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Ethical Approval
This study was approved by the institutional review board and retrospectively registered at
PMC9851777
Conflicts of Interest
The authors declare that there are no conflicts of interest.
PMC9851777
Supplementary Materials
drowsiness, Pain, postoperative nausea and vomiting, pain, PONV
REGRESSION, POSTOPERATIVE COMPLICATIONS
Supplementary material: the supplementary material was the raw data of this study.Click here for additional data file.The CONSORT study participant flow diagram.(a) Pain score at rest. (b) Pain score upon movement. (c) Pain score upon movement in the combination group. (d) Cumulative dose of sufentanil. (e) High-sensitivity C-reactive protein (hs-CRP). (f) Knee range of motion (ROM). ▲ indicates a significant difference compared with a previous time point in the combination group, which suggests that the pain scores upon movement in the combined group significantly decreased continuously over time. a indicates a significant difference compared with the placebo group (Linear regression analysis. The mean pain score upon movement within 48 hours after surgery was the independent variable (General characteristics of the patients.ASA, American Society of Anesthesiologists. HSS score, hospital for special surgery rating scale. VAS, visual analog scale (0: no pain to 10: worst possible pain); Pain upon movement: pain upon maximum flexion. Difference is significant at the VAS pain scores and the cumulative dose of sufentanil.VAS, visual analog scale (0: no pain to 10: worst possible pain); pain upon movement: pain upon maximum flexion; difference was significant at the hs-CRP level and knee functional indicator.hs-CRP, high-sensitivity C-reactive protein; ROM, knee range of motion. a means there was a significant difference compared with the placebo group (Incidence of postoperative complications.Sedation was scored as 0 = no sedation; 1 = intermittent drowsiness; 2 = patient drowsy but arousable to verbal stimulus; and 3 = impossible to arouse verbally. PONV: postoperative nausea and vomiting; the difference was significant at the
PMC9851777
Keywords
PMC10689247
Malaria elimination and control over the past decades
Malaria
PARASITIC DISEASE, MALARIA
Malaria is a parasitic disease transmitted by infected
PMC10689247
Rethinking malaria
malaria
MALARIA
High- and low-burden countries require different approaches to increase the impact of malaria-related interventions. Value-based health services delivery is a relatively new key term for sub-national tailoring of malaria control strategies in line with the needs of local communities
PMC10689247
CHW as an extension of health care- and surveillance systems
malaria
MALARIA, DISEASE, DISEASES
An important factor contributing to preventable malaria morbidity and mortality, as well as morbidity and mortality from other preventable diseases is a lack of access to the healthcare system CHWs often are lay people trained on program-specific health care interventions. Due to their access to hard-to-reach communities, CHWs can contribute valuably to disease prevention and control and thus be an important addition to national malaria control programs As CHWs are often embedded in and trusted by their communities, they can serve as resource for their community's challenges. In the absence of surveillance systems for post-marketing pharmacovigilance, they can feed back important information about drug safety and other relevant observations to regulators which can help identify and understand reduced effectiveness of therapies or safety concerns.
PMC10689247
Community health workers in clinical research
RECRUITMENT
In research, CHWs can be deployed to improve post-hospital outcomes or adherence to routine medical interventions An equally important basis for the successful conduct of clinical research projects is a trusting relationship between CHWs and communities. As CHWs often live in the communities they serve, CHW-centered recruitment may be facilitated by their inside knowledge of comorbidities, pregnancies, and other important medical histories of the individuals they are responsible for.
PMC10689247
Importance of adequate training
An important prerequisite for a functional collaboration with and inclusion of CHWs into the health care system is provision of adequate protocols and training [
PMC10689247
The role of CHW in the CANTAM-
malaria, HIV or viral hepatitis
MALARIA
The CANTAM-The trial was conducted at six centers in five African countries with the main objective to assess the safety of PA in malaria patients with underlying liver function abnormalities, comorbidities like HIV or viral hepatitis, and in children under 1 year of age To evaluate safety and real-world effectiveness, participants were primarily followed up by CHWs trained specifically in the trial procedures. Depending on the country's strategies, most CHWs were recruited either from a pre-existing pool or through structured processes set up by e.g., the Ministry of Health. CHWs needed to be rapidly deployable and serve as a mobile link between the participants living at varying distances from the study centers and the investigator teams. They provided oversight of participant safety while intervening as little as possible with the participants’ healthcare-seeking behavior to mirror the real-world patient-doctor interactions in the management of uncomplicated malaria.
