Shiga toxin-producing Escherichia coli-associated hemolytic uremic syndrome (STEC-HUS) is considered a toxemic disorder in which early intervention with neutralizing antibodies may have therapeutic benefits. INM004, composed of F(ab’)2 fragments from equine immunoglobulins, neutralizes Stx1/Stx2, potentially preventing the onset of HUS. A single-center, randomized, Phase 1, single-blind, placebo-controlled clinical trial to evaluate INM004 safety, tolerance, and pharmacokinetics (PK) in healthy adult volunteers, was conducted; In Stage I, eight subjects were divided in two cohorts (n=4) to receive a single INM004 dose of 2 or 4 mg.kg-1, or placebo (INM004:placebo rate 3:1). In Stage II six subjects received either three INM004 doses of 4 mg.kg-1 repeated every 24 h, or placebo (INM004:placebo rate of 5:1). Hospital discharged was 24 hours after the last infusion. INM004 was quantified by ELISA in serum samples obtained at predefined times. Safety and tolerability were assessed in both Stages by monitoring adverse events (AEs), laboratory test values, and vital signs. Eight subjects (57.1%) experienced treatment-emergent AEs (TEAEs), that resolved within 24 hours without requiring changes in treatment or additional intervention. No serious AEs were reported. Most TEAEs were of mild or moderate intensity, and four were possibly drug-related. Peak concentrations (Cmax) of INM004 were 45.1 µg.mL-1 and 77.7 µg.mL-1 for different doses, within two hours after infusion. The serum concentration declined in a biphasic manner (t1/2 range 30.7-52.9 hours). Systemic exposures showed accumulation in the repeated dose regimen (Cmax Day1 85.7 vs.149 µg.mL-1 Day3). These results supporting progression into the phase 2 trial in children with HUS

Introduction: Prazosin is an antihypertensive medication which can be used to help with post-traumatic stress disorder (PTSD) symptoms. Little data is currently available on its safety in pregnancy. Objective: To assess the fetal and pregnancy safety associated with Prazosin exposures in early Pregnancy. Methods: Subjects were 11 patients who took Prazosin during pregnancy and were counselled at the FRAME clinic in London Health Sciences Centre (Ontario, Canada) between January 1, 2000 to December 31, 2021. Data on their other exposures and pregnancy outcomes were collected from medical records and through telephone questionnaires. Results: It was found that 6 /11 (54.5%) subjects did not report any adverse outcomes and were uneventful pregnancies. There were 2 miscarriages. Birthweights were within the normal range for the remaining 9 pregnancies. Adverse events reported were consistent with background population expectation, including: 1 postpartum hemorrhage, 1 case of preeclampsia, 1 preterm birth, 2 NICU admissions, and 2 caesarean sections. Discussion / Conclusion: For these 11 subjects, pregnancy outcomes after exposure to Prazosin were consistent with typical outcomes from unexposed pregnancies. More data are needed to conclude that Prazosin is safe for use in pregnant subjects. However, the lack of adverse effects above baseline is reassuring to future patients who may be unintentionally exposed to Prazosin while pregnant. Therefore, this study contributes valuable data toward monitoring safety of Prazosin in Pregnancy.

It is unfortunately true that clinicians lack the necessary evidence to know how to use medications properly in large sections of the population, and we do not have optimal drugs to use in many Neglected Tropical Diseases (NTDs). NTD’s often disproportionately affect neglected populations such as children and pregnant women. As reliable access to safe, effective preventives and treatments can break the cycle of poverty, illness, and ensuing debility that further perpetuates poverty, it is of paramount importance to investigate and develop new medicines for neglected populations suffering from NTDs. Furthermore, there is not only a need to develop and evaluate novel therapies, but also to ensure that these are affordable, available, and adapted to the communities who need them. With this editorial, the British Pharmacological Society hereby launches a call for high-quality articles focusing on NTDs in special populations, to facilitate the reversal of this dual neglect.

Introduction: Chagas disease (CD) is a worldwide problem, with over 8 million people infected in both rural and urban areas. CD was first described over a century ago, but only two drugs are currently available for CD treatment, benznidazole (BZN) and nifurtimox (NF). Treating CD infected patients, especially children and women of reproductive age, is vital in order to prevent long term sequelae such as heart and gastrointestinal disfunction, but this aim is still far from being accomplished. Currently, the strongest data to support benefit-risk considerations come from trials in children. Finally, treatment response biomarkers need further development as serology is being questioned as the best method to assess treatment response. Areas covered: This article is a narrative review on the pharmacology of drugs for CD, particularly BZN and NF. Data on drug biopharmaceutical characteristics, safety and efficacy of both drugs are summarized from a clinical perspective. Current data on alternative compounds under evaluation for CD treatment, and new possible treatment response biomarkers are also discussed. Conclusion: Early diagnosis and treatment of CD, especially in pediatric patients, is vital for an effective and safe use of the available drugs (i.e. BZN and NF). New biomarkers for CD are urgently needed for the diagnosis and evaluation of treatment efficacy, and to guide efforts from academia and pharmaceutical companies to accelerate the process of new drugs development.

Background: Benefits of early Cystic Fibrosis (CF) detection using newborn screening (NBS) lead to widespread use in NBS programs. Since 2002, a two-stage immunoreactive trypsinogen (IRT/IRT) screening strategy has been used as CFNBS method in all public maternities in the City of Buenos Aires, Argentina. However, novel screening strategies may be more efficient. The aim of the study is to prospectively compare two CFNBS strategies, IRT/IRT and IRT/PAP (pancreatitis-associated protein). Methods: A two-year prospective study was performed. IRT was measured in dried blood samples collected 48–72 hours after birth. When IRT value was abnormal, PAP was determined, and a second visit was scheduled to obtain another sample for IRT before 25 days of life. Newborns with a positive CFNBS were referred for confirmatory sweat test. Results: There were 69,827 births in the City of Buenos Aires during the period studied; 918 (1.31%) had an abnormal IRT. A total of 207 children (22.5%) failed to return for the second IRT, but only two PAP (0.2%) were not performed. IRT/IRT was more likely to lead to a referral for sweat testing than IRT/PAP (OR 2.3 [95% CI 1.8;2.9], p<0.001). Sensitivity, specificity, positive predictive value, and negative predictive value were: 80% and 100%, 86.5% and 82.6%, 4.04% and 4.2%, 99.84% and 100% for IRT/IRT and IRT/PAP strategies, respectively. Conclusion: The IRT/PAP strategy is more sensitive than IRT/IRT; it avoids a second appointment and the need of unnecessary sweat testing, and decreases loss to follow up in our population.