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Optivate is a high purity factor VIII/von Willebrand factor (FVIII/VWF) concentrate, which is manufactured using two antiviral processes: solvent/detergent and terminal dry heating (80°C for 72 h). A multicentre, non-randomized open-label study in 15 patients was conducted to test the pharmacokinetics (PK) of Optivate. PK variables were analysed for the patients' prior FVIII product (PK1), their first dose of Optivate (PK2) and at 3 months therapy (PK3). Mean non-compartmental half-lives (h) were 14.1, 12.4 and 12.1, respectively ( P = 0.45), mean clearances (mL h kg) were 3.6, 3.2 and 3.1, respectively ( P = 0.051), MRTs (h) were 19.0, 17.3 and 17.4, respectively ( P = 0.39) and mean AUC (h IU mL) were 14.3, 15.4 and 16.6, respectively ( P = 0.051) and mean AUC (h IU mL) were 15.9, 16.4 and 17.9, respectively ( P = 0.18). The recovery data from this PK study was aggregated with recovery data collected from another study, with similar design but devoid of the other PK measurements. A total of 309 recoveries were conducted in 70 patients. The overall mean recovery per subject across 27 Optivate batches was 2.7 IU dL per IU kg. There were no clinical differences between Optivate and other FVIII products, and except for volume of distribution (Vd), no statistically significant differences were seen with respect to any of the other PK variables, or in recovery between weeks 0 and 12. Therefore, the PK of FVIII is not affected by the processes used to manufacture Optivate, which can be expected to be effective in the management of patients with haemophilia A. [ABSTRACT FROM AUTHOR]

Forty patients severely immunocompromised because of the nature of their underlying disease (marrow aplasia, acute leukaemia or solid tumour) and/or the treatment they were receiving, received ketoconazole 400 mg daily. All patients also received gut decontamination with non-absorbable antibiotics, skin antisepsis, sterile food and oral co-trimoxazole. Mean (±S.D.) peak serum ketoconazole levels of 5·14±1·4 mg/l occurred 3 h after drug intake. In patients not receiving an allogeneic bone marrow transplant (BMT), the mean serum level at 2 h post-dose remained in the range of 3 to 5 mg/l during prolonged therapy. In contrast, serum ketoconazole levels in allogeneic BMT patients declined during continued treatment. In addition, the incidence of fungal infections was significantly higher in allogeneic-BMT patients than in the other group (<0·005). [ABSTRACT FROM PUBLISHER]

Presents a letter to the editor about P.S. Tillard's suggestion that ozone could be used as a bactericide to combat methicillin-resistant staphylococcus aureus, which appeared in the June/July 2005 issue of "Engineering Management."

The influence of fathers, grandmothers and other family members on maternal, infant and young child nutrition practices has been well documented for decades, yet many social and behavioural interventions continue to reach only mothers. While recent guidelines recommend involving fathers, grandmothers and other family members in maternal and child nutrition, we lack a comprehensive review of interventions that have engaged them. This scoping review aimed to address this gap by describing social and behavioural interventions to engage family members in maternal and child nutrition in low- and middle-income countries. We systematically searched PubMed, Scopus, Web of Science, Global Health and CINAHL for peer-reviewed studies meeting inclusion criteria. We screened 6,570 abstracts, evaluated 179 full-text articles, and included 87 articles from 63 studies. Studies reported a broad range of approaches to engage fathers, grandmothers and other family members to support maternal nutrition (n = 6); breastfeeding (n = 32); complementary feeding (n = 6) and multiple maternal and child nutrition practices (n = 19). Interventions were facility and community based; included individual and group-based interpersonal communication, community mobilization, mass media and mHealth; and reached mothers and family members together or separately. Most interventions were located within the health sector; rare exceptions included nutrition-sensitive agriculture, social protection, early child development and community development interventions. Few interventions addressed gender norms, decision-making, and family dynamics or described formative research or theories informing intervention design. These diverse studies can shed light on innovative programme approaches to increase family support for maternal and child nutrition., (© 2021 The Authors. Maternal & Child Nutrition published by John Wiley & Sons Ltd.)

