The IDENTIFY study: the investigation and detection of urological neoplasia in patients referred with suspected urinary tract cancer - a multicentre observational study

Objective To evaluate the contemporary prevalence of urinary tract cancer (bladder cancer, upper tract urothelial cancer [UTUC] and renal cancer) in patients referred to secondary care with haematuria, adjusted for established patient risk markers and geographical variation. Patients and Methods This was an international multicentre prospective observational study. We included patients aged ≥16 years, referred to secondary care with suspected urinary tract cancer. Patients with a known or previous urological malignancy were excluded. We estimated the prevalence of bladder cancer, UTUC, renal cancer and prostate cancer; stratified by age, type of haematuria, sex, and smoking. We used a multivariable mixed-effects logistic regression to adjust cancer prevalence for age, type of haematuria, sex, smoking, hospitals, and countries. Results Of the 11 059 patients assessed for eligibility, 10 896 were included from 110 hospitals across 26 countries. The overall adjusted cancer prevalence (n = 2257) was 28.2% (95% confidence interval [CI] 22.3–34.1), bladder cancer (n = 1951) 24.7% (95% CI 19.1–30.2), UTUC (n = 128) 1.14% (95% CI 0.77–1.52), renal cancer (n = 107) 1.05% (95% CI 0.80–1.29), and prostate cancer (n = 124) 1.75% (95% CI 1.32–2.18). The odds ratios for patient risk markers in the model for all cancers were: age 1.04 (95% CI 1.03–1.05; P < 0.001), visible haematuria 3.47 (95% CI 2.90–4.15; P < 0.001), male sex 1.30 (95% CI 1.14–1.50; P < 0.001), and smoking 2.70 (95% CI 2.30–3.18; P < 0.001). Conclusions A better understanding of cancer prevalence across an international population is required to inform clinical guidelines. We are the first to report urinary tract cancer prevalence across an international population in patients referred to secondary care, adjusted for patient risk markers and geographical variation. Bladder cancer was the most prevalent disease. Visible haematuria was the strongest predictor for urinary tract cancer

Developing a Diagnostic Multivariable Prediction Model for Urinary Tract Cancer in Patients Referred with Haematuria: Results from the IDENTIFY Collaborative Study

377siBackground: Patient factors associated with urinary tract cancer can be used to risk stratify patients referred with haematuria, prioritising those with a higher risk of cancer for prompt investigation. Objective: To develop a prediction model for urinary tract cancer in patients referred with haematuria. Design, setting, and participants: A prospective observational study was conducted in 10 282 patients from 110 hospitals across 26 countries, aged ≥16 yr and referred to secondary care with haematuria. Patients with a known or previous urological malignancy were excluded. Outcome measurements and statistical analysis: The primary outcomes were the presence or absence of urinary tract cancer (bladder cancer, upper tract urothelial cancer [UTUC], and renal cancer). Mixed-effect multivariable logistic regression was performed with site and country as random effects and clinically important