Adverse Drug Event-Related Hospital Admissions Among Australian Aged Care Residents: A Cross-Sectional Study.

OBJECTIVES: To investigate the proportion, characteristics, causality, severity, preventability, and independently associated factors for adverse drug event (ADE)-related admissions in aged care residents admitted to the major public hospitals in Tasmania, Australia. DESIGN: Retrospective cross-sectional study. SETTING AND PARTICIPANTS: Residential aged care facility (RACF) patients aged ≥65 years who had an unplanned admission to one of the 4 Tasmanian public hospitals between July 1, 2018, and June 30, 2021. METHODS: We accessed the medical records of RACF patients. The ADEs were initially identified via chart review and a trigger tool. Hospitalizations attributable to ADEs were then determined by expert consensus. The causality, preventability, and severity of each ADE admission were assessed using standard criteria. RESULTS: Ninety-one residents (18.2%) of 500 randomly selected experienced potential ADE-related hospitalizations. ADEs were considered possible (n = 58, 64%) or definite/probable (n = 33, 36%). The most common ADEs were falls (n = 19, 21%), hypotension (n = 16, 18%), and confusion or delirium (n = 10, 11%). ADEs were frequently associated with renin-angiotensin system inhibitors (n = 43, 47.3%), opioids (n = 43, 47.3%), and diuretics (n = 40, 44%). Most ADEs were of moderate severity (n = 90, 99%) and considered not preventable (n = 60, 66%). Rheumatologic disease [odds ratio (OR) 1.89, 95% CI 1.09-3.30; P = .024] and previous adverse drug reaction (ADR) (OR 12.91, 95% CI 6.84-24.37; P < .001) were associated with ADE hospitalizations. CONCLUSIONS AND IMPLICATIONS: This study highlights that hospitalization for moderately severe ADEs is common among RACF residents. Opioids and antihypertensives were the common drug classes associated with harm. Rheumatologic disease (due to opioids) and previous ADR were identified as independently associated factors, which may warrant tailored interventions.

Improvement in sleep latency with extended-release once-nightly sodium oxybate for the treatment of adults with narcolepsy: Analysis from the phase 3 REST-ON clinical trial.

Background: In the REST-ON clinical trial (NCT02720744), mean sleep latency on the Maintenance of Wakefulness Test (MWT) was significantly improved with extended-release once-nightly sodium oxybate (ON-SXB) vs placebo (P < 0.001) in participants with narcolepsy. This post hoc analysis assessed response to treatment and improvement in excessive daytime sleepiness. Methods: Participants with narcolepsy aged ≥16 years were randomized 1:1 to receive ON-SXB (4.5 g, week 1; 6 g, weeks 2-3; 7.5 g, weeks 3-8; and 9 g, weeks 9-13) or placebo. Mean sleep latency on the MWT was measured across 5 trials of ≤30 min each. Post hoc assessments included percentage of participants whose sleep latency improved ≥5, ≥10, ≥15, and ≥20 min and with a mean sleep latency of 30 min. Results: Significantly more participants receiving ON-SXB vs placebo experienced increased mean sleep latency ≥5 min (all doses P < 0.001), ≥10 min (all doses P < 0.001), ≥15 min (6 and 7.5 g, P < 0.001; 9 g, P < 0.01), and ≥20 min (6 g, P < 0.01; 7.5 g, P < 0.001; 9 g, P < 0.05). More participants receiving ON-SXB had mean sleep latency of 30 min vs placebo (6 g, 5.7 % vs 0 %, respectively [P < 0.05]; 7.5 g, 10.5 % vs 1.3 % [P < 0.05]; 9 g, 13.2 % vs 5.1 % [P = 0.143]). Conclusions: Significantly more participants who received ON-SXB experienced increased mean sleep latency ≥5 to ≥20 min; at the 2 highest doses, >10 % remained awake for the entirety of the MWT. ON-SXB offers a once-at-bedtime treatment option for adults with narcolepsy.

Predictors of Adverse Drug Reaction-Related Hospitalisations Among People with Dementia: A Retrospective Case-Control Study.

