(1) Although emerging evidence suggests that proton pump inhibitor (PPI)-induced dysbiosis negatively alters treatment response to immune checkpoint inhibitors (ICIs) in cancer patients, no study ...systematically investigates the association between PPIs, ICIs, and chemotherapy; (2) Cochrane Library, Embase, Medline, and PubMed were searched from inception to 20 May 2022, to identify relevant studies involving patients receiving ICIs or chemotherapy and reporting survival outcome between PPI users and non-users. Survival outcomes included overall survival (OS) and progression-free survival (PFS). Network meta-analyses were performed using random-effects models.
-scores, with a value between 0 and 1, were calculated to quantify the treatment ranking, with a higher score suggesting a higher probability of greater effectiveness. We also conducted pairwise meta-analyses of observational studies to complement our network meta-analysis; (3) We identified 62 studies involving 26,484 patients (PPI = 8834; non-PPI = 17,650), including non-small cell lung cancer (NSCLC), urothelial carcinoma (UC), melanoma, renal cell carcinoma (RCC), hepatocellular carcinoma (HCC), and squamous cell carcinoma (SCC) of the neck and head. Eight post-hoc analyses from 18 randomized-controlled trials were included in our network, which demonstrated that, in advanced NSCLC and UC, patients under ICI treatment with concomitant PPI (
-score: 0.2016) are associated with both poorer OS (HR, 1.49; 95% CI, 1.37 to 1.67) and poorer PFS (HR, 1.41; 95% CI, 1.25 to 1.61) than those without PPIs (
-score: 1.000). Patients under ICI treatment with concomitant PPI also had poorer OS (HR, 1.18; 95% CI, 1.07 to 1.31) and poorer PFS (HR, 1.30; 95% CI, 1.14 to 1.48) in comparison with those receiving chemotherapy (
-score: 0.6664), implying that PPIs may compromise ICI's effectiveness, making it less effective than chemotherapy. Our pairwise meta-analyses also supported this association. Conversely, PPI has little effect on patients with advanced melanoma, RCC, HCC, and SCC of the neck and head who were treated with ICIs; (4) "PPI-induced dysbiosis" serves as a significant modifier of treatment response in both advanced NSCLC and UC that are treated with ICIs, compromising the effectiveness of ICIs to be less than that of chemotherapy. Thus, clinicians should avoid unnecessary PPI prescription in these patients. "PPI-induced dysbiosis", on the other hand, does not alter the treatment response to ICIs in advanced melanoma, RCC, HCC, and SCC of the head and neck.
Studies comparing the effectiveness of either adjuvant oral uracil-tegafur (UFT) or intravenous chemotherapy on early-stage (stage I and II) non-small cell lung cancer (NSCLC) patients treated with ...complete surgical treatment remain limited.
From January 2011 to December 2017, patients with early-stage NSCLC (defined as tumor size >3 cm without mediastinal lymph node involvement or any distant metastasis) receiving either adjuvant oral UFT or intravenous chemotherapy after surgical resection were identified from the Taiwan Cancer Registry. Overall survival (OS) and relapse-free survival (RFS) were the primary and secondary outcomes, respectively. Propensity matching was used for controlling confounders.
A total of 840 patients receiving adjuvant therapy after surgery (including 595 oral UFT and 245 intravenous chemotherapy) were enrolled. Before matching, patients using oral UFT had significantly longer OS (HR: 0.69, 95% CI: 0.49-0.98, p = 0.0387) and RFS (HR: 0.79, 95% CI: 0.61-0.97, p = 0.0392) than those with intravenous chemotherapy. A matched cohort of 352 patients was created using 1:1 propensity score-matching. In the Cox regression analysis, the UFT and the matched chemotherapy groups had similar OS (HR: 0.80, 95% CI: 0.48-1.32, p = 0.3753) and RFS (HR: 0.98, 95% CI: 0.72-1.34, p = 0.9149). Among subgroup analysis, oral UFT use was associated with longer RFS among the subgroups of non-drinker (HR: 0.66, 95% CI: 0.34-0.99, p = 0.0478) and patients with stage IB disease (HR: 0.67, 95% CI: 0.42-0.97, p = 0.0341).
