Effects of intraoperative liposomal bupivacaine on postoperative opioid usage in kidney transplant recipients.

This study retrospectively evaluated the use of intraoperative locally infiltrated peri-incisional liposomal bupivacaine in kidney transplant recipients with the primary outcome of oral morphine equivalent reduction during the transplant admission. Secondary outcomes included pain scores, time to first bowel movement and length of stay. Postoperative morphine equivalents were significantly lower in the liposomal bupivacaine group <24 hours (50% reduction, p < 0.05) and 24-48 hours (56.5% reduction, p < 0.05). When accounting for analgesic medication choices, liposomal bupivacaine did not result in a significant reduction in opioid use within 48 hours postoperatively with the exception of a 51% (p = 0.02) median reduction in fentanyl patient-controlled analgesia morphine equivalents <24 hours postoperatively. Morphine equivalence reductions >48 hours, differences in pain scores, time to first bowel movement or length of stay did not reach significance. Intraoperative liposomal bupivacaine reduced kidney transplant recipient's postoperative opioid requirements, but this benefit did not reliably extend past 24 hours postoperatively.

Promising role for pleural vent in pneumothorax following CT-guided biopsy of lung lesions.

OBJECTIVES: To evaluate the safety, effectiveness and cost-benefit of ambulatory pleural vent compared to conventional chest drain for pneumothorax following CT-guided biopsy of lung lesions (CTGB). METHODS: We retrospectively analysed electronic hospital records of patients requiring intervention for pneumothorax following CTGB. All patients treated with pleural vent over a 2-year period (August 2017-July 2019) were included and compared to a control group of all patients treated with chest drain over a previous 2-year period (August 2014-July 2016). RESULTS: Patients managed with a pleural vent had a shorter length of hospital stay compared to the chest drain group (median 0 days vs 4.5 days, p < 0.01). The mean cost of follow-up in the pleural vent group was £530.36 per patient compared to a mean of £2699.38 per patient in the chest drain group (p-value < 0.01). CONCLUSION: Pleural vent can be a safe and effective alternative to conventional chest drain for the management of CTGB-related pneumothorax which allows patients to be managed on an outpatient basis with reduced hospital stays and lower associated healthcare costs. ADVANCES IN KNOWLEDGE: To the best of our knowledge, this is the first study demonstrating the safety and effectiveness of pleural vent for CTGB-related pneumothorax.

Vaccine-induced protection against hepatitis B in pediatric solid organ transplant patients.

BACKGROUND: Vaccination against hepatitis B virus (HBV) has led to a worldwide reduction in disease burden and mortality. Vaccine immunogenicity data in transplanted children are limited, and vaccine-induced protection may be reduced. We evaluated HBV vaccination coverage, seroprotection rates, and factors influencing vaccine immunity among pediatric solid organ transplant (SOT) patients. METHODS: We retrospectively identified patients ≤21 years of age evaluated for SOT and/or transplanted at our center between January 1, 2015, and December 31, 2018. A detailed chart review was conducted using a standard questionnaire to gather information on demographic, clinical, and laboratory features of patients' HBV vaccination, and hepatitis B surface antibody (HBsAb) titers. RESULTS: A total of 381 patients undergoing evaluation and/or transplantation were included: 139 (36.5%) liver, 138 (36.2%) kidney, and 104 (27.3%) heart. Overall, HBsAb at evaluation was reactive in 216 (56.7%), indeterminate in 17 (4.5%), non-reactive in 138 (36.2%), and not available in 10 (2.6%). Of those that completed a primary HBV vaccine series (n = 304), HBsAb was reactive in 164 (53.9%), indeterminate in 13 (4.3%), non-reactive in 119 (39.1%), and not available in 8 (2.6%). For those up to date for age on HBV vaccinations with non-reactive/indeterminate titers at evaluation, revaccination and a follow-up HBsAb were available in 45 patients of which 33 (73.3%) seroconverted to a reactive HBsAb titer. CONCLUSION: Vaccine-induced protection against HBV infection among high-risk pediatric SOT recipients can be improved by serology-based intervention. Though the absence of HBsAb does not always indicate loss of protection, boosting or completing primary series is recommended.

