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BACKGROUND: Venous thromboembolism (VTE) is a preventable medical condition which has substantial impact on patient morbidity, mortality, and disability. Unfortunately, adherence to the published best practices for VTE prevention, based on patient centered outcomes research (PCOR), is highly variable across U.S. hospitals, which represents a gap between current evidence and clinical practice leading to adverse patient outcomes. This gap is especially large in the case of traumatic brain injury (TBI), where reluctance to initiate VTE prevention due to concerns for potentially increasing the rates of intracranial bleeding drives poor rates of VTE prophylaxis. This is despite research which has shown early initiation of VTE prophylaxis to be safe in TBI without increased risk of delayed neurosurgical intervention or death. Clinical decision support (CDS) is an indispensable solution to close this practice gap; however, design and implementation barriers hinder CDS adoption and successful scaling across health systems. Clinical practice guidelines (CPGs) informed by PCOR evidence can be deployed using CDS systems to improve the evidence to practice gap. In the Scaling AcceptabLE cDs (SCALED) study, we will implement a VTE prevention CPG within an interoperable CDS system and evaluate both CPG effectiveness (improved clinical outcomes) and CDS implementation. METHODS: The SCALED trial is a hybrid type 2 randomized stepped wedge effectiveness-implementation trial to scale the CDS across 4 heterogeneous healthcare systems. Trial outcomes will be assessed using the RE2-AIM planning and evaluation framework. Efforts will be made to ensure implementation consistency. Nonetheless, it is expected that CDS adoption will vary across each site. To assess these differences, we will evaluate implementation processes across trial sites using the Exploration, Preparation, Implementation, and Sustainment (EPIS) implementation framework (a determinant framework) using mixed-methods. Finally, it is critical that PCOR CPGs are maintained as evidence evolves. To date, an accepted process for evidence maintenance does not exist. We will pilot a Living Guideline process model for the VTE prevention CDS system. DISCUSSION: The stepped wedge hybrid type 2 trial will provide evidence regarding the effectiveness of CDS based on the Berne-Norwood criteria for VTE prevention in patients with TBI. Additionally, it will provide evidence regarding a successful strategy to scale interoperable CDS systems across U.S. healthcare systems, advancing both the fields of implementation science and health informatics. TRIAL REGISTRATION: Clinicaltrials.gov - NCT05628207. Prospectively registered 11/28/2022, https://classic. CLINICALTRIALS: gov/ct2/show/NCT05628207 .

Objective Methods Results Conclusion To evaluate the available literature on ureteric stent‐related infections, the use of antibiotics and bacterial colonisation to identify the current incidence of stent‐related infections, unveil knowledge gaps and generate potential hypotheses for future research.A literature review was conducted using PubMed, Cochrane and urological association websites identifying relevant English literature published between 1983 and January 2024.There is a worldwide lack of guidelines for antibiotic prophylaxis for stent placement, exchange or extraction. In patients with a negative preoperative urine culture undergoing ureteroscopy and stent placement, it may be considered to only provide prophylaxis in presence of risk factors. However, in pre‐stented patients a preoperative urine culture is important to guide prophylaxis during endourological surgery. During stent indwell time, antibiotic prophylaxis does not show any advantage in preventing urinary tract infections (UTIs). There is no strong evidence to support the use of antibiotics at time of stent removal. In the absence of any clear evidence, management strategies for treating UTIs in patients with ureteric stents vary widely. Stent exchange could be considered to remove the biofilm as a potential source of bacteria. Stent culture can help to guide treatment during infection as urine culture and stent culture can differ.In terms of good antibiotic stewardship, urologists should be aware that unnecessary use of antibiotics provokes bacterial resistance. There is a great need for further research in the field of antibiotic prophylaxis and stent‐related infections to develop evidence that can help shape clear guidelines for this very common urological practice. [ABSTRACT FROM AUTHOR]

Objective Background Methods Results Conclusions This study was conducted to assess the efficacy of daily 2000 mg eicosapentaenoic acid (EPA) supplementation in individuals with chronic migraine.Chronic migraine is characterized by a minimum of 15 headache days/month, necessitating a focus on preventive treatment strategies. EPA, a polyunsaturated fatty acid recognized for its anti‐inflammatory properties, is examined for its potential effectiveness in chronic migraine management.A randomized, blinded, placebo‐controlled trial of eligible participants with a confirmed diagnosis of chronic migraine were enrolled. The intervention group received 1000 mg of EPA twice daily for 8 weeks, while the control group received two placebo softgels. Symptoms were recorded at 4 and 8 weeks. The primary outcome was assessed using the Headache Impact Test‐6 to evaluate changes in patients. Secondary outcomes encompassed migraine headache days, headache severity measured via a visual analog scale, and the number of consumed painkillers. Descriptive analyses were reported in mean (± standard deviation [SD]).A total of 60 patients were included in the study and finally, 56 patients completed the study according to the protocol, including 47 (84%) females. The data comparison at baseline did not show any significant difference between the two groups except in the number of patients using valproic acid as prophylaxis (21 patients in the EPA group, and 13 in the placebo group; p = 0.037). The results showed after 8 weeks, a mean (SD) difference of Headache Impact Test‐6 in the EPA and placebo groups was −6.96 (3.34) and −4.43 (5.24), respectively (p = 0.084). Regarding migraine headache days, participants reported a mean (SD) −9.76 (4.15) and −4.60 (4.87) decline in days with headache, respectively (p < 0.001). The number of attacks per month after 8 weeks was 3.0 (95% confidence interval [CI] 2.0–4.0) and 4.0 (95% CI 3.0–6.0), respectively (p < 0.001). Regarding severity, there was no significant difference between the two groups (mean [SD] difference: −0.76 [1.13] and –0.73 [1.04], respectively; p = 0.906). In terms of adverse events, two patients in the EPA group reported intolerable nausea and vomiting, and one patient in the placebo group reported dizziness.This study's findings support the potential of a daily 2000 mg EPA as a prophylactic pharmacotherapy in chronic migraine management, specifically in mitigating migraine attacks, migraine headache days, and overall quality of life. [ABSTRACT FROM AUTHOR]

Bloodstream infections (BSI) are one of the leading causes of morbidity and mortality in children and young adults receiving chemotherapy for malignancy or undergoing hematopoietic stem cell transplantation (HSCT). Antibiotic prophylaxis is commonly used to decrease the risk of BSI; however, antibiotics carry an inherent risk of complications. The aim of this manuscript is to review levofloxacin prophylaxis in pediatric oncology patients and HSCT recipients. We reviewed published literature on levofloxacin prophylaxis to prevent BSI in pediatric oncology patients and HSCT recipients. Nine manuscripts were identified. The use of levofloxacin is indicated in neutropenic children and young adults receiving intensive chemotherapy for leukemia or undergoing HSCT. These results support the efficacy of levofloxacin in pediatric patients with leukemia receiving intensive chemotherapy and should be considered in pediatric patients undergoing HSCT prior to engraftment. [ABSTRACT FROM AUTHOR]

Purpose: Pneumocystis jirovecii pneumonia (PJP) prophylaxis is required by provincial and national drug monographs during glioma treatment using temozolomide (TMZ) concurrently with radiation (TMZ-RT). However, real-world data suggest the potential benefits of PJP prophylaxis may not outweigh its potential harms in this population. Methods: We conducted a single-center patient survey and a national physician survey to explore the role of PJP prophylaxis amongst glioma patients undergoing TMZ-RT. Results: 23% (31/133) of physicians and 60% (44/73) of patients completed a survey. The median patient age was 42 (range 20–77); 85% (34/40) had completed adjuvant TMZ. Although only 2.4% (1/41) of patients received PJP prophylaxis, only one person (without PJP prophylaxis) was hospitalized for pneumonia. When presented with hypothetical PJP risks, 13.2% (5/38) of patients were concerned about PJP infection, while 26% (10/38) were concerned about potential side effects from prophylactic antibiotics. Most physicians (77%, 17/22) perceived the evidence for PJP prophylaxis as weak; 58% (11/19) did not routinely prescribe prophylaxis, and 73% (16/22) felt that PJP prophylaxis should be limited to patients with additional risk factors. Over 95% of physicians estimated that the incidence of PJP was < 1% in their last 5 years of practice regardless of PJP prophylaxis. For 73% (16/22) of physicians, to prescribe PJP prophylaxis, the risk of PJP infection needed to be 3–8%. Conclusion: The current recommendation to routinely prescribe PJP prophylaxis in patients receiving TMZ-RT in the absence of other risk factors warrants reconsideration. [ABSTRACT FROM AUTHOR]