INTRODUCTION: Adverse drug reactions (ADRs) are common among people with dementia; however, little is known about the magnitude and predictors associated with ADR-related hospitalisation among these individuals. This study aimed to determine the magnitude, types, drugs implicated and predictors of ADRs associated with hospitalisation among people with dementia. METHODS: This retrospective case-control study analysed medical records of individuals aged ≥ 65 years with dementia admitted to major public hospitals in Tasmania, Australia, from July 2010 to July 2021. Adverse drug reactions and implicated drugs were identified using administrative data and cross-checked with hospital medical records, with consensus reached among the research team. RESULTS: Of the 7928 people admitted to hospital at least once within the study period, 1876 (23.7%) experienced at least one ADR-related hospitalisation. Of these, 300 case patients with 311 ADRs and 300 control patients were randomly selected. The most common types of ADRs were renal (acute kidney injury; AKI) (36.0%), followed by neuropsychiatric (17.6%), cardiovascular (16.0%) and haematological (13.1%). Diuretics, renin-angiotensin system (RAS) inhibitors and anti-thrombotics constituted the main implicated drug classes. The ADR-related hospitalisation was associated with: chronic kidney disease (CKD) (OR 8.00, 95% CI 2.63-24.28, p < 0.001), Australian-born (OR 1.62, 95% CI 1.08-2.43, p = 0.019), hypertension (OR 1.48, 95% CI 1.01-2.17, p = 0.044) and the number of medicines (OR 1.06, 95% CI 1.00-1.12, p = 0.022). Potentially inappropriate medication use and anticholinergic burden did not predict ADR-related hospitalisation. CONCLUSIONS: These predictors could help identify the individuals at the highest risk and enable targeted interventions to be designed.

Circadian variation in muscle force output in males using isokinetic, isometric dynamometry: can we observe this in multi-joint movements using the muscleLab force-velocity encoder and are they similar in peak and magnitude?

We have investigated the magnitude of circadian variation in Isokinetic and Isometric strength of the knee extensors and flexors, as well as back squat and bench press performance using the MuscleLab force velocity transducer. Ten resistance-trained males (mean±SD: age 21.5 ± 1.1 years; body mass 78.3 ± 5.2 kg; height 1.71 ± 0.07 m) underwent a) three to four familiarization sessions on each dynamometer and b) four sessions at different times of day (03:00, 09:00, 15:00 and 21:00 h). Each session was administered in a counterbalanced order and included a period when Perceived onset of mood states (POMS), then rectal and muscle temperature (Trec, Tm) was measured at rest, after which a 5-min standardized 150 W warm-up was performed on a cycle ergometer. Once completed, Isokinetic (60 and 240°·s-1 for extension and flexion) and Isometric dynamometry with peak torque (PT), time-to-peak-torque (tPT) and peak force (PF) and % activation was measured. Lastly, Trec and Tm were measured before the bench press (at 30, 50 and 70 kg) and back squat (at 40, 60 and 80 kg) exercises. A linear encoder was attached to an Olympic bar used for the exercises and average force (AF), peak velocity (PV) and time-to-peak-velocity (tPV) were measured (MuscleLab software; MuscleLab Technology, Langesund, Norway) during the concentric phase of the movements. Five-min recovery was allowed between each set with three repetitions being completed. General linear models with repeated measures and cosinor analysis were used to analyse the data. Values for Trec and Tm at rest were higher in the evening compared to morning values (Acrophase Φ: 16:35 and 17:03 h, Amplitude A: 0.30 and 0.23°C, Mesor M: 36.64 and 37.43°C, p < 0.05). Vigor, happy and fatigue mood states responses showed Φ 16:11 and 16:03 h and 02:05 h respectively. Circadian rhythms were apparent for all variables irrespective of equipment used where AF, PF and PT values peaked between 16:18 and 18:34 h; PV, tPV and tPT peaked between 05:54 and 08:03 h (p < 0.05). In summary, circadian rhythms in force output (force, torque, power, and velocity) were shown for isokinetic, isometric dynamometers and complex multi-joint movements (using a linear encoder); where tPV and tPT occur in the morning compared to the evening. Circadian rhythms in strength can be detected using a portable, low-cost instrument that shows similar cosinor characteristics as established dynamometers. Hence, muscle-strength can be measured in a manner that is more directly transferable to the world of athletic and sports performance.