This population-based study in the real-world setting of Taiwan demonstrates comparable effectiveness between oral UFT and intravenous chemotherapy in terms of clinical outcomes for early-stage NSCLC patients after surgery.
To implement the ACGME Anesthesiology Milestone Project in a non-North American context, a process of indigenization is essential. In this study, we aim to explore the differences in perspective ...toward the anesthesiology competencies among residents and junior and senior visiting staff members and co-produce a preliminary framework for the following nation-wide survey in Taiwan.
The expert committee translation and Delphi technique were adopted to co-construct an indigenized draft of milestones. Descriptive analysis, chi-square testing, Pearson correlation testing, and repeated-measures analysis of variance in the general linear model were employed to calculate the F values and mean differences (MDs).
The translation committee included three experts and the consensus panel recruited 37 participants from four hospitals in Taiwan: 9 residents, 13 junior visiting staff members (JVSs), and 15 senior visiting staff members (SVSs). The consensus on the content of the 285 milestones was achieved after 271 minor and 6 major modifications in 3 rounds of the Delphi survey. Moreover, JVSs were more concerned regarding patient care than were both residents (MD = - 0.095, P < 0.001) and SVSs (MD = 0.075, P < 0.001). Residents were more concerned regarding practice-based learning improvement than were JVSs (MD = 0.081; P < 0.01); they also acknowledged professionalism more than JVSs (MD = 0.072; P < 0.05) and SVSs (MD = 0.12; P < 0.01). Finally, SVSs graded interpersonal and communication skills lower than both residents (MD = 0.068; P < 0.05) and JVSs (MD = 0.065; P < 0.05) did.
Most ACGME anesthesiology milestones are applicable and feasible in Taiwan. Incorporating residents' perspectives may bring insight and facilitate shared understanding to a new educational implementation. This study helped Taiwan generate a well-informed and indigenized draft of a competency-based framework for the following nation-wide Delphi survey.
Limited studies have investigated risk factors for postoperative urinary retention (POUR) following elective spine surgery. Furthermore, some discrepancies have been found in the results of existing ...observational studies.
This study aimed to review the available literature on risk factors associated with POUR following elective spine surgery.
A systematic review with meta-analysis was performed.
A total of 31,251 patients (POUR=2,858, no POUR=28,393) were included in the meta-analysis.
Demographics, type of elective spine surgery, country, definition of POUR, and potential risk factors for POUR were evaluated.
The Cochrane Library, Embase, and Medline electronic databases were searched to identify relevant studies. Binary outcomes were reported as odds ratio (OR). Weighted mean differences (WMD) or standardized mean differences (SMD), with 95% confidence intervals (CI), were used for meta-analysis of continuous outcomes.
Eleven studies (2 prospective and 9 retrospective) were included in the analysis. Patients with POUR were older than those without POUR (WMD, 7.13; 95% CI, 4.50–9.76). Male patients were found to have an increased risk of POUR (OR, 1.31; 95% CI, 1.04–1.64). The following variables were also identified as significant risk factors for POUR: benign prostatic hyperplasia (BPH; OR, 3.79; 95% CI, 1.89–7.62), diabetes mellitus (DM; OR, 1.50; 95% CI, 1.17–1.93), and previous urinary tract infection (UTI; OR, 1.70; 95% CI, 1.28–2.24). Moreover, longer operative time (WMD, 19.88; 95% CI, 5.01–34.75) and increased intraoperative fluid support (SMD, 0.37; 95% CI, 0.23–0.52) were observed in patients with POUR. In contrast, spine surgical procedures involving fewer levels (OR, 0.75; 95% CI, 0.65–0.86), and ambulation on the same day as surgery (OR, 0.65; 95% CI, 0.52–0.81) were associated with a decreased risk of POUR.
Based on our meta-analysis, older age, male gender, BPH, DM, and a history of UTI are risk factors for POUR following elective spine surgery. We also found that longer operative time and increased intravenous fluid support would increase the risk of POUR. Additionally, multi-level spine surgery may have a negative effect on postoperative voiding.
