Corrigendum: Low rates of headache and migraine associated with intravenous immunoglobulin infusion using a 15-minute rate escalation protocol in 123 patients with primary immunodeficiency.

[This corrects the article DOI: 10.3389/fimmu.2022.1075527.].

Hereditary factor X deficiency in America survey: impact on quality of life and burden of disease in patients and caregivers.

Hereditary factor X deficiency (HFXD) is a rare bleeding disorder causing delayed haemostasis and potentially life-threatening bleeds. Patient/caregiver burden and diagnosis path have not been well characterized. THE AIM OF THIS STUDY WAS TO: describe the diagnosis path, disease burden, and HFXD impact on quality of life (QoL) in patients and caregivers.This was a prospective, cross-sectional, web-based survey of patients with HFXD and caregivers addressing the patient/caregiver experience, QoL, humanistic and unmet needs.Thirty patients and 38 caregivers completed the survey with mean ages 24.7 and 44.6 years, respectively. Mean age at diagnosis was 4.1 years. The diagnostic process was somewhat/very difficult for 23% of patients and 26% of caregivers. Approximately half (53%) received single factor replacement (SFR) as prophylaxis or on-demand. Most patients (71%) reported regular prophylaxis treatment. Over one-fourth (27%) reported treatment with fresh frozen plasma. Bleeding episodes were less common in patients using SFR versus non-SFR: three bleeds or fewer were reported by 92% SFR and 75% non-SFR patients. HFXD patients reported low well being in work/school/social activities with mean HFXD-adapted Hemophilia Well being Index. Patient symptoms negatively impacted caregiver burden with a mean HFXD-adapted Hemophilia Caregiver Index (±SD) of 15.9 (4.6), but also unexpectedly had a positive impact on self-worth and inner strength.To our knowledge, this is the first study to assess patient and caregiver burden of HFXD and impact on QoL. Improvements in symptom recognition, prompt diagnosis, and adherence to expert recommendations for treatment could improve QoL and decrease burden on HFXD patients and caregivers.

A real-world study of quality of life following treatment with xylometazoline hydrochloride in individuals with common cold.

BACKGROUND: The common cold is a frequent, acute, and mild upper respiratory human disease. Nasal congestion has been considered the most bothersome symptom in the common cold, impacting quality of life (QoL). Topical decongestants containing steroids benefit QoL in allergic rhinitis, but no published research has assessed the impact of topical decongestants on QoL in the common cold. OBJECTIVE: To evaluate the effects of xylometazoline hydrochloride 0.1% (Otrivin, GSK Consumer Healthcare SARL, Switzerland) for up to 7 days on QoL in participants with nasal congestion associated with the common cold. DESIGN: This was a decentralized, longitudinal, open-label study. METHODS: The study enrolled 136 participants (⩾18 years) with early symptoms of the common cold, of which 102 were included in the modified intention-to-treat (mITT) population. Within 24 h of study product receipt, participants confirmed a 'plugged nose' and ⩾1 other common cold symptom. Primary endpoints were Wisconsin Upper Respiratory Symptom Survey-21 (WURSS-21) total score, total and individual symptom scores, and total QoL score. Secondary endpoints were additional QoL scores. Exploratory and post hoc analyses included median days to resolution for each QoL factor and analyses of five QoL categories. RESULTS: Consistent improvements in symptoms and QoL were seen in the mITT population. From day 1, improvements were seen in the 'plugged nose' symptom (p = 0.0023), WURSS-21 total QoL score, and all individual QoL scores (p < 0.0001 for all). After the last dose needed, significant improvements were seen in sleep quality (73%), vitality (76%), physical activity (71%), social activity (80%), and sensation (81%). No serious or unexpected adverse events were reported. CONCLUSION: This study is the first to demonstrate in a real-life setting that treating nasal congestion in adults with xylometazoline hydrochloride 0.1% during the common cold positively impacts QoL factors relevant to daily living [Otrivin: Quality of Life (QoL) Impact in a Real-World Setting; https://clinicaltrials.gov/study/NCT05556148].