Introduction: Tuberculosis is one of the infectious diseases with greater morbidity and mortality worldwide. Cancer causes an important immunosuppression with increased risk of infections. There is an enlarged bidirectional incidence between tuberculosis and cancer, mainly due to latent tuberculosis. Guidelines review: There is great discrepancy between recommendations for screening and prophylaxis of latent tuberculosis in patients with solid tumors and systemic cancer therapy among different medical societies and guidelines. Most infectious diseases guidelines recommend it, while most oncology guidelines do not. Discussion: Patients with solid tumours generally have a limited life expectancy and a state of intermittent immunosuppression, resulting in a lower risk of tuberculosis reactivation than other risky populations. There is a lack of prospective and retrospective studies analysing the benefit of screening and prophylaxis in this population. The first step is to study the incidence of active tuberculosis in this population to estimate the real magnitude of the problem. [ABSTRACT FROM AUTHOR]

A study published in the journal Transplant Infectious Disease examines the risk of opportunistic infections after solid organ transplantation in patients with a sulfonamide allergy label. The study found that the presence of a sulfonamide allergy label influenced prescribing practices, with a decreased use of trimethoprim/sulfamethoxazole (TMP-SMX) and an increased use of alternative prophylactic agents. While the sulfonamide allergy label was not associated with an increased risk of Pneumocystis jirovecii infection, it was associated with a significantly increased risk of Toxoplasma and Nocardia infections. The study highlights the importance of managing SOT recipients with sulfonamide allergy labels and suggests that a careful history is essential in guiding decision-making. The article discusses the use of trimethoprim/sulfamethoxazole (TMP-SMX) as a prophylactic agent in solid organ transplant (SOT) recipients and the challenges associated with sulfonamide allergy labels. The authors highlight the importance of reassessing sulfonamide allergy labels in SOT recipients and suggest the use of direct oral TMP-SMX challenge as a safe and easier alternative to desensitization. They also emphasize the need for a simple and practical sulfonamide allergy clinical decision rule to enable point-of-care risk assessment and direct oral TMP-SMX challenge. The article concludes by emphasizing the importance of using TMP-SMX in eligible SOT recipients to prevent opportunistic infections. [Extracted from the article]

Background: Levetiracetam (LEV), an antiepileptic drug, has been effective in adult migraine prevention but lacks extensive research in children. This study evaluates LEV's efficacy and safety for pediatric migraine prophylaxis. Methods: We reviewed randomized controlled trials (RCTs) and non-RCTs in major databases through 8 January 2024, focusing on four efficacy endpoints and adverse drug reactions (ADRs). Data synthesis involved pooled relative risks or odds ratios for dichotomous outcomes and mean differences for continuous outcomes, using fixed- or random-effects models as appropriate. Results: Eight studies with 190 participants showed that after taking LEV, the mean headache frequency decreased 5.19 per month (MD: -5.19, 95% CI: -7.11 to -3.27, p < 0.00001) and improved headache-free rates to 28% (95% CI: 0.17-0.41). More than 83% experienced a >50% reduction in monthly headache frequency. The migraine disability score decreased by 33.51 points (MD: -33.51, 95% CI: -38.46 to -28.55, p < 0.00001). ADR incidence did not significantly differ between LEV and control groups (RR: 1.06, 95% CI: 0.39 to 2.85, p = 0.91), with an overall ADR rate of 18% (95% CI: 0.13-0.24). The most common ADR was irritability (12%), leading to treatment discontinuation in 13% of cases (95% CI: 0.05-0.30). Conclusion: LEV has shown good efficacy in preventing pediatric migraines. However, its safety requires further confirmation through more extensive and well-designed RCTs. [ABSTRACT FROM AUTHOR]

Background: Having knowledge of the dental procedures that necessitate endocarditis prophylaxis is of high importance. Therefore, the aim of the present study was to determine the knowledge level and attitudes of general medical and dental practitioners, dental specialists, and cardiologists in Tehran and Hamadan about endocarditis. Methods: This cross-sectional study was carried out on 420 general medical and dental practitioners, dental specialists, and cardiologists in Tehran and Hamadan provinces in 2015. The questionnaire used in this research consisted of three parts as follows: part one: information on cardiac diseases; part two: dental procedures requiring endocarditis prophylaxis; part three: antibiotic diet in endocarditis prophylaxis. Independent t-test, one-way ANOVA, and chi-square tests were conducted to analyze the data. All the analyses were performed in SPSS version 16. Results: The results showed that 86.7 had a relatively favorable and 10.5% of subjects had a favorable level of knowledge about endocarditis. Also, 58.6% of subjects had a poor attitude toward endocarditis prophylaxis. There was a significant relationship between knowledge and attitude, age, gender, and work experience (P < 0.001). There was a significant relationship between knowledge and attitude, and job groups; dental specialists had a more favorable knowledge and positive attitude than others (P < 0.001). Conclusion: We recommended developing more practical training programs in dental schools on cardiac diseases, and dental procedures requiring endocarditis prophylaxis and antibiotic diets. [ABSTRACT FROM AUTHOR]

BACKGROUND: Cytomegalovirus (CMV) reactivation occurs in up to 70% of CMV-seropositive patients undergoing allogeneic hematopoietic stem-cell transplantation (HSCT) and carries a high rate of morbidity and mortality. Ganciclovir and foscarnet have been used for the prevention of CMV; however, both drugs have undesirable adverse events (AEs). In 2017, letermovir was approved for CMV prophylaxis in adults, but data in the pediatric and adolescent and young adult (AYA) populations are limited. OBJECTIVE: To evaluate the efficacy and safety of letermovir for CMV prophylaxis in pediatric and AYA populations. METHODS: This retrospective chart review assessed patients who had HSCT and received letermovir for CMV prophylaxis at Monroe Carell Jr Children’s Hospital at Vanderbilt between January 1, 2017, and December 31, 2021. The patients were eligible for letermovir prophylaxis if they met the following criteria: they were a donor or recipient with CMV seropositivity, were aged >12 years, weighed >35 kg, and had outpatient insurance approval for treatment with letermovir. The dose and length of letermovir treatment were recorded. Patient response was determined by CMV reactivation occurrences. The AEs that were related to letermovir treatment were also evaluated. RESULTS: A total of 11 patients were evaluated, with a median transplant age of 18 years (range, 14-28 years) and a median weight of 76.5 kg (range, 48.2-130.4 kg). Of these 11 patients, 10 received letermovir 480 mg daily, and 1 patient received 240 mg daily. Two (18.2%) patients had CMV reactivation that required intervention, both of which occurred at least 1 month after the discontinuation of letermovir treatment, whereas 9 (81.8%) patients did not have CMV reactivation that required intervention. The AEs that were associated with letermovir treatment were mild: 27.3% of patients had cough, 18.2% each had headaches and myalgia, and 9.1% each had tachycardia, edema, and dyspnea. Of the total patients, 72.7% had nausea and vomiting and 63.6% had diarrhea; however, these AEs are unlikely to be directly related to treatment with letermovir and are as a result of other explainable causes. CONCLUSION: Based on the high prevention rate of CMV reactivation in the pediatric and AYA patients and the tolerable AEs observed within these cohorts, letermovir prophylaxis is a reasonable treatment option for pediatric and AYA patients. [ABSTRACT FROM AUTHOR]

