Streptomyces rare codon UUA: from features associated with 2 adpA related locations to candidate phage regulatory translational bypassing.

In Streptomyces species, the cell cycle involves a switch from an early and vegetative state to a later phase where secondary products including antibiotics are synthesized, aerial hyphae form and sporulation occurs. AdpA, which has two domains, activates the expression of numerous genes involved in the switch from the vegetative growth phase. The adpA mRNA of many Streptomyces species has a UUA codon in a linker region between 5' sequence encoding one domain and 3' sequence encoding its other and C-terminal domain. UUA codons are exceptionally rare in Streptomyces, and its functional cognate tRNA is not present in a fully modified and acylated form, in the early and vegetative phase of the cell cycle though it is aminoacylated later. Here, we report candidate recoding signals that may influence decoding of the linker region UUA. Additionally, a short ORF 5' of the main ORF has been identified with a GUG at, or near, its 5' end and an in-frame UUA near its 3' end. The latter is commonly 5 nucleotides 5' of the main ORF start. Ribosome profiling data show translation of that 5' region. Ten years ago, UUA-mediated translational bypassing was proposed as a sensor by a Streptomyces phage of its host's cell cycle stage and an effector of its lytic/lysogeny switch. We provide the first experimental evidence supportive of this proposal.

Bypassing of nearest labor & delivery unit is contingent on rurality, wealth, and race.

Patient decisions to bypass the closest labor & delivery (L&D) facility in favor of other birthing locations can have consequences for the provision of health care in rural and micropolitan areas as patient volumes decline and payer mixes change. Among 220 589 uncomplicated births in Iowa, we document characteristics of birth parents who bypass their closest birthing facility, show how this bypassing behavior results in changed travel times to delivery facilities across the rural/urban divide, and indicate the parts of the state where bypassing behavior is most prevalent. From 2013 to 2019, 55.2% of deliveries occurred in facilities that were further from birthing parents' residences than the closest L&D facility. Bypassing is associated with White, non-Hispanic race/ethnicity, and private insurance status. Although bypassing is least common among micropolitan birth parents, this group has the greatest travel burden to birthing facilities and exhibits increasing rates of bypassing over time. Perinatal quality improvement programs can target locations and populations where low-risk birthing parents can be encouraged to deliver close to home if medically appropriate, particularly in small towns and rural areas. This can potentially alleviate the risk of obstetric deserts by ensuring L&D units maintain patient volumes necessary to continue operations.

Bypassing Heaven's Gate Technique Using Black-Box Testing.

In recent years, the number and sophistication of malware attacks on computer systems have increased significantly. One technique employed by malware authors to evade detection and analysis, known as Heaven's Gate, enables 64-bit code to run within a 32-bit process. Heaven's Gate exploits a feature in the operating system that allows the transition from a 32-bit mode to a 64-bit mode during execution, enabling the malware to evade detection by security software designed to monitor only 32-bit processes. Heaven's Gate poses significant challenges for existing security tools, including dynamic binary instrumentation (DBI) tools, widely used for program analysis, unpacking, and de-virtualization. In this paper, we provide a comprehensive analysis of the Heaven's Gate technique. We also propose a novel approach to bypass the Heaven's Gate technique using black-box testing. Our experimental results show that the proposed approach effectively bypasses and prevents the Heaven's Gate technique and strengthens the capabilities of DBI tools in combating advanced malware threats.

Acquired Hemophilia A: Bleeding Pattern and Hemostatic Therapeutic Strategies.

