterococcus spp. Drinking water is also monitored for heterotrophic bacteria, which are not a human health risk, but can serve as an index of bacteriological water quality. Therefore, a rapid, accurate, and cost-effective method for the identification of these colonies would improve our understanding of the culturable bacteria of drinking water and facilitate the task of water management by treatment facilities. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) is potentially such a method, although most of the currently available mass spectral libraries have been developed in a clinical setting and have limited environmental applicability. In this work, a MALDI-TOF MS drinking water library (DWL) was defined and developed by targeting bacteria present in water intended for human consumption. This database, made up of 319 different bacterial strains, can contribute to the routine microbiological control of either treated drinking water or mineral bottled water carried out by water treatment and distribution operators, offering a faster identification rate compared to a clinical sample-based library. The DWL, made up of 96 bacterial genera, 44 of which are not represented in the MALDI-TOF MS bacterial Bruker Daltonics (BDAL) database, was found to significantly improve the identification of bacteria present in drinking water.

PMID:34433109 | DOI:10.1016/j.watres.2021.117543

Behav Res Ther. 2021 Aug 15;145:103947. doi: 10.1016/j.brat.2021.103947. Online ahead of print.

ABSTRACT

Preliminary evidence suggests mental imagery-based episodic simulation of planned reward activities may amplify motivation and promote greater behavioural engagement, particularly for activities with high motivational barriers (Renner, Murphy, Ji, Manly, & Holmes, 2019). This study conducted a conceptual replication and extension of Renner et al. (2019). N = 81 first-year university students self-selected and scheduled two reward activities (one hedonic, one mastery) for the following week before being randomly allocated to either an Imagery-Experiential elaboration condition (n = 27), a Verbal-Reasoning elaboration condition (n = 28), or a Scheduling-only Control condition (n = 26). Following the lab session, all participants received standardized daily prompts to complete daily activity diaries online for seven days. The Imagery-Experiential condition reported greater increases in anticipatory pleasure (state mood), anticipated pleasure, and self-reported motivation compared to the Scheduling-only Control condition, and greater increases in anticipatory pleasure (state mood), but not anticipated pleasure or motivation, relative to the Verbal-Reasoning condition. Consistent with Renner et al. (2019), the Imagery-Experiential condition, but not the Verbal-Reasoning condition, reported more frequent engagement in high motivational barrier activities than the Scheduling-only Control condition. Exploratory mediational analyses suggested that mental imagery may exert unique motivational impacts via its impact on anticipatory pleasure (state mood), although indirect effects were only observed for self-reported motivation change in the lab, with real world behavioural effects falling short of statistical significance.

PMID:34433114 | DOI:10.1016/j.brat.2021.103947

Ann Vasc Surg. 2021 Aug 22:S0890-5096(21)00527-6. doi: 10.1016/j.avsg.2021.05.049. Online ahead of print.

ABSTRACT

INTRODUCTION: Complications following vascular procedures involving the groin can lead to significant morbidity. Achieving stable soft tissue coverage over sites of revascularization can help mitigate complications. Prior evidence supports the use of muscle flaps in reoperative groins and in high risk patient populations to reduce postoperative complications. Data regarding the use of prophylactic muscle flap coverage of the groin is lacking. Therefore, the purpose of this study is to evaluate the effect of immediate prophylactic muscle flap coverage of vascular wounds involving the groin.

METHODS: A retrospective cohort study was performed on all patients undergoing primary open vascular procedures involving the groin for occlusive, aneurysmal, or oncologic disease between 2014 and 2020 at a single institution where plastic surgery was involved in closure. Patient demographics, comorbidities, surgical details, and postoperative complications were compared between patients who had sartorius muscle flap coverage of the vascular repair versus layered closure alone.

RESULTS: A total of 133 consecutive groins were included in our analysis. A sartorius flap was used in 115 groins (86.5%) and a layered closure was used in 18 (13.5%). Wound breakdown was similar between groups (25.2% sartorius vs. 38.9% layered closure, p=0.26). However, the rate of reoperation was significantly higher in the layered closure group (50.0% vs. 12.2%, p<0.01). Among patients who experienced wound breakdown (N = 36), a larger proportion of layered closure patients required operative intervention (71.4% vs. 20.7%, p=0.02). Other rates of complications were not statistically different between groups.

CONCLUSIONS: In patients undergoing primary open vascular procedures involving the groin, patients who underwent prophylactic sartorius muscle flap closure had lower rates of reoperation. Although incisional breakdown was similar between the groups overall, the presence of a vascularized muscle flap overlying the vascular repair was associated with reduced need for reoperation and allowed more wounds to be managed with local wound care alone. Consideration should be given to this low morbidity local muscle flap in patients undergoing vascular procedures involving the groin.

PMID:34433093 | DOI:10.1016/j.avsg.2021.05.049

Ann Epidemiol. 2021 Aug 22:S1047-2797(21)00265-9. doi: 10.1016/j.annepidem.2021.08.015. Online ahead of print.

ABSTRACT

Estimates of HIV prevalence, and how it changes over time, are needed to inform action (e.g., resource allocation) to improve HIV-related public health. However, creating adequate estimates of (diagnosed and undiagnosed) HIV prevalence is challenging due to biases in samples receiving HIV testing and due to difficulties enumerating key risk populations. To our knowledge, estimates of HIV prevalence among high risk heterosexuals in the United States produced for geographic areas smaller than the entire nation have to date been only for single years and/or for single cities (or other single geographic locations). The present study addresses these gaps by using multilevel modeling on multiple data series, in combination with previous estimates of HIV prevalence among heterosexuals from the extant literature, to produce annual estimates of HIV prevalence among high risk heterosexuals for each of 89 metropolitan statistical areas, from 1992-2013. It also produces estimates for these MSAs and years by racial/ethnic subgroup to allow for an examination of change over time in racial/ethnic disparities in HIV prevalence among high risk heterosexuals. The resulting estimates suggest that HIV prevalence among high risk heterosexuals has decreased steadily, on average, from 1992-2013. Examination of these estimates by racial/ethnic subgroup suggests that this trend is primarily due to decreases among Black and Hispanic/Latino high risk heterosexuals. HIV prevalence among white high risk heterosexuals remained steady over time at around 1 percent during the study period. Although HIV prevalence among Black and Hispanic/Latino high risk heterosexuals was much higher (approximately 3.5% and 3.3%, respectively) than that among whites in 1992, over time these differences decreased as HIV prevalence decreased over time among these subgroups. By 2013, HIV prevalence among Hispanic/Latino high risk heterosexuals was estimated to be very similar to that among white high risk heterosexuals (approximately 1 percent), with prevalence among Black high risk heterosexuals still estimated to be almost twice as high. It is likely that as HIV incidence has decreased among heterosexuals from 1992-2013, mortality due to all causes has remained disparately high among racial/ethnic minorities, thereby outpacing new HIV cases. Future research should aim to empirically examine this by comparing changes over time in estimated HIV incidence among heterosexuals to changes over time in mortality and causes of death among HIV-positive heterosexuals, by racial/ethnic subgroup.

PMID:34433105 | DOI:10.1016/j.annepidem.2021.08.015