Background: Cytomegalovirus (CMV) mismatched, donor IgG‐positive/recipient IgG‐negative, solid organ transplant recipients (SOTRs) are at high risk of CMV invasive disease. Post‐prophylaxis disease is an issue in this population. Some programs employ surveillance after prophylaxis (SAP) to limit the incidence of post‐prophylaxis disease. Methods: This was a single‐center retrospective cohort study that included all CMV mismatched SOTRs from 2003 to 2017. Patients underwent SAP with weekly CMV plasma viral load for 12 weeks. The subjects were classified into three post‐prophylaxis DNAemia patterns: no DNAemia, one episode of DNAemia, and multiple episodes of DNAemia. We calculated the cumulative incidence of each DNAemia pattern. We also determined 5‐year mortality based on DNAemia pattern stratified by organ transplant type. Results: Post‐prophylaxis recurrent DNAemia occurred in 63% of lung recipients and 32% of non‐lung recipients (p =.003). Tissue invasive CMV disease was diagnosed in 3% of the population and CMV syndrome was diagnosed in 33%. Recurrent DNAemia was not associated with 5‐year mortality. Conclusion: In this cohort, undergoing SAP tissue invasive disease was uncommon and CMV DNAemia recurrence did not have an impact on long‐term mortality. [ABSTRACT FROM AUTHOR]

Background: Manual calf massage and passive ankle motion (CaM) can reduce the incidence of venous thromboembolism (VTE) after total hip arthroplasty (THA). However, these methods cannot be used in all patients; thus, elastic bandage (EB) compression is an alternative method. The efficacy of EB compression in preventing VTE has not yet been investigated; thus, this study aimed to compare the effects of EB compression and manual calf massage. Methods: Of the 363 patients who underwent unilateral primary THA at our hospital between 1 August 2018 and 31 October 2023, CaM without anticoagulation therapy was administered to 206 patients (CaM group) and 157 patients underwent EB without anticoagulation therapy (EB group). Duplex ultrasonography was performed 7 days postoperatively to check for deep vein thrombosis (DVT) in both legs. Results: The surgical time (122.2 min vs. 155.5 min), the incidence of DVT (4.5% vs. 4.8%) and pulmonary thromboembolism (PTE) (0% vs. 0.7%), intraoperative bleeding (305.4 mL vs. 301 mL), and estimated actual blood loss (846.6 mL vs. 811.6 mL) were not significantly different between the CaM and EB group. However, there was one case of symptomatic PTE in the EB group. Conclusions: The incidences of DVT, PTE, and intraoperative bleeding were not significantly different between the groups. Moreover, EB can be administered to patients with DVT and is considered to be a DVT prophylaxis method that can be used in a larger number of patients. Therefore, we recommend that EB be performed in all the patients undergoing THA. [ABSTRACT FROM AUTHOR]

Purpose: Severe Pneumocystis jirovecii pneumonia (PJP) requiring intensive care has been the subject of few prospective studies. It is unclear whether delayed curative antibiotic therapy may impact survival in these severe forms of PJP. The impact of corticosteroid therapy combined with antibiotics is also unclear. Methods: This multicentre, prospective observational study involving 49 adult intensive care units (ICUs) in France was designed to evaluate the severity, the clinical spectrum, and outcomes of patients with severe PJP, and to assess the association between delayed curative antibiotic treatment and adjunctive corticosteroid therapy with mortality. Results: We included 158 patients with PJP from September 2020 to August 2022. Their main reason for admission was acute respiratory failure (n = 150, 94.9%). 12% of them received antibiotic prophylaxis for PJP before ICU admission. The ICU, hospital, and 6-month mortality were 31.6%, 35.4%, and 40.5%, respectively. Using time-to-event analysis with a propensity score-based inverse probability of treatment weighting, the initiation of curative antibiotic treatment after 96 h of ICU admission was associated with faster occurrence of death [time ratio: 6.75; 95% confidence interval (95% CI): 1.48–30.82; P = 0.014]. The use of corticosteroids for PJP was associated with faster occurrence of death (time ratio: 2.48; 95% CI 1.01–6.08; P = 0.048). Conclusion: This study showed that few patients with PJP admitted to intensive care received prophylactic antibiotic therapy, that delay in curative antibiotic treatment was common and that both delay in curative antibiotic treatment and adjunctive corticosteroids for PJP were associated with accelerated mortality. [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]

Dactylogyrosis is caused by more than 900 reported species of Dactylogyrus (gill fluke), mostly in Cyprinoidei fish leading to low to severe mortality in different culture systems and also in rivers/lakes. Dactylogyrus has been reported worldwide where Cyprinoidei is endemic. In recent years, incidents of infection and infectivity of different species of Dactylogyrus have increased many-fold due to several predisposing factors like intensification of culture, environmental quality, climatic change, poor quality fish seed, etc. These parasites are host choosy, either generalist or specialist. Dactylogyrus infection causes major changes in the anatomy and physiology of gill function. Necrosis, hyperplasia and hypertrophy of gill lamellae are the common pathologies observed during infection, which in turn invites other secondary pathogens leading to heavy mortalities. Currently, very few drugs or chemicals are available for controlling dactylogyrosis. Very few attempts have been made to develop vaccines against this important parasite. Here, we review the innate and adaptive immune responses modulated by Dactylogyrus infection and a hypothetical immunological model has been proposed to understand host-pathogen interaction based on our findings. The information collected and analysed in this review on the biology and host-pathogen interaction will help in the development of prophylactic and other sustainable management measures to reduce the loss associated with dactylogyrosis. [ABSTRACT FROM AUTHOR]

Background: While ursodeoxycholic acid is used in treating parenteral nutrition‐associated cholestasis (PNAC) in neonates, its role in prevention is unclear. Objectives: In this systematic review and meta‐analysis, we attempted to determine the role of ursodeoxycholic acid in preventing PNAC in neonates. Methods: PubMed, Embase, Cochrane Library, Scopus, and CINAHL databases were searched on September 16, 2023, for interventional studies comparing ursodeoxycholic acid with placebo. Results: Of the 6180 unique records identified, five studies were eligible for inclusion (three randomised and two nonrandomised). Evidence from randomised trials showed that ursodeoxycholic acid prophylaxis did not reduce cholestasis, mortality, sepsis, and necrotising enterocolitis. Ursodeoxycholic acid prophylaxis reduced feed intolerance (RR 0.23 (0.09, 0.64); 1 RCT, 102 neonates), peak conjugated bilirubin levels (MD −0.13 (−0.22, −0.04) mg/dL; 1 RCT, 102 neonates), and time to full enteral feeds (MD −2.7 (−5.09, −0.31) days; 2 RCTs, 76 neonates). There was no decrease in hospital stay and parenteral nutrition duration. Data from nonrandomised studies did not show benefit in any of the outcomes. The certainty of the evidence was low to very low. Conclusion: Because of the very low‐quality evidence and lack of evidence on critical outcomes, definitive conclusions could not be made on using ursodeoxycholic acid to prevent parenteral nutrition‐associated cholestasis in neonates. [ABSTRACT FROM AUTHOR]

In May 2024, the Swedish Reference Group on Antiviral Therapy updated the guidelines on management of HIV infection in pregnancy. The most important recommendations and revisions were: (i) ART during pregnancy should be started as early as possible and continue after delivery; (ii) Suppressive ART should normally not be modified; (iii) The treatment target of HIV RNA <20 copies/ml remains; (iv) Dolutegravir/emtricitabine/tenofovir DF is the first-line drug combination also in pregnant women and women planning pregnancy; (v) There is no evidence of an increased risk of neural tube defects associated with dolutegravir; (vi) Mode of delivery for women with effective ART and HIV RNA <200 copies/ml should follow standard obstetric procedures; (vii) Caesarean section is recommended if HIV RNA ≥200 copies/ml; (viii) Scalp electrode, foetal blood sampling and/or vacuum delivery should be used on strict indications, but does not necessitate intensified infant prophylaxis; (ix) Management and mode of delivery in case of premature or full-term rupture of membranes should follow standard obstetric procedures; (x) Recommended infant antiretroviral prophylaxis has been updated; (xi) The duration of infant antiretroviral prophylaxis (gestational age ≥35 weeks and mother on effective ART and HIV RNA <200 copies/ml) has been changed from 4 to 2 weeks; (xii) Infants born to women with HIV RNA ≥200 copies/ml should receive 4 weeks of combination prophylaxis; (xiii) Fertility evaluation and assisted reproduction should be offered to women on suppressive ART according to the same principles as for other women; (xiv) Women living with HIV should still be advised against breastfeeding; (xv) Women who nevertheless opt to breastfeed should be offered intensified support and follow-up. [ABSTRACT FROM AUTHOR]