Impact of xylometazoline hydrochloride 0.1% on quality of life in people with blocked nose associated with the common coldThe common cold is a widespread, mild respiratory illness for which a hallmark symptom is a blocked or stuffy nose, which makes breathing and sleeping difficult. This study focused on how a nasal spray called Otrivin (containing xylometazoline hydrochloride 0.1%) impacts the quality of life (QoL) of people suffering from nasal congestion due to the common cold.Participants answered a questionnaire called the Wisconsin Upper Respiratory Symptom Survey-21 (WURSS-21), which helped understand how people experience respiratory symptoms and how different aspects of QoL were impacted. Participants also responded to eight additional QoL questions not covered in the WURSS-21.The results showed that from the first day of using the nasal spray, participants experienced significant relief from the blocked nose symptom and reported an overall improvement in their QoL and well-being, such as in sleep quality, energy levels, senses, and physical and social activities.In conclusion, this real-world study demonstrated that using xylometazoline hydrochloride 0.1% nasal spray during the common cold can significantly improve nasal congestion and various aspects of a person's daily life. These findings provide valuable evidence for using this nasal spray to relieve symptoms and enhance the overall well-being of individuals with the common cold.

Low rates of headache and migraine associated with intravenous immunoglobulin infusion using a 15-minute rate escalation protocol in 123 patients with primary immunodeficiency.

Introduction: Headache and migraine adverse events are common concerns in the administration of intravenous immune globulins (IVIG). Trials of IVIG for primary immunodeficiency (PI) are typically small and have reported headache and migraine data inconsistently. Methods: We analyzed headache and migraine in pooled data from three pivotal trials of Gammaplex® 5% and 10% in PI (NCT00278954 from January 18, 2006; NCT01289847 from January 27, 2011; NCT01963143 from September 13, 2013). The trials were pooled in a retrospective analysis that included two 12-month open-label non-comparative trials of the 5% IVIG product and one 6-month open-label crossover bioequivalence trial comparing the 5% IVIG and 10% IVIG products. The population included adult and pediatric patients, who received IVIG infusions of 300-800 mg/kg/infusion every 21 or 28 days using a 15-minute rate escalation protocol. Results: In total, 1482 infusions were administered to 123 patients, with 94.6% of infusions achieving the maximum infusion rate. At least one product-related headache was reported in 6.1% (90/1482) of infusions. At least one product-related migraine was reported in 0.5% (7/1482) of infusions. Headache rates were higher for adults vs pediatric patients, females vs males, and 21-day vs 28-day dosing schedules, but were similar for the 5% and 10% IVIG products. Most headaches and migraines occurred during or within 72 hours of the infusion. Rates decreased after the first few infusions. Discussion: Patients receiving this IVIG product on a 15-minute rate escalation protocol had low rates of headache and migraine for both the 5% and 10% formulations.

A bitter pill to swallow: registered nurses and medicines regulation in remote Australia.

INTRODUCTION: Access to essential medicines is a human right and an objective of the National Medicines Policy in Australia. Health workforce distribution characteristics in remote Australia implies registered nurses (RNs) may find themselves responsible for a broader range of activities in the medication management cycle than they would be elsewhere in the nation. The regulation of health professionals and their training requirements provides essential but complex protections for the public. These protections include the National Registration and Accreditation Scheme for health practitioners and the Australian Health Practitioner Regulation Agency. Other levels of control or regulation are also exerted over health professionals via mechanisms such as salaries and funding arrangements, insurance requirements, admitting rights to healthcare facilities, and legislation controlling the use of medicines and therapeutic devices. This study aimed to examine national legislation and regulations concerning the use of medications from a nursing perspective, focusing on the context of health service delivery in remote areas. METHODS: Australian state and territory medicines legislation and regulations was interrogated for answers to the questions 'Can an RN prescribe a medication?', 'Can an RN dispense a medication?', 'Can an RN supply or issue a medication?' and 'Can an RN administer a medication?' RESULTS: Inconsistencies were identified nationally in the names and general structure of the legislation, the location of information relating to authorised roles with regards to medications and key terms used to describe medicines and the elements of the medication management cycle. Administrations of Schedule 4 and 8 medicine according to an order from an authorised prescriber are the only nationally consistent roles RNs are authorised to undertake with regards to medicines. Twenty-eight variations were identified with regards to additional authorisations for RNs. CONCLUSION: RNs make up more than half of the registered Australian health professional workforce and are the most consistently distributed across the nation, yet their legislated responsibilities in relation to working with medicines are inconsistent. Given the inconsistencies, RNs providing health care in remote Australia may be unable to undertake aspects of the medication management cycle that their work environment demands in the best interest of their patients and absence of other healthcare providers. The lack of legislative consistency nationally for medicines in Australia is likely to impede timely access to medications for patients. Regulatory inconsistencies may also result in RNs working well below or beyond their legal scope of practice, thereby creating clinical and workforce risks. Such risks are a significant matter for remote health service provision. Resolving these issues will require a collaborative national approach with consideration given to how the health workforce is distributed, current nursing responsibilities and relevant service delivery models for remote Australia.

