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Nevin Manimala Statistics

Association of tranexamic acid with decreased blood loss in patients undergoing laminectomy and fusion with posterior instrumentation: a systematic review and meta-analysis

J Neurosurg Spine. 2021 Nov 5:1-8. doi: 10.3171/2021.7.SPINE202217. Online ahead of print.

ABSTRACT

OBJECTIVE: Tranexamic acid (TXA) is an antifibrinolytic agent associated with reduced blood loss and mortality in a wide range of procedures, including spine surgery, traumatic brain injury, and craniosynostosis. Despite this wide use, the safety and efficacy of TXA in spine surgery has been considered controversial due to a relative scarcity of literature and lack of statistical power in reported studies. However, if TXA can be shown to reduce blood loss in laminectomy with fusion and posterior instrumentation, more surgeons may include it in their armamentarium. The authors aimed to conduct an up-to-date systematic review and meta-analysis of the efficacy of TXA in reducing blood loss in laminectomy and fusion with posterior instrumentation.

METHODS: A systematic review and meta-analysis, abiding by PRISMA guidelines, was performed by searching the databases of PubMed, Web of Science, and Cochrane. These platforms were queried for all studies reporting the use of TXA in laminectomy and fusion with posterior instrumentation. Variables retrieved included patient demographics, surgical indications, involved spinal levels, type of laminectomy performed, TXA administration dose, TXA route of administration, operative duration, blood loss, blood transfusion rate, postoperative hemoglobin level, and perioperative complications. Heterogeneity across studies was evaluated using a chi-square test, Cochran’s Q test, and I2 test performed with R statistical programming software.

RESULTS: A total of 7 articles were included in the qualitative study, while 6 articles featuring 411 patients underwent statistical analysis. The most common route of administration for TXA was intravenous with 15 mg/kg administered preoperatively. After the beginning of surgery, TXA administration patterns were varied among studies. Blood transfusions were increased in non-TXA cohorts compared to TXA cohorts. Patients administered TXA demonstrated a significant reduction in blood loss (mean difference -218.44 mL; 95% CI -379.34 to -57.53; p = 0.018). TXA administration was not associated with statistically significant reductions in operative durations. There were no adverse events reported in either the TXA or non-TXA patient cohorts.

CONCLUSIONS: TXA can significantly reduce perioperative blood loss in cervical, thoracic, and lumbar laminectomy and fusion procedures, while demonstrating a minimal complication profile.

PMID:34740174 | DOI:10.3171/2021.7.SPINE202217

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Baseline parameters and the prediction of treatment failure in patients with intravenous drug use-associated spinal epidural abscesses

J Neurosurg Spine. 2021 Nov 5:1-10. doi: 10.3171/2021.7.SPINE21689. Online ahead of print.

ABSTRACT

OBJECTIVE: Despite the increasing incidence of spinal epidural abscess (SEA), the baseline parameters potentially predictive of treatment failure remain poorly characterized. In this study, the authors identify the relevant baseline parameters that predict multimodal treatment failure in patients with either intravenous drug use (IVDU)-associated SEA or non-IVDU-associated SEA.

METHODS: The authors reviewed the electronic medical records of a large institutional series of consecutive patients with diagnosed SEA between January 2011 and December 2017 to characterize epidemiological trends as well as the complement of baseline measures that are predictive of failure after multimodal treatment in patients with and without concomitant IVDU. The independent impact of clinical and imaging factors in detecting treatment failure was assessed by performing stepwise binary logistic regression analysis.