PMC10689247
Community health worker training and participant follow-up in the CANTAM-
bleeding, contusions, nausea;, fatigue, fever, malaria, stomachache, faintness, hepatotoxicity, Hypersensitivity, rash, jaundice, pruritus, breathlessness, ill, flushing
BLEEDING, ADVERSE EVENTS, MALARIA, HYPERSENSITIVITY, LOSS OF APPETITE, REMISSION, MALARIA, EVENTS, HYPERSENSITIVITY
To neither jeopardize participants’ reporting behavior nor overlook important safety signals, continuous training was paramount for CHWs to remain alert of their responsibilities. Training was given during the site initiation visit and included an explanation of material and procedures as well as role play. Role plays were used to simulate real-life scenarios and discuss solutions. CHWs who had previously been involved in studies with home-based participant follow-up shared their experiences with the others. Re-trainings were provided by the site investigators during formalized training sessions or regular team meetings, and during monitoring visits as needed.For self-training purposes, CHWs received a “memory aid” to carry with them for reference but they were not supposed to use it during direct participant contact to avoid any bias in participants’ reporting. The memory aid contained a general part, with a description of the seriousness criteria and the query whether treatment or medical attention was necessary. If any of the listed was answered with “yes”, the CHW was required to inform the investigator immediately and direct the participant to the study center to receive further medical attention. The second part of the memory aid focused on adverse events of special interest, these being hepatotoxicity and hypersensitivity. Warning signs for hepatotoxicity included fatigue of unusual intensity that remained after cure of the malaria episode or worsened; fever that either remained after cure of the malaria episode or returned after initial remission; nausea; vomiting; loss of appetite; stomachache; pruritus or skin rash. In addition, images of dark urine; putty or mastic colored stools; jaundice, and contusions, indicating spontaneous sub-cutaneous bleeding, were provided to facilitate CHWs in recognizing these signs. Hypersensitivity events were identified by any signs of flushing; the appearance of wheals/urticaria; breathlessness and faintness and/or decrease in blood pressure. CHWs found the memory aid to be a useful and self-explanatory tool.To reflect real-life conditions as much as possible and avoid over-reporting of adverse events, suggestive questions were not permitted. Instead, the CHW was instructed to ask open questions and document (1) whether the participant noticed anything special or abnormal concerning their health status since the last contact with study staff or since the study drug intake and (2) whether the CHW noticed anything special or abnormal in the participant. In case the participant reported specific medical conditions or the CHW observed danger signs, they were referred to the study center for further investigation.Home visits also included additional examinations within the CHW competence in the respective country. On day 7 ± 1 day, measurement of body temperature; enquiry of pregnancy status; assessment of compliance to study drug intake, and documentation of signs and symptoms of malaria and new and concomitant medication were performed. In addition, at day 28 ± 2 days, measurement of body temperature; pregnancy test where relevant; preparation of thick blood smear and blood spots on filter paper were conducted. Where CHWs were not allowed to collect blood, they were accompanied by a laboratory technician. If malaria or pregnancy was suspected, the CHW was instructed to refer the participant to the study center immediately.Source documents for all home visits of the day, i.e., the standardized notes taken by the CHW, were reviewed by and discussed with the site investigator on the CHW's return to the study center. The investigator was responsible for the final judgment, documentation on the case report form, and further actions for adverse events. Based on this, if the investigator spotted the need for further medical evaluation or treatment, the participant was notified and instructed to attend the study center for further investigation. Malaria microscopy was performed on all thick blood smears at the center to assess response to the study treatment. In case a blood smear was positive participants were notified and directed to the study center to receive antimalarial rescue treatment.Overall, CHWs appeared to be highly trusted by the target population and participants referred their peers to the CHWs for study participation when they were ill. This trust was largely based on the CHWs’ long-term activities in the communities and/or the fact that the CHWs were trusted community members. None of the study sites reported barriers when talking to participants. Challenges sometimes arose when participants lived far from the study site when participants’ residential areas were not well mapped, or when participants were not at home for scheduled visits. This was mitigated by calling participants, providing CHWs with cars or other means of transport, and being creative in describing participants’ homes (e.g., near the banana market, etc.).
PMC10689247
Other examples of community health workers-centered research
CHW-centered approaches are also being implemented by other research projects and surveillance programs. An example of a CHW-centered research project is the MiMBa Pregnancy Registry to assess the safety of antimalarial use in pregnancy
PMC10689247
Conclusion
malaria
MALARIA
CHW involvement can be key to targeting hard-to-reach and vulnerable populations and constitutes a crucial role in malaria control and elimination in sub-Saharan Africa. In the CANTAM-The CANTAM-
PMC10689247
Declarations of competing interest
MALARIA
IBF and SD are full-time employees at Medicines for Malaria Venture, JS is a full-time employee at Shin-Poong Pharmaceutical and SAB is a consultant paid by Shin-Poong Pharmaceutical. The other authors declare no conflict of interest.
PMC10689247
References
PMC10689247
Funding
MALARIA
This work was supported by Medicines for Malaria Venture (MMV), Geneva, Switzerland. A full list of donors to MMV is available on its website [
PMC10689247
Ethical approval
Ethical approval was not required for this manuscript.
PMC10689247
Author contributions
Conceptualization: IBF, SAB, MG, SD, GMN; Data curation: not applicable; Formal analysis: not applicable; Funding acquisition: SD, IBF, JS, SAB; Investigation: MG; Methodology: MG, IBF, SD, GMN; Project administration: SD, MG, FN, AAA, GTL, GMN, SBA, JDB, NYN; Resources: SD, IBF, SAB, JS, PGK, FN, AAA, GTL, GMN, SBA, JDB; Software: not applicable; Supervision: IBF, SAB, MR, PGK, GMN; Validation: IBF, SD, SAB, GMN, JS; Visualization: writing – original draft: MG; Writing – review & editing: IBF, SAB, SD, GMN, PGK, AAA, GTL, SBA, JDB, NYN, MR, JS, FN; All authors contributed to the development of the paper, provided critical review, and approved the final version for submission. All authors had access to all the data in the study and accept responsibility for submitting it for publication. No medical writer or editor was involved in the creation of this manuscript.
PMC10689247
Purpose
advanced/metastatic
ASTRIS study aimed the largest to evaluate the effectiveness and safety of second- or higher-line osimertinib in patients with advanced/metastatic epidermal growth factor receptor (
PMC10423102
Methods
Adults with
PMC10423102
Results
TTD
EVENTS, ADVERSE EVENT
A total of 1350 patients were included. Response rate was 55.7% (95% confidence interval [CI] 0.53–0.58). The median PFS and the median TTD were 11.7 months (95% CI 11.1–12.5) and 13.9 months (95% CI 13.1–15.2), respectively. Overall, 389 patients (28.8%) had at least one protocol-specified adverse event (AE); AEs of interstitial lung diseases/pneumonitis-like events and QT prolongation were reported in 3 (0.2%) and 59 (4.4%) patients, respectively.
PMC10423102
Conclusion
T790M-positive NSCLC
EVENTS
Osimertinib was effective in Chinese patients with T790M-positive NSCLC who had progressed after first- or second-generation EGFR-TKI in real-word setting and the results were consistent with ASTRIS study overall population and AURA studies. No new safety signals or events were identified.
PMC10423102
Clinical trial number
NCT02474355.
PMC10423102
Keywords
PMC10423102
Introduction
NSCLC, deaths, Lung cancer
LUNG CANCER, NSCLC
Lung cancer is the leading cause of cancer-related deaths worldwide, with a mortality rate of 18% (Sung et al. Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are the recommended first-line treatment strategy for patients with advanced NSCLC harboring the Osimertinib is an oral, irreversible EGFR-TKI that selectively inhibits both
PMC10423102
Materials and methods
PMC10423102
Study design
ASTRIS is an open-label, single-arm, multinational, real-world study. The study was approved by the Institutional Review Board/Ethics Committee and conducted in accordance with the International Conference on Harmonization Good Clinical Practice guidelines, the Declaration of Helsinki, local regulatory requirements, and the policy on bioethics and human biologic samples of AstraZeneca. The study protocol was designed by the sponsor (AstraZeneca, Södertälje, Sweden) in collaboration with investigators and is registered at clinicaltrials.gov (NCT02474355). All patients provided their written informed consent.
