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Nevin Manimala Statistics

Cardiovascular and Venous Thromboembolic Risk With Janus Kinase Inhibitors in Immune-Mediated Inflammatory Diseases: A Systematic Review and Meta-Analysis of Randomized Trials

ACR Open Rheumatol. 2022 Jul 28. doi: 10.1002/acr2.11479. Online ahead of print.

ABSTRACT

OBJECTIVE: Janus kinase (JAK) inhibition effectively treats immune-mediated inflammatory diseases (IMIDs); however, concern over the risk of major adverse cardiac events (MACE) and venous thromboembolism (VTE) remains. We aimed to evaluate the safety (VTE and MACE outcomes) of JAK inhibitors in the treatment of IMIDs.

METHODS: A search in PubMed, Embase, and ClinicalTrials.gov databases was conducted for randomized clinical trials (RCTs) of JAK inhibitors across IMIDs. Primary outcomes were VTE and MACE with JAK inhibitors compared with placebo and active comparator arms stratified by follow-up time.

RESULTS: Sixty-six RCTs enrolled 38,574 patients with a mean age of 48.8 years and a mean follow-up of 10.5 months. JAK inhibitors had a numerically higher rate of VTE when compared with controls (odds ratio [OR] 1.65; 95% confidence interval [CI]: 0.97-2.79), driven by trials with a follow-up duration of 12 or more months (OR 2.17; 95% CI: 1.16-4.05; Pinteraction = 0.05). When compared with active comparators, JAK inhibitors increased VTE in clinical trials with 12 or more months’ versus less than 12 months’ follow-up time (OR 2.38 [95% CI: 1.24-4.57] vs 0.30 [95% CI: 0.07-1.26], respectively; Pinteraction = 0.01). No increased risk of VTE was seen when comparing JAK inhibitors with placebo arms. For the outcome of MACE, the results were largely similar but did not reach statistical significance (OR 1.19; 95% CI: 0.86-1.64).

CONCLUSION: JAK inhibitors when compared with active comparator arms increased the risk of VTE, which was dependent on duration of exposure. Future clinical trials with extended follow-up are needed to clarify the safety profiles of JAK inhibitors.

PMID:35903881 | DOI:10.1002/acr2.11479

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Process optimisation for enzymatic clarification of indigenous wild watermelon (Citrullus lanatus) juice

Food Sci Technol Int. 2022 Jul 29:10820132221117457. doi: 10.1177/10820132221117457. Online ahead of print.

ABSTRACT

A fundamental step in improving the quality and consumer acceptability of wild watermelon (Citrullus lanatus) is the process of juice clarification. The aim of this research was to investigate the physicochemical properties of crude wild watermelon (Citrullus lanatus) juice and to optimise the processing conditions, incubation time, incubation temperature and enzyme concentration for the enzymatic clarification of the crude juice. Crude wild watermelon juice samples were treated with pectinase enzyme in different concentrations (0.05 to 0.15 w/w%), at different incubation temperatures (30-50oC) and for different incubation durations (60-180 min). The effects of the different treatments on turbidity, clarity, viscosity, lightness, and brix were determined. The response models adequately predicted turbidity, clarity, and viscosity at R2 > 0.5, but not lightness considering that R2 < 0.5. The model was statistically significant in predicting turbidity (R2 = 0.86), clarity (R2 = 0.81), viscosity (R2 = 0.97) and brix (R2 = 0.94) – but not lightness (R2 = 0.24) at p < 0.05. The enzyme concentration did not significantly affect turbidity, clarity, and lightness, but it did significantly affect brix positively (p < 0.05). Response surface methodology software was used to determine optimal clarification conditions. In conclusion, the optimum conditions for crude watermelon juice clarification were 0.15 w/w% enzyme concentration, 60 min incubation time and 60 oC incubation temperature. The optimum output parameters were 14.18 NTU for turbidity, 0.04 Abs for clarity, 52.30 L* value for lightness, 1.96 cps for viscosity and 3.08% for brix.

PMID:35903911 | DOI:10.1177/10820132221117457

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Candida species detection in patients with chronic periodontitis: A systematic review and meta-analysis

Clin Exp Dent Res. 2022 Jul 28. doi: 10.1002/cre2.635. Online ahead of print.

ABSTRACT

OBJECTIVES: To assess the Candida species occurrence rate and concentration in periodontal pockets in chronic periodontitis (CP) by meta-analysis.