RESULTS: A total of 324 consecutive patients with diagnosed SEA were identified. Overall, 226 patients (69.8%) had SEA related to other causes and 98 (30.2%) had a history of recent IVDU. While non-IVDU SEA admission rates remained constant, year-over-year admissions of patients with IVDU SEA nearly tripled. At baseline, patients with IVDU SEA were distinct in many respects including younger age, greater unemployment and disability, less frequent diabetes mellitus (DM), and more frequent methicillin-resistant Staphylococcus aureus infection. However, differences in length of stay, loss to follow-up, and treatment failure did not reach statistical significance between the groups. The authors constructed independent multivariate logistic regression models for treatment failure based on identified parameters in the two cohorts. For the non-IVDU cohort, the authors identified four variables as independent factors: DM, hepatitis B/C, osteomyelitis, and compression deformity severity. In contrast, for patients with IVDU, the authors identified three variables: albumin, endocarditis, and endplate destruction. Receiver operating characteristic and area under the curve (AUC) analyses were undertaken for the multivariate models predicting the likelihood of treatment failure in the two cohorts (AUC = 0.88 and 0.89, respectively), demonstrating that the derived models could adequately predict the risk of multimodal treatment failure. Treatment failure risk factor point scales were derived for the identified variables separately for both cohorts.

CONCLUSIONS: Patients with IVDU SEA represent a unique population with a distinct set of baseline parameters that predict treatment failure. Identification of relevant prognosticating factors will allow for the design of tailored treatment and follow-up regimens.

PMID:34740181 | DOI:10.3171/2021.7.SPINE21689

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Developmental and epilepsy spectrum of Poirier-Bienvenu neurodevelopmental syndrome: Description of a new case study and review of the available literature

Seizure. 2021 Oct 27;93:133-139. doi: 10.1016/j.seizure.2021.10.019. Online ahead of print.

ABSTRACT

AIM: To better characterize the clinical phenotype of Poirier-Bienvenu neurodevelopmental syndrome (OMIM ID: 618,732) due to pathogenic variants of the CSNK2B gene.

METHOD: We reviewed the electro-clinical and developmental data of all 14 patients with de novo mutations of the CSNK2B gene reported in the literature and describe a further individual with a novel CSNK2B pathogenic variant.

RESULTS: Clustered generalized tonic-clonic or myoclonic seizures with onset before the age of 18 months and delayed neurodevelopment were present in more than 75% of patients. Epilepsy was pharmaco-resistant in 40%. All the individuals (27%) with normal neurological development had pharmaco-sensitive epilepsy. The severity of cognitive and motor impairments was higher in the group with pharmaco-resistant epilepsy, and a statistically significant correlation between seizure control and the severity of cognitive impairment was documented (χ2(3) = 9.44; p = .024) INTERPRETATION: Early seizure onset, clustered seizures and delayed development in both males and females were early clinical markers in most patients with CSNK2B mutations. The entity of neurodevelopmental abnormalities was related to epilepsy severity. Prospective studies are required to better assess the relationship between epilepsy and developmental outcomes in this condition.

PMID:34740143 | DOI:10.1016/j.seizure.2021.10.019

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Morphological analysis of the brain subcortical gray structures in restless legs syndrome

Sleep Med. 2021 Oct 22;88:74-80. doi: 10.1016/j.sleep.2021.10.025. Online ahead of print.

ABSTRACT

BACKGROUND: Although several studies have shown the involvement of specific structures of the central nervous system, the dopaminergic system, and iron metabolism in restless legs syndrome (RLS), the exact location and extent of its anatomical substrate is not yet known. The scope of this new study was to investigate the brain subcortical gray structures, by means of structural magnetic resonance imaging (MRI) studies, in RLS patients in order to assess the presence of any volume or shape abnormalities involving these structures.

METHODS: Thirty-three normal controls (24 females and nine males) and 45 RLS patients (34 females and 11 males) were retrospectively recruited and underwent a 1.5 Tesla MRI study with two-dimensional T1 sequences in the sagittal plane. Post-processing was performed by means of the Functional Magnetic Resonance Imaging of the Brain Analysis Group Integrated Registration and Segmentation Tool (FIRST) software, and both volumetric and morphological analyses of the thalamus, caudate, putamen, globus pallidus, brainstem, hippocampus, and amygdala, bilaterally, were carried out.

RESULTS: A statistically significant volumetric reduction in the left amygdala and left globus pallidus was found in subjects with RLS, as well as large surface morphological alterations affecting the amygdala bilaterally and other less widespread surface changes in both hippocampi, the right caudate, the left globus pallidus, and the left putamen.