PMC10423102
Participants
NSCLC, ILD
INTERSTITIAL LUNG DISEASE, SYSTEMIC DISEASE, NSCLC, CNS METASTASES
Chinese adults (≥ 18 years) with locally advanced (stage IIIB) or metastatic (stage IV) NSCLC (based on TNM staging, AJCC 7th edition), WHO performance status (PS) score of 0–2, confirmed T790M mutation and who had received prior EGFR-TKI therapy in any treatment line were included in the study. Patients with asymptomatic or stable CNS metastases were allowed.Patients with a history of interstitial lung disease (ILD) or symptoms of uncontrolled/severe systemic disease were excluded. The cardiac exclusion criteria were either a mean resting corrected QT interval > 470 ms as per Fredericia formula (Cadogan
PMC10423102
Interventions
Patients were given 80 mg osimertinib orally once daily and were continued on treatment if they still receiving clinical benefit, as judged by the investigator.
PMC10423102
Study outcomes and endpoints
death, TTD
ADVERSE EVENTS, EVENTS
The effectiveness and safety data were collected at the treatment visit (every 6 weeks) and termination visit (30 days post last dose). The outcomes included investigator-assessed response rate, PFS, time-to-treatment discontinuation (TTD) and safety profile. This study only collected the incidence of protocol-defined adverse events (AEs), including serious adverse events (SAEs), AEs of special interest (ILD or pneumonitis-like events and QTs prolongation events), and AEs leading to dose modification or discontinuation or death.
PMC10423102
Statistical analysis
TTD
ADVERSE EVENT
All time-to-event outcomes and safety analyses were performed on the full analysis set (FAS) that included all patients receiving at least one dose of osimertinib. The response rate analyses were assessed on the response evaluable set, defined as those patients in the FAS who had at least one documented response assessment by the investigator. Patients who transitioned to a commercial product following national reimbursement were censored at the time of this transition. Time-to-event outcomes (PFS and TTD), including their 95% CIs were estimated using the Kaplan–Meier plot. All AEs and SAEs leading to study drug discontinuation or dose modification were summarized by Medical Dictionary for Regulatory Activities (MedDRA) preferred term (Version 23.1) and Common Terminology Criteria for Adverse Events (CTCAE) class. All statistical analyses were performed using SAS® (SAS Institute, North Carolina) version 9.2 (or later).
PMC10423102
Results
PMC10423102
Progression-Free survival
death
DISEASE PROGRESSION
Disease progression or death was reported in 1059 patients (78.4%). The median PFS was 11.7 months (95% CI 11.1–12.5) for the overall population. The median PFS by tissue testing and plasma testing was 13.1 months (95% CI 12.5–13.8) and 10.0 months (95% CI 9.5–11.0), respectively (Fig. Kaplan-Meir plot for PFS in
PMC10423102
Clinical response rate
T790M-positive
CNS METASTASES
Response evaluation was available from 1322 patients; of them, 736 patients (55.7%) had an investigator-assessed best overall response as “responding” (95% CI 52.9–58.4). The response rate in patients with T790M-positive status by tissue testing and plasma testing was 60.4% (95% CI 56.9–63.9) and 48.9% (95% CI 44.6–53.2), respectively. The response rate in patients with and without CNS metastases was 58.2% (95% CI 52.7–63.6) and 57.9% (95% CI 53.0–62.6).
PMC10423102
Time to treatment discontinuation
T790M-positive, TTD
Of 1350 enrolled patients, 349 patients (25.9%) transitioned to the commercial drug at the time of national reimbursement; the remaining 1001 patients (74.1%) discontinued the treatment, with a median TTD of 13.9 months (95% CI 13.1–15.2). The median TTD in patients with T790M-positive status by tissue testing and plasma testing was 16.1 months (95% CI 15.2–16.8) and 11.6 months (95% CI 11.0–12.6), respectively (Fig. Kaplan-Meir plot for TTD in
PMC10423102
Discussion
CNS METASTASES
This study aimed to assess the effectiveness and safety of second-line or higher osimertinib in a real-world setting in patients with The median PFS observed in our study was 11.7 months (95% CI 11.1–12.5), which was comparable with that reported in ASTRIS global population (Marinis et al. The effectiveness was also analyzed by the presence of CNS metastases. The benefit of osimertinib treatment was also found to be extended to the subgroup of Chinese Osimertinib was well-tolerated and no new safety signals were observed in our study. The safety profile was similar to that observed in the ASTIRS global population (Marinis et al. Although our study gives a better understanding of the effectiveness and safety aspects of osimertinib in a real-world scenario in a Chinese setting complementing the results of a global setting, certain limitations must be taken care of before drawing any conclusion. Considering the fact that due to many patients transitioning to commercial supply following national reimbursement as per ASTRIS protocol, the follow-up was incomplete and the exposure may have been underestimated. Also, the response rates were investigator-assessed as per institutional standards. Not all patients were assessed at baseline for the CNS metastases and the types of samples used and the availability of the type of testing methods for T790M at different study sites could also have introduced bias in the study results.
PMC10423102
Acknowledgements
The authors thank all the patients and their families, investigators, trial staff, and participants of the study. The authors also thank Dr. Tanushree Goswami and Dr. Ramandeep Singh from Indegene Pvt. Ltd. for providing medical writing and editorial services in accordance with Good Publication Practice (GPP3) guidelines.
PMC10423102
Author contributions
W-LZ, C-YZ
QZ conceptualization, methodology, and writing-review and editing. H-LZ writing-review and editing. L-YJ writing-review and editing. Y-KS writing-review and editing. YC Writing-review and editing. J-MY writing-review and editing. C-CZ writing-review and editing. YH writing-review and editing. Y-PH writing-review and editing. Z-AL writing-review and editing. Y-YP writing-review and editing. W-LZ writing-review and editing. Yong Song: writing-review and editing. GW writing-review and editing. G-YC writing-review and editing. YL writing-review and editing. C-YZ writing-review and editing. Y-PZ writing-review and editing. YC writing-review and editing. SL writing-review and editing. C-LW writing-review and editing. J-YZ writing-review and editing. Y-PL writing-review and editing. J-XH writing-review and editing. JW writing-review and editing. Y-LW writing-review and editing.