ONCR-177, an Oncolytic HSV-1 Designed to Potently Activate Systemic Antitumor Immunity.

ONCR-177 is an engineered recombinant oncolytic herpes simplex virus (HSV) with complementary safety mechanisms, including tissue-specific miRNA attenuation and mutant UL37 to inhibit replication, neuropathic activity, and latency in normal cells. ONCR-177 is armed with five transgenes for IL12, FLT3LG (extracellular domain), CCL4, and antagonists to immune checkpoints PD-1 and CTLA-4. In vitro assays demonstrated that targeted miRNAs could efficiently suppress ONCR-177 replication and transgene expression, as could the HSV-1 standard-of-care therapy acyclovir. Although ONCR-177 was oncolytic across a panel of human cancer cell lines, including in the presence of type I IFN, replication was suppressed in human pluripotent stem cell-derived neurons, cardiomyocytes, and hepatocytes. Dendritic cells activated with ONCR-177 tumor lysates efficiently stimulated tumor antigen-specific CD8+ T-cell responses. In vivo, biodistribution analyses suggested that viral copy number and transgene expression peaked approximately 24 to 72 hours after injection and remained primarily within the injected tumor. Intratumoral administration of ONCR-177 mouse surrogate virus, mONCR-171, was efficacious across a panel of syngeneic bilateral mouse tumor models, resulting in partial or complete tumor regressions that translated into significant survival benefits and to the elicitation of a protective memory response. Antitumor effects correlated with local and distant intratumoral infiltration of several immune effector cell types, consistent with the proposed functions of the transgenes. The addition of systemic anti-PD-1 augmented the efficacy of mONCR-171, particularly for abscopal tumors. Based in part upon these preclinical results, ONCR-177 is being evaluated in patients with metastatic cancer (ONCR-177-101, NCT04348916).

CDDO-Me Alters the Tumor Microenvironment in Estrogen Receptor Negative Breast Cancer.

The tumor microenvironment (TME) is an essential contributor to the development and progression of malignancy. Within the TME, tumor associated macrophages (TAMs) mediate angiogenesis, metastasis, and immunosuppression, which inhibits infiltration of tumor-specific cytotoxic CD8+ T cells. In previous work, we demonstrated that the synthetic triterpenoid CDDO-methyl ester (CDDO-Me) converts breast TAMs from a tumor-promoting to a tumor-inhibiting activation state in vitro. We show now that CDDO-Me remodels the breast TME, redirecting TAM activation and T cell tumor infiltration in vivo. We demonstrate that CDDO-Me significantly attenuates IL-10 and VEGF expression but stimulates TNF production, and reduces surface expression of CD206 and CD115, markers of immunosuppressive TAMs. CDDO-Me treatment redirects the TAM transcriptional profile, inducing signaling pathways associated with immune stimulation, and inhibits TAM tumor infiltration, consistent with decreased expression of CCL2. In CDDO-Me-treated mice, both the absolute number and proportion of splenic CD4+ T cells were reduced, while the proportion of CD8+ T cells was significantly increased in both tumors and spleen. Moreover, mice fed CDDO-Me demonstrated significant reductions in numbers of CD4+ Foxp3+ regulatory T cells within tumors. These results demonstrate for the first time that CDDO-Me relieves immunosuppression in the breast TME and unleashes host adaptive anti-tumor immunity.

Profibrotic Activation of Human Macrophages in Systemic Sclerosis.

