The interplay between suicidal experiences, psychotic experiences and interpersonal relationships: a qualitative study.

BACKGROUND: Suicidal thoughts, acts, plans and deaths are considerably more prevalent in people with non-affective psychosis, including schizophrenia, compared to the general population. Social isolation and interpersonal difficulties have been implicated in pathways which underpin suicidal experiences in people with severe mental health problems. However, the interactions between psychotic experiences, such as hallucinations and paranoia, suicidal experiences, and the presence, and indeed, absence of interpersonal relationships is poorly understood and insufficiently explored. The current study sought to contribute to this understanding. METHODS: An inductive thematic analysis was conducted on transcripts of 22, individual, semi-structured interviews with adult participants who had both non-affective psychosis and recent suicidal experiences. A purposive sampling strategy was used. Trustworthiness of the analysis was assured with researcher triangulation. RESULTS: Participants relayed both positive and negative experiences of interpersonal relationships. A novel conceptual model is presented reflecting a highly complex interplay between a range of different suicidal experiences, psychosis, and aspects of interpersonal relationships. Three themes fed into this interplay, depicting dynamics between perceptions of i. not mattering and mattering, ii. becoming disconnected from other people, and iii. constraints versus freedom associated with sharing suicidal and psychotic experiences with others. CONCLUSION: This study revealed a detailed insight into ways in which interpersonal relationships are perceived to interact with psychotic and suicidal experiences in ways that can be both beneficial and challenging. This is important from scientific and clinical perspectives for understanding the complex pathways involved in suicidal experiences. TRIAL REGISTRATION: ClinicalTrials.gov (NCT03114917), 14th April 2017. ISRCTN (reference ISRCTN17776666 .); 5th June 2017). Registration was recorded prior to participant recruitment commencing.

Automated processing of fluorescence in-situ hybridization slides for HER2 testing in breast and gastro-esophageal carcinomas.

BACKGROUND: HER2 fluorescence in-situ hybridization (FISH) is used in breast and gastro-esophageal carcinoma for determining HER2 gene amplification and patients' eligibility for HER2 targeted therapeutics. Traditional manual processing of the FISH slides is labor intensive because of multiple steps that require hands on manipulation of the slides and specifically timed intervals between steps. This highly manual processing also introduces inter-run and inter-operator variability that may affect the quality of the FISH result. Therefore, we sought to incorporate an automated processing instrument into our FISH workflow. METHODS: Twenty-six cases including breast (20) and gastro-esophageal (6) cancer comprising 23 biopsies and three excision specimens were tested for HER2 FISH (Pathvysion, Abbott) using the Thermobrite Elite (TBE) system (Leica). Up to 12 slides can be run simultaneously. All cases were previously tested by the Pathvysion HER2 FISH assay with manual preparation. Twenty cells were counted by two observers for each case; five cases were tested on three separate runs by different operators to evaluate the precision and inter-operator variability. RESULTS: There was 100% concordance in the scoring between the manual and TBE methods as well as among the five cases that were tested on three runs. Only one case failed due to poor probe hybridization. In total, seven cases were positive for HER2 amplification (HER2:CEP17 ratio >2.2) and the remaining 19 were negative (HER2:CEP17 ratio <1.8) utilizing the 2007 ASCO/CAP scoring criteria. Due to the automated denaturation and hybridization, for each run, there was a reduction in labor of 3.5h which could then be dedicated to other lab functions. CONCLUSION: The TBE is a walk away pre- and post-hybridization system that automates FISH slide processing, improves work flow and consistency and saves approximately 3.5h of technologist time. The instrument has a small footprint thus occupying minimal counter space. TBE processed slides performed exceptionally well in comparison to the manual technique with no disagreement in HER2 amplification status.

A pilot study exploring quality of life experienced by patients undergoing negative-pressure wound therapy as part of their wound care treatment compared to patients receiving standard wound care.

The use of negative pressure wound therapy (NPWT) has been widely documented as a technique to help heal complex wounds. This article presents the findings of a preliminary study which aimed to explore quality of life (QoL) experienced by patients undergoing NPWT as part of their wound care treatment in comparison to that of patients with a wound using traditional (standard) wound care therapies. A quasi-experimental study was undertaken, with patients treated in wound care/vascular clinics with chronic/acute wounds. QoL impact was measured using the Cardiff Wound Impact Schedule and administered post-consent at timed intervals. Our results identified that there were no real differences in QoL scores recorded by patients over the 12-week period. Although there was no overall interaction between the therapies used for wound healing, NPWT did have an effect on social life: during the first 2 weeks of the application of therapy, patients in the NPWT group reported an increase in the social life domain. The authors conclude that true QoL can only be elicited if an accurate baseline is established or if data is collected over a long enough period to allow comparison of scores over time.