The Highs and Lows of Making a Bucket List-Quantifying Potential Mosquito Breeding Habitats in Metropolitan Backyards.

While the development of land for residential housing along the Swan and Canning Rivers in Perth, WA, Australia has reduced natural mosquito breeding sites, the role of backyard container breeding remains a relatively unknown factor. Local Governments responsible for these areas focus management and control efforts on low lying, tidally driven mosquito habitats to control Aedes vigilax (Skuse) and Aedes camptorhynchus (Thomson) mosquitoes in an effort to reduce both the nuisance and disease risk to residents. In spite of their efforts, Local Governments continue to receive complaints regarding mosquito nuisance, even when environmental conditions do not favor hatching and development of the two species in the Swan River tidal flats. In this study, 150 backyard inspections were conducted in the residential suburb of Bassendean, Perth, WA, Australia, situated in close proximity to the Swan River tidal plain. The occurrence and species composition of the mosquito fauna found in residential backyards was documented. Of the backyards inspected, 94% were found to possess containers capable of breeding mosquitoes, although only 3% contained mosquito larvae. Nine species of mosquito were collected from containers ranging in capacity from 0.05 to 50 L across the study area. Additionally, encephalitis virus surveillance trapping was conducted within residential properties and compared to the tidally driven natural habitat at Ashfield Flats and a tidally influenced brackish creekline at Bindaring Park. The species composition of the fauna at the three habitat types differed significantly, with Aedes notoscriptus (Skuse) dominating residential lots and A. vigilax more prevalent at the saltmarsh site. Bindaring Park had an adult composition at the mid-point of these two habitats, reflecting its proximity to both the Swan River and residential lots.

"Looking over the Backyard Fence": Householders and Mosquito Control.

(1) Background: Vector-borne diseases are a significant public health problem in Western Australia. Mosquitoes are responsible for the transmission of a number of pathogens and may pose a serious nuisance problem. Prevention efforts in the State are multi-faceted and include physical, chemical, and cultural control methods for restricting mosquito breeding. This is less complex where breeding areas are located within public open spaces. In Australia's developed urban areas, breeding sites are, however, frequently located within private residential landholdings, where the scope of public health officials to act is constrained by law and practicality. Consequently, mosquito prevention in these locations is predominantly the responsibility of the residents. This research addressed a gap, both in understanding the degree to which "backyard" mosquito breeding has the potential to contribute to local mosquito problems, and in assessing what residents "think and do" about mosquito control within their home environment. (2) Methods: The study was conducted in the Town of Bassendean, a metropolitan Local Government Area of Perth, Western Australia, in close proximity to two natural, productive mosquito breeding sites, namely Ashfield Flats and Bindaring Park. A total of 150 householders were randomly surveyed during the summer of 2015-2016, to gauge residents' knowledge, attitudes, and practices (KAP (knowledge, attitudes, and practices) Survey) in regards to mosquitoes, their breeding and ecology, and avoidance or minimization strategies. The survey comprised nine questions covering residents' knowledge (3 questions), attitudes (3 questions), and practices (3 questions), as well as additional questions regarding the basic demographics of the resident. Larvae were collected from backyard containers and reared to adults for species identification. A series of Encephalitis Vector Surveillance carbon dioxide (EVS CO2) traps were also deployed, to assess adult mosquito density and species composition. (3) Results: Aedes notoscriptus (Skuse), a known container-inhabiting species, accounted for just over 50% of all mosquitoes identified. Most residents were aware of mosquito-borne disease and its risk in their local area. While the majority (79%) of the sample correctly identified Ross River virus as the most common infection in WA, a significant gap in the general knowledge of residents in regards to mosquito biology and breeding habits, was noted. Furthermore, only 50% of residents reported using personal protective measures to reduce mosquito bites and only one in six residents undertook physical or chemical mosquito control around their home. Additionally, 60% of respondents believed that mosquito control was "a job for the council and the state government", rather than for individual householders. (4) Conclusions: A significant gap in the knowledge of residents in the study area existed in regards to the general knowledge of mosquitoes and their breeding habits; types of treatments that could be employed within the home; and the residents' responsibility for the management of mosquito breeding on their private property. A public education campaign has been deployed to educate the residents.

