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Advances in medical capability should be accompanied by discussion of their ethical implications. In the military medical context there is a growing interest in developing prophylactic interventions that will mitigate the effects of trauma and improve survival. The ethics of this novel capability are currently unexplored. This paper describes the concept of trauma prophylaxis (Left Of Bang Interventions in Trauma) and outlines some of the ethical issues that need to be considered, including within concept development, research and implementation. Trauma prophylaxis can be divided into interventions that do not (type 1) and those that do (type 2) have medical enhancement as an unintended side effect of their prophylactic action. We conclude that type 1 interventions have much in common with established military medical prophylaxis, and the potentially enhancing qualities of type 2 interventions raise different issues. We welcome further debate on both interventions., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Vaccination plays an essential role in preventing diseases, safeguarding the health and welfare of the population. The objective of this review is to design vaccination plans for companion animals and production systems in equines and bovines located in the state of Meta (Colombia). In felines and canines, vaccination can provide protection against possible bacterial, virulent and parasitic agents with infectious and/or zoonotic capacity and thus reduce losses in veterinary expenses associated with the treatment of sick animals. In equines, it is prophylactic against encephalomyelitis and equine influenza, avoiding animal suffering and possible economic losses; while, in bovine production, it can be highly preventive against conditions such as brucellosis and foot-and-mouth disease, which can have serious economic consequences in the industry. Therefore, it is of crucial importance to adopt a solid and clear focus on prevention through contextualized vaccination programs, in this case for the state of Meta, protecting only one health. [ABSTRACT FROM AUTHOR]

Nephrolithiasis is a disease with a high risk of recurrence: 50% within five years and up to 80–90 % within 10 years after the first episode. Often, with this diagnosis, there is only symptomatic treatment with the aim of expelling the kidney stone and removing the pain. In such patients, however, initial stratification of the risk of recurrence based on the risk factors present is essential. Every patient with nephrolithiasis, whether it is a single episode or recurrent, should follow general measures to prevent kidney stones. Depending on the results of the kidney stone analysis and the risk of recurrence, it is necessary to carry out a specialised nephrological metabolic examination which is performed by a nephrologist in Slovakia, with subsequent personalised recommendations depending on the cause of recurrent nephrolithiasis. These include dietary and regimen measures, as well as pharmacological treatment. In the following article we summarize specific measures for individual types of nephrolithiasis, as well as basic preventive measures for the recurrence of kidney stones, with a focus on dietary risk and protective factors. [ABSTRACT FROM AUTHOR]

To study the effect of prophylactic intracameral moxifloxacin (ICM) on microbiological profile and antimicrobial sensitivity of culture-proven postoperative endophthalmitis (POE). This study evaluated culture-proven POE diagnosed within 6 weeks of cataract surgery over two periods, period-1 (January 2010-March 2015) and period-2 (April 2015-December 2019), before and after introduction of prophylactic ICM, respectively. In period-1, 100 cases of culture-positive POE were reported (1 in 4879, 0.02%), while 20 cases (1 in 24635, 0.004%) were reported in period-2 (5-fold reduction, p <.001). The cumulative culture positivity rate decreased from 27.6% to 17.1% (1.6-fold). Coagulase-negative Staphylococci (CoNS) were significantly reduced (p =.005). ICM reduced the incidence of culture-proven POE, CoNS in particular. In future, POE caused by rarer pathogens may become more prevalent due to reduction in the rate of commoner and more virulent pathogens with use of intracameral antibiotics. The moxifloxacin sensitivity of CONS did not show change with the use of ICM. Studies with larger population of POE will be more helpful to understand the trend better. [ABSTRACT FROM AUTHOR]

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Background: Children undergoing allo-HCT are at high risk of EBV-related complications. The objective of the study was to analyze the impact of prophylactic post-transplant rituximab on EBV infection and EBV-PTLD in children after allo-HCT, to determine the risk factors for the development of EBV infection and EBV-PTLD and to determine their outcomes. Additionally, the impact of EBV-driven complications on transplant outcomes was analyzed. Methods: Single center retrospective analysis of EBV-related complications in pediatric population undergoing allo-HCT, based on strategy of prophylaxis with rituximab. Overall 276 consecutive children, including 122 on prophylaxis, were analyzed for EBV-driven complications and transplant outcomes. Results: Prophylaxis with rituximab resulted in significant reduction of EBV infection (from 35.1% to 20.5%; HR=2.7; p<0.0001), and EBV-PTLD (from 13.0% to 3.3%; HR=0.23; p=0.0045). A trend for improved survival was also observed (HR=0.66; p=0.068), while non-relapse mortality was comparable in both cohorts. The peak value of viral load was a risk factor in the development of EBV-PTLD: 10-fold higher peak viral load in comparison to the baseline 104 copies/mL, caused a 3-fold (HR=3.36; p<0.001) increase in the risk of EBV-PTLD. Rituximab treatment was effective as a preemptive therapy in 91.1%, and in 70.9% in EBV-PTLD. Patients who developed PTLD had dismal 5-year overall survival (29% vs 60%; p<0.001), and an increased risk of relapse (72% vs 35%; p=0.024). Conclusions: Rituximab for prophylaxis of EBV infection and EBV-PTLD was highly effective in pediatric population. Treatment of EBV-PTLD was successful in 70%, however the occurrence of EBV-PTLD was associated with an increased risk of relapse of primary malignant disease. [ABSTRACT FROM AUTHOR]

The aim of this article it is to study the origin, development and consequences of the cholera epidemic of 1885 in Segovia, emphasizing first the number of infections and then the number of victims, focusing both on the differential mortality by age, gender and profession, as in the space, showing the possible sources of appearance, progress and prophylaxis. For this, based mainly on the analysis of primary sources, we aim to reconstruct the course of the disease and its comparison with the rest of the country. [ABSTRACT FROM AUTHOR]

Hereditary angioedema (HAE) is a rare inherited disorder causing recurrent episodes of swelling that can be potentially life threatening. Treatment of HAE can be divided into on-demand treatment for swelling, and prophylaxis. The last UK consensus on HAE was in 2014 and since then, new medications for prophylaxis have been developed, with more drugs in the pipeline. International guidelines currently recommend the use of long-term prophylaxis (LTP) as the only way of achieving disease control and normalizing patient lives. Modern prophylactic medications are available in the UK, although access is restricted primarily by HAE attack frequency. To establish an updated view of UK clinicians and patients, a Delphi process was used to develop statements regarding LTP as well as other aspects of HAE management. There was consensus that UK access criteria for modern LTP agents based on numerical frequency of attacks alone are too simplistic and potentially disadvantage a cohort of patients who may benefit from LTP. Additionally, there was agreement that patients should be seen in expert centres, remote monitoring of patients is popular post-pandemic, and that the use of patient-reported outcome measures has the potential to improve patient care. Psychological health is an area in which patients may benefit, and recognition of this is important for future research and development. To establish an updated view of UK clinicians and patients, a Delphi process was used to develop statements regarding long-term prophylaxis and other aspects of hereditary angioedema management. UK access criteria for modern LTP agents based on numerical frequency of attacks alone were thought to be too simplistic, and potentially disadvantage a cohort of patients who may benefit from LTP. There was agreement that patients should be seen in expert centres, remote monitoring of patients is popular post-pandemic, patient-reported outcome measures has the potential to improve patient care, and psychological support may benefit patients. [ABSTRACT FROM AUTHOR]

Background: The performance of serum galactomannan (GM) for the diagnosis of invasive aspergillosis (IA) has been studied mainly in adults. Paediatric data are scarce and based on small and heterogeneous cohorts. Objective: To evaluate the performance of serum GM for the diagnosis of IA in a paediatric oncologic population at high risk of IA and to clarify the impact of antifungal prophylaxis on this test. Methods: We performed a retrospective study from January 2014 to December 2020 in the paediatric oncologic haematologic department of the University Hospital of Bordeaux. The diagnosis of IA was made using the recommendations of the EORTC and the MSGERC. Results: Among the 329 periods at high risk of IA in 222 patients, the prevalence of IA was 1.8% (3 proven and 3 probable IA). In the total population, the sensitivity, and the positive predictive value (PPV) were respectively 50% and 17.6%. Under antifungal prophylaxis, the sensitivity and PPV dropped, respectively, to 33.3% and 14.3%. In this group, the post‐test probability of IA was 2% for a negative serum GM and only 14%. Conclusion: In this large cohort of children at high risk of IA, the incidence of IA is low and the diagnostic performance of GM is poor, especially in the case of mould‐active prophylaxis. Screening should be targeted rather than systematic and should be reserved for patients at highest risk for IA without mould‐active prophylaxis. Combination with other tests such as Aspergillus PCR would increase the accuracy of GM in screening setting. [ABSTRACT FROM AUTHOR]

