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Low-frequency pre-treatment HIV drug resistance: effects on 2-year outcome of first-line efavirenz-based antiretroviral therapy

AIDS. 2022 Nov 15;36(14):1949-1958. doi: 10.1097/QAD.0000000000003361. Epub 2022 Aug 18.

ABSTRACT

OBJECTIVES: Assess the impact of pre-treatment high-frequency and low-frequency drug-resistant HIV variants on long-term outcomes of first-line efavirenz-based antiretroviral therapy (ART).

DESIGN: Prospective observational study.

METHODS: Participants’ pre-treatment plasma RNA had two sections of HIV pol encoding reverse transcriptase sequenced (Illumina, MiSeq) using unique molecular identifiers to detect wild-type (pre-treatment drug-resistant variants less than 1% of viral quasispecies), low-frequency (1-9%) or high-frequency drug-resistant variants (10-100%). Associations between pre-treatment drug resistance and virologic outcomes over 24 months of efavirenz-based ART were assessed for the number and frequency of mutations by drug class and other resistance parameters.

RESULTS: Virologic failure was detected in 30 of 352 (9%) and pre-treatment drug-resistant variants were detected in the viral quasispecies of 31 of 352 (9%) participants prescribed efavirenz-based ART. Survival analyses revealed statistically significant associations between pre-treatment drug resistance at low (P < 0.0001) and high (P < 0.001) frequencies, at oligonucleotide ligation assay (OLA) (P < 0.00001) and non-OLA (P < 0.01) codons, to a single-antiretroviral class (P < 0.00001), and a shorter time to virologic failure of efavirenz-based ART. Regression analyses detected independent effects across resistance categories, including both low-frequency (P < 0.01) and high-frequency (P < 0.001) drug-resistant variants.

CONCLUSION: We observed that pre-treatment HIV drug resistance detected at low frequencies increased the risk of virologic failure over 24 months of efavirenz-based ART, but that most failures, regardless of drug-resistant variants’ frequencies, were detected within a year of ART initiation. These observations suggest that when efavirenz-based ART is prescribed, screening for pre-treatment drug resistance by an assay capable of detecting low-frequency variants, including OLA, may guide clinicians to prescribe more effective ART.

PMID:36305180 | DOI:10.1097/QAD.0000000000003361

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Effect Of Fibroblast Growth Factor-21 Molecule On Coronary Collateral Development

Comb Chem High Throughput Screen. 2022 Oct 26. doi: 10.2174/1386207326666221026151525. Online ahead of print.

ABSTRACT

BACKGROUND: Collateral arteries provide an alternative source to myocardium resulting from ischemia due to occlusive coronary artery disease and may help preserve myocardial function in the case of coronary artery disease (CAD)[1]. Although the collateral development is so important, its pathophysiology has not been fully elucidated. Until now, there is no study investigating the relationship between Fibroblast growth factor-21(FGF-21) and coronary collateral.

OBJECTIVE: This study aims to investigate the pathophysiology of coronary collateral development.

METHODS: In our study, which we planned as a case control, 60 consecutive patients with ≥90 stenosis in at least one large coronary artery as a result of coronary angiography (CAG) and 30 patients with normal coronary angiography were included in the study cross-sectional. Demographic, echocardiographic and laboratory data were recorded. Coronary collateral circulation was evaluated using the Rentrop-Cohen method [2]. FGF-21 levels were measured in all individuals.

RESULTS: In the analysis, no significant difference was observed between the two groups in basic biochemical parameters other than HDL (p>0.05 for all). FGF-21 level was found to be statistically significantly higher in the patient group compared to the control group (p:0.003). Also, FGF-21 level was found to be statistically significantly higher in the good collateral circulation group to the poor collateral circulation group (p:0.006). Univariate and multivariate logistic regression analysis was performed to predict the presence of collateral. We found that FGF-21(p=0.006), C-reactive protein (p=0.020) predicted the presence of collateral independently.

