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Surgical site infection (SSI) is a worldwide problem which has morbidity, mortality and financial consequences. The incidence rate of SSI is high in Low- and Middle-Income countries (LMICs) compared to high income countries, and the costly surgical complication can raise the potential risk of financial catastrophe. The aim of the study is to critically appraise studies on the cost of SSI in a range of LMIC studies and compare these estimates with a reference standard of high income European studies who have explored similar SSI costs. A systematic review was undertaken using searches of two electronic databases, EMBASE and MEDLINE In-Process & Other Non-Indexed Citations, up to February 2019. Study characteristics, comparator group, methods and results were extracted by using a standard template. Studies from 15 LMIC and 16 European countries were identified and reviewed in full. The additional cost of SSI range (presented in 2017 international dollars) was similar in the LMIC ($174-$29,610) and European countries ($21-$34,000). Huge study design heterogeneity was encountered across the two settings. SSIs were revealed to have a significant cost burden in both LMICs and High Income Countries in Europe. The magnitude of the costs depends on the SSI definition used, severity of SSI, patient population, choice of comparator, hospital setting, and cost items included. Differences in study design affected the comparability across studies. There is need for multicentre studies with standardized data collection methods to capture relevant costs and consequences of the infection across income settings.

Little is known about the quality of surgery globally because robust reports of postoperative death rates are available for only 29 countries.2 The rate of postoperative deaths is a measure of the success of surgical care systems, and improving this metric is a global priority. England's combined Hospital Episode Statistics and Office of National Statistics (HES-ONS) dataset is one of the world's most comprehensive procedure-specific resources on mortality, reporting national coverage from a universal health-care system. The funder had no role in the study design, data collection, analysis, interpretation, or the writing of this Correspondence.

Pneumonia is a common and severe complication of abdominal surgery, it is associated with increased length of hospital stay, healthcare costs, and mortality. Further, pulmonary complication rates have risen during the SARS-CoV-2 pandemic. This study explored the potential cost-effectiveness of administering preoperative chlorhexidine mouthwash versus no-mouthwash at reducing postoperative pneumonia among abdominal surgery patients. A decision analytic model taking the South African healthcare provider perspective was constructed to compare costs and benefits of mouthwash versus no-mouthwash-surgery at 30 days after abdominal surgery. We assumed two scenarios: (i) the absence of COVID-19; (ii) the presence of COVID-19. Input parameters were collected from published literature including prospective cohort studies and expert opinion. Effectiveness was measured as proportion of pneumonia patients. Deterministic and probabilistic sensitivity analyses were performed to assess the impact of parameter uncertainties. The results of the probabilistic sensitivity analysis were presented using cost-effectiveness planes and cost-effectiveness acceptability curves. In the absence of COVID-19, mouthwash had lower average costs compared to no-mouthwash-surgery,$3,675 (R 63,770) versus $ 3,958 (R 68,683), and lower proportion of pneumonia patients, 0.029 versus 0.042 (dominance of mouthwash intervention). In the presence of COVID-19, the increase in pneumonia rate due to COVID-19, made mouthwash more dominant as it was more beneficial to reduce pneumonia patients through administering mouthwash. The cost-effectiveness acceptability curves shown that mouthwash surgery is likely to be cost-effective between$0 (R0) and $ 15,000 (R 260,220) willingness to pay thresholds. Both the absence and presence of SARS-CoV-2, mouthwash is likely to be cost saving intervention for reducing pneumonia after abdominal surgery. However, the available evidence for the effectiveness of mouthwash was extrapolated from cardiac surgery; there is now an urgent need for a robust clinical trial on the intervention on non-cardiac surgery.