Acquired Hemophilia A (AHA) is a rare autoimmune disorder characterized by the onset of a sudden and unexpected bleeding episode in a patient with no personal or family history of bleeding diathesis, and with a typical laboratory feature, i.e., a prolonged activated partial thromboplastin time that is not otherwise explained. This bleeding disorder is caused by autoantibodies directed against the coagulation factor VIII (FVIII). AHA is idiopathic in 50% of cases and is secondary to well-defined diseases in the remaining 50%. AHA affects elderly patients although it has also been observed in the post-partum period. Bleeding manifestations are heterogeneous, ranging from mild to life-threatening bleeds involving limbs and organs. Severe bleeding with a significant decrease in hemoglobin levels must be promptly and adequately treated in order to avoid a worsening of the hemorrhages and their complications. According to international recommendations, the bypass agents (i.e., activated prothrombin complex concentrate and activated recombinant factor VII) and the replacement therapy with recombinant porcine FVIII are considered as the first-line therapy for bleeding control, due to their proven clinical efficacy. Plasma-derived or recombinant FVIII concentrates could be used as second-line treatments. Emicizumab may represent a valid and interesting therapeutic option for prophylaxis of bleeding recurrences.

Inhibitors: Diagnostic challenges, unknowns of inhibitor development, treatment of bleeding and surgery, and insights into diagnosis and treatment in China.

Factor (F) VIII inhibitors develop in around 30% of previously untreated patients (PUPs) with severe haemophilia, to a lesser extend in moderate and mild haemophilia A and in up to 10% in severe haemophilia B. Diagnostic challenges and questions remain including access to high quality testing, the role for functional inhibitor testing and binding antibody testing, and the adaptations needed in the presence of non-factor replacement therapy. Despite significant gains in knowledge there are still many unanswered questions underlying the immunologic mechanisms of inhibitor development and tolerance. Therapeutic options include eradication of inhibitors using immune tolerance induction therapy (ITI), prophylaxis with bypassing agents (i.e., recombinant activated factor VII /rFVIIa or activated prothrombin complex concentrate/aPCC) or non-factor replacement therapies (e.g., emicizumab) and treatment of bleeds or coverage of surgeries/invasive procedure. Recently a haemophilia centre capacity building program was launched in China to further develop the infrastructure and support needed to improve the diagnosis of haemophilia, detection of inhibitors, and continue to improve the care of patients with haemophilia and inhibitors.

Management of haemophilia A with inhibitors: A regional cross-talk.

INTRODUCTION: The development of inhibitors with factor VIII (FVIII) replacement therapy is one of the most common and challenging complications of haemophilia A (HA) treatment, jeopardising treatment efficacy and predisposing patients to high risks of morbidity and mortality. The management of patients with inhibitors is particularly challenging in countries where resources are limited. AIM: To provide a comprehensive summary of the management of HA with inhibitors while focusing on differences in practice between Western and non-Western countries and how resource scarcity can impact HA management, leading to suboptimal outcomes in patients with inhibitors. METHODS: Summary of key evidence and regional expert opinion. RESULTS: We address, particularly, the diagnosis of and testing for inhibitors, as well as the epidemiology of inhibitors, including incidence, prevalence and disease burden. Secondly, we provide an overview of the current treatment landscape in HA with inhibitors regarding the eradication of inhibitors with immune tolerance induction and the treatment and prevention of bleeding with bypassing agents, non-factor replacement agents and other experimental therapies. This is complemented with insights from the authors around the applicability of, and challenges associated with, such therapies in their settings of practice. CONCLUSIONS: We conclude by proposing some key steps towards bridging the gaps in the management of HA with inhibitors in resource-limited countries, including: (1) the collection of quality data that can inform healthcare reforms and policies; (2) improving disease knowledge among healthcare practitioners and patients with the aim of standardising disease management across centres and (3) working towards promoting equal access to HA care and therapies for everyone.

A low-dose rituximab regimen for first-line treatment of acquired haemophilia A.

