Influence of genetic variants of opioid-related genes on opioid-induced adverse effects in patients with lung cancer: A STROBE-compliant observational study: Erratum.
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PROVIDER: S-EPMC8702238 | biostudies-literature | 2021 Dec
REPOSITORIES: biostudies-literature
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Influence of genetic variants of opioid-related genes on opioid-induced adverse effects in patients with lung cancer: A STROBE-compliant observational study: Erratum.
Medicine 20211201 51
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Project description:AbstractDespite the dramatic advancement of cancer chemotherapy and immunotherapy, the insufficient progress has been made in basic or translational research on personalization of opioid therapy. Predicting the effectiveness of opioid analgesic therapy and the risk of adverse effects prior to therapy are expected to enable safer and more appropriate opioid therapy for cancer patients. In this study, we compared the incidence of opioid-induced adverse effects between patients with different variants of the genes related to responsiveness to opioid analgesics.Participants were 88 patients with lung cancer who provided general consent for exome sequencing and were treated with morphine or oxycodone at Shizuoka Cancer Center Hospital between April 2014 and August 2018. Incidence rates for 6 adverse effects of opioid therapy (somnolence, nausea, constipation, delirium, urinary retention, and pruritus) were determined and the influence of single nucleotide polymorphisms in coding regions of the opioid μ receptor 1 (OPRM1) (rs1799971), opioid δ receptor 1 (rs2234918), opioid κ receptor 1 (rs1051660), catechol-O-methyltransferase (COMT) (rs4680), dopamine receptor D2 (rs6275), adenosine triphosphate binding cassette B1 (rs1045642), G-protein regulated inward rectifier potassium channel 2 (rs2070995), and fatty acid amide hydrolase (rs324420) genes on those adverse effects were analyzed.Analysis of OPRM1 gene variant status (Asn133Asp A > G) showed that G/G homozygotes were at significantly lower risk of somnolence compared with A allele carriers (0% vs 28.4%; Fisher exact test, P = .005; OR, 0; 95% CI, 0-0.6), and analysis of COMT gene variant status (Val158Met, G > A) showed that G/G homozygotes were at significantly higher risk of somnolence compared with A allele carriers (35.0% vs 10.4%; Fisher exact test, P = .008; OR, 4.5; 95% CI, 1.4-18.1). No relationship between variant status and adverse effects was found for the other genes.These findings demonstrate that OPRM1 and COMT gene variants influence the risk of somnolence as an adverse effect of opioid analgesic therapy.
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Project description:Megsin is a mesangial cell-predominant gene that encodes a serpin family protein which is expressed in the renal mesangium. Overexpression of megsin has been observed in the glomeruli of patients with IgA nephropathy (IgAN). The aim of this study was to evaluate the association of megsin polymorphisms (rs1055901 and rs1055902) with IgAN in a Chinese population.We examined 351 patients with histologically proven IgAN and compared them with 310 age, sex, and ethnicity-matched healthy subjects. Two single nucleotide polymorphisms (SNPs) in megsin were genotyped by Sequenom MassARRAY. SPSS 18.0 was used for statistical analyses, and SNP Stats to test for associations between these polymorphisms and IgAN risk. Odds ratios with 95% confidence intervals were used to assess the relationships.We found that rs1055901 and rs1055902 SNPs were not correlated with susceptibility to IgAN in Northwest Chinese population. Analyses of the relationship between genotypes and clinical variables indicated that in patients with IgAN, rs1055901 was associated with 24-hour proteinuria, an increase in blood pressure, and Lee's grade (P = 0.04, 0.02, and 0.04, respectively), and rs1055902 was associated with 24-hour proteinuria and Lee's grade (P = 0.03 and 0.01, respectively). However, the results showed no association between these gene variants and sex of the patients.These results indicate that megsin gene variants may play a role in the severity, development, and/or progression of IgAN in Northwest Chinese population.