Illuminating the function of the orphan transporter, SLC22A10, in humans and other primates.

SLC22A10 is an orphan transporter with unknown substrates and function. The goal of this study is to elucidate its substrate specificity and functional characteristics. In contrast to orthologs from great apes, human SLC22A10, tagged with green fluorescent protein, is not expressed on the plasma membrane. Cells expressing great ape SLC22A10 orthologs exhibit significant accumulation of estradiol-17ß-glucuronide, unlike those expressing human SLC22A10. Sequence alignments reveal a proline at position 220 in humans, which is a leucine in great apes. Replacing proline with leucine in SLC22A10-P220L restores plasma membrane localization and uptake function. Neanderthal and Denisovan genomes show proline at position 220, akin to modern humans, indicating functional loss during hominin evolution. Human SLC22A10 is a unitary pseudogene due to a fixed missense mutation, P220, while in great apes, its orthologs transport sex steroid conjugates. Characterizing SLC22A10 across species sheds light on its biological role, influencing organism development and steroid homeostasis.

Distinct Serum Glial Fibrillary Acidic Protein and Neurofilament Light Time-Courses After Rapid Head Rotations.

Traumatic brain injury (TBI) causes significant neurophysiological deficits and is typically associated with rapid head accelerations common in sports-related incidents and automobile accidents. There are over 1.5 million TBIs in the United States each year, with children aged 0-4 being particularly vulnerable. TBI diagnosis is currently achieved through interpretation of clinical signs and symptoms and neuroimaging; however, there is increasing interest in minimally invasive fluid biomarkers to detect TBI objectively across all ages. Pre-clinical porcine models offer controlled conditions to evaluate TBI with known biomechanical conditions and without comorbidities. The objective of the current study was to establish pediatric porcine healthy reference ranges (RRs) of common human serum TBI biomarkers and to report their acute time-course after nonimpact rotational head injury. A retrospective analysis was completed to quantify biomarker concentrations in porcine serum samples collected from 4-week-old female (n = 215) and uncastrated male (n = 6) Yorkshire piglets. Subjects were assigned to one of three experimental groups (sham, sagittal-single, sagittal-multiple) or to a baseline only group. A rapid nonimpact rotational head injury model was used to produce mild-to-moderate TBI in piglets following a single rotation and moderate-to-severe TBI following multiple rotations. The Quanterix Simoa Human Neurology 4-Plex A assay was used to quantify glial fibrillary acidic protein (GFAP), neurofilament light (Nf-L), tau, and ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1). The 95% healthy RRs for females were calculated and validated for GFAP (6.3-69.4 pg/mL), Nf-L (9.5-67.2 pg/mL), and UCH-L1 (3.8-533.7 pg/mL). Rising early, GFAP increased significantly above the healthy RRs for sagittal-single (to 164 and 243 pg/mL) and increased significantly higher in sagittal-multiple (to 494 and 413 pg/mL) groups at 30 min and 1 h postinjury, respectively, returning to healthy RRs by 1-week postinjury. Rising later, Nf-L increased significantly above the healthy RRs by 1 day in sagittal-single (to 69 pg/mL) and sagittal-multiple groups (to 140 pg/mL) and rising further at 1 week (single = 231 pg/mL, multiple = 481 pg/mL). Sagittal-single and sagittal-multiple UCH-L1 serum samples did not differ from shams or the healthy RRs. Sex differences were observed but inconsistent. Serum GFAP and Nf-L levels had distinct time-courses following head rotations in piglets, and both corresponded to load exposure. We conclude that serum GFAP and Nf-L offer promise for early TBI diagnosis and intervention decisions for TBI and other neurological trauma.

Secondary analysis of Staphylococcus aureus whole genomes reveals diverse antimicrobial resistance profiles.