ALI is a grave medical ailment that manifests as abrupt inflammation of the lungs and diminished oxygen levels. It poses a considerable challenge to the medical fraternity, with elevated rates of ...morbidity and mortality. Our research endeavors to investigate the potential of hibifolin, a flavonoid glucuronide, imbued with potent antioxidant properties, and its molecular mechanism to combat LPS‐induced ALI in mice. The study utilized ICR mice to create an ALI model induced by LPS. Prior to LPS administration, hibifolin was given at 10, 30, or 50 mg/kg, or dexamethasone was given at 1 mg/kg to assess its preventative impact. Changes in lung tissue, pulmonary edema, and lipid peroxidation were analyzed using H&E stain assay, lung wet/dry ratio assay, and MDA formation assay, respectively. Activity assay kits were used to measure MPO activity and antioxidative enzymes (SOD, CAT, GPx) activity in the lungs. Western blot assay was used to determine the phosphorylation of Nrf‐2 and AMPK2 in the lungs. Hibifolin demonstrated a concentration‐dependent improvement in LPS‐induced histopathologic pulmonary changes. This treatment notably mitigated pulmonary edema, lipid peroxidation, and MPO activity in ALI mice. Additionally, hibifolin successfully restored antioxidative enzyme activity in the lungs of ALI mice. Moreover, hibifolin effectively promoted Nrf‐2 phosphorylation and reinstated AMPK2 phosphorylation in the lungs of ALI mice. The results indicate that hibifolin could effectively alleviate the pathophysiological impact of LPS‐induced ALI. This is likely due to its antioxidative properties, which help to restore antioxidative enzyme activity and activate the AMPK2/Nrf2 pathway. These findings are valuable in terms of enhancing our knowledge of ALI treatment and pave the way for further investigation into hibifolin as a potential therapeutic option for lung injuries.
Aims and objectives
To investigate the knowledge of and attitudes towards palliative care for advanced dementia and their associations with demographics among nursing staff, including nurses and ...nursing assistants, in long‐term care settings.
Background
Nursing facilities are places where persons with dementia die; therefore, providing quality end‐of‐life care to residents with advanced dementia is crucial. To date, little attention has been paid to palliative care practice for patients with advanced dementia.
Design
A descriptive, cross‐sectional, survey design was used.
Methods
In total, a sample of 300 nurses (n = 125) and nursing assistants (n = 175) working in long‐term care settings in Taiwan participated in this study. Two instruments were administered: demographic characteristics and responses to the Questionnaire of Palliative Care for Advanced Dementia. Descriptive statistics and multiple regression were used for data analysis.
Results
Overall, the nurses and nursing assistants had moderate mean scores for both knowledge of and attitudes regarding palliative care for advanced dementia. Additionally, nursing staff who were nurses with greater work experience and those who had received palliative care and hospice training had greater knowledge of palliative care. In addition, nursing staff who had received dementia care training and who had worked in nursing homes had higher levels of positive attitudes towards palliative care.
Conclusions
This study indicates the need to provide nurses and nursing assistants with more information about palliative care practice for people with advanced dementia. Particularly, providing education to those who are nursing assistants, who have less working experience, who have not received palliative and dementia care training, and who have not worked in nursing homes can improve overall nursing staff knowledge of and attitudes towards palliative care.
Relevance to clinical practice
Continuing education in principles of palliative care for advanced dementia is necessary for currently practicing nursing staff and should be developed according to their educational background and needs.
A number of simple models containing frequency‐independent elements have been presented to simulate unbounded soil in dynamic soil‐structure interaction problems. Most of the existing models were ...established through a traditional top‐down strategy with significant computational complexities. This study develops an alternative method based on a bottom‐up strategy, in which the optimal element layout is determined by an adaptive refinement procedure considering finite modularized units. This innovation eliminates the need for lengthy procedures to establish simple models. The proposed three‐parameter model is used to simulate the layered soil for rigid foundations undergoing vertical vibration. The accuracy of the model is validated by comparing the magnified responses obtained when a foundation is subjected to harmonic forces with those obtained via theoretical solutions and advanced numerical simulations. The proposed model is found to effectively simulate a layered half‐space and a soil layer on rock. Compared to two existing models, the proposed model performs better and has fewer parameters and a higher degree of adaptivity. Therefore, the adaptivity of simple models obtained using the proposed method may allow simulation of a variety of layered soil systems.