To systematically evaluate the evidence across surgical specialties as to whether staples or sutures better improve patient and provider level outcomes. A systematic review of systematic reviews and panoramic meta-analysis of pooled estimates. Eleven systematic reviews, including 13,661 observations, met the inclusion criteria. In orthopaedic surgery sutures were found to be preferable, and for appendicial stump sutures were protective against both surgical site infection and post surgical complications. However, staples were protective against leak in ilecolic anastomosis. For all other surgery types the evidence was inconclusive with wider confidence intervals including the possibly of preferential outcomes for surgical site infection or post surgical complication for either staples or sutures. Whilst reviews showed substantial variation in mean differences in operating time (I(2) 94%) there was clear evidence of a reduction in average operating time across all surgery types. Few reviews reported on length of stay, but the three reviews that did (I(2) 0%, including 950 observations) showed a non significant reduction in length of stay, but showed evidence of publication bias (P-value for Egger test 0.05). Evidence across surgical specialties indicates that wound closure with staples reduces the mean operating time. Despite including several thousand observations, no clear evidence of superiority emerged for either staples or sutures with respect to surgical site infection, post surgical complications, or length of stay.

Background Large-scale quality improvement interventions demand robust trial designs with flexibility for delivery in different contexts, particularly during a pandemic. We describe innovative features of a batched stepped wedge trial, ESCP sAfe Anastomosis proGramme in CoLorectal SurgEry (EAGLE), intended to reduce anastomotic leak following right colectomy, and reflect on lessons learned about the implementation of quality improvement programmes on an international scale. Methods Surgical units were recruited and randomised in batches to receive a hospital-level education intervention designed to reduce anastomotic leak, either before, during, or following data collection. All consecutive patients undergoing right colectomy were included. Online learning, patient risk stratification and an in-theatre checklist constituted the intervention. The study was powered to detect an absolute risk reduction of anastomotic leak from 8.1 to 5.6%. Statistical efficiency was optimised using an incomplete stepped wedge trial design and study batches analysed separately then meta-analysed to calculate the intervention effect. An established collaborative group helped nurture strong working relationships between units/countries and a prospectively designed process evaluation will enable evaluation of both the intervention and its implementation. Results The batched trial design allowed sequential entry of clusters, targeted research training and proved to be robust to pandemic interruptions. Staggered start times in the incomplete stepped wedge design with long lead-in times can reduce motivation and engagement and require careful administration. Conclusion EAGLE’s robust but flexible study design allowed completion of the study across globally distributed geographical locations in spite of the pandemic. The primary outcome analysed in conjunction with the process evaluation will ensure a rich understanding of the intervention and the effects of the study design. Trial registration National Institute of Health Research Clinical Research Network portfolio IRAS ID: 272,250. Health Research Authority approval 18 October 2019. ClinicalTrials.gov, identifier NCT04270721, protocol ID RG_19196.

Correspondence to Professor Dion G Morton; dion.morton@uhb.nhs.uk Surgical teams, including managers, nurses, anaesthetists and surgeons, play a pivotal role in delivering essential health services, strengthening the wider health systems, especially in the face of external threats from pandemics, extremes of weather or war. There is good evidence that linking PHC facilities to the (first referral) hospitals improves the health outcomes.1 However, primary research evidence linking community and PHC facilities to surgical care is still lacking and is required to justify service expansion. Because surgery is easily measured and outcomes directly accountable, surgical teams are ideally placed to evaluate the impact of such service changes on the hospital system and the individual patients they care for. Kamarajah and colleagues argue, in the accompanying article,2 that this lack of prioritisation may also be due to a failure of integration of surgery into health systems and the absence of robust evidence supporting the principle that surgical service development will strengthen the health system and improve the health outcomes. Delay in care leads to emergency presentation and adverse outcomes including death,3 even for simple conditions such as appendicitis4 or inguinal hernia.5 These pathways can strengthen other components of the health system through training for community health workers, improving referral for emergency medical conditions and elective management of NCDs.6 The expanding surgical and perioperative research networks across the low- and middle-income countries (LMICs) could be better used, especially by the health system community, given their capability and promise to develop the evidence base and evaluate the impact of change both on the health system and on the individual patients.