Antimicrobial resistance (AMR) in microorganisms is an ongoing threat to human health across the globe. To better characterize the AMR profiles of six strains of Staphylococcus aureus , we performed a secondary analysis that consisted of the following steps: 1) download fastq files from the Sequence Read Archive, 2) perform a de novo genome assembly from the sequencing reads, 3) annotate the assembled contigs, 4) predict the presence of antimicrobial resistance genes. We predicted the presence of 75 unique genes that conferred resistance against 22 unique antimicrobial compounds.

Controlled Antenatal Thyroid Screening Study III: Effects of gestational thyroid status on adolescent brain morphology.

CONTEXT: Children born to mothers with gestational hypo- or hyperthyroidism may have increased risk of adverse neurodevelopmental outcomes. However, the effects of maternal thyroid status on offspring brain development are unclear. OBJECTIVE: To establish whether adolescent brain morphology is affected by suboptimal gestational thyroid function (SGTF). DESIGN AND SETTING: The Controlled Antenatal Thyroid Screening (CATS) study randomized mothers with SGTF to levothyroxine or no supplementation from ∼12 weeks' gestation. At age 9, children born to mothers who were over-treated with levothyroxine had a higher risk of conduct and hyperactivity traits. For the current CATS III study, children underwent neuroimaging studies, including T1-weighted structural magnetic resonance imaging (MRI). PARTICIPANTS: A total of 85 children aged 11-16 years had usable T1-weighted MRI data (exposed to untreated SGTF (n=21), normal GTF (n=24), or treated SGTF (optimally-treated (n=21), over-treated (n=20)). MAIN OUTCOME MEASURES: Primary outcome: to examine the association of SGTF and its treatment with global brain volumes. Secondary and exploratory outcomes: to investigate the association of maternal TSH and free T4 levels with global and subregional brain volumes. Results were adjusted for age, sex and pubertal scores. RESULTS: There were no significant differences in global brain volumetric measures between groups, including total gray matter volume (p=0.373). Weak positive correlations were found between maternal TSH, but not FT4, levels and several brain volumes, but these did not survive testing for multiple comparisons. CONCLUSIONS: We found no evidence that SGTF was associated with differences in adolescent brain morphology, and no impact of levothyroxine supplementation.

Caterpillar movement mediates spatially local interactions and determines the relationship between population density and contact.

BACKGROUND: While interactions in nature are inherently local, ecological models often assume homogeneity across space, allowing for generalization across systems and greater mathematical tractability. Density-dependent disease models are a prominent example of models that assume homogeneous interactions, leading to the prediction that disease transmission will scale linearly with population density. In this study, we examined how the scale of larval butterfly movement interacts with the resource landscape to influence the relationship between larval contact and population density in the Baltimore checkerspot (Euphydryas phaeton). Our study was inspired by the recent discovery of a viral pathogen that is transmitted horizontally among Baltimore checkerspot larvae. METHODS: We used multi-year larvae location data across six Baltimore checkerspot populations in the eastern U.S. to test whether larval nests are spatially clustered. We then integrated these spatial data with larval movement data in different resource contexts to investigate whether heterogeneity in spatially local interactions alters the assumed linear relationship between larval nest density and contact. We used Correlated Random Walk (CRW) models and field observations of larval movement behavior to construct Probability Distribution Functions (PDFs) of larval dispersal, and calculated the overlap in these PDFs to estimate conspecific contact within each population. RESULTS: We found that all populations exhibited significant spatial clustering in their habitat use. Subsequent larval movement rates were influenced by encounters with host plants and larval age, and under many movement scenarios, the scale of predicted larval movement was not sufficient to allow for the "homogeneous mixing" assumed in density dependent disease models. Therefore, relationships between population density and larval contact were typically non-linear. We also found that observed use of available habitat patches led to significantly greater contact than would occur if habitat use were spatially random. CONCLUSIONS: These findings strongly suggest that incorporating larval movement and spatial variation in larval interactions is critical to modeling disease outcomes in E. phaeton. Epidemiological models that assume a linear relationship between population density and larval contact have the potential to underestimate transmission rates, especially in small populations that are already vulnerable to extinction.

Differential influence of quadriceps rate of torque development on single- and double-leg landing mechanics in anterior cruciate ligament reconstructed and control females.