OBJECTIVE: Genome-wide gene expression studies implicate macrophages as mediators of fibrosis in systemic sclerosis (SSc), but little is known about how these cells contribute to fibrotic activation in SSc. We undertook this study to characterize the activation profile of SSc monocyte-derived macrophages and assessed their interaction with SSc fibroblasts. METHODS: Plasma and peripheral blood mononuclear cells (PBMCs) were obtained from whole blood from SSc patients (n = 24) and age- and sex-matched healthy controls (n = 12). Monocytes were cultured with autologous or allogeneic plasma to differentiate cells into macrophages. For reciprocal activation studies, macrophages were cocultured with fibroblasts using Transwell plates. RESULTS: The gene expression signature associated with blood-derived human SSc macrophages was enriched in SSc skin in an independent cohort and correlated with skin fibrosis. SSc macrophages expressed surface markers associated with activation and released CCL2, interleukin-6, and transforming growth factor ß under basal conditions (n = 8) (P < 0.05). Differentiation of healthy donor monocytes in plasma from SSc patients conferred the immunophenotype of SSc macrophages (n = 13) (P < 0.05). Transwell experiments demonstrated that coculture of SSc macrophages with SSc fibroblasts induced fibroblast activation (n = 3) (P < 0.05). CONCLUSION: These data demonstrate that the activation profile of SSc macrophages is profibrotic. SSc macrophages are activated under basal conditions and release mediators and express surface markers associated with both alternative and inflammatory macrophage activation. These findings also suggest that activation of SSc macrophages arises from soluble factors in local microenvironments. These studies implicate macrophages as likely drivers of fibrosis in SSc and suggest that therapeutic targeting of these cells may be beneficial in ameliorating disease in SSc patients.

Long-term (5-year) clinical evaluation of the Resolute zotarolimus-eluting coronary stent: The RESOLUTE US clinical trial.

OBJECTIVES: To assess the long-term safety and efficacy of the Resolute zotarolimus-eluting stent (R-ZES). BACKGROUND: The R-ZES has been associated with low rates of adverse events over short-intermediate term follow-up. However, reliable assessment of the safety and efficacy of any implanted device requires long-term evaluation. METHODS: The RESOLUTE US trial was a prospective, observational study conducted at 116 U.S. sites and enrolled patients with de novo coronary lesions. Patients were followed clinically for 5 years with independent event adjudication and data monitoring. RESULTS: A total of 1,402 patients (1,573 lesions) were enrolled; 34% had diabetes mellitus and 75% had ACC type B2/C lesions. The 5-year rate of target lesion failure (TLF) was 12.3%, target lesion revascularization was 6.5%, target vessel myocardial infarction was 3.2%, and cardiac death was 4.1%. Dual antiplatelet therapy usage was 94% at 1 year and 47% at 5 years, with a 0.1% and 0.5% respective incidence of definite or probable stent thrombosis. The 5-year rate of TLF was 16.9% among patients with diabetes mellitus and 14.7% in patients with at least one small (≤2.5 mm) vessel treated. Covariates independently associated with 5-year TLF in multivariable analysis included diabetes mellitus (odds ratio [OR] 1.89, p < .001), prior coronary artery bypass grafting (OR 2.28, p < .001), prior myocardial infarction (OR 1.85, p = .002), and smaller reference vessel diameter (OR 1.75, p = .004). CONCLUSIONS: Results from the fully adjudicated and monitored RESOLUTE US trial demonstrate long-term 5-year safety and efficacy of the R-ZES stent among a relatively low-risk population of patients, including a 0.5% rate of stent thrombosis at 5 years.

Use of Natural Language Processing to identify Obsessive Compulsive Symptoms in patients with schizophrenia, schizoaffective disorder or bipolar disorder.

