Trends in Shortages of Lead Chelators From 2001 to 2022.

OBJECTIVE: The study aims to describe drug shortages affecting lead chelators in the United States from 2001 through 2022. METHODS: Drug shortage data were retrieved from the University of Utah Drug Information Service from January 1, 2001, through December 31, 2022. Shortages of first- and second-line lead chelators were analyzed. Drug class, formulation, administration route, shortage reason, shortage duration, generic status, single-source status, and presence of temporally overlapping shortages were examined. Total shortage months, percentages of study period on shortage, and median shortage durations were calculated. RESULTS: Thirteen lead chelator shortages were reported during the study period. Median duration was 7.4 months and the longest shortage (24.8 months) involved calcium disodium edetate. Calcium disodium edetate and dimercaprol had the greatest number of shortages, 4 each, and 61.5% of shortages involved parenteral medications. Median shortage duration was 14.2 months for parenteral agents and 2.2 months for non-parenteral agents. All shortages involved generic, single-source products. Supply/demand and manufacturing problems were the most common shortage reasons provided. Overlapping shortages occurred for 3.7% of the study period. Median shortage duration increased from 3 to 11 months in the second half of the study period, and 61.5% of shortages occurred in the second half of the study period. CONCLUSIONS: All chelators experienced multiple shortages, which became increasingly frequent and prolonged over time. Concurrent shortages occurred, potentially hampering substitution between different agents. Health care stakeholders must build supply chain resilience and develop guidelines regarding how to modify chelation therapy based on shortage conditions.

Frequency-dependent behavior of paretic and non-paretic leg force during standing post stroke.

Maintaining upright posture in quiet standing is an important skill that is often disrupted by stroke. Despite extensive study of human standing, current understanding is incomplete regarding the muscle coordination strategies that produce the ground-on-foot force (F) that regulates translational and rotational accelerations of the body. Even less is understood about how stroke disrupts that coordination. Humans produce sagittal plane variations in the location (center of pressure, xCP) and orientation (Fx/Fz) of F that, along with the force of gravity, produce sagittal plane body motions. As F changes during quiet standing there is a strong correlation between the xCP and Fx/Fz time-varying signals within narrow frequency bands. The slope of the correlation varies systematically with frequency in non-disabled populations, is sensitive to changes in both environmental and neuromuscular control factors, and emerges from the interaction of body mechanics and neural control. This study characterized the xCP versus Fx/Fz relationship as frequency-dependent Intersection Point (IP) heights for the paretic and non-paretic legs of individuals with history of a stroke (n = 12) as well as in both legs of non-disabled controls (n = 22) to reveal distinguishing motor coordination patterns. No inter-leg difference of IP height was present in the control group. The paretic leg IP height was lower than the non-paretic, and differences from control legs were in opposite directions. These results quantify disrupted coordination that may characterize the paretic leg balance deficit and non-paretic leg compensatory behavior, providing a means of monitoring balance impairment and a target for therapeutic interventions.

Deletion of Aurora kinase A prevents the development of polycystic kidney disease in mice.

Aurora Kinase A (AURKA) promotes cell proliferation and is overexpressed in different types of polycystic kidney disease (PKD). To understand AURKA's role in regulating renal cyst development we conditionally deleted the gene in mouse models of Autosomal Dominant PKD (ADPKD) and Joubert Syndrome, caused by Polycystin 1 (Pkd1) and Inositol polyphosphate-5-phosphatase E (Inpp5e) mutations respectively. We show that while Aurka is dispensable for collecting duct development and homeostasis, its deletion prevents cyst formation in both disease models. Cross-comparison of transcriptional changes implicated AKT signaling in cyst prevention and we show that (i) AURKA and AKT physically interact, (ii) AURKA regulates AKT activity in a kinase-independent manner and (iii) inhibition of AKT can reduce disease severity. AKT activation also regulates Aurka expression, creating a feed-forward loop driving renal cystogenesis. We find that the AURKA kinase inhibitor Alisertib stabilises the AURKA protein, agonizing its cystogenic functions. These studies identify AURKA as a master regulator of renal cyst development in different types of PKD, functioning in-part via AKT.

Male patient attendances at Sexual Assault Treatment Units in Ireland: An analysis of 381 cases and a comparison with female patients.