In 2011, the American Academy of Orthopaedic Surgeons released a consensus recommending venous thromboembolism (VTE) prophylaxis after total knee arthroplasty (TKA). The purpose of our study was to examine (1) incidences of postoperative complications, including pulmonary embolism (PE), deep vein thrombosis (DVT), and transfusion rates; (2) trends from 2016 to 2021 in VTE prophylaxis; and (3) independent risk factors for 90-day total complications following TKA between aspirin, enoxaparin, rivaroxaban, and warfarin. Using a national, all-payer database from 2016 to 2021, we identified all patients who underwent primary TKA. Exclusions included all patients who had prescribed anticoagulants within 1 year prior to TKA, hypercoagulable states, and cancer. Data were collected on baseline demographics, including age, sex, diabetes, and a comorbidity index, in each of the VTE prophylaxis cohorts. Postoperative outcomes included rates of PE, DVT, and transfusion. Multivariable regressions were performed to determine independent risk factors for total complications at 90 days following TKA. From 2016 to 2021, aspirin was the most used anticoagulant (n = 62,054), followed by rivaroxaban (n = 26,426), enoxaparin (n = 20,980), and warfarin (n = 13,305). The cohort using warfarin had the highest incidences of PE (1.8%) and DVT (5.7%), while the cohort using aspirin had the lowest incidences of PE (0.6%) and DVT (1.6%). The rates of aspirin use increased the most from 2016 to 2021 (32.1% to 70.8%), while the rates of warfarin decreased the most (19.3% to 3.0%). Enoxaparin, rivaroxaban, and warfarin were independent risk factors for total complications at 90 days. An epidemiological analysis of VTE prophylaxis use from 2016 to 2021 shows an increase in aspirin following TKA compared to other anticoagulant cohorts in a nationally representative population. This approach provides more insight and a better understanding of anticoagulation trends over this time period in a nationally representative sample. [ABSTRACT FROM AUTHOR]

One of the most serious diseases affecting dairy cattle, causing significant losses both in breeding and economy, is mastitis, an inflammation of the mammary gland. Due to the economic importance of this issue, many research teams are striving to develop an easy-to-apply and, most importantly, effective method to prevent mastitis. The use of traditional methods for mastitis detecting and treating, as well as improvement in hygienic conditions, have not yielded the expected results in combating this disease combating. Currently, the main task is to find the tools that would allow for the rapid detection of mastitis and the improvement of udder health in cows while maintaining high milk production, which is essential for the profitability of dairy cattle farming. Accurate and rapid diagnostic tools, with the simultaneous capability of identifying pathogens, may help to reduce losses. Sufficient sensitivity and specificity for tests are required to minimize the number of false-positive and false-negative cases. Efforts are also being made to determine the optimal threshold value for detecting the disease at its earliest possible stage. The estimation of somatic cell count (SCC) as a phenotypic indicator of mastitis is widely used. A more precise parameter for accurately describing udder health is the differential somatic cell count (DSCC). The well-known California Mastitis Test (CMT) is an inexpensive, easy, and rapid method for mastitis detection useful on farms. The latest diagnostic methods for mastitis utilize tests based on the activity of N-acetyl-β-d-glucosaminidase (NAGase) or lactate dehydrogenase (LDH) as well as the determination of acute phase proteins (APPs) in blood serum and milk (such as haptoglobin, serum amyloid A, fibrinogen, and ceruloplasmin). Research also focuses on the genomic improvement of mastitis resistance in successive generations, and for this purpose, many quantitative trait loci (QTLs) and single nucleotide polymorphisms (SNPs) have been identified. In recent years, immunotherapy has become an increasingly common area of research, including vaccinations, T/B cell immunotherapy, RNA immunotherapy, epigenetic immunotherapy, stem cell therapy, and native secretory factors. An important aspect of the control of mastitis is the implementation of strategies that focus primarily on preventing the disease through appropriate breeding and farm management practices. In the forthcoming years, a significant challenge will be the development of universal diagnostic and therapeutic strategies that can be effectively implemented as alternatives to antibiotic therapy. Future research should prioritize the advancement of preventive and therapeutic techniques, such as immunotherapies, bacteriocins, herbal therapy, and nanoparticle technology. [ABSTRACT FROM AUTHOR]

Purpose of Review: The purpose of this review is to summarize and evaluate most recent evidence on the epidemiology of infections and associated risk factors in patients with primary systemic vasculitides (PSV), as well as discuss mitigation strategies including the risk of antibiotic prophylaxis. Recent Findings: Infections remain one of the leading causes of mortality in patients with PSV, with rates of severe infection ranging from 16 to 40% in different cohorts. Older age, frailty, renal and pulmonary involvement, and higher burden of comorbidities have been recognized as important patient-associated risk factors. Treatments including higher cumulative doses of glucocorticoids are associated with an increased risk of infections, and recent studies show the potential benefit of interventions such as reduced-dose glucocorticoid regimens. Existing mitigation strategies include screening, vaccination, and infection prophylaxis. The latter remains particularly important for Pneumocystis jirovecii pneumonia; however, the benefit-risk ratio seems to be less clear outside of induction phase (i.e., high dose of glucocorticoids) and optimal treatment duration remains less clear. Summary: Patients with PSV are at increased risk of infections, due to disease itself, comorbidities, and treatment side effects. Awareness of the timing and types of infection, as well as mitigation strategies are imperative to ensure treatment success and survival for patients. [ABSTRACT FROM AUTHOR]

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]

Background Primary antifungal prophylaxis with mold-active azoles is used to prevent invasive fungal infections in patients with high-risk hematological disorders; however, breakthrough infections occur, and the reasons for treatment failure are still not fully understood. To help inform clinical decisions, we sought to define microbiological, clinical, and pharmacological characteristics of proven and probable breakthrough invasive fungal infections (bIFIs) in patients with high-risk hematological disorders receiving voriconazole or posaconazole prophylaxis. Methods We performed a systematic review of the literature following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The search strategy was last conducted on 19 April 2023. Results We assessed 5293 studies for eligibility, and 300 were selected for data extraction. These studies described 1076 cases of bIFIs occurring under voriconazole (42.5%) or posaconazole (57.5%). The most commonly found pathogens were Aspergillus (40%), Mucorales (20%), Candida (18%), and Fusarium (9%) species. Mucorales were more frequent among voriconazole-emerging cases, whereas Aspergillus and Fusarium were more prevalent among posaconazole-emerging cases. Definitive, putative, or probable antifungal resistance was found in 31% of cases. Therapeutic drug monitoring showed subtherapeutic azole concentration in 32 of 90 (36%) cases. Infection-related mortality was reported in 117 cases and reached 35%. Conclusions In our systemic review, the most common bIFIs were aspergillosis, mucormycosis, candidiasis, and fusariosis. Antifungal resistance explains only a minority of cases. Subtherapeutic prophylaxis was frequent but rarely reported. Prospective studies are needed to better understand these infections and to establish optimal management. [ABSTRACT FROM AUTHOR]

