Tag: statistics

Circulation. 2022 Aug 23:101161CIRCULATIONAHA122059435. doi: 10.1161/CIRCULATIONAHA.122.059435. Online ahead of print.

ABSTRACT

BACKGROUND: Pulmonary arterial hypertension (PAH) is a type of pulmonary hypertension (PH) characterized by obliterative pulmonary vascular remodeling, resulting in right-sided heart failure. Although the pathogenesis of PAH is not fully understood, inflammatory responses and cytokines have been shown to be associated with PAH, in particular, with connective tissue disease-PAH. In this sense, Regnase-1, an RNase that regulates mRNAs encoding genes related to immune reactions, was investigated in relation to the pathogenesis of PH.

METHODS: We first examined the expression levels of ZC3H12A (encoding Regnase-1) in peripheral blood mononuclear cells from patients with PH classified under various types of PH, searching for an association between the ZC3H12A expression and clinical features. We then generated mice lacking Regnase-1 in myeloid cells, including alveolar macrophages, and examined right ventricular systolic pressures and histological changes in the lung. We further performed a comprehensive analysis of the transcriptome of alveolar macrophages and pulmonary arteries to identify genes regulated by Regnase-1 in alveolar macrophages.

RESULTS: ZC3H12A expression in peripheral blood mononuclear cells was inversely correlated with the prognosis and severity of disease in patients with PH, in particular, in connective tissue disease-PAH. The critical role of Regnase-1 in controlling PAH was also reinforced by the analysis of mice lacking Regnase-1 in alveolar macrophages. These mice spontaneously developed severe PAH, characterized by the elevated right ventricular systolic pressures and irreversible pulmonary vascular remodeling, which recapitulated the pathology of patients with PAH. Transcriptomic analysis of alveolar macrophages and pulmonary arteries of these PAH mice revealed that Il6, Il1b, and Pdgfa/b are potential targets of Regnase-1 in alveolar macrophages in the regulation of PAH. The inhibition of IL-6 (interleukin-6) by an anti-IL-6 receptor antibody or platelet-derived growth factor by imatinib but not IL-1β (interleukin-1β) by anakinra, ameliorated the pathogenesis of PAH.

CONCLUSIONS: Regnase-1 maintains lung innate immune homeostasis through the control of IL-6 and platelet-derived growth factor in alveolar macrophages, thereby suppressing the development of PAH in mice. Furthermore, the decreased expression of Regnase-1 in various types of PH implies its involvement in PH pathogenesis and may serve as a disease biomarker, and a therapeutic target for PH as well.

PMID:35997026 | DOI:10.1161/CIRCULATIONAHA.122.059435

Stroke. 2022 Aug 23:101161STROKEAHA122039086. doi: 10.1161/STROKEAHA.122.039086. Online ahead of print.

ABSTRACT

BACKGROUND: Although chronic kidney disease (CKD) is associated with worse stroke outcomes, data regarding the influence of CKD on intravenous thrombolysis outcomes are scarce. We sought to assess the efficacy and safety of intravenous thrombolysis for acute ischemic stroke with unknown onset time in patients with CKD.

METHODS: Patients with an acute stroke of unknown onset time from the EOS trials (Evaluation of Unknown Onset Stroke Thrombolysis) collaboration were evaluated using an individual patient-level database of randomized controlled trials comparing intravenous thrombolysis with placebo/standard treatment. CKD was defined as baseline estimated glomerular filtration rate of <60 ml/min/1.73m² Mixed-effect logistic-regression analysis was performed to evaluate treatment effects. A favorable outcome was defined as a modified Rankin Scale score of 0 to 1 at 90 days. Safety outcomes were symptomatic intracranial hemorrhage at 22 to 36 hours and 90-day mortality.

RESULTS: Baseline data on renal function were available for 688 of 843 patients. Of these, CKD was present in 146 (21%), including 69 of 351 patients receiving alteplase and 77 of 337 patients receiving placebo/standard treatment. Overall, treatment with alteplase was associated with higher odds of favorable outcome, and CKD did not modify the treatment effect (P_interaction=0.834). A favorable outcome was observed in 31 of 69 (46%) patients with CKD in the alteplase group and in 28 of 77 (36%) patients with CKD in the control group (adjusted odds ratio, 1.19 [95% CI, 0.55-2.58]). Among patients with CKD, symptomatic intracranial hemorrhage occurred in 2 patients (3%) in the alteplase group but in none of the controls (P=0.133). At 90 days, death was reported in 3 patients (4%) in the alteplase group compared with 2 patients (3%) in the controls (P=0.539).