MATERIALS AND METHODS: A search was performed of articles published between January 1, 2010, and October 1, 2020, in English and in Russian, in the electronic databases MEDLINE-PubMed, Google Scholar, The Cochrane Library, ClinicalTrials.gov, Research Gate, eLIBRARY, and Cyberleninka (PROSPEROCRD42021234831). The odds ratio (OR), standardized mean difference (SMD), and 95% confidence interval (CI) were calculated using Review Manager 5.4.1 to compare the risk of CP when Candida spp. were detected in the gingival sulcus or periodontal pocket and to compare Candida spp. density counts in patients with CP and periodontally healthy patients.

RESULTS: Twenty-six studies were included in the systematic review and 11 were included in the meta-analysis. The results showed that Candida spp. may increase the chance of CP development by 1.76 times (OR = 1.76; 95% CI = 1.04-2.99; Z = 2.10; p = .04; I2 = 61%). More Candida spp. were found in patients with CP than in periodontally healthy patients (SMD = 1.58; 95% CI = 0.15-3.02; p = .03; I2 = 98%). No data were found relating to the statistically significant influence of Candida glabrata, Candida krusei and Candida tropicalis on CP development.

CONCLUSION: We found that Candida albicans insignificantly increased the risk of CP development but, due to the heterogeneity of the included studies, further research is necessary to determine the exact role of Candida spp. in the development and course of the inflammatory periodontal diseases.

PMID:35903878 | DOI:10.1002/cre2.635

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Correlation between quantitative parameters of CEUS and Ki-67 labeling index in soft-tissue sarcoma

Acta Radiol. 2022 Jul 28:2841851221115081. doi: 10.1177/02841851221115081. Online ahead of print.

ABSTRACT

BACKGROUND: Apart from the immunohistochemical Ki-67 labeling index (LI), clinicians need a non-invasive and convenient way to predict the prognosis of patients with soft-tissue sarcoma (STS).

PURPOSE: To investigate the correlation between quantitative parameters of contrast-enhanced ultrasound (CEUS) and Ki-67 LI in STS.

MATERIAL AND METHODS: A total of 25 patients diagnosed with STS who underwent CEUS examination using SonoVue®, between January 2019 to November 2020, were included in the study. They were then divided into a high-proliferation group and low-proliferation group according to 30% Ki-67 positive tumor cells. The quantitative parameters in the semi-automatic time intensity curve analysis software, including arrival time, time to peak, peak intensity, rise time (RT), rise slope, 50% wash-out time, and 50% wash-out intensity, were extracted from the time intensity curve of CEUS by two independent observers. Statistical evaluation of the correlation and difference between CEUS quantitative parameters and Ki-67 LI between the two groups was performed. According to the area under the curve (AUC) analysis, optimal cutoff points of parameters with significant difference were determined.

RESULTS: CEUS RT of the high-proliferation group in STS was significantly higher than that of the low-proliferation group (ρ = 0.509, P = 0.01). The most reasonable cutoff to distinguish between low- and high-proliferation groups was 10.84 s. The sensitivity, specificity, and the AUC were 86.7%, 80%, and 0.80, respectively.

CONCLUSION: CEUS RT was correlated with Ki-67 LI of STS, which can be used as a minimally invasive auxiliary tool to predict the prognosis of STS in clinical practice.

PMID:35903876 | DOI:10.1177/02841851221115081

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Mental distress and substance use among rural Black South African youth who are not in employment, education or training (NEET)

Int J Soc Psychiatry. 2022 Jul 28:207640221114252. doi: 10.1177/00207640221114252. Online ahead of print.

ABSTRACT

BACKGROUND: South Africa (SA) has one of the highest rates of youth unemployment and youth who are not in employment, education or training (NEET), even higher among Black South Africans. SA’s NEET rates are 3 times those of UK; 5.4 times of Germany; 1.3 times of Brazil; and 2.5 times of Malaysia. Given that youths between 15 and 24 years of age make up 24% of the total population, these are significant challenges for the economy and further fuel the cyclical, pervasive and enduring nature of poverty. We hypothesised that rural youth who are NEET would have a greater prevalence of mental disorders and higher rates of substance use compared to their non-NEET counterparts. The objective of the study is to determine the differences in rates of psychological distress and substance use between NEET and non-NEET rural African 14- to 24-year-old young men.