BACKGROUND: Sexual violence is a crime that affects people of all genders. While focus is frequently on female survivors, it is crucial to acknowledge that males also experience sexual violence and to ensure that gender-sensitive services are available to all survivors. Understanding the prevalence of, and factors associated with, sexual violence against males is a critical first step in addressing this issue. We aim to address the lack of data in relation to sexual violence against males. METHODS: A cross-sectional study of all male attendances at 6 Sexual Assault Treatment Units (SATU) in the Republic of Ireland over a 6-year period and, where applicable, comparison with corresponding female attendances. RESULTS: There were 381 male attendances with an average age of 28.5 years over the study period, representing 7 % of all SATU patients. There was a 24 % increase in male attendances during the study period. 39.1 % presented within 24 h of the assault. 61.9 % reported the crime to the police. Employment status included 37.3 % employed, 24.9 % unemployed, and 26.2 % students, with 86.7 % being Irish nationals. Most incidents occurred on weekdays (53.3 %) and at night (56.7 %). Referrals were primarily from police (55.9 %), and psychological support was provided in 62.3 % of cases. Alcohol (60.4 %) and illicit drugs (20.5 %) were reported before assaults. 18.6 % suspected drug-facilitated assaults. Male assailants constituted 90.1 %, with 13.9 % involving multiple assailants. Male attenders were significantly more likely than females to be assaulted in their assailant's home and to be assaulted by more than one assailant. They were significantly less likely than females to report the crime to the police or to have consumed alcohol. CONCLUSION: To our knowledge, this is one of the largest case series of male patients attending a sexual assault treatment service to be published in the international literature. Male patients are a distinct group that are increasingly accessing SATU services. Significant differences exist between male and female patients' reported experiences of sexual violence. Knowledge of these factors will support appropriate tailoring of treatment & service provision, prevention and awareness strategies to help modify the impact and reduce the incidence of sexual violence in this cohort.

Modulating inflammation with interleukin 37 treatment ameliorates murine Autosomal Dominant Polycystic Kidney Disease.

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a leading cause of kidney failure and is associated with substantial morbidity and mortality. Interstitial inflammation is attributed to the action of infiltrating macrophages and is a feature thought to aggravate disease progression. Here, we investigated the therapeutic potential of the anti-inflammatory IL37b cytokine as a treatment for ADPKD using genetic mouse models, demonstrating that transgenic expression of human IL37b reduced collecting duct cyst burden in both early and adult-onset ADPKD rodent models. Moreover, injection of recombinant human IL37b could also reduce cyst burden in early onset ADPKD mice, an observation not associated with increased macrophage number at early stages of cyst formation. Interestingly, transgenic IL37b expression also did not alter macrophage numbers in advanced disease. Whole kidney RNA-seq highlighted an IL37b-mediated upregulation of the interferon signaling pathway and single-cell RNA-seq established that these changes originate at least partly from kidney resident macrophages. We further found that blocking type I interferon signaling in mice expressing IL37b resulted in increased cyst number, confirming this as an important pathway by which IL37b exerts its beneficial effects. Thus, our studies show that IL37b promotes interferon signaling in kidney resident macrophages which suppresses cyst initiation, identifying this protein as a potential therapy for ADPKD.

Ozonolysis can produce long-lived greenhouse gases from commercial refrigerants.

Hydrofluoroolefins are being adopted as sustainable alternatives to long-lived fluorine- and chlorine-containing gases and are finding current or potential mass-market applications as refrigerants, among a myriad of other uses. Their olefinic bond affords relatively rapid reaction with hydroxyl radicals present in the atmosphere, leading to short lifetimes and proportionally small global warming potentials. However, this type of functionality also allows reaction with ozone, and whilst these reactions are slow, we show that the products of these reactions can be extremely long-lived. Our chamber measurements show that several industrially important hydrofluoroolefins produce CHF3 (fluoroform, HFC-23), a potent, long-lived greenhouse gas. When this process is accounted for in atmospheric chemical and transport modeling simulations, we find that the total radiative effect of certain compounds can be several times that of the direct radiative effect currently recommended by the World Meteorological Organization. Our supporting quantum chemical calculations indicate that a large range of exothermicity is exhibited in the initial stages of ozonolysis, which has a powerful influence on the CHF3 yield. Furthermore, we identify certain molecular configurations that preclude the formation of long-lived greenhouse gases. This demonstrates the importance of product quantification and ozonolysis kinetics in determining the overall environmental impact of hydrofluoroolefin emissions.

