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Cancer Chemotherapy-associated Pigmentation of the Oral Mucosa

In Vivo. 2023 Jul-Aug;37(4):1880-1885. doi: 10.21873/invivo.13280.

ABSTRACT

BACKGROUND/AIM: Oral adverse events caused by anticancer drugs are diverse, but few reports have examined pigmentation of the oral mucosa. The aim of this study was to clarify the prevalence of oral mucosal pigmentation caused by anticancer drugs.

PATIENTS AND METHODS: This single-centre retrospective study investigated patients who underwent oral examination in our hospital during cancer chemotherapy for 3 years from April 1, 2019 to March 31, 2021. Inclusion criteria were patients who could be followed-up for ≥3 months after completing chemotherapy with drugs that caused pigmentation. The primary predictive variable was the cancer chemotherapeutic agent used. The primary outcome variable was pigmentation of the oral mucosa. Collected data were statistically analysed using the χ2 test or Fisher’s exact test, with the level of significance set at p<0.05.

RESULTS: A total of 388 patients were enrolled in the study. Eleven patients (2.8%) showed oral mucosal pigmentation. Drugs causing pigmentation [deposition rate (number of patients with deposits/users)] were TS-1 (combination of tegafur, gimeracil, and oteracil potassium) [12.2% (5/41)], paclitaxel [4.0% (2/50)], gemcitabine [5.0% (1/20)], cyclophosphamide [2.3% (1/42)], carboplatin [1.6% (1/64)], fluorouracil [2.3% (1/43)], and capecitabine [3.4% (1/29)].

CONCLUSION: Oral pigmentation due to cancer chemotherapy was found in 2.8% of patients. TS-1, carboplatin, cyclophosphamide, capecitabine, fluorouracil, gemcitabine, and paclitaxel caused pigmentation of the oral mucosa. Among these, TS-1 was the most likely to cause pigmentation, affecting 12.2% of users.

PMID:37369479 | DOI:10.21873/invivo.13280

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Investigation of miR221 and miR222 as Biomarkers in Non-small Cell Lung Cancer

In Vivo. 2023 Jul-Aug;37(4):1603-1608. doi: 10.21873/invivo.13245.

ABSTRACT

BACKGROUND/AIM: MicroRNAs (miRNA) are a class of small non-coding RNAs of 18-25 nucleotides, which regulate gene expression at the post-transcriptional level by disrupting or blocking translation of messenger RNA targets. Non-small cell lung cancer (NSCLC) represents approximately 85% of all lung cancers. Early and accurate diagnosis of the disease affects the probability of success of treatment. The purpose of this study was to investigate the expression levels of serum specific miRNA221 and miRNA222 as a biomarker in NSCLC.

MATERIALS AND METHODS: Thirty-two NSCLC cases and 30 healthy control cases that were diagnosed at Istanbul Yedikule Chest Diseases and Thoracic Surgery Training Hospital were included in this study. miRNAs were detected using miRNA-specific quantitative real-time-PCR. The relative expression of miRNAs was calculated using the 2-ΔΔCt method.

RESULTS: miR221 and miR222 showed 1.46 and 1.63-fold higher expression in the samples from patients with NSCLC compared to controls, and the difference of expression was statistically significant for miR221 (p=0.000095) but not for miR222 (p=0.084470). In the presence of metastasis in NSCLC patients, miR221 levels were 2.33-fold higher compared to non-metastatic cases (p=0.014), and those of miR221 and miR222 were expressed 1.44 and 1.52-fold higher, respectively, in advanced stage compared to early stage (p=0.000387, p=0.000302).

CONCLUSION: The levels of miR221 and miR222 in the serum of patients could be used as biomarkers for the diagnosis, treatment, and prognosis of NSCLC.

PMID:37369478 | DOI:10.21873/invivo.13245

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Alteration of STK11 Expression Associated With Cholangiocarcinoma Progression

In Vivo. 2023 Jul-Aug;37(4):1638-1648. doi: 10.21873/invivo.13249.