CONCLUSIONS: The present analysis indicates that the benefit of alteplase does not differ between stroke patients with unknown onset time with and without CKD, although the statistical power was lacking to confirm the efficacy in subgroups. This study only applies to mild-to-moderate or predialysis CKD.

PMID:35997023 | DOI:10.1161/STROKEAHA.122.039086

Hypertension. 2022 Aug 23:101161HYPERTENSIONAHA12219183. doi: 10.1161/HYPERTENSIONAHA.122.19183. Online ahead of print.

ABSTRACT

BACKGROUND: Pulmonary arterial hypertension maintains rapid cell proliferation and vascular remodeling through metabolic reprogramming. Recent studies suggested that circRNAs play important role in pulmonary vascular remodeling and pulmonary arterial smooth muscle cells proliferation. However, the relationship between circRNA, cell proliferation, and metabolic reprogramming in pulmonary arterial hypertension has not been investigated.

METHODS: RNA-seq and qRT-PCR reveal the differential expression profile of circRNA in pulmonary arteries of pulmonary arterial hypertension rat models. Transfection was used to examine the effects of circSMOC1 on pulmonary artery smooth muscle cells, and the roles of circSMOC1 in vivo were investigated by adenoassociated virus. Mass spectrometry, RNA pull-down, RNA immunoprecipitation, and dual-luciferase reporter assay were performed to investigate the signaling pathway of circSMOC1 regulating the metabolic reprogramming.

RESULTS: CircSMOC1 was significantly downregulated in pulmonary arteries of pulmonary arterial hypertension rats. CircSMOC1 knockdown promoted proliferation and migration and enhanced aerobic glycolysis of pulmonary artery smooth muscle cells. CircSMOC1 overexpression in vivo alleviates pulmonary vascular remodeling, right ventricular pressure, and right heart hypertrophy. In the nucleus, circSMOC1 directly binds to PTBP1 (polypyrimidine tract-binding protein), competitively inhibits the specific splicing of PKM (pyruvate kinase M) premRNA, resulting in the upregulation of PKM2 (pyruvate kinase M2), the key enzyme of aerobic glycolysis, to enhance glycolysis. In the cytoplasm, circSMOC1 acted as a miR-329-3p sponge, and its reduction in pulmonary arterial hypertension suppressed PDHB (pyruvate dehydrogenase E1 subunit beta) expression, leading to the impairment of mitochondrial oxidative phosphorylation.

CONCLUSIONS: circSMOC1 is crucially involved in the metabolic reprogramming of pulmonary artery smooth muscle cells through PTBP1 and miR-329-3p to regulate pulmonary vascular remodeling in pulmonary arterial hypertension.

PMID:35997022 | DOI:10.1161/HYPERTENSIONAHA.122.19183

Chem Commun (Camb). 2022 Aug 23. doi: 10.1039/d2cc03598g. Online ahead of print.

ABSTRACT

Advancements in computer science and software engineering have greatly facilitated mass spectrometry (MS)-based untargeted metabolomics. Nowadays, gigabytes of metabolomics data are routinely generated from MS platforms, containing condensed structural and quantitative information from thousands of metabolites. Manual data processing is almost impossible due to the large data size. Therefore, in the “omics” era, we are faced with new challenges, the big data challenges of how to accurately and efficiently process the raw data, extract the biological information, and visualize the results from the gigantic amount of collected data. Although important, proposing solutions to address these big data challenges requires broad interdisciplinary knowledge, which can be challenging for many metabolomics practitioners. Our laboratory in the Department of Chemistry at the University of British Columbia is committed to combining analytical chemistry, computer science, and statistics to develop bioinformatics tools that address these big data challenges. In this Feature Article, we elaborate on the major big data challenges in metabolomics, including data acquisition, feature extraction, quantitative measurements, statistical analysis, and metabolite annotation. We also introduce our recently developed bioinformatics solutions for these challenges. Notably, all of the bioinformatics tools and source codes are freely available on GitHub (https://www.github.com/HuanLab), along with revised and regularly updated content.

PMID:35997016 | DOI:10.1039/d2cc03598g

ESC Heart Fail. 2022 Aug 23. doi: 10.1002/ehf2.14112. Online ahead of print.

ABSTRACT

AIMS: Implantation of left ventricular-assist devices (LVAD) to treat end-stage heart failure is of increasing relevance due to donor shortage. Infections of the driveline are common adverse events. LVAD infections can lead to high urgency listings for transplantation. However, transplantation in patients with infection leads to worse post-transplantation outcomes. This study aims to evaluate specific risk factors for driveline infections at the time of implantation.