Background: Malaria continues to wreak havoc on the well-being of the community. Resistant parasites are jeopardizing the treatment. This is a wake-up call for better medications. Folk plants are the key starting point for antimalarial drug discovery. After crushing and mixing the leaves of Coriandrum sativum with water, one cup of tea is drunk daily for a duration of three to five days as a remedy for malaria by local folks in Ethiopia. Additionally, in vitro experiments conducted on the plant leaf extract elsewhere have also demonstrated the plant's malaria parasite inhibitory effect. There has been no pharmacologic research to assert this endowment in animals, though. This experiment was aimed at evaluating the antimalarial efficacy of C. sativum in Plasmodium berghei infected mice. Methods: The plant's leaf was extracted using maceration with distilled water. The extract was examined for potential acute toxicity. An evaluation of secondary phytoconstituents was done. Standard antimalarial screening models (prophylactic, chemosuppressive, curative tests) were utilized to assess the antiplasmodial effect. In each test, thirty mice were organized into groups of five. To the three categories, the test substance was given at doses of 100, 200 and 400 mg/kg/day before or after the commencement of P. berghei infection. Positive and negative control mice were provided Chloroquine and distilled water, respectively. Rectal temperature, parasitemia, body weight, survival time and packed cell volume were ultimately assessed. Analysis of the data was performed using Statistical Package for Social Sciences. Results: No toxicity was manifested in mice. The extract demonstrated a significant inhibition of parasitemia (p < 0.05) in all the models. The inhibition of parasite load was highest with the upper dose in the suppressive test (82.74%) followed by the curative procedure (78.49%). Likewise, inhibition of hypothermia, weight loss hampering, improved survival and protection against hemolysis were elicited by the extract. Conclusions: The results of our experimental study revealed that the aqueous crude leaf extract of C. sativum exhibits significant antimalarial efficacy in multiple in vivo models involving mice infected with P. berghei. Given this promising therapeutic attribute, in depth investigation on the plant is recommended. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion Chagas disease (ChD) is endemic in many parts of the world and can be transmitted through organ transplantation or reactivated by immunosuppression. Organs from infected donors are occasionally used for transplantation, and the best way of managing the recipients remains a subject of debate.We present a single‐center cohort study describing a 10‐year experience of kidney transplantation in patients at risk of donor‐derived ChD and or reactivation. Patients received prophylactic treatment with Benznidazole and were monitored for transmission or reactivation. Monitoring included assessing direct parasitemia, serology, and polymerase chain reaction (PCR).Fifty‐seven kidney transplant recipients (KTRs) were enrolled in the study. Forty‐four patients (77.2%) were at risk of primary ChD infection, nine patients (15.8%) were at risk of disease reactivation, and four patients (7.0%) were at risk of both. All patients received Benznidazole prophylaxis, starting on the first day after transplantation. Parasitemia was assessed in 51 patients (89.5%), serology also in 51 patients (89.5%), and PCR in 40 patients (70.2%). None of the patients exhibited clinically or laboratory‐detectable signs of disease. A single patient experienced a significant side effect, a cutaneous rash with intense pruritus. At 1‐year post‐transplantation, the patient and graft survival rates were 96.5% and 93%, respectively.In this study, no donor‐derived or reactivation of Trypanosoma cruzi infection occurred in KTRs receiving Benznidazole prophylaxis. [ABSTRACT FROM AUTHOR]

Background: Home-based prophylaxis is recommended for optimal management of hemophilia. However, barriers limit its implementation in developing countries like India. This study aimed to identify barriers to home therapy in India. Materials and Methods: A qualitative study was conducted through interviews of 20 participants including persons with hemophilia, caregivers, healthcare workers and volunteers. Participants were randomly selected and interviewed using a semi-structured guide. Data was analysed thematically to identify barriers. Results: Four major categories of barriers emerged - technical expertise in self-infusion, logistical challenges of home care, lack of motivation among patients and caregivers, and inadequate advocacy efforts. Difficulties finding veins, fear of improper injection, issues maintaining cold chain, and reluctance to start therapy due to complexity were reported. Discussion: Barriers identified align with previous studies from other developing nations. Addressing skills-training, logistics, motivation and advocacy through targeted interventions like enhanced education, counselling and community engagement can help optimize home therapy uptake. Conclusion: The study provides guidance on key barriers preventing optimal home prophylaxis in India to inform development of context-specific solutions. [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: Graft Versus Host Disease (GvHD), which can be observed at a rate of 30-80% after allogeneic stem cell transplantation (ASCT) is an important complication that adversely affects the survival and quality of the life of patients. Posttransplant cyclophosphamide (PTCy) effectively prevents GvHD after HLA-haploidentical ASCT. In our study, the use of PTCy in 1-antigen HLA-mismatched unrelated donor (9/10MMUD) ASCT was compared with standard GvHD prophylaxis in HLA-identical related donor (MRD) ASCT. Materials and Methods: We conducted a retrospective study of the comparison of 42 patients with 9/10 MMUD ASCT receiving PTCy+Methotrexate (MTX)+Calcineurin Inhibitor (CNI) and 37 patients with HLA-identical MRD who received MTX+CNI in 3 bone marrow transplantation centers. Results: Cumulative incidences of grade I-II (64.6% vs 45.4%, p=0.187) or grade III to IV acute GvHD (35.4% vs54.6%, p=0.187) and chronic GvHD (11.9% vs 29.7%, p=0.096) were similar in the PTCy group and control group. No statistically significant differences were observed between PTCy and the control group in overall survival rate (52.4% vs 62.2%, p=0.381), progression-free survival (1483.97 vs 1200.70 days, p=0.502), relapsed-related mortality rate (21.4% vs 16.2%, p=0.556) and treatment-related mortality rate (16.7% vs 21.6%, p=0.575). Conclusion: With the addition of PTCy to standard GvHD prophylaxis in 9/10MMUD ASCT, the risk of GvHD due to incompatibility and unrelated transplantation is eliminated, and transplantation success is achieved with MRD ASCT. PTCy-based prophylaxis is an effective and safe strategy to prevent GvHD in 9/10 MMUD ASCT without increasing the risk of relapse and treatment-related mortality. [ABSTRACT FROM AUTHOR]

Although advances in the management of pediatric neoplasms have profoundly improved infectious disease outcomes, invasive fungal diseases (IFDs) remain a major cause of morbidity and mortality in children and adolescents with high-risk hematological malignancies. A retrospective study was conducted in the Pediatric Hematology–Oncology Department of the University General Hospital of Heraklion for 2013–2022 to estimate the prevalence and describe the clinical and epidemiological characteristics of IFDs for pediatric and adolescent patients with neoplasia. Demographic, clinical, and laboratory parameters were analyzed to identify risk factors for the development of IFD. The overall prevalence of IFDs was estimated to be 7.8% (12/154 patients) throughout the study. The mean age at IFD diagnosis was 9.8 years (SD 6.4 years). The most common IFD was possible/probable invasive pulmonary aspergillosis (IPA; in ≈50%), followed by candidemia/invasive candidiasis (in 44%). Candida parapsilosis was the most prevalent Candida species (4/6 events). Of interest, the majority (75%) of IFDs were breakthrough infections. Patients with increased risk for IFDs were those who were colonized by fungi in sites other than the oral cavity, hospitalized in the intensive care unit for >7 days, received >7 different antimicrobials in the last 3 months, or had severe neutropenia for >44 days. Two children out of a total of 12 with IFD died due to refractory disease or relapse (16.7%). More detailed and prospective epidemiological studies on fungal infections in pediatric patients with hematological or solid neoplasms can contribute to the optimization of prevention and treatment. [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]