ContextEstrogens affect the incidence and progression of colorectal cancer (CRC), although the precise molecular mechanisms remain ill-defined.ObjectiveThe present study investigated prereceptor estrogen metabolism through steroid sulphatase (STS) and 17β-hydroxysteroid dehydrogenase activity and subsequent nongenomic estrogen signaling in human CRC tissue, in The Cancer Genome Atlas colon adenocarcinoma data set, and in in vitro and in vivo CRC models. We aimed to define and therapeutically target pathways through which estrogens alter CRC proliferation and progression.Design, Setting, Patients, and InterventionsHuman CRC samples with normal tissue-matched controls were collected from postmenopausal female and age-matched male patients. Estrogen metabolism enzymes and nongenomic downstream signaling pathways were determined. CRC cell lines were transfected with STS and cultured for in vitro and in vivo analysis. Estrogen metabolism was determined using an ultra-performance liquid chromatography–tandem mass spectrometry method.Primary Outcome MeasureThe proliferative effects of estrogen metabolism were evaluated using 5-bromo-2′-deoxyuridine assays and CRC mouse xenograft studies.ResultsHuman CRC exhibits dysregulated estrogen metabolism, favoring estradiol synthesis. The activity of STS, the fundamental enzyme that activates conjugated estrogens, is significantly (P < 0.001) elevated in human CRC compared with matched controls. STS overexpression accelerates CRC proliferation in in vitro and in vivo models, with STS inhibition an effective treatment. We defined a G-protein–coupled estrogen receptor (GPER) proproliferative pathway potentially through increased expression of connective tissue growth factor in CRC.ConclusionHuman CRC favors estradiol synthesis to augment proliferation via GPER stimulation. Further research is required regarding whether estrogen replacement therapy should be used with caution in patients at high risk of developing CRC.We studied how estrogen metabolism affects human colorectal cancer (CRC). We found CRC favored estrogen synthesis, which was proproliferative via a novel G-protein–coupled estrogen receptor pathway.

Malnutrition is an independent predictor for postoperative complications in low- and middle-income countries (LMICs). We systematically reviewed evidence on the impact of preoperative oral nutrition supplementation (ONS) on patients undergoing gastrointestinal cancer surgery in LMICs. We searched EMBASE, Cochrane Library, Web of Science, Scopus, WHO Global Index Medicus, SciELO, Latin American and Caribbean Health Sciences Literature (LILACS) databases from inception to March 21, 2022 for randomised controlled trials evaluating preoperative ONS in gastrointestinal cancer within LMICs. We evaluated the impact of ONS on all postoperative outcomes using random-effects meta-analysis. Seven studies reported on 891 patients (446 ONS group, 445 control group) undergoing surgery for gastrointestinal cancer. Preoperative ONS reduced all cause postoperative surgical complications (risk ratio (RR) 0.53, 95% CI 0.46–0.60, P < 0.001, I 2  = 0%, n = 891), infection (0.52, 0.40–0.67, P = 0.008, I 2  = 0%, n = 570) and all-cause mortality (0.35, 0.26–0.47, P = 0.014, I 2  = 0%, n = 588). Despite heterogeneous populations and baseline rates, absolute risk ratio (ARR) was reduced for all cause (pooled effect −0.14, −0.22 to −0.06, P = 0.006; number needed to treat (NNT) 7) and infectious complications (−0.13, −0.22 to −0.06, P < 0.001; NNT 8). Preoperative nutrition in patients undergoing gastrointestinal cancer surgery in LMICs demonstrated consistently strong and robust treatment effects across measured outcomes. However additional higher quality research, with particular focus within African populations, are urgently required.

