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The antipsychotic aripiprazole is often used in the treatment of first-episode psychosis. Measuring aripiprazole blood levels provides an objective measure of treatment adherence, but this currently involves taking a venous blood sample and sending to a laboratory for analysis.
To detail the development, validation and utility of a new point of care (POC) test for finger-stick capillary blood concentrations of aripiprazole.
Analytical performance (sensitivity, precision, recovery and linearity) of the assay were established using spiked whole blood and control samples of varying aripiprazole concentration. Assay validation was performed over a 14-month period starting in July 2021. Eligible patients were asked to provide a finger-stick capillary sample in addition to their usual venous blood sample. Capillary blood samples were tested by the MyCare™ Insite POC analyser, which provided measurement of aripiprazole concentration in 6 min, and the venous blood sample was tested by the standard laboratory method.
A total of 101 patients agreed to measurements by the two methods. Venous blood aripiprazole concentrations as assessed by the laboratory method ranged from 17 to 909 ng/mL, and from 1 to 791 ng/mL using POC testing. The correlation coefficient between the two methods (r) was 0.96 and there was minimal bias (slope 0.91, intercept 4 ng/ml).
The MyCare Insite POC analyser is sufficiently accurate and reliable for clinical use. The availability of this technology will improve the assessment of adherence to aripiprazole and the optimising of aripiprazole dosing.
To minimise infection during COVID-19, the clozapine haematological monitoring interval was extended from 4-weekly to 12-weekly intervals in South London and Maudsley NHS Foundation Trust.
To investigate the impact of this temporary policy change on clinical and safety outcomes.
All patients who received clozapine treatment with extended (12-weekly) monitoring in a large London National Health Service trust were included in a 1-year mirror-image study. A comparison group was selected with standard monitoring. The proportion of participants with mild to severe neutropenia and the proportion of participants attending the emergency department for clozapine-induced severe neutropenia treatment during the follow-up period were compared. Psychiatric hospital admission rates, clozapine dose and concomitant psychotropic medication in the 1 year before and the 1 year after extended monitoring were compared. All-cause clozapine discontinuation at 1-year follow-up was examined.
Of 569 participants, 459 received clozapine with extended monitoring and 110 controls continued as normal. The total person-years were 458 in the intervention group and 109 in the control group, with a median follow-up time of 1 year in both groups. During follow-up, two participants (0.4%) recorded mild to moderate neutropenia in the intervention group and one (0.9%) in the control group. There was no difference in the incidence of haematological events between the two groups (IRR = 0.48, 95% CI 0.02–28.15, P = 0.29). All neutropenia cases in the intervention group were mild, co-occurring during COVID-19 infection. The median number of admissions per patient during the pre-mirror period remained unchanged (0, IQR = 0) during the post-mirror period. There was one death in the control group, secondary to COVID-19 infection.
There was no evidence that the incidence of severe neutropenia was increased in those receiving extended monitoring.
In the aftermath of the COVID-19 pandemic and amid the present reconfiguring of corporate purpose, there is an opportunity to realign actions focused on prolonging working lives. We put forward a transformative agenda concerned with workforce ageing that aligns with contemporary expectations regarding sustainability, inequality, and emerging conceptualisations of management. In this article, the new concept of Common Good human resource management (HRM) is utilised as a potential means of encouraging business responses focused on grand challenges such as population ageing. We suggest how these principles might be applied to the issue of managing age in workplaces, to recast debate about issues of age and work, to be used as an advocacy tool encouraging employer engagement, while providing a framework that might direct organisational leadership.
This article increases understanding of university labour processes. The antecedents and characteristics of early retirement schemes implemented by Australian universities between 2010 and 2020 were considered. Twenty-eight schemes were identified across 20 universities. Content analysis of descriptions of the schemes contained in official documents was undertaken. This revealed somewhat common justifications for the schemes, linked to concerns about organisational sustainability/resilience in the face of external threats and the implementation of modernising efforts. Such justifications appeared to be underpinned by similar ageist biases on the part of management. Despite this broad commonality, however, the schemes manifested a multifurcation of possible work-retirement pathways across institutions. Such reorganisation of labour processes, based on ageist representations that potentially place established workers in conflict with others, represents an incongruence between the market-oriented objectives of universities and areas of public policy responding to workforce ageing. It is argued that drawing momentum from emerging conceptions of sustainability and current diversity initiatives such as Athena Swan and Age Friendly Universities it may be possible to sever the link university leadership perceive between the divestment of older workers and the fulfilment of modernising agendas.