patient-level candidate predictors, chosen a priori, as fixed effects. Predictors were selected primarily using clinical reasoning, in addition to backward stepwise selection. Calibration and discrimination were calculated, and bootstrap validation was performed to calculate optimism. Results and limitations: The unadjusted prevalence was 17.2% (n = 1763) for bladder cancer, 1.20% (n = 123) for UTUC, and 1.00% (n = 103) for renal cancer. The final model included predictors of increased risk (visible haematuria, age, smoking history, male sex, and family history) and reduced risk (previous haematuria investigations, urinary tract infection, dysuria/suprapubic pain, anticoagulation, catheter use, and previous pelvic radiotherapy). The area under the receiver operating characteristic curve of the final model was 0.86 (95% confidence interval 0.85-0.87). The model is limited to patients without previous urological malignancy. Conclusions: This cancer prediction model is the first to consider established and novel urinary tract cancer diagnostic markers. It can be used in secondary care for risk stratifying patients and aid the clinician's decision-making process in prioritising patients for investigation. Patient summary: We have developed a tool that uses a person's characteristics to determine the risk of cancer if that person develops blood in the urine (haematuria). This can be used to help prioritise patients for further investigation.noneopenKhadhouri, Sinan; Gallagher, Kevin M.; MacKenzie, Kenneth R.; Shah, Taimur T.; Gao, Chuanyu; Moore, Sacha; Zimmermann, Eleanor F.; Edison, Eric; Jefferies, Matthew; Nambiar, Arjun; Anbarasan, Thineskrishna; Mannas, Miles P.; Lee, Taeweon; Marra, Giancarlo; Gómez Rivas, Juan; Marcq, Gautier; Assmus, Mark A.; Uçar, Taha; Claps, Francesco; Boltri, Matteo; La Montagna, Giuseppe; Burnhope, Tara; Nkwam, Nkwam; Austin, Tomas; Boxall, Nicholas E.; Downey, Alison P.; Sukhu, Troy A.; Antón-Juanilla, Marta; Rai, Sonpreet; Chin, Yew-Fung; Moore, Madeline; Drake, Tamsin; Green, James S.A.; Goulao, Beatriz; MacLennan, Graeme; Nielsen, Matthew; McGrath, John S.; Kasivisvanathan, Veeru; Chaudry, Aasem; Sharma, Abhishek; Bennett, Adam; Ahmad, Adnan; Abroaf, Ahmed; Suliman, Ahmed Musa; Lloyd, Aimee; McKay, Alastair; Wong, Albert; Silva, Alberto; Schneider, Alexandre; MacKay, Alison; Knight, Allen; Grigorakis, Alkiviadis; Bdesha, Amar; Nagle, Amy; Cebola, Ana; Dhanasekaran, Ananda Kumar; Kondža, Andraž; Barcelos, André; Galosi, Andrea Benedetto; Ebur, Andrea; Minervini, Andrea; Russell, Andrew; Webb, Andrew; de Jalón, Ángel García; Desai, Ankit; Czech, Anna Katarzyna; Mainwaring, Anna; Adimonye, Anthony; Das, Arighno; Figueiredo, Arnaldo; Villers, Arnauld; Leminski, Artur; Chippagiri, Arvinda; Lal, Asim Ahmed; Yıldırım, Asıf; Voulgaris, Athanasios Marios; Uzan, Audrey; Oo, Aye Moh Moh; Younis, Ayman; Zelhof, Bachar; Mukhtar, Bashir; Ayres, Ben; Challacombe, Ben; Sherwood, Benedict; Ristau, Benjamin; Lai, Billy; Nellensteijn, Brechtje; Schreiter, Brielle; Trombetta, Carlo; Dowling, Catherine; Hobbs, Catherine; Benitez, Cayo Augusto Estigarribia; Lebacle, Cédric; Ho, Cherrie Wing Yin; Ng, Chi-Fai; Mount, Chloe; Lam, Chon