Background: Ayush (Ayurveda, Yoga and Naturopathy, Unani, Siddha, and Homeopathy) system of medicine has been extensively used in India for the prevention and management of coronavirus disease 2019 (COVID-19). The present report is the second update of a living systematic review and meta-analysis and has been intended to assess the preventive potential and safety of Ayush drugs against COVID-19. Methods: A search of databases such as PubMed, the Cochrane central register of controlled trials, the World Health Organization (WHO) COVID-19 database, the clinical trial registry-India, the AYUSH research portal, and preprint repositories was performed till March 1, 2023. Randomized controlled trials or analytical observational studies were included. Incidences of COVID-19 infections and mortality were taken as primary outcome measures; and symptomatic severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) infection, incidences of hospital admissions, and adverse events were taken as secondary outcomes. The risk of bias was evaluated by version 2 of the Cochrane risk-of-bias tool for randomized trials (RoB-2) and the Risk of Bias in Non-Randomized Studies-of Interventions (ROBINS-I) tool. Data were synthesized through the RevMan 5.4 tool, and the certainty of the evidence was ranked through the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Results: Out of 2350 articles, 15 studies were included in the review. The pooled estimate of Guduchi [Tinospora cordifolia (Thunb.) Miers], Chyawanprasha, and Ayuraksha kit was obtained. Meta-analysis of the data suggested that Guduchi may reduce the incidences of COVID-19 infections (risk ratio [RR]: 0.67 [95% confidence interval, CI: 0.48–0.95]) and the symptom development among the infected (RR: 0.88 [95% CI: 0.73–1.08]), however, no change was observed in hospital admissions (RR: 0.96 [95% CI: 0.20–4.53]). It is uncertain that Chyawanprasha reduces the incidence of COVID-19 infection (RR: 0.28; [95% CI: 0.07–1.08]). Ayuraksha kit as chemoprophylaxis may reduce the incidences of COVID-19 infections (RR: 0.49; [95% CI: 0.32–0.77]). The certainty of the evidence was low to moderate mainly due to the serious risk of bias. Conclusion: Prophylactic use of Ayush medicines for populations at risk may help to prevent COVID-19 infection by reducing incidence and severity. However, considering the certainty and fewer studies, high-quality studies are still desired to confirm the efficacy and safety of Ayush chemoprophylaxis for COVID-19. Nevertheless, this update will serve as a torchbearer for policymakers, physicians, and other stakeholders for their decision-making through evidence-based medicine. [ABSTRACT FROM AUTHOR]

Introduction: Non‐factor replacement therapies are emerging as prophylactic treatment options in haemophilia A or B (HA/HB) with and without inhibitors. Concizumab is an anti‐tissue factor pathway inhibitor (TFPI) monoclonal antibody preventing factor (F)Xa inhibition and enhancing thrombin generation. Based on experience with other non‐factor therapies and extended half‐life products, there is a focus on potential interference with common clinical coagulation assays used to monitor patients treated with concizumab. Aim: To evaluate the impact of concizumab on standard clinical coagulation assays. Methods: Plasma samples (normal, HA/HB with/without inhibitors) in the presence/absence of added concizumab (250–16,000 ng/mL) were analysed in clinical assays including activated partial thromboplastin time (aPTT), prothrombin time (PT), FVIII and FIX one‐stage clot and chromogenic substrate assay, assays for detecting FVIII or FIX inhibitors and other assays for coagulation factors. Results: Concizumab did not impact PT assays, but resulted in a small shortening of aPTT (up to 5 s in haemophilia plasma and 0.4 s in normal plasma). Concizumab had no, or only a minor impact on FVIII and FIX activity assays or Bethesda inhibitor assays. FXI and FXII activity in normal plasma, as measured by single factor aPTT‐based assay, was significantly increased in the presence of concizumab (+11% each). This was also the case for FVII and FX measured by PT‐based assays using plasma with 25% of FVII or FX (+64% and +22%, respectively). Conclusion: The presence of concizumab did not, or only slightly, influence the outcome of standard clinical coagulation assays relevant for HA and HB. [ABSTRACT FROM AUTHOR]

Introduction: Reduced doses of emicizumab improve the affordability among patients in developing countries. However, the relationship between variant dose selection and efficacy in the real world of China is still unclear. Aim: This study aimed to investigate the efficacy and safety of emicizumab especially in those on reduced dose regimens in a real‐world setting. Methods: We carried out a multicentre study from 28 hospitals between June 2019 and June 2023 in China and retrospectively analysed the characteristics including demographics, diagnosis, treatment, bleeding episodes, and surgical procedures. Results: In total, 127 patients with haemophilia A, including 42 with inhibitors, were followed for a median duration of 16.0 (IQR: 9.0–30.0) months. Median age at emicizumab initiation was 2.0 (IQR: 1.0–4.0) years. Median (IQR) consumption for loading and maintenance was 12.0 (8.0–12.0) and 4.2 (3.0–6.0) mg/kg/4 weeks, respectively. While on emicizumab, 67 (52.8%) patients had no bleeds, whereas 60 (47.2%) patients had any bleeds, including 26 with treated bleeds. Compared to previous treatments, patients on emicizumab had significantly decreased annualized bleeding rate, annualized joint bleeding rate, target joints and intracerebral haemorrhage. Different dosages had similar efficacy except the proportion of patients with treated spontaneous bleeds and target joints. Adverse events were reported in 12 (9.4%) patients. Postoperative excessive bleeding occurred following two of nine procedures. Conclusion: This is the largest study describing patients with HA receiving emicizumab prophylaxis on variant dose regimens in China. We confirmed that nonstandard dose is efficacious and can be considered where full‐dose emicizumab is ill affordable. [ABSTRACT FROM AUTHOR]

Introduction: Gastrointestinal (GI) bleeding events (BEs) in von Willebrand disease (VWD) are difficult to diagnose and often recurrent. Limited data from clinical trials has led to lack of consensus on treatment options. Aim: Describe current treatments and outcomes for GI BEs in people with VWD. Methods: This retrospective, observational, multicentre chart review study was conducted from January 2018 through December 2019 and included patients with inherited VWD with ≥1 GI BE in the preceding 5 years. Baseline characteristics, number and aetiology of BEs, associated GI‐specific morbidities/lesions, treatment and outcomes were analysed descriptively. Results: Sixty bleeds were reported in 20 patients with type 1 (20%), type 2 (50%) and type 3 (30%) VWD. During the 5‐year study period, 31 (52%) BEs had one identified or suspected cause; multiple causes were reported in 11 (18%). Most GI BEs (72%) were treated with a combination of von Willebrand factor (VWF), antifibrinolytics and/or other haemostatic or non‐haemostatic treatments. Time to resolution did not differ by VWF treatment use; however, BEs treated with non‐VWF treatments tended to resolve later. In patients with GI‐specific morbidities/lesions, 84% resolved with first‐line treatment; time to resolution tended to be longer than in patients without such morbidities/lesions. Thirteen BEs occurred in patients receiving prophylaxis and 47 in patients receiving on‐demand treatment; 18 BEs resulted in a switch to prophylaxis after bleed resolution. Conclusions: This study confirms the unmet need for the management of recurrent GI BEs in people with VWD and the need for prospective data, especially on prophylaxis. [ABSTRACT FROM AUTHOR]

Background: Abiotic factors play a significant role in the evolution of Leishmania infantum infection due to its vectorial nature. This study aims to assess the evolution in the detection of new L. infantum infection cases in Valdeorras (Ourense, Northwestern Spain) over a 20-year period and how different climatic variables and preventive measures may have affected it. Methods: Indirect immunofluorescence antibody tests (IFAT) were performed on serum samples collected from dogs attending the 'Servicios Veterinarios de Sil' veterinary clinic (Valdeorras, Northwestern Spain) between May 2003 and April 2023 to detect L. infantum exposure. The percentage of new cases of L. infantum infection was calculated from May of one year to April of the following year. Climatic conditions in the region, global sales of ectoparasiticides and the number of vaccines against L. infantum delivered in the veterinary clinic from 2003 to 2022 were recorded. Statistical analyses were conducted to determine the associations between these factors and the percentage of new cases of L. infantum infection. Results: A total of 2909 dogs were assessed, and 3785 IFAT tests were performed between May 2003 and April 2023. The mean percentage of new seropositive cases over the 20-year period studied was 21.65 ± 10.8%, with a decline from the beginning to the end of the period studied. The percentage was significantly higher between May 2003 and April 2008 compared with the other periods (May 2008 to April 2013, May 2013 to April 2018 and May 2018 to April 2023). There was a positive correlation between the percentage of new cases of L. infantum infection and the maximum relative humidity in winter. Conversely, there was a negative correlation between the percentage of new cases and sales of ectoparasiticides and vaccination against L. infantum. Conclusions: This study is one of the longest evaluations of the evolution of L. infantum infection in a fixed location and its association with external factors including climatic conditions and preventive measures. The results confirm that Valdeorras is a high-risk area for L. infantum infection. The use of ectoparasiticides and vaccines against L. infantum has been shown to play a significant role in preventing L. infantum infection, highlighting the crucial role of veterinarians in the fight against this disease. [ABSTRACT FROM AUTHOR]