ABSTRACT

BACKGROUND/AIM: Serine/threonine kinase 11 (STK11), a tumor suppressor, controls 5′ AMP-activated protein kinase (AMPK) signaling in a variety of cellular functions. Mutated STK11 has been identified as a novel driver gene that promotes cancer progression. The purpose of this study was to investigate the alteration of STK11 and its correlation with clinicopathological data in cholangiocarcinoma (CCA).

MATERIALS AND METHODS: Gene mutation and expression analyses were performed using cBioportal and Gene Expression Profiling Interactive Analysis version 2 (GEPIA2). qRT-PCR was performed to measure STK11 mRNA levels and immunohistochemistry was performed to investigate STK11 protein expression in CCA tissues.

RESULTS: The results from publicly available cancer datasets showed that 2.7% of CCA cases had STK11 mutations. Most of STK11 gene mutations are of the truncating type and result in low STK11 mRNA and protein expression. We detected a correlation between STK11 mutation status and the tendency for shorter patient survival. The results of qRT-PCR revealed that STK11 mRNA levels were statistically significantly lower in CCA patients with mutated STK11 compared to those with wild-type STK11 (p-value=0.013). Immunohistochemical staining showed high STK11 expression in 43.8% and low expression in 56.2% of CCA tissues examined. Low STK11 protein expression resulted in poor prognosis compared with high STK11 expression, especially in CCA papillary carcinoma. Univariate and multivariate analysis revealed that high STK11 expression was associated with a decreased hazard ratio of patient survival rates (HR=0.696, p-value=0.06 and HR=0.666, p-value=0.04, respectively).

CONCLUSION: Alteration of STK11 mutational or mRNA/protein status might be used as a potential predictive biomarker for the prognosis of the clinical outcomes in CCA patients.

PMID:37369462 | DOI:10.21873/invivo.13249

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Adopting Urinary Tract Infection Guidelines to Promote Antibiotic Stewardship in the Time of Telehealth Medicine

J Dr Nurs Pract. 2023 Jun 27:JDNP-2022-0026.R1. doi: 10.1891/JDNP-2022-0026. Online ahead of print.

ABSTRACT

Background: The most modifiable risk factor contributing to antibiotic resistance is the inappropriate prescription of antibiotics. Urinary tract infections (UTIs) are a common outpatient infection in the United States, with increasing antimicrobial resistance to uropathogens. As empiric UTI treatment is often appropriate, telemedicine offers an opportunity to enhance practice by adopting current clinical practice guidelines. Objective: The project aims to improve appropriate first-line antibiotic choice and decrease urinalysis and urine culture orders in the telehealth management of uncomplicated UTIs. Methods: Chart reviews of women aged 18-65 years diagnosed with an uncomplicated UTI and/or symptoms during a telehealth primary care visit were conducted for a period of 30 days prior to and following a provider educational intervention. Results: Improvement (37.5%-62.1%, p = .133), though not significant, of appropriate first-line antibiotics prescribing postintervention was achieved. There was a minimal (3%) improvement in the appropriate urine labs ordered. Conclusion: Following the intervention, there was not a statistically significant practice change, albeit somewhat of an improvement in the ordering of first-line antibiotics. Adopting evidence-based practice in telehealth could provide an opportunity to improve antibiotic stewardship. Providers are potentially better engaged through the presence of champions, in-person education sessions, and the availability of streamlined algorithms.

PMID:37369453 | DOI:10.1891/JDNP-2022-0026

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The Effect of an Office-Based Strategy on Treatment Outcome and Adoption of Measurement-Based Care Into Psychiatric Treatment at a Nonprofit, Outpatient Clinic

J Dr Nurs Pract. 2023 Jun 27:JDNP-2021-0042.R1. doi: 10.1891/JDNP-2021-0042. Online ahead of print.