General practice trainees' understanding of post-sexual assault care: the impact of a specialist educational intervention.

BACKGROUND: Sexual assault (SA) is a highly prevalent issue, with significant adverse health sequelae. Given that general practitioners (GPs) may serve as the first point of contact for many SA victims, their awareness of post-SA care and appropriate understanding of referral pathways to a sexual assault treatment unit (SATU) are critically important. This study evaluated GP trainees' knowledge of and comfort with post-SA care. METHODS: Educational intervention study using a didactic teaching session was delivered by a specialist forensic examiner on post-SA care. A pre and post-study questionnaire was implemented to assess participants' knowledge and comfort levels with subject material. Significance was set at p-value below 0.05. RESULTS: Seventy-five GP-trainees attended the teaching session. Fifty-three completed the pre-teaching questionnaire and 50 completed the post-teaching questionnaire. Only a minority of trainees had received prior teaching in post-SA care as a medical student (13.2% n = 7) or as a postgraduate (28.3% n = 15). After the teaching session, there was a significant improvement trainees' comfort levels in explaining a forensic examination (p < 0.0001), referral pathways to a SATU (p < 0.0001) and offering advice in relation to emergency contraception (p < 0.0001). There was also a significant improvement in understanding HIV post-exposure prophylaxis (PEP) (p < 0.001) and forensic examination (FE) time-lines (p < 0.001). CONCLUSION: This study reveals that GP-trainees have had limited exposure to teaching on post-SA care. Additionally, significant improvements were observed following a 1-h didactic teaching session on post-SA care. Trainees demonstrated increased understanding of SATU referral pathways, understanding of immediate medical care after SA, including PEP and FE timelines.

The molecular and cellular anatomy of a fetal programming defect - the impact of low protein diet on the developing kidney.

Low nephron number correlates with the development of hypertension and chronic kidney disease later in life. While intrauterine growth restriction caused by maternal low protein diet (LPD) is thought to be a significant cause of reduced nephron endowment in impoverished communities, its influence on the cellular and molecular processes which drive nephron formation are poorly understood. We conducted a comprehensive characterization of the impact of LPD on kidney development using tomographic and confocal imaging to quantify changes in branching morphogenesis and the cellular and morphological features of nephrogenic niches across development. These analyses were paired with single-cell RNA sequencing to dissect the transcriptional changes that LPD imposes during renal development. Differences in the expression of genes involved in metabolism were identified in most cell types we analyzed, yielding imbalances and shifts in cellular energy production. We further demonstrate that LPD impedes branching morphogenesis and significantly reduces the number of pretubular aggregates - the initial precursors to nephron formation. The most striking observation was that LPD changes the developmental trajectory of nephron progenitor cells, driving the formation of a partially committed cell population which likely reflects a failure of cells to commit to nephron formation and which ultimately reduces endowment. This unique profile of a fetal programming defect demonstrates that low nephron endowment arises from the pleiotropic impact of changes in branching morphogenesis and nephron progenitor cell commitment, the latter of which highlights a critical role for nutrition in regulating the cell fate decisions underpinning nephron endowment. Significance Statement: While a mother's diet and behavior can negatively impact the number of nephrons in the kidneys of her offspring, the root cellular and molecular drivers of these deficits have not been rigorously explored. In this study we use advanced imaging and gene expression analysis in mouse models to define how a maternal low protein diet, analogous to that of impoverished communities, results in reduced nephron endowment. We find that low protein diet has pleiotropic effects on metabolism and the normal programs of gene expression. These profoundly impact the process of branching morphogenesis necessary to establish niches for nephron generation and change cell behaviors which regulate how and when nephron progenitor cells commit to differentiation.

Simultaneously Measured Kinetics of Two Amyloid Polymorphs Using Cross Peak Specific 2D IR Spectroscopy.