A low-dose rituximab regimen for first-line treatment of acquired haemophilia A. INTRODUCTION: Acquired haemophilia A (AHA) is a rare disease caused by the development of autoantibodies against FVIII. Diagnosis involves confirmation of FVIII deficiency and the presence of an inhibitor via the Bethesda assay. Severe bleeding is often managed with bypassing agents such as recombinant factor VII. This is then followed by eradication of the inhibitor with immunosuppression which typically includes a corticosteroid backbone. AIM: Review the current management and outcomes of AHA in Queensland, Australia. Determine the incidence, demographics and clinical characteristics of AHA patients. METHODS: Retrospective case series of AHA diagnosed between May 2014 and August 2018. Data were derived from the Australian Bleeding Disorders Registry and state-wide pathology database. Data collection proforma was completed by the treating haematologist and reviewed/compiled centrally. RESULTS: 24 patients were identified (incidence 1 in 1.27 million). The median age was 76.5 years. Median follow-up was 20 months. Index bleed was atraumatic and skin/soft tissue in the majority of patients. Recombinant FVIIa was the most commonly used haemostatic therapy and effective in 85% of patients. Immunosuppression and steroid usage were uniform. Upfront second agent was used in 75% of patients and was most commonly rituximab. 87.5% of patients achieved a complete remission in a median time of 48 days. Low-dose rituximab was frequently used and equally as efficacious as standard dose. CONCLUSION: Immunosuppression with combination therapy, notably rituximab, appears to be non-inferior and has a favourable side effect profile.

Bubbles help male flowers overcome obstacles during pollination in Hydrilla verticillata.

PREMISE: Pollination in many aquatic plants takes place on the water surface, and the male flowers or stamens often produce gas bubbles underwater; however, the generation mechanism and function of these bubbles are unknown. METHODS: A common submerged plant, Hydrilla verticillata, was used as experimental material to observe the structure of male flowers, analyze the process of bubble generation, and simulate the movement process of the male flower with attached gas bubble in water. RESULTS: The aerenchyma inside the male plants of H. verticillata transported the gas produced by the plant's branches during photosynthesis to the male flower, and the formed gas bubbles became attached to the edge of the perianth. The gas accumulation rate in the attached bubbles increased with light intensity. Once the bubble diameter increased to approximately 3.3 mm, the male flowers with the bubble detached from the plant and floated to the water surface. The removal of the attached bubbles did not affect the male flower detached from the plant; however, the surfacing of male flowers without gas bubbles was easily prevented by the plant's branches in the water, and they could not reach the water surface to complete pollen dispersal. CONCLUSIONS: The gas bubbles produced by male flowers of H. verticillata came from the gas produced by branches under light. These bubbles can help ascending male flowers bypass the obstacles in water and reach the surface to complete pollination.

Eptacog Beta for Bleeding Treatment and Prevention in Congenital Hemophilia A and B With Inhibitors: A Review of Clinical Data and Implications for Clinical Practice.

OBJECTIVE: To review the pharmacology, dosing and administration, safety, clinical efficacy, and role of eptacog beta in the treatment of congenital hemophilia with inhibitors. DATA SOURCES: A literature search of PubMed (1966 to August 2021) was conducted using the keywords eptacog beta, recombinant FVII, and hemophilia. STUDY SELECTION AND DATA EXTRACTION: All relevant published articles and prescribing information on eptacog beta for the treatment of congenital hemophilia with inhibitors were reviewed. DATA SYNTHESIS: Eptacog beta is a novel recombinant activated factor VII (rVIIa) product that demonstrated efficacy in controlling bleeding and associated pain in patients with hemophilia A or B with inhibitors. Eptacog beta has limited Food and Drug Administration-approved and off-label indications compared with other bypassing agents (BPAs; activated prothrombin complex concentrates [aPCC; eptacog alfa]). Eptacog beta costs less than eptacog alfa, but still more than aPCCs. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: This review provides insight into the role of eptacog beta for treatment of congenital hemophilia with inhibitors and reviews important health system formulary considerations for available BPAs. CONCLUSIONS: Eptacog beta is more cost-effective than eptacog alfa and, as such, may become the preferred rVIIa formulary product. However, eptacog alfa availability remains necessary for the treatment of disorders where eptacog beta has limited data. aPCC should remain the first-line BPA for the treatment of bleeding in patients with inhibitors with no contraindications to use because of its equivocal efficacy and safety and in light of the magnitude of cost savings associated with this strategy.

