The barriers and facilitators for the implementation of clinical practice guidelines in healthcare: an umbrella review of qualitative and quantitative literature.

OBJECTIVES: To identify barriers and facilitators of clinical practice guidelines (CPGs) implementation, and map those factors to the theoretical domains framework (TDF) and behavior change wheel (BCW). METHODS: We conducted an umbrella review of systematic reviews. PubMed, Embase, and the Cochrane Library were searched. Two investigators independently screened the studies, extracted the data, and assessed the methodological quality. The identified barriers and facilitators of CPG implementation were categorized and mapped to the TDF domains and BCW components. RESULTS: Thirty-seven studies were included, and 193 barriers and 140 facilitators were identified. Intrinsic aspects (35 barriers and 28 facilitators) mainly included the CPGs' impracticality, complexity, and inaccessibility. Extrinsic aspects (158 barriers and 113 facilitators) mainly included lack of resources, training, funding, or awareness of CPG content in barriers; audits and feedback; strong leadership and management support; and educating and training about CPGs in facilitators. Environmental context and resources (n = 97, 19.48%) were the most reported barriers in TDF domains. Physical opportunity and social opportunity were the most frequently mentioned models in BCW. CONCLUSION: Multiple barriers and facilitators for healthcare CPG implementation are identified, with further links to TDF and BCW. Future knowledge translation strategies should be developed accordingly in specified health care settings.

Intravenous ibuprofen in postoperative pain and fever management in adults: A systematic review and meta-analysis of randomized controlled trials.

This study aims to evaluate the efficacy and safety of multiple or single-dosage intravenous ibuprofen (IVIB) in managing postoperative pain and fever in adults who are unable to take oral medications. A systematic review and meta-analysis was conducted based on randomized controlled trials (RCTs) comparing IVIB with placebo or other analgesic and antipyretic medications for postoperative pain and fever management. Data were collected from 8 main databases from the inception to June 2022. Risk of bias assessment was performed, and the GRADE methodology was used to assess the certainty of pooled evidence. Primary outcomes included visual analogue scale (VAS) scores within 24 h postoperative and reduction of temperature. Meta-analyses were conducted to calculate the mean difference (MD) or risk ratios (RR) and 95% CIs. As a result, a total of twenty-three RCTs with 3716 participants were included. For postoperative pain, with moderate-to-low certainty evidence, IVIB was associated with lower postoperative VAS scores than placebo, with MD ranging from -3.53 (95% CI, -4.32 to -2.75) at 0 min to -0.96 (95% CI, -1.35 to -0.57) at 24 h. Compared with intravenous acetaminophen, IVIB demonstrated lower VAS scores (MD, -1.54 at 0 min; -0.36 at 24 h). For fever, IVIB showed satisfactory antipyretic efficiency in a short period of time, but no difference was observed between IVIB and intravenous acetaminophen. IVIB was well-tolerated for both pain and fever management. In conclusion, moderate-to-low certainty evidence supports the use of IVIB for adults with postoperative pain and fever who are unable to take oral medications.

Potential antifungal targets based on histones post-translational modifications against invasive aspergillosis.

As a primary cause of death in patients with hematological malignancies and transplant recipients, invasive aspergillosis (IA) is a condition that warrants attention. IA infections have been increasing, which remains a significant cause of morbidity and mortality in immunocompromised patients. During the past decade, antifungal drug resistance has emerged, which is especially concerning for management given the limited options for treating azole-resistant infections and the possibility of failure of prophylaxis in those high-risk patients. Histone posttranslational modifications (HPTMs), mainly including acetylation, methylation, ubiquitination and phosphorylation, are crucial epigenetic mechanisms regulating various biological events, which could modify the conformation of histone and influence chromatin-associated nuclear processes to regulate development, cellular responsiveness, and biological phenotype without affecting the underlying genetic sequence. In recent years, fungi have become important model organisms for studying epigenetic regulation. HPTMs involves in growth and development, secondary metabolite biosynthesis and virulence in Aspergillus. This review mainly aims at summarizing the acetylation, deacetylation, methylation, demethylation, and sumoylation of histones in IA and connect this knowledge to possible HPTMs-based antifungal drugs. We hope this research could provide a reference for exploring new drug targets and developing low-toxic and high-efficiency antifungal strategies.