Meng; Blick, Chris; Brown, Christian; Gallegos, Christopher; Higgs, Claire; Browne, Clíodhna; McCann, Conor; Plaza Alonso, Cristina; Beder, Daniel; Cohen, Daniel; Gordon, Daniel; Wilby, Daniel; Gordon, Danny; Hrouda, David; Lau, David Hua Wu; Karsza, Dávid; Mak, David; Martin-Way, David; Suthaharan, Denula; Patel, Dhruv; Carrion, Diego M; Nyanhongo, Donald; Bass, Edward; Mains, Edward; Chau, Edwin; Canelon Castillo, Elba; Day, Elizabeth; Desouky, Elsayed; Gaines, Emily; Papworth, Emma; Yuruk, Emrah; Kilic, Enes; Dinneen, Eoin; Palagonia, Erika; Xylinas, Evanguelos; Khawaja, Faizan; Cimarra, Fernando; Bardet, Florian; Kum, Francesca; Peters, Francesca; Kovács, Gábor; Tanasescu, Geroge; Hellawell, Giles; Tasso, Giovanni; Lam, Gitte; La Montagna, Giuseppe; Pizzuto, Giuseppe; Lenart, Gordan; MacLennan, Graeme; Özgür, Günal; Bi, Hai; Lyons, Hannah; Warren, Hannah; Ahmed, Hashim; Simpson, Helen; Burden, Helena; Gresty, Helena; Rios Pita, Hernado; Clarke, Holly; Serag, Hosam; Kynaston, Howard; Crawford-Smith, Hugh; Mostafid, Hugh; Otaola-Arca, Hugo; Koo, Hui Fen; Ibrahim, Ibrahim; Ouzaid, Idir; Puche-Sanz, Ignacio; Tomašković, Igor; Tinay, Ilker; Sahibzada, Iqbal; Thangasamy, Isaac; Cadena, Iván Revelo; Irani, Jacques; Udzik, Jakub; Brittain, James; Catto, James; Green, James; Tweedle, James; Hernando, Jamie Borrego; Leask, Jamie; Kalsi, Jas; Frankel, Jason; Toniolo, Jason; Raman, Jay D.; Courcier, Jean; Kumaradeevan, Jeevan; Clark, Jennifer; Jones, Jennifer; Teoh, Jeremy Yuen-Chun; Iacovou, John; Kelly, John; Selph, John P.; Aning, Jonathan; Deeks, Jon; Cobley, Jonathan; Olivier, Jonathan; Maw, Jonny; Herranz-Yagüe, José Antonio; Nolazco, Jose Ignacio; Cózar-Olmo, Jose Manuel; Bagley, Joseph; Jelski, Joseph; Norris, Joseph; Testa, Joseph; Meeks, Joshua; Hernandez, Juan; Vásquez, Juan Luis; Randhawa, Karen; Dhera, Karishma; Gronostaj, Katarzyna; Houlton, Kathleen; Lehman, Kathleen; Gillams, Kathryn; Adasonla, Kelvin; Brown, Kevin; Murtagh, Kevin; Mistry, Kiki; Davenport, Kim; Kitamura, Kosuke; Derbyshire, Laura; Clarke, Laurence; Morton, Lawrie; Martinez, Levin; Goldsmith, Louise; Paramore, Louise; Cormier, Luc; Dell'Atti, Lucio; Simmons, Lucy; Martinez-Piñeiro, Luis; Rico, Luis; Chan, Luke; Forster, Luke; Ma, Lulin; Moore, Madeline; Gallego, Maria Camacho; Freire, Maria José; Emberton, Mark; Feneley, Mark; Antón-Juanilla, Marta; Rivero, Marta Viridiana Muñoz; Pirša, Matea; Tallè, Matteo; Crockett, Matthew; Liew, Matthew; Trail, Matthew; Peters, Max; Cooper, Meghan; Kulkarni, Meghana; Ager, Michael; He, Ming; Li, Mo; Omran Breish, Mohamed; Tarin, Mohamed; Aldiwani, Mohammed; Matanhelia, Mudit; Pasha, Muhammad; Akalın, Mustafa Kaan; Abdullah, Nasreen; Hale, Nathan; Gadiyar, Neha; Kocher, Neil; Bullock, Nicholas; Campain, Nicholas; Pavan, Nicola; Al-Ibraheem, Nihad; Bhatt, Nikita; Bedi, Nishant; Shrotri, Nitin; Lobo, Niyati; Balderas, Olga; Kouli, Omar; Capoun, Otakar; Oteo Manjavacas, Pablo; Gontero, Paolo; Mariappan, Paramananthan; Marchiñena, Patricio Garcia; Erotocritou, Paul; Sweeney, Paul; Planelles, Paula; Acher, Peter; Black, Peter C.; Osei-Bonsu, Peter K; Østergren, Peter; Smith, Peter; Willemse, Peter-Paul Michiel; Chlosta, Piotr L.; Ul