PMC10423102
Funding
This study was supported by AstraZeneca (Södertälje, Sweden).
PMC10423102
Data availability
The datasets that were used and analysed during the current study are available from the corresponding authors on reasonable request.
PMC10423102
Declarations
PMC10423102
Conflict of interest
ONCOLOGY
QZ reports honoraria from AstraZeneca, Boehringer Ingelheim, BMS, Eli Lilly, MSD, Pfizer, Roche, and Sanofi. C–C Z reports personal fees from Lily China, Sanofi, BI, Roche China, MSD, Qilu, Hengrui, Innovent Biologics, C-stone, LUYE Pharma, TopAlliance Biosciences Inc, Amoy Diagnostics. SL received research support and speaker fees from AstraZeneca, Hutchison, BMS, Heng Rui, Beigene, Roche, and Hansoh and acted as an advisor and consultant with AstraZeneca, Pfizer, Boehringer Ingelheim, Hutchison MediPharma, Simcere, ZaiLab, GenomiCare, Yuhan Corporation, PrIME Oncology, Menarini, and Roche. Y-LW reports advisory services for AstraZeneca, Boehringer Ingelheim, Novartis, Takeda; personal fees from AstraZeneca, Beigene, Boehringer Ingelheim, BMS, Eli Lilly, MSD, Pfizer, Roche, Sanofi; and grants from AstraZeneca, Boehringer Ingelheim, BMS, Hengrui, and Roche. The remaining authors have no conflicts of interest to declare.
PMC10423102
Ethical approval
The study was conducted in accordance with the International Conference on Harmonization Good Clinical Practice guidelines, the Declaration of Helsinki, local regulatory requirements, and the policy on bioethics and human biologic samples of AstraZeneca.
PMC10423102
Consent to participate
Informed consent was obtained from all the participants included in the study.
PMC10423102
Consent to publish
Not applicable.
PMC10423102
References
PMC10423102
Purpose
postoperative pain, Femoral nerve block
Femoral nerve block (FNB) is widely used in patients undergoing knee arthroscopy. However, the most commonly used concentration of ropivacaine (0.2% or above) may cause an unexpected decrease in the muscle strength of the quadriceps. Therefore, a lower concentration of ropivacaine (0.1%) for FNB was administered to investigate the effect on quadriceps strength and postoperative pain after knee arthroscopy.
PMC10598127
Methods
knee mobility, NRS, pain
REGRESSION
This was a double-blind, randomized, controlled trial (ChiCTR2000041404). A total of 83 patients scheduled for elective knee arthroscopy were randomized to receive 0.1% or 0.2% ropivacaine for FNB under ultrasound guidance. The primary outcomes were quadriceps strength and numerical rating scale (NRS) pain score. Quadriceps strength was measured before surgery and 6 h and 24 h after surgery, while NRS score was recorded before surgery, at the postanaesthesia care unit (PACU), and 6 h and 24 h after surgery. Multiple linear regression tests were used to compare the differences in quadriceps strength and NRS score between the two groups. Two-factor analysis of variance, using the factors group and time of measurement, was used for repeated NRS scores. Secondary outcomes included knee mobility, side effects, patient satisfaction, and length of hospital stay.
PMC10598127
Results
The mean (SD) quadriceps strength at 6 h after surgery was 7.5 (5.7) kg for the 0.1% ropivacaine group and 3.0 (4.4) kg for the 0.2% ropivacaine group. The mean difference adjusted for baseline characteristics was − 5.2 (95% CI − 7.2 to − 3.1) kg (
PMC10598127
Conclusions
Compared with 0.2% ropivacaine, 0.1% ropivacaine for FNB preserved quadriceps strength at 6 h after knee arthroscopy while providing similar analgesic effects.
PMC10598127
Level of evidence
I.
PMC10598127
Keywords
PMC10598127
Introduction
Postoperative pain, arthroplasty
Postoperative pain after knee arthroscopy and arthroplasty is a main factor affecting the early postoperative joint mobility and rehabilitation of patients [Ropivacaine is a pure S (-) isomer named S-(-)-1-propyl-2′,6′-pipecoloxylidide hydrochloride monohydrate. It has a pKa of 8.07 in 0.1 M KCl solution, which is approximately the same as that of bupivacaine (8.1) and is similar to that of mepivacaine. However, ropivacaine has an intermediate degree of lipid solubility compared to bupivacaine and mepivacaine. Because of its physical and chemical properties, ropivacaine produces a marked difference in sensory and motor blockades [
PMC10598127
Materials and methods
PMC10598127
Study design and participants
ligament rupture, knee pain, trauma
CHRONIC PAIN
This blinded randomized study was approved by the Ethical Committee of the Shanghai Tenth People’s Hospital, Shanghai, China (No. SHSY-IEC-KY-4.0/19-79/01) and was registered with a clinical trials registry (ChiCTR2000041404). Written informed consent was obtained from all patients. This study was conducted between July 2019 and June 2020 and adhered to the applicable CONSORT guidelines.The inclusion criteria were as follows: (1) American Society of Anaesthesiologists (ASA) physical status I or II; (2) aged 20–70 years; and (3) elective knee arthroscopy surgery. The exclusion criteria were as follows: (1) known intolerance or contraindication for local anaesthetics, paracetamol, nonsteroidal anti-inflammatory drugs, or opioids; (2) difficulty in mouth opening, preventing the laryngeal mask airway from being placed; (3) chronic pain with oral opioids or other analgesics used ≥ 1 year; and (4) significant limitation of knee motion during the acute phase of trauma, ligament rupture, or knee pain.
PMC10598127
Randomization
Using computer-generated random sequence tables and sealed envelopes, patients were randomized to one of two groups: 0.1% ropivacaine or 0.2% ropivacaine. The envelopes, which contained the prepared local anaesthetics for FNB and a computer-generated number, were opened just before the surgery when the patients arrived in the operating room. The patients, anaesthesiologists, orthopaedists, and research assistants were not informed about the concentration of ropivacaine used for FNB.
