Association of BNT162b2 SARS-CoV-2 vaccination during pregnancy with postnatal outcomes in premature infants.

AIM: The effect of COVID-19 vaccine given during pregnancy on premature infants is unknown. This study aims to determine the association between maternal COVID-19 vaccine with postnatal outcome in premature infants. METHODS: This is a single-centre retrospective case-control study of infants born before 35 weeks gestation to mothers who received SARS-CoV-2 vaccine during pregnancy compared with infant born to non-vaccinated mothers. RESULTS: A total of 78 infants in each group were included. Infants in the vaccinated group had less respiratory distress syndrome (RDS) (p = 0.02) and less need for respiratory support (p = 0.002), and maternal vaccine had a protective effect on RDS [adjustable OR 0.38 (0.17-0.85)]. Vaccination during the first compared to the second trimester was associated with earlier gestational age (32.3 ± 2.1 vs. 33.3 ± 1.1 weeks, p = 0.03). CONCLUSION: We demonstrated that maternal SARS-CoV-2 vaccine is not associated with postnatal adverse effect in premature infants and potentially has a protective effect on RDS. Earlier gestational age among the infants born to mothers who received COVID-19 vaccine during the first trimester did not translate to higher rate of postnatal complications. These findings might suggest that COVID-19 vaccine is safe in high-risk pregnancies, but timing of administration should be considered. Further studies are needed to confirm our findings and the biological mechanism.

Thiyl radical induced cis/trans isomerism in double bond containing elastomers.

This report presents an evaluation of thiyl radical-induced cis/trans isomerism in double bond-containing elastomers, such as natural, polychloroprene, and polybutadiene rubbers. The study aims to extensively investigate structural changes in polymers after functionalisation using thiol-ene chemistry, a useful click reaction for modifying polymers and developing materials with new functionalities. The paper reports on the use of different thiols, and cis/trans isomerism was detected through 1H NMR analysis, even at very low alkene/thiol mole ratios. The study finds that the configurational arrangements between non-functionalised elastomer units and thiolated units followed a trans-functionalised-cis units arrangement up to an alkene/thiol mole feed ratio of 0.3, while from 0.4 onward, a combination of trans-functionalised-cis and cis-functionalised-trans configurations are found. Additionally, it is observed that by increasing the level of functionalisation, the glass transition temperature of the resulting modified elastomer also increases. Overall, this study provides valuable insights into the effects of thiol-ene chemistry on the structure and properties of elastomers and could have important implications for the development of new materials with enhanced functionality.

Achieving HIV Epidemic Control and Improving Maternal Healthcare Services with Community-Based HIV Service Delivery in Zambia: Mixed-Methods Assessment of the SMACHT Project.

Novel community-based approaches are needed to achieve and sustain HIV epidemic control in Zambia. Under the Stop Mother and Child HIV Transmission (SMACHT) project, the Community HIV Epidemic Control (CHEC) differentiated service delivery model used community health workers to support HIV testing, ART linkage, viral suppression, and prevention of mother-to-child transmission (MTCT). A multi-methods assessment included programmatic data analysis from April 2015 to September 2020, and qualitative interviews from February to March 2020. CHEC provided HIV testing services to 1,379,387 clients; 46,138 were newly identified as HIV-positive (3.3% yield), with 41,366 (90%) linked to ART. By 2020, 91% (60,694/66,841) of clients on ART were virally suppressed. Qualitatively, healthcare workers and clients benefitted from CHEC, with provision of confidential services, health facility decongestion, and increased HIV care uptake and retention. Community-based models can increase uptake of HIV testing and linkage to care, and help achieve epidemic control and elimination of MTCT.

SARS-CoV-2 Infection of Young Infants during the Omicron Wave: A Case Series.

We describe the clinical course of 4 infants infected with severe acute respiratory syndrome coronavirus 2. All were admitted to our tertiary care neonatal intensive care unit during the Omicron variant wave in our region. All 4 infants, who were less than 3 months of age, including three born prematurely, presented with critical illness. However, their clinical presentation varied considerably. Of them, two infants presented with apnea, one with respiratory distress, and one with gastrointestinal manifestation. Our experience with these four infants provides evidence for a severe form of disease and varied clinical presentation in neonates and young infants speculated to be infected with Omicron variant.