METHODS AND RESULTS: Four hundred forty-one patients receiving either Heartmate II or Heartware system from August 2009 to October 2013 were assessed. An expert committee sorted patients into four different groups concerning the likeliness of infection. Twenty-eight (6%) of discussed infection cases were judged as secured, 33 (7%) as likely, 18 (4%) as possible, and 20 (4%) as unlikely. The remaining 342 (78%) subjects showed either no signs of infection at all times (329 [75%]) or developed signs of infection in a second observation period within 1 year after ending of the first observation period (13 [3%]). For a better discriminatory power, cases of secured and likely infections were tested against the group with no infection at all times in a Cox proportional hazard model. Among all variables tested by univariate analysis (significance level P < 0.15), only age (P = 0.07), LVAD-type (P = 0.12), need for another thoracic operation (P = 0.02), and serum creatinine value (P = 0.02) reached statistical significance. These were subsequently subjected to multivariate analysis to calculate the cumulative risk of developing a drive infection. The multivariate analysis showed that of all the potential risk factors tested, only the necessity of re-thoracotomy or secondary thoracic closure had a significant, protective effect (hazard ratio [95% CI] = 0.45 [0.21-0.95]; P = 0.04).

CONCLUSION: This single-centre cohort study shows that driveline infections are common adverse events. The duration of support represents the major risk factor for LVAD driveline infections.

PMID:35997005 | DOI:10.1002/ehf2.14112

Elife. 2022 Aug 23;11:e76989. doi: 10.7554/eLife.76989. Online ahead of print.

ABSTRACT

Foraging mammals exhibit a familiar yet poorly characterized phenomenon, ‘alternation’, a pause to sniff in the air preceded by the animal rearing on its hind legs or raising its head. Rodents spontaneously alternate in the presence of airflow, suggesting that alternation serves an important role during plume-tracking. To test this hypothesis, we combine fully-resolved simulations of turbulent odor transport and Bellman optimization methods for decision-making under partial observability. We show that an agent trained to minimize search time in a realistic odor plume exhibits extensive alternation together with the characteristic cast-and-surge behavior observed in insects. Alternation is linked with casting and occurs more frequently far downwind of the source, where the likelihood of detecting airborne cues is higher relative to ground cues. Casting and alternation emerge as complementary tools for effective exploration with sparse cues. A model based on marginal value theory captures the interplay between casting, surging and alternation.

PMID:35996954 | DOI:10.7554/eLife.76989

Nepal J Ophthalmol. 2022 Jan;14(27):122-129. doi: 10.3126/nepjoph.v14i1.34285.

ABSTRACT

INTRODUCTION: Major cause of irreversible blindness is glaucoma which is increasing as a significant global health problem. Knowledge of glaucoma burden and its clinical characteristics in this region is essential.

MATERIALS AND METHODS: This was a cross-sectional hospital -based study conducted at Glaucoma unit in CHEERS Hospital, Bhaktapur from August 2015 to July 2019. Patients’ demographic profile, along with comprehensive eye examination findings were reviewed from the records. Data analysis was done with IBM SPSS version 24 and was presented in mean (±SD), frequency and proportions and a chi- square test was applied. P value < 0.05 was considered statistically significant.

RESULTS: Total of 310 glaucoma cases were included in this study. The mean age presentation was 61.89±14.4 years, and the majority of patients (52.9%) were in the age group 60-79 years. Most patients had primary open angle glaucoma (171, 55.2%) followed by primary angle closure glaucoma (92, 29.7%).

CONCLUSION: Primary open angle glaucoma is the most common form of glaucoma. The proportion of glaucoma increased with increasing age (> 40 years). Provision of screening programs targeting persons with risk factors and opportunistic eye examinations would be beneficial in detection of glaucoma.

PMID:35996911 | DOI:10.3126/nepjoph.v14i1.34285

Nepal J Ophthalmol. 2022 Jan;14(27):72-81. doi: 10.3126/nepjoph.v14i1.37965.

ABSTRACT

INTRODUCTION: This study aims to evaluate outcomes and complications of temporary suture tarsorrhaphy (TST) in cases of impending corneal ulcer perforation.

MATERIALS AND METHODS: Case records of patients who underwent temporary suture tarsorrhaphy at Mechi Eye Hospital during a period of 18 months were retrospectively evaluated. All the smear positive fungal keratitis with more than 5mm infiltration involving central and/or paracentral cornea with impending corneal perforation were included. Demographic and clinical profile including – visual acuity, indication for temporary suture tarsorrhaphy, duration of signs and symptoms were noted. The outcomes were evaluated after 1 month and 3 months post tarsorrhaphy, in relation with time to epithelial healing, anatomical success rate, best corrected visual acuity, complications associated with non-healing corneal ulcer, number of temporary suture tarsorrhaphy needed and complications of TST.