PMC10598127
Anaesthesia and surgical procedure
femoral nerve block
All surgeries were performed according to the standard hospital protocol. Before the induction of general anaesthesia, patients in the 0.1% ropivacaine group received 20 ml of 1 mg/ml ropivacaine, while patients in the 0.2% ropivacaine group received 20 ml of 2 mg/ml ropivacaine for ultrasound-guided femoral nerve block. Laryngeal mask airways were inserted after patients were induced with 2 mg/kg propofol, 0.2 mg/kg etomidate, 0.15 mg/kg cisatracurium, and 0.3 μg/kg sufentanil. Inhalation of 1–2% sevoflurane and continuous infusion of 2–4 mg kg
PMC10598127
Outcomes
NRS pain, pain
Data collection, including conducting all functional tests, was performed by blinded research assistants. The primary outcomes were NRS pain score and quadriceps strength. NRS pain score (0 = no pain and 10 = worst possible pain) was assessed before the operation, at the PACU, and 6 h and 24 h after the operation. The average NRS score was measured when patients were at rest, while the maximum NRS was measured when patients were asked to raise their legs. Quadriceps strength was assessed before the operation and 6 h and 24 h after the operation using the quadriceps strength test (QST) [
PMC10598127
Statistical analysis
NRS
Forty participants were needed to reach significance with a power of 85% and an alpha error of 0.025 when the noninferiority margin of the NRS was set to 0.5 and the standard deviation (SD) was set to 1. Taking patient withdrawal and other reasons for loss to follow-up during the study period into consideration, 45 participants were enrolled for each group.Continuous variables are reported as the mean values and SDs and were analysed using independent Student’s
PMC10598127
Discussion
postoperative pain, fascia iliaca block, Postoperative pain, nerve block, pain, NRS
HAND INFECTION, LOCAL INFILTRATION
The most important finding of the present study was that 0.1% ropivacaine for FNB showed less impact on quadriceps strength at 6 h after knee arthroscopy. Effective pain management and early mobilization are crucial for patients following knee surgery [Various types of regional anaesthesia, including FNB, ACB, fascia iliaca block, interspace between the popliteal artery and capsule of the posterior knee (IPACK) block, and local infiltration, are used for postoperative analgesia following knee arthroscopy or arthroplasty [With regard to postoperative pain, the NRS score was similar between the two groups, except for the NRS score in the PACU. Although knee arthroscopic surgery is less invasive, a minority of patients experience moderate to severe postoperative pain [Postoperative pain and infection are the two most frequent reasons for legal action [Our study has several limitations. A hand-held dynamometer was used for assessing motor strength, which is not as accurate as the dynamometer chair. Additionally, although all blocks were performed by one experienced anaesthesiologist, we did not assess the block success rate or onset and duration of FNB, although most patients in the two groups did not have the complete ability to raise their legs in the PACU. Because the dosages in the two groups were different, the duration of nerve block should be different.Currently, with the increasing use of FNB in routine arthroscopic knee surgery, an increasing number of patients experience lower extremity immobilization within 24 h after surgery. The application of 0.1% ropivacaine for FNB has less effect on quadriceps strength while providing a sufficient analgesic effect for postoperative pain. The patient can get out of bed earlier after the operation, which speeds up the patient’s recovery.
PMC10598127
Conclusions
Compared with 0.2% ropivacaine, 0.1% ropivacaine for FNB had less effect on quadriceps strength at 6 h after knee arthroscopy, while the analgesic effects of the two doses were equivalent within 24 h.
PMC10598127
Acknowledgements
The authors thank Yingyi Qin (Ph.D., department of Military Health Statistics, Naval Medical University, Shanghai, China), statistical and methodological consultant, for his advice and assistance in the statistical analyses. The authors also thank Biao Chen (M.D., Ph.D., department of orthopaedics, Tongji Hospital, Shanghai, China), sports medicine consultant, for his advice and assistance in the functional tests.
PMC10598127
Author contributions
TZ conceived of this project, performed study design and conception, assisted with analysing data, and wrote the manuscript. TZ helped devise the statistical analysis plan, interpreted the data, and wrote the manuscript. XN helped obtain data, analyse the data, and reviewed and edited the manuscript. LL helped obtain the data. JG helped obtain the data. MC helped perform study design, analysed the data, and reviewed and revised the manuscript. XZ performed study design, reviewed and revised the manuscript, and approved the manuscript.
PMC10598127
Funding
This work was supported by grants from the National Natural Science Foundation of China (82201362) to Tingting Zhang, and Clinical Research Project from Shanghai Tenth People’s Hospital (YNCR2C024) to Xiaoyin Niu and (SHYCS03) to Xuan Zhao.
PMC10598127
Declarations
PMC10598127
Conflict of interest
The author(s) declare that they have no competing interests.
PMC10598127
Ethical approval
This study was approved by the Ethical Committee of the Shanghai Tenth People’s Hospital, Shanghai, China (No. SHSY-IEC-KY-4.0/19-79/01), and was registered with a clinical trials registry (
PMC10598127
Informed consent
Informed consent was obtained from all individual participants included in this study.
PMC10598127
References
PMC10598127
Aims
Lazarus [Lazarus and Folkman in Stress
The aim of this study was to investigate whether shifting the focus to solution orientation and developing coping strategies for common errors could increase the efficiency of laparoscopic training and influence learning motivation. The concept of coping has been particularly defined by the psychologist Richard Lazarus [Lazarus and Folkman in Stress, appraisal, and coping, Springer publishing company, New York, 1984]. Based on this model, we examined the use of observational learning with a coping model for its effectiveness as a basic teaching model in laparoscopic training.
PMC10156798
Methods
55 laparoscopically naive medical students learned a standardized laparoscopic knot tying technique with video-based instructions. The control group was only offered a mastery video that showed the ideal technique and was free from mistakes. The intervention group was instructed on active error analysis and watched freely selectable videos of common errors including solution strategies (coping model) in addition to the mastery videos.
PMC10156798
Results
There was no statistically significant difference between the intervention and control groups for number of knot tying attempts until proficiency was reached (18.8 ± 5.5 vs. 21.3 ± 6.5,
PMC10156798
Conclusion
COMPLICATIONS
Using video-based learning of coping strategies for common errors improves learning motivation and understanding of the technique with a significant difference in its qualitative implementation in laparoscopy training. The ability to think in a solution-oriented, independent way is necessary in surgery in order to recognize and adequately deal with technical difficulties and complications.
PMC10156798
Supplementary Information
The online version contains supplementary material available at 10.1007/s00464-023-09969-w.