Recommendations for procurement of starting materials by apheresis for advanced therapy medicinal products.

Activities involved in the production of certain advanced therapy medicinal products (ATMPs) require standardized approaches to mononuclear cell procurement to ensure the highest product quality, safety and process efficiency. These aims must be achieved while meeting regulatory and accreditation requirements for the procurement of mononuclear cells as starting materials. Mononuclear cells constitute the starting materials for many ATMPs, and this article sets out recommendations for procurement by clinical apheresis, addressing the variation among existing working practices and different manufacturers' requirements that currently poses a challenge when managing multiple different protocols.

Novel Crosslinking System for Poly-Chloroprene Rubber to Enable Recyclability and Introduce Self-Healing.

The introduction of dynamic bonds capable of mediating self-healing in a fully cross-linked polychloroprene network can only occur if the reversible moieties are carried by the cross-linker itself or within the main polymer backbone. Conventional cross-linking is not suitable for such a purpose. In the present work, a method to develop a self-healable and recyclable polychloroprene rubber is presented. Dynamic disulfide bonds are introduced as part of the structure of a crosslinker (liquid polysulfide polymer, Thiokol LP3) coupled to the polymer backbone via thermally initiated thiol-ene reaction. The curing and kinetic parameters were determined by isothermal differential scanning calorimetry and by moving die rheometer analysis; tensile testing was carried to compare the tensile strength of cured compound, healed compounds and recycled compounds, while chemical analysis was conducted by surface X-ray Photoelectron Spectroscopy. Three formulations with increasing concentrations of Thiokol LP-3 were studied (2, 4, 6 phr), reaching a maximum ultimate tensile strength of 22.4 MPa and ultimate tensile strain of 16.2 with 2 phr of Thiokol LP-3, 11.7 MPa and 10.7 strain with 4 phr and 5.6 MPa and 7.3 strain with 6 phr. The best healing efficiencies were obtained after 24 h of healing at 80 °C, increasing with the concentration of Thiokol LP-3, reaching maximum values of 4.5% 4.4% 13.4% with 2 phr, 4 phr and 6 phr, respectively, while the highest recycling efficiency was obtained with 4 phr of Thiokol LP-3, reaching 11.2%.

Treatment patterns and healthcare resource utilization among patients with hereditary angioedema in the United States.

BACKGROUND: Real-world data on usage and associated outcomes with hereditary angioedema (HAE)-specific medications introduced to the United States (US) market since 2009 are very limited. The purpose of this retrospective study was to evaluate real-world treatment patterns of HAE-specific medications in the US and to assess their impact on healthcare resource utilization (HCRU). This analysis used IMS PharMetrics PlusTM database records (2006-2014) of patients with HAE, ≥1 insurance claim for an HAE-specific medication, and continuous insurance enrollment for ≥3 months following the first HAE prescription claim. RESULTS: Of 631 total patients, 434 (68.8%) reported C1-INH(IV) use; 396 (62.8%) reported using ecallantide and/or icatibant. There were 306 episodes of prophylactic use of C1-INH(IV) (defined by continuous refills averaging ≥1500 IU/week for ≥13 weeks) in 155 patients; use of ≥1 on-demand rescue medication was implicated during 53% (163/306) of those episodes. Sixty-eight (20.2%) of 336 C1-INH(IV) users eligible for the HCRU analysis were hospitalized at least once, and 191 (56.8%) visited the emergency department (ED). Eighteen patients (5.4%) had a central venous access device (CVAD); of these, 5 (27.7%) required hospitalization and 14 (77.7%) had an ED visit. The adjusted relative risk of hospitalization and/or ED visits for patients with a CVAD was 2.6 (95% CI: 0.17, 39.23) compared to C1-INH(IV) users without a CVAD. CONCLUSIONS: Despite widespread availability of modern HAE medications in the US, we identified a subset of patients requiring long-term prophylaxis who continue to be burdened by frequent rescue medication usage and/or complications related to the use of CVADs for intravenous HAE medication.

Health-Related Quality of Life with Subcutaneous C1-Inhibitor for Prevention of Attacks of Hereditary Angioedema.

