Novel risk patterns of vasovagal reactions in NZ blood donations complicated by COVID-19 restrictions.

Introduction: Vasovagal reactions (VVRs) are common but complex donor adverse reactions (DAEs) in blood donations. VVRs have been extensively studied with a multitude of risk factors identified including young age, female gender and first-time donor status. How they may interplay remains obscure. Methods: A total of 1,984,116 blood donations and 27,952 immediate VVRs (iVVRs) and 1,365 delayed VVRs (dVVRs) reported between 2011 and 2021 in NZ were used in multivariate logistic regression analyses each concerning donations with iVVRs as cases and those free of DAEs as controls. For each analysis stepwise selection was used to identify the best model and risk factors carrying significant main effects and/or interactions. Identified interactions informed further in-depth regression analyses to dissect iVVR risk patterns. Results: Over 95% of VVRs were iVVRs that had lower female preponderance and deferrals than dVVRs. iVVRs had a school seasonal pattern in whole blood donations driven by first-time donors from schools/colleges, and interactions between gender and age group differentiating the first-time from repeat donations. Subsequent regression analyses identified the known and novel risk factors of year and mobile collection sites and their interactions. iVVR rates were roundly elevated in 2020 and 2021 probably because of COVID-19 restrictions like facemask wearing. Exclusion of the 2020 and 2021 data removed the interactions with year, but confirmed interactions of gender with mobile collection sites (p = 6.2e-07) in first-time donations only and with age group in repeat donations only (p < 2.2e-16), together indicating young female donors at the highest risk of iVVRs. Our results also revealed that donation policy changes contributed to the year effects; donors had a lower iVVR risk at mobile sites than well-medicalized donation centers probably because of under-reporting. Conclusion: Modeling statistical interactions is valuable in identifying odds and revealing novel iVVR risk patterns and insights into blood donations.

Behavioural video to navigate predoctoral dental students toward safer practice (revision of EJE-21-4739).

INTRODUCTION: Local anaesthesia is considered essential knowledge within the dental profession as it helps to address pain management. Operator percutaneous needlestick injuries associated with the delivery of dental anaesthesia are common for dental healthcare providers. The study proposes a supplemental technique to reduce self-inducing novice operator needlestick injury to complement existing pedagogies for the preclinical local anaesthesia curriculum. The purpose of the study is to evaluate whether a local anaesthesia behavioural video can navigate students to safer clinical practice. Further, a supplemental technique is proposed in whether assessing instrument retraction technique in clinical patient care leads to decreased self-inducing intraoral needle stick injury for novice predoctoral dental operator. MATERIALS AND METHODS: Beginning in 2011, predoctoral dental students were asked to view a "what not to do" video within a summative assessment and identify at least five behaviours that were unacceptable errors for delivering local anaesthesia. Operator intraoral needlestick injury was also tracked per the bloodborne exposure reports within predoctoral patient clinics. RESULTS: Data from the learners' responses identified progression in recognising unacceptable errors from behavioural video. Intraoral needlestick injury, 8 and 9 years prior and after the introduction of video showed significance with a low correlation coefficient. CONCLUSION: More data need to be gathered and evaluated in other dental school settings to determine whether this supplemental educational video decreases needlestick injury in novice operators. Results suggest this behavioural video may guide novice operators to overall safer clinical practice.

The Role of Extracellular Vesicles as a Shared Disease Mechanism Contributing to Multimorbidity in Patients With COPD.