METHODS: The study took place in a remote and rural district municipality in KwaZulu-Natal, South Africa. We divided the district’s five sub-municipalities into two clusters (large and small) and randomly selected one from each cluster for inclusion in the study. We further randomly selected wards from each sub-municipality and then rural settlements from each ward, for inclusion in the study. We recruited young men as part of a larger study to explore sociocultural factors important in gender-based violence in rural SA. We compared 15- to 19-year old and 20- to 24-year old youth NEET and non-NEET on rates of psychological distress symptoms (depression, anxiety, suicidal thoughts, hopelessness and worthlessness) and substance misuse (including alcohol, cannabis, other recreational drugs) using a Multivariate Analysis of Variance (MANOVA) statistics at p < .005 level of significance level.

RESULTS: About 23% of the 355 male participants were NEET. There were no statistically significant differences in psychological distress or substance use between youth NEET and non-NEET, controlling for age.

CONCLUSION: The study highlights difficult transitions to post-secondary education and work for Black youth in rural SA where opportunities for employment are limited. Education, training and employment appear to offer limited benefit.

PMID:35903872 | DOI:10.1177/00207640221114252

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Menopausal hormone therapy and subclinical cardiovascular disease in women with and without HIV

Clin Infect Dis. 2022 Jul 29:ciac620. doi: 10.1093/cid/ciac620. Online ahead of print.

ABSTRACT

BACKGROUND: Estrogen-based hormone therapy (HT) may have beneficial cardiovascular effects when initiated in early menopause. This has not been examined in women with HIV who have heightened immune activation and cardiovascular risks.

METHODS: Among 609 post-menopausal women (1,234 person-visits) in the Women’s Interagency HIV Study, we examined the relationship of ever HT use (oral, patch, or vaginal) with subclinical atherosclerosis – carotid artery intima-media thickness (CIMT), distensibility, and plaque assessed via repeated B-mode ultrasound imaging (2004-2013). We also examined associations of HT with cross-sectional biomarkers of immune activation and D-dimer. Statistical models were adjusted for sociodemographic, behavioral, and cardiometabolic factors.

RESULTS: Women (mean age = 51, 80% HIV+) who ever used HT at baseline were older, and more likely to be non-Hispanic White and report higher income, than never users. Women who ever used HT had 43% lower prevalence of plaque (prevalence ratio = 0.57; 95% CI = [0.40, 0.80]; p < 0.01), 2.51 µm less progression of CIMT per year (95% CI = [-4.60, -0.41]; p = 0.02), and marginally lower incidence of plaque over ∼7 years (risk ratio = 0.38; 95% CI = [0.14, 1.03]; p = 0.06), compared with never users, adjusting for covariates; ever HT use was not associated with distensibility. These findings were similar for women with and without HIV. Ever HT use was associated with lower serum D-dimer, but not with biomarkers of immune activation after covariate adjustment.

CONCLUSIONS: HT may confer a subclinical cardiovascular benefit in women with HIV. These results begin to fill a knowledge gap in menopausal care for women with HIV, in whom uptake of HT is very low.

PMID:35903868 | DOI:10.1093/cid/ciac620

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Plasma metabolomics in a deep vein thrombosis rat model based on ultra-high performance liquid chromatography-electrostatic field orbitrap high resolution mass spectrometry

Se Pu. 2022 Aug;40(8):736-745. doi: 10.3724/SP.J.1123.2021.12024.