BACKGROUND: Hereditary angioedema with C1-inhibitor deficiency (C1-INH-HAE) impairs health-related quality of life (HRQoL). OBJECTIVE: The objective of this study was to assess HRQoL outcomes in patients self-administering subcutaneous C1-INH (C1-INH[SC]; HAEGARDA) for routine prevention of HAE attacks. METHODS: Post hoc analysis of data from the placebo-controlled, crossover phase III COMPACT study (Clinical Studies for Optimal Management of Preventing Angioedema with Low-Volume Subcutaneous C1-Inhibitor Replacement Therapy). Ninety patients with C1-INH-HAE were randomized to 1 of 4 treatment sequences: C1-INH(SC) 40 or 60 IU/kg twice weekly for 16 weeks, preceded or followed by 16 weeks of twice weekly placebo injections. All HAE attacks were treated with open-label on-demand treatment as necessary. HRQoL assessments at week 14 (last visit) included the European Quality of Life-5 Dimensions Questionnaire (EQ-5D-3L), the Hospital Anxiety and Depression Scale (HADS), the Work Productivity and Activity Impairment Questionnaire (WPAI), and the Treatment Satisfaction Questionnaire for Medication (TSQM). RESULTS: Compared with placebo (on-demand treatment alone), treatment with twice weekly C1-INH(SC) (both doses combined) was associated with better EQ-5D visual analog scale general health, less HADS anxiety, less WPAI presenteeism, work productivity loss, and activity impairment, and greater TSQM effectiveness and overall treatment satisfaction. More patients self-reported a "good/excellent" response during routine prevention with C1-INH(SC) compared with on-demand only (placebo prophylaxis) management. For each HRQoL measure, a greater proportion of patients had a clinically meaningful improvement during C1-INH(SC) treatment compared with placebo. CONCLUSIONS: In patients with frequent HAE attacks, a treatment strategy of routine prevention with self-administered twice weekly C1-INH(SC) had a greater impact on improving multiple HAE-related HRQoL impairments, most notably anxiety and work productivity, compared with on-demand treatment alone (placebo prophylaxis).

Patient satisfaction and experience with intravenously administered C1-inhibitor concentrates in the United States.

BACKGROUND: Hereditary angioedema (HAE) is a rare genetic disorder with substantial morbidity and mortality. Despite expanded choices for effective acute treatment, prophylactic options are more limited. Intravenous C1 esterase inhibitor (C1-INH[IV]) is licensed and used to prevent HAE symptoms. OBJECTIVE: To better understand patient experiences with using C1-INH(IV), including level of satisfaction and types and frequency of complications. METHODS: Fifty adult members (≥18 years of age) of the US HAE Association who had HAE type I or II completed a self-administered internet survey. Eligible participants were experiencing at least 1 HAE attack per month and must have been receiving treatment with C1-INH(IV) as prophylaxis or acute therapy. RESULTS: Almost all respondents (n = 47; 94%) were using C1-INH(IV) for HAE prophylaxis. Most patients reported administration of C1-INH(IV) through a peripheral vein (n = 34) and 19 were currently (n = 17) or previously (n = 2) using a central venous port. Most respondents (62%) who used a peripheral vein to administer treatment reported having difficulty finding a usable vein or getting the infusion to work properly at least some of the time. Issues accessing veins, exhausted veins, and frequency of attacks were the main reasons physicians recommended ports to respondents. Although ports allow easier administration of therapy, 47% of respondents with ports experienced problems such as occlusion, thrombosis, and infection. Respondents using C1-INH prophylaxis reported a mean of 2.3 attacks per month during the previous 6 months. CONCLUSION: The survey results identified clinical challenges with IV HAE medication use, including venous access issues and ongoing monthly attack occurrence despite prophylactic C1-INH(IV) administration.

The Arc of Human Immunodeficiency Virus Capacity Development: Insights from a Decade of Partnership for Medical Education in Zambia.

AbstractZambia and other sub-Saharan nations suffer from a critical shortage of trained health-care professionals to combat the human immunodeficiency virus/acquired immunodeficiency syndrome crisis. The University of Maryland and the Zambian Ministry of Health have partnered over the past decade to develop health-care capacity among physicians, nurses, and community health workers. We describe novel interventions to train health-care workers at all levels and argue that our collaboration represents a successful model for such partnerships between western medical institutions and African governmental health agencies.

