Category: Statistics

Arch Gynecol Obstet. 2022 Jun 11. doi: 10.1007/s00404-022-06565-6. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the efficacy of manifold ovarian stimulation protocols for patients with poor ovarian response.

METHODS: PubMed, Embase, Cochrane Library and Web of Science were systematically searched until February 14, 2021. Primary outcomes included clinical pregnancy rate per initiating cycle and low risk of cycle cancellation. Secondary outcomes included number of oocytes retrieved, number of metaphase II (MII) oocytes, number of embryos obtained, number of transferred embryos, endometrial thickness on triggering day and estradiol (E₂) level on triggering day. The network plot, league table, rank probabilities and forest plot of each outcome measure were drawn. Therapeutic effects were displayed as risk ratios (RRs) or mean differences (MDs) with 95% confidence intervals (CIs).

RESULTS: This network meta-analysis included 15 trials on 2173 participants with poor ovarian response. Delayed start GnRH antagonist was the best regimen in terms of clinical pregnancy rate per initiating cycle (74.04% probability of being the optimal), low risk of cycle cancellation (75.30%), number of oocytes retrieved (68.67%), number of metaphase II (MII) oocytes (97.98%) and endometrial thickness on triggering day (81.97%), while for E₂ level on triggering day, microdose GnRH agonist (99.25%) was the most preferred. Regarding number of embryos obtained and number of transferred embryos, no statistical significances were found between different ovarian stimulation protocols.

CONCLUSION: Delayed start GnRH antagonist and microdose GnRH agonist were the two superior regimens in the treatment of poor ovarian response, providing favorable clinical outcomes. Future investigation is needed to confirm and enrich our findings.

PMID:35689674 | DOI:10.1007/s00404-022-06565-6

Nephrol Dial Transplant. 2022 Jun 11:gfac170. doi: 10.1093/ndt/gfac170. Online ahead of print.

ABSTRACT

BACKGROUND: Hemodialysis treatment causes significant reductions in quality of life (QoL). When enrolled in a clinical trial, some patients are lost prior to follow-up either because they die or receive a kidney transplant. It is unclear how these patients are dealt with in the analysis of QoL data. There are questions surrounding the consistency of how QoL measures are used, reported and analysed.

METHODS: A systematic search of electronic databases for trials measuring QoL in hemodialysis patients using any variation of the Kidney Disease Quality of Life (KDQoL) Questionnaire. The review was conducted in Covidence version2. Quantitative analysis was conducted in STATA version16.

RESULTS: We included 61 trials in the review, of which 82% reported dropouts. The methods to account for missing data due to dropouts include imputation (7%) and complete case analysis (72%). Few trials (7%) conducted sensitivity analysis to assess the impact of missing data on the study results. Single imputation techniques were used which are only valid under strong assumptions regarding the type and pattern of missingness. There was inconsistency in the reporting of the KDQoL, with many papers (54%) amending the validated questionnaires or reporting only statistically significant results.

CONCLUSIONS: Missing data are not dealt with according to the missing data mechanism, which may lead to biased results. Inconsistency in the use of patient reported outcome measures raises questions about the validity of these trials. Methodological issues in nephrology trials could be a contributing factor to why there are limited effective interventions to improve QoL in this patient group.

PROSPERO REGISTRATION NUMBER: CRD42020223869.

PMID:35689670 | DOI:10.1093/ndt/gfac170

Rheumatology (Oxford). 2022 Jun 11:keac337. doi: 10.1093/rheumatology/keac337. Online ahead of print.

ABSTRACT

OBJECTIVES: Rheumatoid Arthritis (RA) and primary Sjögren’s Syndrome (SS) carry increased atherosclerotic risk, while B cell activating factor holds a vital role in disease pathogenesis and atherosclerosis. We aimed to compare subclinical atherosclerosis profiles between the two clinical entities and define whether BAFF genetic variants alter atherosclerotic risk.