Self-referrals and associated factors among laboring mothers at Dilla University Referral Hospital, Dilla, Gedeo Zone, Ethiopia: a cross-sectional study.

BACKGROUND: When medical cases are difficult to manage at the level of primary health care units (PHCU), formal referral assists patients transferring to a higher level of care. In contrast, self-referral and bypassing are synonymously used in literature to describe the phenomenon of patients skipping their units to get basic medical services, even though they are close to their residence. Though proper and timely referral prevents the majority of deaths from obstetric complications in developing countries, more than 50% of referrals are self-referral trends. Such patient practice is increasingly becoming a concern for many health-care systems. OBJECTIVE: To assess the magnitude of self-referrals and associated factors among laboring mothers at Gedeo Zone, Ethiopia. METHODS: Facility-based cross-sectional study was conducted from August 1-September 30/2021 among laboring mothers at Dilla University Referral Hospital. A systematic random sampling technique was used to select 375 laboring mothers. Data were collected using a face-to-face interview with a structured questionnaire. Data were entered into a computer using Epi-Data 4.6 statistical program and then exported to STATA version 16 for analysis. In bivariate analysis variables with a p-value ≤ 0.25 were selected as a candidate variable for the multivariable analysis. P-value < 0.05 at 95% confidence interval considered as a statistically significant associations in the multivariable analysis. RESULT: 375 eligible mothers participated in the study, with a response rate of 98.16%. The magnitude of self-referrals among laboring mothers was 246 (65.6%) with 95% CI (0.60-0.70). Time ≥ 30 min to reach nearby facilities (AOR = 1.74, 95% CI, 1.08, 2.81), having no medicine supplies at nearby facilities (AOR = 1.75, 95% CI, 1.08, 2.82), having no equipment and supplies at nearby facilities (AOR = 1.70, 95% CI, 1.03, 2.78), having ANC visits ˃ 3 times (AOR = 0.29, 95% CI, 0.15, 0.55) and having poor perception of health provider technical competence at nearby facilities (AOR = 2.97, 95% CI, 1.83, 4.79) were found as significant factors for self-referral. CONCLUSION: The magnitude of self-referral was high. Frequent Antenatal visits were protective, however time to reach the nearest facilities, perception towards health care providers, medicine, equipment and supplies at the nearest facilities were positive influencing factors. Government stakeholders should keep working on improving the quality of health service, especially at primary health care units(PHCU).

Health care seeking in modern urban LMIC settings: evidence from Lusaka, Zambia.

BACKGROUND: In an effort to improve population health, many low- and middle-income countries (LMICs) have expanded access to public primary care facilities and removed user fees for services in these facilities. However, a growing literature suggests that many patients bypass nearby primary care facilities to seek care at more distant or higher-level facilities. Patients in urban areas, a growing segment of the population in LMICs, generally have more options for where to seek care than patients in rural areas. However, evidence on care-seeking trajectories and bypassing patterns in urban areas remains relatively scarce. METHODS: We obtained a complete list of public health facilities and interviewed randomly selected informal sector households across 31 urban areas in Lusaka District, Zambia. All households and facilities listed were geocoded, and care-seeking trajectories mapped across the entire urban area. We analyzed three types of bypassing: i) not using health centers or health posts for primary care; ii) seeking care outside of the residential neighborhood; iii) directly seeking care at teaching hospitals. RESULTS: A total of 620 households were interviewed, linked to 88 health facilities. Among 571 adults who had recently sought non-emergency care, 65% sought care at a hospital. Among 141 children who recently sought care for diarrhea, cough, fever, or fast breathing, 34% sought care at a hospital. 71% of adults bypassed primary care facilities, 26% bypassed health centers and hospitals close to them for more distant facilities, and 8% directly sought care at a teaching hospital. Bypassing was also observed for 59% of children, who were more likely to seek care outside of the formal care sector, with 21% of children treated at drug shops or pharmacies. CONCLUSIONS: The results presented here strongly highlight the complexity of urban health systems. Most adult patients in Lusaka do not use public primary health facilities for non-emergency care, and heavily rely on pharmacies and drug shops for treatment of children. Major efforts will likely be needed if the government wants to instate health centers as the principal primary care access point in this setting.