CONCLUSIONS: These findings seem to indicate that the basic mechanisms of RLS might include a pathway involving not only the hypothalamus-spinal dopaminergic circuit (nucleus A11), but also pathways including the basal ganglia and structures that are part of the limbic system; moreover, structural alterations in RLS seem to concern the morphology as well as the volume of the above structures. The role of basal ganglia in the complex neurophysiological and neurochemical mechanism of RLS needs to carefully reconsidered.

PMID:34740168 | DOI:10.1016/j.sleep.2021.10.025

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Aptamer/AuNPs encoders endow precise identification and discrimination of lipoprotein subclasses

Biosens Bioelectron. 2021 Oct 30;196:113743. doi: 10.1016/j.bios.2021.113743. Online ahead of print.

ABSTRACT

Lipoproteins are composed of lipid and apolipoproteins in conjunction with noncovalent bonds. Different lipoprotein categories, particularly Low-Density Lipoprotein (LDL), High-Density Lipoprotein (HDL) and Very Low-Density Lipoprotein (VLDL) disagree in roles for the occurrence and development of cardiovascular disease, and their exact discrimination are critically required. Herein, a multiplexed sensor platform combined with an encoder system is introduced for accurate analysis of multiple lipoproteins in complex matrix. Three encoders, i.e., bare AuNPs, AuNPs-anti-LDL aptamer (AuNPs-apt) and AuNPs-non-aptamer DNA (AuNPs-n), facilitate precise discrimination for lipoprotein subclasses at a fairly low level of 0.490 nM. The binding of single-stranded DNA (ssDNA) with AuNPs prevents them from gathering in a relatively higher level of salt. In targets stimuli, the weaker binding between ssDNA and AuNPs is destroyed to certain degrees depending on the differential affinities among DNA, AuNPs, and multifarious proteins. It results in distinct aggregation states of encoders to cause diverse ultraviolet absorption, which may be statistically characterized to achieve highly facile and precise identification for lipoprotein subclasses. Remarkably, LDL at 0.05-37.5 μg/mL could be identified by the encoder system. 11 typical proteins including three lipoprotein subclasses in human serum were also precisely discriminated. Furthermore, the accurate identification of lipoprotein subclasses with different molar ratios from real clinical serum samples were obtained.

PMID:34740115 | DOI:10.1016/j.bios.2021.113743

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Sensitivity Improvement for Spectrofluorimetric Determination of Commonly Used Antifungal Drug “Nystatin”: Application for Oral Suspension

Luminescence. 2021 Nov 5. doi: 10.1002/bio.4154. Online ahead of print.

ABSTRACT

In this paper, two simple, rapid and highly sensitive spectrofluorimetric methods were developed and validated for nystatin determination in its pure form and pharmaceutical dosage form (oral suspension). The first method is based on measuring of nystatin native fluorescence after dilution with isopropyl alcohol at 407 nm (excitation 303 nm). The floursence intensity is linered dependant on the nystatin concentrartion within the specified range 50-500 ngmL-1 . The second is based on micellar enhancement of nystatin fluoescence by using sodium dodecyl sulphate (SDS). In the presence of 2% w/v SDS, about 1.9 -fold enhancement can be achieved in the relative fluorescence intensity (RFI) of nystatin. The linear range for the second method was 20-100 ngmL-1 . The limit of quantification and detection were found to be 43.23 ngmL-1 and 14.27 ngmL-1 (method I), 6.08 ngmL-1 and 2.0 ngmL-1 (method II). According to percentage recoveries and relative standard deviations (RSDs) obtained, the proposed methods are precise (RSDs were less than 2%), reproducible, and accurate and could be successfully applied for quantitative estimation of nystatin in its dosage form. The statistical results of this method were compared with that of the reported method and showed excellent agreement in respect for accuracy and precision.

PMID:34738720 | DOI:10.1002/bio.4154

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Serious adverse drug reactions in sub-Saharan Africa in the era of antiretroviral treatment: A systematic review

Pharmacol Res Perspect. 2021 Dec;9(6):e00875. doi: 10.1002/prp2.875.