Maternity-care: measuring women's perceptions.

PURPOSE: Achieving maternity-care outcomes that align with women's needs, preferences and expectations is important but theoretically driven measures of women's satisfaction with their entire maternity-care experience do not appear to exist. The purpose of this paper is to outline the development of an instrument to assess women's perception of their entire maternity-care experience. DESIGN/METHODOLOGY/APPROACH: A questionnaire was developed on the basis of previous research and informed by a framework of standard service quality categories covering the spectrum of typical consumer concerns. A pilot survey with a sample of 195 women who had recent experience of birth was undertaken to establish valid and reliable scales pertaining to different stages of maternity care. Exploratory factor analysis was used to interpret scales and convergent validity was assessed using a modified version of the Client Satisfaction Questionnaire. FINDINGS: Nine theoretically informed, reliable and valid stand-alone scales measuring the achievement of different dimensions of women's expectancies of public maternity care were developed. The study scales are intended for use in identifying some potential areas of focus for quality improvement in the delivery of maternity care. RESEARCH LIMITATIONS/IMPLICATIONS: Reliable and valid tools for monitoring the extent to which services respond to women's expectations of their entire maternity care form part of the broader toolkit required to adequately manage health-care quality. This study offers guidance on the make-up of such tools. ORIGINALITY/VALUE: The scales produced from this research offer a means to assess maternity care across the full continuum of care and are brief and easy to use.

A Matrix Mentoring Model That Effectively Supports Clinical and Translational Scientists and Increases Inclusion in Biomedical Research: Lessons From the University of Utah.

Physician-scientists and scientists in all the health professions are vital members of the U.S. biomedical workforce, but their numbers at academic health centers are declining. Mentorship has been identified as a key component in retention of faculty members at academic health centers. Effective mentoring may promote the retention of clinician-scientists in the biomedical workforce. The authors describe a holistic institutional mentoring program to support junior faculty members engaged in clinical and translational science at the University of Utah. The clinical and translational scholars (CATS) program leverages the resources of the institution, including the Center for Clinical and Translational Science, to augment departmental resources to support junior faculty investigators and uses a multilevel mentoring matrix that includes self, senior, scientific, peer, and staff mentorship. Begun in the Department of Pediatrics, the program was expanded in 2013 to include all departments in the school of medicine and the health sciences. During the two-year program, scholars learn management essentials and have leadership training designed to develop principal investigators. Of the 86 program participants since fiscal year 2008, 92% have received extramural awards, 99% remain in academic medicine, and 95% remain at the University of Utah. The CATS program has also been associated with increased inclusion of women and underrepresented minorities in the institutional research enterprise. The CATS program manifests institutional collaboration and coordination of resources, which have benefited faculty members and the institution. The model can be applied to other academic health centers to support and sustain the biomedical workforce.

Maternity care: a narrative overview of what women expect across their care continuum.

OBJECTIVES: to provide a narrative overview of the values schema underpinning women׳s expectations of public maternity-care services using an episodes-of-care framework. DESIGN: focus-group discussions and in-depth interviews were undertaken with Western Australian women who had opted for public maternity care to determine the values schema apparent in their expectations of their care. SETTING: public maternity-care services in metropolitan (i.e. Armadale, Osborne Park and Rockingham) and regional (i.e. Broome, Geraldton, Bunbury) Western Australia. FINDINGS: women interviewed were found to have consistent values schema underpinning their maternity-care expectations and evaluations. CONCLUSIONS: the current study suggests that while women׳s choices and experiences of maternity care may differ on a range of dimensions, the values schema underlying their care expectations and subsequent evaluations are similar. The study findings resonate with past Australian research regarding women׳s expectations of public maternity care, but complement it by providing a coherent narrative of core underpinning stage-specific values schema. These may assist maternity-care policy makers, practitioners and researchers seeking to better understand and comprehensively respond to women׳s maternity-care expectations.

