Procedural sedation and analgesia versus general anesthesia for hysteroscopic myomectomy (PROSECCO trial) : a multicenter randomized controlled trial

BackgroundHysteroscopic resection is the first-choice treatment for symptomatic type 0 and 1 fibroids. Traditionally, this was performed under general anesthesia. Over the last decade, surgical procedures are increasingly being performed in an outpatient setting under procedural sedation and analgesia. However, studies evaluating safety and effectiveness of hysteroscopic myomectomy under procedural sedation are lacking. This study aims to investigate whether hysteroscopic myomectomy under procedural sedation and analgesia with propofol is noninferior to hysteroscopic myomectomy under general anesthesia.Methods and findingsThis was a multicenter, randomized controlled noninferiority trial conducted in 14 university and teaching hospitals in the Netherlands between 2016 and 2021. Inclusion criteria were age >= 18 years, maximum number of 3 type 0 or 1 fibroids, maximum fibroid diameter 3.5 cm, American Society of Anesthesiologists class 1 or 2, and having sufficient knowledge of the Dutch or English language. Women with clotting disorders or with severe anemia (Hb < 5.0 mmol/L) were excluded. Women were randomized using block randomization with variable block sizes of 2, 4, and 6, between hysteroscopic myomectomy under procedural sedation and analgesia (PSA) with propofol or under general anesthesia (GA).Primary outcome was the percentage of complete resections, assessed on transvaginal ultrasonography 6 weeks postoperatively by a sonographer blinded for the treatment arm and surgical outcome. Secondary outcomes were the surgeon's judgment of completeness of procedure, menstrual blood loss, uterine fibroid related and general quality of life, pain, recovery, hospitalization, complications, and surgical reinterventions. Follow-up period was 1 year.The risk difference between both treatment arms was estimated, and a Farrington-Manning test was used to determine the p-value for noninferiority (noninferiority margin 7.5% of incomplete resections). Data were analyzed according to the intention-to-treat principle, including a per-protocol analysis for the primary outcome.A total of 209 women participated in the study and underwent hysteroscopic myomectomy with PSA (n = 106) or GA (n = 103). Mean age was 45.1 [SD 6.4] years in the PSA group versus 45.0 [7.7] years in the GA group. For 98/106 women in the PSA group and 89/103 women in the GA group, data were available for analysis of the primary outcome.Hysteroscopic resection was complete in 86/98 women (87.8%) in the PSA group and 79/89 women (88.8%) in the GA group (risk difference -1.01%; 95% confidence interval (CI) -10.36 to 8.34; noninferiority, P = 0.09). No serious anesthesiologic complications occurred, and conversion from PSA to GA was not required. During the follow-up period, 15 serious adverse events occurred (overnight admissions). All were unrelated to the intervention studied. Main limitations were the choice of primary outcome and the fact that our study proved to be underpowered.ConclusionsNoninferiority of PSA for completeness of resection was not shown, though there were no significant differences in clinical outcomes and quality of life. In this study, hysteroscopic myomectomy for type 0 and 1 fibroids with PSA compared to GA was safe and led to shorter hospitalization. These results can be used for counseling patients by gynecologists and anesthesiologists. Based on these findings, we suggest that hysteroscopic myomectomies can be performed under PSA in an outpatient setting

Surgical site infection after gastrointestinal surgery in children : an international, multicentre, prospective cohort study

Introduction Surgical site infection (SSI) is one of the most common healthcare-associated infections (HAIs). However, there is a lack of data available about SSI in children worldwide, especially from low-income and middle-income countries. This study aimed to estimate the incidence of SSI in children and associations between SSI and morbidity across human development settings. Methods A multicentre, international, prospective, validated cohort study of children aged under 16 years undergoing clean-contaminated, contaminated or dirty gastrointestinal surgery. Any hospital in the world providing paediatric surgery was eligible to contribute data between January and July 2016. The primary outcome was the incidence of SSI by 30 days. Relationships between explanatory variables and SSI were examined using multilevel logistic regression. Countries were stratified into high development, middle development and low development groups using the United Nations Human Development Index (HDI). Results Of 1159 children across 181 hospitals in 51 countries, 523 (45 center dot 1%) children were from high HDI, 397 (34 center dot 2%) from middle HDI and 239 (20 center dot 6%) from low HDI countries. The 30-day SSI rate was 6.3% (33/523) in high HDI, 12 center dot 8% (51/397) in middle HDI and 24 center dot 7% (59/239) in low HDI countries. SSI was associated with higher incidence of 30-day mortality, intervention, organ-space infection and other HAIs, with the highest rates seen in low HDI countries. Median length of stay in patients who had an SSI was longer (7.0 days), compared with 3.0 days in patients who did not have an SSI. Use of laparoscopy was associated with significantly lower SSI rates, even after accounting for HDI. Conclusion The odds of SSI in children is nearly four times greater in low HDI compared with high HDI countries. Policies to reduce SSI should be prioritised as part of the wider global agenda.Peer reviewe

Tailored anticoagulant treatment after a first venous thromboembolism: protocol of the Leiden Thrombosis Recurrence Risk Prevention (L-TRRiP) study - cohort-based randomised controlled trial

Introduction Patients with a first venous thromboembolism (VTE) are at risk of recurrence. Recurrent VTE (rVTE) can be prevented by extended anticoagulant therapy, but this comes at the cost of an increased risk of bleeding. It is still uncertain whether patients with an intermediate recurrence risk or with a high recurrence and high bleeding risk will benefit from extended anticoagulant treatment, and whether a strategy where anticoagulant duration is tailored on the predicted risks of rVTE and bleeding can improve outcomes. The aim of the Leiden Thrombosis Recurrence Risk Prevention (L-TRRiP) study is to evaluate the outcomes of tailored duration of long-term anticoagulant treatment based on individualised assessment of rVTE and major bleeding risks.Methods and analysis The L-TRRiP study is a multicentre, open-label, cohort-based, randomised controlled trial, including patients with a first VTE. We classify the risk of rVTE and major bleeding using the L-TRRiP and VTE-BLEED scores, respectively. After 3 months of anticoagulant therapy, patients with a low rVTE risk will discontinue anticoagulant treatment, patients with a high rVTE and low bleeding risk will continue anticoagulant treatment, whereas all other patients will be randomised to continue or discontinue anticoagulant treatment. All patients will be followed up for at least 2 years. Inclusion will continue until the randomised group consists of 608 patients; we estimate to include 1600 patients in total. The primary outcome is the combined incidence of rVTE and major bleeding in the randomised group after 2 years of follow-up. Secondary outcomes include the incidence of rVTE and major bleeding, functional outcomes, quality of life and cost-effectiveness in all patients.Ethics and dissemination The protocol was approved by the Medical Research Ethics Committee Leiden-Den Haag-Delft. Results are expected in 2028 and will be disseminated through peer-reviewed journals and during (inter)national conferences.Trial registration number NCT06087952

Treating MERS-CoV during an outbreak

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p<0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05-2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p<0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication. Funding: DFID-MRC-Wellcome Trust Joint Global Health Trial Development Grant, National Institute of Health Research Global Health Research Unit Grant