Paucity of Intact Non-Induced Provirus with Early, Long-Term Antiretroviral Therapy of Perinatal HIV Infection.

The latent reservoir is a major barrier to HIV eradication. Reservoir size is emerging as an important biomarker to assess the likelihood of HIV remission in the absence of antiretroviral therapy (ART) and may be reduced by earlier initiation of ART that restricts HIV spread into CD4+ T cells. Reservoir size is traditionally measured with a quantitative viral outgrowth assay (QVOA) that induces replication-competent HIV production through in vitro stimulation of resting CD4+ T cells. However, the recent identification of replication-intact, non-induced proviral genomes (NIPG) suggests the QVOA significantly underestimates (by 62-fold) latent reservoir size in chronically-infected adults. Whether formation and persistence of Intact, NIPG is thwarted by early ART initiation and long-term virologic suppression in perinatal infection is unclear. Here, we show that the latent reservoir in 11 early treated, long-term suppressed perinatally infected children and adolescents was not inducible by QVOA and dominated by defective, NIPG. Single genome analysis of 164 NIPG from 232 million cultured resting CD4+ T cells revealed no replication-intact, near-full length sequences. Forty-three (26%) NIPG contained APOBEC3G-mediated hypermutation, 115 (70%) NIPG contained large internal deletions, one NIPG contained nonsense mutations and indels, and 5 (3%) NIPG were assigned as "Not Evaluable" due to multiple failed sequencing attempts that precluded further classification. The lack of replication competent inducible provirus and intact NIPG in this cohort indicate early, long-term ART of perinatal infection leads to marked diminution of replication-competent HIV-1 reservoirs, creating a favorable state towards interventions aimed at virologic remission.

At-line process analytical technology (PAT) for more efficient scale up of biopharmaceutical microfiltration unit operations.

Tangential flow microfiltration (MF) is a cost-effective and robust bioprocess separation technique, but successful full scale implementation is hindered by the empirical, trial-and-error nature of scale-up. We present an integrated approach leveraging at-line process analytical technology (PAT) and mass balance based modeling to de-risk MF scale-up. Chromatography-based PAT was employed to improve the consistency of an MF step that had been a bottleneck in the process used to manufacture a therapeutic protein. A 10-min reverse phase ultra high performance liquid chromatography (RP-UPLC) assay was developed to provide at-line monitoring of protein concentration. The method was successfully validated and method performance was comparable to previously validated methods. The PAT tool revealed areas of divergence from a mass balance-based model, highlighting specific opportunities for process improvement. Adjustment of appropriate process controls led to improved operability and significantly increased yield, providing a successful example of PAT deployment in the downstream purification of a therapeutic protein. The general approach presented here should be broadly applicable to reduce risk during scale-up of filtration processes and should be suitable for feed-forward and feed-back process control.

Chemically modified peptides based on the membrane-proximal external region of the HIV-1 envelope induce high-titer, epitope-specific nonneutralizing antibodies in rabbits.

Broadly neutralizing monoclonal antibodies (bNAbs) 2F5 and 4E10 bind to the membrane proximal external region (MPER) of gp41 and also cross-react with phospholipids. In this study, we investigated if chemical modifications on the MPER adjacent to 2F5 and 4E10 epitopes using mimetics of inflammation-associated posttranslational modifications to induce 2F5- and 4E10-like bNAbs can break tolerance. We synthesized a series of chemically modified peptides spanning the MPER. The serine, threonine, and tyrosine residues in the peptides were modified with sulfate, phosphate, or nitrate moieties and presented in liposomes for rabbit immunizations. All immunizations resulted in high antisera titers directed toward both the modified and unmodified immunogens. Tyrosine modification was observed to significantly suppress antiepitope responses. Sera with strong anti-gp140 titers were purified by affinity chromatography toward the MPER peptide and found to possess a higher affinity toward the MPER than did the bNAbs 2F5 and 4E10. Modest neutralization was observed in the H9 neutralization assay, but neutralization was not observed in the TZM-bl cell or peripheral blood mononuclear cell (PBMC) neutralization assay platforms. Although neutralizing antibodies were not induced by this approach, we conclude that chemical modifications can increase the immune responses to poorly immunogenic antigens, suggesting that chemical modification in an appropriate immunization protocol should be explored further as an HIV-1 vaccine strategy.