PMC10156798
Keywords
Open Access funding enabled and organized by Projekt DEAL.Laparoscopic suturing and knot tying is a complex skill to learn and is a key competence for many basic and advanced laparoscopic surgical procedures [A widely used instructional approach in laparoscopy training is 1:1 instruction and supervision by an expert [A precondition for proficiency-based training is a standardized assessment. In order to measure learning progress, performance should be assessed using objective, standardized criteria in addition to measured training time and number of attempts [Principles of self-regulated learning (SRL) continue to become more common in medical education. This encourages the ability to continually evaluate and adjust one’s strategies and behaviors to optimize learning and performance [The aim of this study was to improve laparoscopy training by video-based learning of coping strategies for common errors as a pragmatic, efficient, and cost-effective learning approach in the concept of video instruction and self-regulated learning [
PMC10156798
Materials and methods
PMC10156798
Setting and participants
This study was conducted as part of a voluntary elective course for medical students in the clinical part of their studies at Heidelberg University. This study took place in the training center for MIS of the Department of General, Visceral and Transplantation Surgery at Heidelberg University Hospital. Only laparoscopically naïve students, i.e., those who had never previously participated in a laparoscopic training course and had less than two hours of laparoscopic experience, were included. They received a standardized, 4-h basic skill training on box and virtual reality (VR) trainers. All participants were informed of the duration, procedures, methods, and objectives of the study before written informed consent was obtained [Sample size was calculated based on data from a pilot study with a comparable setting (All participants were randomized in a 1:1 ratio and assigned to an intervention or control group. Randomization was performed with a block size of 12 using an online tool (In each case, participant characteristics were recorded before training. To become familiar with the laparoscopic setting, all participants underwent the same basic training. In addition, they were asked to answer the validated questionnaires (Questionnaire on Current Motivation (QCM), self-efficacy expectations scale (ASKU), self-assessment of satisfaction with own performance) for further participant characterization [To ensure consistent video-based instruction in the performance of laparoscopic knot tying on the box trainer using C-loop technique, all study participants were shown an error-free instructional video as a mastery model three times [The checklists included the 5-point Likert scale for assessing knot quality [The checklists were available as online questionnaires and each score was recorded. In addition, the time required for each knot was measured. The time limit per laparoscopic knot was 20 min. The proficiency criteria were achieved if at least 4 of 5 points in the Knot Quality Score, 11 of 13 points in the OSATS Procedural Checklist (corresponding to ≥ 80% of the maximum score), and a knot time of max 2:00 min (min:s) were obtained. This matches performance levels achieved by experienced surgeons [
PMC10156798
Study design
mistakes
In this randomized controlled monocentric study, subjects were assigned to either the control or intervention group. Both groups learned laparoscopic suturing and knot tying in teams of two by video-based instructions. The intervention group was provided with laparoscopic suturing and knot tying instruction videos with various coping strategies for common errors (coping videos), as well as error-free instruction (mastery video). In addition, the intervention group was regularly instructed to actively analyze their own mistakes by means of a questionnaire (Fig. Flowchart of the study [Primary endpoint of the study represented the number of knot attempts and total training time until reaching proficiency criteria based on Knot Quality Score, the OSATS Procedural Checklist, and knot time of max 2:00 min. Secondary endpoints were parameters relevant to learning psychology–satisfaction with own expectation, self-efficacy expectation, and current motivation recorded by the validated questionnaires.
PMC10156798
Materials
Tissue damage, ‟Needle
PAD, BITE
The study was performed on a Szabo–Berci–Sackier box trainer and a standard laparoscopy tower (KARL STORZ GmbH & Co. KG, Tuttlingen, Germany). Participants sutured with two laparoscopic needle holders and a braided, absorbable Polysorb 3-0 suture with CV-25 cone ½ 22-mm needle (Medtronic Minimally Invasive Therapies TM, Minneapolis, MN, USA) shortened to 12 cm on a fixed silicone suture pad with predefined entry and exit points (Big Bite Medical GmbH, Heidelberg, Germany).Coping videos used in this study were designed specifically for this purpose [Content and main focus of the coping videos [1. ‟Needle load”  (a) Improper needle loadGrasp needle 2/3 from tip and perpendicular to needle holder(i) Directly from the silicone pad(ii) Allow needle to stand up with light pressure into tissue with needle holder slightly open(iii) Rotate needle in front of camera to check orientation12Pull the thread to the starting position(i) On the silicone pad(ii) With needle loosely gripped by non-dominant hand2. ‟Tissue and instrument handling”  (a) Traumatic tissue handlingPierce at a 90° anglePierce by slightly rotating the wrist to follow the shape of the needle347891011153. “Tail length”  (a) Tissue damage due to incisionFor pulling through, deflection principle, keep thread end as short as possible, grip in rear third(If necessary, loosen knot again first)454. ‟Needle orientation during knot tying”  (a) Wrapping not possibleRegrasp or bring needle to appropriate angle(i) With rotational movement of the instrument/wrist(ii) With needle loosely grasped with non-dominant hand by pulling on thread Clean C-loop7897895. “Lift and drift”  (a) Grasped needle leaves field of view7891115In addition, validated questionnaires were used to survey learning psychology parameters, such as current motivation, satisfaction with own performance, and self-efficacy [
PMC10156798
Ethical considerations
The study protocol was approved by the institutional ethics committee at Heidelberg Faculty of Medicine (S-436/2018) and informed consent was obtained from every participant.
