A tuning fork-shaped bisbenzothiazole derivative as a pH-responsive digital fluorescent probe and its ex vivo evaluation.

A new highly emissive pH-responsive near-IR active digital probe was designed and synthesized. The probe is based on a bisbenzothiazole motif with a highly vulnerable hydrogen unit attached in an intramolecular fashion. The probe produced a large Stokes shift which was observed to be highly pH dependent. The optical pH dependence can be used for sensing pH over a wide range.

What is the role of doctors in respect of suspects with mental health and intellectual disabilities in police custody?

People with severe mental illness and intellectual disabilities are overrepresented in the criminal justice system worldwide and this is also the case in Ireland. Following Ireland's ratification of the United Nations' Convention on the Rights of People with Disabilities in 2018, there has been an increasing emphasis on ensuring access to justice for people with disabilities as in Article 13. For people with mental health and intellectual disabilities, this requires a multi-agency approach and a useful point of intervention may be at the police custody stage. Medicine has a key role to play both in advocacy and in practice. We suggest a functional approach to assessment, in practice, and list key considerations for doctors attending police custody suites. Improved training opportunities and greater resources are needed for general practitioners and psychiatrists who attend police custody suites to help fulfill this role.

Does Lent affect rates of deliberate self-harm?

BACKGROUND: Research has shown that religious affiliation has a protective effect against deliberate self-harm. This is particularly pronounced in periods of increased religious significance, such as periods of worship, celebration, and fasting. However, no data exist as to whether this effect is present during the Christian period of Lent. Our hypothesis was that Lent would lead to decreased presentations of self-harm emergency department (ED) in a predominantly Catholic area of Ireland. METHODS: Following ethical approval, we retrospectively analysed data on presentations to the ED of University Hospital Limerick during the period of Lent and the 40 days immediately preceding it. Frequency data were compared using Pearson's chi-squared tests in SPSS. RESULTS: There was no significant difference in the overall number of people presenting to the ED with self-harm during Lent compared to the 40 days preceding it (χ2 = 0.75, df = 1, p > 0.05), and there was no difference in methods of self-harm used. However, there was a significant increase in attendances with self-harm during Lent in the over 50's age group (χ2 = 7.76, df = 1, p = 0.005). CONCLUSIONS: Based on our study, Lent is not a protective factor for deliberate self-harm and was associated with increased presentations in the over 50's age group. Further large-scale studies are warranted to investigate this finding as it has implications for prevention and management of deliberate self-harm.

European Society of Cardiology quality indicators for the prevention and management of cancer therapy-related cardiovascular toxicity in cancer treatment.

AIMS: To develop quality indicators (QIs) for the evaluation of the prevention and management of cancer therapy-related cardiovascular toxicity. METHODS AND RESULTS: We followed the European Society of Cardiology (ESC) methodology for QI development which comprises (i) identifying the key domains of care for the prevention and management of cancer therapy-related cardiovascular toxicity in patients on cancer treatment, (ii) performing a systematic review of the literature to develop candidate QIs, and (iii) selecting of the final set of QIs using a modified Delphi process. Work was undertaken in parallel with the writing of the 2022 ESC Guidelines on Cardio-Oncology and in collaboration with the European Haematology Association, the European Society for Therapeutic Radiology and Oncology and the International Cardio-Oncology Society. In total, 5 main and 9 secondary QIs were selected across five domains of care: (i) Structural framework, (ii) Baseline cardiovascular risk assessment, (iii) Cancer therapy related cardiovascular toxicity, (iv) Predictors of outcomes, and (v) Monitoring of cardiovascular complications during cancer therapy. CONCLUSION: We present the ESC Cardio-Oncology QIs with their development process and provide an overview of the scientific rationale for their selection. These indicators are aimed at quantifying and improving the adherence to guideline-recommended clinical practice and improving patient outcomes.

Rationale and design of the PRevention of cArdiac Dysfunction during Adjuvant breast cancer therapy (PRADA II) trial: a randomized, placebo-controlled, multicenter trial.