Obsessive and Compulsive Symptoms (OCS) or Obsessive Compulsive Disorder (OCD) in the context of schizophrenia or related disorders are of clinical importance as these are associated with a range of adverse outcomes. Natural Language Processing (NLP) applied to Electronic Health Records (EHRs) presents an opportunity to create large datasets to facilitate research in this area. This is a challenging endeavour however, because of the wide range of ways in which these symptoms are recorded, and the overlap of terms used to describe OCS with those used to describe other conditions. We developed an NLP algorithm to extract OCS information from a large mental healthcare EHR data resource at the South London and Maudsley NHS Foundation Trust using its Clinical Record Interactive Search (CRIS) facility. We extracted documents from individuals who had received a diagnosis of schizophrenia, schizoaffective disorder, or bipolar disorder. These text documents, annotated by human coders, were used for developing and refining the NLP algorithm (600 documents) with an additional set reserved for final validation (300 documents). The developed NLP algorithm utilized a rules-based approach to identify each of symptoms associated with OCS, and then combined them to determine the overall number of instances of OCS. After its implementation, the algorithm was shown to identify OCS with a precision and recall (with 95% confidence intervals) of 0.77 (0.65-0.86) and 0.67 (0.55-0.77) respectively. The development of this application demonstrated the potential to extract complex symptomatic data from mental healthcare EHRs using NLP to facilitate further analyses of these clinical symptoms and their relevance for prognosis and intervention response.

Arming oHSV with ULBP3 drives abscopal immunity in lymphocyte-depleted glioblastoma.

Oncolytic viruses induce local tumor destruction and inflammation. Whether virotherapy can also overcome immunosuppression in noninfected tumor areas is under debate. To address this question, we have explored immunologic effects of oncolytic herpes simplex viruses (oHSVs) in a genetically engineered mouse model of isocitrate dehydrogenase (IDH) wild-type glioblastoma, the most common and most malignant primary brain tumor in adults. Our model recapitulates the genomics, the diffuse infiltrative growth pattern, and the extensive macrophage-dominant immunosuppression of human glioblastoma. Infection with an oHSV that was armed with a UL16-binding protein 3 (ULBP3) expression cassette inhibited distant tumor growth in the absence of viral spreading (abscopal effect) and yielded accumulation of activated macrophages and T cells. There was also abscopal synergism of oHSVULBP3 with anti-programmed cell death 1 (anti-PD-1) against distant, uninfected tumor areas; albeit consistent with clinical trials in patients with glioblastoma, monotherapy with anti-PD-1 was ineffective in our model. Arming oHSV with ULBP3 led to upregulation of antigen processing and presentation gene sets in myeloid cells. The cognate ULBP3 receptor NKG2D, however, is not present on myeloid cells, suggesting a noncanonical mechanism of action of ULBP3. Overall, the myeloid-dominant, anti-PD-1-sensitive abscopal effect of oHSVULBP3 warrants further investigation in patients with IDH wild-type glioblastoma.

Mycophenolate Mofetil Treatment of Systemic Sclerosis Reduces Myeloid Cell Numbers and Attenuates the Inflammatory Gene Signature in Skin.

Fewer than half of patients with systemic sclerosis demonstrate modified Rodnan skin score improvement during mycophenolate mofetil (MMF) treatment. To understand the molecular basis for this observation, we extended our prior studies and characterized molecular and cellular changes in skin biopsies from subjects with systemic sclerosis treated with MMF. Eleven subjects completed ≥24 months of MMF therapy. Two distinct skin gene expression trajectories were observed across six of these subjects. Three of the six subjects showed attenuation of the inflammatory signature by 24 months, paralleling reductions in CCL2 mRNA expression in skin and reduced numbers of macrophages and myeloid dendritic cells in skin biopsies. MMF cessation at 24 months resulted in an increased inflammatory score, increased CCL2 mRNA and protein levels, modified Rodnan skin score rebound, and increased numbers of skin myeloid cells in these subjects. In contrast, three other subjects remained on MMF >24 months and showed a persistent decrease in inflammatory score, decreasing or stable modified Rodnan skin score, CCL2 mRNA reductions, sera CCL2 protein levels trending downward, reduction in monocyte migration, and no increase in skin myeloid cell numbers. These data summarize molecular changes during MMF therapy that suggest reduction of innate immune cell numbers, possibly by attenuating expression of chemokines, including CCL2.