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Project description:The Global Registry of Acute Coronary Events (GRACE) risk score independently predicts major adverse cardiac events (MACEs) in patients with acute coronary syndrome (ACS). This study aims to evaluate whether the level of plasma homocysteine in addition to the GRACE score enhances the predictive value for MACEs in patients with acute coronary syndrome.A total of 361 patients with ACS evaluated at our hospital were included in the study and tested for blood homocysteine levels. We recorded 40 (11.1%) instances of MACE during a median follow-up of 43.3 months (quartile 40.6-44.4 months), including 29 cases (8.0%) of all-cause death and 11 cases (3.1%) of nonfatal myocardial infarction.The GRACE score was significantly associated with homocysteine levels, and multivariate Cox regression analysis showed that both the GRACE risk score and homocysteine content were independent predictors of MACEs (HR 2.63; 95% confidence interval (CI) 1.54 to 4.49; P?<?.001 and 2.27; 1.06 to 4.86; P?=?.035, respectively). Moreover, meta-analysis showed that as the homocysteine level increased, the incidence of MACEs also increased (log-rank 8.41; P?=?.015). GRACE scores adjusted by homocysteine level increased the area under the curve (AUC) from 0.78 to 0.83 (P?=?0.006).Blood homocysteine levels are significantly associated with the GRACE risk score, and using both parameters can further improve risk stratification in patients with acute coronary syndrome.
| S-EPMC6200518 | biostudies-other
Project description:Peroxisome proliferator-activated receptor ? (PPAR?) is an important regulator of glucose and lipid metabolism, and is predominantly expressed in the liver. We aimed to evaluate the effect of donor hepatic PPAR? gene polymorphisms on the development of metabolic disorders following liver transplantation (LT).A total of 176 patients undergoing primary LT were included in this Review Board-approved study. Genomic DNA was extracted from fresh frozen donor liver tissues (biopsy specimens for pathological testing at surgery). Eight single nucleotide polymorphisms in the PPAR? gene were chosen from either the HapMap CHB database or previous reports.The distribution of metabolic disorders differed significantly between the wild-type and variant genotypes of both the rs5767743 and rs5767700 loci (P < 0.05 for all). After an adjustment for other factors (body mass index and tacrolimus blood concentration), the rs5767743 genetic variant was found to be an independent protective factor (P = 0.005, odds ratio = 0.416 per C allele, 95% confidence interval? = 0.225-0.768). When compared with the wild-type genotype, the variant genotypes rs5767743 and rs5767700 correlated with significantly increased PPAR? and CYP3A4 mRNA expression and lower tacrolimus trough concentration/dose ratios (P < 0.05 for all).Donor PPAR? gene polymorphisms influence the susceptibility to metabolic disorders following LT and may also be associated with a fasten tacrolimus metabolism because of elevated CYP3A4 expression.
| S-EPMC4616503 | biostudies-literature
Project description:The evidence regarding the influence of allowing patients to participate in postoperative pain treatment decisions on acute pain management is contradictory. This study aimed to identify the role of patient participation in influencing pain-related patient-reported outcomes (PROs). This is a cross-sectional study. The data were provided by PAIN OUT (www.pain-out.eu). A dataset specific to adult Chinese patients undergoing orthopedic surgery was selected. The PROs were assessed on postoperative day 1. The patient participant was assessed using an 11-point scale. Participants who reported >5 were allocated to the "participation" group, and those who reported ≤5 were allocated to the "nonparticipation" group. A 1:1 propensity score matching was conducted. The primary outcome was the desire for more pain treatment. All other items of PROs were the secondary outcomes comprising pain intensity, interference of pain with function, emotional impairment, adverse effects, and other patient perception. From February 2014 to November 2020, 2244 patients from 20 centers were approached, of whom 1804 patients were eligible and 726 pairs were matched. There was no significant difference between the groups in the desire for more pain treatment either before (25.4% vs 28.2%, risk ratio [95% CI]: 0.90 [0.77, 1.05], P = .18) or after matching (26.7% vs 28.8%, risk ratio [95% CI]: 0.93 [0.79, 1.10], P = .43). After matching, patients in the participation group reported significantly better PROs, including pain intensity (less time spent in severe pain [P < .01]), emotional impairment (less anxiety [P < .01]), interference with function (less interference with sleep [P < .01]), adverse effects (less drowsiness [P = .01]), and patient perception (more pain relief [P < .01] and more satisfaction [P < .01]), than the nonparticipation group. Patient participation in pain treatment decisions was associated with improved pain experience but failed to mitigate the desire for more treatment.