CONCLUSION: Collateral formation and cardiac prognosis are closely related. Our study is the first to investigate the relationship between collateral formation and FGF-21. Our study showed that FGF-21 level is an independent predictor of collateral formation. In addition, there was a significant difference between bad and good collateral formation in terms of FGF-21 levels.

PMID:36305157 | DOI:10.2174/1386207326666221026151525

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The impact of initial admission department on the management and prognosis of retinal artery occlusion

Curr Neurovasc Res. 2022 Oct 27. doi: 10.2174/1567202620666221027091249. Online ahead of print.

ABSTRACT

BACKGROUND/OBJECTIVE: Retinal artery occlusion (RAO) is an emergency condition in both neurology and ophthalmology departments. However, the management and visual outcome of RAO in different initial departments remain unclear. Therefore, we aimed to investigate the impact of the initial department on the management and prognosis of RAO.

METHODS: Consecutive cases of RAO between January 2011 and December 2021 were retrospectively analyzed. The baseline characteristics, relevant evaluation, and treatment were compared between the neurology and ophthalmology departments. The primary outcome was the visual recovery rate. The secondary outcomes were newly diagnosed cardiovascular factors, concurrent stroke and new-onset cardiovascular events.

RESULTS: A total of 74 RAO patients were included. The median age was 54 years, and 67.6% were male. There were 42 (56.8%) patients admitted to the neurology department and 32 (43.2%) in the ophthalmology department. The visual recovery rate was higher in the neurology department than in the ophthalmology department, although the difference did not reach statistical significance (27.8 vs. 12.5%, p= 0.120). Risk factor evaluation and secondary prevention were taken more frequently in the neurology department (p < 0.001). Cardiovascular risk factors and concurrent stroke were all discovered in the neurology department. However, the incidence of new-onset cardiovascular events was similar between the two departments.

CONCLUSIONS: The study demonstrated that the visual prognosis of RAO was devastating regardless of the neurology and ophthalmology department. Given the admission delay, inadequate management, and high risk of cardiovascular risk factors and stroke, stroke centers should be recommended as initial admission departments for RAO patients.

PMID:36305143 | DOI:10.2174/1567202620666221027091249

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Lacrimal gland histopathology and secretory function in Sjögren’s syndrome mice model treated with Moringa oleifera Lam. leaf extract

Antiinflamm Antiallergy Agents Med Chem. 2022 Oct 26. doi: 10.2174/1871523022666221026145110. Online ahead of print.

ABSTRACT

BACKGROUND: The pathogenesis of Sjögren’s syndrome involves the activation of NF-κB, producing proinflammatory cytokines such as tumor necrosis factor-α, interleukin (IL)-1α, IL-1β, IL-6, IL-17, and interferon-γ. Through oxidative stress, they will cause necrosis and apoptosis of lacrimal gland cells, resulting in impaired secretory function or reduced tear production. Moringa oleifera leaf extract is known to have strong anti-inflammatory and antioxidant activities.

OBJECTIVE: To determine the effect of Moringa oleifera leaf extract on lacrimal gland histopathology and secretory function in Sjögren’s syndrome mice model.

METHODS: The experimental study had a post-test only control group design with 32 eight-week-old male mice of the BALB/c strain divided into four groups, negative control (C-), which was not induced by SS, positive control (C+), treatment 1 (T1), and treatment 2 (T2) induced by Sjögren’s syndrome by immunizing with the 60-kD Ro antigen (SSA) as much as 100 µg. After 42 days, the T1 group was given dexamethasone 1.23 mg/kg BW/day orally for 14 days, whereas T2 was given dexamethasone 1.23 mg/kg BW/day and Moringa oleifera leaf ethanol extract 200 mg/kg BW/day orally for 14 days. At the end of the study, lacrimal gland histopathology and secretory function (tear production) were examined. Statistical analysis using F ANOVA/Kruskal-Wallis was followed by partial difference test with the Least Significant Difference post hoc test/Mann-Whitney. Significant if p < 0.05.