ABSTRACT

Deep vein thrombosis (DVT) is a venous thromboembolic disease characterized by high incidence, mortality, and sequelae. Therefore, the effective prevention of DVT has become a critical public health concern. However, due to its complexity, the pathophysiological mechanism of DVT remains unclear. Metabolomics can be employed to analyze disease characteristics and provide scientific evidence on the underlying mechanisms. In this study, an established left femoral vein ligation rat model of DVT (n=10) was used and compared with sham surgery controls (n=10). In the DVT group, rats were anesthetized using an intraperitoneal injection of 10% chloral hydrate (300 mg/kg), after which the hair was shaved and the groin disinfected. A 2-cm longitudinal incision was made along the midpoint of the left groin area, and then the left femoral vein was separated. The vein was partially ligated at its proximal end to shrink the blood vessel lumen to approximately half. Then, 0.4 mL of 10% hypertonic saline was slowly injected from the distal end of the left femoral vein. At the same time, the femoral vein turned dark red, which indicated the formation of thrombosis. Finally, the incision was sutured after verifying bleeding in the surrounding tissue. Keeping all other procedures the same as the DVT group, the vein in the control group was not ligated or stimulated using hyper-tonic saline. The abdominal aorta plasma from rats in each group was collected seven days later. Untargeted metabolomics analysis based on ultra-high performance liquid chromatography-electrostatic field orbitrap high resolution mass spectrometry (UHPLC-Orbitrap HRMS) was conducted to investigate the plasma metabolic profiles of the sham surgery control and DVT groups. Principal component analysis (PCA) and orthogonal to partial least squares discrimi-nant analysis (OPLS-DA) on metabolome data for multivariate statistical analysis were employed to assess differences in the metabolic profile between the two groups. The results revealed distinct profiles for the DVT and control groups. The selection criteria for the differential metabolites were the variable importance in the projection (VIP) values of OPLS-DA (VIP>1) and fold changes (FC) in the DVT group (FC≤0.5 or FC≥2, P<0.05). The resulting 27 differential metabolites reflecting a metabolic disorder in the DVT group were selected and analyzed. Of these, the levels of 17 metabolites significantly increased in the DVT group, including trimethylamine N-oxide (TMAO), 4-amino-2-methyl-1-naphthol, chenodeoxycholic acid, and 7-ketocholesterol, whereas the levels of 10 metabolites decreased, including 3-dehydroxycarnitine, phosphatidylcholine 22∶6/20∶2 (PC 22∶6/20∶2), diglyceride 18∶3/20∶4 (DG 18∶3/20∶4) and anserine. To identify the changes in the metabolic pathway reflected by these differential metabolites, a differential abundance (DA) analysis based on the Kyoto Encyclopedia of Genes and Genomes metabolic pathway was conducted. The results showed that the differences in the metabolic pathways between the DVT and control groups were mainly manifested in the primary bile acid biosynthesis, bile secretion, histidine metabolism, linoleic acid metabolism, glycerophospholipid metabolism, and β-alanine metabolism pathways. Among them, the primary bile acid biosynthesis and bile secretion pathways were upregulated in the DVT group, whereas the glycerophospholipid metabolism, linoleic acid metabolism, and β-alanine metabolism pathways were downregulated. The histidine metabolism pathway contained upregulated as well as downregulated metabolites, resulting in a DA score of 0. In conclusion, these results indicate that the plasma metabolic profiling of the DVT group was significantly altered, while the disordered metabolites and metabolic pathways could provide a reference to further understand the pathological mechanism of DVT and identify new drug targets.

PMID:35903841 | DOI:10.3724/SP.J.1123.2021.12024

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Association of changes in histologic severity of nonalcoholic steatohepatitis and changes in patient-reported quality of life

Hepatol Commun. 2022 Jul 28. doi: 10.1002/hep4.2044. Online ahead of print.

ABSTRACT

Nonalcoholic steatohepatitis (NASH) is a prevalent chronic disease that is associated with a spectrum of liver fibrosis and can lead to cirrhosis. Patients with NASH report lower health-related quality of life (HRQoL) than the general population. It remains uncertain how changes in histologic severity are associated with changes in HRQoL. This is a secondary analysis of the Farnesoid X Receptor Ligand Obeticholic Acid in NASH Treatment (FLINT) and Pioglitazone, Vitamin E, or Placebo for Nonalcoholic Steatohepatitis (PIVENS) randomized controlled trials in patients with biopsy-proven NASH. HRQoL was assessed using short form-36 at baseline and at follow-up biopsy (at 72 and 96 weeks, respectively). Adjusted linear regression models were used to examine the association between changes in liver fibrosis (primary analysis), nonalcoholic fatty liver disease (NAFLD) activity score (secondary analysis), and changes in HRQoL scores. Compared with stable fibrosis, improvement of fibrosis by at least one stage was significantly associated with improvements only in the physical function component by 1.8 points (95% confidence interval, 0.1, 3.5). Worsening of fibrosis by at least one stage was not associated with statistically significant changes in any HRQoL domain compared with stable fibrosis. Associations between HRQoL and NAFLD disease activity score in the secondary analysis were of similar magnitude. Weight loss was associated with small improvements in physical function, general health, and energy levels. Conclusion: Improvements in fibrosis stage were associated with improvements in the physical component of HRQoL, but the clinical impact was modest. As improving fibrosis may not meaningfully improve well-being, treatment for NASH will be cost effective only if it prevents long-term hepatic and cardiovascular disease.

PMID:35903833 | DOI:10.1002/hep4.2044

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Pattern of Orthopedic Injuries Related to Road Traffic Accidents Among Patients Managed at the Emergency Department in Black Lion Hospital, Addis Ababa, Ethiopia, 2021

Open Access Emerg Med. 2022 Jul 21;14:347-354. doi: 10.2147/OAEM.S368324. eCollection 2022.