Chronic obstructive pulmonary disease (COPD) is one of the leading causes of death worldwide. Individuals with COPD typically experience a progressive, debilitating decline in lung function as well as systemic manifestations of the disease. Multimorbidity, is common in COPD patients and increases the risk of hospitalisation and mortality. Central to the genesis of multimorbidity in COPD patients is a self-perpetuating, abnormal immune and inflammatory response driven by factors including ageing, pollutant inhalation (including smoking) and infection. As many patients with COPD have multiple concurrent chronic conditions, which require an integrative management approach, there is a need to greater understand the shared disease mechanisms contributing to multimorbidity. The intercellular transfer of extracellular vesicles (EVs) has recently been proposed as an important method of local and distal cell-to-cell communication mediating both homeostatic and pathological conditions. EVs have been identified in many biological fluids and provide a stable capsule for the transfer of cargo including proteins, lipids and nucleic acids. Of these cargo, microRNAs (miRNAs), which are short 17-24 nucleotide non-coding RNA molecules, have been amongst the most extensively studied. There is evidence to support that miRNA are selectively packaged into EVs and can regulate recipient cell gene expression including major pathways involved in inflammation, apoptosis and fibrosis. Furthermore changes in EV cargo including miRNA have been reported in many chronic diseases and in response to risk factors including respiratory infections, noxious stimuli and ageing. In this review, we discuss the potential of EVs and EV-associated miRNA to modulate shared pathological processes in chronic diseases. Further delineating these may lead to the identification of novel biomarkers and therapeutic targets for patients with COPD and multimorbidities.

Continuous subcutaneous insulin infusion therapy is associated with reduced retinopathy progression compared with multiple daily injections of insulin.

AIMS/HYPOTHESIS: We aimed to compare diabetic retinopathy outcomes in people with type 1 diabetes following introduction of continuous subcutaneous insulin infusion (CSII) therapy with outcomes in people receiving continuing therapy with multiple daily insulin injections (MDI). METHODS: This is a retrospective cohort study using the Scottish Care Information - Diabetes database for retinal screening outcomes and HbA1c changes in 204 adults commenced on CSII therapy between 2013 and 2016, and 211 adults eligible for CSII during the same period but who continued on MDI therapy. Diabetic retinopathy progression (time to minimum one-grade worsening in diabetic retinopathy from baseline grading) was plotted for CSII and MDI cohorts using Kaplan-Meier curves, and outcomes were compared using multivariate Cox regression analysis adjusting for age, sex, baseline HbA1c, blood pressure, cholesterol, smoking status and socioeconomic quintile. Impact of baseline HbA1c and change in HbA1c on diabetic retinopathy progression was assessed within CSII and MDI cohorts. RESULTS: CSII participants were significantly younger, were from less socially deprived areas, and had lower HbA1c and higher diastolic BP at baseline. There was a larger reduction in HbA1c at 1 year in those on CSII vs MDI (-6 mmol/mol [-0.6%] vs -2 mmol/mol [-0.2%], p < 0.01). Diabetic retinopathy progression occurred in a smaller proportion of adults following commencement of CSII vs continued MDI therapy over mean 2.3 year follow-up (26.5% vs 18.6%, p = 0.0097). High baseline HbA1c (75 mmol/mol [9%]) was associated with diabetic retinopathy progression in the MDI group (p = 0.0049) but not the CSII group (p = 0.93). Change in HbA1c at follow-up, irrespective of baseline glycaemic status, did not significantly affect diabetic retinopathy progression in either group. CONCLUSIONS/INTERPRETATION: CSII was associated with reduced diabetic retinopathy progression compared with continued MDI therapy, and may be protective against diabetic retinopathy progression for those with high baseline HbA1c. Progression of diabetic retinopathy over 3 years was not associated with a change in HbA1c.

Effects of islet transplantation on microvascular and macrovascular complications in type 1 diabetes.