RESULTS: The comparison of lacrimal gland histopathology in T1 (p = 0.044) and T2 groups (p = 0.020) obtained significant results (p < 0.05) when compared to C+. However, the comparison of tear production in T1 (p = 0.127) and T2 groups (p = 0.206) was not significant (p > 0.05) when compared to the C+ group.

CONCLUSION: The administration of Moringa oleifera leaf extract 200 mg/kg BW for 14 days could significantly improve lacrimal gland histopathology but was not effective in increasing tear production in Sjögren’s syndrome mice model.

PMID:36305140 | DOI:10.2174/1871523022666221026145110

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Sex Differences in Serum Prolactin Levels in Children and Adolescents on Antipsychotics: a Systematic Review and Meta-analysis

Curr Neuropharmacol. 2022 Oct 27. doi: 10.2174/1570159X21666221027143920. Online ahead of print.

ABSTRACT

BACKGROUND: Serum prolactin levels are influenced by sex, physical development and medications among other factors. Antipsychotics usually increase serum prolactin levels in both adults and younger patients, but no study had reviewed the potential association between sex and vulnerability for developing hyperprolactinemia among children and adolescents.

OBJECTIVE: Systematic review and meta-analysis of serum prolactin levels in children and adolescents on antipsychotic treatment for any psychiatric diagnosis to determine the effect of sex.

METHODS: A systematic search was performed in MEDLINE/PubMed/Web of Science and Cochrane databases for randomized controlled trials of antipsychotics in children and adolescents reporting serum prolactin levels by sex.

RESULTS: Of 1278 identified records, seven studies were included, comparing different single antipsychotics to placebo (risperidone N=4; lurasidone N=1; olanzapine N=1; queriapine N=1). Both male and female children and adolescents on antipsychotics presented a significant increase of prolactin levels relative to subjects receiving placebo. (Male: 16.53 with 95%CI: 6.15 – 26.92; Female: 26.97 with 95%CI: 9.18 – 44.75). The four studies using risperidone had similar findings (Male: 26.49 with 95%CI: 17.55 – 35.43; Female: 37.72 with 95%CI: 9.41 – 66.03). In the direct comparison between sexes, females showed somewhat greater increases of prolactin, but the differences were not statistically significant.

CONCLUSION: Serum prolactin levels are increased in children and adolescents of both sexes on antipsychotics; with females showing a slightly greater increase than males. Further research is needed to clarify the influence of sex and pubertal status on prolactin levels in children and adolescents taking antipsychotics.

PMID:36305138 | DOI:10.2174/1570159X21666221027143920

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Impact of GSTT1 and GSTM1 Polymorphisms in the Susceptibility to Philadelphia Negative Chronic Myeloid Leukaemia

Curr Cancer Drug Targets. 2022 Oct 27. doi: 10.2174/1568009623666221027103845. Online ahead of print.

ABSTRACT

The objective of our research was to clarify the role of genetic polymorphisms in GST (T1 and M1) in the development of Ph-ve CML.

MATERIALS AND METHODS: We report on a case-control study, with 126 participants, divided into 26 patients with Ph-ve CML (57.7% male, 42.3% female) and 100 healthy volunteers (51% male, 49% female) with no medical history of cancer as a control population. All Ph-ve CML patients were diagnosed according to standard hematologic and cytogenetic criteria based on CBC, confirmed by Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) to determine the presence or absence of the BCR-ABL gene, followed by bone marrow (BM) examination.

RESULTS: Of the 26 studied cases, 50% had the GSTT1 null genotype against 21% of the control group, a statistically significant difference (CI= 1.519 – 9.317; p-value= 0.004). The GSTM1 null genotype was detected in 23.1% of cases and 35% of controls, a difference not statistically significant (OR= 0.557; CI= 0.205-1.515; p-value= 0.252). Distribution of GSTT1 and GSTM1 polymorphisms was also examined according to gender, age and ethnic grouping, these findings revealing no statistically significant differences.