PMC10156798
Statistical analysis
All continuous data are presented as mean values with standard deviation and were compared using Mann–Whitney
PMC10156798
Results
anxiety
SECONDARY
A total of 60 participants were recruited for the study. 55 were included in the analysis. Two participants did not meet the inclusion criteria. Three additional participants dropped out during the study and thus were not analyzed. Both groups showed similar demographic distribution (Table Baseline characteristicsMean ± sdRegarding pre-test data collected in the beginning of the study with the baseline questionnaires for satisfaction with own performance, self-efficacy as well as the four components of the questionnaire current motivation, no difference was seen between the two groups (Table Baseline results of parameters of psychology of learningSatisfaction (using a Likert scale with a range of 0–100, with 100 corresponding to maximum satisfaction), Self-Efficacy Short Scale (ASKU) (using a Likert scale of 1(does not apply at all)–5(applies completely)), and Questionnaire on Current Motivation (QCM) (measuring four components specific to the learning and performance situation with 18 items on a Likert scale of 1(does not apply at all)–7(applies completely))Mean ± sd, * significant for At pre-test, there was no difference between the two groups for the OSATS procedural checklist, the time per knot, and the knot quality score (Table Baseline knot attemptsMean ± sd, * significant for Video-based learning of coping strategies for common errors did not result in a significant difference between the intervention and control group in terms of total number of knot attempts until proficiency level in this study (18.8 ± 5.5 vs. 21.3 ± 6.5; There was a significantly higher proportion for the number of technically successful knots after the first intervention (attempt 5) for the intervention group than for the control group (0.7 ± 0.1 vs. 0.6 ± 0.2; Proportion of knots achieving technical proficiency from the first intervention onward, *significant for Looking at the knot attempts assessed by a blinded rater (proficiency attempts as well as individual samples), it is noticeable that the proportion of blinded attempts that met the criteria for technical proficiency (i.e., only failed to meet the time limit) was significantly higher for the intervention group at 60.9% vs. 38.0% in the control group (In the final survey (after reaching proficiency level), there was no difference in satisfaction with own performance. The self-efficacy short scale as secondary endpoint also showed no significant difference between the groups. The probability of success, challenge, and anxiety components of current motivation showed no difference. Interest was significantly higher for the intervention group (Table Secondary endpoints (satisfaction, ASKU, QCM)Mean ± sd, * significant for All participants were asked to complete the questionnaires on current motivation, satisfaction with own performance, and self-efficacy on a frequent interval during the study [The intervention group completed an online survey after each use of the coping videos to analyze errors and the usefulness of the coping videos [Four items most frequently rated as problematic on the OSATS procedure score were second winding of the knot (item 8; 24.3% of surveys), correct guidance of the needle when piercing the tissue (item 4; 22.5%), picking up the needle (item 1; 21.6%), and first winding of the knot (item 7; 19.8%).81.1% of the participants from the intervention group rated the coping videos as helpful. The control group did not perform any such error analysis, because they only had access to the mastery video [After the end of the study, the subjects were asked about aspects of their subjective learning success (Table Subjective learning successMean ± standard deviation, * significant for
PMC10156798
Discussion
In the present randomized controlled study, the use of video-based learning of coping strategies for common errors in laparoscopy training [Video-based learning of coping strategies for common errors did not reduce total training time but significantly improved technical implementation of laparoscopic suturing and knot tying in laparoscopy training [The motivational component interest was significantly higher using video-based learning of coping strategies for common errors. With regard to changes in motivation to learn with coping strategies, numerous variables are related to the onset and maintenance of readiness to learn. These include interest, perceived relevance, goal orientation, and self-efficacy [Considering technical understanding and subjective confidence as prerequisites for surgical work, this study showed that subjective learning success increased significantly in all parameters using video-based learning of coping strategies [
PMC10156798
Limitations
In contrast to the mastery video, the coping videos were only available from a right-handed perspective. The influence of this circumstance remains questionable, since the focus of the coping videos was on individual technical errors and not on the overall motion sequence. In addition, a total of only four left-handers participated in the study, three of whom were in the intervention group [
PMC10156798
Conclusion
The use of video-based training for coping strategies for common errors resulted in improved implementation of the knot tying technique, but the total training duration could not be reduced. The motivation to learn, especially the interest in the task, was increased. Understanding of the technique and subjective confidence in knot tying was increased, and error awareness was significantly greater for participants in the intervention group who learned with video-based training for common errors using the coping model. For the future, it will be interesting to see whether the use of coping models will not only positively change the learning condition but also show an improvement in real operations in particular, thus increasing patient safety.
PMC10156798
Author contributions
FN, FL, AG, and MS contributed to conception and design. FL, AG, and CW contributed to acquisition of data. AG, FN, MW, and FL contributed to analysis and interpretation of data. FL and AG contributed to preparation of manuscript and graphics. FN, EW, MS, MW, and BPM-S contributed to critical reviewing.
PMC10156798
Funding
Open Access funding enabled and organized by Projekt DEAL.
PMC10156798
Declarations
PMC10156798
Disclosures
P.
SCHMIDT
Franziska Lang, Annabelle Sofia Gerhäuser, Caroline Wild, Erica Wennberg, Mona Schmidt, Martin Wagner, Beat P. Müller-Stich, and Felix Nickel have no conflicts of interest or financial ties to disclose.
PMC10156798
References
PMC10156798
Objective
To assess the impact of different vertical positions on lung aeration in patients receiving invasive mechanical ventilation.
PMC10802776
Methods
An open-label randomized crossover clinical trial was conducted between January and July 2020. Adults receiving invasive mechanical ventilation for > 24 hours and < 7 days with hemodynamic, respiratory and neurological stability were randomly assigned at a 1:1 ratio to the sitting position followed by passive orthostasis condition or the passive orthostasis followed by the sitting position condition. The primary outcome was lung aeration assessed using the lung ultrasound score (score ranges from 0 [better] to 36 [worse]).
PMC10802776
Results
orthostasis
A total of 186 subjects were screened; of these subjects, 19 were enrolled (57.8% male; mean age, 73.2 years). All participants were assigned to receive at least one verticalization protocol. Passive orthostasis resulted in mean lung ultrasound scores that did not differ significantly from the sitting position (11.0
PMC10802776
Conclusion
orthostasis
This analysis did not find significant differences in lung aeration between the sitting and passive orthostasis groups. A randomized crossover clinical trial assessing the impact of vertical positioning on lung aeration in patients receiving invasive mechanical ventilation is feasible. Unfortunately, the study was interrupted due to the need to treat COVID-19 patients.ClinicalTrials.gov registry:
PMC10802776
INTRODUCTION
critically ill, ventilator-associated lung aeration/perfusion, neuromuscular damage
CRITICALLY ILL
Invasive mechanical ventilation (IMV), despite saving lives in the intensive care unit (ICU), may result in neuromuscular damage and represents a risk factor for developing ventilator-associated lung aeration/perfusion and impairment of respiratory system function.Body positioning is associated with lung ventilation (aeration) and perfusion changes and has positive effects on the respiratory systems of patients receiving IMV, mainly when performed outside the bed. For example, the combination of sitting in a chair and physical activity can improve lung aeration during IMVDespite the benefits of mobilizing patients outside the bed, evidence is still limited on the effects of vertical positioning on lung aeration, especially when vertical positioning is performed passively in the orthostatic position. Therefore, this study aimed to assess the effects of different vertical positions on lung aeration in critically ill patients receiving IMV. Based on the physiological ventilatory changes in the upright posture, we hypothesized that the verticalization of the chest would improve the pulmonary aeration of patients receiving IMV. The specific objectives were to evaluate variations in the tidal volume, respiratory rate and minute volume of patients receiving IMV and the safety of mobilizing patients outside of bed. Considering the demand on professionals to verticalize patients receiving IMV, we tried to determine the number of team members necessary to position patients receiving IMV in different positions outside of bed.
