Tag: statistics

J Clin Neurosci. 2022 Jan 12;96:101-106. doi: 10.1016/j.jocn.2021.12.022. Online ahead of print.

ABSTRACT

Renal dysfunction has been reported to be associated with larger hematoma volume in intracerebral hemorrhage (ICH) due to concomitant nutritional imbalances and platelet dysfunction; however, this association remains controversial. This study analyzed the association between potential risk factors and hematoma volume in patients with ICH. This retrospective cohort study used data from 456 patients with ICH at a single comprehensive stroke center. We assessed the association of estimated glomerular filtration rate (eGFR) and Controlling Nutritional Status score with hematoma volume using multivariable non-linear regression models. The effect of the use of antithrombotic agents on hematoma volume was analyzed using outcome-adaptive double/debiased machine learning approach, considering many covariates. The median and interquartile range of age and eGFR were 64 (54-75) years and 56.1 (39.3-66.7) mL/min/1.73 m², respectively. The multivariable non-linear regression model showed that (1) eGFR and hematoma volume had a positive linear association, which was not statistically significant, and (2) nutritional status was positively associated with hematoma volume, although not significantly. Outcome-adaptive double/debiased machine learning revealed that patients receiving antithrombotic agents did not present with significantly larger hematoma volume than those who were not receiving antithrombotic agents (estimated mean difference of hematoma volume [95% confidence interval] = 15.32 [-6.02 to 36.65]). Our analysis shows no statistically or clinically significant relationship between renal function and hematoma volume; however, nutritional status and the use of antithrombotic agents showed an increasing tendency of the degree of hematoma in patients with ICH.

PMID:35032897 | DOI:10.1016/j.jocn.2021.12.022

Mult Scler Relat Disord. 2022 Jan 10;58:103517. doi: 10.1016/j.msard.2022.103517. Online ahead of print.

ABSTRACT

BACKGROUND: Spasticity is a common and disabling problem in multiple sclerosis (MS), but its effect in other CNS inflammatory demyelinating diseases (CNSIDDs), such as neuromyelitis optica spectrum disorder (NMOSD) is not widely studied. This study aims to compare subjective and objective measurements of spasticity in NMOSD patients and determine associated factors.

METHODS: A prospective cross-sectional study was performed on CNSIDD patients attending the Multiple Sclerosis and Related Disorders Clinic at Siriraj Hospital, a tertiary hospital in Thailand, from June to November 2020 was performed. MS, NMOSD, and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) patients were included. Patients’ self-rated Numeric Rating Scale (NRS) for spasticity and clinician-evaluated Modified Ashworth Scale (MAS) scores on the same visit were compared and assessed for correlations. Data on characteristics of patients including demographics, number of transverse myelitis (TM) attacks, disease duration, and Expanded Disability Status Scale (EDSS) score were collected.

RESULTS: Seventy-nine CNSIDD patients were included with 25 MS, 53 NMOSD, and 1 MOGAD. There was a statistically significant correlation between NRS and MAS scores (r = 0.934, p < 0.001). Spasticity was more commonly observed in NMOSD patients compared to MS (34% vs 8%, p = 0.016). Clinical characteristics strongly associated with spasticity were higher number of TM attacks (p < 0.001), severe TM attacks (p < 0.001), longitudinally extensive transverse myelitis attacks (p < 0.001), longer disease duration (p = 0.025), higher EDSS (p < 0.001), and pyramidal Functional System Scale scores (p = 0.001).

CONCLUSIONS: Patients’ self-reported NRS score had a good correlation with clinician-evaluated MAS score for spasticity assessment in NMOSD and CNSIDD patients overall. Number and severity of TM attacks were associated with spasticity. Spastic patients had more disability measured by EDSS.

PMID:35032877 | DOI:10.1016/j.msard.2022.103517

Mult Scler Relat Disord. 2022 Jan 4;58:103496. doi: 10.1016/j.msard.2022.103496. Online ahead of print.