Type 1 diabetes is associated with high morbidity and mortality from microvascular and macrovascular disease with considerable economic cost to society. Islet cell transplantation (ICT) is a treatment option recommended by National Institute for Health and Care Excellence (NICE) for people with debilitating hypoglycaemia due to type 1 diabetes, including those with renal failure where kidney transplantation may also be indicated. The primary aim of ICT is to improve glycaemic control, reduce severe hypoglycaemia, stabilise glycaemic variability and restore awareness of hypoglycaemia where this is compromised. Insulin independence, although not a primary aim, should also be considered a therapeutic goal. The impact ICT has on the progression of microvascular and macrovascular diabetes complications is derived from small studies and has not been examined in large clinical trials. Lifelong immunosuppression, which is necessary to avoid transplant rejection, has adverse effects on lipid metabolism, hypertension and renal function, which must also be considered. In this review, we discuss the role of ICT in type 1 diabetes management and the available evidence with respect to microvascular and macrovascular disease progression post-transplantation. We conclude that, following ICT, microvascular complications including retinopathy and neuropathy are stabilised or improved. Effects on nephropathy can be complicated by coexisting kidney transplantation and the impact of immunosuppression, the latter leading to an early decline in renal function; however, there is evidence to suggest stable renal outcomes in the long term. Short-term studies have demonstrated a positive impact of ICT on surrogate markers of macrovascular disease; however, long-term studies and trials in this area are lacking.

Adapting the role of handheld echocardiography during the COVID-19 pandemic: A practical guide.

The COVID-19 pandemic has altered our approach to inpatient echocardiography delivery. There is now a greater focus to address key clinical questions likely to make an immediate impact in management, particularly during the period of widespread infection. Handheld echocardiography (HHE) can be used as a first-line assessment tool, limiting scanning time and exposure to high viral load. This article describes a potential role for HHE during a pandemic. We propose a protocol with a reporting template for a focused core dataset necessary in delivering an acute echocardiography service in the setting of a highly contagious disease, minimising risk to the operator. We cover the scenarios typically encountered in the acute cardiology setting and how an expert trained echocardiography team can identify such pathologies using a limited imaging format and include cardiac presentations encountered in those patients acutely unwell with COVID-19.

Predictors of Nephrolithiasis, Osteoporosis, and Mortality in Primary Hyperparathyroidism.

CONTEXT: Primary hyperparathyroidism (PHPT) has a prevalence of 0.86% and is associated with increased risk of nephrolithiasis and osteoporosis. PHPT may also be associated with increased risk of cardiovascular disease and mortality. OBJECTIVE: To identify risk factors for nephrolithiasis, osteoporosis, and mortality in PHPT. DESIGN: Retrospective cohort study. SETTING: University teaching hospital. PATIENTS: Presented with PHPT between 2006 and 2014 (n = 611). MAIN OUTCOME MEASURE: Assessment of nephrolithiasis, osteoporosis, and mortality. RESULTS: Of patients with PHPT, 13.9% had nephrolithiasis. Most had previously documented stone disease, and only 4.7% of asymptomatic patients who were screened for renal stones had calculi identified, not very dissimilar to the rate in the non-PHPT population. Younger age (P < 0.001) and male sex (P = 0.003) were the only independent predictors of nephrolithiasis. Of patients with dual-energy X-ray absorptiometry data, 48.4% had osteoporosis (223/461). Older age (P < 0.001), lower body mass index (P = 0.002), and lower creatinine (P = 0.006) were independently associated with a diagnosis of osteoporosis. Higher PTH was independently associated with lower z score at the hip (P = 0.009); otherwise, calcium and PTH were not associated with lower z scores. Mortality in PHPT was associated with older age (P < 0.008), social deprivation (P = 0.028), and adjusted calcium (P = 0.009) but not independently with PTH at diagnosis. CONCLUSIONS: Screening for nephrolithiasis has a low yield, particularly in lower risk patients. Osteoporosis is only minimally associated with biochemical indices of PHPT. Mortality is associated with higher calcium (and possibly vitamin D deficiency) but not PTH.

Presentation, diagnostic assessment and surgical outcomes in primary hyperparathyroidism: a single centre's experience.