Natural language processing to extract symptoms of severe mental illness from clinical text: the Clinical Record Interactive Search Comprehensive Data Extraction (CRIS-CODE) project.

OBJECTIVES: We sought to use natural language processing to develop a suite of language models to capture key symptoms of severe mental illness (SMI) from clinical text, to facilitate the secondary use of mental healthcare data in research. DESIGN: Development and validation of information extraction applications for ascertaining symptoms of SMI in routine mental health records using the Clinical Record Interactive Search (CRIS) data resource; description of their distribution in a corpus of discharge summaries. SETTING: Electronic records from a large mental healthcare provider serving a geographic catchment of 1.2 million residents in four boroughs of south London, UK. PARTICIPANTS: The distribution of derived symptoms was described in 23 128 discharge summaries from 7962 patients who had received an SMI diagnosis, and 13 496 discharge summaries from 7575 patients who had received a non-SMI diagnosis. OUTCOME MEASURES: Fifty SMI symptoms were identified by a team of psychiatrists for extraction based on salience and linguistic consistency in records, broadly categorised under positive, negative, disorganisation, manic and catatonic subgroups. Text models for each symptom were generated using the TextHunter tool and the CRIS database. RESULTS: We extracted data for 46 symptoms with a median F1 score of 0.88. Four symptom models performed poorly and were excluded. From the corpus of discharge summaries, it was possible to extract symptomatology in 87% of patients with SMI and 60% of patients with non-SMI diagnosis. CONCLUSIONS: This work demonstrates the possibility of automatically extracting a broad range of SMI symptoms from English text discharge summaries for patients with an SMI diagnosis. Descriptive data also indicated that most symptoms cut across diagnoses, rather than being restricted to particular groups.

Association of cannabis use with hospital admission and antipsychotic treatment failure in first episode psychosis: an observational study.

OBJECTIVE: To investigate whether cannabis use is associated with increased risk of relapse, as indexed by number of hospital admissions, and whether antipsychotic treatment failure, as indexed by number of unique antipsychotics prescribed, may mediate this effect in a large data set of patients with first episode psychosis (FEP). DESIGN: Observational study with exploratory mediation analysis. SETTING: Anonymised electronic mental health record data from the South London and Maudsley NHS Foundation Trust. PARTICIPANTS: 2026 people presenting to early intervention services with FEP. EXPOSURE: Cannabis use at presentation, identified using natural language processing. MAIN OUTCOME MEASURES: admission to psychiatric hospital and clozapine prescription up to 5 years following presentation. MEDIATOR: Number of unique antipsychotics prescribed. RESULTS: Cannabis use was present in 46.3% of the sample at first presentation and was particularly common in patients who were 16-25, male and single. It was associated with increased frequency of hospital admission (incidence rate ratio 1.50, 95% CI 1.25 to 1.80), increased likelihood of compulsory admission (OR 1.55, 1.16 to 2.08) and greater number of days spent in hospital (ß coefficient 35.1 days, 12.1 to 58.1). The number of unique antipsychotics prescribed, mediated increased frequency of hospital admission (natural indirect effect 1.09, 95% CI 1.01 to 1.18; total effect 1.50, 1.21 to 1.87), increased likelihood of compulsory admission (natural indirect effect (NIE) 1.27, 1.03 to 1.58; total effect (TE) 1.76, 0.81 to 3.84) and greater number of days spent in hospital (NIE 17.9, 2.4 to 33.4; TE 34.8, 11.6 to 58.1). CONCLUSIONS: Cannabis use in patients with FEP was associated with an increased likelihood of hospital admission. This was linked to the prescription of several different antipsychotic drugs, indicating clinical judgement of antipsychotic treatment failure. Together, this suggests that cannabis use might be associated with worse clinical outcomes in psychosis by contributing towards failure of antipsychotic treatment.

