Category: Statistics

Liver Transpl. 2022 Feb 6. doi: 10.1002/lt.26425. Online ahead of print.

ABSTRACT

Cardiovascular disease (CVD) is an important cause of mortality among liver transplantation (LT) recipients, however, the data on CVD risk stratification following LT is limited. Thus, the primary aim of the current study was to evaluate the association between decline in renal function early after LT and atherosclerotic events.

METHOD: This retrospective study included all patients receiving LT between 2007 and 2019. Early renal function was quantified as estimated glomerular filtration rate (GFR) 6 months after LT. The primary endpoint for the study was a composite atherosclerotic cardiovascular event of 3-point major adverse cardiovascular events (MACE), which includes non-fatal myocardial infarction (MI), non-fatal stroke, or death from CVD.

RESULTS: A total of 553 LT recipients met entry criteria. After a median follow up of 74 months (IQR 46, 111), 94 (17%) LT recipients died and CVD associated death occurred in 20 patients. MACE-3 occurred in 66 (12%) with non-fatal myocardial infarction being the most common event (n=30). A strong inverse relationship between early GFR and MACE-3 was noted in unadjusted analysis with HR 0.96 (95% CI 0.95, 0.98, p=0.0001) and remained significant even after accounting for age, gender, coronary artery disease, diabetes, hypertension, calcineurin inhibitor use, and Framingham Risk Score (FRS) (HR 0.96, 95% CI 0.95, 0.97, p=0.0001 per unit increase in GFR). Furthermore, an independent interaction between GFR, FRS and likelihood of developing a MACE-3 was noted.

CONCLUSION: Glomerular filtration rate 6 months following LT is a strong predictor of developing atherosclerotic events. This relationship is independent of traditional CVD risk-stratification model (FRS), thus, has the potential to be incorporated into CVD risk assessment after LT but requires further validation.

PMID:35124881 | DOI:10.1002/lt.26425

Stat Med. 2022 Feb 6. doi: 10.1002/sim.9323. Online ahead of print.

ABSTRACT

Sequential, multiple assignment, randomized trials (SMARTs) compare sequences of treatment decision rules called dynamic treatment regimes (DTRs). In particular, the Adaptive Treatment for Alcohol and Cocaine Dependence (ENGAGE) SMART aimed to determine the best DTRs for patients with a substance use disorder. While many authors have focused on a single pairwise comparison, addressing the main goal involves comparisons of >2 DTRs. For complex comparisons, there is a paucity of methods for binary outcomes. We fill this gap by extending the multiple comparisons with the best (MCB) methodology to the Bayesian binary outcome setting. The set of best is constructed based on simultaneous credible intervals. A substantial challenge for power analysis is the correlation between outcome estimators for distinct DTRs embedded in SMARTs due to overlapping subjects. We address this using Robins’ G-computation formula to take a weighted average of parameter draws obtained via simulation from the parameter posteriors. We use non-informative priors and work with the exact distribution of parameters avoiding unnecessary normality assumptions and specification of the correlation matrix of DTR outcome summary statistics. We conduct simulation studies for both the construction of a set of optimal DTRs using the Bayesian MCB procedure and the sample size calculation for two common SMART designs. We illustrate our method on the ENGAGE SMART. The R package SMARTbayesR for power calculations is freely available on the Comprehensive R Archive Network (CRAN) repository. An RShiny app is available at https://wilart.shinyapps.io/shinysmartbayesr/.

PMID:35124836 | DOI:10.1002/sim.9323

Stat Med. 2022 Feb 6. doi: 10.1002/sim.9343. Online ahead of print.

ABSTRACT

Censoring often occurs in data collection. This article, considers nonparametric regression when the covariate is censored under general settings. In contrast to censoring in the response variable in survival analysis, regression with censored covariates is more challenging but less studied in the literature, especially for dependent censoring. We propose to estimate the regression function using conditional hazard rates. The asymptotic normality of our proposed estimator is established. Both theoretical results and simulation studies demonstrate that the proposed method is more efficient than the estimation based on complete observations and other methods, especially when the censoring rate is high. We illustrate the usefulness of the proposed method using a data set from the Framingham heart study and a data set from a randomized placebo-controlled clinical trial of the drug D-penicillamine.