ABSTRACT

We aimed to summarize and describe the burden of serious adverse drug reactions (ADRs) in sub-Saharan Africa (SSA) in the era of antiretroviral therapy. We searched Medline, CINAHL, Africa-Wide Information, Scopus, and Web of Science, without language restriction up to March 2021. We hand-searched reference lists, conference abstracts, and dissertation databases. We included studies reporting proportions of admissions attributed to ADRs, admissions prolonged by ADRs, or in-hospital deaths attributed to ADRs. Two reviewers independently screened the studies, reviewed the study quality using a previously published tool, and extracted the data. We tested for heterogeneity using I2 -statistics and summarized the study results using medians and interquartile ranges. Subgroup analyses summarized the results by study quality, setting, methodology, and population. From 1005 unique references identified, we included 15 studies. Median study quality was 7/10; heterogeneity was very high. Median [IQR] proportion of admissions attributed to ADRs was 4.8% [1.5% to 7.0%] (14 studies) and 6.4% [4.0% to 8.4%] in nine active surveillance studies in adults. Two pediatric studies reported the proportion of admissions prolonged by ADRs (0.29% and 0.99%). Three studies reported the proportion of in-hospital deaths attributed to ADRs (2.5%, 13%, and 16%). Antiretroviral and antituberculosis drugs were often implicated in serious ADRs. Evidence of the burden of serious ADRs in SSA is patchy and heterogeneous. A few high-quality studies suggest that the burden is considerable, and that it reflects the regional impact of the HIV pandemic. Further characterization of this burden is required, ideally in studies of standardized methodology.

PMID:34738728 | DOI:10.1002/prp2.875

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Comparative cardiovascular and renal effectiveness of sodium-glucose co-transporter 2 inhibitors and glucagon-like peptide 1 receptor-agonists: Scandinavian cohort study

Diabetes Obes Metab. 2021 Nov 5. doi: 10.1111/dom.14598. Online ahead of print.

ABSTRACT

AIMS: To assess the comparative cardiovascular and renal effectiveness of SGLT2 inhibitors vs GLP-1-receptor-agonists in routine clinical practice.

MATERIALS AND METHODS: Cohort study of nationwide registers from Sweden, Denmark and Norway, 2013-2018, including 87525 new users of SGLT2 inhibitors and 63921 new users of GLP-1-receptor-agonists, analyzed intention-to-treat. Coprimary outcomes, analyzed intention to treat, were major adverse cardiovascular events (MACE; myocardial infarction/stroke/cardiovascular death), heart failure (hospitalization for heart failure/heart failure death) and serious renal events (renal replacement therapy/hospitalization for renal events/death from renal causes).

RESULTS: Use of SGLT2 inhibitors vs GLP-1-receptor-agonists, was associated with higher risk of MACE (adjusted incidence rate: 15.2 vs 14.4 events per 1000 person-years; HR 1.07 [95% CI 1.01-1.15]), similar risk of heart failure (6.0 vs 6.0 events per 1000 person-years; HR 1.02 [0.92-1.12]) and lower risk of serious renal events (2.9 vs 4.0 events per 1000 person-years; HR 0.76 [0.66-0.87]). In as-treated analyses, the HR (95% CI) was 1.11 (1.00-1.24) for MACE, 0.88 (0.74-1.04) for heart failure and 0.60 (0.47-0.77) for serious renal events. In secondary outcome analyses, use of SGLT2 inhibitors vs GLP-1-receptor-agonists was not associated with statistically significant differences in risk of myocardial infarction (HR 1.09 [95% CI 1.00-1.19]), cardiovascular death (HR 0.97 [95% CI 0.84-1.12]), death from renal causes (HR 0.75 [95% CI 0.41-1.35]) or any cause death (HR 1.01 [95% CI 0.94-1.09]) while risk of stroke was higher (HR 1.14 [95% CI 1.03-1.26]) and risk of renal replacement therapy (HR 0.74 [95% CI 0.56-0.97]) and hospitalization for renal events (HR 0.75 [95% CI 0.65-0.88]) was lower among users of SGLT2 inhibitors.