Ain, Qurrat; Barratt, Rachel; Esler, Rachel; Khalid, Raihan; Hsu, Ray; Stamirowski, Remigiusz; Mangat, Reshma; Cruz, Ricardo; Ellis, Ricky; Adams, Robert; Hessell, Robert; Oomen, Robert J.A.; McConkey, Robert; Ritchie, Robert; Jarimba, Roberto; Chahal, Rohit; Andres, Rosado Mario; Hawkins, Rosalyn; David, Rotimi; Manecksha, Rustom P.; Agrawal, Sachin; Hamid, Syed Sami; Deem, Samuel; Goonewardene, Sanchia; Swami, Satchi Kuchibhotla; Hori, Satoshi; Khan, Shahid; Mohammud Inder, Shakeel; Sangaralingam, Shanthi; Marathe, Shekhar; Raveenthiran, Sheliyan; Horie, Shigeo; Sengupta, Shomik; Parson, Sian; Parker, Sidney; Hawlina, Simon; Williams, Simon; Mazzoli, Simone; Grzegorz Kata, Slawomir; Pinheiro Lopes, Sofia; Ramos, Sónia; Rai, Sonpreet; Rintoul-Hoad, Sophie; O'Meara, Sorcha; Morris, Steve; Turner, Stacey; Venturini, Stefano; Almpanis, Stephanos; Joniau, Steven; Jain, Sunjay; Mallett, Susan; Nikles, Sven; Shahzad, null; Yan, Sylvia; Lee, Taeweon; Uçar, Taha; Drake, Tamsin; Toma, Tarq; Cabañuz Plo, Teresa; Bonnin, Thierry; Muilwijk, Tim; Wollin, Tim; Chu, Timothy Shun Man; Appanna, Timson; Brophy, Tom; Ellul, Tom; Austin, Tomas; Smrkolj, Tomaž; Rowe, Tracey; Sukhu, Troy; Patel, Trushar; Garg, Tullika; Çaşkurlu, Turhan; Bele, Uros; Haroon, Usman; Crespo-Atín, Víctor; Parejo Cortes, Victor; Capapé Poves, Victoria; Gnanapragasam, Vincent; Gauhar, Vineet; During, Vinnie; Kumar, Vivek; Fiala, Vojtech; Mahmalji, Wasim; Lam, Wayne; Fung Chin, Yew; Filtekin, Yigit; Chyn Phan, Yih; Ibrahim, Youssed; Glaser, Zachary A; Abiddin, Zainal Adwin; Qin, Zijian; Zotter, Zsuzsanna; Zainuddin, ZulkifliKhadhouri, Sinan; Gallagher, Kevin M.; Mackenzie, Kenneth R.; Shah, Taimur T.; Gao, Chuanyu; Moore, Sacha; Zimmermann, Eleanor F.; Edison, Eric; Jefferies, Matthew; Nambiar, Arjun; Anbarasan, Thineskrishna; Mannas, Miles P.; Lee, Taeweon; Marra, Giancarlo; Gómez Rivas, Juan; Marcq, Gautier; Assmus, Mark A.; Uçar, Taha; Claps, Francesco; Boltri, Matteo; La Montagna, Giuseppe; Burnhope, Tara; Nkwam, Nkwam; Austin, Tomas; Boxall, Nicholas E.; Downey, Alison P.; Sukhu, Troy A.; Antón-Juanilla, Marta; Rai, Sonpreet; Chin, Yew-Fung; Moore, Madeline; Drake, Tamsin; Green, James S. A.; Goulao, Beatriz; Maclennan, Graeme; Nielsen, Matthew; Mcgrath, John S.; Kasivisvanathan, Veeru; Chaudry, Aasem; Sharma, Abhishek; Bennett, Adam; Ahmad, Adnan; Abroaf, Ahmed; Suliman, Ahmed Musa; Lloyd, Aimee; Mckay, Alastair; Wong, Albert; Silva, Alberto; Schneider, Alexandre; Mackay, Alison; Knight, Allen; Grigorakis, Alkiviadis; Bdesha, Amar; Nagle, Amy; Cebola, Ana; Dhanasekaran, Ananda Kumar; Kondža, Andraž; Barcelos, André; Galosi, Andrea Benedetto; Ebur, Andrea; Minervini, Andrea; Russell, Andrew; Webb, Andrew; de Jalón, Ángel García; Desai, Ankit; Czech, Anna Katarzyna; Mainwaring, Anna; Adimonye, Anthony; Das, Arighno; Figueiredo, Arnaldo; Villers, Arnauld; Leminski, Artur; Chippagiri, Arvinda; Lal, Asim Ahmed; Yıldırım, Asıf; Voulgaris, Athanasios Marios; Uzan, Audrey; Oo, Aye Moh Moh; Younis, Ayman; Zelhof, Bachar; Mukhtar, Bashir; Ayres, Ben; Challacombe, Ben; Sherwood, Benedict; Ristau, Benjamin; Lai, Billy; Nellensteijn, Brechtje; Schreiter, Brielle; Trombetta, Carlo; Dowling, Catherine; Hobbs, Catherine; Benitez, Cayo