PMID:35124839 | DOI:10.1002/sim.9343

Hepatology. 2022 Feb 6. doi: 10.1002/hep.32395. Online ahead of print.

ABSTRACT

BACKGROUND & AIMS: The Veterans Health Administration (VHA) provides care for more than 80,000 Veterans with cirrhosis. This longitudinal, multi-method evaluation of a novel cirrhosis care quality improvement program aimed to 1) identify implementation strategies associated with evidence-based, guideline-concordant cirrhosis care over time, and 2) use qualitative interviews to operationalize strategies for a manualized intervention.

APPROACH & RESULTS: VHA providers were surveyed annually about the use of 73 implementation strategies to improve cirrhosis care in fiscal years 2018 (FY18) and 2019 (FY19). Implementation strategies linked to guideline-concordant cirrhosis care were identified using bivariate statistics and comparative configurational methods. Semi-structured interviews were conducted with 12 facilities in the highest quartile of cirrhosis care to specify the successful implementation strategies and their mechanisms of change. A total of 106 VHA facilities (82%) responded at least once over the 2-year period (FY18: n=63, FY19: n=100). Facilities reported using a median of 12 (IQR 20) implementation strategies in FY18 and 10 (IQR 19) in FY19. Of 73 strategies, 35 (48%) were positively correlated with provision of evidence-based cirrhosis care. Configurational analysis identified multiple strategy pathways directly linked to more guideline-concordant cirrhosis care. Across both methods, a subset of eight strategies was determined to be core to cirrhosis care improvement and specified using qualitative interviews.

CONCLUSIONS: In a national cirrhosis care improvement initiative, a multi-method approach identified a core subset of successful implementation strategy combinations. This process of empirically identifying and specifying implementation strategies may be applicable to other implementation challenges in hepatology.

PMID:35124820 | DOI:10.1002/hep.32395

Acta Anaesthesiol Scand. 2022 Feb 6. doi: 10.1111/aas.14040. Online ahead of print.

ABSTRACT

INTRODUCTION: Existing multimodal pathways for patients undergoing acute high-risk abdominal surgery for intestinal obstruction (IO) and perforated viscus (PV) has focused on rescue in the immediate perioperative period. However, there is little focus on the peri-operative pathophysiology of recovery in this patient group, as done to develop enhanced recovery pathways in elective care. Acute inflammation is a main driver of the perioperative pathophysiology leading to adverse outcomes. Pre-operative high-dose glucocorticoids provide reduction in the inflammatory response after surgery, effective pain relief in several major surgical procedures, as well as reducing fatigue and improving endothelial dysfunction.

AIM: To evaluate the effect of high-dose glucocorticoid on inflammatory response, fluid distribution and recovery after acute high-risk abdominal surgery in patients with IO and PV.

METHODS: AHA STEROID trial is a sponsor-initiated single center, randomized, double-blind placebo-controlled trial, assessing preoperative high-dose Dexamethasone (1mg/kg) versus placebo (normal saline) in patients undergoing emergency high-risk abdominal surgery. We plan to enroll 120 patients. Primary outcome is reduction in C-reactive protein on postoperative day one as a marker of successful attenuation of acute stress response. Secondary outcomes include perioperative change in endothelial and other inflammatory markers, fluid distribution, pulmonary function, pain, fatigue, and mobilization. The statistical plan is outlined in the protocol.

DISCUSSION: The AHA STEROID trial will provide important evidence to guide the potential use of high-dose glucocorticoids in emergency high-risk abdominal surgery, with respect to different pathophysiologies.

PMID:35124808 | DOI:10.1111/aas.14040

Ann N Y Acad Sci. 2022 Feb 5. doi: 10.1111/nyas.14749. Online ahead of print.

