Treatment Option For Prophylaxis Research Articles

How much prophylaxis is enough in haemophilia?

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?'. 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. 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. 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'.

Evaluating the efficacy and safety of a novel prophylactic nasal spray in the prevention of SARS-CoV-2 infection: A multi-centre, double blind, placebo-controlled, randomised trial.

Background The COVID-19 pandemic continues to devastate communities all over the world. The aim of this study was to evaluate the efficacy and safety of the test agent as a prophylaxis against SARS-CoV-2 infection in a population of high-risk healthcare workers.Methods The study was a multi-centre, prospective, double blind, randomized, placebo-controlled trial. Key eligibility criteria included absence of significant co-morbidity and no previous SARS-CoV-2 infection or vaccination. Participants were randomised to either the active agent nasal spray or placebo using computer generated random number tables. The nasal spray was administered 3 times daily over a 45 day course. The primary end point was the percentage of subjects who tested positive for IgGS (anti-spike, immunoglobulin G specific to the spike protein of SARS-CoV-2) at day 45.Results Between 16th April 2021 and 26th July 2021, 556 participants were analysed for the primary endpoint (275 Test; 281 Placebo). The test agent significantly reduced SARS-CoV-2 infection compared to placebo [36 cases (13.1%) Vs 97 cases (34.5%); OR 0.29 (95% CI; 0.18–0.45), p < 0.0001]. Fewer clinical symptoms were also seen in the test group [57 cases (17.6%) vs 112 cases (34.6%); OR 0.40, (95% CI; 0.27–0.59), p < 0.0001]. No harmful effects were associated with taking the test agent.Conclusion The test agent significantly reduced SARS-CoV-2 infection in healthcare workers, with 62% fewer infections when compared to placebo. It was found to be safe and well tolerated and offers a novel treatment option for prophylaxis against SARS-CoV-2 infection.

Prophylactic Effects of NFκB Essential Modulator-Binding Domain Peptides on Bone Infection: An Experimental Study in a Rabbit Model.

IntroductionOsteomyelitis is characterized by intensive inflammatory bone disease and remains a clinical challenge in orthopedic surgery, despite the advances made in medical and surgical therapies. Staphylococcus aureusis a major causative agent of osteomyelitis, causing the progressive inflammatory destruction of bone. Prophylaxis of osteomyelitis during orthopedic surgery is necessary. NFκB essential modulator–binding domain (NBD) peptides are cell-permeable peptide inhibitors of the IκB-kinase complex. The prophylactic effect of NBD peptides in relieving inflammation and inhibiting bone defects in osteomyelitis is still under investigation. Our purpose was to determine the preventive effect of NBD peptides in S. aureus infection–induced bone defects in osteomyelitis.MethodsAn S. aureus osteomyelitis rabbit model was used in this study. The rabbits were divided into four groups: NBD, cefazolin, control, and PBS. Clinical and laboratory indicators of erythrocyte-sedimentation rate, CRP, and TNFα levels were assessed to monitor systemic reactions. The efficacy of NBD peptides in S. aureus–induced osteomyelitis was evaluated by radiological, histological, and microbiological examinations, immunohistochemistry, immunofluorescence, and micro-CT scans.ResultsIn general, NBD peptides effectively reduced clinical signs in rabbits when compared with the control group. Radiography indicated that there was more severe osteomyelitis in the bacterium-infection control group. There was no significance between cefazolin- and NBD-group average scores. The histological results of the lesion slices further confirmed different severity among the groups. Additionally, significant pathological differences were found between the cefazolin and NBD groups, and the PBS group showed no obvious pathological changes.ConclusionProphylactic administration of NBD peptides to bone-defect areas inhibited bacterial spread and promoted bone regeneration, making NBD peptides a possible treatment option for prophylaxis in bone infections.

Converting factor and nonfactor usage into a single metric to facilitate benchmarking the resources consumed for haemophilia care across jurisdictions and over time.

The World Federation of Hemophilia started measuring factor utilization at the country level as IU/capita (International Units of factor concentrates used per country population) in 2001 for its Annual Global Survey. IU/capita have been used to benchmark a country's usage over time and for advocacy. The introduction of a common metric usage spanning across standard half-life (SHL), and extended half-life (EHL) clotting factor concentrates (CFCs) and emicizumab would be a valuable simplification for national healthcare policymaking and industrial production planning. Develop and examine a method of converting IU of SHL or EHL, and milligrams of emicizumab into a single metric. We developed conversion factors from manufacturer's recommended dose for prophylaxis with SHL, EHL, and emicizumab as reported on the licensing information for the United States and Europe. We validate the accuracy of these conversion factors against real-world usage data. The prescribing information in the United States and Europe is marginally different. The SHL/EHL conversion factors are higher when calculated based on the prescribing information than on real-world studies, which are considered more representative of clinical practice. The best estimate of the SHL/EHL conversion factors for FVIII and FIX were 1.04 and 1.87. The conversion factor for emicizumab to SHL is 70IU/mg. We have generated robust estimates of conversion factors for currently used treatment options for prophylaxis in haemophilia. Usage of a single, harmonized metric will facilitate benchmarking across different countries or longitudinally irrespective of the case-mix of treatment options.

PP100 Economic Evaluation Of A New Non-Antibiotic First-line Treatment Of Recurrent Urinary Tract Infections

INTRODUCTION:Urinary tract infections (UTIs) are common in female patients in general practice. These bacterial infections affect half of all women at least once in their life. Antibiotics are usually prescribed for UTIs, and continuous low antimicrobial prophylaxis is administered to patients at high risk of recurrent UTI (rUTIs) (1). However, a major concern arises due to the increased rates of severe treatment-related side effects and emergence of antimicrobial resistance, which makes rUTIs management more challenging while seeking the use of more expensive alternatives. On this basis, clinical evaluations of rUTI interventions should be accompanied by economic evaluations in order to guide healthcare policy and decision processes about healthcare resources allocation. The aim of this work was to perform a cost-effectiveness analysis of a novel effective non-antibiotic treatment option for prophylaxis of female patients with a history of rUTIs, based on intravesical administration of hyaluronic acid (HA) plus chondroitin sulfate (CS), as compared to recommended 1st-line antibiotic therapy (2).METHODS:A cost-utility analysis was performed in order to estimate the effectiveness of each treatment, according to the number of UTIs annual episodes, and the incremental cost-effectiveness (ICER) for patients with UTI, starting from data collected during a multicentric observational case-cross-over clinical trial involving seven European centers (2). The economic model includes the costs of HA treatment and the costs associated with each UTI, such as costs of UTI diagnostics and antibiotic treatment, additional care by the elderly-care physician, additional nursing care, and hospitalizations, as well as the expected QALY, measured through the Short Form Health Survey (SF-36) questionnaires administered to patients, for both groups (3).RESULTS:At this stage, preliminary findings suggest that HA plus CS is a cost-effective alternative to antibiotics for the treatment of recurrent UTIs, that could reduce UTIs events in female patients with a history of recurrent UTI at an acceptable cost.CONCLUSIONS:The results of this study support the use of HA plus CS against antimicrobials as 1st-line therapy in the management of rUTIs.