PURPOSE: The capacity to explosively contract quadriceps within the critical timeframe associated with anterior cruciate ligament (ACL) injury, quantified by the rate of torque development, is potentially essential for safe landing mechanics. This study aimed to investigate the influence of explosive quadriceps strength on ACL-related sagittal-plane landing mechanics in females with and without ACL reconstruction (ACLR). METHODS: Quadriceps explosive strength and landing mechanics were assessed in 19 ACLR and 19 control females during isometric contractions and double- and single-leg jump landings. A stepwise multiple linear regression model determined the variance in each of the landing biomechanics variables for the ACLR limb and nondominant limb of controls that could be explained by the group, rate of torque development and/or their interaction. If peak kinetic variables could be predicted by the rate of torque development or interaction, additional analyses were conducted, accounting for knee flexion as a covariate in the regression model. RESULTS: During single-leg landings, ACLR females exhibited greater knee flexion at initial contact than controls (p = 0.04). Greater quadriceps rate of torque development predicted higher peak posterior ground reaction force and anterior tibial shear force in both groups (p = 0.04). However, after controlling for knee flexion angle at those peak forces, quadriceps rate of torque development was not predictive. In double-leg landings, greater explosive quadriceps strength was associated with quicker attainment of peak knee extension moment and posterior ground reaction force in the ACLR limb (p = 0.03). CONCLUSION: Regardless of ACL injury status, females with greater explosive quadriceps strength adopted safer single-leg landings through increased knee flexion, potentially mitigating ACL loading despite encountering higher peak forces. During double-leg landings, a greater explosive quadriceps strength of the ACLR limb is associated with faster achievement of peak force upon landing. Incorporating explosive quadriceps strengthening into post-ACLR rehabilitation and injury prevention programmes may enhance landing mechanics for reducing primary and subsequent ACL injury risks. LEVEL OF EVIDENCE: Level II.

DNAJC9 prevents CENP-A mislocalization and chromosomal instability by maintaining the fidelity of histone supply chains.

The centromeric histone H3 variant CENP-A is overexpressed in many cancers. The mislocalization of CENP-A to noncentromeric regions contributes to chromosomal instability (CIN), a hallmark of cancer. However, pathways that promote or prevent CENP-A mislocalization remain poorly defined. Here, we performed a genome-wide RNAi screen for regulators of CENP-A localization which identified DNAJC9, a J-domain protein implicated in histone H3-H4 protein folding, as a factor restricting CENP-A mislocalization. Cells lacking DNAJC9 exhibit mislocalization of CENP-A throughout the genome, and CIN phenotypes. Global interactome analysis showed that DNAJC9 depletion promotes the interaction of CENP-A with the DNA-replication-associated histone chaperone MCM2. CENP-A mislocalization upon DNAJC9 depletion was dependent on MCM2, defining MCM2 as a driver of CENP-A deposition at ectopic sites when H3-H4 supply chains are disrupted. Cells depleted for histone H3.3, also exhibit CENP-A mislocalization. In summary, we have defined novel factors that prevent mislocalization of CENP-A, and demonstrated that the integrity of H3-H4 supply chains regulated by histone chaperones such as DNAJC9 restrict CENP-A mislocalization and CIN.

On the association between intention and visual word identification.

One of the most fundamental distinctions in cognitive psychology is between processing that is "controlled" and processing that is "automatic." The widely held automatic processing account of visual word identification asserts that, among other characteristics, the presentation of a well-formed letter string triggers sublexical, lexical, and semantic activation in the absence of any intention to do so. Instead, the role of intention is seen as independent of stimulus identification and as restricted to selection for action using the products of identification (e.g., braking in response to a sign saying "BRIDGE OUT"). We consider four paradigms with respect to the role of an intention-defined here as a "task set" indicating how to perform in the current situation-when identifying single well-formed letter strings. Contrary to the received automaticity view, the literature regarding each of these paradigms demonstrates that the relation between an intention and stimulus identification is constrained in multiple ways, many of which are not well understood at present. One thing is clear: There is no simple relation between an intention, in the form of a task set, and stimulus identification. Automatic processing of words, if this indeed ever occurs, certainly is not a system default. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Head Impact Kinematics and Brain Tissue Strains in High School Lacrosse.