ABSTRACT

BACKGROUND: Studies showed that each year people lose their life on the road and many people are disabled. The majority of this disability was caused by orthopedic injury related to road traffic accidents. However, in the context of Ethiopia, studies ascribed to orthopedic injuries related to road traffic accidents are limited. The study aimed to assess the pattern of orthopedic injuries related to road traffic accidents among patients managed at the emergency department of Black Lion Hospital.

METHODS: An institutional-based cross-sectional study was conducted on 354 victims of road traffic accidents with orthopedic injuries who were visiting the Emergency department of Black Lion Hospital. Patient charts were selected by systematic random sampling technique and the data was entered into Epi-data version 4.4.2.2 and exported to the static package for social science window version 26, and descriptive statistics were used for analysis.

RESULTS: The study reveals that males were mostly injured persons (71.7%) with the age group of 13-24 were the most injured. Passenger car accounts 36.3% of causes of injury followed by motorbikes (27.4%) and lower limbs were the most common anatomic site of injuries (47.9). Of all injury types, a fracture is the most common one with 71.1%, especially lower limb fracture (42.1%). More than half victims (59.5%) had open wounds, and almost half of the study subjects (51.8%) experience Road traffic accidents while they are crossing or walking along the way.

CONCLUSION: Orthopedic injuries related to road traffic accidents are the main cause of death and disability in many individuals, especially in reproductive age groups. Therefore, policy-makers should be aware of different patterns of orthopedic injuries associated with a victim of road traffic accidents to have an appropriate and sustainable capacity to manage the orthopedic injuries.

PMID:35903799 | PMC:PMC9314752 | DOI:10.2147/OAEM.S368324

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The Effect of Non-immersive Virtual Reality Exergames Versus Band Stretching on Cardiovascular and Cerebral Hemodynamic Response: A Functional Near-Infrared Spectroscopy Study

Front Hum Neurosci. 2022 Jul 12;16:902757. doi: 10.3389/fnhum.2022.902757. eCollection 2022.

ABSTRACT

BACKGROUND: Exercise is one of the effective ways to improve cognition. Different forms of exercises, such as aerobic exercise, resistance exercise, and coordination exercise, have different effects on the improvement of cognitive impairment. In recent years, exergames based on Non-Immersive Virtual Reality (NIVR-Exergames) have been widely used in entertainment and have gradually been applied to clinical rehabilitation. However, the mechanism of NIVR-Exergames on improving motor cognition has not been clarified. Therefore, the aim of this study is to find whether NIVR-Exergames result in a better neural response mechanism to improve the area of the cerebral cortex related to motor cognition under functional near-infrared spectroscopy (fNIRS) dynamic monitoring in comparison with resistance exercise (resistance band stretching).

METHODS: A cross-over study design was adopted in this study, and 15 healthy young subjects (18-24 years old) were randomly divided into group A (n = 8) and group B (n = 7) according to a computerized digital table method. Task 1 was an NIVR-Exergame task, and Task 2 was resistance band stretching. Group A first performed Task 1, rested for 30 min (i.e., a washout period), and then performed Task 2. Group B had the reverse order. The fNIRS test was synchronized in real time during exercise tasks, and heart rate measurements, blood pressure measurements, and 2-back task synchronization fNIRS tests were performed at baseline, Post-task 1, and Post-task 2. The primary outcomes were beta values from the general linear model (GLM) in different regions of interest (ROIs), and the secondary outcomes were heart rate, blood pressure, reaction time of 2-back, and accuracy rate of 2-back.

RESULTS: The activation differences of Task 1 and Task 2 in the right premotor cortex (PMC) (P = 0.025) and the left PMC (P = 0.011) were statistically significant. There were statistically significant differences in the activation of the right supplementary motor area (SMA) (P = 0.007), left dorsolateral prefrontal cortex (DLPFC) (P = 0.031), left and right PMC (P = 0.005; P = 0.002) between baseline and Post-task 1. The differences in systolic pressure (SBP) between the two groups at three time points among women were statistically significant (P1 = 0.009, P2 < 0.001, P3 = 0.044).

CONCLUSION: In this study, we found that NIVR-Exergames combined with motor and challenging cognitive tasks can promote the activation of SMA, PMC and DLPFC in healthy young people compared with resistance exercise alone, providing compelling preliminary evidence of the power for the rehabilitation of motor and cognitive function in patients with central nervous system diseases.

PMID:35903784 | PMC:PMC9314640 | DOI:10.3389/fnhum.2022.902757