Pneumocystis jirovecii pneumonia (PCP) is a common opportunistic infection among people living with HIV (PWH), particularly among new and untreated cases. Several regimens are available for the prophylaxis of PCP, including trimethoprim-sulfamethoxazole (TMP-SMX), dapsone-based regimens (DBRs), aerosolized pentamidine (AP), and atovaquone. To compare the efficacy and safety of PCP prophylaxis regimens in PWH by network meta-analysis. Embase, MEDLINE, and CENTRAL from inception to June 21, 2023. Comparative randomized controlled trials (RCTs). PWH. Regimens for PCP prophylaxis either compared head-to-head or versus no treatment/placebo. Cochrane risk-of-bias tool for RCTs 2. Title or abstract and full-text screening and data extraction were performed in duplicate by two independent reviewers. Data on PCP incidence, all-cause mortality, and discontinuation due to toxicity were pooled and ranked by network meta-analysis. Subgroup analyses of primary versus secondary prophylaxis, by year, and by dosage were performed. A total of 26 RCTs, comprising 55 treatment arms involving 7516 PWH were included. For the prevention of PCP, TMP-SMX was ranked the most favourable agent and was superior to DBRs (risk ratio [RR] = 0.54; 95% CI, 0.36–0.83) and AP (RR = 0.53; 95% CI, 0.36–0.77). TMP-SMX was also the only agent with a mortality benefit compared with no treatment/placebo (RR = 0.79; 95% CI, 0.64–0.98). However, TMP-SMX was also ranked as the most toxic agent with a greater risk of discontinuation than DBRs (RR = 1.25; 95% CI, 1.01–1.54) and AP (7.20; 95% CI, 5.37–9.66). No significant differences in PCP prevention or mortality were detected among the other regimens. The findings remained consistent within subgroups. TMP-SMX is the most effective agent for PCP prophylaxis in PWH and the only agent to confer a mortality benefit; consequently, it should continue to be recommended as the first-line agent. Further studies are necessary to determine the optimal dosing of TMP-SMX to maximize efficacy and minimize toxicity. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: There is practice heterogeneity in the use, type, and duration of prophylactic antiseizure medications (ASMs) in patients with moderate–severe traumatic brain injury (TBI). Methods: We conducted a systematic review and meta-analysis of articles assessing ASM prophylaxis in adults with moderate–severe TBI (acute radiographic findings and requiring hospitalization). The population, intervention, comparator, and outcome (PICO) questions were as follows: (1) Should ASM versus no ASM be used in patients with moderate–severe TBI and no history of clinical or electrographic seizures? (2) If an ASM is used, should levetiracetam (LEV) or phenytoin/fosphenytoin (PHT/fPHT) be preferentially used? (3) If an ASM is used, should a long versus short (> 7 vs. ≤ 7 days) duration of prophylaxis be used? The main outcomes were early seizure, late seizure, adverse events, mortality, and functional outcomes. We used Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology to generate recommendations. Results: The initial literature search yielded 1998 articles, of which 33 formed the basis of the recommendations: PICO 1: We did not detect any significant positive or negative effect of ASM compared to no ASM on the outcomes of early seizure, late seizure, adverse events, or mortality. PICO 2: We did not detect any significant positive or negative effect of PHT/fPHT compared to LEV for early seizures or mortality, though point estimates suggest fewer late seizures and fewer adverse events with LEV. PICO 3: There were no significant differences in early or late seizures with longer versus shorter ASM use, though cognitive outcomes and adverse events appear worse with protracted use. Conclusions: Based on GRADE criteria, we suggest that ASM or no ASM may be used in patients hospitalized with moderate–severe TBI (weak recommendation, low quality of evidence). If used, we suggest LEV over PHT/fPHT (weak recommendation, very low quality of evidence) for a short duration (≤ 7 days, weak recommendation, low quality of evidence). [ABSTRACT FROM AUTHOR]

The article discusses the use of pre-emptive therapy (PET) and prophylaxis (PRO) for preventing cytomegalovirus (CMV) disease in liver transplant recipients. The authors compare their real-world experience with PET and PRO to the findings of a previous study. They found that PET did not significantly reduce the incidence of CMV disease compared to PRO, and PET was associated with higher costs. The authors suggest that PET may not have advantages over PRO in certain real-world settings. They also highlight the importance of carefully conducting PET according to rigorous standards for optimal efficacy. [Extracted from the article]

Cancer-associated thrombosis is the second leading cause of death in cancer patients, and its incidence has been increasing in recent years. This survey was aimed at gathering information regarding the management of thromboembolic prophylaxis within the MITO (Multicenter Italian Trials in Ovarian Cancer)-MaNGO (Mario Negri Gynecologic Oncology) groups. We designed a self-administered, multiple-choice online questionnaire available only for MITO-MaNGO members for one month, starting in May 2022 and ending in June 2022. We processed one response form per center, and 50 responses were analyzed, with most of the respondents (78%) over 40 years old. We found that 82% of them consider thromboembolic prophylaxis in gynecologic oncology to be relevant. In 82% of the centers, a standardized protocol on venous thromboembolism (VTE) prophylaxis is used, which is applied to both patients undergoing surgery and those undergoing chemotherapy. In the remaining 18% of centers, prophylaxis is used exclusively for patients undergoing chemotherapy treatment. Prophylaxis of patients undergoing surgery and chemotherapy treatment is managed in most cases by the surgeon (72%) and oncologist (76%), respectively. Only 26% of respondents use a thromboembolic risk assessment scale, and of these, those used are the Caprini Score (6%), Khorana Score (6%), and Wells Score (2%). The respondents have good knowledge of low-molecular-weight heparin (90%) and average knowledge of dicumarolics (40%), direct oral anticoagulants (DOACs) (68%), and antiplatelet agents (40%). The results of our survey indicate that there is a good awareness of thromboembolic prophylaxis in gynecologic oncology. Nevertheless, it is used less in outpatients than in patients undergoing surgery. Moreover, the thromboembolic risk assessment scores are barely used. [ABSTRACT FROM AUTHOR]

Allogeneic haematopoietic cell transplant (allo-HCT) recipients who are cytomegalovirus (CMV)-seronegative have better post-transplant outcomes than CMV-seropositive recipients. Letermovir (LTV) is approved for CMV primary prophylaxis in adults who are CMV-seropositive after allo-HCT, and its use is associated with improved long-term post-transplant outcomes. We analysed whether LTV has affected the relationship between CMV serostatus and post-transplant outcomes. We conducted a retrospective single-centre cohort study of allo-HCT recipients, stratified according to donor (D) and recipient (R). CMV serostatus and the use of LTV: D−/R−, R+/LTV−, and R+/LTV+. Outcomes measured were all-cause and non-relapse mortality, clinically significant CMV infection, graft-versus-host disease, and relapse up to week 48 after allo-HCT. The D−/R− group served as the reference for comparisons in univariate, competing risk regression, and cumulative incidence functions. The analysis included 1071 consecutive allo-HCT recipients: 131 D−/R−, 557 R+/LTV−, and 383 R+/LTV+. All-cause mortality by day 100 was 6.1% for the D−/R− group, compared with 14.0% (p 0.024) and 7.8% (p 0.7) for the R+/LTV− and R+/LTV + groups, respectively. Non-relapse mortality by day 100 was 11.0%, 6.8% and 3.8% for R+/LTV−, R+/LTV+, and D−/R− groups, respectively, without significant difference. When including relapse as a competing event, the hazard ratio for non-relapse mortality was 1.83 (95% CI: 1.12–2.99, p 0.017) for R+/LTV− compared with D−/R− and 1.05 (95% CI 0.62–1.77, p 0.85) for R+/LTV + compared with D−/R−. CMV primary prophylaxis with LTV abrogated the mortality gap based on CMV serostatus, a protective effect that persisted after discontinuation of primary prophylaxis. [ABSTRACT FROM AUTHOR]