RESULTS: The study included 119 cases of smear positive fungal keratitis with mean age of 51.34 + 15.56 years. In this study, 56.30% of the patients developed epithelial healing at 2 – 4 weeks with mean duration of 23.24 + 12.09 days of temporary suture tarsorrhaphy. Out of 119 patients, the corneal ulcer healed in 84 patients (70.6%), whereas 35 (29.4%) did not heal. Among those with non-healing ulcers, 15 patients (12.6%) had to undergo evisceration. The anatomical success rate was 87.39% which was statistically significant (P = 0.001). Regarding visual outcome, in 62 patients (52.10%) BCVA improved by 2 or more lines, which was statistically significant (P<0.05) resulting in a functional success of 26.89%.

CONCLUSION: This study concludes that temporary suture tarsorrhaphy could be a useful option for management of corneal ulcers with impending perforation in eye centers with limited resources settings and high disease burden with good anatomical and functional outcome.

PMID:35996906 | DOI:10.3126/nepjoph.v14i1.37965

Nepal J Ophthalmol. 2022 Jan;14(27):49-58. doi: 10.3126/nepjoph.v14i1.35401.

ABSTRACT

INTRODUCTION: Hypertensive retinopathy is a common complication in patients with hypertension. This study aims to assess the prevalence, associated factors and awareness of hypertensive retinopathy among an elderly population with hypertension in Bhaktapur, Nepal.

MATERIALS AND METHODS: This is a population-based, cross-sectional study conducted from 2013 to 2015 in Bhaktapur district, Nepal. The sample size was 2100 subjects aged 60 years and above. From this sample, all diagnosed patients with hypertension were analyzed. A detailed history was obtained, and an ocular examination was performed.

RESULTS: Information was complete for 1860 (88.57%) subjects. The age of the study population ranged from 60 to 95 years with the mean age of 69.64±7.31 years. Hypertension was found in 643 subjects (34.61%), of which 224 (12.04%) were newly diagnosed cases. Among the subjects with hypertension, hypertensive retinopathy was found in 81 cases (12.6%). Hypertensive retinopathy was more frequent in the age group 70-79 years (15.23%), males (13.25%), illiterates (13.56%), diabetics (16.49%), and body mass index (BMI) ≥25 kg/m2 (14%). None of the factors was found to be statistically significant. Among the study participants, awareness regarding the effect of hypertension on eye, retina and vision was found to be 13.84%, 8.4%, and 11.98% respectively.

CONCLUSION: Prevalence of hypertension and hypertensive retinopathy among an elderly population of 60 years and above in Bhaktapur district, Nepal were similar to other countries. Hypertensive retinopathy was higher among males, illiterates, diabetes and BMI> 25kg/m2. Awareness of hypertensive retinopathy was 8.4% among hypertensive subjects. Emphasis should be directed toward improving awareness campaigns.

PMID:35996903 | DOI:10.3126/nepjoph.v14i1.35401

Diabet Med. 2022 Aug 23:e14941. doi: 10.1111/dme.14941. Online ahead of print.

ABSTRACT

AIMS: The objectives of this scoping review were to: 1) identify the target audience and contexts in which strategies to improve type 2 diabetes mellitus (T2DM) medication adherence have been used, 2) provide an overview of behaviour change techniques (BCTs) used, 3) describe the determinants of behaviour targeted by strategies, and 4) to identify current gaps in strategies.

METHODS: A systemic search for articles related to T2DM, medication adherence, and strategies was conducted in EMBASE, Ovid MEDLINE and Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily using the OvidSP platform on March 11, 2021. All publications involving strategies to overcome medication non-adherence among adults with T2DM were included. Strategies were categorized according to the BCT taxonomy and the determinants of behaviour targeted by each strategy was classified by using the Theoretical Domains Framework (TDF).

RESULTS: The search identified 58 articles and 61 strategies. The BCT categories Antecedents and Natural consequences and BCTs Feedback on outcome(s) of behaviour, Adding objects to the environment, and Information about health consequences were identified most frequently as components of strategies resulting in statistically significant improvement in medication adherence. Strategies targeting the TDF domains Reinforcement and Beliefs about Consequences most often resulted in statistically significant improvements in adherence measures.

CONCLUSIONS: The findings from this review identify BCTs and targeted behaviours with demonstrated success. Further exploration of the myriad of BCTs and the corresponding determinants of behaviour which were not accessed may be warranted for the development of future strategies to improve medication adherence in type 2 diabetes.

PMID:35996880 | DOI:10.1111/dme.14941