Preeclampsia and preterm birth are among the most common pregnancy complications and are the leading causes of maternal and fetal morbidity and mortality in the United States. Adverse pregnancy outcomes are multifactorial in nature and increasing evidence suggests that the pathophysiology behind preterm birth and preeclampsia may be similar-specifically, both of these disorders may involve abnormalities in placental vasculature. A growing body of literature supports that exposure to environmental contaminants in the air, water, soil, and consumer and household products serves as a key factor influencing the development of adverse pregnancy outcomes. In pregnant women, toxic metals have been detected in urine, peripheral blood, nail clippings, and amniotic fluid. The placenta serves as a "gatekeeper" between maternal and fetal exposures, because it can reduce or enhance fetal exposure to various toxicants. Proposed mechanisms underlying toxicant-mediated damage include disrupted placental vasculogenesis, an up-regulated proinflammatory state, oxidative stressors contributing to prostaglandin production and consequent cervical ripening, uterine contractions, and ruptured membranes and epigenetic changes that contribute to disrupted regulation of endocrine and immune system signaling. The objective of this review is to provide an overview of studies examining the relationships between environmental contaminants in the US setting, specifically inorganic (eg, cadmium, arsenic, lead, and mercury) and organic (eg, per- and polyfluoroalkyl substances) toxicants, and the development of preeclampsia and preterm birth among women in the United States., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Fathers, grandmothers, and other family members' influence on maternal, infant, and young child nutrition (MIYCN) is widely recognized, yet synthesis of the effectiveness of engaging them to improve nutrition practices during the first 1000 d is lacking. We examined the impact of behavioral interventions to engage family members in MIYCN in low- and middle-income countries through a mixed-methods systematic review. We screened 5733 abstracts and included 35 peer-reviewed articles on 25 studies (16 with quantitative and 13 with qualitative data). Most quantitative studies focused on early breastfeeding, primarily engaging fathers or, less often, grandmothers. Most found positive impacts on exclusive breastfeeding rates and family members' knowledge and support. The few quantitative studies on complementary feeding, maternal nutrition, and multiple outcomes also suggested benefits. Qualitative themes included improved nutrition behaviors, enhanced relationships, and challenges due to social norms. Interventions engaging family members can increase awareness and build support for MIYCN, but more rigorous study designs are needed. This systematic review is registered at PROSPERO as CRD42018090273, https://www.crd.york.ac.uk/prospero/display&#95;record.php?RecordID=90273., (Copyright © The Author(s) on behalf of the American Society for Nutrition 2020.)

Ovine pestiviruses have the potential to reduce productivity in the British sheep flock. However, their prevalence and impact are currently poorly understood. This study aimed to estimate the exposure to pestiviruses in adult breeding ewe stock. Blood samples collected for metabolic profiling before lambing were tested using an ELISA that detected antibodies raised to both bovine viral diarrhoea virus and Border disease virus. A group of 15 animals were tested per flock. A total of 34 farms were tested, of which 13 had at least one seropositive animal. In those positive flocks between one and nine of the animals tested antibody-positive. Positive flocks were identified in all regions of Great Britain. This work suggests that exposure to ovine pestiviruses is widespread, and that it is timely to investigate flock-level prevalence and possible production impacts of endemic infection., Competing Interests: Competing interests: None declared., (© British Veterinary Association 2018. No commercial re-use. See rights and permissions. Published by BMJ.)

The aim of this study was to examine the variation in antibiotic usage between 207 commercial sheep flocks using their veterinary practice prescribing records. Mean and median prescribed mass per population corrected unit (mg/PCU) was 11.38 and 5.95, respectively and closely correlated with animal defined daily dose (ADDD) 1.47 (mean), 0.74 (median) (R 2 =0.84, P<0.001). This is low in comparison with the suggested target (an average across all the UK livestock sectors) of 50 mg/PCU. In total, 80 per cent of all antibiotic usage occurred in the 39 per cent of flocks where per animal usage was greater than 9.0 mg/PCU. Parenteral antibiotics, principally oxytetracycline, represented 82 per cent of the total prescribed mass, 65.5 per cent of antibiotics (mg/PCU) were prescribed for the treatment of lameness. Oral antibiotics were prescribed to 49 per cent of flocks, 64 per cent of predicted lamb crop/farm. Lowland flocks were prescribed significantly more antibiotics than hill flocks. Variance partitioning apportioned 79 per cent of variation in total antibiotic usage (mg/PCU) to the farm level and 21 per cent to the veterinary practice indicating that veterinary practices have a substantial impact on overall antimicrobial usage. Reducing antibiotic usage in the sheep sector should be possible with better understanding of the drivers of high usage in individual flocks and of veterinary prescribing practices., Competing Interests: Competing interests: None declared., (© British Veterinary Association (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