Clozapine is licensed for treatment-resistant psychosis and remains underutilised. This may berelated to the stringent haematological monitoring requirements that are mandatory in most countries. We aimed to compare guidelines internationally and develop a novel Stringency Index. We hypothesised that the most stringent countries would have increased healthcare costs and reduced prescription rates.
We conducted a literature review and survey of guidelines internationally. Guideline identification involved a literature review and consultation with clinical academics. We focused on the haematological monitoring parameters, frequency and thresholds for discontinuation and rechallenge after suspected clozapine-induced neutropenia. In addition, indicators reflecting monitoring guideline stringency were scored and visualised using a choropleth map. We developed a Stringency Index with an international panel of clozapine experts, through a modified-Delphi-survey. The Stringency Index was compared to health expenditure per-capita and clozapine prescription per 100 000 persons.
One hundred twocountries were included, from Europe (n = 35), Asia (n = 24), Africa (n = 20), South America (n = 11), North America (n = 7) and Oceania and Australia (n = 5). Guidelines differed in frequency of haematological monitoring and discontinuation thresholds. Overall, 5% of included countries had explicit guidelines for clozapine-rechallenge and 40% explicitly prohibited clozapine-rechallenge. Furthermore, 7% of included countries had modified discontinuation thresholds for benign ethnic neutropenia. None of the guidelines specified how long haematological monitoring should continue. The most stringent guidelines were in Europe, and the least stringent were in Africa and South America. There was a positive association (r = 0.43, p < 0.001) between a country's Stringency Index and healthcare expenditure per capita.
Recommendations on how haematological function should be monitored in patients treated with clozapine vary considerably between countries. It would be useful to standardise guidelines on haematological monitoring worldwide.
There has been a notable increase in requests for psychiatric reports from District Courts for persons remanded to Ireland’s main remand prison, Cloverhill. We aimed to identify if reports were prepared for persons with severe mental illness and if they led to therapeutic benefits such as diversion to healthcare. Measures of equitability between Cloverhill and other District Courts were explored.
For District Court-requested reports completed by the Prison Inreach and Court Liaison Service (PICLS) at Cloverhill Prison from 2015 to 2017, we recorded clinical variables and therapeutic outcomes such as diversion to inpatient psychiatric settings.
Of 236 cases, over half were diverted to inpatient or outpatient psychiatric care. One-third of remand episodes were admitted to a psychiatric hospital, mainly in non-forensic settings. Nearly two-thirds had major mental illness, mainly schizophrenia and related conditions. Almost half had active psychosis. Cases in Cloverhill District Court and other District Courts were similarly likely to have active psychosis (47% overall) and hospital admission (33% overall). Voluntary reports were more likely to identify active psychosis, with over 90% diverted to inpatient or outpatient community treatment settings.
This is the first large scale study of diversion outcomes following requests for psychiatric advice from District Courts in Ireland. Requests were mainly appropriate. Over half led to diversion from the criminal justice system to healthcare settings. There is a need for a complementary network of diversion initiatives at every stage of the criminal justice system to effectively divert mentally ill individuals to appropriate settings at the earliest possible stage.
It has often been stated by older people's advocates that discrimination affecting older people is commonplace and ongoing in the Australian labour market. In this article, we contrast such rhetoric with a review of evidence from recent large-scale surveys which demonstrates that low and declining numbers of Australians experience age discrimination, while highlighting the complexity of the phenomenon. We identify the emergence of a fake ‘age’ advocacy that is acting to the detriment of an informed public discourse concerning issues of older workers’ employment. To counter this we propose five underlying principles for advocacy on ageing and work: countering myths concerning the extent and nature of age barriers in the labour market; avoiding and challenging the use of age stereotypes in making the business case for older workers’ employment; recognition that age interacts in complex ways with a range of other factors in determining people's experiences of the labour market; challenging public understanding that is grounded in the notion that generational conflict is inevitable; and discarding traditional notions of the lifecourse in order to overcome disjunctions and contradictions that hamper efforts to encourage and support longer working lives.