OBJECTIVE: Primary hyperparathyroidism (PHPT) is a common reason for referral to endocrinology but the evidence base guiding assessment is limited. We evaluated the clinical presentation, assessment and subsequent management in PHPT. DESIGN: Retrospective cohort study. PATIENTS: PHPT assessed between 2006 - 2014 (n = 611) in a university hospital. MEASUREMENTS: Symptoms, clinical features, biochemistry, neck radiology and surgical outcomes. RESULTS: Fatigue (23.8%), polyuria (15.6%) and polydipsia (14.9%) were associated with PHPT biochemistry. Bone fracture was present in 16.4% but was not associated with biochemistry. A history of nephrolithiasis (10.0%) was associated only with younger age (P = 0.006) and male gender (P = 0.037). Thiazide diuretic discontinuation was not associated with any subsequent change in calcium (P = 0.514). Urine calcium creatinine clearance ratio (CCCR) was <0.01 in 18.2% of patients with confirmed PHPT. Older age (P < 0.001) and lower PTH (P = 0.043) were associated with failure to locate an adenoma on ultrasound (44.0% of scans). When an adenoma was identified on ultrasound the lateralization was correct in 94.5%. Non-curative surgery occurred in 8.2% and was greater in those requiring more than one neck imaging modality (OR 2.42, P = 0.035). CONCLUSIONS: Clinical features associated with PHPT are not strongly related to biochemistry. Thiazide cessation does not appear to attenuate hypercalcaemia. PHPT remains the likeliest diagnosis in the presence of low CCCR. Ultrasound is highly discriminant when an adenoma is identified but surgical failure is more likely when more than one imaging modality is required.

An Interactive Online Approach to Teaching Evidence-Based Dentistry with Web 2.0 Technology.

At many dental schools, evidence-based dentistry (EBD) is taught in a traditional lecture format. To avoid the constraints of lectures, in 2012 the EBD unit was redesigned for online delivery at the Arthur A. Dugoni School of Dentistry at the University of the Pacific with a Web 2.0 tool called Voicethread. The aim of this study was to assess the impact of Voicethread-based online learning on students' perceptions of learning EBD, their participation and engagement, and their acceptance of this new online delivery approach. Students' perceptions were collected from two sources: a self-assessment quiz and a question on their self-reported preparedness in EBD from the 2014 American Dental Education Association (ADEA) Survey of Dental School Seniors. The Voicethread analytics tool provided data on students' participation and engagement. Students' responses to the survey questions on the self-assessment quiz provided data on their acceptance of Voicethread-based learning. The average score of the 124 students (91% of total) taking the quiz was 7.3 out of 8. The percentage of students who reported in the 2014 ADEA survey that they were "well prepared" in EBD was 45.2%, compared with the national average of 31.2%. Responses to this question for the Classes of 2013 and 2015, who received instruction in the traditional lecture format, were 35.2% and 34.6%, respectively. With Voicethread, students actively participated and interacted with their peers through questions and answers. They perceived Voicethread to be more effective than other delivery approaches and reported that it made learning more active and engaging. These findings suggest that Voicethread may be an effective tool for students to learn EBD since it adds interactivity to online learning.

Novice therapist attachment and perceived ruptures and repairs: a pilot study.

Although extensively discussed in theoretical articles, empirical studies of therapist attachment and perceptions of ruptures and repairs are lacking. The present study examined the relationship between therapist attachment anxiety and avoidance and their perceptions of rupture tension, effort, and repair. Twenty-two novice therapists completed a measure of adult romantic attachment and a measure to assess perceptions of ruptures and repairs following the eighth session with their first clients. Results revealed that there was a strong positive correlation between therapist attachment anxiety and effort spent focused on perceived ruptures and a moderate positive correlation between attachment anxiety and rupture tension. There was no significant relationship between attachment anxiety and perceived repairs of ruptures. Attachment avoidance was not significantly correlated with either perceptions of the ruptures or repairs. Therapists who were higher on anxiety and avoidance, more fearful therapists, reported the most ruptures. Limitations and implications of the findings are presented.

Return to play in elite rugby union: application of global positioning system technology in return-to-running programs.