'What women want': Using image theory to develop expectations of maternity care framework.

OBJECTIVES: to develop, in consultation with women, a theoretically-grounded framework to guide the assessment of women's maternity-care experiences. DESIGN: qualitative research was undertaken with women to examine the appropriateness of Image Theory as a heuristic for understanding how women plan and evaluate their maternity-care experiences. SETTING: maternity-care services in metropolitan and regional communities in Western Australia. OUTCOMES: an Episodes of Maternity Care Framework grounded in Image Theory was established that addressed various domains of women's perceptions and expectations of their maternity-care experience. CONCLUSIONS: previously-identified weaknesses of methods used to measure patient satisfaction were addressed and a valid framework for investigating women's perception of their maternity-services experiences was developed. This framework has the potential to contribute to the ongoing development and improvement of maternity-care service.

A use case study on late stent thrombosis for ontology-based temporal reasoning and analysis.

In this paper, we show how we have applied the Clinical Narrative Temporal Relation Ontology (CNTRO) and its associated temporal reasoning system (the CNTRO Timeline Library) to trend temporal information within medical device adverse event report narratives. 238 narratives documenting occurrences of late stent thrombosis adverse events from the Food and Drug Administration's (FDA) Manufacturing and User Facility Device Experience (MAUDE) database were annotated and evaluated using the CNTRO Timeline Library to identify, order, and calculate the duration of temporal events. The CNTRO Timeline Library had a 95% accuracy in correctly ordering events within the 238 narratives. 41 narratives included an event in which the duration was documented, and the CNTRO Timeline Library had an 80% accuracy in correctly determining these durations. 77 narratives included documentation of a duration between events, and the CNTRO Timeline Library had a 76% accuracy in determining these durations. This paper also includes an example of how this temporal output from the CNTRO ontology can be used to verify recommendations for length of drug administration, and proposes that these same tools could be applied to other medical device adverse event narratives in order to identify currently unknown temporal trends.

A pilot study comparing the effect of flaxseed, aromatase inhibitor, and the combination on breast tumor biomarkers.

Use of complementary approaches is common among breast cancer survivors. Potential interactions between aromatase inhibitors (AI) and high phytoestrogen foods, such as flaxseed (FS), are not often described. We conducted a pilot 2 × 2 factorial, randomized intervention study between tumor biopsy and resection, in 24 postmenopausal women with estrogen receptor positive (ER+) breast cancer, to assess the effects of FS and anastrozole, and possible interactions between them, on serum steroid hormone and tumor-related characteristics associated with long-term survival (Roswell Park Cancer Institute, 2007-2010). The effect of each treatment vs. placebo on outcomes was determined by linear regression adjusting for pretreatment measure, stage, and grade. Although not statistically significant, mean ERß expression was approximately 40% lower from pre- to postintervention in the FS + AI group only. We observed a statistically significant negative association (ß ± SE -0.3 ± 0.1; P = 0.03) for androstenedione in the FS + AI group vs. placebo and for DHEA with AI treatment (ß ± SE -1.6 ± 0.6; P = 0.009). Enterolactone excretion was much lower in the FS + AI group compared to the FS group. Our results do not support strong effects of FS on AI activity for selected breast tumor characteristics or serum steroid hormone levels but suggest AI therapy might reduce the production of circulating mammalian lignans from FS.

Beyond teacher training: the critical role of professional development in maintaining curriculum fidelity.