ABSTRACT

Background: Measurement-based care (MBC) is a method for demonstrating performance outcomes but is rarely used in behavioral health settings despite it being an evidence-based practice. As psychiatry moves to value-based care and payment for performance, the adoption of MBC will be essential. Objective: The purpose of the study was to test proactive reporting of patient self-reported measurement tool results to providers on treatment outcomes to promote the adoption of MBC. Methods: The study entailed a mixed methods design with a pre-/post-test quantitative measurement of scores on the Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 and a semistructured qualitative interview with providers following data collection. Results: Results showed, during the intervention period, statistically significant decreases in anxiety scores for all patients. Depression symptom decreases trended toward significance for female patients. After initial disregard for scores, all providers found a benefit to continued use of MBC. Conclusions: Identification and removal of barriers can assist in the adoption of evidence-based practices in healthcare. Implications for Nursing: Successful change can be accomplished with minor adjustments to an already-established workflow and a team approach to the process.

PMID:37369450 | DOI:10.1891/JDNP-2021-0042

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Characterization of direct and/or indirect genetic associations for multiple traits in longitudinal studies of disease progression

Genetics. 2023 Jun 27:iyad119. doi: 10.1093/genetics/iyad119. Online ahead of print.

ABSTRACT

When quantitative longitudinal traits are risk factors for disease progression and subject to random biological variation, joint model analysis of time-to-event and longitudinal traits can effectively identify direct and/or indirect genetic association of single nucleotide polymorphisms (SNPs) with time-to-event. We present a joint model that integrates: i) a multivariate linear mixed model describing trajectories of multiple longitudinal traits as a function of time, SNP effects, and subject-specific random effects, and ii) a frailty Cox survival model that depends on SNPs, longitudinal trajectory effects, and subject-specific frailty accounting for dependence among multiple time-to-event traits. Motivated by complex genetic architecture of type 1 diabetes complications (T1DC) observed in the Diabetes Control and Complications Trial (DCCT), we implement a two-stage approach to inference with bootstrap joint covariance estimation and develop a hypothesis testing procedure to classify direct and/or indirect SNP association with each time-to-event trait. By realistic simulation study, we show that joint modelling of two time-to-T1DC (retinopathy, nephropathy) and two longitudinal risk factors (HbA1c, systolic blood pressure) reduces estimation bias in genetic effects and improves classification accuracy of direct and/or indirect SNP associations, compared to methods that ignore within-subject risk factor variability and dependence among longitudinal and time-to-event traits. Through DCCT data analysis, we demonstrate feasibility for candidate SNP modelling, and quantify effects of sample size and Winner’s curse bias on classification for two SNPs identified as having indirect associations with time-to-T1DC traits. Joint analysis of multiple longitudinal and multiple time-to-event traits provides insight into complex trait architecture.

PMID:37369448 | DOI:10.1093/genetics/iyad119

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Clinical parameters affecting survival outcomes in patients with low-grade serous ovarian carcinoma: an international multicentre analysis

Can J Surg. 2023 Jun 27;66(3):E310-E320. doi: 10.1503/cjs.017020. Print 2023 May-Jun.

ABSTRACT

BACKGROUND: Women with low-grade ovarian serous carcinoma (LGSC) benefit from surgical treatment; however, the role of chemotherapy is controversial. We examined an international database through the Ovarian Cancer Association Consortium to identify factors that affect survival in LGSC.

METHODS: We performed a retrospective cohort analysis of patients with LGSC who had had primary surgery and had overall survival data available. We performed univariate and multivariate analyses of progression-free survival and overall survival, and generated Kaplan-Meier survival curves.

RESULTS: Of the 707 patients with LGSC, 680 (96.2%) had available overall survival data. The patients’ median age overall was 54 years. Of the 659 patients with International Federation of Obstetrics and Gynecology stage data, 156 (23.7%) had stage I disease, 64 (9.7%) had stage II, 395 (59.9%) had stage III, and 44 (6.7%) had stage IV. Of the 377 patients with surgical data, 200 (53.0%) had no visible residual disease. Of the 361 patients with chemotherapy data, 330 (91.4%) received first-line platinum-based chemotherapy. The median follow-up duration was 5.0 years. The median progression-free survival and overall survival were 43.2 months and 110.4 months, respectively. Multivariate analysis indicated a statistically significant impact of stage and residual disease on progression-free survival and overall survival. Platinum-based chemotherapy was not associated with a survival advantage.