Objective: To compare bleeding and thromboembolic events in low body weight patients receiving reduced-dose venous thromboembolism (VTE) prophylaxis versus standard-dose VTE prophylaxis. Design: Multicenter, retrospective, cohort study. Setting: Five Ascension Health Hospitals. Patients: Adult, critically ill, low body weight (≤50 kg) patients who received either reduced-dose VTE prophylaxis (n = 140) or standard-dose VTE prophylaxis (n = 279) for at least 48 h. Intervention: Reduced-dose prophylaxis (enoxaparin 30 mg daily or heparin 5000 units every 12 h subcutaneously) or standard-dose prophylaxis (enoxaparin 40 mg daily, enoxaparin 30 mg every 12 h, or heparin 5000 units every 8 h subcutaneously). Measurements and Main Results: A total of 419 patients were included with a mean weight of 45.1 ± 4.2 kg in the standard-dose group and 44.0 ± 5.1 kg in the reduced-dose prophylaxis group (P =.02). The primary endpoint, composite bleeding, was significantly lower in patients receiving reduced-dose prophylaxis (5% vs 12.5%, P =.02). After adjusting for confounding factors, results remained consistent demonstrating reduced composite bleeding with reduced-dose prophylaxis (odds ratio: 0.36, 95% confidence interval: 0.14-0.96). Major bleeding events occurred in 3.6% of reduced-dose patients compared with 8.6% in standard-dose patients (P =.056). Clinically relevant nonmajor bleeding (5.4% vs 2.9%, P =.24) and VTE (2.2% vs 0%, P =.08) events were similar between groups. Conclusions: A reduced-dose VTE prophylaxis strategy in low body weight, critically ill patients was associated with a lower risk of composite bleeding and similar rate of thromboembolism. [ABSTRACT FROM AUTHOR]

Aim and background: Searching is ongoing to find an alternative prophylactic magnesium sulphate regimen for severe preeclampsia despite 24 hours recommendation of the World Health Organization (WHO). This review finds the provision of any such substitute prophylactic instead of the recommended ones searching through the recently published trials. Objectives: To endorse any alternative prophylactic magnesium sulphate regimen effective for severe preeclampsia. Methods: Data sources: Studies are retrieved from the bibliographic databases of PubMed, Scopus, and Cochrane Library. Eligibility Criteria, Participants, and Interventions: Included studies are recently published trials intended to compare the efficacy of different modified regimens of magnesium sulphate prophylaxis for women with severe preeclampsia in contrast to the standard regimen. Results: Out of a total of fifteen, eight studies evaluated different abbreviated regimens of magnesium sulphate prophylaxis. A lower maintenance dose of magnesium sulphate as preeclampsia-prophylaxis was assessed by two. In addition, four studies evaluated the efficacy of only loading doses of magnesium sulphate as prophylaxis. Finally, one study estimated a placebo in the postpartum period compared to the standard regimen. No incidence of eclampsia was reported in any group of eight studies. Even in the rest seven studies, eclampsia incidences did not appear significantly higher in the study group allocated for either abbreviated or low dose or loading-dose regimens. However, a statistically significant number of women in the study groups needed extension/reinstitution of prophylaxis. Low-dose and loading dose prophylaxis are found unsuitable for a recommendation. Apart from the established safety potential, abbreviated/short-course prophylaxes of magnesium sulphate have been found to generate different secondary benefits. Conclusions: The abbreviated postpartum regimen of magnesium sulphate can be recommended as prophylaxis for severe preeclampsia instead of recommended schedule if applied judicially. [ABSTRACT FROM AUTHOR]

Introduction: Cytomegalovirus (CMV) remains the predominant opportunistic infection following solid organ transplantation (SOT). While valganciclovir is the drug of choice for CMV prophylaxis, its utility can be compromised due to the risk of cytopenia. Letermovir, a novel agent approved for CMV prophylaxis in allogeneic hematopoietic stem cell transplant recipients and high‐risk kidney transplant recipients, exhibits reduced toxicity. This study aims to present the practical application of letermovir as both primary and secondary prophylaxis against CMV in heart transplant recipients (HTR). Methods: In this observational, retrospective, single‐center study, we included all consecutive adult HTRs from June 2020 to January 2022 who were administered letermovir for CMV prophylaxis. We documented instances of CMV breakthrough infections, side effects related to letermovir, changes in neutropenia following the switch from valganciclovir to letermovir, and any drug interactions with the immunosuppressive regimen. Results: The study comprised 10 patients: two received primary prophylaxis with letermovir due to a high risk of CMV infection (donor‐positive, recipient‐negative serostatus), and eight received it as secondary prophylaxis following a CMV infection. The median duration of letermovir administration was 8 months (range 3–12 months). No CMV breakthrough infections were reported while on prophylaxis. However, three patients experienced CMV breakthrough infections after discontinuing letermovir prophylaxis (30%). No significant side effects were observed, although one patient reported digestive intolerance. Among the nine patients on tacrolimus, six needed reduced doses after switching to letermovir. Conclusion: This real‐life study appears to support the effectiveness of letermovir prophylaxis in HTR. Nonetheless, the risk of CMV infection post‐treatment cessation is notable. Further drug monitoring and research on the efficacy of letermovir for CMV prophylaxis in SOT patients is warranted. [ABSTRACT FROM AUTHOR]

Introduction: Tailored prophylaxis is the current treatment regimen for patients with severe haemophilia A. Recently, published guidelines describe two possible approaches, based on clinical characteristics or estimation of pharmacokinetic parameters. However, both have strengths and weaknesses, and their characteristics need to be integrated to optimize treatment appropriately. In this paper, we present a model that considers together the characteristics of prophylaxis and the relevance of each. Methods: The age at initiation of prophylaxis, number of bleeding events, treatment regimen, therapeutic adherence, FVIII trough levels, and joint status were analyzed in 59 patients followed at La Paz University Hospital between January 2000 and December 2019. Results: The mean duration of primary prophylaxis of 113.37 ± 57.79 months. Eighty‐three percent (n = 49) had no joint status involvement at the end of follow‐up (HJHS and HEAD‐US = 0). The median ABR was 0.7 (IQR 0.2 –1.0) and 54.2% presented trough levels of FVIII during follow‐up >1 IU/dL. 72,9% engaged in some type of physical activity and overall adherence was over 85% in all patients evaluated. The regression analysis performed, considering all these factors, showed that the initiation of prophylaxis before 21 months of age was the most relevant protective factor against the appearance of joint involvement (OR 88.33 p.031 CI 95% 1.49‐5224.40) Conclusion: Early initiation of prophylaxis was the most relevant factor in the protection of joint status. More comprehensive analysis models adapted to the characteristics of each population, are needed to adequately individualize treatment. [ABSTRACT FROM AUTHOR]

Study Design. Single-center retrospective chart review study. Objective. This study aimed to assess the clinical outcomes of prophylactic inferior vena cava (IVC) filter use for pulmonary embolism (PE) prevention in spine surgery patients. Summary of Background Data. IVC filters can serve an important prophylactic role in preventing PE, though research involving spine surgery patients is sparse. Materials and Methods. This Institutional Review Board-approved single-center retrospective study assessed the characteristics and outcomes of patients who underwent spine surgery and received perioperative IVC filters for PE prophylaxis from January 2007 until December 2021. Clinical outcomes centered primarily on the occurrence of venous thromboembolism (VTE) as well as complications related to filter placement and retrieval. Thrombi that may have been entrapped by the filters were recorded incidentally on computed tomography or during the filter retrieval procedure. Results. This cohort included 380 spine surgery patients (female 51%/male 49%; median age, 61) who had received perioperative prophylactic IVC filters. The mean dwell time was 6.7 months (1-39 mo), with an overall 62% retrieval rate. Retrievals were further categorized by retrieval complexity, with 92% classified as routine and 8% as involving advanced removal techniques, while complications involved 1% (four retrievals) and were all minor. Regarding VTE event occurrence, deep vein thrombi (DVT) were experienced by 11% of patients in the postplacement period, with 1% (n=4) experiencing a PE. There were 11 incidences of thrombi that were found within or near the filters (2.9%). A multivariate analysis further assessed patient characteristics that correlated with the occurrence of PE, DVT, entrapped filter thrombi, advanced technique filter removal, and removal complications. Conclusions. IVC filters in this high-risk spine surgery cohort achieved a relatively low rate of DVT and PE as well as a low complication rate, whereas several patient characteristics were identified that correlated with VTE events and filter retrieval outcomes. [ABSTRACT FROM AUTHOR]