ABSTRACT

BACKGROUND: Cognitive impairment is a symptom present in part of patients with neuromyelitis optica spectrum disorder (NMOSD) and its pathophysiology is unknown. Dysfunction of the GABAergic/glutamatergic pathways involving inhibitory and excitatory neurotransmitters have been implicated in several neurological disorders. This study aimed to investigate the changes in inhibitory gamma-aminobutyric acid (GABA) and excitatory glutamate and glutamine (Glx) neurotransmitter levels and their correlations with cognitive functions in patients with NMOSD.

METHODS: A total of 29 patients with NMOSD and 28 sex-, age-, and education-matched healthy controls (HCs) were included in the study. All participants underwent clinical and cognitive assessments and proton magnetic resonance spectroscopy scanning. Meshcher-Garwood point-resolved spectroscopy was used to measure GABA and Glx levels in the medial prefrontal cortex (mPFC) and left thalamus. Total creatine (tCr) was applied as an internal reference. The GABA and Glx levels in the patient group were compared with those in HCs and correlated with cognitive scores and clinical variables.

RESULTS: Patients with NMOSD showed lower GABA+/tCr levels in the mPFC compared with HCs (P = 0.028). The GABA+/tCr levels in the mPFC were significantly associated with verbal memory performance (r = 0.462, P = 0.027) and overall cognition (r = 0.440, P = 0.035) in the NMOSD group. The GABA+/tCr levels in the left thalamus or Glx/tCr levels in both regions were not significantly different between groups, nor were they related to any cognitive domain in patients with NMOSD (all P values > 0.05).

CONCLUSION: The GABA+ levels in the mPFC decreased and correlated with cognitive dysfunction in patients with NMOSD, suggesting that the changes in regional GABA+ levels might be a potential metabolic feature of cognitive decline in patients with NMOSD.

PMID:35032882 | DOI:10.1016/j.msard.2022.103496

Pathol Res Pract. 2021 Dec 31;230:153756. doi: 10.1016/j.prp.2021.153756. Online ahead of print.

ABSTRACT

BACKGROUND: Mesenchymal stromal cells (MSC) have demonstrated ability to improve diabetic nephropathy (DN) in experimental models, as well as by improving kidney endogenous progenitor cells proliferation and differentiation. Many studies have demonstrated the effect of hypoxia on MSC improving their functionality but the potential enhancement of the nephroprotective properties of MSC cultured under low oxygen concentration has been explored in few studies, none of them in the context of DN. On the other hand, diabetes is associated with abnormalities in MSCs functionality. These findings related to the hypoxia preconditioning ability to enhance adipose-tissue derived-MSC (ASC) performance have led us to wonder if hypoxia could increase the known beneficial effect of normal ASC in DN and if it could correct the expected inability of diabetic rat-derived ASC to exert this effect in vivo. To answer these questions, in the present study we have used ASC from healthy and diabetic-induced rats, cultured under standard conditions or hypoxia preconditioned, in a DN rat model induced by streptozotocin (STZ).

METHODS: Diabetes was induced in Wistar-rats by 60 mg/kg streptozotocin (STZ) intraperitoneal injection. Fifteen days thereafter, five diabetic-induced rats and five healthy, previously injected with saline, were sacrificed and used as ASC donors . Both healthy and diabetic rat-derived ASC (cASC and dASC, respectively) were cultured under standard conditions (21%O2)(N) or were subjected to a 48 h conditioning period in hypoxia (3%O2)(H). Thus, four types of cells were generated depending on their origin (healthy or diabetic-induced rats) and the culture conditions(N or H):cASC-N, cASC-H, dASC-N and dASC-H. DN experimental study were carried out fifteen days after STZ induction of diabetes in fifty-two healthy rats. DN-induced-animals were randomly assigned to be injected with 200 µL saline as placebo or with 3 × 106 cASC-N, cASC-H, dASC-N or dASC-H, according to the study group. Serum glucose, urea and creatinine, and urine albumin levels were measured at 2-weeks intervals until day+ 45 after ND-induction.Animals were sacrificed and kidneys extracted for histopathological and transmission electron microcopy analysis RESULTS: None of the four study groups that received cell treatment showed significant changes in serum glucose, urea and creatinine levels, urine albumin concentration and body weight compared to placebo ND-induced group. Interestingly, only the group that received cASC-H showed a reduction in glucose and creatinine levels although it did not reach statistical significance.All DN-induced groups treated with ASC reduced significantly renal lesions such as mesangial expansion, mesangiolysis, microaneurysms and acute tubular necrosis compared to ND-induced placebo group (p ≤ 0.05). Renal injuries such as clear tubular cell changes, thickening of tubular basement membrane, tubular cysts and interstitial fibrosis significantly showed reduction in ND-induced rats treated with cASC-H regarding to their received cASCN (p ≤ 0.05). Non statistical differences were observed in the improvement capacity of cASC and dASC culture under standard condition.However, hypoxia preconditioning reduces the presence of tubular cysts (p ≤ 0.01).