Augusto Estigarribia; Lebacle, Cédric; Ho, Cherrie Wing Yin; Ng, Chi-Fai; Mount, Chloe; Lam, Chon Meng; Blick, Chris; Brown, Christian; Gallegos, Christopher; Higgs, Claire; Browne, Clíodhna; Mccann, Conor; Plaza Alonso, Cristina; Beder, Daniel; Cohen, Daniel; Gordon, Daniel; Wilby, Daniel; Gordon, Danny; Hrouda, David; Lau, David Hua Wu; Karsza, Dávid; Mak, David; Martin-Way, David; Suthaharan, Denula; Patel, Dhruv; Carrion, Diego M; Nyanhongo, Donald; Bass, Edward; Mains, Edward; Chau, Edwin; Canelon Castillo, Elba; Day, Elizabeth; Desouky, Elsayed; Gaines, Emily; Papworth, Emma; Yuruk, Emrah; Kilic, Enes; Dinneen, Eoin; Palagonia, Erika; Xylinas, Evanguelos; Khawaja, Faizan; Cimarra, Fernando; Bardet, Florian; Kum, Francesca; Peters, Francesca; Kovács, Gábor; Tanasescu, Geroge; Hellawell, Giles; Tasso, Giovanni; Lam, Gitte; La Montagna, Giuseppe; Pizzuto, Giuseppe; Lenart, Gordan; Maclennan, Graeme; Özgür, Günal; Bi, Hai; Lyons, Hannah; Warren, Hannah; Ahmed, Hashim; Simpson, Helen; Burden, Helena; Gresty, Helena; Rios Pita, Hernado; Clarke, Holly; Serag, Hosam; Kynaston, Howard; Crawford-Smith, Hugh; Mostafid, Hugh; Otaola-Arca, Hugo; Koo, Hui Fen; Ibrahim, Ibrahim; Ouzaid, Idir; Puche-Sanz, Ignacio; Tomašković, Igor; Tinay, Ilker; Sahibzada, Iqbal; Thangasamy, Isaac; Cadena, Iván Revelo; Irani, Jacques; Udzik, Jakub; Brittain, James; Catto, James; Green, James; Tweedle, James; Hernando, Jamie Borrego; Leask, Jamie; Kalsi, Jas; Frankel, Jason; Toniolo, Jason; Raman, Jay D.; Courcier, Jean; Kumaradeevan, Jeevan; Clark, Jennifer; Jones, Jennifer; Teoh, Jeremy Yuen-Chun; Iacovou, John; Kelly, John; Selph, John P.; Aning, Jonathan; Deeks, Jon; Cobley, Jonathan; Olivier, Jonathan; Maw, Jonny; Herranz-Yagüe, José Antonio; Nolazco, Jose Ignacio; Cózar-Olmo, Jose Manuel; Bagley, Joseph; Jelski, Joseph; Norris, Joseph; Testa, Joseph; Meeks, Joshua; Hernandez, Juan; Vásquez, Juan Luis; Randhawa, Karen; Dhera, Karishma; Gronostaj, Katarzyna; Houlton, Kathleen; Lehman, Kathleen; Gillams, Kathryn; Adasonla, Kelvin; Brown, Kevin; Murtagh, Kevin; Mistry, Kiki; Davenport, Kim; Kitamura, Kosuke; Derbyshire, Laura; Clarke, Laurence; Morton, Lawrie; Martinez, Levin; Goldsmith, Louise; Paramore, Louise; Cormier, Luc; Dell'Atti, Lucio; Simmons, Lucy; Martinez-Piñeiro, Luis; Rico, Luis; Chan, Luke; Forster, Luke; Ma, Lulin; Moore, Madeline; Gallego, Maria Camacho; Freire, Maria José; Emberton, Mark; Feneley, Mark; Antón-Juanilla, Marta; Rivero, Marta Viridiana Muñoz; Pirša, Matea; Tallè, Matteo; Crockett, Matthew; Liew, Matthew; Trail, Matthew; Peters, Max; Cooper, Meghan; Kulkarni, Meghana; Ager, Michael; He, Ming; Li, Mo; Omran Breish, Mohamed; Tarin, Mohamed; Aldiwani, Mohammed; Matanhelia, Mudit; Pasha, Muhammad; Akalın, Mustafa Kaan; Abdullah, Nasreen; Hale, Nathan; Gadiyar, Neha; Kocher, Neil; Bullock, Nicholas; Campain, Nicholas; Pavan, Nicola; Al-Ibraheem, Nihad; Bhatt, Nikita; Bedi, Nishant; Shrotri, Nitin; Lobo, Niyati; Balderas, Olga; Kouli, Omar; Capoun, Otakar; Oteo Manjavacas, Pablo; Gontero, Paolo; Mariappan, Paramananthan; Marchiñena, Patricio Garcia; Erotocritou, Paul; Sweeney, Paul; Planelles, Paula; Acher, Peter; Black, Peter