CONCLUSION: Our study reveals a strong correlation between GSTT1 polymorphism and Ph-ve CML, whereas the data for GSTM1 polymorphisms indicates no role in the initial development of the disease. More studies are required to further clarify the roles that these and other genes may play in disease development.

PMID:36305131 | DOI:10.2174/1568009623666221027103845

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Changes in the disease spectrum in the pediatric intensive care units within 2 years before and after the outbreak of coronavirus disease 2019

Zhongguo Dang Dai Er Ke Za Zhi. 2022 Oct 15;24(10):1098-1103. doi: 10.7499/j.issn.1008-8830.2205074.

ABSTRACT

OBJECTIVES: To investigate the changes in the disease spectrum among hospitalized children in the pediatric intensive care units (PICU) within 2 years before and after the outbreak of coronavirus disease 2019 (COVID-19).

METHODS: The related data on disease diagnosis were collected from all children who were hospitalized in the PICU of Affiliated Hospital of Jining Medical College from January 2018 to December 2019 (pre-COVID-19 group) and from January 2020 to December 2021 (post-COVID-19 group). A statistical analysis was performed for the disease spectrum of the two groups.

RESULTS: There were 2 368 children in the pre-COVID-19 group and 1 653 children in the post-COVID-19 group. The number of children in the post-COVID-19 group was reduced by 30.19% compared with that in the pre-COVID-19 group. There was a significant difference in age composition between the two groups (P<0.05). The top 10 diseases in the pre-COVID-19 group by number of cases were respiratory diseases, neurological diseases, sepsis, critical illness, circulatory system diseases, severe neurosurgical diseases, digestive system diseases, unintentional injuries, endocrine system diseases, and tumors. The top 10 diseases in the post-COVID-19 group by number of cases were respiratory diseases, neurological diseases, sepsis, circulatory system diseases, unintentional injuries, endocrine system diseases, severe neurosurgical diseases, acute abdomen, trauma surgical diseases, and digestive system diseases. The proportions of respiratory diseases, critical illness and severe neurosurgical diseases in the post-COVID-19 group were lower than those in the pre-COVID-19 group (P<0.05), while the proportions of unintentional injuries, acute abdomen, endocrine system diseases, trauma surgical diseases and sepsis were higher than those in the pre-COVID-19 group (P<0.05).

CONCLUSIONS: COVID-19 epidemic has led to a significant reduction in the number of children admitted to the PICU, and there are significant changes in the disease spectrum within 2 years before and after the outbreak of COVID-19. Relevant prevention and control measures taken during the COVID-19 epidemic can reduce the incidence of respiratory diseases, neurological diseases, and other critical illness in children, but it is necessary to strengthen the prevention of unintentional injuries and chronic disease management during the epidemic.

PMID:36305109 | DOI:10.7499/j.issn.1008-8830.2205074

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Structural connectivity between the hippocampus and cortical/subcortical area relates to cognitive impairment in schizophrenia but not in mood disorders

J Neuropsychol. 2022 Oct 28. doi: 10.1111/jnp.12298. Online ahead of print.