Is EGD Needed in all Patients after Suicidal or Exploratory Caustic Ingestions?

BACKGROUND: Caustic ingestions are relatively uncommon, but remain a significant source of morbidity. Patients with caustic injury often undergo an urgent EGD, although it is not clear if an EGD is routinely needed in an asymptomatic patient. The study has two primary objectives; 1) to determine the utility of routine EGD in asymptomatic suicidal caustic ingestions; 2) to determine if asymptomatic unintentional acidic ingestions can be managed with observation alone, similar to basic ingestions. METHODS: This retrospective study, which took place at 14 hospitals in three countries evaluated all patients who presented with a caustic ingestion between 2014-2020. The presence of symptoms and esophageal injury, demographic information, pH of ingested substance, reason for the ingestion, and outcome were recorded. RESULTS: 409 patients were identified; 203 (46.9%) were male. The median (IQR) age was 18 (4-31) years; overall range 10 months to 78 years. Suicidal ingestions accounted for 155 (37.9%) of cases. Dysphagia or dysphonia were more likely in those with significant esophageal injury compared to those without (59.3% vs. 12.6% respectively; OR 10.1; 95% CI 4.43-23.1). Among 27 patients with significant esophageal injury, 48% were found in suicidal patients, compared with 51.9% in non-suicidal patients (p = NS). On multivariate regression, there was no difference in the rate of significant esophageal injury among suicidal vs. non suicidal patients (aOR 1.55; p = 0.45, 95% CI 0.45-5.33). Most ingestions involved basic substances (332/409; 81.2%). Unknown or mixed ingestions accounted for 25 (6.11%) of the ingestions. Significant esophageal burns were found in 6/52 (11.5%) of acid ingestions, compared with 21/332 (6.3%) of basic ingestions. Of the 42 cases of acidic ingestions without dysphagia or odynophagia, 2 (4.8%; 0.58-16.1%) had significant esophageal burns, compared with 9 (3.2%; 95% CI 1.4-5.9%) of the 284 basic ingestions; p = 0.64). On multivariate logistic regression, patients with acidic ingestions were not more likely to experience a significant burn (aOR 1.7; p = 0.11, 95% CI 0.9-3.1) compared to those with basic ingestions. No patient with significant esophageal burns was asymptomatic. CONCLUSION: In this study, there was no statistical differences in the rates of significant burns between acidic and basic caustic ingestions. There were no significant esophageal injuries noted among asymptomatic patients.

Final year student nurses' experiences of wound care: an evaluation.

This article reports on research to explore if pre-registration nursing students felt prepared to manage patients' skin integrity effectively on registration. Final year nursing students completing adult, child and mental health fields were invited to complete questionnaires to investigate the amount of teaching sessions delivered in university in relation to managing skin integrity during their 3-year training programme, discover if pre-registration nursing students received supplementary management of skin integrity teaching in the clinical areas, explore which member of staff in the clinical areas supported the students' learning in the area of skin integrity. Data was collected on 217 final year students (196 females and 21 males) at two higher education institutions in the north of England. The majority of respondents (n = 146; 68%) reported receiving less than 10 hours formal teaching at university on the subject of skin integrity over their 3-year courses. Of those registered on degree courses, 134 students (71%) reported receiving less than 10 hours formal teaching over their 3-year courses, compared with only 12 students (46%) registered on diploma courses. Some 198 (99%) of respondents reported that their clinical teaching was undertaken by registered nurses all or some of the time. Other health professionals were reported to provide substantially less clinical teaching; with the next largest contribution reported to be provided by specialist nurses, who provided all clinical teaching to 36 respondents (19%) and some clinical teaching to 115 respondents (59%). Some 149 respondents (70%) reported that the teaching they received had developed their knowledge and skills to maintain skin integrity for all patients. Respondents claimed that teaching received had developed their knowledge and skills, reporting an average of 16.9 hours spent in directed study; whereas those who did not claim that teaching they had received had developed their knowledge and skills reported an average of 7.6 hours spent in directed study. The results of this study suggest that diplomate nurses are likely to feel more confident and competent than their graduate counterparts, despite spending the same amount of time with mentors and their peers.

Validation of a rapid HLA-DQA1*05 pharmacogenomics assay to identify at-risk resistance to anti-tumor necrosis factor therapy among patients with inflammatory bowel disease.