The split upper eyelid defect (SUED) is a congenital defect of the upper eyelid thought to be exclusive to multihorned sheep. Eleven flocks with a high proportion of multihorned Hebridean sheep were visited in 2011. Statistical analysis was performed generating Pearson's chi-squared analysis, as well as (1) logistic regression, (2) ordinal logistic regression and (3) linear regression models. Four hundred and seventy-three pure-bred Hebridean sheep and one crossbred lamb were examined. Of all the multihorned animals inspected in 2011, 9.7 per cent of adults had evidence of SUED in one or more eyelids, with 17.6 per cent of lambs presented with one or more eyelid affected. Having five or more horns was protective in the linear regression model on eye-level data (p=0.045). Forward-facing horns were consistently associated with a 'worst' eye score in the eye-level data, with an odds ratio (OR) as high as 9.4 when compared with a base of backward-facing horns (p=0.002). Eyes positive for SUED were significantly more likely to be rose bengal stain-positive in all four analysis, including multilevel mixed effect ordered logistic regression (p<0.001, OR 149.3). A novel lesion was identified during the course of the study, with 3.4 per cent of lambs presented with dermoid. SUED was also identified in a crossbred animal. Further work is needed to quantify the exact cost to animals with unilateral or bilateral SUED with subtle and production cost of SUED., Competing Interests: Competing interests: None declared., (© British Veterinary Association (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background and Objectives: A multi-centre, non-comparative study examining the efficacy and safety of Subgam, a normal immunoglobulin (IgG) given weekly as a rapid subcutaneous infusion to patients with primary immune deficiency (PID), is reported. Also included is a summary of adverse drug reactions associated with the use of marketed Subgam in the UK., Materials and Methods: 50 patients with stable PID on IgG therapy were enrolled: Stage 1 included three infusions with prior IgG product followed by 6 months with Subgam, Stage 2 involved long-term Subgam therapy up to 4 years., Results: Stage 1, 85% of the subjects aged >12 years and 93% of the subjects aged <12 years achieved IgG levels ≥6 and ≥4 g/L, respectively at all observations. There were 3.62 infections/patient/year during Subgam treatment. The most common product-related events were infusion site reactions (50% of patients). Recent post-hoc pharmacokinetics analysis of the post-infusion serum total IgG concentration indicated that the mean dose-normalised incremental IgG AUCτ following intravenous dosing (120.5 g.day/L) was 1.64-fold that of the dose-normalised mean incremental IgG AUCτ following subcutaneous dosing (73.6 g.day/L), corresponding to an estimated IgG bioavailability for subcutaneous dosing of 61%. Only 34 post-licensing adverse reactions have been received in 30 patients over a period of 10 years; fourteen were classed as serious as defined by the ICH guidelines on good clinical practice. The most common post-licensing adverse reaction was infusion site reaction (7 reports). There were 7 reports of flu-like symptoms (pyrexia/shivering/rigors/feeling hot or cold), 2 other reports of combined flu-like symptoms and infusion site reactions, 5 reports of generalised skin reactions, and 3 reports of combined infusion site and skin reactions. There were also reports of anaphylaxis (2 reports) and 8 other adverse events (including headache). In conclusion, Subgam is effective and well tolerated in the treatment of PID., Trial Registration: ClinicalTrials.gov NCT02247141.

Purpose: To assess the safety of a plasma-derived highly purified factor IX concentrate (Replenine) in routine clinical use., Methods: Following guidelines entitled Safety Assessment of Marketed Medicines (SAMM), safety data were collected in the UK by retrospective review of the hospital notes of 114 patients who received an estimated 14.8 million IU of Replenine. Included were 40 patients undergoing 44 surgical procedures or dental extractions [corrected]., Results: The study detected a total of nine adverse events (AEs), four of which were possibly product-related, four that were unrelated to the product and one whose causality was unknown. None of these cases had been notified to the manufacturer through conventional spontaneous reporting procedures. One patient was switched from Replenine because of infusion site irritation, but no unexpected adverse reactions were noted. There were no reports of virus transmission or new factor IX inhibitor development. The mean factor IX recovery value was 1.44 IU/dl per IU/kg (95%CI: 1.31-1.57 IU/dl per IU/kg)., Conclusions: The study was a practical application of the SAMM guidelines to the collection of pharmacovigilance data on patients with Haemophilia B. Replenine is well tolerated in routine clinical practice.

It has been found that in BHK 21 cells caffeine potentiates cell killing by both UV irradiation and N-methyl-N-nitrosoguanidine (MNNG). The potentiating effect is greater with UV than with MNNG. While non-toxic concentrations of caffeine inhibit the joining of newly-replicated DNA fragments into large molecular weight DNA (post-replication repair) after UV irradiation, they have no such effect after MNNG treatment. Furthermore, the joining of DNA fragments continues in the cells treated with 3 microgram/ml of MNNG, a dose which leads to less than 5% cell survival. While inhibition of the synthesis of large molecular weight DNA can explain the synergistic effect of caffeine upon cell survival after UV irradiation, it cannot explain the similar effect after MNNG treatment.