C.; Osei-Bonsu, Peter K; Østergren, Peter; Smith, Peter; Willemse, Peter-Paul Michiel; Chlosta, Piotr L.; Ul Ain, Qurrat; Barratt, Rachel; Esler, Rachel; Khalid, Raihan; Hsu, Ray; Stamirowski, Remigiusz; Mangat, Reshma; Cruz, Ricardo; Ellis, Ricky; Adams, Robert; Hessell, Robert; Oomen, Robert J. A.; Mcconkey, Robert; Ritchie, Robert; Jarimba, Roberto; Chahal, Rohit; Andres, Rosado Mario; Hawkins, Rosalyn; David, Rotimi; Manecksha, Rustom P.; Agrawal, Sachin; Hamid, Syed Sami; Deem, Samuel; Goonewardene, Sanchia; Swami, Satchi Kuchibhotla; Hori, Satoshi; Khan, Shahid; Mohammud Inder, Shakeel; Sangaralingam, Shanthi; Marathe, Shekhar; Raveenthiran, Sheliyan; Horie, Shigeo; Sengupta, Shomik; Parson, Sian; Parker, Sidney; Hawlina, Simon; Williams, Simon; Mazzoli, Simone; Grzegorz Kata, Slawomir; Pinheiro Lopes, Sofia; Ramos, Sónia; Rai, Sonpreet; Rintoul-Hoad, Sophie; O'Meara, Sorcha; Morris, Steve; Turner, Stacey; Venturini, Stefano; Almpanis, Stephanos; Joniau, Steven; Jain, Sunjay; Mallett, Susan; Nikles, Sven; Shahzad, Null; Yan, Sylvia; Lee, Taeweon; Uçar, Taha; Drake, Tamsin; Toma, Tarq; Cabañuz Plo, Teresa; Bonnin, Thierry; Muilwijk, Tim; Wollin, Tim; Chu, Timothy Shun Man; Appanna, Timson; Brophy, Tom; Ellul, Tom; Austin, Tomas; Smrkolj, Tomaž; Rowe, Tracey; Sukhu, Troy; Patel, Trushar; Garg, Tullika; Çaşkurlu, Turhan; Bele, Uros; Haroon, Usman; Crespo-Atín, Víctor; Parejo Cortes, Victor; Capapé Poves, Victoria; Gnanapragasam, Vincent; Gauhar, Vineet; During, Vinnie; Kumar, Vivek; Fiala, Vojtech; Mahmalji, Wasim; Lam, Wayne; Fung Chin, Yew; Filtekin, Yigit; Chyn Phan, Yih; Ibrahim, Youssed; Glaser, Zachary A; Abiddin, Zainal Adwin; Qin, Zijian; Zotter, Zsuzsanna; Zainuddin, Zulkifl

Prospective observational cohort study on grading the severity of postoperative complications in global surgery research

Background The Clavien–Dindo classification is perhaps the most widely used approach for reporting postoperative complications in clinical trials. This system classifies complication severity by the treatment provided. However, it is unclear whether the Clavien–Dindo system can be used internationally in studies across differing healthcare systems in high- (HICs) and low- and middle-income countries (LMICs). Methods This was a secondary analysis of the International Surgical Outcomes Study (ISOS), a prospective observational cohort study of elective surgery in adults. Data collection occurred over a 7-day period. Severity of complications was graded using Clavien–Dindo and the simpler ISOS grading (mild, moderate or severe, based on guided investigator judgement). Severity grading was compared using the intraclass correlation coefficient (ICC). Data are presented as frequencies and ICC values (with 95 per cent c.i.). The analysis was stratified by income status of the country, comparing HICs with LMICs. Results A total of 44 814 patients were recruited from 474 hospitals in 27 countries (19 HICs and 8 LMICs). Some 7508 patients (16·8 per cent) experienced at least one postoperative complication, equivalent to 11 664 complications in total. Using the ISOS classification, 5504 of 11 664 complications (47·2 per cent) were graded as mild, 4244 (36·4 per