OBJECTIVES: This systematic review compiles the existing knowledge on lidocaine's PK properties and published popPK models, with a focus on significant covariates.
METHODS: A systematic search on Cochrane CENTRAL, Medline, and EMBASE was performed from inception to June 2023. Original clinical studies that administered IV lidocaine to adults and performed PK analyses using a nonlinear mixed effects modelling approach were included. The quality of the included studies was assessed by compliance with the Clinical Pharmacokinetics (ClinPK) statement checklist.
RESULTS: Seven studies were included, which involved a diverse adult population, including both volunteers and patients with various comorbidities. Lidocaine PK was primarily characterised by a two- or three-compartment model. The volume of distribution at steady state ranged from 66 to 194 L, and the total clearance ranged from 22 to 49 L/h. Despite adjusting for significant covariates like heart failure status, alpha-1-acid glycoprotein, duration of lidocaine infusion, and body weight, each study revealed substantial variability in PK parameters. The potential impact of hepatic or renal function biomarkers on these PK parameters calls for further investigation. Incomplete reporting of key aspects of developed models may hinder the models' reliability and clinical application.
CONCLUSION: The findings emphasise the importance of tailoring drug dosage to ensure the safe and effective use of intravenous lidocaine. Optimal design methodologies may be incorporated for a more efficient identification of important covariates. Utilising contemporary model evaluation methods like visual predictive checks and bootstrapping would enhance the robustness of popPK models and the reliability of their predictions. This comprehensive review advances our understanding of lidocaine's pharmacokinetics and lays the groundwork for further research in this critical area of perioperative pain management. Review protocol registered on 25 August 2023 in PROSPERO (CRD42023441113). This work was supported by the Fundamental Research Grant Scheme, the Ministry of Higher Education, Malaysia (FRGS/1/2020/SKK01/UM/02/2).
METHODS: A single-masked randomized trial was conducted in a single tertiary care center from July 2021 to January 2022. Two hundred fourteen participants aged 18 years or older who were scheduled for outpatient Pipelle endometrial sampling were randomized: 107 each to having a full bladder (by oral water intake) or standard process (without delayed sampling and bladder status not taken into account). Women with known cervical stenosis, gynecologic malignancy, uterine anomalies, leiomyoma distorting the uterine cavity, acute cervicitis, urge bladder dysfunction, intense anxiety, need for anesthesia or analgesic before the procedure, positive pregnancy test, or previous failed office endometrial sampling were excluded. The primary outcome was the insertion failure rate of endometrial sampling at first attempt. Secondary outcomes were pain during procedure, satisfaction score, analgesia use, procedure duration, and need for cervical manipulation. Factoring in a baseline insertion failure rate of 30.0%, relative risk of 0.45, α of 0.05, 80.0% power, and a dropout rate of 10.0%, we needed 107 participants in each arm.
RESULTS: The insertion failure rate was significantly lower in the full bladder group compared with standard process: 25 of 107 (23.4%) compared with 45 of 107 (42.1%) (relative risk 0.56, 95% CI, 0.37-0.84; number needed to treat to benefit 6.0, 95% CI, 3.20-15.70). Pain score (median) during the procedure (interquartile range) was 4 (3-6) compared with 5 (3-8) ( P =.004); patient satisfaction score was 8 (7-9) compared with 7 (4-8) ( P
OBJECTIVE: The systematic review and meta-analysis aims to gather evidence regarding the effectiveness of EALs for WL determination when compared to different imaging techniques along with postoperative pain associated with WL determination, the number of radiographs taken during the procedure, the time taken, and the adverse effects.
METHODS: For the review, clinical studies with cross-over and parallel-arm randomized controlled trials (RCTs) were searched in seven electronic databases, followed by cross-referencing of the selected studies and related research synthesis. Risk of bias (RoB) assessment was carried out with Cochrane's RoB tool and a random-effects model was used. The meta-analysis was performed with the RevMan software 5.4.1.
