23 research outputs found

    Global economic burden of unmet surgical need for appendicitis

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    Background: There is a substantial gap in provision of adequate surgical care in many low-and middle-income countries. This study aimed to identify the economic burden of unmet surgical need for the common condition of appendicitis. Methods: Data on the incidence of appendicitis from 170 countries and two different approaches were used to estimate numbers of patients who do not receive surgery: as a fixed proportion of the total unmet surgical need per country (approach 1); and based on country income status (approach 2). Indirect costs with current levels of access and local quality, and those if quality were at the standards of high-income countries, were estimated. A human capital approach was applied, focusing on the economic burden resulting from premature death and absenteeism. Results: Excess mortality was 4185 per 100 000 cases of appendicitis using approach 1 and 3448 per 100 000 using approach 2. The economic burden of continuing current levels of access and local quality was US 92492millionusingapproach1and92 492 million using approach 1 and 73 141 million using approach 2. The economic burden of not providing surgical care to the standards of high-income countries was 95004millionusingapproach1and95 004 million using approach 1 and 75 666 million using approach 2. The largest share of these costs resulted from premature death (97.7 per cent) and lack of access (97.0 per cent) in contrast to lack of quality. Conclusion: For a comparatively non-complex emergency condition such as appendicitis, increasing access to care should be prioritized. Although improving quality of care should not be neglected, increasing provision of care at current standards could reduce societal costs substantially

    Laparoscopy in management of appendicitis in high-, middle-, and low-income countries: a multicenter, prospective, cohort study.

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    BACKGROUND: Appendicitis is the most common abdominal surgical emergency worldwide. Differences between high- and low-income settings in the availability of laparoscopic appendectomy, alternative management choices, and outcomes are poorly described. The aim was to identify variation in surgical management and outcomes of appendicitis within low-, middle-, and high-Human Development Index (HDI) countries worldwide. METHODS: This is a multicenter, international prospective cohort study. Consecutive sampling of patients undergoing emergency appendectomy over 6 months was conducted. Follow-up lasted 30 days. RESULTS: 4546 patients from 52 countries underwent appendectomy (2499 high-, 1540 middle-, and 507 low-HDI groups). Surgical site infection (SSI) rates were higher in low-HDI (OR 2.57, 95% CI 1.33-4.99, p = 0.005) but not middle-HDI countries (OR 1.38, 95% CI 0.76-2.52, p = 0.291), compared with high-HDI countries after adjustment. A laparoscopic approach was common in high-HDI countries (1693/2499, 67.7%), but infrequent in low-HDI (41/507, 8.1%) and middle-HDI (132/1540, 8.6%) groups. After accounting for case-mix, laparoscopy was still associated with fewer overall complications (OR 0.55, 95% CI 0.42-0.71, p < 0.001) and SSIs (OR 0.22, 95% CI 0.14-0.33, p < 0.001). In propensity-score matched groups within low-/middle-HDI countries, laparoscopy was still associated with fewer overall complications (OR 0.23 95% CI 0.11-0.44) and SSI (OR 0.21 95% CI 0.09-0.45). CONCLUSION: A laparoscopic approach is associated with better outcomes and availability appears to differ by country HDI. Despite the profound clinical, operational, and financial barriers to its widespread introduction, laparoscopy could significantly improve outcomes for patients in low-resource environments. TRIAL REGISTRATION: NCT02179112

    Pooled analysis of WHO Surgical Safety Checklist use and mortality after emergency laparotomy

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    Background The World Health Organization (WHO) Surgical Safety Checklist has fostered safe practice for 10 years, yet its place in emergency surgery has not been assessed on a global scale. The aim of this study was to evaluate reported checklist use in emergency settings and examine the relationship with perioperative mortality in patients who had emergency laparotomy. Methods In two multinational cohort studies, adults undergoing emergency laparotomy were compared with those having elective gastrointestinal surgery. Relationships between reported checklist use and mortality were determined using multivariable logistic regression and bootstrapped simulation. Results Of 12 296 patients included from 76 countries, 4843 underwent emergency laparotomy. After adjusting for patient and disease factors, checklist use before emergency laparotomy was more common in countries with a high Human Development Index (HDI) (2455 of 2741, 89.6 per cent) compared with that in countries with a middle (753 of 1242, 60.6 per cent; odds ratio (OR) 0.17, 95 per cent c.i. 0.14 to 0.21, P <0001) or low (363 of 860, 422 per cent; OR 008, 007 to 010, P <0.001) HDI. Checklist use was less common in elective surgery than for emergency laparotomy in high-HDI countries (risk difference -94 (95 per cent c.i. -11.9 to -6.9) per cent; P <0001), but the relationship was reversed in low-HDI countries (+121 (+7.0 to +173) per cent; P <0001). In multivariable models, checklist use was associated with a lower 30-day perioperative mortality (OR 0.60, 0.50 to 073; P <0.001). The greatest absolute benefit was seen for emergency surgery in low- and middle-HDI countries. Conclusion Checklist use in emergency laparotomy was associated with a significantly lower perioperative mortality rate. Checklist use in low-HDI countries was half that in high-HDI countries.Peer reviewe