CDDO-Me Redirects Activation of Breast Tumor Associated Macrophages.

Tumor-associated macrophages can account for up to 50% of the tumor mass in breast cancer patients and high TAM density is associated with poor clinical prognosis. Because TAMs enhance tumor growth, development, and metastatic potential, redirection of TAM activation may have significant therapeutic benefit. Our studies in primary human macrophages and murine breast TAMs suggest that the synthetic oleanane triterpenoid CDDO-methyl ester (CDDO-Me) reprograms the activation profile of TAMs from tumor-promoting to tumor-inhibiting. We show that CDDO-Me treatment inhibits expression of IL-10 and VEGF in stimulated human M2 macrophages and TAMs but increases expression of TNF-α and IL-6. Surface expression of CD206 and CD163, which are characteristic of M2 activation, is significantly attenuated by CDDO-Me. In contrast, CDDO-Me up-regulates surface expression of HLA-DR and CD80, which are markers of M1 activation, and importantly potentiates macrophage activation of autologous T cells but inhibits endothelial cell vascularization. These results show for the first time that CDDO-Me redirects activation of M2 macrophages and TAMs from immune-suppressive to immune-stimulatory, and implicate a role for CDDO-Me as an immunotherapeutic in the treatment of breast and potentially other types of cancer.

Toward clinical genomics in everyday medicine: perspectives and recommendations.

Precision or personalized medicine through clinical genome and exome sequencing has been described by some as a revolution that could transform healthcare delivery, yet it is currently used in only a small fraction of patients, principally for the diagnosis of suspected Mendelian conditions and for targeting cancer treatments. Given the burden of illness in our society, it is of interest to ask how clinical genome and exome sequencing can be constructively integrated more broadly into the routine practice of medicine for the betterment of public health. In November 2014, 46 experts from academia, industry, policy and patient advocacy gathered in a conference sponsored by Illumina, Inc. to discuss this question, share viewpoints and propose recommendations. This perspective summarizes that work and identifies some of the obstacles and opportunities that must be considered in translating advances in genomics more widely into the practice of medicine.

Identification of Adverse Drug Events from Free Text Electronic Patient Records and Information in a Large Mental Health Case Register.

OBJECTIVES: Electronic healthcare records (EHRs) are a rich source of information, with huge potential for secondary research use. The aim of this study was to develop an application to identify instances of Adverse Drug Events (ADEs) from free text psychiatric EHRs. METHODS: We used the GATE Natural Language Processing (NLP) software to mine instances of ADEs from free text content within the Clinical Record Interactive Search (CRIS) system, a de-identified psychiatric case register developed at the South London and Maudsley NHS Foundation Trust, UK. The tool was built around a set of four movement disorders (extrapyramidal side effects [EPSEs]) related to antipsychotic therapy and rules were then generalised such that the tool could be applied to additional ADEs. We report the frequencies of recorded EPSEs in patients diagnosed with a Severe Mental Illness (SMI) and then report performance in identifying eight other unrelated ADEs. RESULTS: The tool identified EPSEs with >0.85 precision and >0.86 recall during testing. Akathisia was found to be the most prevalent EPSE overall and occurred in the Asian ethnic group with a frequency of 8.13%. The tool performed well when applied to most of the non-EPSEs but least well when applied to rare conditions such as myocarditis, a condition that appears frequently in the text as a side effect warning to patients. CONCLUSIONS: The developed tool allows us to accurately identify instances of a potential ADE from psychiatric EHRs. As such, we were able to study the prevalence of ADEs within subgroups of patients stratified by SMI diagnosis, gender, age and ethnicity. In addition we demonstrated the generalisability of the application to other ADE types by producing a high precision rate on a non-EPSE related set of ADE containing documents. AVAILABILITY: The application can be found at http://git.brc.iop.kcl.ac.uk/rmallah/dystoniaml.