CONCLUSION: This multicentre analysis indicates that complete surgical cytoreduction to no visible residual disease has the most impact on improved survival in LGSC. This finding could immediately inform and change practice.

PMID:37369443 | DOI:10.1503/cjs.017020

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Association between chronic obstructive pulmonary disease and periodontal disease: a systematic review and meta-analysis

BMJ Open. 2023 Jun 26;13(6):e067432. doi: 10.1136/bmjopen-2022-067432.

ABSTRACT

OBJECTIVES: Studies have suggested contradictory results on the relationship between chronic obstructive pulmonary disease (COPD) and periodontal disease (PD). The aim of this study was to determine whether PD increased the risk of COPD and COPD-related clinical events.

DESIGN: A systematic review and meta-analysis.

DATA SOURCES: PubMed, Ovid EMBASE and Ovid CENTRAL were searched from inception to 22 February 2023.

ELIGIBILITY CRITERIA FOR STUDIES: We included trials and observational studies evaluating association of PD with the risk of COPD or COPD-related events (exacerbation and mortality), with statistical adjustment for smoking.

DATA EXTRACTION AND SYNTHESIS: Two investigators independently extracted data from selected studies using a standardised Excel file. Quality of studies was evaluated using the Newcastle-Ottawa Scale. OR with 95% CI was pooled in a random-effect model with inverse variance method.

RESULTS: 22 observational studies with 51 704 participants were included. Pooled analysis of 18 studies suggested that PD was weakly associated with the risk of COPD (OR: 1.20, 95% CI 1.09 to 1.32). However, in stratified and subgroup analyses, with strict adjustment for smoking, PD no longer related to the risk of COPD (adjusting for smoking intensity: OR: 1.14, 95% CI 0.86 to 1.51; smokers only: OR: 1.46, 95% CI 0.92 to 2.31; never smokers only: OR: 0.93, 95% CI 0.72 to 1.21). Moreover, PD did not increase the risk of COPD-related exacerbation or mortality (OR: 1.18, 95% CI 0.71 to 1.97) in the pooled result of four studies.

CONCLUSIONS: This study demonstrates PD confers no risk for COPD and COPD-related events when strictly adjusted by smoking. Large-scale prospective cohort studies with control of potential confounding factors are warranted to validate the present findings.

PMID:37369414 | DOI:10.1136/bmjopen-2022-067432

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Music to prevent deliriUm during neuroSurgerY (MUSYC): a single-centre, prospective randomised controlled trial

BMJ Open. 2023 Jun 27;13(6):e069957. doi: 10.1136/bmjopen-2022-069957.

ABSTRACT

OBJECTIVES: Delirium is a serious complication following neurosurgical procedures. We hypothesise that the beneficial effect of music on a combination of delirium-eliciting factors might reduce delirium incidence following neurosurgery and subsequently improve clinical outcomes.

DESIGN: Prospective randomised controlled trial.

SETTING: Single centre, conducted at the neurosurgical department of the Erasmus Medical Center, Rotterdam, the Netherlands.

PARTICIPANTS: Adult patients undergoing craniotomy were eligible.

INTERVENTIONS: Patients in the intervention group received preferred recorded music before, during and after the operation until day 3 after surgery. Patients in the control group were treated according to standard of clinical care.

PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome was presence or absence of postoperative delirium within the first 5 postoperative days measured with the Delirium Observation Screening Scale (DOSS) and, in case of a daily mean score of 3 or higher, a psychiatric evaluation with the latest Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria. Secondary outcomes included anxiety, heart rate variability (HRV), depth of anaesthesia, delirium severity and duration, postoperative complications, length of stay and location of discharge.