Summary: The hallmark of haemophilia A (HA) therapy is prophylaxis, aimed at spontaneous bleeding prevention. Emicizumab provides a viable alternative to intravenous factor replacement therapy. However, data on its use in infants are limited. This single‐centre open arm prospective study reports on emicizumab prophylaxis in infants. We included severe HA patients under 1 year who started emicizumab prophylaxis since 2018, with longitudinal follow‐up. The study collected data on demographics, clinical and laboratory variables, the occurrence of bleeding events, surgeries and treatment outcomes. Of the 27 enrolled infants, whose median age at prophylaxis initiation was 7 months, 24 primarily choose to start emicizumab therapy (3/27 switched from FVIII prophylaxis due to development of FVIII inhibitors). The median age for prophylaxis initiation decreased to 3 months in 2023. Following emicizumab initiation, the median calculated ABR decreased, and no intracranial haemorrhages were observed. Thrombin generation showed a significant improvement in peak height and endogenous thrombin potential at steady state after a loading period. Our study highlights a shift towards early prophylaxis in the era of non‐replacement therapies. It underscores the need for continuous evaluation and refinement of treatment approaches, emphasizing personalized care and diligent monitoring in the evolving field of paediatric haemophilia care. [ABSTRACT FROM AUTHOR]

Introduction: This study aims to show the bacteriologic picture of acute prostatitis and bacteremia caused by infective agent after transrectal ultrasound-guided prostate biopsy (TRUSBx) and to determine the resistance rates of the infections in patients undergoing transrectal biopsy and to guide prophylaxis approach before biopsy. Methodology: The retrospective data of 935 patients who underwent TRUSBx between January 2010 to January 2019 were reviewed. Prebiopsy urine cultures and antimicrobial susceptibility were obtained. Subsequently, patients admitted to the hospital with any complaint after biopsy were examined for severe infection complications. Results: Of the 430 (61.7%) patients who underwent urine culture before the procedure, 45 (10.5%) had growth; 30 (66.7%) of the growing microorganisms were Escherichia coli. Twenty (44.4%) of all Gram-negative agents in pre-biopsy urine culture were susceptible to quinolone. Post TRUSBx bacteremia was present in 18.2%, urinary system infection in 83.6%, and hospitalization in 61.8% of 55 patients who were admitted to the hospital. In the isolated gram-negative microorganisms, fluoroquinolones resistance in urinary system infections was seen in 40% and bacteremia was seen in 70% of the cases. ESBL-producing Gram-negative bacteria were determined in 40% of infections in blood and 38.5% of urinary system infections in the post biopsy period in the current study. Conclusions: These high antibiotic resistance rates suggest that we better review our pre-procedure prophylaxis approaches. [ABSTRACT FROM AUTHOR]

Introduction: Prophylaxis has become standard of care for all persons with haemophilia (PWH) with a severe phenotype. However, 'standard prophylaxis' with either factor or non‐factor therapies (currently only emicizumab available) is prohibitively expensive for much of the world. We sought to address the question of 'How much prophylaxis is enough?' and 'Can it be individualized?' and specifically 'Can emicizumab be individualized?'. Methods: We reviewed the literature on prophylaxis in haemophilia since its inception in the 1950s to the present, the development of more and less intense factor prophylaxis regimens and their outcomes and additionally the published outcomes of prophylaxis with low dose emicizumab. Results: What these experiences collectively show is that low dose emicizumab does result in significant benefits to patients whilst being much less expensive than a "one size fits all" emicizumab prophylaxis approach. We also took note that some non‐factor therapies still in development are individualized given that high doses of these can potentially put patients at risk. Conclusions: Prophylaxis is now clearly accepted as standard of care for PWH with a severe phenotype but now in a very short time a large assortment of different treatment options for prophylaxis have become/are becoming available and the haemophilia community will need to determine how to best use these recognizing that no 'one treatment fits all'. [ABSTRACT FROM AUTHOR]

Background: Infections are one of the most common causes of death after lung transplant (LT). However, the benefit of 'targeted' prophylaxis in LT recipients pre-colonized by Gram-negative (GN) bacteria is still unclear. Methods: All consecutive bilateral LT recipients admitted to the Intensive Care Unit of the University Hospital of Padua (February 2016–2023) were retrospectively screened. Only patients with pre-existing GN bacterial isolations were enrolled and analyzed according to the antimicrobial surgical prophylaxis ('standard' vs. 'targeted' on the preoperative bacterial isolation). Results: One hundred eighty-one LT recipients were screened, 46 enrolled. Twenty-two (48%) recipients were exposed to 'targeted' prophylaxis, while 24 (52%) to 'standard' prophylaxis. Overall prevalence of postoperative multi-drug resistant (MDR) GN bacteria isolation was 65%, with no differences between the two surgical prophylaxis (p = 0.364). Eleven (79%) patients treated with 'standard' prophylaxis and twelve (75%) with 'targeted' therapy reconfirmed the preoperative GN pathogen (p = 0.999). The prevalence of postoperative infections due to MDR GN bacteria was 50%. Of these recipients, 4 belonged to the 'standard' and 11 to the 'targeted' prophylaxis (p = 0.027). Conclusions: The administration of a 'targeted' prophylaxis in LT pre-colonized recipients seemed not to prevent the occurrence of postoperative MDR GN infections. [ABSTRACT FROM AUTHOR]

Background: Extended half-life (EHL) factor IX (FIX) concentrates allow for prophylaxis with prolonged dosing intervals and high bleeding protection in persons with hemophilia B. Long-term real-world studies are lacking. Methods: In a retrospective–prospective study, the six-year use of prophylaxis with the EHL recombinant FIX–albumin fusion protein (rIX-FP) was analyzed, comparing outcomes with previous standard half-life (SHL) FIX in patients already on prophylaxis. Results: Prophylaxis with rIX-FP was prescribed in 15 patients (10 severe, 5 moderate; follow-up: 57 ± 17 months). Based on a pharmacokinetic assessment and clinical needs, the first regimen was 47 ± 7 IU/Kg every 9 ± 2 days. All but one patient remained on rIX-FP prophylaxis, adjusting infusion frequency and/or dose; the last prescribed frequency was ≥10 days in 10/13 patients, being reduced in seven and increased in four vs. the first regimen. The weekly FIX dose was unchanged; FIX trough levels were >5% in all patients. The annual infusion number and FIX IU/Kg significantly decreased (~60%) in eight patients previously on SHL FIX prophylaxis, with similar concentrate costs. Very low bleeding rates (most traumatic bleeds and the last quartile of the infusion interval), improved orthopedic and pain scores, unchanged HEAD-US scores and problem joints, and high treatment adherence (>90%) and satisfaction were registered. Conclusions: Personalized, carefully adjusted rIX-FP regimens contribute to the diffusion and optimization of prophylaxis in persons with severe and moderate hemophilia B, with long-term favorable bleeding, joint, and patient-reported outcomes. [ABSTRACT FROM AUTHOR]

Brain metastasis (BM) prognosis is incredibly poor and is often associated with considerable morbidity. Seizures are commonly present in these patients, and their biopsychosocial impact can be dangerous. The use of antiepileptic drugs (AEDs) as primary prophylaxis remains controversial. This systematic review and meta-analysis aim to evaluate the efficacy of AED prophylaxis in patients with BM. MEDLINE via PubMed, Web of Science, EMBASE, and Cochrane were searched for articles pertinent to AED prophylaxis use in patients with BM. Patients with BM previously treated for cancer who were seizure naive at the time of inclusion were included. Data regarding patient characteristics, type of AED, prior treatments, and groups at a high risk of seizure were extracted. Seizure prevalence was obtained. Eight studies were included in this systematic review and meta-analysis; 1902 total patients with BM were included, with 381 receiving antiepileptic prophylaxis, and 1521 receiving no prophylaxis. Although the odds of a seizure in the treatment group was found to be 1.158 times the odds of a seizure in the control group, the odds ratio was not statistically significant (t-statistic = 0.62, P value = 0.5543). There was no significant difference in the odds of seizure development in control groups compared to patients receiving prophylactic antiepileptic therapy. As patients with BM present with heterogeneity in tumor characteristics and receive various treatment modalities, future research is needed to identify groups that may benefit more significantly from AED prophylaxis. [ABSTRACT FROM AUTHOR]