| S-EPMC9509085 | biostudies-literature
Project description:Chronic myeloproliferative disorders such as polycythemia vera (PV), essential thrombocytosis (ET), and idiopathic myelofibrosis arise from clonal proliferation of neoplastic stem cells in the bone marrow. Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that have potential to degrade all types of extracellular matrix (ECM) and also play a role in remodeling of the ECM. It is known that MMPs play a role in bone marrow remodeling.The primary goal of our study is to explore the relationship between chronic myeloproliferative diseases and some of MMP gene polymorphisms. The demonstration of a relationship will help to understand whether these polymorphisms may be a potential early diagnosis marker of the diseases.Patients were selected from outpatient clinics of Turgut Ozal University Hospital, Ankara, Turkey, between December 2010 and May 2011. Twenty-eight patients that previously diagnosed and followed-up with PV, 17 with secondary polycythemia (SP), and 12 with ET were enrolled in the study, along with a control group of 22 healthy people.DNA was isolated from peripheral blood. Using polymerase chain reaction-restriction fragment length polymorphism method, MMP2 and MMP9 gene polymorphisms were analyzed with agarose gel electrophoresis. There was a statistically significant difference between the study groups and the control group in terms of Gln279Arg polymorphisms rates of MMP9. The highest MMP9 Gln279Arg polymorphism rate was observed in the ET group. But nobody from the control group had polymorphic MMP9. There was no statistically significant difference between the groups in terms of MMP2-735 C > T polymorphism rates.In conclusion, MMP9 gene Gln279Arg polymorphism was associated with ET, SP, and PV diseases. Hence, we believe that these gene polymorphisms may play a role in the mechanism of bone marrow fibrosis and may be a factor that increases the risk of thrombosis. Illumination of the molecular basis of the relationship between MMP-thrombosis and MMP-fibrosis provides a better understanding of the pathophysiology of PV and ET diseases and will allow new approaches to diagnosis and treatment.
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Project description:Background and aimPreferences of service users is an important consideration for developing health-care services. This study aimed to assess the experiences of the patients with substance use disorders who were admitted to a tertiary health-care facility in India.MethodThis cross-sectional sectional study recruited adult inpatients who stayed for a period of 7 days or more. The Picker Patient Experience questionnaire (PPE-15) was used to gather information about the views of the patients about the care received at the center.ResultsResponses were available from 113 inpatients. Majority of the participants were males and were dependent on opioids. The experience was generally positive about being treated with respect and dignity and access to information. The participants were most satisfied with opportunity being given to discuss anxiety and fear about the condition or treatment (91.2% positive response) and least satisfied with differences in responses from doctors and nurses (43.4% positive response). Further attention seemed desired about communication with the staff and patients' involvement in their own treatment-related decision-making.ConclusionEfforts need to be made to involve patients in their own treatment-related decision-making and to improve communication with the treatment team. This might lead to better involvement in treatment process, which could enhance the treatment outcomes in this vulnerable population.