BACKGROUND: Recent advances in the treatment algorithms of early breast cancer have markedly improved overall survival. However, anthracycline- and trastuzumab-associated cardiotoxicity may lead to dose-reduction or halt in potentially life-saving adjuvant cancer therapy. Early initiated neurohormonal blockade may prevent or attenuate the cardiotoxicity-induced reduction in cardiac function, but prior studies have been inconclusive. The angiotensin receptor-neprilysin inhibitor sacubitril/valsartan has been shown to be superior to traditional treatment in heart failure with reduced ejection fraction, but its cardioprotective effects in the cardio-oncology setting remains to be tested. OBJECTIVE: To assess if sacubitril/valsartan given concomitantly with early breast cancer treatment regimens including anthracyclines, with or without trastuzumab, may prevent cardiac dysfunction. METHODS: PRADA II is a randomized, placebo-controlled, double blind, multi-center, investigator-initiated clinical trial. Breast cancer patients from four university hospitals in Norway, scheduled to receive (neo-)adjuvant chemotherapy with epirubicin independently of additional trastuzumab/pertuzumab treatment, will be randomized 1:1 to sacubitril/valsartan or placebo. The target dose is 97/103 mg b.i.d. The patients will be examined with cardiovascular magnetic resonance (CMR), echocardiography, circulating cardiovascular biomarkers and functional testing at baseline, at end of anthracycline treatment and following 18 months after enrolment. The primary outcome measure of the PRADA II trial is the change in left ventricular ejection fraction (LVEF) by CMR from baseline to 18 months. Secondary outcomes include change in LV function by global longitudinal strain by CMR and echocardiography and change in circulating cardiac troponin concentrations. RESULTS: The study is ongoing. Results will be published when the study is completed. CONCLUSION: PRADA II is the first randomized, placebo-controlled study of sacubitril/valsartan in a cardioprotective setting during (neo-)adjuvant breast cancer therapy. It may provide new insight in prevention of cardiotoxicity in patients receiving adjuvant or neo-adjuvant therapy containing anthracyclines. Furthermore, it may enable identification of patients at higher risk of developing cardiotoxicity and identification of those most likely to respond to cardioprotective therapy. TRIAL REGISTRATION: The trial is registered in the ClinicalTrials.gov registry (identifier NCT03760588 ). Registered 30 November 2018.

Patients and carers as teachers in psychiatric education: a literature review and discussion.

INTRODUCTION: The direct involvement of patients and carers in psychiatric education is driven by policy in the United Kingdom and Ireland. The benefits of this involvement are well known, however, it is important to consider the ethical aspects. This paper suggests how further research could explore and potentially mitigate adverse outcomes. METHOD: A literature search evaluating the role of patients and carer involvement in psychiatric education was undertaken to summarise existing evidence relating to the following: methods of involvement, evidence of usefulness, patient's/carer's views and learners' views. RESULTS: The Medline search produced 231 articles of which 31 were included in the literature review based on the key themes addressed in the paper. DISCUSSION/CONCLUSION: The available evidence is generally positive regarding the use of patients and carers in psychiatric education. However, available research is varied in approach and outcome with little information on the ethical consequences. More research is required to inform policies on teaching regarding potential adverse effects of service user involvement.

The prevalence of major mental illness, substance misuse and homelessness in Irish prisoners: systematic review and meta-analyses.

AimsTo systematically review studies from Irish prisons that estimate the prevalence of major mental illness, alcohol and substance misuse, and homelessness at the time of committal. METHODS: Healthcare databases were searched for studies quantifying the point prevalence for each outcome of interest. Searches were augmented by scanning of bibliographies and searches of governmental and non-governmental websites. Proportional meta-analyses were completed for each outcome. RESULTS: We found eight, six and five studies quantifying the point prevalence of major mental illness, substance misuse, and homelessness respectively. Considerable heterogeneity was found for each subgroup (except psychosis where substantial heterogeneity was observed) and random effects models were used to calculate pooled percentages. The pooled percentage for psychotic disorder was 3.6% [95% confidence interval (CI) 3.0-4.2%], for affective disorder 4.3% (95% CI 2.1-7.1%), for alcohol use disorder 28.3% (95% CI 19.9-37.4%), for substance use disorder 50.9% (95% CI 37.6-64.2%) and for those who were homeless on committal 17.4% (95% CI 8.7-28.4%). CONCLUSIONS: Estimates for the prevalence of psychotic illness and substance abuse amongst Irish prisoners are in keeping with international estimates of morbidity in prisons, whilst those for affective disorders are lower. The prevalence of homelessness in committal to Irish prisons is higher than some international estimates. Rates for psychoses, alcohol and substance misuse as well as homelessness in Irish prisons are significantly higher than the general population prevalence of these vulnerabilities. A need for service development is discussed.