Introduction: Damoctocog alfa pegol (BAY 94‐9027, Jivi®) is an approved extended half‐life factor VIII (FVIII) for treatment of previously treated patients with haemophilia A aged ≥12 years. We report the final results of an interventional, post‐marketing study of damoctocog alfa pegol prophylaxis in patients with severe haemophilia A. Methods: In this open‐label, interventional, post‐marketing, phase 4 trial (NCT04085458), previously FVIII‐treated patients with severe haemophilia A aged ≥18 years received damoctocog alfa pegol for ≥100 exposure days (EDs). Patients initially received 45 IU/kg every 5 days (recommended) or 40 IU/kg twice‐weekly. At Visit 3, patients' doses could be increased, or treatment frequency adapted. The primary endpoint was FVIII inhibitor development (titre ≥.6 Bethesda units). Secondary endpoints included anti‐polyethylene glycol (PEG) antibody development, treatment‐emergent adverse events (AEs) and annualized bleeding rate (ABR). Results: Overall, 36 patients were enrolled; 32 patients received treatment, of whom, 27 completed the study. No patients developed FVIII inhibitors; three tested transiently positive for low‐titre anti‐PEG antibodies without clinical relevance. Three patients reported study‐drug‐related AEs of mild or moderate intensity. Two patients discontinued the study due to AEs. No deaths occurred. Most patients (70%) were treated with E5D/E7D regimens. The median (Q1;Q3) total ABR (N = 30) was 3.0 (.0;9.0) pre‐study and 1.8 (.7;5.9) during the study. Conclusion: Damoctocog alfa pegol individualized prophylaxis regimens were well‐tolerated with no immunogenicity concerns. ABRs improved following the switch from pre‐study prophylaxis to damoctocog alfa pegol prophylaxis. These results support the favourable safety and efficacy profile of damoctocog alfa pegol prophylaxis. [ABSTRACT FROM AUTHOR]

This document is a corrigendum for an article on the treatment patterns of antiviral prophylaxis for cytomegalovirus (CMV) among adult kidney transplant recipients. The corrigendum acknowledges mistakes in the original article and provides corrected versions of the affected elements. The text provides information on the duration of CMV prophylaxis in kidney transplant recipients based on their risk group. Factors such as geographic location, comorbidities, and wait time were associated with a higher likelihood of discontinuing CMV prophylaxis. The document also includes baseline demographic, clinical, and medication-related characteristics of adult kidney transplant recipients. [Extracted from the article]

Limited data exist on cytomegalovirus (CMV) antiviral treatment patterns among kidney transplant recipients (KTRs). Using United States Renal Database System registry data and Medicare claims (1 January 2011-31 December 2017), we examined CMV antiviral use in 20,601 KTRs who received their first KT from 2011 to 2016. Three-quarters of KTRs started CMV prophylaxis (86.9% of high-, 83.6% of intermediate-, and 31.7% of low-risk KTRs). Median time to prophylaxis discontinuation was 121, 90, and 90 days for high-, intermediate-, and low-risk KTRs, respectively. Factors associated with receiving CMV prophylaxis were highrisk status, diabetes, receipt of a well-functioning kidney graft, greater time on dialysis before KT, panel reactive antibodies =80%, and use of antithymocyte globulin, alemtuzumab, and tacrolimus. KTRs were more likely to discontinue CMV prophylaxis if they developed leukopenia/neutropenia, had liver disease, or had a deceased donor. These findings suggest that adherence to the recommended duration of CMV-prophylaxis for high and intermediate-risk patients is suboptimal, and CMV prophylaxis is overused in low-risk patients. [ABSTRACT FROM AUTHOR]

OBJECTIVES Enoxaparin for the prevention of venous thromboembolism (VTE) in pediatric patients is typically dosed twice a day. The use of once-daily dosing like that used in adult patients is limited because of a lack of safety and efficacy data. The aim of this study was to evaluate the safety and efficacy of once-daily versus twice-daily dosing of enoxaparin for pediatric VTE prophylaxis based on incidence of thrombotic and bleeding events. METHODS This was a 3-year retrospective chart review of enoxaparin received for VTE prophylaxis at Cohen Children's Medical Center, New Hyde Park, NY. Exclusion criteria were age 18 years or older, and renal dysfunction. RESULTS A total of 177 enoxaparin courses (81 in the once-daily and 96 in the twice-daily group) were included. The median dose in the once-daily group was 0.68 mg/kg/dose with dose capping at 40 mg/dose in 70% of patients. One patient in the once-daily group had a VTE, whereas no patients in the twice-daily group experienced a VTE. One major bleeding event occurred in the once-daily group (p = 0.46); however, minor bleeding events were comparable between the 2 groups (p = 0.69). CONCLUSIONS Once-daily enoxaparin prophylaxis appears to be safe and effective based on minimal differences in incidence of thrombotic and bleeding events when compared to twice-daily dosing. Based on this study, it may be reasonable to consider once-daily enoxaparin dosing for prophylaxis, especially in older children. A larger multicenter cohort study evaluating once-daily dosing for prophylaxis is warranted to validate the safety and efficacy specifically for risk-based dosing strategies. [ABSTRACT FROM AUTHOR]

Background Many centers use universal antifungal prophylaxis after lung transplant, but risk factors for invasive fungal infection (IFI) in this setting are poorly described.- Methods This retrospective, single-center cohort study including 603 lung transplant recipients assessed risk factors for early (within 90 days of transplant) invasive candidiasis (IC) and invasive mold infection (IMI) and late (90–365 days after transplant) IMI using Cox proportional hazard regression. Results In this cohort, 159 (26.4%) patients had 182 IFIs. Growth of yeast on donor culture (hazard ratio [HR], 3.30; 95% CI, 1.89–5.75) and prolonged length of stay (HR, 1.02; 95% CI, 1.01–1.03) were associated with early IC risk, whereas transplantation in 2016 or 2017 (HR, 0.21; 95% CI, 0.06–0.70; HR, 0.25; 95% CI, 0.08–0.80, respectively) and female recipient sex (HR, 0.53; 95% CI, 0.30–0.93) were associated with reduced risk. Antimold therapy (HR, 0.21; 95% CI, 0.06–0.78) was associated with lower early IMI risk, and female donor sex (HR, 0.40; 95% CI, 0.22–0.72) was associated with lower late IMI risk. Recent rejection was a risk factor for late IMI (HR, 1.73; 95% CI, 1.02–2.95), and renal replacement therapy predisposed to early IC, early IMI, and late IMI (HR, 5.67; 95% CI, 3.01–10.67; HR, 7.54; 95% CI, 1.93–29.45; HR, 5.33; 95% CI, 1.46–19.49, respectively). Conclusions In lung transplant recipients receiving universal antifungal prophylaxis, risk factors for early IC, early IMI, and late IMI differ. [ABSTRACT FROM AUTHOR]

Urinary tract infections (UTIs) commonly affect many patient populations. Recurrent UTIs (rUTIs) can be particularly problematic and lead to potential hospitalizations, multiple antibiotic courses, and have a potential negative impact on quality of life. To prevent UTIs, antibiotics are frequently used for prophylaxis; however, antibiotic prophylaxis has notable untoward consequences including but not limited to potential adverse effects and development of antibiotic resistance. Methenamine, an antiseptic agent initially available in 1967, has re‐emerged as a potential option for UTI prophylaxis in various populations, including older adults and renal transplant recipients. The objective of this systematic review was to evaluate the clinical effectiveness and safety of methenamine for UTI prophylaxis. A systematic review following the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidance was performed. A PubMed, Embase, and Cochrane library search was conducted to identify relevant English‐language studies evaluating methenamine for UTI prophylaxis including randomized controlled trials, case–control studies, and meta‐analyses through June 2023. Articles were excluded if the studies did not primarily describe or evaluate methenamine for UTI prophylaxis, were commentaries/viewpoints articles, point prevalence studies, review articles, studies that evaluated methenamine used with another agent, and any duplicate publications from searched databases. A total of 11 articles were identified for inclusion. This systematic review suggests methenamine generally appears to be an effective and well‐tolerated antibiotic‐sparing option for UTI prophylaxis. Furthermore, the pharmacology, dosage and formulation, warnings, precautions, and safety considerations of methenamine that provide potential clinical considerations regarding its use for UTI prophylaxis are described. Further studies are needed to evaluate the clinical utility of methenamine for UTI prophylaxis. [ABSTRACT FROM AUTHOR]

