Asian guidelines for UTIs & STIs UTI section: Complicated UTIs with neurogenic bladder.

EPIDEMIOLOGY AND PATHOGENESIS: Urinary tract infection (UTI) in patients with neurogenic bladder causes significant morbidity and mortality. DIAGNOSIS: UTI in neurogenic bladder causes atypical symptomatology. Urine tests are pivotal in confirming or excluding UTI, and in guiding appropriate antibiotic treatment. TREATMENT: 1. Symptomatic UTI warrants appropriate antibiotic treatment with reference to culture results and local antibiotic resistance patterns. Asymptomatic bacteriuria should not be treated, and antibiotic prophylaxis is generally not recommended.2. Adequate bladder drainage is essential in reducing the occurrence of urinary tract infections.3. Recurrent UTI in neurogenic bladder may necessitate the treatment of neurogenic detrusor overactivity and the restoration of low bladder pressure during bladder storage and voiding by drugs or surgery.

Performance and impact of an airway management team launched during the COVID-19 pandemic.

PURPOSE: To determine the performance and impact of an airway management team (AMT) assembled during the COVID-19 pandemic. METHODS: We conducted a retrospective cohort review of all adult patients who had received airway management services from the AMT (n = 269) and administered a survey questionnaire targeting physicians who had the option to activate the AMT (n = 77). The retrospective review determined the performance of the AMT, and the physicians' survey evaluated the impact of the AMT. The study was conducted at a large Canadian health centre (1,133 beds) from 28 March to 30 June 2020. We included patients in the cohort review who were ≥18 yr of age, whose chart showed that the AMT was activated, and whose airway was managed outside the operating room. We reviewed both electronic medical records and paper chart documentation. Outcomes included intubation success, number of intubation attempts, intubation time, team response time, patient contact time, intubation complications, and breaches of personal protective equipment (PPE) protocol. The physicians' survey evaluated the relevance, performance, reasonableness, and clinical utility of the AMT. RESULTS: The AMT intubated 231 patients. Charts showed that 91% of intubations were accomplished on first attempt. The mean (standard deviation) intubation time was 2.1 (0.2) min. The complication rate was minimal. The incidence of breaching PPE protocol items was less than 6%. No AMT members reported COVID-19 symptoms. The response rate for the physician's survey was 36%. The consensus among the participants was that the AMT had considerable clinical utility during the COVID-19 pandemic. CONCLUSION: An AMT assembled during the COVID-19 pandemic showed high competency and effectiveness, and had favourable impact on the main responsible physicians who activated the team.

RéSUMé: OBJECTIF: Déterminer la performance et l'impact d'une équipe de prise en charge des voies aériennes (AMT - Airway Management Team) assemblée pendant la pandémie de COVID-19. MéTHODE: Nous avons réalisé une revue de cohorte rétrospective de tous les patients adultes qui avaient bénéficié des services de prise en charge des voies aériennes par l'AMT (n = 269) et avons soumis un questionnaire aux médecins qui avaient eu la possibilité de faire appel à l'AMT (n = 77). La revue rétrospective a permis de déterminer la performance de l'AMT, et le sondage auprès des médecins a évalué l'impact de cette équipe dédiée. L'étude a été réalisée dans un grand centre de santé canadien (1133 lits) du 28 mars au 30 juin 2020. Dans la revue de cohorte, nous avons inclus des patients âgés de ≥18 ans, dans le dossier médical desquels il était fait mention de l'activation de l'AMT et dont les voies aériennes avaient été prises en charge à l'extérieur de la salle d'opération. Nous avons passé en revue à la fois la documentation des dossiers médicaux informatisés et des dossiers papier. Les résultats mesurés comprenaient le succès de l'intubation, le nombre de tentatives d'intubation, le temps pour intubation, le temps de réponse de l'équipe, le temps de contact avec le patient, les complications de l'intubation et les violations du protocole relatif aux équipements de protection individuelle (EPI). Le sondage auprès des médecins a évalué la pertinence, la performance, le caractère raisonnable et l'utilité clinique de l'AMT. RéSULTATS: L'AMT a intubé 231 patients. Les dossiers ont montré que 91 % des intubations ont réussi à la première tentative. Le temps moyen (écart type) d'intubation était de 2,1 (0,2) min. Le taux de complications était minime. L'incidence d'infractions aux articles du protocole pour les EPI était inférieure à 6 %. Aucun membre de l'AMT n'a rapporté de symptômes de COVID-19. Le taux de réponse au sondage auprès des médecins était de 36 %. Le consensus parmi les participants était que l'AMT était d'une utilité clinique considérable pendant la pandémie de COVID-19. CONCLUSION: Une équipe de prise en charge des voies aériennes assemblée pendant la pandémie de COVID-19 a démontré une compétence et une efficacité élevées et a eu un impact favorable sur les principaux médecins en charge qui ont fait appel à l'équipe.