Conbercept for Treatment of Neovascular Age-Related Macular Degeneration and Visual Impairment due to Diabetic Macular Edema or Pathologic Myopia Choroidal Neovascularization: A Systematic Review and Meta-Analysis.

Background: Conbercept is a new anti-vascular endothelial growth factor (VEGF) drug. Here, we systematically conducted the efficacy, safety, compliance, and pharmacoeconomic evaluation of intravitreal conbercept (IVC) compared with other treatments in patients with neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME), or pathologic myopia choroidal neovascularization (pmCNV). Methods: Databases of PubMed, Embase, Cochrane Library, ClinicalTrials.gov, SinoMed, China National Knowledge Infrastructure, and WanFang Data were systematically searched from the inception to July 27, 2021. Randomized clinical trials and pharmacoeconomic studies comparing IVC with control groups in adults with nAMD, DME, or pmCNV were reviewed and selected. Meta-analyses were performed using the fixed-effects model when pooled data were homogeneous. Heterogeneous data were analyzed using the random-effects model. Primary outcomes included visual improvement rate, mean change in visual acuity or best corrected visual acuity, and pharmacoeconomic outcomes. Additional outcomes were the mean change in fundus examination values, adverse events (AEs), quality-of-life measures, and number of injections. Results: Among 3,591 screened articles, 22 original studies with 1,910 eyes of patients were finally included. For nAMD and DME, IVC was significantly associated with better visual acuity or best corrected visual acuity improvement and fundus quantitative measures than placebo, laser photocoagulation (LP), or intravitreal triamcinolone acetonide (IVT). However, IVC showed non-inferior efficacy to intravitreal ranibizumab (IVR) according to low quality of evidence, and there was lack of trials comparing the priority of IVC to other anti-VEGF regimens. No definitive increased risk of ocular or non-ocular AEs were observed in the study groups. All patients with AEs recovered after symptomatic treatments, and no severe AEs occurred. Patients treated with IVC might have higher quality-of-life scores than those in IVR in nAMD or LP in DME. Additionally, IVC showed cost-utility advantages in nAMD and cost-effectiveness advantages than IVR in pmCNV in China. Conclusion: IVC is well-tolerated and effective for improving vision acuity and quantitative measures in fundus condition in patients with nAMD and DME compared with LP, IVT, and placebo, but gains comparable efficacy to IVR. However, well-designed, large-sample, and long-term evaluation of IVC shall be conducted in additional studies worldwide.

Efficacy and safety of sapropterin dihydrochloride in patients with phenylketonuria: A meta-analysis of randomized controlled trials.

AIMS: The aim of the present meta-analysis was to evaluate the efficacy and safety of sapropterin dihydrochloride in phenylketonuria (PKU) patients. METHODS: The following databases were searched for randomized controlled trials (RCT) regarding PKU patients treated with sapropterin dihydrochloride: PubMed, Embase, Cochrane Library and clinicaltrials. Two authors independently selected studies, assessed the risk of bias and extracted data. The meta-analysis was performed in RevMan 5.3 provided by the Cochrane Collaboration. RESULTS: Four studies met the inclusion criteria. In PKU patients with low blood phenylalanine (Phe) concentration, no significant difference was indicated for the decrease of Phe level (weighted mean difference (WMD) = -7.75 µmol L-1 ; 95% confidence intervals (CI): -82.63 to 67.13, P = 0.84, I2  = 0%), however, the dietary Phe tolerance was significantly improved in the sapropterin group (WMD = 19.89 mg kg-1  d-1 ; 95% CI: 10.26 to 29.52, P < 0.0001, I2  = 0%). In PKU patients with high blood Phe level, sapropterin showed a significant lowering in blood Phe concentration (WMD = -225.31 µmol L-1 ; 95% CI: -312.28 to -138.34, P < 0.00001, I2  = 0%). There was no significant difference for adverse events. CONCLUSIONS: Sapropterin could bring benefit for PKU patients with high or low Phe level, due to Phe reduction in a short time or dietary Phe tolerance improvement respectively. Sapropterin has an acceptable safety profile.