Background: Cytomegalovirus (CMV) is associated with morbidity and mortality following allogeneic hematopoietic cell transplantation (alloHCT). Letermovir is a novel antiviral agent that prevents CMV reactivation in alloHCT patients, with limited data regarding influence on post‐alloHCT outcomes. Methods: We retrospectively examined 273 alloHCT recipients, 158 in the non‐letermovir cohort (NLC), and 115 in the cohort using letermovir prophylaxis (LC). Patients that received letermovir were CMV‐seropositive and met criteria for high risk of CMV reactivation. Results: Median start of letermovir was 21 days post‐alloHCT, median duration of prophylaxis was 86 days. Letermovir prophylaxis demonstrated a statistically significant reduction in first CMV reactivation (at 200 days post 63.9% in the NLC vs. 35.7% in the LC; p <.001). On univariate analysis at 1 year, overall survival (OS) for NLC was 79.6% and 79.5% for LC (p =.54). Non relapse mortality (NRM) at 1 year for NLC was 12% and 12.3% for LC (p =.69). Cumulative incidence of relapse (CIR) at 1 year was 13.9% for NLC versus 17.1 for the LC (p =.27). On multivariable analysis, there was no significant difference between the two cohorts for OS, NRM, and CIR. Conclusions: Letermovir prophylaxis started at day +21 post‐alloHCT reduced CMV reactivation, with no impact on posttransplant outcomes. [ABSTRACT FROM AUTHOR]

Background: Antibacterial prophylaxis in children and adolescents undergoing allogeneic hematopoietic cell transplantation (HCT) is controversial and not recommended by international guidelines. We analyzed relevant posttransplant outcomes following discontinuation of antibacterial prophylaxis at a major European pediatric transplant center. Methods: The single‐center retrospective audit included all pediatric allogeneic HCT patients (pts) transplanted between 2011 and 2020 before (≤2014) and after (≥2015) stopping routine antibacterial prophylaxis with penicillin, metronidazole, and ciprofloxacin upon start of the conditioning regimen. The primary endpoint was overall survival until the first hospital discharge. Secondary endpoints included the occurrence of fever; bacterial infections; and cumulative days with antibacterial agents until discharge. Results: A total of 257 HCT procedures were performed in 249 pts (median age: 10 years, range, 0.2–22.5) for leukemia/lymphoma (n = 150) and nonmalignant disorders (n = 107). Of these, 104 procedures were performed before (cohort 1) and 153 after (cohort 2) stopping prophylaxis. Overall survival until discharge was 90.4% in cohort 1 and 96.1% in cohort 2 (p =.06). No differences were observed in the occurrence of fever (92.3 vs. 94.1%; p =.57) and bacterial infections (34.6 vs. 25.5%; p =.11). The median number of days on antibacterial agents was significantly lower in cohort 2 (39 vs. 34; p =.002). Detection rates of resistant organisms were overall low. Conclusion: In this single‐center audit, the stop of routine antibacterial prophylaxis had no effect on the occurrence of fever, bacterial infections, resistant organisms, and GVHD. Overall antibiotic use was significantly reduced, and survival was noninferior to the historical control cohort. [ABSTRACT FROM AUTHOR]

Letermovir for CMV prevention in CMV-seropositive adults undergoing allo-HCT was implemented at our program in 2021. This study investigates the results from the use of letermovir. The study includes all the 140 CMV-seropositive patients who underwent an allo-HCT during the years 2020, 2021, and 2022 at our institution. Thirty-eight (27.4%) of these patients received letermovir, administered from day + 7 to day + 100 and restarted if patients were on treatment with steroids. The day + 180 and 1-year cumulative incidences of CMV reactivation were 5.3% and 12.1% for patients who received letermovir and 52.9% and 53.9% for those who did not (P < 0.001) (HR 0.19, P < 0.001). Four (10.5%) of these thirty-eight patients had a CMV reactivation, but only 2 (5.3%) cases occurred during the administration of letermovir. During the first year after allo-HCT, 13 (9.2%) patients had CMV disease; the day + 180 and 1-year cumulative incidences were 2.6% and 6.0% for patients who received letermovir and 9.9% and 12.3% for those who did not (P = 0.254) (HR 1.01, P = 0.458). Two (4.2%) of the patients included in the letermovir group had CMV disease, but both of them after letermovir discontinuation. Letermovir induced a protective effect on CMV reactivation risk, but its use was not associated with a significant reduction of CMV disease. The fact that the CMV disease in patients who received letermovir occurred after the discontinuation of the drug, questions whether CMV prophylaxis should be used in patients with high risk for CMV reactivation or disease. [ABSTRACT FROM AUTHOR]

Background Pneumocystis jirovecii pneumonia (PJP) remains a significant threat in immunocompromised cases. Recent data on epidemiology and risk factors for PJP in non-HIV cases are scarce, and guidelines on appropriate prophylaxis are lacking. Methods In this multicenter retrospective trial, all non-HIV adult cases admitted to hospitals in Québec City, Canada, between January 2011 and January 2021 with a diagnosis of PJP were assessed for eligibility. Results An overall 129 cases of PJP were included. More than two-thirds had an underlying hematologic disease or an autoimmune/inflammatory condition. Prior to diagnosis, 83.7% were taking corticosteroids, 71.3% immunosuppressive agents (alone or in combination with corticosteroids), and 62% both. A diagnosis of PJP was noted in 22 patients receiving corticosteroids for treatment <28 days. Two patients developed PJP while undergoing corticosteroid monotherapy at a mean daily prednisone-equivalent dose <20 mg/d; 4.7% of our cohort received a PJP prophylaxis. Current recommendations or accepted clinical practices for PJP prophylaxis would not have applied to 48.8% of our patients. Conclusions The use of corticosteroids—in monotherapy or in coadministration with other immunosuppressive agents—remains the principal risk factor for PJP in the non-HIV population. Current prophylaxis guidelines and accepted practices are insufficient to adequately prevent PJP and need to be broadened and updated. [ABSTRACT FROM AUTHOR]

Background: Venous thromboembolic complications are an uncommon but significant cause of morbidity & mortality after live donor hepatectomy. The precise incidence of these events and the current practices of centers performing living donor liver transplantation worldwide are unknown. Methods: An online survey was shared amongst living donor liver transplantation centers containing questions regarding center activity, center protocols for donor screening, peri‐operative thromboembolic prophylaxis and an audit of ‐perioperative venous thromboembolic events after live donor hepatectomy in the previous five years (2016–2020). Results: Fifty‐one centers from twenty countries completed the survey. These centers had cumulatively performed 11500 living donor liver transplants between 2016–2020. All centers included pre‐operative l assessment for thromboembolic risk amongst potential liver donors in their protocols. Testing for inherited prothrombotic conditions was performed by 58% of centers. Dual‐mode prophylaxis was the most common practice (65%), while eight and four centers used single mode or no routine prophylaxis respectively. Twenty (39%) and 15 (29%) centers reported atleast one perioperative deep venous thrmobosis or pulmonary embolism event respectively. There was one donor mortality directly related to post‐operative pulmonary embolism. Overall incidence of deep venous thrombosis and pulmonary embolism events was 3.65 and 1.74 per 1000 live donor hepatectomies respectively. Significant variations in center practices and incidence of thromboembolic events was identified in the survey primarily divided along world regions. 75% of participating centers agreed on the need for clear international guidelines. Conclusion: Venous thromboembolic events after live donor hepatectomy are an uncommon but important cause of donor morbidity. There is significant variation in practice among centers. Evidence‐based guidelines regarding risk assessment, and peri‐operative prophylaxis are needed. [ABSTRACT FROM AUTHOR]

Cytomegalovirus (CMV) infection is a major infectious complication following allogeneic hematopoietic cell transplantation (allo-HCT). Although letermovir (LMV) prophylaxis dramatically reduces the incidence of early clinically significant CMV (csCMV) infection, it remains unclear whether it has a beneficial effect on nonrelapse mortality (NRM) and overall survival (OS). Herein, we evaluated the impact of LMV prophylaxis on posttransplant outcomes using the registry database of the Japanese Society for Transplantation and Cellular Therapy. Adult patients who underwent allo-HCT between 2017 and 2019 were analyzed (n = 6004). LMV prophylaxis was administered to 1640 patients (LMV group) and it significantly reduced the incidence of csCMV infection compared with those not administered LMV prophylaxis (15.4% vs 54.1%; p < 0.01). However, it did not improve the 1-year NRM (hazard ratio [HR], 0.93; p = 0.40) and OS (HR, 0.96; p = 0.49). In the LMV group, 74 patients had breakthrough csCMV infection and showed inferior NRM (HR, 3.44; p < 0.01) and OS (HR, 1.93; p = 0.02) compared with those without infection. After completing LMV prophylaxis, 252 patients had late csCMV infection and showed inferior NRM (HR, 1.83; p < 0.01) and OS (HR, 1.58; p < 0.01). Our findings suggest that managing breakthrough and late csCMV infections is important for improving long-term outcomes. [ABSTRACT FROM AUTHOR]