ABSTRACT

Cognitive impairment in schizophrenia and other psychiatric disorders is a challenge to be overcome in order to maintain patients’ quality of life and social function. The neurological pathogenesis of cognitive impairment requires further elucidation. In general, the hippocampus interacts between the cortical and subcortical areas for information processing and consolidation and has an important role in memory. We examined the relationship between structural connectivity of the hippocampus and cortical/subcortical areas and cognitive impairment in schizophrenia, major depressive disorder and bipolar disorder. Subjects comprised 21 healthy controls, 19 patients with schizophrenia, 20 patients with bipolar disorder and 18 patients with major depressive disorder. Diffusion-weighted tensor images data were processed using ProbtrackX2 to calculate the structural connectivity between the hippocampus and cortical/subcortical areas. Cognitive function was assessed using the Brief Assessment of Cognition in schizophrenia composite score. Hippocampal structural connectivity index was significantly correlated with composite score in the schizophrenia group but not in the healthy control, major depressive disorder or bipolar disorder groups. There were no statistically significant differences in hippocampal structural connectivity index between the four groups. Structural connectivity between the hippocampus and cortical/subcortical areas is suggested to be a pathophysiological mechanism of comprehensive cognitive impairment in schizophrenia.

PMID:36305099 | DOI:10.1111/jnp.12298

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Association between rs1799971 in the mu opioid receptor gene and methadone maintenance treatment response

J Clin Lab Anal. 2022 Oct 28:e24750. doi: 10.1002/jcla.24750. Online ahead of print.

ABSTRACT

OBJECTIVE: Genetic variations can affect individual response to methadone maintenance treatment (MMT) for heroin addiction. The A118G variant (rs1799971) in the mu opioid receptor gene (OPRM1) is a potential candidate single nucleotide polymorphism (SNP) for personalized MMT. This study determined whether rs1799971 is related to MMT response or dose.

METHODS: We recruited 286 MMT patients from a Han Chinese population. The rs1799971 genotype was determined via TaqMan genotyping assay. The genetic effect of this SNP on MMT response or dose was evaluated using logistic regression. A meta-analysis was performed to merge all available data to evaluate the role of rs1799971 in MMT using RevMan 5.3 software.

RESULTS: No statistical significance was observed in the association between the OPRM1 rs1799971 and MMT response or dose in our Chinese cohort. Meta-analysis indicated that the OPRM1 A118G variation was not significantly associated with MMT response or dose requirement.

CONCLUSION: The results suggest that rs1799971 in OPRM1 might not play a critical role alone in influencing MMT response or dose.

PMID:36305091 | DOI:10.1002/jcla.24750

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An evaluation of value-based outcomes for women admitted to a dialectical behaviour therapy intergrated practice unit: a follow-up study

Behav Cogn Psychother. 2022 Oct 28:1-6. doi: 10.1017/S1352465822000467. Online ahead of print.

ABSTRACT

BACKGROUND: An earlier evaluation (Fox et al., ) highlighted reductions in risk behaviours and restrictive practices for women admitted to low secure dialectical behaviour therapy (DBT) unit. Since then, a value-based healthcare model has been adopted.

AIMS: To explore changes in health, social and psychological functioning, risk, quality of life, and in incidents of violence and restrictive practices, over the initial 12-month period of admission to a specialist DBT service.

METHOD: Data were extracted from electronic clinical records for 41 women with emotionally unstable personality disorder admitted to a specialist integrated practice unit (IPU) providing a comprehensive DBT programme. Secondary analysis was conducted on an anonymous dataset of routinely collected outcome measures at baseline admission, and 6 and 12 months post-admission. ANOVAs and pairwise post hoc comparisons, and non-parametric equivalents, were conducted to examine changes in outcomes.

RESULTS: Findings showed statistically significant improvements in mental health scores on the ReQOL (p<.01), global, wellbeing, problems, functioning and risk scores on the COREOM (all p<.01), and severe disturbance, emotional wellbeing, socioeconomic status, risk and need scores on the HoNOS-Secure (all p<.05). Significant reductions in risk behaviours (p<.01) and restrictive practices (p<.01) were also apparent. The most substantiative improvements were largely demonstrated over a 12-month admission period.

CONCLUSIONS: Admission to the DBT IPU yielded significant improvements on outcomes pertaining to quality of life, psychological distress, and risk. Importantly, these are outcomes that aligned with patients’ perceptions of recovery.

PMID:36305087 | DOI:10.1017/S1352465822000467