Management of separated endodontic instruments: case reports.

Successful management of separated endodontic instruments is difficult, but several techniques are available for the retrieval of a separated instrument (SI). An appropriate treatment plan depends on various factors, including the anatomy and location of the tooth; the size, type, and location of the SI; and the skill of the clinician. However, the selection of the most appropriate management technique based on these factors can be a challenging decision that directly influences the success of the procedure. This article presents 4 symptomatic cases of SIs managed with various modalities as well as 1-year clinical and radiographic follow-up results. The management techniques applied in these cases included the use of ultrasonic tips, the wire loop method, safe-sided H-files, the braiding technique, and bypassing of the file. The medical history of the patients was noncontributory except for a single patient who had type 2 diabetes mellitus, which might have delayed healing. After instrument retrieval, the patients were evaluated clinically for relief of signs and symptoms as well as for their responses to various tests such as percussion, palpation, and tooth mobility. Radiographic evaluation at the 12-month follow-up was used to determine the periapical index. The clinical and radiographic results and patient-reported outcomes were satisfactory in all cases. The 4 cases presented demonstrate that the keys to successful management of an SI are understanding the factors that influence the case and selecting an appropriate therapeutic technique.

Nonconsensual neurocorrectives, bypassing, and free action.

As neuroscience progresses, we will not only gain a better understanding of how our brains work, but also a better understanding of how to modify them, and as a result, our mental states. An important question we are faced with is whether the state could be justified in implementing such methods on criminal offenders, without their consent, for the purposes of rehabilitation and reduction of recidivism; a practice that is already legal in some jurisdictions. By focusing on a prominent type of view of free action, which I call bypassing views, this paper evaluates how such interventions may negatively impact the freedom of their subjects. The paper concludes that there will be a tension between the goals of rehabilitation and reduction of recidivism, on the one hand, and the negative impact such interventions may have on free action, on the other. Other things equal, the better that a particular intervention is at achieving the former, the more likely it is to result in the latter.

Identification of a modified coagulation factor X with enhanced activation properties as potential hemostatic agent.

Hemophilia A and hemophilia B are X-linked inherited bleeding disorders caused by a deficiency of coagulation factor VIII and IX, respectively. Standard of care is prophylactic factor replacement therapy; however, the development of neutralizing antibodies against these factors represents serious complications underlining the need for alternative treatment approaches. Human coagulation factor X has a central role within the blood coagulation system making it an attractive target for the development of alternative treatment strategies for patients with hemophilia. This study focuses on a modified variant of the human coagulation factor X with enhanced hemostatic bypass activity due to insertion of a factor IX derived activation sequence. This molecule design leads to the direct activation of the modified factor X protein by factor XIa allowing it to bypass the need for coagulation factor VIIIa/factor IXa. The modified variant was able to correct in-vitro activated partial prothrombin time of human and murine factor VIII/factor IX deficient plasma. Furthermore, reduced blood loss in factor VIII knock-out mice was observed after intravenous application of the modified factor X variant. In conclusion, these data suggest that the factor X variant described here could potentially serve as a bypassing agent independent of the inhibitor status of hemophilia patients. However, more research is needed to further investigate the potential of this molecule.

Comparison of bypassing agents in patients on emicizumab using global hemostasis assays.