The origin of in vitro amyloid fibril polymorphs is debated, in part, because few techniques can simultaneously monitor the formation kinetics of multiple amyloid polymorphs. Using a cross-peak specific polarization scheme, ⟨0°,0°,60°,-60°⟩, we resolve 22 previously unseen cross peaks in the 2D IR spectra of amyloid fibrils formed by the human islet amyloid polypeptide (hIAPP). Those cross peaks include a subset assigned to a second fibril polymorph, which forms on a slower time scale. We simulated the data with three different kinetic models for polymorph formation. Only a model based on secondary nucleation reproduces the cross peak kinetics. These experiments are evidence that fibrils formed by secondary nucleation have a different polymorphic structure than the parent fibrils and illustrate the enhanced structural resolution of this new cross peak specific polarization scheme.

Wearable sensing for understanding and influencing human movement in ecological contexts.

Wearable sensors offer a unique opportunity to study movement in ecological contexts - that is, outside the laboratory where movement happens in ordinary life. This article discusses the purpose, means, and impact of using wearable sensors to assess movement context, kinematics, and kinetics during locomotion, and how this information can be used to better understand and influence movement. We outline the types of information wearable sensors can gather and highlight recent developments in sensor technology, data analysis, and applications. We close with a vision for important future research and key questions the field will need to address to bring the potential benefits of wearable sensing to fruition.

Besieged in the Bronx: Lessons from an in-hospital mass casualty.

BACKGROUND: An active shooter in a hospital is an emergency extraordinaire. We report a single institution's response to the largest active shooter mass casualty event in American History. METHODS: Review of notification, flow of prioritized patients, and key elements of the day's dynamic after a hospital attack by a lone gunman were commenced. The review includes outcomes on seven victims and assailants. RESULTS: "Code Silver" announced: open display of a weapon. Concise, known, and published chain of command implemented. All house staff to the Emergency Department (ED) via text blast. Operating room (OR) notified. Injured to ED, then triaged to OR. Armed NYPD stationed throughout OR. Senior surgeons controlled key triage during attack with flow controlled from the ED and OR control desk. One fatality plus shooter. CONCLUSION: Success favors the prepared. The response to attack, readiness of medical personnel, mitigation, and recovery have brought the following recommendations: (1) single entrance access; (2) armed, professional guards at all entrances; (3) camouflage metal detectors; (4) mandatory, recurrent hospital-wide active shooter training, mock, and table top; (5) published physician chain of command; (6) intercom code system known to all hospital personnel indicating a weapon is openly displayed; (7) a "no fly" list of former employees who are prohibited on premises; (8) stop the bleed training with kits on every floor; (9) one voice, one face to disseminate information. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level I.

Hydroxyapatite coatings on cement paste as barriers against radiological contamination.

A novel method for precipitating hydroxyapatite (HAp) onto cement paste is investigated for protecting concrete infrastructure from radiological contamination. Legacy nuclear sites contain large volumes of contaminated concrete and are expensive and dangerous to decommission. One solution is to 'design for decommissioning' by confining contaminants to a thin layer. Current layering methods, including paints or films, offer poor durability over plant lifespans. Here, we present a mineral-HAp-coated cement, which innovatively serves as a barrier layer to radioactive contaminants (e.g. Sr, U). HAp is shown to directly mineralise onto a cement paste block in a layer several microns thick via a two-step process: first, applying a silica-based scaffold onto a cement paste block; and second, soaking the resulting block in a PO4-enriched Ringer's solution. Strontium ingression was tested on coated and uncoated cement paste (~ 40 × 40 × 40mm cement, 450 mL, 1000 mg L- 1 Sr) for a period of 1-week. While both coated and uncoated samples reduced the solution concentration of Sr by half, Sr was held within the HAp layer of coated cement paste and was not observed within the cement matrix. In the uncoated samples, Sr had penetrated further into the block. Further studies aim to characterise HAp before and after exposure to a range of radioactive contaminants and to develop a method for mechanical layer separation.

ADAPTations to low load blood flow restriction exercise versus conventional heavier load resistance exercise in UK military personnel with persistent knee pain: protocol for the ADAPT study, a multi-centre randomized controlled trial.