ABSTRACT

In Basque-Spanish bilinguals, statistical learning (SL) in the visual modality was more efficient on nonlinguistic than linguistic input; in the auditory modality, we found the reverse pattern of results. We hypothesize that SL was shaped for processing nonlinguistic environmental stimuli and only later, as the language faculty emerged, recycled for speech processing. This led to further adaptive changes in the neurocognitive mechanisms underlying speech processing, including SL. By contrast, as a recent cultural innovation, written language has not yet led to adaptations. The current study investigated whether such phylogenetic influences on SL can be modulated by ontogenetic influences on a shorter timescale, over the course of individual development. We explored how SL is modulated by the ambient linguistic environment. We found that SL in the auditory modality can be further modulated by exposure to a bilingual environment, in which speakers need to process a wider range of diverse speech cues. This effect was observed only on linguistic, not nonlinguistic, material. We conclude that ontogenetic factors modulate the efficiency of already existing SL ability, honing it for specific types of input, by providing new targets for selection via exposure to different cues in the sensory input.

PMID:35124815 | DOI:10.1111/nyas.14749

Perspect Psychiatr Care. 2022 Feb 5. doi: 10.1111/ppc.13043. Online ahead of print.

ABSTRACT

PURPOSE: This study was conducted to determine the effect of sleep hygiene training given to elderly individuals on daytime sleepiness and fatigue.

DESIGN AND METHODS: The sample size was calculated by G. Power and determined as 134 elderly individuals. The experimental group was trained in sleep, two sessions a week for a total of 2 weeks.

FINDINGS: The difference between Epworth Sleepiness Scale and Fatigue Severity Scale posttest mean scores of the elderly individuals in the experimental and control groups were found to be statistically significant (p < 0.05).

PRACTICE IMPLICATIONS: Sleep hygiene training reduced daytime sleepiness and fatigue in older adults.

PMID:35124807 | DOI:10.1111/ppc.13043

Ther Innov Regul Sci. 2022 Feb 5. doi: 10.1007/s43441-022-00379-z. Online ahead of print.

ABSTRACT

OBJECTIVE: Spontaneous reports of adverse drug reactions (ADRs) are an essential data source for pharmacovigilance activities. However, spontaneous reporting is affected by under-reporting, which can lead to bias in statistical signal detection and failure to identify potential drug-associated risks. This study aimed to estimate the degree of under-reporting of suspected serious ADRs (sADRs) in spontaneous reports in Japan.

METHODS: The new active ingredients approved in Japan between 2010 and 2016 for which all-case surveillance was conducted were selected for this study. Data of sADR reports were extracted from the Japanese Adverse Drug Event Report database (JADER). An interrupted time series (ITS) analysis was conducted to compare the number of sADR reports (sADR cases) obtained in the all-case surveillance period with that obtained in the spontaneous report period (after all-case surveillance had been completed).

RESULTS: The ITS analysis of all sADR cases revealed that 24 (68.6%) of the 35 investigated drugs showed a statistically significant decrease in the intercept (level) in the spontaneous reporting period compared with that in the all-case surveillance period. The median of the reduction rate of the level was 60.1%. The number of drugs with a statistically significant decrease in the level of cases with sADRs in the Important Medical Event list and in that leading to death was 19/35(54.3%) and 6/35 (17.1%), respectively.

CONCLUSION: This study demonstrated the existence of sADR under-reporting in spontaneous reports in Japan quantitatively. Meanwhile, it was suggested that information on sADRs was reported appropriately according to their level of severity.

PMID:35124790 | DOI:10.1007/s43441-022-00379-z

Allergy. 2022 Feb 6. doi: 10.1111/all.15247. Online ahead of print.

ABSTRACT

BACKGROUND: Homologous and heterologous SARS-CoV-2 vaccinations yield different spike protein-directed humoral and cellular immune responses. This study aimed to explore their currently unknown interdependencies.

