Reducing surgical site infections in low-income and middle-income countries (FALCON): a pragmatic, multicentre, stratified, randomised controlled trial

Background
Surgical site infection (SSI) is the most common postoperative complication worldwide. WHO guidelines to prevent SSI recommend alcoholic chlorhexidine skin preparation and fascial closure using triclosan-coated sutures, but called for assessment of both interventions in low-resource settings. This study aimed to test both interventions in low-income and middle-income countries.

Methods
FALCON was a 2 × 2 factorial, randomised controlled trial stratified by whether surgery was clean-contaminated, or contaminated or dirty, including patients undergoing abdominal surgery with a skin incision of 5 cm or greater. This trial was undertaken in 54 hospitals in seven countries (Benin, Ghana, India, Mexico, Nigeria, Rwanda, and South Africa). Patients were computer randomised 1:1:1:1 to: (1) 2% alcoholic chlorhexidine and non-coated suture, (2) 2% alcoholic chlorhexidine and triclosan-coated suture, (3) 10% aqueous povidone–iodine and non-coated suture, or (4) 10% aqueous povidone–iodine and triclosan-coated suture. Patients and outcome assessors were masked to intervention allocation. The primary outcome was SSI, reported by trained outcome assessors, and presented using adjusted relative risks and 95% CIs. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, NCT03700749.

Findings
Between Dec 10, 2018, and Sept 7, 2020, 5788 patients (3091 in clean-contaminated stratum, 2697 in contaminated or dirty stratum) were randomised (1446 to alcoholic chlorhexidine and non-coated suture, 1446 to alcoholic chlorhexidine and triclosan-coated suture, 1447 to aqueous povidone–iodine and non-coated suture, and 1449 to aqueous povidone–iodine and triclosan-coated suture). 14·0% (810/5788) of patients were children and 66·9% (3873/5788) had emergency surgery. The overall SSI rate was 22·0% (1163/5284; clean-contaminated stratum 15·5% [454/2923], contaminated or dirty stratum 30·0% [709/2361]). For both strata, there was no evidence of a difference in the risk of SSI with alcoholic chlorhexidine versus povidone–iodine (clean-contaminated stratum 15·3% [223/1455] vs 15·7% [231/1468], relative risk 0·97 [95% CI 0·82–1·14]; contaminated or dirty stratum 28·3% [338/1194] vs 31·8% [371/1167], relative risk 0·91 [95% CI 0·81–1·02]), or with triclosan-coated sutures versus non-coated sutures (clean-contaminated stratum 14·7% [215/1459] vs 16·3% [239/1464], relative risk 0·90 [95% CI 0·77–1·06]; contaminated or dirty stratum 29·4% [347/1181] vs 30·7% [362/1180], relative risk 0·98 [95% CI 0·87–1·10]). With both strata combined, there were no differences using alcoholic chlorhexidine or triclosan-coated sutures.

Interpretation
This trial did not show benefit from 2% alcoholic chlorhexidine skin preparation compared with povidone–iodine, or with triclosan-coated sutures compared with non-coated sutures, in preventing SSI in clean-contaminated or contaminated or dirty surgical wounds. Both interventions are more expensive than alternatives, and these findings do not support recommendations for routine use.

Protocol for a systematic review of outcomes from microsurgical free-tissue transfer performed on short-term collaborative surgical trips in low-income and middle-income countries

Background
In many units around the world, microsurgical free-tissue transfer represents the gold standard for reconstruction of significant soft tissue defects following cancer, trauma or infection. However, many reconstructive units in low-income and middle-income countries (LMICs) do not yet have access to the resources, infrastructure or training required to perform any microsurgical procedures. Long-term international collaborations have been formed with annual short-term reconstructive missions conducting microsurgery. In the first instance, these provide reconstructive surgery to those who need it. In the longer-term, they offer an opportunity for teaching and the development of sustainable local services.