There has been a growing interest in venous thromboembolism following spinal surgery over the past few years. However, there currently needs to be a bibliometric report on this field. This study aims to construct the knowledge structure of venous thromboembolism after spinal surgery and explores the current status of research productivity, research directions, hotspots, and trends. All articles related to venous thromboembolism after spinal surgery from the Web of Science Core Collection database for 1990 to 2023 were retrieved. For bibliometric analysis, information extraction involves country/region, institutions, journals, authors, references, and keyword-related data. In this study, a total of 814 articles were identified. Studies related to venous thromboembolism after spinal surgery are showing an increasing trend, with the United States contributing the most. JOHNS HOPKINS UNIVERSITY is a high-productivity institution. The journal "SPINE" is highly productive. Research directions cover venous thromboembolism and bleeding, risk factors and prevention, complications, and perioperative blood protection strategies. Current research hotspots are risk factors, surgical location and approach, and perioperative blood protection strategies. Future research trends include establishing a predictive system for venous thromboembolism after spinal surgery to guide personalized prevention and treatment. This study constructed the knowledge structure of venous thromboembolism after spinal surgery, revealing current research hotspots and future trends. Future research trends include personalized prevention and treatment strategies for venous thromboembolism after spinal surgery, especially safe and effective chemical prophylaxis. It is hoped that this study can lay the foundation for subsequent research. [Display omitted] [ABSTRACT FROM AUTHOR]

Nanobodies are the smallest known antigen-binding molecules to date. Their small size, good tissue penetration, high stability and solubility, ease of expression, refolding ability, and negligible immunogenicity in the human body have granted them excellence over conventional antibodies. Those exceptional attributes of nanobodies make them promising candidates for various applications in biotechnology, medicine, protein engineering, structural biology, food, and agriculture. This review presents an overview of their structure, development methods, advantages, possible challenges, and applications with special emphasis on infectious diseases-related ones. A showcase of how nanobodies can be harnessed for applications including neutralization of viruses and combating antibiotic-resistant bacteria is detailed. Overall, the impact of nanobodies in vaccine design, rapid diagnostics, and targeted therapies, besides exploring their role in deciphering microbial structures and virulence mechanisms are highlighted. Indeed, nanobodies are reshaping the future of infectious disease prevention and treatment. [ABSTRACT FROM AUTHOR]

There is lack of guidance for immune monitoring and infection prevention after administration of ex vivo genetically modified hematopoietic stem cell therapies (GMHSCT). We reviewed current infection prevention practices as reported by providers experienced with GMHSCTs across North America and Europe, and assessed potential immunologic compromise associated with the therapeutic process of GMHSCTs described to date. Based on these assessments, and with consensus from members of the International Society for Cell & Gene Therapy (ISCT) Stem Cell Engineering Committee, we propose risk-adapted recommendations for immune monitoring, infection surveillance and prophylaxis, and revaccination after receipt of GMHSCTs. Disease-specific and GMHSCT-specific considerations should guide decision making for each therapy. [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]

Introduction/Aims: Glucocorticoids (GC) are first‐line therapy for many neuromuscular diseases. There is a lack of guidelines regarding the prevention and management of GC complications in the context of neuromuscular disease, introducing the potential for practice variation, that may compromise quality of care. Our aim was to evaluate the practice patterns among Canadian adult neuromuscular neurologists on the screening, management, and treatment of GC‐related complications and to identify variances in practice. Methods: A web‐based anonymous questionnaire was disseminated to 99 Canadian adult neuromuscular neurologists. Questions addressed patterns of screening, prevention, monitoring, and treatment of GC‐induced adverse events, including infection prophylaxis, vaccination, bone health, hyperglycemia, and other complications. Results: Seventy‐one percent completed the survey. Of those, 52% perform screening blood work prior to initiating GC, 56% screen for infections, and 18% for osteoporosis. The majority monitor glycemic control and blood pressure (>85%). Thirty‐two (46%) reported that they do not primarily monitor GC complications, but rather provide recommendations to the primary care physician. Pneumocystis jiroveci pneumonia prophylaxis was never used by 29%, and 29% recommend vaccinations prior to GC initiation. Calcium supplementation was recommended by 80% to prevent osteoporosis. Only 36% were aware of any existing guidelines for preventing GC complications, and 91% endorsed a need for neurology‐specific guidelines. Discussion: There is substantial variability in the management of GC adverse effects among neuromuscular neurologists, often not corresponding to limited published literature. Our results support the need for improved education and neurology‐specific guidelines to help standardize practice and improve and prevent complications. [ABSTRACT FROM AUTHOR]

Background: In recent decades, venous thromboembolism (VTE) has been acknowledged as a health issue that can be prevented. Among hospitalized patients, thromboembolism is a serious complication. Patients in the intensive care unit (ICU) are more susceptible to thrombotic events because of supplementary risk factors like central catheters, mechanical ventilation, and immobilization. Aim: This study aims to assess the appropriateness of VTE prophylaxis practices in a medical ICU of a tertiary care hospital. The IMPROVE VTE RAM was compared with clinical judgment for any significant difference in the risk assessment. Methods: It was a retrospective cross sectional observational study carried out on the patients admitted to the medical ICU of the Vascular Surgery department from March 2023 to August 2023. Medical records and risk assessment were done using the IMPROVE VTE RAM. The prophylaxis was given to patients based on American Society of Haematology (ASH) guidelines. Results: This was a 6 months retrospective study and a total number of 50 patients were included in the study. However, appropriate risk assessment was not done in any patient. Based on IMPROVE VTE RAM 1 patient (2%) was in low risk, 37 (74%) in moderate risk, and 12 (24%) in high risk for VTE. Thus Prophylaxis was given to a total of 44 patients out of which 27 received unfractionated heparin and the rest of all patients received Low Molecular Weight Heparin. Mechanical prophylaxis was given to 2 patients. The regular emphasis on DVT prophylaxis and the critical care nurses' ongoing daily audit were able to commence DVT prophylaxis in the majority of patients. According to IMPROVE VTE RAM, the accuracy of clinicians' judgment in comparison to validated risk assessment tools was only 89%. Conclusion: Critically ill admitted patients are more likely to experience VTE and bleeding episodes. Therefore adequate prophylaxis is essential but unfortunately is not routinely used in critical care settings. There is an urgent need to identify the gaps and address areas such as thromboprophylaxis and consistent care that require attention. Healthcare professionals must be made aware of the significance of risk assessment for bleeding and VTE in all critically ill patients, using any validated risk assessment tool. [ABSTRACT FROM AUTHOR]

Hemophilia A/B are caused by deficiency or lack of coagulation factors VIII (FVIII) or factor IX (FIX), respectively, in plasma. A person with hemophilia develops bleeding in the joints and muscles at an early age, which, if left untreated, leads to early arthropathy. Preventive treatment can be achieved by regular (prophylactic) administration of FVIII/FIX. In 1958, this was implemented on a small scale in Sweden with FVIII in patients with severe hemophilia A, and in those with hemophilia B in 1972 when FIX became available. However, there were problems with human immunodeficiency virus and hepatitis infection from contaminated blood products. In the 1990s, recombinant FVIII and FIX concentrates were introduced. The major remaining problems then were the development of inhibitors, and the need for a venous route for the injections in very young children. High-titer inhibitors were treated by immune tolerance induction according to a modified model of the original Bonn high-dose protocol. A central venous line, i.e., Port-A-Cath, has enabled early prophylaxis in many children with poor venous access and has enabled the early start of home treatment with adequate injection frequency. Scoring systems for X-rays, magnetic resonance imaging, and function of joints were developed early in Sweden and have been widely disseminated worldwide, partly with modifications. Extended half-life products with half-life increased three to five times have been developed, which can provide superior bleed protection when dosed once-weekly and can maintain therapeutic trough levels when administered less frequently. The ultimate prophylaxis therapy in the future may be gene therapy. [ABSTRACT FROM AUTHOR]