Cannabis use and treatment resistance in first episode psychosis: a natural language processing study.

BACKGROUND: Cannabis is frequently used among individuals with first episode psychosis and is associated with poor clinical outcomes. However, little is known about the effect of cannabis use on the response to antipsychotic medications and how use could affect outcomes. Using natural language processing on clinical data from a large electronic case register, we sought to investigate whether resistance to antipsychotic treatment mediated poor clinical outcomes associated with cannabis use. METHODS: Data were obtained from 2026 people with first episode psychosis in south London, UK. Cannabis use documented in free text clinical records was identified with natural language processing. Data for age, sex, ethnicity, marital status, psychotic disorder diagnosis, subsequent hospital admission, and number of unique antipsychotic medications prescribed were obtained using the Clinical Record Interactive Search instrument. The association of these variables with cannabis use was analysed with multivariable regression and mediation analysis. FINDINGS: 939 people (46·3%) with first episode psychosis were using cannabis at first presentation. Cannabis use was most strongly associated with being 16-25 years old, male, and single, and was also associated with an increase in number of hospital admissions (incidence rate ratio 1·50, 95% CI 1·25-1·80), compulsory hospital admission (odds ratio 1·55, 1·16-2·08), and number of days spent in hospital (ß coefficient 35·1 days, 12·1-58·1) over 5 years' follow-up. An increase in number of unique antipsychotic medications mediated an increase in number of hospital admissions (natural indirect effect 1·11, 1·04-1·17; total effect 1·41, 1·22-1·64), compulsory hospital admission (1·27, 1·10-1·45; 1·71, 1·05-2·78), and number of days spent in hospital (16·1, 6·7-25·5; 19·9, 2·5-37·3). INTERPRETATION: We showed that a substantial number of people with first episode psychosis used cannabis and that its use was associated with increased likelihood of hospital admission and number of days spent in hospital. These associations were partly mediated by an increase in number of unique antipsychotic medications prescribed. These findings suggest that cannabis might reduce response to conventional antipsychotic treatment and highlight the importance of strategies to reduce its use. FUNDING: National Institute for Health Research, UK Medical Research Council.

Mood instability is a common feature of mental health disorders and is associated with poor clinical outcomes.

OBJECTIVES: Mood instability is a clinically important phenomenon but has received relatively little research attention. The objective of this study was to assess the impact of mood instability on clinical outcomes in a large sample of people receiving secondary mental healthcare. DESIGN: Observational study using an anonymised electronic health record case register. SETTING: South London and Maudsley NHS Trust (SLaM), a large provider of inpatient and community mental healthcare in the UK. PARTICIPANTS: 27,704 adults presenting to SLaM between April 2006 and March 2013 with a psychotic, affective or personality disorder. EXPOSURE: The presence of mood instability within 1 month of presentation, identified using natural language processing (NLP). MAIN OUTCOME MEASURES: The number of days spent in hospital, frequency of hospital admission, compulsory hospital admission and prescription of antipsychotics or non-antipsychotic mood stabilisers over a 5-year follow-up period. RESULTS: Mood instability was documented in 12.1% of people presenting to mental healthcare services. It was most frequently documented in people with bipolar disorder (22.6%), but was common in people with personality disorder (17.8%) and schizophrenia (15.5%). It was associated with a greater number of days spent in hospital (ß coefficient 18.5, 95% CI 12.1 to 24.8), greater frequency of hospitalisation (incidence rate ratio 1.95, 1.75 to 2.17), greater likelihood of compulsory admission (OR 2.73, 2.34 to 3.19) and an increased likelihood of prescription of antipsychotics (2.03, 1.75 to 2.35) or non-antipsychotic mood stabilisers (2.07, 1.77 to 2.41). CONCLUSIONS: Mood instability occurs in a wide range of mental disorders and is not limited to affective disorders. It is generally associated with relatively poor clinical outcomes. These findings suggest that clinicians should screen for mood instability across all common mental health disorders. The data also suggest that targeted interventions for mood instability may be useful in patients who do not have a formal affective disorder.