Methods
A PRISMA-compliant systematic review and meta-analysis will be performed. A comprehensive, predetermined search strategy will be applied to the MEDLINE and Embase electronic databases from inception to August 2021. All clinical studies presenting sufficient data on free-tissue transfer performed on short-term collaborative surgical trips (STCSTs) in LMICs will be eligible for inclusion. The primary outcomes are rate of free flap failure, rate of emergency return to theatre for free flap salvage and successful salvage rate. The secondary outcomes include postoperative complications, cost effectiveness, impact on training, burden of disease, legacy and any functional or patient reported outcome measures. Screening of studies, data extraction and assessments of study quality and bias will be conducted by two authors. Individual study quality will be assessed according to the Oxford Evidence-based Medicine Scales of Evidence 2, and risk of bias using either the ‘Revised Cochrane risk of bias tool for randomized trials’ (Rob2), the ‘Risk of bias in non-randomized studies of interventions’ (ROBINS-I) tool, or the National Institute for Health Quality Assessment tool for Case Series. Overall strength of evidence will be assessed according to the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach.

Discussion
To-date the outcomes of microsurgical procedures performed on STCSTs to LMICs are largely unknown. Improved education, funding and allocation of resources are needed to support surgeons in LMICs to perform free-tissue transfer. STCSTs provide a vehicle for sustainable collaboration and training. Disseminating microsurgical skills could improve the care received by patients living with reconstructive pathology in LMICs, but this is poorly established. This study sets out a robust protocol for a systematic review designed to critically analyse outcomes.

Vision impairment and traffic safety outcomes in low-income and middle-income countries: a systematic review and meta-analysis

Background
Road traffic injuries are a major public health concern and their prevention requires concerted efforts. We aimed to systematically analyse the current evidence to establish whether any aspects of vision, and particularly interventions to improve vision function, are associated with traffic safety outcomes in low-income and middle-income countries (LMICs).

Methods
We did a systematic review and meta-analysis to assess the association between poor vision and traffic safety outcomes. We searched MEDLINE, Embase, PsycINFO, CINAHL, Web of Science, Cochrane Database of Systematic Reviews, and the Cochrane Central Register of Controlled Trials in the Cochrane Library from database inception to April 2, 2020. We included any interventional or observational studies assessing whether vision is associated with traffic safety outcomes, studies describing prevalence of poor vision among drivers, and adherence to licensure regulations. We excluded studies done in high-income countries. We did a meta-analysis to explore the associations between vision function and traffic safety outcomes and a narrative synthesis to describe the prevalence of vision disorders and adherence to licensure requirements. We used random-effects models with residual maximum likelihood method. The systematic review protocol was registered on PROSPERO, CRD-42020180505.

Findings
We identified 49 (1·8%) eligible articles of 2653 assessed and included 29 (59·2%) in the various data syntheses. 15 394 participants (mean sample size n=530 [SD 824]; mean age of 39·3 years [SD 9·65]; 1167 [7·6%] of 15 279 female) were included. The prevalence of vision impairment among road users ranged from 1·2% to 26·4% (26 studies), colour vision defects from 0·5% to 17·1% (15 studies), and visual field defects from 2·0% to 37·3% (ten studies). A substantial proportion (range 10·6–85·4%) received licences without undergoing mandatory vision testing. The meta-analysis revealed a 46% greater risk of having a road traffic crash among those with central acuity visual impairment (risk ratio [RR] 1·46 [95% CI 1·20–1·78]; p=0·0002, 13 studies) and a greater risk among those with defects in colour vision (RR 1·36 [1·01–1·82]; p=0·041, seven studies) or the visual field (RR 1·36 [1·25–1·48]; p<0·0001, seven studies). The I2 value for overall statistical heterogeneity was 63·4%.

Interpretation
This systematic review shows a positive association between vision impairment and traffic crashes in LMICs. Our findings provide support for mandatory vision function assessment before issuing a driving licence.