CONCLUSIONS: Hypoxia preconditioning enhances the ability of healthy rat-derived ASC to improve kidney injury in a rat model of DN. Moreover, diabetic-derived ASC exhibits a similar ability to healthy ASC which is clearly more than expected, but it is not significantly modified by hypoxia preconditioning.

PMID:35032832 | DOI:10.1016/j.prp.2021.153756

Environ Int. 2022 Jan 12;160:107054. doi: 10.1016/j.envint.2021.107054. Online ahead of print.

ABSTRACT

BACKGROUND: Exposure to phthalates during pregnancy may alter DNA methylation in the placenta, a crucial organ for the growth and development of the fetus.

OBJECTIVES: We studied associations between urinary concentrations of phthalate biomarkers during pregnancy and placental DNA methylation.

METHODS: We measured concentrations of 11 phthalate metabolites in maternal spot urine samples collected between 22 and 29 gestational weeks in 202 pregnant women. We analyzed DNA methylation levels in placental tissue (fetal side) collected at delivery. We first investigated changes in global DNA methylation of repetitive elements Alu and LINE-1. We then performed an adjusted epigenome-wide association study using IlluminaHM450 BeadChips and identified differentially methylated regions (DMRs) associated with phthalate exposure.

RESULTS: Monobenzyl phthalate concentration was inversely associated with placental methylation of Alu repeats. Moreover, all phthalate biomarkers except for monocarboxy-iso-octyl phthalate and mono(2-ethyl-5-hydroxyhexyl) phthalate were associated with at least one DMR. All but three DMRs showed increased DNA methylation with increased phthalate exposure. The largest identified DMR (22 CpGs) was positively associated with monocarboxy-iso-nonyl phthalate and encompassed heat shock proteins (HSPA1A, HSPA1L). The remaining DMRs encompassed transcription factors and nucleotide exchange factors, among other genes.

CONCLUSIONS: This is the first description of genome-wide modifications of placental DNA methylation in association with pregnancy exposure to phthalates. Our results suggest epigenetic mechanisms by which exposure to these compounds could affect fetal development. Of interest, four identified DMRs had been previously associated with maternal smoking, which may suggest particular sensitivity of these genomic regions to the effect of environmental contaminants.

PMID:35032864 | DOI:10.1016/j.envint.2021.107054

Eur J Cancer. 2022 Jan 12;163:44-54. doi: 10.1016/j.ejca.2021.12.023. Online ahead of print.

ABSTRACT

INTRODUCTION: Malignant pleural mesothelioma (MPM) is a tumour associated with asbestos exposure. Approximately, 10% of patients with MPM carry a germline pathogenic variant (PV), mostly in DNA repair genes, suggesting the occurrence of inherited predispositions.

AIM: This article aimed to 1) search for new predisposing genes and assess the prevalence of PVs in DNA repair genes, by next-generation sequencing (NGS) analysis of germline DNA from 113 unselected patients with MPM and 2) evaluate whether these patients could be sensitive to tailored treatments.

METHODS: NGS was performed using a custom panel of 107 cancer-predisposing genes. To investigate the response to selected drugs in conditions of DNA repair insufficiency, we created a three-dimensional-MPM cell model that had a defect in ataxia telangiectasia mutated (ATM), the master regulator of DNA repair.