METHODS: DNA from 166 RA, 148 primary SS patients and 200 healthy controls of similar age and sex distribution was subjected to PCR-based assay for the detection of five single nucleotide polymorphisms of the BAFF gene (rs1224141, rs12583006, rs9514828, rs1041569, and rs9514827). Genotype and haplotype frequencies were determined by SNPStats software and statistical analysis was performed by SPSS and Graphpad Software. Subclinical atherosclerosis was defined by the presence of carotid/femoral plaque formation and arterial wall thickening.

RESULTS: Atherosclerotic plaque formation was more frequently detected in the RA vs primary SS group (80.7% vs 62.2%, p-value <0.001), along with higher rates of family CVD history, current steroid dose, and serum inflammatory markers. The TT genotype of the rs1224141 variant was more prevalent in RA but not primary SS patients with plaque and arterial wall thickening vs their counterparts without. Regarding the rs1014569 variant, among RA patients the TT genotype increased the risk for plaque formation while in primary SS patients the AT genotype conferred increased risk. Haplotype GTTTT was protective in the RA cohort, while TATTT and TTCTT haplotypes increased susceptibility for arterial wall thickening in the primary SS cohort.

CONCLUSIONS: Increased inflammatory burden, higher steroid doses and distinct BAFF gene variations imply chronic inflammation and B cell hyperactivity as key contributors for the augmented atherosclerotic risk among autoimmune patients.

PMID:35689637 | DOI:10.1093/rheumatology/keac337

Syst Biol. 2022 Jun 11:syac040. doi: 10.1093/sysbio/syac040. Online ahead of print.

ABSTRACT

Whole-genome duplication (WGD) occurs broadly and repeatedly across the history of eukaryotes, and is recognized as a prominent evolutionary force, especially in plants. Immediately following WGD, most genes are present in two copies as paralogs. Due to this redundancy, one copy of a paralog pair commonly undergoes pseudogenization and is eventually lost. When speciation occurs shortly after WGD, however, differential loss of paralogs may lead to spurious phylogenetic inference resulting from the inclusion of pseudoorthologs-paralogous genes mistakenly identified as orthologs because they are present in single copes within each sampled species. The influence and impact of including pseudoorthologs versus true orthologs as a result of gene extinction (or incomplete laboratory sampling) is only recently gaining empirical attention in the phylogenomics community. Moreover, few studies have yet to investigate this phenomenon in an explicit coalescent framework. Here, using mathematical models, numerous simulated data sets, and two newly assembled empirical data sets, we assess the effect of pseudoorthologs on species tree estimation under varying degrees of incomplete lineage sorting (ILS) and differential gene loss scenarios following WGD. When gene loss occurs along the terminal branches of the species tree, alignment-based (BPP) and gene-tree-based (ASTRAL, MP-EST, and STAR) coalescent methods are adversely affected as the degree of ILS increases. This can be greatly improved by sampling a sufficiently large number of genes. Under the same circumstances, however, concatenation methods consistently estimate incorrect species trees as the number of genes increases. Additionally, pseudoorthologs can greatly mislead species tree inference when gene loss occurs along the internal branches of the species tree. Here, both coalescent and concatenation methods yield inconsistent results. These results underscore the importance of understanding the influence of pseudoorthologs in the phylogenomics era.

PMID:35689633 | DOI:10.1093/sysbio/syac040

Genetics. 2022 Jun 11:iyac088. doi: 10.1093/genetics/iyac088. Online ahead of print.

ABSTRACT

We develop a computationally efficient alternative, TwinEQTL, to a linear mixed-effects model (LMM) for twin genome-wide association study (GWAS) data. Instead of analyzing all twin samples together with LMM, TwinEQTL first splits twin samples into two independent groups on which multiple linear regression analysis can be validly performed separately, followed by an appropriate meta-analysis-like approach to combine the two non-independent test results. Through mathematical derivations, we prove the validity of TwinEQTL algorithm and show that the correlation between two dependent test statistics at each single-nucleotide polymorphism (SNP) are independent of its minor allele frequency (MAF). Thus the correlation is constant across all SNPs. Through simulations, we show empirically that TwinEQTL has well controlled type I error with negligible power loss compared to the gold-standard linear mixed effects models. To accommodate eQTL analysis with twin subjects, we further implement TwinEQTL into a R package with much improved computational efficiency. Our approaches provide a significant leap in terms of computing speed for GWAS and eQTL analysis with twin samples.