cent) as moderate and 1916 (16·4 per cent) as severe. Using Clavien–Dindo, 6781 of 11 664 complications (58·1 per cent) were graded as I or II, 1740 (14·9 per cent) as III, 2408 (20·6 per cent) as IV and 735 (6·3 per cent) as V. Agreement between classification systems was poor overall (ICC 0·41, 95 per cent c.i. 0·20 to 0·55), and in LMICs (ICC 0·23, 0·05 to 0·38) and HICs (ICC 0·46, 0·25 to 0·59). Conclusion Caution is recommended when using a treatment approach to grade complications in global surgery studies, as this may introduce bias unintentionally

Critical care admission following elective surgery was not associated with survival benefit:prospective analysis of data from 27 countries

Purpose: As global initiatives increase patient access to surgical treatments, there is a need to define optimal levels of perioperative care. Our aim was to describe the relationship between the provision and use of critical care resources and postoperative mortality. Methods: Planned analysis of data collected during an international 7-day cohort study of adults undergoing elective in-patient surgery. We used risk-adjusted mixed-effects logistic regression models to evaluate the association between admission to critical care immediately after surgery and in-hospital mortality. We evaluated hospital-level associations between mortality and critical care admission immediately after surgery, critical care admission to treat life-threatening complications, and hospital provision of critical care beds. We evaluated the effect of national income using interaction tests. Results: 44,814 patients from 474 hospitals in 27 countries were available for analysis. Death was more frequent amongst patients admitted directly to critical care after surgery (critical care: 103/4317 patients [2%], standard ward: 99/39,566 patients [0.3%]; adjusted OR 3.01 [2.10–5.21]; p &lt; 0.001). This association may differ with national income (high income countries OR 2.50 vs. low and middle income countries OR 4.68; p = 0.07). At hospital level, there was no association between mortality and critical care admission directly after surgery (p = 0.26), critical care admission to treat complications (p = 0.33), or provision of critical care beds (p = 0.70). Findings of the hospital-level analyses were not affected by national income status. A sensitivity analysis including only high-risk patients yielded similar findings. Conclusions: We did not identify any survival benefit from critical care admission following surgery

The surgical safety checklist and patient outcomes after surgery: a prospective observational cohort study, systematic review and meta-analysis

© 2017 British Journal of Anaesthesia Background: The surgical safety checklist is widely used to improve the quality of perioperative care. However, clinicians continue to debate the clinical effectiveness of this tool. Methods: Prospective analysis of data from the International Surgical Outcomes Study (ISOS), an international observational study of elective in-patient surgery, accompanied by a systematic review and meta-analysis of published literature. The exposure was surgical safety checklist use. The primary outcome was