Male lacrosse and female lacrosse have differences in history, rules, and equipment. There is current debate regarding the need for enhanced protective headwear in female lacrosse like that worn by male lacrosse players. To inform this discussion, 17 high school lacrosse players (6 female and 11 male) wore the Stanford Instrumented Mouthguard during 26 competitive games over the 2021 season. Time-windowing and video review were used to remove false-positive recordings and verify head acceleration events (HAEs). The HAE rate in high school female lacrosse (0.21 per athlete exposure and 0.24 per player hour) was approximately 35% lower than the HAE rate in high school male lacrosse (0.33 per athlete exposure and 0.36 per player hour). Previously collected kinematics data from the 2019 high school male and female lacrosse season were combined with the newly collected 2021 kinematics data, which were used to drive a finite element head model and simulate 42 HAEs. Peak linear acceleration (PLA), peak angular velocity (PAV), and 95th percentile maximum principal strain (MPS95) of brain tissue were compared between HAEs in high school female and male lacrosse. Median values for peak kinematics and MPS95 of HAEs in high school female lacrosse (PLA, 22.3 g; PAV, 10.4 rad/s; MPS95, 0.05) were lower than for high school male lacrosse (PLA, 24.2 g; PAV, 15.4 rad/s; MPS95, 0.07), but the differences were not statistically significant. Quantifying a lower HAE rate in high school female lacrosse compared to high school male lacrosse, but similar HAE magnitudes, provides insight into the debate regarding helmets in female lacrosse. However, due to the small sample size, additional video-verified data from instrumented mouthguards are required.

HSV-1 employs UL56 to antagonize expression and function of cGAMP channels.

DNA sensing is important for antiviral immunity. The DNA sensor cGAS synthesizes 2'3'-cyclic GMP-AMP (cGAMP), a second messenger that activates STING, which induces innate immunity. cGAMP not only activates STING in the cell where it is produced but cGAMP also transfers to other cells. Transporters, channels, and pores (including SLC19A1, SLC46A2, P2X7, ABCC1, and volume-regulated anion channels (VRACs)) release cGAMP into the extracellular space and/or import cGAMP. We report that infection with multiple human viruses depletes some of these cGAMP conduits. This includes herpes simplex virus 1 (HSV-1) that targets SLC46A2, P2X7, and the VRAC subunits LRRC8A and LRRC8C for degradation. The HSV-1 protein UL56 is necessary and sufficient for these effects that are mediated at least partially by proteasomal turnover. UL56 thereby inhibits cGAMP uptake via VRAC, SLC46A2, and P2X7. Taken together, HSV-1 antagonizes intercellular cGAMP transfer. We propose that this limits innate immunity by reducing cell-to-cell communication via the immunotransmitter cGAMP.

Oral health educators' reflections on teaching 2022 and beyond.

INTRODUCTION: The global pandemic prompted changes in health science education affecting both teaching and learning. This multi-institutional study assesses the near-term implications of these changes on faculty and faculty development. The project goals were to: (1) describe faculty experiences of teaching during the pandemic; (2) identify ways to sustain new pedagogical approaches, (3) describe the types of support faculty members need, and (4) offer recommendations to enhance oral health professions education. METHODS: A mixed-method approach using exploratory sequential design was conducted in two phases collecting qualitative and quantitative data. Focus group participants included didactic, pre-clinical, and clinical faculty in dental school (DMD/DDS), dental hygiene and dental therapy programs, and also faculty members serving in administrative roles in these programs (N = 37). One hundred forty-four faculty participated in the multi-institutional follow-up survey. RESULTS: Focus group and survey results led to 14 recommendations (nine structural and five individual) for oral health profession institutions and educators. CONCLUSION: Oral health profession education faculty were dramatically impacted by the pandemic and new faculty development needs were identified. Traditional faculty development topics and practices may be no longer applicable in the post-COVID-19 environment. Additionally, the pandemic stimulated creative approaches for curriculum design, teaching, and assessment in oral health profession education. Strategies need to be implemented to sustain these innovations.