Ten years of transfusion practitioners and better blood transfusion in Scotland.

After the Department of Health's Better Blood Transfusion recommendations ( DH 2002 ) ten years ago, a network of 18 transfusion practitioners supported by a central team in the Scottish National Blood Transfusion Service was established. This article discusses the impact that transfusion practitioners in Scotland have had in driving local transfusion teams to promote safe and effective transfusion practice across Scotland. They have done this through education, audit and raising awareness of current guidelines.

Application of the OMERACT filter to measures of core outcome domains in recent clinical studies of acute gout.

OBJECTIVE: To determine the extent to which instruments that measure core outcome domains in acute gout fulfill the Outcome Measures in Rheumatology (OMERACT) filter requirements of truth, discrimination, and feasibility. METHODS: Patient-level data from 4 randomized controlled trials of agents designed to treat acute gout and 1 observational study of acute gout were analyzed. For each available measure, construct validity, test-retest reliability, within-group change using effect size, between-group change using the Kruskall-Wallis statistic, and repeated measures generalized estimating equations were assessed. Floor and ceiling effects were also assessed and minimal clinically important difference was estimated. These analyses were presented to participants at OMERACT 11 to help inform voting for possible endorsement. RESULTS: There was evidence for construct validity and discriminative ability for 3 measures of pain [0 to 4 Likert, 0 to 10 numeric rating scale (NRS), 0 to 100 mm visual analog scale (VAS)]. Likewise, there appears to be sufficient evidence for a 4-point Likert scale to possess construct validity and discriminative ability for physician assessment of joint swelling and joint tenderness. There was some evidence for construct validity and within-group discriminative ability for the Health Assessment Questionnaire as a measure of activity limitations, but not for discrimination between groups allocated to different treatment. CONCLUSION: There is sufficient evidence to support measures of pain (using Likert, NRS, or VAS), joint tenderness, and swelling (using Likert scale) as fulfilling the requirements of the OMERACT filter. Further research on a measure of activity limitations in acute gout clinical trials is required.

Nanoskiving core-shell nanowires: a new fabrication method for nano-optics.

This paper describes the fabrication of functional optical devices by sectioning quantum-dot-in-nanowires systems with predefined lengths and orientations. This fabrication process requires only two steps, embedding the nanowires in epoxy and using an ultramicrotome to section them across their axis ("nanoskiving"). This work demonstrates the combination of the following four capabilities: (i) the control of the length of the nanowire sections at the nanometer scale; (ii) the ability to process the nanowires after cutting using wet etching; (iii) the possibility of modifying the geometry of the wire by varying the sectioning angle; and (iv) the generation of as many as 120 consecutive slabs bearing nanowires that have uniform size and approximately reproducible lateral patterns and that can subsequently be transferred to different substrates. The quantum dots inside the nanowires are functional and of a high optical quality after the sectioning process and exhibit photoluminescent emission with wavelengths in the range of 650-710 nm.

Interventions to reduce wrong blood in tube errors in transfusion: a systematic review.

This systematic review addresses the issue of wrong blood in tube (WBIT). The objective was to identify interventions that have been implemented and the effectiveness of these interventions to reduce WBIT incidence in red blood cell transfusion. Eligible articles were identified through a comprehensive search of The Cochrane Library, MEDLINE, EMBASE, Cinahl, BNID, and the Transfusion Evidence Library to April 2013. Initial search criteria were wide including primary intervention or observational studies, case reports, expert opinion, and guidelines. There was no restriction by study type, language, or status. Publications before 1995, reviews or reports of a secondary nature, studies of sampling errors outwith transfusion, and articles involving animals were excluded. The primary outcome was a reduction in errors. Study characteristics, outcomes measured, and methodological quality were extracted by 2 authors independently. The principal method of analysis was descriptive. A total of 12,703 references were initially identified. Preliminary secondary screening by 2 reviewers reduced articles for detailed screening to 128 articles. Eleven articles were eventually identified as eligible, resulting in 9 independent studies being included in the review. The overall finding was that all the identified interventions reduced WBIT incidence. Five studies measured the effect of a single intervention, for example, changes to blood sample labeling, weekly feedback, handwritten transfusion requests, and an electronic transfusion system. Four studies reported multiple interventions including education, second check of ID at sampling, and confirmatory sampling. It was not clear which intervention was the most effective. Sustainability of the effectiveness of interventions was also unclear. Targeted interventions, either single or multiple, can lead to a reduction in WBIT; but the sustainability of effectiveness is uncertain. Data on the pre- and postimplementation of interventions need to be collected in future trials to demonstrate effectiveness, and comparative studies are needed of different interventions.