Automated discovery of noncovalent inhibitors of SARS-CoV-2 main protease by consensus Deep Docking of 40 billion small molecules.

Recent explosive growth of 'make-on-demand' chemical libraries brought unprecedented opportunities but also significant challenges to the field of computer-aided drug discovery. To address this expansion of the accessible chemical universe, molecular docking needs to accurately rank billions of chemical structures, calling for the development of automated hit-selecting protocols to minimize human intervention and error. Herein, we report the development of an artificial intelligence-driven virtual screening pipeline that utilizes Deep Docking with Autodock GPU, Glide SP, FRED, ICM and QuickVina2 programs to screen 40 billion molecules against SARS-CoV-2 main protease (Mpro). This campaign returned a significant number of experimentally confirmed inhibitors of Mpro enzyme, and also enabled to benchmark the performance of twenty-eight hit-selecting strategies of various degrees of stringency and automation. These findings provide new starting scaffolds for hit-to-lead optimization campaigns against Mpro and encourage the development of fully automated end-to-end drug discovery protocols integrating machine learning and human expertise.

Augmentation cystoplasty: Urodynamic and metabolic outcomes at 10-year follow-up.

OBJECTIVE: To review the urodynamic outcomes, renal function and metabolic complications after augmentation cystoplasty with at least 10 years of follow-up. METHODS: Augmentation cystoplasty performed in two tertiary referral centers from 1995 to 2004 were reviewed. Ten years or more postoperative course was studied by review of the clinical notes, urodynamic reports and laboratory results. RESULTS: A total of 40 patients were included in this study. The mean age at surgery was 43 years, and 47.5% of patients were female. Median follow up was 13 years. Bladder capacity significantly increased from 283 ± 151 to 492 ± 123 mL (P < 0.01), with a percentage change of +130%. The compliance of the bladder was increased by 87%, and detrusor overactivity decreased by 54.2%. There were no significant changes in preoperative and postoperative estimated glomerular filtration rate (68.3 mL/min vs. 76.6 mL/min, P = 0.798). Three patients (7.5%) had more than one episode of symptomatic urinary tract infection per year. CONCLUSION: The present study confirms the effectiveness of augmentation cystoplasty in increasing bladder capacity, improving bladder compliance and reducing detrusor overactivity. The preservation of renal function and low metabolic complication rate provide solid evidence for carrying out this time-honored procedure in patients with neurogenic or non-neurogenic bladder dysfunction.

Off-label use of recombinant activated factor VII in surgical and non-surgical patients at 16 Canadian hospitals from 2007 to 2010 (Canadian Registry Report).

PURPOSE: Recombinant activated factor VII (rFVIIa) is a pro-hemostatic drug that is approved for treatment of bleeding in hemophilia patients, but it is frequently used off-label in non-hemophiliacs. The purpose of this study was to determine if the off-label use of rFVIIa is expanding and whether this poses a net harm to patients. METHODS: For this historical cohort study, data were collected on all non-hemophilia patients who received rFVIIa from 2007 to 2010 at 16 Canadian centres, and the pattern of use was examined. Logistic regression was used to determine the prognostic importance of severity of bleeding and the presence of an rFVIIa dose-effect relationship with major adverse events. RESULTS: One thousand three hundred seventy-eight patients received rFVIIa off-label, and 987 (72%) of these patients underwent cardiac surgery. The median [interquartile range] dose was 57 [36-85] µg·kg(-1). Usage increased from 2007 to 2008 (n = 341 and 380, respectively) but decreased in 2009 and 2010 (n = 350 and 307, respectively). Dose of rFVIIa and bleeding severity were associated with measured adverse events (P < 0.05). After adjusting for bleeding severity, dose was not associated with any of the adverse events. CONCLUSIONS: The off-label use of rFVIIa in Canada remains stable. Since severity of bleeding is prognostically important, the benefits of rapidly gaining control of bleeding that is non-responsive to conventional therapies may at times warrant the use of potent hemostatic drugs with established risk profiles, such as rFVIIa.

Percutaneous nephrostomy, nephrolithotomy and combined ureteroscopic lithotripsy using the supine approach.