RESULTS: We identified PVs in approximately 7% of patients with MPM (8/113) and a new PV in BAP1 in a further patient with familial MPM. Most of these PVs were in genes involved or supposedly involved in DNA repair (BRCA1, BRIP1, CHEK2, SLX4, FLCN and BAP1). In vitro studies showed apoptosis induction in ATM-silenced/inhibited MPM spheroids treated with an enhancer of zeste homologue 2 inhibitor (tazemetostat).

CONCLUSIONS: Overall these data suggest that patients with MPM and DNA repair insufficiency may benefit from this treatment, which induces synthetic lethality.

PMID:35032816 | DOI:10.1016/j.ejca.2021.12.023

Respir Med. 2022 Jan 6;192:106736. doi: 10.1016/j.rmed.2022.106736. Online ahead of print.

ABSTRACT

BACKGROUND: A1006E is a Cystic Fibrosis (CF) mutation that is still not widely known. We report phenotypic features and geographic distribution of the largest cohort of people with CF (pwCF) carrying A1006E to date.

METHODS: Study of European pwCF carrying A1006E mutation, included in the European CF Society Patient Registry (ECFSPR). Genotype, ancestries and all variables recorded were compared to a cohort of F508del/F508del patients. Rate of decline in percentage-of-predicted FEV₁ (ppFEV₁) was also analyzed using the 2010-2017 ECFSPR.

RESULTS: 44 pwCF carrying A1006E were reported (59% males), median age 33 years old (3-58), 54.5% Spanish and 40.9% Italian, most with ancestry in Murcia (Spain) and Lazio (Italy) regions. Compared to F508del homozygous, A1006E-pwCF were significantly older (75% vs. 52.5% ≥ 18 years old) and diagnosed at later median age (6.98 vs. 0.29 years); showed lower rates of meconium ileus (2.33% vs. 17.7%), pancreatic insufficiency (27.91% vs. 99.26%), diabetes (2.33% vs. 21.98%), liver disease (6.98% vs. 36.72%) and Pseudomonas aeruginosa chronic colonization (30.95% vs. 42.51%); and presented better nutrition (BMI z-score 0.44 vs. -0.43) and ppFEV₁ (90.8% vs. 78.6%), with 18.9% (most >40 years old) having a ppFEV₁<70%. Additional ppFEV₁ decline (0.96% per year) was attributed to F508del/F508del genotype (p = 0.0007). None died or needed organ transplantation during the study period.

CONCLUSIONS: A1006E-pwCF are mainly of Western Mediterranean Spanish and Italian descent. When compared with F508del/F508del-pwCF, they usually have a milder form of the disease, associated with pancreatic sufficiency and slower FEV₁ decline. However, some will develop progressive respiratory impairment during adulthood.

PMID:35032736 | DOI:10.1016/j.rmed.2022.106736

J Stroke Cerebrovasc Dis. 2022 Jan 12;31(3):106279. doi: 10.1016/j.jstrokecerebrovasdis.2021.106279. Online ahead of print.

ABSTRACT

OBJECTIVES: Cognitive problems following stroke are of key concern to stroke survivors. Discussing risk of dementia at the time of stroke could have implications for follow-up care. However, informing someone who has just had a stroke about risk of dementia could cause distress. This survey explored healthcare professionals’ views on discussing risk of post-stroke dementia at the time of stroke.

MATERIALS AND METHODS: This online survey was aimed at all UK healthcare professionals who care for patients with stroke. The survey was distributed via the mailing lists of seven professional stroke-related organisations and Twitter. Descriptive statistics were used to summarise findings.

RESULTS: Sixty healthcare professionals completed the survey. Healthcare professionals were aware of the main risk factors associated with post-stroke dementia (e.g. previous stroke, age). Most respondents (N=34/60, 57%) thought that patients with acute stroke would benefit from knowing if they are at high risk of dementia, and 75% (N=45/60) agreed that carers would benefit. Despite this, the majority of healthcare professionals (N=47/53, 89%) who cared for patients with acute stroke in the past year said they rarely/never discussed dementia with their patients. Most respondents (N=46/60, 77%) thought risk of dementia should be discussed 1-6 months post-stroke.