in-hospital mortality and the secondary outcome was postoperative complications. In the ISOS cohort, a multivariable multi-level generalized linear model was used to test associations. To further contextualise these findings, we included the results from the ISOS cohort in a meta-analysis. Results are reported as odds ratios (OR) with 95% confidence intervals. Results: We included 44 814 patients from 497 hospitals in 27 countries in the ISOS analysis. There were 40 245 (89.8%) patients exposed to the checklist, whilst 7508 (16.8%) sustained ≥1 postoperative complications and 207 (0.5%) died before hospital discharge. Checklist exposure was associated with reduced mortality [odds ratio (OR) 0.49 (0.32–0.77); P\u3c0.01], but no difference in complication rates [OR 1.02 (0.88–1.19); P=0.75]. In a systematic review, we screened 3732 records and identified 11 eligible studies of 453 292 patients including the ISOS cohort. Checklist exposure was associated with both reduced postoperative mortality [OR 0.75 (0.62–0.92); P\u3c0.01; I2=87%] and reduced complication rates [OR 0.73 (0.61–0.88); P\u3c0.01; I2=89%). Conclusions: Patients exposed to a surgical safety checklist experience better postoperative outcomes, but this could simply reflect wider quality of care in hospitals where checklist use is routine

Search for intermediate-mass black hole binaries in the third observing run of Advanced LIGO and Advanced Virgo

International audienceIntermediate-mass black holes (IMBHs) span the approximate mass range 100−105 M⊙, between black holes (BHs) that formed by stellar collapse and the supermassive BHs at the centers of galaxies. Mergers of IMBH binaries are the most energetic gravitational-wave sources accessible by the terrestrial detector network. Searches of the first two observing runs of Advanced LIGO and Advanced Virgo did not yield any significant IMBH binary signals. In the third observing run (O3), the increased network sensitivity enabled the detection of GW190521, a signal consistent with a binary merger of mass ∼150 M⊙ providing direct evidence of IMBH formation. Here, we report on a dedicated search of O3 data for further IMBH binary mergers, combining both modeled (matched filter) and model-independent search methods. We find some marginal candidates, but none are sufficiently significant to indicate detection of further IMBH mergers. We quantify the sensitivity of the individual search methods and of the combined search using a suite of IMBH binary signals obtained via numerical relativity, including the effects of spins misaligned with the binary orbital axis, and present the resulting upper limits on astrophysical merger rates. Our most stringent limit is for equal mass and aligned spin BH binary of total mass 200 M⊙ and effective aligned spin 0.8 at 0.056 Gpc−3 yr−1 (90% confidence), a factor of 3.5 more constraining than previous LIGO-Virgo limits. We also update the estimated rate of mergers similar to GW190521 to 0.08 Gpc−3 yr−1.Key words: gravitational waves / stars: black holes / black hole physicsCorresponding author: W. Del Pozzo, e-mail: [email protected]† Deceased, August 2020

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field