PMC10802776
METHODS
arrhythmia
MYOCARDIAL ISCHEMIA, ARRHYTHMIA
The present study was designed as an open-label, randomized, crossover, two-center clinical trial to assess the impact of different vertical positions on lung aeration in hospitalized ICU patients receiving IMV. Patients were enrolled from January to July 2020 and followed from the medical-surgical ICUs of All consecutive subjects ≥ 18 years of age admitted to the ICU and ventilated for ≥ ¬¬24 hours and ≤ 7 days, without an extubation plan on the day of the study protocols, were eligible for inclusion. The exclusion criteria were as follows: a noradrenaline level > 0.2mcg/kg/minute; a > 50% increase in the dose of noradrenaline (as long as it exceeded 0.1 mcg/kg/minute) within 2 hours prior to enrollment; a sodium nitroprusside level > 1 mcg/kg/minute; a heart rate < 40 or > 130bpm; active myocardial ischemia; a systolic blood pressure > 200mmHg or a mean arterial blood pressure < 65 mmHg; arrhythmia; the presence of an intra-aortic balloon counterpulsation; a fraction of inspired oxygen > 60%; a positive end-expiratory pressure ≥ 10cmH
PMC10802776
Randomization, washout, and blinding
orthostasis
Subjects were randomized at a 1:1 ratio to one of two verticalization groups: the sitting position followed by passive orthostasis group or the passive orthostasis followed by the sitting position group. Participants were randomized on the same day they were deemed to be suited to participate in the study. Randomization was performed using blocks of different sizes and stratified by center. Allocation sequencing and concealment were ensured through the use of a centralized web-based randomization platform (REDCap, Vanderbilt University, Nashville, TN, USA).
PMC10802776
Outcomes
bradycardia, tachycardia, arrhythmia, orthostasis, agitation, hypotension, tachypnea, hypertension, loss of lung aeration
LUNG, ARRHYTHMIA, ADVERSE EVENTS, LUNG CONSOLIDATION, HYPERTENSION
The primary outcome was lung aeration assessed using the lung ultrasound score (LUS) at the end of each verticalization protocol (sitting position and passive orthostasis), while the patients were in the vertical position. The LUS was also measured at 3 additional time points to assess the consistency of the findings: while in the supine position in bed (baseline), while in the supine position in bed after the sitting position, and while in the supine position in bed after passive orthostasis. For measurements while in the supine position, the subjects were placed with the headboard elevated to 30°. Lung aeration was assessed through chest ultrasound (Sonosite®), for which a convex transducer was used. The intercostal spaces of the anterior, lateral and posterior regions of both lungs were investigated. The division landmark was the anterior and posterior axillary lines, with each area being divided into upper and lower regions. Thus, six representative zones of each lung were assessed. Following the standards already established by the LUS, normal aeration was represented by pleural sliding and horizontal A-lines or by at least three vertical B-lines, and a score of 0 was assigned in this case. When a moderate loss of aeration occurred, characterized by multiple B-lines, either regularly or irregularly spaced, originating from the pleural line or small juxtapleural consolidations, a score of 1 was assigned. When coalescent B-lines were present in several intercostal spaces occupying the whole intercostal space and characterizing a severe loss of lung aeration, a score of 2 was assigned. If there was a total lung aeration loss, as observed in lung consolidation, with tissue echogenicity and static and dynamic air bronchograms, the investigated region was given a score of 3. The total LUS score was determined by summing the 12 areas examined, with scores ranging from 0 to 36; the higher the score was, the worse the lung aeration.Secondary outcomes included the variation tidal volume (expressed in mL), respiratory rate (expressed in bpm), minute volume (expressed in L/minute) and number of professionals required to perform the chest verticalization protocols. Tidal volume and respiratory rate data were collected directly from the mechanical ventilator monitor immediately at end 30 minutes of each vertical position (as well as in the 3 moments in bed). The measurements were standardized. We followed the proposal by Conti et al.The safety of the interventions was assessed by monitoring the occurrence of following adverse events: hypertension (defined as a systolic blood pressure > 200mmHg or a mean arterial blood pressure > 110mmHg) or hypotension (defined as a mean arterial blood pressure < 65mmHg); a saturation drop (defined as a peripheral oxygen saturation < 88%); tachycardia or bradycardia (defined as a heart rate > 130bpm or < 40bpm, respectively); the onset of arrhythmia; tachypnea or bradypnea (defined as a respiratory rate > 40bpm or < 5bpm, respectively); patient suffering (evidenced by nonverbal signals or gestures); agitation (an RASS score > +1); reduced level of consciousness; becoming physically combative; patient falls; traction or the removal of any devices from the patient; and the interruption of continuous hemodialysis catheter flow. If any adverse events occurred, the protocol was interrupted, and the patient was treated and monitored by the assistant team until clinical stabilization.
PMC10802776
Sample size
Thirty-six subjects were required to achieve a power of 90% to detect an absolute mean difference (MD) in the LUS of 2.0 points (standard deviation - SD, 3.5 points)
PMC10802776
Statistical analysis
SECONDARY
Baseline categorical variables are described as absolute and relative frequencies, while baseline quantitative variables are expressed as the mean and SD or median and interquartile range (IQR). Subjects were analyzed according to their randomization group, regardless of the treatment they received. Data distribution was evaluated using graphical analysis and the Shapiro‒Wilk test. Paired Student’s t test was used to compare the primary outcome between the two interventions and perform sensitivity analysis. The Friedman test was used to compare the 5 time points. For the secondary outcomes, categorical outcomes were assessed using McNemar’s test, symmetrical continuous outcomes were evaluated using paired Student’s t test, and continuous asymmetrical outcomes were assessed using Wilcoxon’s signed-rank test. Analyses were performed using R software,
PMC10802776