Summary There are limited data on the optimal choice of anticoagulation in multiple myeloma (MM) patients receiving immunomodulatory drugs (IMiDs). We conducted a propensity score‐matched cohort ...study using the TriNetX database to compare the efficacy and safety of factor Xa inhibitors and warfarin in this patient population. Compared to warfarin, factor Xa inhibitors had a similar risk of deep vein thrombosis (hazard ratio HR: 1.11 95% CI: 0.50–2.46) or pulmonary embolism (HR: 1.08 95% CI: 0.59–2.00). There were no differences in the risk of gastrointestinal or intracranial bleeding. Factor Xa inhibitor‐treated patients had lower all‐cause mortality (HR: 0.56 95% CI: 0.36–0.86) compared with warfarin. These data suggest that factor Xa inhibitors had similar safety and efficacy compared with warfarin for MM patients on IMiDs.
Hepatitis D virus (HDV) infection increases the risk of hepatocellular carcinoma (HCC) in the natural course of chronic hepatitis B (CHB) patients. Its role in patients treated with ...nucleotide/nucleoside analogues (NAs) is unclear. We aimed to study the role of hepatitis D in the development of HCC in CHB patients treated with NAs. Altogether, 1349 CHB patients treated with NAs were tested for anti-HDV antibody and RNA. The incidence and risk factors of HCC development were analyzed. Rates of anti-HDV and HDV RNA positivity were 2.3% and 1.0%, respectively. The annual incidence of HCC was 1.4 per 100 person-years after a follow-up period of over 5409.5 person-years. The strongest factor association with HCC development was liver cirrhosis (hazard ratio HR/95% confidence interval CI 9.98/5.11-19.46, P < 0.001), followed by HDV RNA positivity (HR/ CI 5.73/1.35-24.29, P = 0.02), age > 50 years old (HR/CI 3.64/2.03-6.54, P < 0.001), male gender (HR/CI 2.69/1.29-5.60, P: 0.01), and body mass index (BMI, HR/CI 1.11/1.03-1.18, P = 0.004). The 5-year cumulative incidence of HCC was 7.3% for patients with HDV RNA negativity compared to that of 22.2% for patients with HDV RNA positivity (P = 0.01). In the subgroup of cirrhotic patients, the factors associated with HCC development were HDV RNA positivity (HR/CI 4.45/1.04-19.09, P = 0.04) and BMI (HR/CI 1.11/1.03-1.19, P = 0.01). HDV viremia played a crucial role in HCC development in CHB patients who underwent NA therapy.
To improve patient tolerability and satisfaction as well as minimize complications, procedural sedation has been widely used. Propofol is the most widely used agent for induction of anesthesia and ...sedation by anesthesiologists. With a different mechanism compared to propofol, remimazolam is a new short-acting GABA-A receptor agonist. It is an ester-based benzodiazepine. This meta-analysis aims to clarify the efficacy and safety of remimazolam versus propofol for procedure sedation.
Electronic databases were searched for randomized controlled trials (RCTs) comparing efficacy or safety of remimazolam versus propofol. Meta-analysis were conducted using RStudio with "metafor" package with random-effects model.
A total of twelve RCTs were included in the meta-analysis. The pooled results demonstrated that patients with remimazolam for procedural sedation had lower risk of bradycardia (OR 0.28, 95% CI 0.14-0.57), hypotension (OR 0.26, 95% CI 0.22-0.32), and respiratory depression (OR 0.22, 95% CI 0.14-0.36). There was no difference in the risk of developing postoperative nausea and vomiting (PONV) (OR 0.65, 95% CI 0.15-2.79) and dizziness (OR 0.93, 95% CI 0.53-1.61) between the remimazolam and propofol groups. Using remimazolam for procedural sedation is significantly associated with less injection pain compared to propofol (OR 0.06, 95% CI 0.03-0.13). Regarding the sedation efficacy, there was no difference in sedation success rate or time to loss of consciousness, recover and discharge between the remimazolam and the propofol groups.
Based on our meta-analysis, patients receiving procedural sedation with remimazolam had lower risk of bradycardia, hypotension, respiratory depression and injection pain compared with propofol. On the other hand, there was no difference in sedation success rate, risk of PONV, dizziness, time to LOC, recovery and discharge between these two sedatives.
CRD42022362950.
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