OBJECTIVES: The HLA-DQA1*05 variant (rs2097432) is associated with increased risk of immunogenicity to tumor necrosis factor antagonists, with subsequent resistance to therapy in patients with inflammatory bowel disease. Identification of these patients would optimize personalized therapeutic selection. METHODS: Genomic DNA was extracted from 80 deidentified samples in an unselected patient population with an unknown rs2097432 genotype. Split sample analysis was performed using a reference laboratory. Primer probes for a TaqMan quantitative polymerase chain reaction (qPCR) assay (Thermo Fisher Scientific) were custom designed. Synthesized genomic-block fragments were used as controls. All qPCR reactions were performed using a TaqMan GTXpress Master Mix (Thermo Fisher Scientific) on the Applied Biosystems 7500 system under fast cycling conditions. RESULTS: Of 80 samples, 50% were wild-type reference genotypes, 22.5% were heterozygous, and 27.5% were homozygous variant calls, comparable to population data. Split analysis samples between 2 independent laboratories were 100% concordant. The detection limit tested across genomic-block controls processed in duplicate was reproducible on sample input from 10 ng titrated down to 1.25 ng across 2 independent runs. Further, analytical specificity assessed with previous wild-type reference and homozygous variant DNA spiked into genomic-block controls produced appropriate heterozygous genotypes. CONCLUSIONS: Here we present validation of a lab-developed test for a rapid HLA-DQA1*05 (rs2097432) pharmacogenomics assay targeting a hotspot identified by genome-wide association studies. Targeted genotyping employed here will allow for expeditious personalized therapeutic selection.

Potential Impact of Pharmacogenomic Single Nucleotide Variants in a Rural Caucasian Population.

BACKGROUND: In the US adverse drug reactions (ADRs) are estimated to cause 100 000 fatalities and cost over $136 billion annually. A patient's genes play a significant role in their response to a drug. Pharmacogenomics aims to optimize drug choice and dose for individual patients by characterizing patients' pharmacologically relevant genes to identify variants of known impact. METHODS: DNA was extracted from randomly selected remnant whole blood samples from Caucasian patients with previously performed complete blood counts. Samples were genotyped by mass spectrometry using a customized pharmacogenomics panel. A third-party result interpretation service used genotypic results to predict likely individual responses to frequently prescribed drugs. RESULTS: Complete genotypic and phenotypic calls for all tested Cytochrome P450 isoenzymes and other genes were obtained from 152 DNA samples. Of these 152 unique genomic DNA samples, 140 had genetic variants suggesting dose adjustment for at least one drug. Cardiovascular and psychiatry drugs had the highest number of recommendations, which included United States Food and Drug Administration warnings for highly prescribed drugs metabolized by CYP2C19, CYP2C9, CYP2D6, HLA-A, and VKORC1. CONCLUSIONS: Risk for each drug:gene pairing primarily depends upon the degree of predicted enzyme impairment or activation, width of the therapeutic window, and whether parent compound or metabolite is pharmacologically active. The resulting metabolic variations range from risk of toxicity to therapeutic failure. Pharmacogenomic profiling likely reduces ADR potential by allowing up front drug/dose selection to fit a patient's unique drug-response profile.

Acceptability of a novel suicide prevention psychological therapy for people who experience non-affective psychosis.

OBJECTIVES: Suicide is a leading cause of death worldwide. People experiencing psychosis are at increased risk of death by suicide. Talking therapies can alleviate suicidal thoughts, plans, and attempts. Therapies need to also be acceptable to recipients. The aim of this study was to investigate the views on psychological therapy for people experiencing psychosis and suicidality using the Theoretical Framework of Acceptability. DESIGN: Qualitative interview study. METHODS: Participants were recruited from a randomised controlled trial comparing suicide prevention psychological therapy with treatment as usual. Individuals had a diagnosis of non-affective psychosis and experience of suicidal thoughts, plans and/or attempts. To assess the acceptability of the therapy, semi-structured interviews were conducted with 20 participants randomised to receive therapy. Data were deductively analysed using an adaptation of the Theoretical Framework of Acceptability. RESULTS: Interviews (Mean = 45 min) were conducted and audio recorded with 21 participants. Data were organised into six themes: 1. Affective attitude, 2. Burden, 3. Alliance, 4. Intervention coherence, 5. Perceived effectiveness, and 6. Self-efficacy. There was no evidence of issues relating to domains of ethicality and opportunity costs associated with receiving therapy. CONCLUSIONS: Talking about suicide was difficult and, at times, distressing, but it was perceived to be useful for understanding experiences. To be acceptable, it is important for therapists to ensure that clients' understanding of therapy aligns with expectations of effectiveness and to invest in building strong therapeutic alliances. Future research will benefit from examining therapists' experiences of delivering therapy through different modes (e.g. online, telephone).