PMID:35689615 | DOI:10.1093/genetics/iyac088

J Surg Oncol. 2022 Jun 11. doi: 10.1002/jso.26982. Online ahead of print.

ABSTRACT

BACKGROUND: Applicability of the albumin-bilirubin (ALBI) grade in preoperative decision-making criteria based on the indocyanine green retention (ICG) test remains unclear. This study aimed to predict abnormal ICG values using standard blood tests and evaluate the impact on postoperative outcomes among patients undergoing hepatectomy for hepatocellular carcinoma (HCC).

METHODS: Data on 949 consecutive HCC patients undergoing curative-intent hepatectomy between 1996 and 2014 were retrospectively assessed. A nomogram using preoperative standard blood tests was created to predict abnormal ICGR15 (>15%).

RESULTS: Three-hundred nine patients had abnormal ICGR15. Predictors of abnormal ICGR15 included in the nomogram were: ALBI grade >1 (hazard ratio [HR]: 2.16, 95% confidence interval [CI]: 1.59-2.94), platelet count <130 000/mm³ (HR: 2.27, 95% CI: 1.68-3.08), aspartate aminotransferase >50 (IU/L) (HR: 1.90, 95% CI: 1.29-2.81), and viral hepatitis infection (HR: 1.46, 95% CI: 1.03-2.07). The nomogram named the PLT-ALBI score was discriminative [C-statistics: 0.719 (0.684-0.754)], and reliable (Hosmer-Lemeshow Chi-Square: 9.05, p = 0.338). The higher PLT-ALBI score was associated with a more frequent incidence of clinically relevant posthepatectomy liver failure and poor overall survival.

CONCLUSIONS: The PLT-ALBI score is applicable in distinguishing HCC patients with abnormal ICGR15. Patients with higher PLT-ALBI score require more careful postoperative care, despite following the ICG criteria.

PMID:35689605 | DOI:10.1002/jso.26982

Electrophoresis. 2022 Jun 11. doi: 10.1002/elps.202200075. Online ahead of print.

ABSTRACT

Affinity capillary electrophoresis was used for the simultaneous measurement of the pKa$p{K_a}$ values and of the binding constants relative to the encapsulation of naturally occurring phenolic acids (rosmarinic and caffeic acids) with cyclodextrins. A thorough study as a function of pH and temperature was coupled to a detailed statistical analysis of the resulting experimental data. A step-by-step curve fitting process was sufficient for obtaining individual binding constant for each experimental condition, but the influence of temperature remained unclear. A quantitative and qualitative gain was then obtained by supplementing this initial analysis with a global multi-parameters optimization. This lead to the estimation of both entropy and enthalpy of reaction, and to the full description of the binding reactions as a function of pH and temperature. The encapsulation was shown to be very sensitive to pH and temperature, with optimal complexation occurring at low pH and low temperature, gaining up to a factor 3 by cooling from 36°C to 15°C, and up to a factor 10 by lowering the pH from 7 to 2. This article is protected by copyright. All rights reserved.

PMID:35689604 | DOI:10.1002/elps.202200075

Schizophr Bull. 2022 Jun 11:sbac053. doi: 10.1093/schbul/sbac053. Online ahead of print.