CONCLUSIONS: Use of SGLT2 inhibitors vs GLP-1-receptor-agonists was associated with a similar risk of heart failure and lower risk of serious renal events while use of GLP-1-receptor-agonists vs SGLT2 inhibitors was associated with a slightly lower risk of MACE. In as-treated analyses, the associations with MACE and serious renal events increased in magnitude and the HR for heart failure tended towards a protective association for SGLT2 inhibitors. This article is protected by copyright. All rights reserved.

PMID:34738703 | DOI:10.1111/dom.14598

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Understanding disparities and barriers associated with pediatric transplant evaluation and time to listing: Moving toward a more comprehensive picture

Pediatr Transplant. 2021 Nov 5:e14182. doi: 10.1111/petr.14182. Online ahead of print.

ABSTRACT

BACKGROUND: Delayed time to listing (TTL) for pediatric transplant patients is associated with increased risks of mortality and morbidity. The full range of health disparities, sociodemographic factors, and other barriers associated with delays in listing in the pediatric transplant candidate evaluation process has not been fully examined.

METHODS: Retrospective chart reviews were conducted for 183 kidney, liver, and heart transplant candidates ages 0-18 who were referred for evaluation during 2012-2015. Demographic information and potential barriers (e g., social/medical factors, financial concerns) were gathered from pre-transplant evaluations and included in a comprehensive model to evaluate mechanisms that explain differences in TTL. Descriptive statistics, logistic regression models, Cox proportional hazards models, and path analysis were used for analyses.

RESULTS: Candidates included 26.8% heart, 33.3% liver, and 39.9% kidney patients. The most common barrier to listing was financial (71.6%), followed by caregiver psychological or substance use (57.9%), and medical problems (49.7%). Higher age, kidney, and liver organ type (relative to the heart), and presence of social, medical, administrative/motivation, and financial barriers were all directly associated with longer TTL. Public insurance was indirectly associated with TTL through social, administrative/motivation, and financial barriers. Organ type was indirectly associated with TTL through financial barriers.

CONCLUSIONS: Results suggest social problems, administrative issues, and financial issues act as mechanisms through which insurance type and liver transplant candidates face increased risk of delays in transplant listing time. There are numerous clinical implications and interventions that are warranted to reduce TTL among pediatric transplant candidates with co-occurring barriers.

PMID:34738706 | DOI:10.1111/petr.14182

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Selective Antisite Defect Formation in WS2 Monolayers via Reactive Growth on Dilute W-Au Alloy Substrates

Adv Mater. 2021 Nov 5:e2106674. doi: 10.1002/adma.202106674. Online ahead of print.

ABSTRACT

Defects are ubiquitous in 2D materials and can not only affect the structure and properties of the materials but can also introduce new functionalities. Methods to adjust the structure and density of defects during bottom-up synthesis are required to control the growth of 2D materials with tailored optical and electronic properties. In this paper, w e present a Au-assisted chemical vapor deposition approach to selectively form SW and S2W antisite defects, whereby one or two sulfur atoms substitute for a tungsten atom in WS2 monolayers. Guided by first-principles calculations, w e describe a new method that can maintain tungsten-poor growth conditions relative to sulfur via the low solubility of W atoms in a gold/W alloy, thereby significantly reducing the formation energy of the antisite defects during the growth of monolayer WS2 . The atomic structure and composition of the antisite defects are unambiguously identified as SW and S2W by Z-contrast scanning transmission electron microscopy and electron energy-loss spectroscopy, and their total concentration is statistically determined, with levels observed up to ∼5.0%. Scanning tunneling microscopy/spectroscopy measurements and first-principles calculations further verified these antisite defects and revealed the localized defect states in the bandgap of WS2 monolayers that are candidates for single photon emitters. This bottom-up synthesis method to form antisite defects should apply in the synthesis of other 2D transition metal dichalcogenides. This article is protected by copyright. All rights reserved.

PMID:34738669 | DOI:10.1002/adma.202106674