Background and Objectives: This study aimed to assess the effectiveness and costs associated with pharmacokinetics-driven (PK) prophylaxis based on the myPKFiT® device in patients affected by hemophilia A (HA) in Italy. Materials and Methods: An observational retrospective study was conducted in three Italian hemophilia centers. All patients with moderate or severe HA, aged ≥ 18 years, capable of having PK estimated using the myPKFiT device, and who had had a clinical visit between 1 November 2019 and 31 March 2022 were included. Differences in clinical, treatment, health resources, and cost data were assessed comparing post-PK prophylaxis with pre-PK. The incremental cost-effectiveness ratio (ICER) was estimated as cost (EUR) per bleed avoided. Results: The study enrolled 13 patients with HA. The mean annual bleeding rate decreased by −1.45 (−63.80%, p = 0.0055) after the use of myPKFiT®. Overall, the consumption of FVIII IU increased by 1.73% during follow-up compared to the period prior the use of the myPKFiT. Prophylaxis based on the myPKFiT resulted in an ICER of EUR 5099.89 per bleed avoided. Conclusions: The results of our study support the idea that the use of PK data in clinical practice can be associated with an improvement in the management of patients, as well as clinical outcomes, with a reasonable increase in costs. [ABSTRACT FROM AUTHOR]

Background: Real-world data on subcutaneous C1INH (C1INH[SC]) usage and patient-level impacts on hereditary angioedema (HAE)-related outcomes and quality of life (QoL) are both lacking and challenging to generate using conventional study methodologies. Using a hybrid study design involving patient interviews supplemented by retrospective medical chart data review, we conducted a real-world assessment of the impact of C1INH(SC) prophylaxis on HAE attack patterns, QoL, and on-demand medication use. Methods: The study was conducted at seven US sites and included 36 adults with HAE who had been treated with C1INH(SC) long-term prophylaxis following ≥ 12 months of on-demand management only. Patients underwent 30-min interviews, facilitated and analyzed by a trained qualitative research specialist. Medical records were reviewed for 12 months before (pre-index) and after (post-index) initiation of C1INH(SC). Using interview data with descriptive terms converted to numerical values, we compared pre- versus post-index attack frequency, severity, and rescue medication usage. Results: Mean (SD) annualized attack frequency per patient decreased 82.0%, from 38.8 (38.8) attacks/year pre-index to 7.0 (15.3) attacks/year (P < 0.001); the median number of attacks decreased by 97.0% (30 pre-index to 1 post-index). For 20 patients, the annualized attack rate after starting C1INH(SC) prophylaxis was ≤ 1 attack/year; 12 of these patients reported 0 attacks. Mean (SD) attack severity (scale: 0 = none/mild to 4 = very severe) decreased from 2.3 (0.7) pre-index to 0.9 (0.9) post-index (P < 0.001). Mean/median rescue medication use decreased by 77.2%/96.3%. Improved QoL was narratively described for many domains. Conclusions: These real-world findings indicate that long-term prophylaxis with C1INH(SC) markedly improves important factors that contribute to the goal of achieving total disease control and normalization of patients' lives, including fewer and less severe attacks, less rescue medication usage, and improved QoL. [ABSTRACT FROM AUTHOR]

The carbamate pyridostigmine bromide (PB) is the only fielded pharmacological prophylaxis for military use against nerve agents. Previous studies have shown differences in the PB-pretreatment efficacy for various nerve agents and in the influence of post-exposure treatment with common antidotes. In the present study, the aim was to evaluate the possibility of using an ex vivo rat precision-cut lung slice model to determine the impact of PB pretreatment on VX-induced bronchoconstriction. In addition, the efficacy of post-exposure treatment with atropine sulfate following PB-prophylaxis was investigated. Bronchoconstriction was induced by electric-field stimulation and was significantly aggravated by 10 µM PB. Airway recovery was decreased by both 1 and 10 µM PB. Evaluation of acetylcholineesterese inhibition by PB showed that the lower concentration met the clinical criteria of residual enzyme activity while the higher concentration completely inhibited the activity. Exposure to VX with or without pretreatment demonstrated similar contractions. However, VX-incubation following pretreatment caused decreased airway relaxation compared to pretreatment alone. Atropine treatment following PB- and VX-exposure significantly decreased the maximum airway contraction and increased the relaxation. In conclusion, no beneficial effect of PB-prophylaxis on VX-induced contractions was observed. The atropine efficacy to relax airways was significant demonstrating the importance of efficient post-exposure therapeutics to protect against the life-threatening respiratory contractions. [ABSTRACT FROM AUTHOR]

To report the long-term prophylaxis management of a child with type 3 von Willebrand disease by switching to Wilate (Octapharma AG), a plasma-derived, double virus-inactivated concentrate of freeze-dried of a 1 to 1 ratio of active Von Willebrand Factor and Factor VIII (pdVWF:pdFVIII) recently marketed as Eqwilate in France. This is a case report of 12.6-year-old boy with congenital Type 3 VWD who had a history of frequent bleeds. Prophylaxis started at the age of 38 months with FVIII-poor pdVWF concentrate (Wilfactin, LFB) and FVIII (Wilstart, LFB). Pharmacokinetics and thrombin generation assay were performed. Annualized bleeding rate was derived from the bleeding episodes documented in the medical record during a 24-month period before and after starting pdVWF:pdFVIII concentrate. Both product injections promptly raised the endogenous thrombin potential (ETP). However, the maximal concentration of formed thrombin was higher following pdVWF:pdFVIII injection. Due to a high bleeds frequency and better results regarding FVIII levels and thrombin generation, the prophylaxis regimen was changed to the same dose and frequency of pdVWF:pdFVIII concentrate (42 IU/kg per day, three times a week). During the last 24 months, annualized total, trauma, and spontaneous bleeding rates were 7.5, 4.5, and 3, respectively. These rates decreased to 2, 1.5, and 0.5 respectively during the next two years. The mother reported a marked improvement in the quality of life of his son and hers. Switch to pdVWF:pdFVIII concentrate for long-term prophylaxis in a young type 3 VWD patient was safe and effective in reducing bleeds. [ABSTRACT FROM AUTHOR]

Introduction: Early postoperative reflux (PR) can compromise anastomotic healing after Ivor Lewis esophagectomy (ILE) and poses a risk for aspiration. Anastomotic insufficiency is the most threatening surgical complication. We present the protective method of pre-emptive active reflux drainage (PARD) with simultaneous enteral feeding. We report our experience with this new safety concept in esophageal surgery in a cohort of 43 patients. Materials and Methods: For PARD we use a double lumen open porous film drainage (dOFD). To create the dOFD, the gastric tube of a Trelumina probe (Freka®Trelumina, Fresenius) is coated with a double-layered open-pore drainage film (Suprasorb®CNP drainage film, Lohmann & Rauscher) over a length of 25 cm. The dOFD is endoscopically inserted into the tubular stomach intraoperatively after completion of the anastomosis. Continuous negative pressure is applied with an electronic pump (−125 mm Hg). The PR is continuously aspirated completely and the stomach and anastomotic region are decompressed. At the same time, nutrition is delivered via an integrated intestinal tube. Depending on the results of the endoscopic control after 5 days, PARD is either continued or terminated. Results: During the observation period (2017–2023), PARD was used in all patients (n = 43) with ILE. The healing rate under PARD was 100% and healing was observed in all anastomoses. No additional endoscopic procedures or surgical revisions of the anastomoses were required. The median duration of PARD was 8 days (range 4–21). We observed problems in the healing of the anastomosis in 20 of 43 patients (47%) for whom we defined endoscopic criteria for at-risk anastomosis. Conclusions: Our results suggest that PARD has a strong protective effect on anastomotic healing and may reduce the risk of anastomotic insufficiency. The integrated feeding tube of the dOFD allows early postoperative enteral feeding while simultaneously applying negative pressure. PARD appears to prevent the negative consequences of impaired anastomotic healing. [ABSTRACT FROM AUTHOR]

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The preferred strategy for preventing CMV in at‐risk populations in alloHCT has undergone a significant practice shift in recent years where the pendulum has swung from a pre‐emptive approach to now offering letermovir prophylaxis to all CMV seropositive recipients. Letermovir prophylaxis has resulted in significant reductions in post‐transplant clinically significant CMV infection (csCMVi) as well as other important outcomes such as CMV disease, resistant, and refractory CMV infections and nonrelapse mortality. However, prophylactic strategies are not without some limitations, namely delayed onset CMV infections, delayed CMV‐specific T cell immune reconstitution, increased drug costs and limited data within pediatric populations. Thus, this review aims to provide an overview of prophylaxis and pre‐emptive CMV preventative strategies, and how they are applicable in the current era of letermovir prophylaxis. [ABSTRACT FROM AUTHOR]