INTRODUCTION: Emicizumab is a humanized bispecific monoclonal antibody licensed for patients with severe haemophilia A with and without inhibitors. Management of breakthrough bleeding in patients with inhibitors on emicizumab involves episodic treatment with bypassing agents (BPA), activated prothrombin complex concentrate (aPCC) or recombinant activated factor VII (rFVIIa). Thrombotic events and thrombotic microangiopathy were reported when patients on emicizumab received concomitant aPCC at relatively high doses yet such events were not reported with rFVIIa. We studied the effect of spiking various concentrations of BPA on plasma taken from patients on emicizumab. MATERIAL AND METHODS: Eleven patients with severe haemophilia A with inhibitors who are on emicizumab were recruited to participate. Blood samples drawn from patients were spiked in vitro with varying concentrations of aPCC and rFVIIa. All samples were tested utilizing global haemostasis assays, thromboelastography and thrombin generation assay. RESULTS: Thrombin generation increased with higher concentrations of spiked BPA with a normalized endogenous thrombin potential at a concentration of 0.05 IU/ml and 4 mcg/ml for aPCC and rFVIIa, respectively. Concentrations of aPCC in the range of licensed dosing led to excessive thrombin generation. Thromboelastography was not sufficiently sensitive. CONCLUSION: Due to the known thrombotic complications when emicizumab is used in conjunction with aPCC, there has been a large-scale abandonment of the use of aPCC in patients on emicizumab. However, it is possible that aPCC can be used safely with emicizumab albeit with lower doses than are typically prescribed. It would be important to test this hypothesis in a clinical study.

Concomitant use of bypassing agents with emicizumab for people with haemophilia A and inhibitors undergoing surgery.

INTRODUCTION: Surgery in people with haemophilia and factor VIII inhibitors is typically managed with perioperative administration of haemostatic agents to prevent or control the occurrence of bleeding events. Practical experience of surgery in patients with inhibitors who are receiving treatment with emicizumab is growing; however, the novelty of the situation means that standardised guidelines are lacking with regard to the concomitant administration of haemostatic agents, including dose and laboratory monitoring. AIM: To review approaches to haemostatic management during major and minor invasive procedures in patients with haemophilia A and inhibitors, and to provide recommendations for controlling bleeding events. METHODS: A search was conducted, limited to the past 4 years (January 2016-April 2020), pertaining to published evidence of surgery for patients receiving emicizumab. Publications identified from the search were manually reviewed to determine studies and case reports relevant for inclusion. RESULTS: Identified literature and practical experience of the authors were used to build a consensus of practical recommendations for the concomitant administration of haemostatic agents during the perioperative period for elective surgery in patients with inhibitors who are receiving emicizumab. CONCLUSIONS: The current evidence base indicates that surgery can be successfully performed in patients with inhibitors who are receiving emicizumab and that bypassing agents can be used concomitantly. Data from prospective studies are required to further support recommendations for haemostatic management of surgery in patients receiving emicizumab.

Optimizing the management of patients with haemophilia A and inhibitors in the era of emicizumab: Recommendations from a German expert panel.

Standard treatment of haemophilia A is based on replacing the missing coagulation factor VIII (FVIII) to treat and prevent bleeding episodes. The most challenging complication of FVIII therapy is the development of neutralizing antibodies (inhibitors) that can render treatment ineffective. Eradication of the inhibitor through immune tolerance induction (ITI) remains the most effective strategy for managing these patients. Bypassing agents can be used to help restore haemostasis in inhibitor patients. Several novel agents have recently been developed, such as the FVIII mimetic agent emicizumab, which has been effective in reducing the annualized bleeding rate in haemophilia A patients with inhibitors. When coadministered with repetitive high doses of activated prothrombin complex concentrate (ie >100 U/kg/d for ≥24 hours), emicizumab was associated with thrombotic microangiopathy and thrombosis events. As a consequence the United Kingdom Haemophilia Centres Doctors' Organisation (UKHCDO) issued the first guidance on the treatment of bleeding episodes in patients receiving emicizumab. To build on and extend this work, a panel of German haemophilia specialists met to discuss the UK guidance, review current evidence and provide additional guidance for German healthcare professionals on how to optimize the management of patients with haemophilia A receiving emicizumab. Recommendations are provided on the use of bypassing and other agents to manage breakthrough bleeding, ITI in the emicizumab era, haemostatic support during surgery and issues relating to laboratory monitoring.