BACKGROUND: Muscle atrophy, muscle weakness and localised pain are commonly reported following musculoskeletal injury (MSKI). To mitigate this risk and prepare individuals to return to sport or physically demanding occupations, resistance training (RT) is considered a vital component of rehabilitation. However, to elicit adaptations in muscle strength, exercise guidelines recommend lifting loads ≥ 70% of an individual's one repetition maximum (1-RM). Unfortunately, individuals with persistent knee pain are often unable to tolerate such high loads and this may negatively impact the duration and extent of their recovery. Low load blood flow restriction (LL-BFR) is an alternative RT technique that has demonstrated improvements in muscle strength, hypertrophy, and pain in the absence of high mechanical loading. However, the effectiveness of high-frequency LL-BFR in a residential rehabilitation environment remains unclear. This study will compare the efficacy of high frequency LL-BFR to 'conventional' heavier load resistance training (HL-RT) on measures of physical function and pain in adults with persistent knee pain. METHODS: This is a multicentre randomised controlled trial (RCT) of 150 UK service personnel (aged 18-55) admitted for a 3-week residential rehabilitation course with persistent knee pain. Participants will be randomised to receive: a) LL-BFR delivered twice daily at 20% 1-RM or b) HL-RT three-times per week at 70% 1-RM. Outcomes will be recorded at baseline (T1), course discharge (T2) and at three-months following course (T3). The primary outcome will be the lower extremity functional scale (LEFS) at T2. Secondary outcomes will include patient reported perceptions of pain, physical and occupational function and objective measures of muscle strength and neuromuscular performance. Additional biomechanical and physiological mechanisms underpinning both RT interventions will also be investigated as part of a nested mechanistic study. DISCUSSION: LL-BFR is a rehabilitation modality that has the potential to induce positive clinical adaptations in the absence of high mechanical loads and therefore could be considered a treatment option for patients suffering significant functional deficits who are unable to tolerate heavy load RT. Consequently, results from this study will have a direct clinical application to healthcare service providers and patients involved in the rehabilitation of physically active adults suffering MSKI. TRIAL REGISTRATION: ClinicalTrials.org reference number, NCT05719922.

Relative Lung Perfusion on Ventilation-Perfusion Scans After Double Lung Transplant.

BACKGROUND: Pulmonary blood flow can be assessed on ventilation-perfusion (VQ) scan with relative lung perfusion, with a 55% to 45% (or 10%) right-to-left differential considered normal. We hypothesized that wide perfusion differential on routine VQ studies at 3 mo posttransplant would be associated with an increased risk of death or retransplantation, chronic lung allograft (CLAD), and baseline lung allograft dysfunction. METHODS: We conducted a retrospective cohort study on all patients who underwent double-lung transplant in our program between 2005 and 2016, identifying patients with a wide perfusion differential of >10% on a 3-mo VQ scan. We used Kaplan-Meier estimates and proportional hazards models to assess the association between perfusion differential and time to death or retransplant and time to CLAD onset. We used correlation and linear regression to assess the relationship with lung function at time of scan and with baseline lung allograft dysfunction. RESULTS: Of 340 patients who met inclusion criteria, 169 (49%) had a relative perfusion differential of ≥ 10% on a 3-mo VQ scan. Patients with increased perfusion differential had increased risk of death or retransplantation ( P = 0.011) and CLAD onset ( P = 0.012) after adjustment for other radiographic/endoscopic abnormalities. Increased perfusion differential was associated with lower lung function at time of scan. CONCLUSIONS: Wide lung perfusion differential was common after lung transplant in our cohort and associated with increased risk of death, poor lung function, and CLAD onset. The nature of this abnormality and its use as a predictor of future risk warrant further investigation.

A genomic data archive from the Network for Pancreatic Organ donors with Diabetes.

The Network for Pancreatic Organ donors with Diabetes (nPOD) is the largest biorepository of human pancreata and associated immune organs from donors with type 1 diabetes (T1D), maturity-onset diabetes of the young (MODY), cystic fibrosis-related diabetes (CFRD), type 2 diabetes (T2D), gestational diabetes, islet autoantibody positivity (AAb+), and without diabetes. nPOD recovers, processes, analyzes, and distributes high-quality biospecimens, collected using optimized standard operating procedures, and associated de-identified data/metadata to researchers around the world. Herein describes the release of high-parameter genotyping data from this collection. 372 donors were genotyped using a custom precision medicine single nucleotide polymorphism (SNP) microarray. Data were technically validated using published algorithms to evaluate donor relatedness, ancestry, imputed HLA, and T1D genetic risk score. Additionally, 207 donors were assessed for rare known and novel coding region variants via whole exome sequencing (WES). These data are publicly-available to enable genotype-specific sample requests and the study of novel genotype:phenotype associations, aiding in the mission of nPOD to enhance understanding of diabetes pathogenesis to promote the development of novel therapies.