Summary Background The increasing prevalence of multiple long-term conditions (MLTC) presents significant challenges to healthcare delivery globally. Although interventions for long-term conditions have predominantly been designed and evaluated in primary care settings, there is a growing recognition of the need to address the management of MLTC within secondary care. This scoping review aims to comprehensively evaluate hospital-initiated complex interventions for people with MLTC. Methods We searched MEDLINE, Embase, PsycINFO, CINAHL Plus and Cochrane Library to identify published studies from Jan 1, 2010, evaluating hospital-initiated interventions initiated for adults (aged ≥ 18 years) with MLTC (PROSPERO: CRD42024498448). Studies reporting patients with frailty only, one long-term condition or orthogeriatric studies that did not focus solely on people with MLTC were excluded. The primary outcome measures were the characteristics of these complex interventions measured as: (i) intervention components, (ii) stakeholders involved; and (iii) implementation strategies, reported according to a theoretical framework (Expert Recommendations for Implementing Change). Secondary outcome measures were clinical and cost implications of these complex interventions, feasibility and sustainability, defined according to the World Health Organisation implementation framework. Findings This scoping review identified 70 studies (56,111 participants). Twelve intervention components were identified in 52 combinations; the most common were medication review and optimisation ( n  = 39), chronic disease management ( n  = 34) and providing detailed care plans ( n  = 23). Majority of studies included two or more interventions components ( n  = 49) delivered by multiple stakeholders ( n  = 38). Of eleven implementation strategies reported, training and educating stakeholders, establishing integrated wards or clinics and regular multidisciplinary team meetings were the most common. Majority of combinations of intervention groups were associated with improved clinical outcomes for patients with MLTC ( n  = 43/70, 61.4%), yet eight studies reported on costs. However, embedding training and education or integrated clinics in delivering these intervention groups were associated with improved clinical outcomes, irrespective of the number of healthcare professionals involved. Majority of studies were evaluated in single centre settings, with limited evaluation of broader implementation measures. Interpretation Hospital-initiated complex interventions that involve multiple stakeholders may be feasible and appear to be clinically useful for people with MLTC. To strengthen impact and support wider scale-up across health systems, closing knowledge gaps around cost-implications and strategies to improve implementation of these complex interventions through training and education or integrated clinics will be crucial.

ObjectiveTo systematically review preoperative and intraoperative Anastomotic Leak Prediction Scores (ALPS) and validation studies to evaluate performance and utility in surgical decision-making. Anastomotic leak (AL) is the most feared complication of colorectal surgery. Individualised leak risk could guide anastomosis and/or diverting stoma.MethodsSystematic search of Ovid MEDLINE and Embase databases, 30 October 2020, identified existing ALPS and validation studies. All records including >1 risk factor, used to develop new, or to validate existing models for preoperative or intraoperative use to predict colorectal AL, were selected. Data extraction followed CHecklist for critical Appraisal and data extraction for systematic Reviews of prediction Modelling Studies guidelines. Models were assessed for applicability for surgical decision-making and risk of bias using Prediction model Risk Of Bias ASsessment Tool.Results34 studies were identified containing 31 individual ALPS (12 colonic/colorectal, 19 rectal) and 6 papers with validation studies only. Development dataset patient populations were heterogeneous in terms of numbers, indication for surgery, urgency and stoma inclusion. Heterogeneity precluded meta-analysis. Definitions and timeframe for AL were available in only 22 and 11 ALPS, respectively. 26/31 studies used some form of multivariable logistic regression in their modelling. Models included 3–33 individual predictors. 27/31 studies reported model discrimination performance but just 18/31 reported calibration. 15/31 ALPS were reported with external validation, 9/31 with internal validation alone and 4 published without any validation. 27/31 ALPS and every validation study were scored high risk of bias in model analysis.ConclusionsPoor reporting practices and methodological shortcomings limit wider adoption of published ALPS. Several models appear to perform well in discriminating patients at highest AL risk but all raise concerns over risk of bias, and nearly all over wider applicability. Large-scale, precisely reported external validation studies are required.PROSPERO registration numberCRD42020164804.