Epilepsy in Irish psychiatric inpatient settings

Aims To ascertain epilepsy prevalence in Irish psychiatric inpatient units and compliance with care planning guidelines. Methods Case records were reviewed in seven psychiatric inpatient units. Results The prevalence of epilepsy across seven psychiatric inpatient units (n=9/267) was three times that of general population estimates. Minimal data was recorded pertaining to seizure type (n=1,11.1%), triggers (n=2,22.2%), clinical investigations relating to epilepsy (n=2,22%) and no epilepsy risk assessments were recorded (n=0,0%). Conclusions The introduction of appropriate care plans is needed to optimise physical and mental wellbeing of those with epilepsy in psychiatric units.

Diversion of Mentally Ill Offenders from the Criminal Justice System in Ireland: Comparison with England and Wales.

AIM: It is generally accepted that certain people who are mentally ill and have contact with the criminal justice system should be diverted to psychiatric care rather than imprisoned. We sought to comment on priorities relating to the development of diversion services in Ireland through comparison with developments in a neighbouring jurisdiction. METHODS: A comparative review was undertaken in relation to the provision for psychiatric diversion across the offender pathway in Ireland and England and Wales. This included legal and service related considerations. RESULTS: In both jurisdictions, services show significant geographical variability. While developments in England and Wales have focussed on the broader offender pathway, diversion services in Ireland are chiefly linked to imprisonment. There is little or no specialist psychiatric expertise available to Gardai in Ireland. Prison In-reach and Court Liaison Services (PICLS) are developing in Ireland but expertise and resourcing are variable geographically. There is a lack of Intensive Care Regional Units (ICRU) in Ireland, in sharp contrast with the availability of Intensive Care and Low Secure Units in England and Wales. There is limited scope to divert to hospital at sentencing stage in the absence of a "hospital order" provision in Irish legislation. CONCLUSIONS: Three areas in the development of Irish diversion services should be prioritised. Firstly, the provision of advice and assistance to Gardai at arrest, custody and initial court hearing stages. Secondly, legislative reform to remove barriers to diverting remand prisoners and facilitating hospital disposal on sentencing. Thirdly, an urgent need to develop of ICRU's (Intensive Care Regional Units) to facilitate provision of appropriate care by local mental health services.

Hunger strikes in prisons: a narrative systematic review of ethical considerations from a physician's perspective.

OBJECTIVES: We sought to identify and review published studies that discuss the ethical considerations, from a physician's perspective, of managing a hunger strike in a prison setting. METHODS: A database search was conducted to identify relevant publications. We included case studies, case series, guidelines and review articles published over a 20-year period. Non-English language publications were translated. RESULTS: The review found 23 papers from 12 jurisdictions published in five languages suitable for inclusion. CONCLUSIONS: Key themes from included publications are identified and summarised in the context of accepted guidelines from the World Medical Association. Whilst there seems to be an overall consensus favouring autonomy over beneficence, tensions along this fine balance are magnified in jurisdictions where legislation leads to a dual loyalty conflict for the physician.

Prospective validation of a novel renal activity index of lupus nephritis.