ABSTRACT

To examine long-term effects of early intervention services (EIS) for first-episode psychosis, we compared Heinrichs-Carpenter Quality of Life (QLS) and Positive and Negative Syndrome Scale (PANSS) scores and inpatient hospitalization days over 5 years with data from the site-randomized RAISE-ETP trial that compared the EIS NAVIGATE (17 sites; 223 participants) and community care (CC) (17 sites; 181 participants). Inclusion criteria were: age 15-40 years; DSM-IV diagnoses of schizophrenia, schizoaffective disorder, schizophreniform disorder, brief psychotic disorder, or psychotic disorder not otherwise specified; first psychotic episode; antipsychotic medication taken for ≤6 months. NAVIGATE-randomized participants could receive NAVIGATE from their study entry date until NAVIGATE ended when the last-enrolled NAVIGATE participant completed 2 years of treatment. Assessments occurred every 6 months. 61% of participants had assessments conducted ≥2 years; 31% at 5 years. Median follow-up length was CC 30 months and NAVIGATE 38 months. Primary analyses assumed data were not-missing-at-random (NMAR); sensitivity analyses assumed data were missing-at-random (MAR). MAR analyses found no significant treatment-by-time interactions for QLS or PANSS. NMAR analyses revealed that NAVIGATE was associated with a 13.14 (95%CI:6.92,19.37) unit QLS and 7.73 (95%CI:2.98,12.47) unit PANSS better improvement and 2.53 (95%CI:0.59,4.47) fewer inpatient days than CC (all comparisons significant). QLS and PANSS effect sizes were 0.856 and 0.70. NAVIGATE opportunity length (mean 33.8 (SD = 5.1) months) was not associated (P = .72) with QLS outcome; duration of untreated psychosis did not moderate (P = .32) differential QLS outcome. While conclusions are limited by the low rate of five-year follow-up, the data support long-term benefit of NAVIGATE compared to community care.

PMID:35689478 | DOI:10.1093/schbul/sbac053

Reprod Domest Anim. 2022 Jun 11. doi: 10.1111/rda.14178. Online ahead of print.

ABSTRACT

The aim of this study was to assess if vulvar morphometric changes occurring in female pigs during proestrus and estrus could be objective, accurate and predictive indicators of the onset to estrus and thus performed artificial inseminations at the most appropriate time. For that purpose, pictures of vulvas from 60 hyperprolific females (30 gilts and 30 sows) during proestrus and estrus were taken once a day. Vulva measurements (area, perimeter, length and width) on these pictures were performed using the image processing ImageJ software. Gilts and sows showed statistical differences (P<0.01) in all vulvar morphometric measurements between proestrus and estrus. Statistical differences in vulvar metrics were detected 24h before the onset to estrus, affecting all vulvar measurements in gilts, whereas only vulvar width was affected in sows. The image analysis used in this study may contribute to the development of smart technology in swine farming.

PMID:35689465 | DOI:10.1111/rda.14178

Urol J. 2022 Jun 11:7195. doi: 10.22037/uj.v19i.7195. Online ahead of print.

ABSTRACT

PURPOSE: To explore the establishment of a scoring system that can provide a reference for clinical decision making regarding the endoscopic treatment of 1-2 cm lower pole stones (LPS).

MATERIALS AND METHODS: The data of patients with renal calculi who were treated with percutaneous nephrolithotomy (PCNL) or retrograde intrarenal surgery (RIRS) in three hospitals from January 2013 to December 2017 were analyzed retrospectively. Multivariable logistic analysis was performed to determine the statistically significant indicators and regression coefficients, which were used to construct the scoring system. The stone-free rate (SFR) and postoperative complication rates of PCNL and RIRS within the two fractional segments of the scoring system were compared to select the optimal procedures.

RESULTS: A total of 137 patients in the PCNL group and 152 patients in the RIRS group were included in this study. Five factors were found to be most predictive of endoscopic treatment choice: stone number, stone diameter, infundibulopelvic angle (IPA), infundibular length (IL), and infundibular width (IW), yielding a total score ranging from 0-5. In the 0-2 segments, the RIRS group had better outcomes than the PCNL group in terms of the postoperative complication rates (6.8% versus 18.0%, P = .026). In segments 3-5, the SFR of the PCNL group was significantly higher than that of the RIRS group (88.5% versus 70.6%, P = .017).

CONCLUSION: Our scoring system was based on the patient’s preoperative imaging examination to measure the stone number, stone diameter, IPA, IL and IW. RIRS was recommended at 0-2 segments, and PCNL was recommended at 3-5 segments. This new scoring system is expected to provide guidance for urologists to make endoscopic treatment decisions for 1-2 cm LPS.

PMID:35689463 | DOI:10.22037/uj.v19i.7195