    Mortality of emergency abdominal surgery in high-, middle- and low-income countries

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    Background: Surgical mortality data are collected routinely in high-income countries, yet virtually no low- or middle-income countries have outcome surveillance in place. The aim was prospectively to collect worldwide mortality data following emergency abdominal surgery, comparing findings across countries with a low, middle or high Human Development Index (HDI). Methods: This was a prospective, multicentre, cohort study. Self-selected hospitals performing emergency surgery submitted prespecified data for consecutive patients from at least one 2-week interval during July to December 2014. Postoperative mortality was analysed by hierarchical multivariable logistic regression. Results: Data were obtained for 10 745 patients from 357 centres in 58 countries; 6538 were from high-, 2889 from middle- and 1318 from low-HDI settings. The overall mortality rate was 1⋅6 per cent at 24 h (high 1⋅1 per cent, middle 1⋅9 per cent, low 3⋅4 per cent; P < 0⋅001), increasing to 5⋅4 per cent by 30 days (high 4⋅5 per cent, middle 6⋅0 per cent, low 8⋅6 per cent; P < 0⋅001). Of the 578 patients who died, 404 (69⋅9 per cent) did so between 24 h and 30 days following surgery (high 74⋅2 per cent, middle 68⋅8 per cent, low 60⋅5 per cent). After adjustment, 30-day mortality remained higher in middle-income (odds ratio (OR) 2⋅78, 95 per cent c.i. 1⋅84 to 4⋅20) and low-income (OR 2⋅97, 1⋅84 to 4⋅81) countries. Surgical safety checklist use was less frequent in low- and middle-income countries, but when used was associated with reduced mortality at 30 days. Conclusion: Mortality is three times higher in low- compared with high-HDI countries even when adjusted for prognostic factors. Patient safety factors may have an important role. Registration number: NCT02179112 (http://www.clinicaltrials.gov)

    Global variation in anastomosis and end colostomy formation following left-sided colorectal resection

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    Background End colostomy rates following colorectal resection vary across institutions in high-income settings, being influenced by patient, disease, surgeon and system factors. This study aimed to assess global variation in end colostomy rates after left-sided colorectal resection. Methods This study comprised an analysis of GlobalSurg-1 and -2 international, prospective, observational cohort studies (2014, 2016), including consecutive adult patients undergoing elective or emergency left-sided colorectal resection within discrete 2-week windows. Countries were grouped into high-, middle- and low-income tertiles according to the United Nations Human Development Index (HDI). Factors associated with colostomy formation versus primary anastomosis were explored using a multilevel, multivariable logistic regression model. Results In total, 1635 patients from 242 hospitals in 57 countries undergoing left-sided colorectal resection were included: 113 (6·9 per cent) from low-HDI, 254 (15·5 per cent) from middle-HDI and 1268 (77·6 per cent) from high-HDI countries. There was a higher proportion of patients with perforated disease (57·5, 40·9 and 35·4 per cent; P < 0·001) and subsequent use of end colostomy (52·2, 24·8 and 18·9 per cent; P < 0·001) in low- compared with middle- and high-HDI settings. The association with colostomy use in low-HDI settings persisted (odds ratio (OR) 3·20, 95 per cent c.i. 1·35 to 7·57; P = 0·008) after risk adjustment for malignant disease (OR 2·34, 1·65 to 3·32; P < 0·001), emergency surgery (OR 4·08, 2·73 to 6·10; P < 0·001), time to operation at least 48 h (OR 1·99, 1·28 to 3·09; P = 0·002) and disease perforation (OR 4·00, 2·81 to 5·69; P < 0·001). Conclusion Global differences existed in the proportion of patients receiving end stomas after left-sided colorectal resection based on income, which went beyond case mix alone