Objectives The renal activity index for lupus (RAIL) score was developed in children with lupus nephritis as a weighted sum of six urine biomarkers (UBMs) (neutrophil gelatinase-associated lipocalin, monocyte chemotactic protein 1, ceruloplasmin, adiponectin, hemopexin and kidney injury molecule 1) measured in a random urine sample. We aimed at prospectively validating the RAIL in adults with lupus nephritis. Methods Urine from 79 adults was collected at the time of kidney biopsy to assay the RAIL UBMs. Using receiver operating characteristic curve analysis, we evaluated the accuracy of the RAIL to discriminate high lupus nephritis activity status (National Institutes of Health activity index (NIH-AI) score >10), from low/moderate lupus nephritis activity status (NIH-AI score ≤10). Results In this mixed racial cohort, high lupus nephritis activity was present in 15 patients (19%), and 71% had proliferative lupus nephritis. Use of the identical RAIL algorithm developed in children resulted in only fair prediction of lupus nephritis activity status of adults (area under the receiver operating characteristic curve (AUC) 0.62). Alternative weightings of the six RAIL UBMs as suggested by logistic regression yielded excellent accuracy to predict lupus nephritis activity status (AUC 0.88). Accuracy of the model did not improve with adjustment of the UBMs for urine creatinine or albumin, and was little influenced by concurrent kidney damage. Conclusions The RAIL UBMs provide excellent prediction of lupus nephritis activity in adults. Age adaption of the RAIL is warranted to optimize its discriminative validity to predict high lupus nephritis activity status non-invasively.

Hepatic venous outflow tract obstruction: treatment outcomes and development of a new prognostic score.

BACKGROUND: Results of endovascular interventions in hepatic venous outflow tract obstruction (HVOTO) have been reported from limited studies. Treatment outcomes and prognostic scores need further validation. AIM: To evaluate treatment outcomes and prognostic scores for hepatic venous outflow tract obstruction in an Indian population. METHODS: Consecutive patients with hepatic venous outflow tract obstruction diagnosed at a tertiary centre were included. Technical success and clinical response after endovascular interventional therapy were documented. Predictors of survival were assessed with Cox-proportional model. A new score was derived from the factors significant on multivariate analysis and compared with Child-Turcotte-Pugh, model for end-stage liver disease (MELD), Rotterdam prognostic index (PI) and Budd-Chiari syndrome-transjugular intrahepatic portosystemic shunt ( BCS-TIPSS) PI. RESULTS: Three hundred and thirty-four patients (56.6% males), median age 24 (3-62) years were included. Hepatic vein was the commonest site of block-isolated hepatic vonous block in 48%, combined hepatic venous-inferior vena cava block in 46%. Endovascular interventional therapy was performed in 233/334 (70%) with 90% technical success. Clinical response was complete in 166 (71.2%), partial in 58 (24.9%) and no response in nine (3.9%). Majority of cases with HV block did not require TIPSS and could be treated with angioplasty (with/without stenting). On Cox-proportional multivariate analysis, Child class C and response to intervention were independent predictors of outcome and used to derive the All India Institute of Medical Sciences (AIIMS) hepatic venous outflow tract obstruction score. The 5-year survival was 92% (95% CI, 81-97%) for score ≤3, 79% (95%CI, 63-88%) for score >3 and ≤4, and 39% (95% CI, 21-57%) for score >4. The performance of AIIMS hepatic venous outflow obstruction score was superior to other prognostic indices. CONCLUSIONS: Advanced Child class and no response to intervention are associated with poor outcomes. The All India Institute of Medical Sciences hepatic venous outflow tract obstruction score predicts survival better than other prognostic scores.

Lung ultrasound in the ICU: from diagnostic instrument to respiratory monitoring tool.

Imaging has greatly contributed to the understanding of lung disease in the critically ill and currently serves as a tool to diagnose lung pathology, monitor its course, and guide clinical management. Lung ultrasound is a real-time imaging modality that is simple, non-invasive, potentially ubiquitous, and free of ionizing radiation. Its increasing popularity and supporting research data substantiate its role as an emerging technique for bedside chest imaging in critical care. Furthermore, the International Consensus Conference on Lung ultrasound (ICC-LUS) promoted by the World Interactive Network Focused on Critical UltraSound (WINFOCUS) recently standardized the nomenclature and technique for lung ultrasound, and provided recommendations supporting its use in clinical practice. While the utility of lung ultrasound in the emergency setting is unquestioned, its potential role in the more complex and resource-rich intensive care environment is still under investigation. The purpose of this paper was to describe current and potential uses of lung ultrasound in the specific setting of adult intensive care, with an emphasis on respiratory monitoring, and to provide a framework for the practical application of this tool at the bedside.