Practical considerations for prostate hypofractionation in the developing world

External beam radiotherapy is an effective curative treatment option for localized prostate cancer, the most common cancer in men worldwide. However, conventionally fractionated courses of curative external beam radiotherapy are usually 8–9 weeks long, resulting in a substantial burden to patients and the health-care system. This problem is exacerbated in low-income and middle-income countries where health-care resources might be scarce and patient funds limited. Trials have shown a clinical equipoise between hypofractionated schedules of radiotherapy and conventionally fractionated treatments, with the advantage of drastically shortening treatment durations with the use of hypofractionation. The hypofractionated schedules are supported by modern consensus guidelines for implementation in clinical practice. Furthermore, several economic evaluations have shown improved cost effectiveness of hypofractionated therapy compared with conventional schedules. However, these techniques demand complex infrastructure and advanced personnel training. Thus, a number of practical considerations must be borne in mind when implementing hypofractionation in low-income and middle-income countries, but the potential gain in the treatment of this patient population is substantial.

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Background
Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality.

Methods
We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis.

Findings
We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middle-income countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in low-income countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality.

Interpretation
Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between low-income, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030.

Infection Prevention and Control at Lira University Hospital, Uganda: More Needs to Be Done

Globally, 5%–15% of hospitalized patients acquire infections (often caused by antimicrobial-resistant microbes) due to inadequate infection prevention and control (IPC) measures. We used the World Health Organization’s (WHO) ‘Infection Prevention and Control Assessment Framework’ (IPCAF) tool to assess the IPC compliance at Lira University hospital (LUH), a teaching hospital in Uganda. We also characterized challenges in completing the tool. This was a hospital-based, cross-sectional study conducted in November 2020. The IPC focal person at LUH completed the WHO IPCAF tool. Responses were validated, scored, and interpreted per WHO guidelines. The overall IPC compliance score at LUH was 225/800 (28.5%), implying a basic IPC compliance level. There was no IPC committee, no IPC team, and no budgets. Training was rarely or never conducted. There was no surveillance system and no monitoring/audit of IPC activities. Bed capacity, water, electricity, and disposal of hospital waste were adequate. Disposables and personal protective equipment were not available in appropriate quantities. Major challenges in completing the IPCAF tool were related to the detailed questions requiring repeated consultation with other hospital stakeholders and the long time it took to complete the tool. IPC compliance at LUH was not optimal. The gaps identified need to be addressed urgently.

Surgical service monitoring and quality control systems at district hospitals in Malawi, Tanzania and Zambia: a mixed-methods study

Background In low-income and middle-income countries, an estimated one in three clinical adverse events happens in non-complex situations and 83% are preventable. Poor quality of care also leads to inefficient use of human, material and financial resources for health. Improving outcomes and mitigating the risk of adverse events require effective monitoring and quality control systems.

Aim To assess the state of surgical monitoring and quality control systems at district hospitals (DHs) in Malawi, Tanzania and Zambia.

Methods A mixed-methods cross-sectional study of 75 DHs: Malawi (22), Tanzania (30) and Zambia (23). This included a questionnaire, interviews and visual inspection of operating theatre (OT) registers. Data were collected on monitoring and quality systems for surgical activity, processes and outcomes, as well as perceived barriers.

Results 53% (n=40/75) of DHs use more than one OT register to record surgical operations. With the exception of standardised printed OT registers in Zambia, the register format (often handwritten books) and type of data collected varied between DHs. Monthly reports were seldom analysed by surgical teams. Less than 30% of all surveyed DHs used surgical safety checklists (n=22/75), and <15% (n=11/75) performed surgical audits. 73% (n=22/30) of DHs in Tanzania and less than half of DHs in Malawi (n=11/22) and Zambia (n=10/23) conducted surgical case reviews. Reports of surgical morbidity and mortality were compiled in 65% (n=15/23) of Zambian DHs, and in less than one-third of DHs in Tanzania (n=9/30) and Malawi (n=4/22). Reported barriers to monitoring and quality systems included an absence of formalised guidelines, continuous training opportunities as well as inadequate accountability mechanisms.