Finding the Optimal Screening Test for Periprosthetic Joint Infection: A Prospective Study.

BACKGROUND: No single test has demonstrated absolute accuracy in the diagnosis of periprosthetic joint infection (PJI). Serological markers are often used as screening tools to avoid unnecessary joint aspiration in cases with a low probability of infection. This study aimed to determine the utility of standard-of-care serological tests as a screening tool for PJI in patients undergoing revision arthroplasty. METHODS: This prospective study enrolled 502 patients undergoing revision hip or knee arthroplasty between May 2017 and August 2021. A PJI was defined using a modified definition of the 2018 International Consensus Meeting criteria. Plasma D-dimer, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and fibrinogen were measured preoperatively. There were 82 patients undergoing reimplantation who were excluded. Additionally, 8 patients who had an inconclusive International Consensus Meeting score were also excluded. Of the 412 included patients, 317 (76.9%) underwent revision for aseptic failure, and 95 (23.1%) had PJI. Receiver operating characteristic curves were used to assess the diagnostic utility of each serological test. A pairwise comparison with Bonferroni correction was performed to determine whether the differences in areas under the curve (AUCs) between the tests were significant. Additional analyses were performed to find the threshold for each test that offered 100% sensitivity, allowing it to be the optimal screening test. RESULTS: All 4 serological markers, D-dimer (AUC 0.860, sensitivity 81.3%, specificity 81.7%), CRP (AUC 0.862, sensitivity 90.4%, specificity 70.0%), ESR (AUC 0.833, sensitivity 73.9%, specificity 85.2%), and fibrinogen (AUC 0.798, sensitivity 74.7%, specificity 75.4%), demonstrated comparable accuracy for the diagnosis of PJI (all P > .05). When maximizing sensitivity to 100%, D-dimer demonstrated the highest specificity (AUC 0.860, specificity 40.2%), outperforming ESR (AUC 0.833, specificity 3.3%), fibrinogen (AUC 0.798, specificity 2.3%), and CRP (AUC 0.862, specificity 0%). A plasma D-dimer level of ≥ 244 ng/mL was identified as the optimal cutoff for use as a screening test. CONCLUSIONS: Although plasma D-dimer demonstrated similar diagnostic accuracy as CRP, ESR, and fibrinogen, it outperformed all 3 aforementioned serological markers when used as a screening test for PJI. LEVEL OF EVIDENCE: Level II.

White phosphorous civilian hand burns - An aid to timely treatment of a rare entity.

First discovered in 1669, white phosphorus is well known for its use in military warfare (Davis, 2002). Its application has since been expanded to include industrial disinfectants, fertilisers and fireworks (Davis, 2002). Exposure to white phosphorus can lead to severe chemical burns with high morbidity and potentially fatal systemic effects. Fortunately, civilian casualties from this potent agent are remarkably rare with few reports in the literature to date (Frank et al., 2008; Aviv et al., 2017). We present the case of a 27-year-old fisherman who sustained a chemical burn to his right hand from a substance suspected to be white phosphorus. We propose an evidence-based algorithm to guide non-military physicians literature on the acute management of white phosphorus burns to optimise timely emergency management of this uncommonly encountered substance.

Productions Need Not Match Study Items to Confer a Production Advantage, But It Helps.

The production effect is the finding that, relative to silent reading, producing information at study (e.g., reading aloud) leads to a benefit in memory. In most studies of this effect, individuals are presented with a set of unique items, and they produce a subset of these items (e.g., they are presented with the to-be-remembered target item TABLE and produce table) such that the production is both unique and representative of the target. Across two preregistered experiments, we examined the influence of a production that is unique but that does not match the target (e.g., producing fence to the target TABLE, producing car to the target TREE, and so on). This kind of production also yielded a significant effect-the mismatching production effect-although it was smaller than the standard production effect (i.e., when productions are both unique and representative of their targets) and was detectable only when targets with standard productions were included in the same study phase (i.e., when the type of production was manipulated within participant). We suggest that target-production matching is an important precursor to the production effect and that the kind of production that brings about a benefit depends on the other productions that are present.