OBJECTIVES: (1) To evaluate the safety and efficacy of supine percutaneous nephrostomy, nephrolithotomy, and combined percutaneous nephrolithotomy and ureteroscopic lithotripsy. (2) To describe the skill-acquiring process in supine procedures and share our initial experience. DESIGN: Three-staged case series with prospective data collection. SETTING: Two public hospitals in Hong Kong. PATIENTS AND INTERVENTION: Stage 1: Forty patients indicated for percutaneous renal access were recruited for supine percutaneous nephrostomy with prospective data collection. Stage 2: A prospective comparative study of percutaneous nephrolithotomy involving 60 patients allocated non-randomly to a supine (n=25) or prone (n=35) approach was conducted. Stage 3: Data of 11 patients who underwent simultaneous supine percutaneous nephrolithotomy and ureteroscopic lithotripsy were prospectively captured. RESULTS: Stage 1: The procedural success rate was 100%. The mean operating time in unilateral procedures was 44 minutes; one patient had perinephric haematoma as a complication. Stage 2: Overall stone-free rates for prone and supine procedures were 46% and 68%, respectively (P=0.087), and mean operating times were 122 and 123 minutes, respectively (P=0.905). Stage 3: Of the 11 patients, six were rendered stone-free after the first combined procedure, and one experienced transient postoperative fever. There was no major complication. CONCLUSION: Percutaneous nephrolithotomy was feasible via both prone and supine approaches. With the exception of staghorn stones, the supine percutaneous approach was an equally safe and effective option for patients with specific conditions favouring such an approach. The ability to incorporate simultaneous ureteroscopic lithotripsy was an additional benefit of adopting the supine approach.

Comprehensive Canadian review of the off-label use of recombinant activated factor VII in cardiac surgery.

BACKGROUND: This observational study sought to identify the off-label use pattern of recombinant activated factor VII (rFVIIa) in cardiac surgery and to identify predictors of its effectiveness and risk. METHODS AND RESULTS: At 18 Canadian centers, 522 nonhemophiliac cardiac surgical patients received rFVIIa during the period 2003 through 2006; data were available, and retrospectively collected, on 503 patients. The median (quartile 1, quartile 3) units of red blood cells transfused from surgery to therapy and in the 24 hours after therapy were 8 (5, 12) and 2 (1, 5), respectively (P<0.0001). Mortality rate was 32%, and mortality or major morbidity rate was 44%. These rates were within expected ranges (mortality, 27% to 35%; mortality or morbidity, 39% to 48%), which were calculated with a separate cohort of cardiac surgical patients who did not receive rFVIIa used as reference. Independent predictors of complications included instability before therapy (multiple inotropes or intra-aortic balloon pump) and increasing red blood cell units transfused before and after therapy. Variables independently associated with nonresponse included abnormal coagulation parameters and >15 red blood cell units transfused before therapy. CONCLUSIONS: In Canada, rFVIIa is used primarily when standard interventions have failed to control bleeding. In this setting, rFVIIa is associated with reduced blood product transfusions and, after risk adjustment, does not appear to be associated with increased or decreased complication rates. The effectiveness of the drug may be enhanced if it is given early in the course of refractory blood loss in the setting of adequate amounts of circulating coagulation factors.

The role of recombinant factor VIIa in on-pump cardiac surgery: proceedings of the Canadian Consensus Conference.

PURPOSE: Recombinant activated factor VII (rFVIIa) is currently not approved by Health Canada or the Food and Drug Administration for treating excessive blood loss in nonhemophiliac patients undergoing on-pump cardiac surgery, but is increasingly being used "off-label" for this indication. A Canadian Consensus Conference was convened to generate recommendations for rFVIIa use in on-pump cardiac surgery. METHODS: The panel undertook a literature review of the use of rFVIIa in both cardiac and non-cardiac surgery. Appropriateness, timing, and dosage considerations were addressed for three cardiac surgery indications: prophylactic, routine, and rescue uses. Recommendations were based on evidence from the literature and derived by consensus following recognized grading procedures. RESULTS: The panel recommended against prophylactic or routine use of rFVIIa, as there is no evidence at this time that the benefits of rFVIIa outweigh its potential risks compared with standard hemostatic therapies. On the other hand, the panel made a weak recommendation (grade 2C) for the use of rFVIIa (one to two doses of 35-70 microg.kg(-1)) as rescue therapy for blood loss that is refractory to standard hemostatic therapies, despite the lack of randomized controlled trial data for this indication. CONCLUSIONS: In cardiac surgery, the risks and benefits of rFVIIa are unclear, but current evidence suggests that its benefits may outweigh its risks for rescue therapy in selected patients. Methodologically rigorous studies are needed to clarify its riskbenefit profile in cardiac surgery patients.