RESULTS: Eleven eligible RCTs were incorporated into the review and eight RCTs into the meta-analysis, of which five had high RoB and the remaining six had unclear RoB. Following meta-analysis, no significant difference in postoperative pain was found among the EAL and radiograph groups (SMD 0.00, CI .29 to .28, 354 participants; P value = 0.98). Radiograph group showed better WL accuracy (SMD 0.55, CI .11 to .99, 254 participants; P value = 0.02), while the EAL group had 10% better WL adequacy (RR 1.10, CI 1.03-1.18, 573 participants; P value = 0.006).
CONCLUSION: We found very low-certainty evidence to support the efficacy of different types of EAL compared to radiography for the outcomes tested. We were unable to reach any conclusions about the superiority of any type of EAL. Well-planned RCTs need to be conducted by standardizing the outcomes and outcome measurement methods.
METHODS: We conducted one-on-one in-depth interviews with ARM and HD patients aged ≥ 11 years who had undergone surgery at four tertiary referral centers. All interviews were audio-recorded and transcribed verbatim. We analyzed transcripts for recurring themes, and data were collected until data saturation was reached. Three researchers independently coded the transcripts for major themes using thematic analysis approach.
RESULTS: We interviewed 16 participants (11 males) between October 2022 and April 2023. Ages ranged from 11 to 26 years. Five major themes emerged: (1) personal impact (subthemes: physical, emotional and mental health, social, school), (2) impact on family, (3) perceptions of their future (subthemes: relationships, career, state of health), (4) sources of support (subthemes: family, peers, partner), and (5) transition care (subthemes: concerns, expectations). Only females expressed concerns regarding future fertility.
CONCLUSION: This study highlights the evolving problems faced by adolescents and young adults with ARM and HD, especially gender-specific concerns. Our findings can inform efforts to provide individualized care.
OBJECTIVE: The study examines the influence of organizational learning capability, organization age on corporate environmental citizenship.
METHODS: The data were collected from 50 Malaysian construction firms using the survey questionnaire and analyzed by using Partial Least Square Structural Equation Modeling (PLS-SEM).
RESULTS: The finding revealed that organizational learning capability positively related to corporate environmental citizenship. Organization age was not found to moderate such relationships.
CONCLUSION: This study establishes that organizational learning capability encourages construction firms to take risks and explore new opportunities are essential for corporate environmental citizenship implementation. This study highlights the role of organizational learning capability to achieve corporate environmental citizenship irrespective of their organization age for construction firms. This study confirms the logic of Natural Resource Based View (NRBV) theory for predicting organizational learning capability as a critical foundation to build corporate environmental citizenship.
OBJECTIVES: To determine the overall effectiveness and safety of dexmedetomidine for sedation and analgesia in newborn infants receiving mechanical ventilation compared with other non-opioids, opioids, or placebo.
SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, and two trial registries in September 2023.
SELECTION CRITERIA: We planned to include randomised controlled trials (RCTs) and quasi-RCTs evaluating the effectiveness of dexmedetomidine compared with other non-opioids, opioids, or placebo for sedation and analgesia in neonates (aged under four weeks) requiring mechanical ventilation.
DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were level of sedation and level of analgesia. Our secondary outcomes included days on mechanical ventilation, number of infants requiring additional medication for sedation or analgesia (or both), hypotension, neonatal mortality, and neurodevelopmental outcomes. We planned to use GRADE to assess the certainty of evidence for each outcome.
MAIN RESULTS: We identified no eligible studies for inclusion. We identified four ongoing studies, two of which appear to be eligible for inclusion; they will compare dexmedetomidine with fentanyl in newborn infants requiring surgery. We listed the other two studies as awaiting classification pending assessment of full reports. One study will compare dexmedetomidine with morphine in asphyxiated newborns undergoing hypothermia, and the other (mixed population, age up to three years) will evaluate dexmedetomidine versus ketamine plus dexmedetomidine for echocardiography. The planned sample size of the four studies ranges from 40 to 200 neonates. Data from these studies may provide some evidence for dexmedetomidine efficacy and safety.
AUTHORS' CONCLUSIONS: Despite the increasing use of dexmedetomidine, there is insufficient evidence supporting its routine use for analgesia and sedation in newborn infants on mechanical ventilation. Furthermore, data on dexmedetomidine safety are scarce, and there are no data available on its long-term effects. Future studies should address the efficacy, safety, and long-term effects of dexmedetomidine as a single drug therapy for sedation and analgesia in newborn infants.