Diets varying in SFA and MUFA content can impact glycaemic control; however, whether underlying differences in genetic make-up can influence blood glucose responses to these dietary fatty acids is unknown. We examined the impact of dietary oils varying in SFA/MUFA content on changes in blood glucose levels (primary outcome) and whether these changes were modified by variants in the stearoyl-CoA desaturase (SCD) gene (secondary outcome). Obese men and women participating in the randomised, crossover, isoenergetic, controlled-feeding Canola Oil Multicenter Intervention Trial II consumed three dietary oils for 6 weeks, with washout periods of ˜6 weeks between each treatment. Diets studied included a high SFA/low MUFA Control oil (36·6 % SFA/28·2 % MUFA), a conventional canola oil (6·2 % SFA/63·1 % MUFA) and a high-oleic acid canola oil (5·8 % SFA/74·7 % MUFA). No differences in fasting blood glucose were observed following the consumption of the dietary oils. However, when stratified by SCD genotypes, significant SNP-by-treatment interactions on blood glucose response were found with additive models for rs1502593 (P = 0·01), rs3071 (P = 0·02) and rs522951 (P = 0·03). The interaction for rs3071 remained significant (P = 0·005) when analysed with a recessive model, where individuals carrying the CC genotype showed an increase (0·14 (sem 0·09) mmol/l) in blood glucose levels with the Control oil diet, but reductions in blood glucose with both MUFA oil diets. Individuals carrying the AA and AC genotypes experienced reductions in blood glucose in response to all three oils. These findings identify a potential new target for personalised nutrition approaches aimed at improving glycaemic control.
Haematopoietic stem cell transplantation is an important and effective treatment strategy for many malignancies, marrow failure syndromes, and immunodeficiencies in children, adolescents, and young adults. Despite advances in supportive care, patients undergoing transplant are at increased risk to develop cardiovascular co-morbidities.
This study was performed as a feasibility study of a rapid cardiac MRI protocol to substitute for echocardiography in the assessment of left ventricular size and function, pericardial effusion, and right ventricular hypertension.
A total of 13 patients were enrolled for the study (age 17.5 ± 7.7 years, 77% male, 77% white). Mean study time was 13.2 ± 5.6 minutes for MRI and 18.8 ± 5.7 minutes for echocardiogram (p = 0.064). Correlation between left ventricular ejection fraction by MRI and echocardiogram was good (ICC 0.76; 95% CI 0.47, 0.92). None of the patients had documented right ventricular hypertension. Patients were given a survey regarding their experiences, with the majority both perceiving that the echocardiogram took longer (7/13) and indicating they would prefer the MRI if given a choice (10/13).
A rapid cardiac MRI protocol was shown feasible to substitute for echocardiogram in the assessment of key factors prior to or in follow-up after haematopoietic stem cell transplantation.
Performing an extended Focused Assessment with Sonography in Trauma (eFAST) exam is common practice in the initial assessment of trauma patients. The objective of this study was to systematically review the published literature on diagnostic accuracy of all components of the eFAST exam.
We searched Medline and Embase from inception through October 2018, for diagnostic studies examining the sensitivity and specificity of the eFAST exam. After removal of duplicates, 767 records remained for screening, of which 119 underwent full text review. Meta-DiSc™ software was used to create pooled sensitivities and specificities for included studies. Study quality was assessed using the Quality in Prognostic Studies (QUADAS-2) tool.
Seventy-five studies representing 24,350 patients satisfied our selection criteria. Studies were published between 1989 and 2017. Pooled sensitivities and specificities were calculated for the detection of pneumothorax (69% and 99% respectively), pericardial effusion (91% and 94% respectively), and intra-abdominal free fluid (74% and 98% respectively). Sub-group analysis was completed for detection of intra-abdominal free fluid in hypotensive (sensitivity 74% and specificity 95%), adult normotensive (sensitivity 76% and specificity 98%) and pediatric patients (sensitivity 71% and specificity 95%).
Our systematic review and meta-analysis suggests that e-FAST is a useful bedside tool for ruling in pneumothorax, pericardial effusion, and intra-abdominal free fluid in the trauma setting. Its usefulness as a rule-out tool is not supported by these results.
Traits of attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are strongly associated in children and adolescents, largely due to genetic factors. Less is known about the phenotypic and aetiological overlap between ADHD and ASD traits in adults.