What is important to service users and staff when implementing suicide-focused psychological therapies for people with psychosis into mental health services?

Introduction: Suicide is a leading cause of death globally. People with psychosis are at increased risk of suicide death and up to half experience suicidal thoughts and/or engage in suicidal behaviors in their lifetime. Talking therapies can be effective in alleviating suicidal experiences. However, research is yet to be translated into practice, demonstrating a gap in service provision. The barriers and facilitators in therapy implementation require a thorough investigation including the perspectives of different stakeholders such as service users and mental health professionals. This study aimed to investigate stakeholders' (health professionals and service users) perspectives of implementing a suicide-focused psychological therapy for people experiencing psychosis in mental health services. Methods: Face-to-face, semi-structured interviews with 20 healthcare professionals and 18 service users were conducted. Interviews were audio recorded and transcribed verbatim. Data were analyzed and managed using reflexive thematic analysis and NVivo software. Results: For suicide-focused therapy to be successfully implemented in services for people with psychosis, there are four key aspects that need to be considered: (i) Creating safe spaces to be understood; (ii) Gaining a voice; (iii) Accessing therapy at the right time; and (iv) Ensuring a straightforward pathway to accessing therapy. Discussion: Whilst all stakeholders viewed a suicide-focused therapy as valuable for people experiencing psychosis, they also recognize that enabling successful implementation of such interventions will require additional training, flexibility, and resources to existing services.

Understanding patient reported outcome measures (PROMs).

Patient-reported outcome measures (PROMs) have been identified as being measures of a patient's health status or health-related quality of life, allowing for health status information to be collected from patients before and after an intervention through completion of a questionnaire. The information collected will provide an indication of the outcomes or quality of care delivered to NHS Patients. The collection of data commenced in April 2009 for specific conditions; NHS-funded unilateral hip replacements, unilateral knee replacements, groin hernia surgery or varicose vein surgery. PROMs will be developed for further conditions in the future, however, at present there are none relating to tissue viability or leg ulceration.

Clinical Validation of a 106-SNV MALDI-ToF MS Pharmacogenomic Panel.

BACKGROUND: Laboratorians have the opportunity to help minimize the frequency of adverse drug reactions by implementing pharmacogenomic testing and alerting care providers to possible patient/drug incompatibilities before drug treatment is initiated. Methods combining PCR with MALDI-ToF MS have allowed for sensitive, economical, and multiplexed pharmacogenomic testing results to be delivered in a timely fashion. METHOD: This study evaluated the analytical performance of the Agena Biosciences iPLEX® PGx 74 panel and a custom iPLEX panel on a MassARRAY MALDI-TOF MS instrument in a clinical laboratory setting. Collectively, these panels evaluate 112 SNVs across 34 genes implicated in drug response. Using commercially available samples (Coriell Biorepository) and in-house extracted DNA, we determined ideal reaction conditions and assessed accuracy, precision, and robustness. RESULTS: Following protocol optimization, the Agena PGx74 and custom panels demonstrated 100% concordance with the 1000 Genomes Project Database and clinically validated hydrolysis probe genotyping assays. 100% concordance was also observed in all assessments of assay precision when appropriate QC metrics were applied. CONCLUSIONS: Significant development time was required to optimize sample preparation and instrumental analysis and 3 assays were removed due to inconsistent performance. Following modification of the manufacturer's protocol and instituting manual review of each assay plate, the Agena PGx74 and custom panel constitute a cost-effective, robust, and accurate method for clinical identification of 106 SNVs involved in drug response.

Thermal oligomerisation of aryl isocyanides: formation of pyrazino[1,2-a:4,5-a']diindoles and indigo diarylimines.

The aryl isocyanides 1-4 are converted at 150 degrees C into the hexameric pyrazino[1,2-a:4,5-a']diindoles 15-19. 4-Fluorophenyl isocyanide, when heated at 135 degrees C, gave the hexamer 19 and the tetrameric indigo di-arylimine 9, and when kept at ambient temperature gave mainly the tetramer 9 in low yield. The structures of the hexamer 19 and the tetramer 9 were established by X-ray crystallography. Mechanisms are proposed for the oligomerisation reactions.