UNLABELLED: Global positioning systems (GPS) are widely used in sport settings to evaluate the physical demands on players in training and competition. The use of these systems in the design and implementation of rehabilitation and return-to-running programs has not yet been elucidated. OBJECTIVE: To demonstrate the application of GPS technology in the management of return to play in elite-club Rugby Union. DESIGN: Case series. SETTING: Professional Rugby Union club team. PARTICIPANTS: 8 elite Rugby Union players (age 27.86 ± 4.78 y, height 1.85 ± 0.08 m, weight 99.14 ± 9.96 kg). INTERVENTION: Players wore GPS devices for the entire duration of a club game. MAIN OUTCOME MEASURES: Variables of locomotion speed and distance were measured. RESULTS: Differences in physical demands between playing positions were observed for all variables. CONCLUSIONS: An analysis of the position-specific physical demands measured by GPS provides key information regarding the level and volume of loads sustained by a player in a game environment. Using this information, sports-medicine practitioners can develop rehabilitation and return-to-running protocols specific to the player position to optimize safe return to play.

Comparison of comparative genomic hybridization technologies across microarray platforms.

In the 2007 Association of Biomolecular Resource Facilities Microarray Research Group project, we analyzed HL-60 DNA with five platforms: Agilent, Affymetrix 500K, Affymetrix U133 Plus 2.0, Illumina, and RPCI 19K BAC arrays. Copy number variation was analyzed using circular binary segmentation (CBS) analysis of log ratio scores from four independently assessed hybridizations of each platform. Data obtained from these platforms were assessed for reproducibility and the ability to detect formerly reported copy number variations in HL-60. In HL-60, all of the tested platforms detected genomic DNA amplification of the 8q24 locus, trisomy 18, and monosomy X; and deletions at loci 5q11.2~q31, 9p21.3~p22, 10p12~p15, 14q22~q31, and 17p12~p13.3. In the HL-60 genome, at least two of the five platforms detected five novel losses and five novel gains. This report provides guidance in the selection of platforms based on this wide-ranging evaluation of available CGH platforms.

Learning from microarray interlaboratory studies: measures of precision for gene expression.

BACKGROUND: The ability to demonstrate the reproducibility of gene expression microarray results is a critical consideration for the use of microarray technology in clinical applications. While studies have asserted that microarray data can be "highly reproducible" under given conditions, there is little ability to quantitatively compare amongst the various metrics and terminology used to characterize and express measurement performance. Use of standardized conceptual tools can greatly facilitate communication among the user, developer, and regulator stakeholders of the microarray community. While shaped by less highly multiplexed systems, measurement science (metrology) is devoted to establishing a coherent and internationally recognized vocabulary and quantitative practice for the characterization of measurement processes. RESULTS: The two independent aspects of the metrological concept of "accuracy" are "trueness" (closeness of a measurement to an accepted reference value) and "precision" (the closeness of measurement results to each other). A carefully designed collaborative study enables estimation of a variety of gene expression measurement precision metrics: repeatability, several flavors of intermediate precision, and reproducibility. The three 2004 Expression Analysis Pilot Proficiency Test collaborative studies, each with 13 to 16 participants, provide triplicate microarray measurements on each of two reference RNA pools. Using and modestly extending the consensus ISO 5725 documentary standard, we evaluate the metrological precision figures of merit for individual microarray signal measurement, building from calculations appropriate to single measurement processes, such as technical replicate expression values for individual probes on a microarray, to the estimation and display of precision functions representing all of the probes in a given platform. CONCLUSION: With only modest extensions, the established metrological framework can be fruitfully used to characterize the measurement performance of microarray and other highly multiplexed systems. Precision functions, summarizing routine precision metrics estimated from appropriately repeated measurements of one or more reference materials as functions of signal level, are demonstrated and merit further development for characterizing measurement platforms, monitoring changes in measurement system performance, and comparing performance among laboratories or analysts.

A general method for describing sources of variance in clinical trials, especially operator variance, in order to improve transfer of research knowledge to practice.