We studied 6866 individuals aged 20–28 years from the Swedish Study of Young Adult Twins. Inattention (IA) and hyperactivity/impulsivity (HI) were assessed using the WHO Adult ADHD Self-Report Scale-V1.1. Repetitive and restricted behaviours (RRB) and social interaction and communication (SIC) were assessed using the Autism-Tics, ADHD, and other Comorbidities inventory. We used structural equation modelling to decompose covariance between these ADHD and ASD trait dimensions into genetic and shared/non-shared environmental components.
At the phenotypic level, IA was similarly correlated with RRB (r = 0.33; 95% Confidence Interval (CI) 0.31–0.36) and with SIC (r = 0.32; 95% CI 0.29–0.34), whereas HI was more strongly associated with RRB (r = 0.38; 95% CI 0.35–0.40) than with SIC (r = 0.24; 95% CI 0.21–0.26). Genetic and non-shared environmental effects accounted for similar proportions of the phenotypic correlations, whereas shared environmental effects were of minimal importance. The highest genetic correlation was between HI and RRB (r = 0.56; 95% 0.46–0.65), and the lowest was between HI and SIC (r = 0.33; 95% CI 0.23–0.43).
We found evidence for dimension-specific phenotypic and aetiological overlap between ADHD and ASD traits in adults. Future studies investigating mechanisms underlying comorbidity between ADHD and ASD may benefit from exploring several symptom-dimensions, rather than considering only broad diagnostic categories.
The tufa deposits of the Ghaap Plateau escarpment provide a rich, yet minimally explored, geological archive of climate and environmental history coincident with hominin evolution in South Africa. This study examines the sedimentary and geochemical records of ancient and modern tufas from Buxton-Norlim Limeworks, Groot Kloof, and Gorrokop, to assess the potential of these sediments for providing reliable chronologies of high-resolution, paleoenvironmental information. Chronometric dating demonstrates that tufa formation has occurred from at least the terminal Pliocene through to the modern day. The stable isotope records show a trend toward higher, more variable δ18O and δ13C values with decreasing age from the end of the Pliocene onwards. The long-term increase in δ18O values corresponds to increasingly arid conditions, while increasing δ13C values reflect the changing proportion of C3/C4 vegetation in the local environment. Analysis of the Thabaseek Tufa, in particular, provides valuable evidence for reconstructing the depositional and chronological context of the enigmatic Taung Child (Australopithecus africanus). Collectively, the results of the present study demonstrate the potential of these deposits for developing high-precision records of climate change and ultimately, for understanding the causal processes relating climate and hominin evolution.
Late Medieval Castles is a companion to Anglo-Norman Castles (2003), a volume that brought together a series of historiographically significant articles on castles and castle-building in the period from the Norman Conquest to the early thirteenth century. The format and themes of the present collection are broadly comparable with the earlier book, but with the focus on those castles dating to the period c.1250–1500.
In the course of bringing Anglo-Norman Castles to publication the somewhat arbitrary cut-off date of c.1225 seemed unsatisfactory for a number of reasons. On a practical level, there were highly relevant articles that could not be included because the subject matter fell outside the chronological range of the volume. A more scholarly concern was the fact that a number of issues pertinent to castle-building in the eleventh and twelfth centuries could not be satisfactorily addressed without reference to subsequent developments in the thirteenth and fourteenth. Allied to this, a focus on Anglo-Norman building (no matter how justifiable in historical terms) does perhaps contribute, albeit unwittingly, to the erroneous idea that the eleventh and twelfth centuries are the most important centuries for castle-building, a time when the ‘true’ castle is to be found, and that the period that follows, particularly after 1300, is something of an anti-climax. The present volume should therefore be seen as a continuation of the broad themes discussed in the introduction to Anglo-Norman Castles, with the aim of pursuing them in a late medieval context.
In the years since 2003 there have been a number of important publications in the field of castle studies, and castles continue to be a source of controversy and to provoke debate. Despite the fact that the availability of some secondary material has been made easier through electronic access, I have been consistently reminded by academic colleagues that a compilation such as this is worthwhile, both for the student reader and those seeking a path into the specialist secondary literature. This author at least also believes that there is value in bringing together in one place a series of important contributions that have defined the subject and which also illustrate a diversity of approaches.