Conclusions Surgical monitoring and quality control systems were not standard among sampled DHs. Improvements are needed in standardisation of quality measures used; and in ensuring data completeness, analysis and utilisation for improving patient outcomes.

Hydrostatic reduction of intussusception with intermittent radiography: an alternative to fluoroscopy or ultrasound-guided reduction in low-income and middle-income countries

Background Although hydrostatic reduction of intussusception with ultrasound (US) or fluoroscopy guidance is well known, it is not yet well established in many low-income and middle-income countries. The aim of the study is to report our results of hydrostatic reduction with intermittent radiography, which has the potential to be practiced in resource-limited settings.

Methods We retrospectively analyzed our patients with intussusception from 2009 to 2019 (11 years). Hydrostatic reduction was performed using water-soluble contrast medium (iopamidol), and reduction was followed with intermittent X-rays taken after every 50 mL of diluted contrast injection. The procedure was not continuously monitored by US or fluoroscopy. Differences in outcome based on age and gender, and yearly trends of admission for intussusception, types of treatment and mortality were analyzed.

Results Among 672 patients, the ratio of boys to girls was 2.46:1.0, and their ages ranged from 1 month to 15 years (median 8 months). Hydrostatic reduction was performed successfully in 351 (52.23%) patients; 308 (45.83%) patients underwent surgery; and 13 (1.93%) patients died before any intervention. There were significant differences in age between patients with successful hydrostatic reduction (median 7 months) and patients needing surgery (median 9 months) (p<0.001). The number of successful hydrostatic reductions increased during the 11 years of the study (R2=0.88). One patient (0.15%) died after hydrostatic reduction, and 10 (1.49%) died after surgery.

Conclusion Hydrostatic reduction with intermittent radiography was performed successfully in more than half of the patients with acceptable complication rates.

Protocol for a Systematic Review of Outcomes From Microsurgical Free Tissue Transfer Performed on Short-term Surgical Missions in Low-income and Middle-income Countries

Background: In many units around the world, microsurgical free tissue transfer represents the gold standard for reconstruction of significant soft tissue defects following cancer, trauma or infection. However, many reconstructive units in low-income and middle-income countries (LMICs) do not yet have access to the resources, infrastructure or training required to perform any microsurgical procedures. Long-term international collaborations have been formed with annual short-term reconstructive missions conducting microsurgery. In the first instance, these provide reconstructive surgery to those who need it. In the longer-term, they offer an opportunity for teaching and the development of sustainable local services.

Methods: A PRISMA-compliant systematic review and meta-analysis will be performed. A comprehensive, predetermined search strategy will be applied to the MEDLINE and Embase electronic databases from inception to December 2020. All clinical studies presenting sufficient data on free tissue transfer performed on short-term surgical missions (STSMs) in LMICs will be eligible for inclusion. The primary outcomes are rate of free flap failure, rate of emergency return to theatre for free flap salvage and successful salvage rate. The secondary outcomes include postoperative complications and any functional or patient reported outcome measures. Screening of studies, data extraction and assessments of study quality and bias will be conducted by two authors. Individual study quality will be assessed according to the Oxford Evidence-based Medicine Scales of Evidence 2, and risk of bias using either the ‘Revised Cochrane risk of bias tool for randomized trials’ (Rob2), or the ‘Risk of bias in non-randomized studies of interventions’ (ROBINS-I) tools. Overall strength of evidence will be assessed according to the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach.

Discussion: To-date the outcomes of microsurgical procedures performed on STSMs to LMICs are largely unknown. Improved education, funding and allocation of resources are needed to support surgeons in LMICs to perform free tissue transfer. STSMs provide a vehicle for sustainable collaboration and training. Disseminating microsurgical skills could improve the care received by patients living with reconstructive pathology in LMICs, but this is poorly established. This study sets out a robust protocol for a systematic review designed to critically analyse outcomes.