METHODS: COV-ADAPT is a prospective, observational cohort study of 417 healthcare workers who received vaccination with homologous ChAdOx1 nCoV-19, homologous BNT162b2 or with heterologous ChAdOx1 nCoV-19/BNT162b2. We assessed humoral (anti-spike-RBD-IgG, neutralizing antibodies, avidity) and cellular (spike-induced T cell interferon-γ release) immune responses in blood samples up to 2 weeks before (T1) and 2 to 12 weeks following secondary immunization (T2).

RESULTS: Initial vaccination with ChAdOx1 nCoV-19 resulted in lower anti-spike-RBD-IgG compared to BNT162b2 (70±114 vs. 226±279 BAU/ml, p<0.01) at T1. Booster vaccination with BNT162b2 proved superior to ChAdOx1 nCoV-19 at T2 (anti-spike-RBD-IgG: ChAdOx1 nCoV-19/BNT162b2 2387±1627 and homologous BNT162b2 3202±2184 vs. homologous ChAdOx1 nCoV-19 413±461 BAU/ml, both p<0.001; spike-induced T cell interferon-γ release: ChAdOx1 nCoV-19/BNT162b2 5069±6733 and homologous BNT162b2 4880±7570 vs. homologous ChAdOx1 nCoV-19 1152±2243 mIU/ml, both p<0.001). No significant differences were detected between BNT162b2-boostered groups at T2. For ChAdOx1 nCoV-19, no booster effect on T cell activation could be observed. We found associations between anti-spike-RBD-IgG levels (ChAdOx1 nCoV-19/BNT162b2 and homologous BNT162b2) and T cell responses (homologous ChAdOx1 nCoV-19 and ChAdOx1 nCoV-19/BNT162b2) from T1 to T2. Additionally, anti-spike-RBD-IgG and T cell response were linked at both time points (all groups combined). All regimes yielded neutralizing antibodies and increased antibody avidity at T2.

CONCLUSIONS: Interdependencies between humoral and cellular immune responses differ between common SARS-CoV-2 vaccination regimes. T cell activation is unlikely to compensate for poor humoral responses.

PMID:35124800 | DOI:10.1111/all.15247

Eur Arch Otorhinolaryngol. 2022 Feb 6. doi: 10.1007/s00405-022-07261-6. Online ahead of print.

ABSTRACT

INTRODUCTION: Oropharyngeal surgery for Obstructive Sleep Apnea (OSA) has evolved from a radical excision of “redundant” soft tissue for the enlargment of the airway to a minimally invasive reconstruction to fulfill both preservation of pharyngeal function and improvement of sleep apnea. Recently, Alianza surgical technique has been successfully introduced as a new, non-resective procedure aimed to treat concentric pharyngeal collapse at the velum using Barbed Sutures. The aim of this study was to show the effectiveness and safety of Alianza technique as standalone surgical treatment in selected patients with moderate-severe OSA and concentric pharyngeal collapse that refused or did not tolerate Continuous Positive Airway Pressure therapy.

MATERIALS AND METHODS: Effectiveness of the surgical procedure was assessed by means of the Epworth Sleepiness Scale (ESS), Home Sleep Test, and a 0-10 snoring VAS.

RESULTS: At the end of our selection process, 26 patients were enrolled, with a mean age of 52.7 ± 9.2 years, that undergone Alianza tecnique. There was a statistically significant reduction in mean post-operative apnea-hypopnea indexes (34.1 ± 11.5-16.3 ± 10.3; p <0.01), mean oxygen desaturation index (29.0 ± 14.5-13.1 ± 9.2; p < 0.01), and mean ESS scores (12.1 ± 5.8 and 5.8 ± 4.4; p < 0.01).There was also a significant decrease in mean post-operative snoring VAS scores (7.85 ± 1.23 vs 3.2 ± 1.7, p < 0.01). There were no major complications.

CONCLUSIONS: Our preliminary results suggest that Alianza technique is a safe and repeatable surgery. Further studies on a larger scale are needed to confirm these encouraging data supporting the role of Alianza alone or in OSA multilevel surgery in selected OSA patients.

PMID:35124744 | DOI:10.1007/s00405-022-07261-6