This study aimed to assess if transient bacteremia developed from dental scaling, root planing (SRP) and dental extraction(s), if the bacteria originated from oral flora, and if the amount of bacteremia produced would warrant the use of pre-, intra-, or post-operative antibiotic therapy in healthy canine patients. Blood cultures were obtained from 13 healthy dogs with chronic periodontal disease that necessitated the extraction of one tooth or multiple teeth. Patients included did not receive any antibiotic therapy for a minimum of 2 weeks prior to their scheduled procedure and did not receive antibiotic therapy intra- or post-operatively. Blood collection occurred at specific time increments to determine the presence of bacteremia and if clearance of the bacteremia occurred post-procedure. The study found transient bacteremia developed at different time increments throughout the dental procedure. At the time of the final sample collection, no bacterial growth was evident in any of the blood cultures. Results of the blood cultures indicated that only four of 13 dogs had evidence of bacterial growth at any one of the time increments; however, by the final collection, there was no bacterial growth suggesting the transient bacteremia had cleared without the use of systemic antimicrobial therapy. The study findings indicate that systemic antibiotic usage is not warranted for severe periodontal disease where an episode of transient bacteremia is produced from SRP and dental extractions in an otherwise healthy patient. [ABSTRACT FROM AUTHOR]

Venous thromboembolism (VTE) is a common cause of morbidity and mortality after bariatric surgery. Morbid obesity is an independent risk factor for VTE, with goals of prophylactic anti-factor Xa levels within 0.2–0.5 IU/mL. The recommended dosing regimen of enoxaparin for VTE prophylaxis in patients with morbid obesity is lacking in available guidelines. To evaluate the achieving prophylactic anti-factor Xa levels with different dosages of enoxaparin for morbid obesity patients. We conducted a study at Chulalongkorn Bariatric and Metabolic Institute, King Chulalongkorn Memorial Hospital. We conducted a randomized controlled trial comparing anti-factor Xa levels 4 h after the administration of enoxaparin. All recruited patients randomly received 40 mg or 60 mg of enoxaparin 12 h before the operation. Blood specimens were collected 4 h after the administration of enoxaparin. In total, 56 patients who presented between April 2019 and March 2020 at King Chulalongkorn Memorial Hospital were recruited. Of these patients, 28 received 40 mg and 28 received 60 mg of enoxaparin. In both groups, the rates of achieving target levels were 53.57% and 78.57%, respectively (p-value = 0.048). The mean anti-factor Xa levels were 0.19 IU/mL ± 0.06 IU/mL and 0.28 and 0.28 ± 0.10 IU/mL, respectively (p < 0.001). No significant difference was found in the estimated blood loss between the groups. No patient obtained anti-factor Xa levels exceeding 0.5 IU/mL. In both groups, no symptomatic VTE occurred. A 60 mg of enoxaparin regimen achieved more prophylactic anti-factor Xa levels than 40 mg in obese patients undergoing bariatric surgery without any adverse events. [ABSTRACT FROM AUTHOR]

Tooth extraction has been avoided in patients receiving antiresorptive agent (ARA) therapy. This study aimed to investigate dental findings associated with medication-related osteonecrosis of the jaw (MRONJ) development in patients. First, in patients treated with high-dose ARAs, the relationship between dental findings and MRONJ development was examined. Next, in patients with MRONJ undergoing surgery, the relationship between dental findings and MRONJ occurring at a site distant from the initial site was examined. MRONJ occurred in 13 of 172 patients (80 of 3725 teeth) during observation. Multiple tooth loss, periodontal ligament space enlargement, alveolar bone loss, periapical osteosclerosis, and local infection symptoms were associated with MRONJ development. Tooth extraction significantly reduced MRONJ development. Regarding other-site recurrence, new MRONJ developed at other sites in 54 of 357 patients with MRONJ (171 of 5038 teeth). Multiple tooth loss, apical lesions, periodontal ligament space enlargement, and periapical osteosclerosis were significantly associated with MRONJ development. In patients with malignant tumors, tooth extraction significantly reduced the subsequent incidence of MRONJ, while in patients with osteoporosis, there was no difference in the incidence of MRONJ between patients with and without tooth extraction. MRONJ was more likely to develop from teeth with local infections. Extraction of teeth with local infection in patients with malignancy may be more effective than tooth preservation in preventing MRONJ. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to assess the efficacy of different oral iron preparations prescribed for prevention of iron deficiency anemia in healthy infants. Methods: This retrospective study enrolled infants aged between 6 and 12 months who were initiated on iron prophylaxis at four months of age. Enrolled children consistently used specific iron preparations (ferrous, ferric or liposomal iron) and had their complete blood counts and serum ferritin levels assessed within the 6–12 month timeframe. Blood values and iron prophylaxis type (ferrous (Fe+2), ferric (Fe+3), liposomal iron) were recorded. Chi-square test was used to compare the hemoglobin and ferritin levels levels between groups. Univariate and multivariate regression analyses assessed the risk of anemia. Results: The study included 371 children (ferrous sulphate - 60, iron hydroxide-polymaltose complex - 137 and liposomal ferric pyrophosphate - 174) with a mean (SD) age 9.1 (1.3) mo. Iron deficiency in different groups were: liposomal iron (46.0%), ferric iron (44.5%), and ferrous iron (5.0%). Mean (SD) serum ferritin levels (µg/L) were higher in the ferrous group [30.1 (10.8)] compared to infants receiving ferric [17.6 (14.50)] and liposomal iron [15.4 (12.1)] (P < 0.001). Mean (SD) hemoglobin levels (g/dL) were significantly higher in the ferrous group [12.4 (0.8)] compared to ferric [11.9 (1.1)] and liposomal iron group [12.0 (1.1)]; P =0.008. Multiple regression analysis showed that ferrous group was associated with a lower risk of iron deficiency [OR (95% CI) 0.04 (0.01–0.15), P < 0.001]. Conclusion: Ferrous iron demonstrated superior efficacy compared to ferric and liposomal iron. Further studies are needed to establish alternative iron preprations in children. [ABSTRACT FROM AUTHOR]

Background/Aim: Heterotopic ossification (HO) is a common complication following total hip arthroplasty. Various prophylactic treatments have been proposed, including radiotherapy (RT). This review summarizes the evidence from meta-analyses on the efficacy of RT in preventing hip HO. Materials and Methods: A literature search was conducted on PubMed. The quality of the metaanalyses was assessed using the AMSTAR-2 tool. Results: Seven meta-analyses were included. One meta-analysis reported a significant reduction in HO occurrence after RT compared to the control group. Comparing RT and nonsteroidal anti-inflammatory drugs, one and two meta-analyses showed significantly greater efficacy of RT in preventing severe HO and better outcomes in patients receiving drugs, respectively. Regarding RT settings, the postoperative and preoperative RT were each supported by one meta-analysis. Furthermore, two meta-analyses showed an advantage of multi-fractionated RT over single fraction RT. The overall confidence rate of the meta-analyses was moderate, low, and critically low in one, three, and three meta-analyses, respectively. Conclusion: RT is a confirmed prophylactic intervention for HO. However, the precise optimization of timing, dosage, and fractionation requires elucidation. Future research should focus on the development of predictive models through large-scale data collection and advanced analytics to refine individualized treatment strategies and assess RT comparative effectiveness with drugs. [ABSTRACT FROM AUTHOR]