PURPOSE: To examine how teacher characteristics affected program fidelity in an impact evaluation study of the Positive Prevention PLUS program, and to propose a comprehensive teacher training and professional development structure to increase program fidelity. METHODS: Curriculum fidelity logs, lesson observations, and teacher surveys were used to measure teacher characteristics and implementation fidelity including adherence, adaptation, and lesson quality. RESULTS: Compared with non-health credentialed teachers, credential health education teachers had greater comfort and self-efficacy regarding sex-related instruction. Teacher self-efficacy and comfort were significant predictors of adherence. CONCLUSIONS: Implementation fidelity may be linked to teacher characteristics that can be enhanced during curriculum training. A 2-day teacher training may not adequately address teacher facilitation skills or the maintenance of institutional supports for implementing a program with fidelity and quality. A new model of comprehensive teacher training and support is offered. This new training infrastructure is intended to contribute to the school district's institutionalization of higher-quality comprehensive sexual health education and increase program fidelity.

What determines the activity of antimicrobial and cytolytic peptides in model membranes.

We previously proposed three hypotheses relating the mechanism of antimicrobial and cytolytic peptides in model membranes to the Gibbs free energies of binding and insertion into the membrane [Almeida, P. F., and Pokorny, A. (2009) Biochemistry 48, 8083-8093]. Two sets of peptides were designed to test those hypotheses, by mutating of the sequences of δ-lysin, cecropin A, and magainin 2. Peptide binding and activity were measured on phosphatidylcholine membranes. In the first set, the peptide charge was changed by mutating basic to acidic residues or vice versa, but the amino acid sequence was not altered much otherwise. The type of dye release changed from graded to all-or-none according to prediction. However, location of charged residues in the sequence with the correct spacing to form salt bridges failed to improve binding. In the second set, the charged and other key residues were kept in the same positions, whereas most of the sequence was significantly but conservatively simplified, maintaining the same hydrophobicity and amphipathicity. This set behaved completely different from predicted. The type of release, which was expected to be maintained, changed dramatically from all-or-none to graded in the mutants of cecropin and magainin. Finally, contrary to the hypotheses, the results indicate that the Gibbs energy of binding to the membrane, not the Gibbs energy of insertion, is the primary determinant of peptide activity.

Making the best of the early years: the Tambellup way.

INTRODUCTION: Tambellup is a small rural town in the Great Southern region of Western Australia (WA), approximately 300 km south-east of state capital Perth. Tambellup has a much higher Aboriginal population than the national average and achieved very positive results for year one children in 2007 regional Australian Early Development Index testing. In 2009 the Great Southern GP Network (which has a facilitating role in providing early intervention strategies to families with young children at risk of disadvantage) requested that public health staff at Edith Cowan University, Perth, WA undertake an exploratory study to discover the factors protective of children's development in Tambellup. This article describes the subsequent research and its findings. METHODS: This 2009 qualitative study interviewed both adult members of the local Aboriginal community (Noongar people; n = 23), and non-Aboriginal leaders from a cross-section of organisations, services and the community (n = 14) to determine what made growing up in Tambellup a positive experience. Aboriginal participants were introduced to the researchers by a local cultural consultant. Non-Aboriginal participants were initially sourced from a list provided by the GSGPN and extended by asking those listed to identify other appropriate contacts. Face-to-face interviews were carried out with Aboriginal participants and telephone interviews were undertaken with non-Aboriginal participants. All interviews were conducted using a standard schedule of questions as a guide, supplemented by clarifying and broadening questions from research team members. Data were analysed in a multi-stage process of collation, extraction of common themes and verification of themes with study participants and other stakeholders. Findings were presented to local Aboriginal leaders at a community meeting and a final report was prepared and circulated to community members. RESULTS: There was substantial evidence of widespread trust and positive relationships in this close-knit community, where adults looked out for and supported both their own and others' children. The primary school played a key role in supporting children's development even before children started school. Good relations generally existed between Aboriginal and non-Aboriginal residents, contributing to the stability of the population and providing many role models in successful cross-cultural relationships. CONCLUSION: Aboriginal people in Tambellup played significant but often under-recognised roles in promoting child and youth wellbeing in the community. The community had the capacity to respond to local needs and challenges. Communication channels were effective and there was a sense of belonging, pride and 'connectedness' in the community that promoted and supported a safe environment for children. High quality services and staff (eg school and community health centre) reinforced children's developmental opportunities. The results suggest that small rural communities offer significant and untapped resources for enhancing the health and wellbeing of children in the critical early years of life.