RESULTS: We enrolled 189 patients (music=95, control=94) from July 2020 through September 2021. Delirium, as assessed by the DOSS, was less common in the music (n=11, 11.6%) than in the control group (n=21, 22.3%, OR:0.49, p=0.048). However, after DSM-5 confirmation, differences in delirium were not significant (4.2% vs 7.4%, OR:0.47, p=0.342). Moreover, music increased the HRV (root mean square of successive differences between normal heartbeats, p=0.012). All other secondary outcomes were not different between groups.

CONCLUSION: Our results support the efficacy of music in reducing the incidence of delirium after craniotomy, as found with DOSS but not after DSM-5 confirmation, substantiated by the effect of music on preoperative autonomic tone. Delirium screening tools should be validated and the long-term implications should be evaluated after craniotomy.

TRIAL REGISTRATION NUMBER: Trialregister.nl: NL8503 and ClinicalTrials.gov: NCT04649450.

PMID:37369412 | DOI:10.1136/bmjopen-2022-069957

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Invasive acupuncture for gastroparesis after thoracic or abdominal surgery: a systematic review and meta-analysis

BMJ Open. 2023 Jun 26;13(6):e068559. doi: 10.1136/bmjopen-2022-068559.

ABSTRACT

OBJECTIVES: This meta-analysis aimed to systematically evaluate the efficacy of acupuncture in treating postsurgical gastroparesis syndrome (PGS) after thoracic or abdominal surgery.

DESIGN: Systematic review and meta-analysis.

DATA SOURCES: Twelve databases (PubMed, Embase, Cochrane Library Cochrane Central Register of Controlled Trials (CENTRAL), Medline (Ovid) (from 1946), Web of Science, EBSCO, Scopus, Open Grey, China National Knowledge Infrastructure (CNKI), Wanfang Database, Chinese Scientific Journals Database (VIP) and China Biology Medicine disc (CBM)) and three registration websites (WHO International Clinical Trials Registry Platform (ICTRP), ClinicalTrials.gov, and Chinese Clinical Trial Registry (ChiCTR)) were searched from the inception to September 2022, and citations of the included literature were screened.

ELIGIBILITY CRITERIA: All randomised controlled trials addressing invasive acupuncture for PGS.

DATA EXTRACTION AND SYNTHESIS: Key information on the included studies was extracted by two reviewers independently. Risk ratio (RR) with 95% CI was used for categorical data, and mean difference with 95% CI for continuous data. The quality of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation. Outcomes were conducted with trial sequential analysis (TSA).

RESULTS: Fifteen studies with 759 patients met the inclusion criteria. Subgroup analyses revealed that compared with the drug group, the drug and acupuncture group had a greater positive effect on the total effective rate (TER) (nine trials, n=427; RR=1.20; 95% CI 1.08 to 1.32; P-heterogeneity=0.20, I2=28%, p=0.0004) and the recovery rate (RCR) (six trials, n = 294; RR = 1.61; 95% CI 1.30 to 1.98; P-heterogeneity=0.29, I2=19%, p<0.0001) of PGS after abdominal surgery. However, acupuncture showed no significant advantages in terms of the TER after thoracic surgery (one trial, p=0.13) or thoracic/abdominal surgery-related PGS (two trials, n = 115; RR=1.18; 95% CI 0.89 to 1.57; P-heterogeneity=0.08, I2=67%, p=0.24) and the RCR after thoracic/abdominal surgery (two trials, n=115; RR=1.40; 95% CI 0.97 to 2.01; P-heterogeneity=0.96, I2=0%, p=0.07). The quality of evidence for TER and RCR was moderate certainty. Only one study reported an acupuncture-related adverse event, in the form of mild local subcutaneous haemorrhage and pain that recovered spontaneously. TSA indicated that outcomes reached a necessary effect size except for clinical symptom score.

CONCLUSION: Based on subgroup analysis, compared with the drug treatment, acupuncture combined drug has significant advantages in the treatment of PGS associated with abdominal surgery, but not with thoracic surgery.

PROSPERO REGISTRATION NUMBER: CRD42022299189.

PMID:37369406 | DOI:10.1136/bmjopen-2022-068559