Spatio-Temporal Clustering of Multi-Location Time Series to Model Seasonal Influenza Spread.

Although seasonal influenza disease spread is a spatio-temporal phenomenon, public surveillance systems aggregate data only spatially, and are rarely predictive. We develop a hierarchical clustering-based machine learning tool to anticipate flu spread patterns based on historical spatio-temporal flu activity, where we use historical influenza-related emergency department records as a proxy for flu prevalence. This analysis replaces conventional geographical hospital clustering with clusters based on both spatial and temporal distance between hospital flu peaks to generate a network illustrating whether flu spreads between pairs of clusters (direction) and how long that spread takes (magnitude). To overcome data sparsity, we take a model-free approach, treating hospital clusters as a fully-connected network, where arcs indicate flu transmission. We perform predictive analysis on the clusters' time series of flu ED visits to determine direction and magnitude of flu travel. Detection of recurrent spatio-temporal patterns may help policymakers and hospitals better prepare for outbreaks. We apply this tool to Ontario, Canada using a five-year historical dataset of daily flu-related ED visits, and find that in addition to expected flu spread between major cities/airport regions, we were able to illuminate previously unsuspected patterns of flu spread between non-major cities, providing new insights for public health officials. We showed that while a spatial clustering outperforms a temporal clustering in terms of the direction of the spread (81% spatial v. 71% temporal), the opposite is true in terms of the magnitude of the time lag (20% spatial v. 70% temporal).

Host Plant Specificity in Web-Building Spiders.

Spiders are ubiquitous generalist predators playing an important role in regulating insect populations in many ecosystems. Traditionally they have not been thought to have strong influences on, or interactions with plants. However, this is slowly changing as several species of cursorial spiders have been reported engaging in either herbivory or inhabiting only one, or a handful of related plant species. In this review paper, we focus on web-building spiders on which very little information is available. We only find well-documented evidence from studies of host plant specificity in orb spiders in the genus Eustala, which are associated with specific species of swollen thorn acacias. We review what little is known of this group in the context of spider-plant interactions generally, and focus on how these interactions are established and maintained while providing suggestions on how spiders may locate and identify specific species of plants. Finally, we suggest ideas for future fruitful research aimed at understanding how web-building spiders find and utilise specific plant hosts.

Shortages of agents used to treat antimuscarinic delirium.

INTRODUCTION: Antimuscarinic delirium (AD), a potentially life-threatening condition frequently encountered by emergency physicians, results from poisoning with antimuscarinic agents. Treatment with physostigmine and benzodiazepines is the mainstay of pharmacotherapy, and use of dexmedetomidine and non-physostigmine centrally-acting acetylcholinesterase inhibitors (cAChEi) such as rivastigmine has also been described. Unfortunately, these medications are subject to drug shortages which negatively impact the ability to provide appropriate pharmacologic treatment of patients with AD. METHODS: Drug shortage data were retrieved from the University of Utah Drug Information Service (UUDIS) database from January 2001 through December 2021. Shortages of first-line agents used to treat AD (physostigmine and parenteral benzodiazepines) and second-line agents (dexmedetomidine and non-physostigmine cAChEi) were examined. Drug class, formulation, route of administration, reason for shortage, shortage duration, generic status, and whether the drug was a single-source product (made by only one manufacturer) were extracted. Shortage overlap and median shortage durations were calculated. RESULTS: Twenty-six shortages impacting drugs used to treat AD were reported to UUDIS from January 1, 2001 to December 31, 2021. Median shortage duration for all medication classes was 6.0 months. Four shortages were unresolved at the end of the study period. The single medication most often on shortage was dexmedetomidine, however benzodiazepines were the most common medication class on shortage. Twenty-five shortages involved parenteral formulations, and one shortage involved the transdermal patch formulation of rivastigmine. The majority (88.5%) of shortages involved generic medications, and 50% of products on shortage were single-source. The most common reported reason for shortage was a manufacturing issue (27%). Shortages were often prolonged and, in 92% of cases, overlapped temporally with other shortages. Shortage frequency and duration increased during the second half of the study period. CONCLUSION: Shortages of agents used in the treatment of AD were common during the study period and affected all agent classes. Shortages were often prolonged and multiple shortages were ongoing at study period end. Multiple concurrent shortages involving different agents occurred, which could hamper substitution as a means of mitigating shortage. Healthcare stakeholders must develop innovative patient- and institution-specific solutions in times of shortage and work to build resilience into the medical product supply chain to minimize future shortages of drugs used for treatment of AD.