Restrictive versus liberal transfusion strategies for older mechanically ventilated critically ill patients: a randomized pilot trial.

OBJECTIVES: To compare hemoglobin concentration (Hb), RBC use, and patient outcomes when restrictive or liberal blood transfusion strategies are used to treat anemic (Hb≤90 g/L) critically ill patients of age≥55 years requiring≥4 days of mechanical ventilation in ICU. DESIGN: Parallel-group randomized multicenter pilot trial. SETTING: Six ICUs in the United Kingdom participated between August 2009 and December 2010. PATIENTS: One hundred patients (51 restrictive and 49 liberal groups). INTERVENTIONS: Patients were randomized to a restrictive (Hb trigger, 70 g/L; target, 71-90 g/L) or liberal (90 g/L; target, 91-110 g/L) transfusion strategy for 14 days or the remainder of ICU stay, whichever was longest. MEASUREMENTS AND MAIN RESULTS: Baseline comorbidity rates and illness severity were high, notably for ischemic heart disease (32%). The Hb difference among groups was 13.8 g/L (95% CI, 11.5-16.0 g/L); p<0.0001); mean Hb during intervention was 81.9 (SD, 5.1) versus 95.7 (6.3) g/L; 21.6% fewer patients in the restrictive group were transfused postrandomization (p<0.001) and received a median 1 (95% CI, 1-2; p=0.002) fewer RBC units. Protocol compliance was high. No major differences in organ dysfunction, duration of ventilation, infections, or cardiovascular complications were observed during intensive care and hospital follow-up. Mortality at 180 days postrandomization trended toward higher rates in the liberal group (55%) than in the restrictive group (37%); relative risk was 0.68 (95% CI, 0.44-1.05; p=0.073). This trend remained in a survival model adjusted for age, gender, ischemic heart disease, Acute Physiology and Chronic Health Evaluation II score, and total non-neurologic Sequential Organ Failure Assessment score at baseline (hazard ratio, 0.54 [95% CI, 0.28-1.03]; p=0.061). CONCLUSIONS: A large trial of transfusion strategies in older mechanically ventilated patients is feasible. This pilot trial found a nonsignificant trend toward lower mortality with restrictive transfusion practice.

A measure of treatment response: patient and physician satisfaction with traditional NSAIDs for osteoarthritis control.

PURPOSE: The clinical response to traditional nonsteroidal anti-inflammatory drugs (tNSAIDs) varies substantially. The objective of this study was to describe physicians' and patients' perceptions of response to tNSAIDs as measured by satisfaction with control of patients' osteoarthritis (OA). PATIENTS AND METHODS: A cross-sectional survey was undertaken in 2009 in Germany, Spain, and the UK. Linked physician and patient questionnaires collected data on OA management, degree of pain and disability, and satisfaction with OA control. RESULTS: The study included 363 treating physicians and 713 patients receiving tNSAIDs. Patient mean (standard deviation) age was 65.5 (11.0) years (range 36-94 years); 60% were women; 86% were white; and one-quarter were obese. Dissatisfaction with control of patients' OA was expressed by physicians or their patients, or both, for 51% of patients, including 208 patients (31%) with mild OA and 478 patients (60%) with moderate or severe OA. Overall, 37% of patients reported dissatisfaction and 34% had a physician who reported dissatisfaction. Patient and physician assessments were the same in 70% of cases; Cohen's κ coefficient was 0.34 (95% confidence interval 0.26-0.41), indicating fair agreement. Of those reporting dissatisfaction, most physicians (79%) and patients (64%) believed that the current control was the best that could be achieved. The most common reasons for which physicians reported dissatisfaction were inadequate response (56%), side effects (11.1%), and poor tolerance (7.8%). CONCLUSION: One-half of patients or their treating physicians were dissatisfied with the control of OA provided by tNSAID therapy; moreover, most believed it was the best control that could be achieved.