Long-term follow-up of the platinum chromium TAXUS Element (ION) stent: The PERSEUS Workhorse and Small Vessel trial five-year results.

BACKGROUND: The TAXUS Element (ION) platinum chromium paclitaxel-eluting stent (PtCr-PES) incorporates a thin (81 µm) strut design with a similar polymer and drug dose density as prior PES. The pivotal PERSEUS trial program consisted of two studies: PERSEUS Workhorse (WH) and PERSEUS Small Vessel (SV). The PERSEUS WH trial demonstrated the PtCr-PES to be non-inferior to the predicate TAXUS Express PES (TE-PES) for target lesion failure (TLF) at 1 year and in-segment angiographic percent diameter stenosis at 9 months. The PERSEUS SV trial demonstrated the PtCr-PES to be superior to a historical bare metal stent (BMS) for angiographic late lumen loss at 9 months. Long-term (5-year) clinical outcomes following PtCr-PES have not been previously reported. METHODS: PERSEUS WH was a prospective, Bayesian, 3:1 randomized (PtCr-PES vs. TE-PES) trial in patients with lesion length ≤28 mm and vessel diameter ≥2.75 to ≤4.0 mm. PERSEUS SV was a prospective, single-arm trial in patients with lesion length ≤20 mm and vessel diameter ≥2.25 to <2.75 mm comparing PtCr-PES to a matched historical BMS control. RESULTS: Among randomized subjects in the PERSEUS WH study, clinical event rates at 5 years were similar between treatment groups, including TLF (12.9% TE-PES vs. 12.1% PtCr-PES; P = 0.66). In the PERSEUS SV study, 5-year rates of MACE, and TLF were significantly lower for PtCr-PES (vs. BMS) following adjustment for baseline characteristics and were primarily due to lower target lesion revascularization rates (27.2% BMS vs. 14.9% PtCr-PES; P = 0.049). CONCLUSIONS: At 5 years, the PtCr-PES provides efficacy and safety that is comparable to the TE-PES and superior efficacy with similar safety when compared with BMS in smaller caliber vessels. Cumulative stent thrombosis rates remained low and similar through 5 years for both DES platforms.

A review on how meditation could be used to comfort the terminally ill.

OBJECTIVE: Our objective was to review how meditation could comfort the terminally ill. METHOD: Our methodology was a literature search, which included books, journals, papers in collections, and online databases. The main search engines employed were Google Scholar and the Durham University Library. The main databases consulted were the Christian Meditation Centre, Project Meditation, and Stress-Related Facts and Well-Being at Monash. We were specifically interested in data acquired from clinical and nonclinical trials. The arguments needed to be based on qualitative and quantitative scientific data. Papers were published between 1985 and 2014. We then subdivided the review into three subcategories: physical, emotional, and self-awareness. When reviewing each category, we put our results into tabular form. In each table, we noted the percentage of terminally ill patients (TIPs) and non-terminally ill patients (NTIPs), and whether meditation had comforted them. RESULTS: Our review demonstrated that there are many areas that have yet to be researched. First, very little work has been done on how meditation affects the physical health of TIPs, including such variables as blood pressure, chronic pain, and sleeping patterns. However, no research has been done on heart disease, hypertension, depression, among others. Second, virtually no research has been conducted on how meditation affects the mental health of TIPs. Notably neglected areas include anxiety, compliance, depression, and stress. Third, no research has been done on whether meditation increases self-awareness in TIPs. In each of these cases, most NTIPs reacted positively; however, no research has been done on why TIPs reacted differently. SIGNIFICANCE OF RESULTS: Our results demonstrate the need for further research on how meditation affects terminally ill patients. In turn, this would enrich the debate on whether meditation should be prescribed for the dying.