Cost-effectiveness of emicizumab vs bypassing agents in the prevention of bleeding episodes in haemophilia A patients with anti-FVIII inhibitors in France.

INTRODUCTION: The development of an anti-FVIII inhibitor is the most serious complication of haemophilia A occurring in up to 30% of severe haemophilic patients. The current management of haemophilia A with inhibitor uses bypassing agents (BPA) and represents a significant therapeutic burden together with a limited adherence to prophylactic treatment. Emicizumab is the first monoclonal antibody developed in haemophilia A approved for the prevention of bleeding episodes in patients with anti-FVIII inhibitor. AIM: The purpose of this study is to evaluate the incremental cost-effectiveness ratio (ICER) of emicizumab versus BPAs. METHODS: A Markov model was developed over a five-year time horizon to estimate the comparative costs and benefits of the different therapeutic approaches in this rare disease. Model inputs were clinical, including annual bleeding rate and quality of life, and economical including mainly costs of prophylaxis, bleeds and adverse events. RESULTS: Emicizumab treatment is dominant, ie lest costly and more effective, in the base-case analysis saving 234 191 € for a gain of 0.88 QALY. This is confirmed by both the deterministic and probabilistic sensitivity analyses. The main limit of the study remains the absence of long-term clinical data allowing to relate treatment consumption to clinical benefit, especially in the progression of haemophilic arthropathy. CONCLUSION: Our results show that emicizumab is a cost-effective treatment allowing to consider an easy to implement prophylactic treatment for haemophilia A patients with anti-FVIII inhibitors.

British Association of Urological Surgeons (BAUS) and Nurses (BAUN) consensus document: management of the complications of long-term indwelling catheters.

OBJECTIVE: To look at best evidence and expert opinion to provide advice in the form of a consensus statement lead by Female, Neurological and Urodynamic Urology (FNUU) section of the British Association of Urological Surgeons (BAUS) in conjunction with the British Association of Urological Nurses (BAUN). METHODS: Initially a literature search was performed with incorporation of aspects of the existing guidance and further informed by UK best practice by core members of the group. The document then underwent reviews by the FNUU Executive Committee members, the BAUN executive committee, a separate experienced urologist and presented at the BAUS annual meeting 2020 to ensure wider feedback was incorporated in the document. RESULTS: Complications of long-term indwelling catheters include catheter-associated urinary tract infections (CAUTI), purple urine bag syndrome, catheter blockages, bladder spasms (causing pain and urinary leakage), loss of bladder capacity, urethral erosion ("catheter hypospadias")/dilatation of bladder outlet and chronic inflammation (metaplasia and cancer risk). CONCLUSIONS: We have provided a list of recommendations and a troubleshooting table to help with the management of the complications of long term catheters.

Surgery with emicizumab prophylaxis for two paediatric patients with severe haemophilia A with inhibitors.

Emicizumab is a prophylaxis for patients with severe haemophilia A with and without inhibitor. Despite weekly administration of emicizumab, coagulation states stay below normal value and cannot be assessed by standard haemostasis tests. In our two patients, we used the thrombin-generation assay (endogenous thrombin potential and Peak) to monitor the patient's clotting status. Under emicizumab, it is necessary to add a bypassing agent (BPA) such as rFVIIa (Novoseven) to avoid bleeding before surgery. The BPA dosage was based on a thrombin-generation assay and collegial consultation.