    Investigating the role of AHNAK2 in Pancreatic Ductal Adenocarcinoma

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    Pancreatic ductal adenocarcinoma (PDAC) has poor overall survival due to infrequency, late presentation and lack of diagnostic biomarkers or effective therapies. Prediction models harnessing machine learning may help in early diagnosis. AHNAK2 is associated with oncogenesis in multiple cancers, has potentially a poor prognostic biomarker potential; however its role is unclear. A case-control study was performed on a prospective cohort of PDAC (N=344) and benign pancreatic disease patients (N=360) recruited between 2008 and 2021 from the Barts Pancreatic Tissue Bank (BPTB) with a prediction model trained using routinely-collected clinical variables. Enzyme linked immunosorbent assays (ELISA) were performed on PDAC patients (N=30) and matches healthy controls (N=30) recruited from the BPTB measuring AHNAK2 concentration in plasma. Immunohistochemistry (IHC) of PDAC patient samples (N=14) was performed. In vitro experiments on multiple PDAC cell lines were performed to explore the mechanistic role of AHNAK2. Increased odds of PDAC were observed for age >75 years (Odds ratio (OR) 10.1 [95% confidence interval, 5.6-18.2]; p<0.001 Fisher’s exact test), jaundice and weight loss (OR 3.12 [1.86-5.21] and 3.06 [2.03-4.6] p<0.001). Reduced sodium (OR 4.2 [1.6-10.6]; p=0.006), red blood cell count (OR 0.44 [0.30-0.63]; p<0.001), Creatinine (OR 3.1 [1.4-6.6]; p=0.008) and raised Bilirubin (OR 4.8 [2.9-8.1]; p<0.001), Alkaline phosphatase (ALP) (OR 4.8 [2.9-8.1]; p<0.001) and Alanine Transferase (ALT) (OR 2.6 [1.5-4.4]; p=0.002), were associated with PDAC. Potentially 96.8% sensitivity can be reached with the prediction model (AUROC=0.90 [0.85, 0.94]; Spiegelhalter’s z=-1.8, p=0.07) using routine clinical parameters leading to earlier detection of 84.7% of the PDAC patients using machine learning. AHNAK2 levels discriminated between PDAC and healthy controls (p<0.001, χ2 test) with an AUROC of 0.903 [0.822, 0.985] performing better than CA 19-9. High tissue AHNAK2 expression was associated with stage III-IV disease (p=0.036, Wilcoxon rank sum test). AHNAK2 co-localised with Cortactin, an essential protein in cellular protrusion and invasion in cancer, in multiple cell lines which was attenuated in hypoxia and on Fibronectin and Collagen I substrates. Knockdown of AHNAK2 reduced invasion of Capan-2 and PS1 co-culture spheroid models significantly (p<0.001, Wilcoxon rank sum test). Further validation work is required for the clinical model for earlier detection of PDAC in primary care. AHNAK2 plasma levels could potentially to be used as a diagnostic biomarker in PDAC. There is strong evidence of AHNAK2s role in oncogenesis in PDAC, particularly in the formation of cellular protrusions and invasion in a hypoxia. Therefore, AHNAK2 could be a potential therapeutic target

    The Obscure Potential of AHNAK2

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    AHNAK2 is a protein discovered in 2004, with a strong association with oncogenesis in various epithelial cancers. It has a large 616 kDa tripartite structure and is thought to take part in the formation of large multi-protein complexes. High expression is found in clear cell renal carcinoma, pancreatic ductal adenocarcinoma, uveal melanoma, and lung adenocarcinoma, with a relation to poor prognosis. Little work has been done in exploring the function and relation AHNAK2 has with cancer, with early studies showing promising potential as a future biomarker and therapeutic target

    Differentiating Ductal Adenocarcinoma of the Pancreas from Benign Conditions Using Routine Health Records: A Prospective Case-Control Study

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    The study aimed to develop a prediction model for differentiating suspected PDAC from benign conditions. We used a prospective cohort of patients with pancreatic disease (n = 762) enrolled at the Barts Pancreas Tissue Bank (2008-2021) and performed a case-control study examining the association of PDAC (n = 340) with predictor variables including demographics, comorbidities, lifestyle factors, presenting symptoms and commonly performed blood tests. Age (over 55), weight loss in hypertensive patients, recent symptoms of jaundice, high serum bilirubin, low serum creatinine, high serum alkaline phosphatase, low red blood cell count and low serum sodium were identified as the most important features. These predictors were then used for training several machine-learning-based risk-prediction models on 75% of the cohort. Models were assessed on the remaining 25%. A logistic regression-based model had the best overall performance in the validation cohort (area-under-the-curve = 0.90; Spiegelhalter’s z = −1·82, p = 0.07). Setting a probability threshold of 0.15 guided by the maximum F2-score of 0.855, 96.8% sensitivity was reached in the full cohort, which could lead to earlier detection of 84.7% of the PDAC patients. The prediction model has the potential to be applied in primary, secondary and emergency care settings for the early distinction of suspected PDAC patients and expedited referral to specialist hepato-pancreatico-biliary services

    Determinants of morbidity and mortality following emergency abdominal surgery in children in lowincome and middle-income countries

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    Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resourcepoor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally. Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged &lt;16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression. Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p&lt;0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed. Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas
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