| S-EPMC6739683 | biostudies-literature
Project description:Burkholderia pseudomallei is the causative agent of meliodosis, and the cases in China are gradually increasing. The present retrospective study aimed to surveil the molecular epidemiological characteristics and antibiotic resistance of B pseudomallei isolates. B pseudomallei strains were isolated and verified from meliodosis patients with relevant epidemiological information from 2004 to 2016 in Hainan, China. Pulsed-field gel electrophoresis based on Spe I digestion was carried out, and antimicrobial resistance of B pseudomallei strains was observed against 9 frequently-used antimicrobials. A total of 164 B pseudomallei isolates were successfully divided into 60 pulsed-field gel electrophoresis (PFGE) patterns, including 33 clusters and 27 single types, at an 85% similarity level. The isolates also exhibited a high level of ceftazidime resistance rate (12.8%, 21/164). B pseudomallei strains were mainly heterogenous with no predominant type, but there were some clonal populations, dominate clusters prevalent and the resistance rates of cephems antimicrobial increased significantly between 2004 and 2016 along with the number of melioidosis cases collected in Hainan (cefoperazone-sulbactam [SCF], rs = 0.96, P = .04; ceftazidime [CAZ], rs = 0.98, P = .01). In conclusion, this study will help to enhance our understanding of molecular characteristics and antibiotic resistance of B pseudomallei.
| S-EPMC6831382 | biostudies-literature
Project description:To explore whether weight-age (W-A) could be applied in clinical practice, this study was designed to verify the normalization ability of W-A by the data from another medical center, and to access the influence of the normalization on glomerular filtration rate (GFR) values in renal patients.Both plasma clearance (pGFR) and camera-based (gGFR), which were separately scaled to W-A and body surface area (BSA), were measured for patients with diffuse renal diseases. The patients (n?=?298) were stratified according to the Chinese body mass index (BMI) criteria and were staged according to the Kidney Disease Outcome Quality Initiatives guideline based on gGFR and pGFR separately.The indices of intraclass correlation coefficient (ICC), concordance correlation coefficient (CCC), and ratio of residual standard deviation to pooled standard deviation (RSD/PSD) suggested that, for all patients and each BMI stratum, W-A was obviously better than BSA in scaling GFR. Both under pGFR or gGFR renal stages, only small amount of the patients encountered stage migrations from BSA to W-A scaled stages. The differences between any 2 of the unscaled, BSA scaled, and W-A scaled gGFR (or pGFR) were not obviously changed. Additionally, in some strata, W-A normalization is better than BSA normalization in decreasing the median bias between pGFR and gGFR.W-A is better than BSA in scaling GFR without obvious modifying GFR values and can be applied in routine clinical practice.
| S-EPMC4998260 | biostudies-literature
Project description:There is limited information about the effects of corticosteroids on severe drug-induced liver injury (DILI). This study aimed to investigate the efficacy and safety of prednisone in severe DILI.Ninety patients with severe DILI were enrolled and studied retrospectively. They were divided into prednisone (n = 66) and control groups (n = 24), undergoing the same treatment regimen except that patients in the prednisone group received a median daily dose of 40 mg prednisone. The primary endpoint was severity reduction (serum total bilirubin [TBIL] <86 μmol/L).During the study, the cumulative rates of severity reduction at 4-, 8-, and 12 days were comparable between the 2 groups (prednisone versus control: 7.6%, 33.3%, and 60.6% versus 12.5%, 37.5%, and 66.7%, P = .331), and were markedly lower in the high-dose group than in the low-dose group (0%, 28.6%, and 35.7% versus 9.6%, 34.6%, and 67.3%, P = .012) or in the control group (0%, 28.6%, and 35.7% versus 12.5%, 37.5%, and 66.7%, P = .023). The 30-day overall survival rate in the prednisone group was significantly higher than in the control group (100% versus 91.7%, P = .018). Serum bilirubin and transaminase values gradually decreased in both groups, which were not significantly different mostly. Cox-regression models revealed that baseline TBIL (hazard ratio: 0.235; 95% confidence interval: 0.084-0.665; P = .006) was the only predictor for severity reduction. No severe adverse event was noted in both groups.Prednisone therapy is safe but not beneficial, and even detrimental at a daily dose > 40 mg for the treatment of severe DILI.
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