Characteristics and clinical needs of young tertiary students attending a specialist mood disorders clinic.

OBJECTIVE: To investigate the clinical characteristics of tertiary students and non-students attending a specialist clinic for severe mood disorders. METHOD: Medical record audit of clients discharged from the Youth Mood Clinic (YMC). Data extracted included depressive symptomatology, suicidal ideation, self-harm, suicide attempt, tertiary education engagement, drop-out and deferral. RESULTS: Data from 131 clients (M age = 19.58 years, SD = 2.66) were analysed, including 46 tertiary students. Relative to non-students, at intake, tertiary students reported more severe depressive symptomatology (d = 0.43). They were more likely to experience suicidal ideation at intake (V = 0.23), and during treatment (V = 0.18). Tertiary students were also more likely to be living separately to their family of origin (V = 0.20) but were less likely to have experienced parental separation (V = 0.19). 21.73% of tertiary students dropped out or deferred study during care. CONCLUSION: In this cohort, those engaged in tertiary education experience more severe depression and more commonly experienced suicidal ideation. These young people require targeted support for their mental health while they undertake tertiary education.

Chronic consumption of probiotics, oats, and apples has differential effects on postprandial bile acid profile and cardiometabolic disease risk markers compared with an isocaloric control (cornflakes): a randomized trial.

BACKGROUND: Dietary components that impact the gut microbiota may beneficially affect cardiometabolic health, possibly by altered bile acid metabolism. However, impacts of these foods on postprandial bile acids, gut microbiota, and cardiometabolic risk markers are unclear. OBJECTIVES: The aim of this study was to determine the chronic effects of probiotics, oats, and apples on postprandial bile acids, gut microbiota, and cardiometabolic health biomarkers. METHODS: Using an acute within chronic parallel design, 61 volunteers (mean ± SD: age 52 ± 12 y; BMI 24.8 ± 3.4 kg/m2) were randomly assigned to consume 40 g cornflakes (control), 40 g oats or 2 Renetta Canada apples each with 2 placebo capsules per day or 40 g cornflakes with 2 Lactobacillus reuteri capsules (>5 × 109 CFU) per day, for 8 wk. Fasting and postprandial serum/plasma bile acids and cardiometabolic health biomarkers, fecal bile acids, and gut microbiota composition were determined. RESULTS: At week 0, oats and apples significantly decreased postprandial serum insulin [area under the curve (AUC): 25.6 (17.4, 33.8) and 23.4 (15.4, 31.4) vs. 42.0 (33.7, 50.2) pmol/L × min and incremental AUC (iAUC): 17.8 (11.6, 24.0) and 13.7 (7.7, 19.8) vs. 29.6 (23.3, 35.8) pmol/L × min] and C-peptide responses [AUC: 599 (514, 684) and 550 (467, 632) vs. 750 (665, 835) ng/mL × min], whereas non-esterified fatty acids were increased [AUC 135 (117, 153) vs. 86.3 (67.9, 105) and iAUC 96.2 (78.8, 114) vs. 60 (42.1, 77.9) mmol/L × min] after the apples vs. control (P ≤ 0.05). Postprandial unconjugated [AUC: predicted means (95% CI) 1469 (1101, 1837) vs. 363 (-28, 754) µmol/L × min and iAUC: 923 (682, 1165) vs. 22.0 (-235, 279) µmol/L × min)] and hydrophobic [iAUC: 1210 (911, 1510) vs. 487 (168, 806) µmol/L × min] bile acid responses were increased after 8 wk probiotic intervention vs. control (P ≤ 0.049). None of the interventions modulated the gut microbiota. CONCLUSIONS: These results support beneficial effects of apples and oats on postprandial glycemia and the ability of the probiotic Lactobacillus reuteri to modulate postprandial plasma bile acid profiles compared with control (cornflakes), with no relationship evident between circulating bile acids and cardiometabolic health biomarkers.