PURPOSE: The purpose of this study was to demonstrate how the skill level of the operator and the clinical challenge provided by the patient affect the outcomes of clinical research in ways that may have hidden influences on the applicability of that research to practice. Rigorous research designs that control or eliminate operator or patient factors as sources of variance achieve improved statistical significance for study hypotheses. These procedures, however, mask sources of variance that influence the applicability of the conclusions. There are summary data that can be added to reports of clinical trials to permit potential users of the findings to identify the most important sources of variation and to predict the likely outcomes of adopting products and procedures reported in the literature. MATERIALS AND METHODS: Provisional crowns were constructed in a laboratory setting in a fully crossed, random-factor model with two levels of material (Treatment), two skill levels of students (Operator), and restorations of two levels of difficulty (Patient). The levels of the Treatment, Operator, and Patient factors used in the study were chosen to ensure that the findings from the study could be transferred to practice settings in a predictable fashion. The provisional crowns were scored independently by two raters using the criteria for technique courses in the school where the research was conducted. RESULTS: The Operator variable accounted for 38% of the variance, followed by Treatment-by-Operator interaction (17%), Treatment (17%), and other factors and their combinations in smaller amounts. Regression equations were calculated for each Treatment material that can be used to predict outcomes in various potential transfer applications. It was found that classical analyses for differences between materials (the Treatment variable) would yield inconsistent results under various sampling systems within the parameters of the study. CONCLUSIONS: Operator and Treatment-by-Operator interactions appear to be significant and previously underrecognized sources of variance. It is suggested that variance estimates of factors thought to significantly influence the transfer of research findings to practice contexts and evidence of representative sampling across practice contexts be regularly included in reports of clinical trials.

The MicroArray Quality Control (MAQC) project shows inter- and intraplatform reproducibility of gene expression measurements.

Over the last decade, the introduction of microarray technology has had a profound impact on gene expression research. The publication of studies with dissimilar or altogether contradictory results, obtained using different microarray platforms to analyze identical RNA samples, has raised concerns about the reliability of this technology. The MicroArray Quality Control (MAQC) project was initiated to address these concerns, as well as other performance and data analysis issues. Expression data on four titration pools from two distinct reference RNA samples were generated at multiple test sites using a variety of microarray-based and alternative technology platforms. Here we describe the experimental design and probe mapping efforts behind the MAQC project. We show intraplatform consistency across test sites as well as a high level of interplatform concordance in terms of genes identified as differentially expressed. This study provides a resource that represents an important first step toward establishing a framework for the use of microarrays in clinical and regulatory settings.

National prevalence and exposure risk for cockroach allergen in U.S. households.

UNLABELLED: We characterized the prevalence of cockroach allergen exposure in a nationally representative sample of U.S. homes and assessed risk factors for elevated concentrations. DESIGN: We used data from the National Survey of Lead and Allergens in Housing, a population-based cross-sectional survey. PARTICIPANTS: Participants were residents of 831 U.S. homes in the survey. EVALUATIONS/MEASUREMENTS: We analyzed allergen, questionnaire, and observational data of 831 U.S. homes. RESULTS: Cockroach allergen (Bla g 1) concentrations exceed 2.0 U/g, a level associated with allergic sensitization, in 11% of U.S. living room floors and 13% of kitchen floors. Concentrations exceed 8.0 U/g, a level associated with asthma morbidity, in 3% of living room floors and 10% of kitchen floors. Elevated concentrations were observed in high-rise apartments, urban settings, pre-1940 constructions, and households with incomes < $20,000. Odds of having concentrations > 8.0 U/g were greatest when roach problems were reported or observed and increased with the number of cockroaches observed and with indications of recent cockroach activity. CONCLUSIONS: Household cockroach allergen exposure is characterized in a nationally representative context. The allergen is prevalent in many settings, at levels that may contribute to allergic sensitization and asthma morbidity. RELEVANCE TO CLINICAL OR PROFESSIONAL PRACTICE: Likelihood of exposure can be assessed by consideration of demographic and household determinants.

The External RNA Controls Consortium: a progress report.

Standard controls and best practice guidelines advance acceptance of data from research, preclinical and clinical laboratories by providing a means for evaluating data quality. The External RNA Controls Consortium (ERCC) is developing commonly agreed-upon and tested controls for use in expression assays, a true industry-wide standard control.