CONCLUSION: Although healthcare professionals felt it would be helpful to discuss risk of post-stroke dementia, in practice, most said that they rarely or never discussed this with their patients. Stroke survivors could benefit from a healthcare system that offers appropriate follow-up care and support to patients at high risk of dementia.

PMID:35032758 | DOI:10.1016/j.jstrokecerebrovasdis.2021.106279

Behav Res Ther. 2022 Jan 8;150:104032. doi: 10.1016/j.brat.2022.104032. Online ahead of print.

ABSTRACT

INTRODUCTION: Cannabis use disorder (CUD) is a growing public health concern, and is highly comorbid with negative affective conditions such as anxiety and depression. Late adolescence and early adulthood represents a time of rapid emotion regulation development, as well as the onset of anxiety, mood, and substance use disorders, especially CUD. Maladaptive cognitive, behavioral, and emotional responding to one’s own negative affect (in an effort to eliminate it) is associated with substance use, and represents a novel treatment target to improve outcomes of treatment for substance misuse.

METHOD: After development of a manual for a novel intervention, Affect Management Treatment (AMT) for CUD, a pilot randomized clinical trial was conducted in 18-25 year-old participants with CUD to evaluate the impact of this approach on negative affect, constructs (e.g., distress intolerance) representing maladaptive reactivity to negative affect, and cannabis use. Participants (N = 52) received either 12 sessions of standard cognitive behavioral therapy (CBT) for CUD or 12 sessions of AMT and were assessed on measures of negative affect, reactivity to negative affect, cannabis use, and cannabis use problems at baseline, throughout treatment, post-treatment, and 6-mo follow-up.

RESULTS: AMT outperformed CBT in reducing negative affect and reactivity to negative affect, and it had a significant impact on cannabis use and cannabis use problems. There were no statistically significant between-group differences on cannabis outcomes.

CONCLUSIONS: AMT offers a novel, successful approach to the treatment of CUD.

PMID:35032700 | DOI:10.1016/j.brat.2022.104032

Diabetes Metab. 2022 Jan 12:101321. doi: 10.1016/j.diabet.2022.101321. Online ahead of print.

ABSTRACT

OBJECTIVE: To investigate the glycemic balance before, during and after the 2016 Paris Marathon using a real-time continuous glucose monitoring (RT-CGM) system in patients with type 1 diabetes mellitus in a prospective single-center observational study.

METHODS: Inclusion criteria were as follows: type 1 diabetes mellitus; age ≥18 years; HbA1c < 9%. Participants performed two 2h-preparatory races (PR) before the Marathon and were monitored with RT-CGM 24h before, during and 72h after each race. Hypoglycemic events were prevented via carbohydrate intake / insulin dose adjustments. The primary outcome was area under the curve (AUC) < 70 and > 200 mg/dl and percentage of time spent in euglycemia, hypoglycemia, and hyperglycemia during the races.

RESULTS: Twelve patients (2F/10M; median HbA1c=6.8%) were included and completed the study. Median AUC < 70 and time spent in hypoglycemia (< 70 mg/dl) during the PRs and Marathon were equal to 0. However, no hypoglycemic episodes occurred during Marathon, while two patients experienced hypoglycemia during PR1 and PR2. There was a significant increase in AUC > 200 mg/dl during races between PR2 and Marathon (P = 0.009) although the median time spent > 200mg/dl was not statistically different in Marathon versus PR2 (48.4% versus 18.4%; P = 0.09). Median time spent in euglycemia (70-200 mg/dl) was lower in Marathon versus PR2 (51.6 versus 58%; P = 0.03).

CONCLUSION: Our study proposes a medical support protocol for extreme endurance physical activity in patients with type 1 diabetes mellitus. Our results suggest that RT-CGM, coupled with adjustments in carbohydrate intake and insulin doses, appears to be effective to prevent hypoglycemia during and after exercise.

PMID:35032674 | DOI:10.1016/j.diabet.2022.101321