Background: The use of fluoroquinolones to prevent infections in neutropenic patients with cancer or undergoing hematopoietic stem cell transplantation (HSCT) is a controversial issue, with international guidelines providing conflicting recommendations. Although potential benefits are clear, concerns revolve around efficacy, potential harms, and antimicrobial resistance (AMR) implications. Discussion: Fluoroquinolone prophylaxis reduces neutropenic fever (NF) bloodstream infections and other serious bacterial infections, based on evidence from systematic reviews, randomized controlled trials, and observational studies in adults and children. Fluoroquinolone prophylaxis may also reduce infection‐related morbidity and healthcare costs; however, evidence is conflicting. Adverse effects of fluoroquinolones are well recognized in the general population; however, studies in the cancer cohort where it is used for a defined period of neutropenia have not reflected this. The largest concern for routine use of fluoroquinolone prophylaxis remains AMR, as many, but not all, observational studies have found that fluoroquinolone prophylaxis might increase the risk of AMR, and some studies have suggested negative impacts on patient outcomes as a result. Conclusions: The debate surrounding fluoroquinolone prophylaxis calls for individualized risk assessment based on patient characteristics and local AMR patterns, and prophylaxis should be restricted to patients at the highest risk of serious infection during the highest risk periods to ensure that the risk‐benefit analysis is in favor of individual and community benefit. More research is needed to address important unanswered questions about fluoroquinolone prophylaxis in neutropenic patients with cancer or receiving HSCT. [ABSTRACT FROM AUTHOR]

The optimal prevention strategy for invasive aspergillosis (IA) in lung transplant recipients (LTXr) is unknown. In 2016, the Danish guidelines were changed from universal to targeted IA prophylaxis. Previously, we found higher rates of adverse events in the universal prophylaxis period. In a Danish nationwide study including LTXr, for 2010–2019, we compared IA rates in time periods with universal vs. targeted prophylaxis and during person-time with vs. person-time without antifungal prophylaxis. IA hazard rates were analyzed in multivariable Cox models with adjustment for time after LTX. Among 295 LTXr, antifungal prophylaxis was initiated in 183/193 and 6/102 during the universal and targeted period, respectively. During the universal period, 62% discontinued prophylaxis prematurely. The median time on prophylaxis was 37 days (IQR 11–84). IA was diagnosed in 27/193 (14%) vs. 15/102 (15%) LTXr in the universal vs. targeted period, with an adjusted hazard ratio (aHR) of 0.94 (95% CI 0.49–1.82). The aHR of IA during person-time with vs. person-time without antifungal prophylaxis was 0.36 (95% CI 0.12–1.02). No difference in IA was found during periods with universal vs. targeted prophylaxis. Prophylaxis was protective of IA when taken. Targeted prophylaxis may be preferred over universal due to comparable IA rates and lower rates of adverse events. [ABSTRACT FROM AUTHOR]

Acute leukemias are complex diseases to treat and have a high mortality rate. The immunosuppression caused by chemotherapy also causes the patient to become susceptible to a variety of infections, including invasive fungal infections. Protocols established in many countries attempt to prevent these infections through the use of pharmacological antifungal prophylaxis. This systematic review and meta-analysis investigates the existing evidence for the use of antifungal prophylaxis in patients undergoing induction chemotherapy for acute leukemia, and how prophylaxis can affect treatment response and mortality. Through the use of a population-variable-outcome strategy, keywords were utilized to search online databases. The included studies were selected and the data was collected to develop descriptive results for all studies, and, for studies that met the criteria, a meta-analysis of the Relative Risk (RR) was analyzed for infection rates, in-hospital mortality, and complete remission. A total of 33 studies were included in this systematic review, with most studies presenting positive results (n = 28/33) from the use of antifungal prophylaxis. Using a random effects model, the pooled results of the meta-analysis presented lower invasive fungal infections in AML (RR: 0.527 (95% CI: 0.391; 0.709). p < 0.001). p < 0.001) and ALL (RR: 0.753 (95% CI: 0.574; 0.988). p = 0.041). when antifungal prophylaxis was used. No discernible difference was encountered in the rate of complete remission when using prophylaxis. Antifungal prophylaxis provides a lower risk of invasive fungal infections and in-hospital mortality in acute leukemia patients undergoing induction chemotherapy. [ABSTRACT FROM AUTHOR]

Summary: Antimicrobial drug resistance is a critical problem in human and veterinary medicine. Antimicrobial drug use and particularly overuse or misuse drive resistance. Surgical antimicrobial prophylaxis (SAP) is one area where misuse and overuse (particularly prolonged SAP) is documented to be at a high level. Infection‐related complications can be devastating to the patient, harm the client/patient–surgeon relationship and damage the reputation of the surgeon. Consequently, surgeons tend to be reluctant to change their antimicrobial prescribing behaviour. There is a plethora of data from human surgery and emerging data from veterinary surgery describing appropriate SAP and supporting the use of shorter duration of SAP. Antimicrobial stewardship programs (ASPs) have been developed and evaluated in human hospitals and this type of collaborative approach would likely have benefit in veterinary hospitals. [ABSTRACT FROM AUTHOR]

Introduction: The standard of care in severe haemophilia A is prophylaxis, which has historically aimed for a factor VIII (FVIII) trough level of ≥1%. However, despite prophylactic treatment, people with haemophilia remain at risk of bleeds that have physical and quality of life implications, and that impact everyday life. Aim: The aim of this review was to evaluate evidence supporting the relationship between targeting higher FVIII activity levels with prophylaxis and improved outcomes in people with haemophilia A. Methods: We conducted a narrative review that defined the unmet needs and treatment goals in people with haemophilia A, evaluated evidence to support targeting higher FVIII activity levels, and highlighted therapies that may support higher and sustained FVIII activity levels and improved outcomes for people with haemophilia A. Results: Despite recent advances in treatment, unmet needs remain, and people with haemophilia continue to experience joint and functional impairment, acute and chronic pain, and poor mental health. All these negatively impact their health‐related quality of life. Evidence suggests that FVIII activity levels of up to 50% may be needed to achieve a near‐zero joint bleed rate. However, achieving high FVIII activity levels with current standard and extended half‐life (EHL) FVIII replacement therapies is associated with a high treatment burden. Innovative treatment options may provide high sustained FVIII activity levels and improved patient outcomes. Conclusion: Evidence suggests that FVIII activity levels in people with haemophilia A should be sustained at higher levels to improve joint and patient outcomes and enable progression towards health equity. [ABSTRACT FROM AUTHOR]

Background: Cytomegalovirus (CMV) infections after heart transplantation (HTx) can cause cardiac allograft vasculopathy. Consequently, monitoring and prophylaxis for cytomegalovirus deoxyribonucleic acid (CMV‐DNAemia) within the first weeks after HTx is recommended. Methods: All patients who underwent HTx between September 2010 and 2021 surviving the first 90 days (n = 196) were retrospectively reviewed. The patients were divided on the prevalence of CMV‐DNAemia during the first postoperative year after the end of the prophylaxis. A total of n = 35 (20.1%) developed CMV‐DNAemia (CMV group) and were compared to patients without CMV‐DNAemia (controls, n = 139). The remaining patients (n = 22) were excluded due to incomplete data. Results: Positive donors and negative recipients (D+/R−) and negative donors and positive recipients (D−/R+) serology was significantly increased and D−/R− decreased in the CMV group (p <.01). Furthermore, the mean age was 57.7 ± 8.7 years but only 53.6 ± 10.0 years for controls (p =.03). Additionally, the intensive care unit (p =.02) and total hospital stay (p =.03) after HTx were approximately 50% longer. Interestingly, the incidence of CMV‐DNAemia during prophylaxis was only numerically increased in the CMV group (5.7%, respectively, 0.7%, p =.10), the same effect was also observed for postoperative infections. Multivariate analyses confirmed that D+/R− and D−/R+ CMV immunoglobulin G match were independent risk factors for postprophylaxis CMV‐DNAemia. Conclusion: Our data should raise awareness of CMV‐DNAemia after the termination of regular prophylaxis, as this affects one in five HTx patients. Especially old recipients as well as D+/R− and D−/R+ serology share an elevated risk of late CMV‐DNAemia. For these patients, prolongation, or repetition of CMV prophylaxis, including antiviral drugs and CMV immunoglobulins, may be considered. [ABSTRACT FROM AUTHOR]