Investigating social deprivation and comorbid mental health diagnosis as predictors of treatment access among patients with an opioid use disorder using substance use services: a prospective cohort study

BackgroundOpioid use is a major public health concern across the globe. Opioid use and subsequent access to care is often shaped by co-occurring issues faced by people using opioids, such as deprivation, mental ill-health, and other forms of substance use. We investigated the role of social deprivation and comorbid mental health diagnoses in predicting re-engagement with substance use services or contact with crisis and inpatient services for individuals with opioid use disorder in secondary mental health care in inner-city London.MethodsWe conducted a prospective cohort study which followed individuals diagnosed with a first episode of opioid use disorder who accessed substance use services between September 2015 and May 2020 for up to 12 months, using anonymised electronic health records. We employed negative binominal regression and Cox proportional survival analyses to assess associations between exposures and outcomes.ResultsComorbid mental health diagnoses were associated with higher contact rates with crisis/inpatient services among people with opioid use disorder: incidence rate ratios (IRR) and 95% confidence intervals (CI) were 3.91 (1.74–9.14) for non-opioid substance use comorbidity, 8.92 (1.81–64.4) for a single comorbid mental health diagnosis, and 15.9 (5.89–47.5) for multiple comorbid mental health diagnoses. Social deprivation was not associated with contact rates with crisis/inpatient services within this sample. Similar patterns were found with time to first crisis/inpatient contact. Social deprivation and comorbid mental health diagnoses were not associated with re-engagement with substance use services.ConclusionComorbid substance and mental health difficulties amongst people with an opioid use disorder led to earlier and more frequent contact with crisis/inpatient mental health services during the first 12 months of follow up. Given the common co-occurrence of mental health and substance use disorders among those who use opioids, a better understanding of their wider needs (such as social, financial and other non-medical concerns) will ensure they are supported in their treatment journeys

Creating European guidelines for Chiropractic Incident Reporting and Learning Systems (CIRLS): relevance and structure

<p>Abstract</p> <p>Background</p> <p>In 2009, the heads of the Executive Council of the European Chiropractors' Union (ECU) and the European Academy of Chiropractic (EAC) involved in the European Committee for Standardization (CEN) process for the chiropractic profession, set out to establish European guidelines for the reporting of adverse reactions to chiropractic treatment. There were a number of reasons for this: first, to improve the overall quality of patient care by aiming to reduce the application of potentially harmful interventions and to facilitate the treatment of patients within the context of achieving maximum benefit with a minimum risk of harm; second, to inform the training objectives for the Graduate Education and Continuing Professional Development programmes of all 19 ECU member nations, regarding knowledge and skills to be acquired for maximising patient safety; and third, to develop a guideline on patient safety incident reporting as it is likely to be part of future CEN standards for ECU member nations.</p> <p>Objective</p> <p>To introduce patient safety incident reporting within the context of chiropractic practice in Europe and to help individual countries and their national professional associations to develop or improve reporting and learning systems.</p> <p>Discussion</p> <p>Providing health care of any kind, including the provision of chiropractic treatment, can be a complex and, at times, a risky activity. Safety in healthcare cannot be guaranteed, it can only be improved. One of the most important aspects of any learning and reporting system lies in the appropriate use of the data and information it gathers. Reporting should not just be seen as a vehicle for obtaining information on patient safety issues, but also be utilised as a tool to facilitate learning, advance quality improvement and to ultimately minimise the rate of the occurrence of errors linked to patient care.</p> <p>Conclusions</p> <p>Before a reporting and learning system can be established it has to be clear what the objectives of the system are, what resources will be required and whether the implementing organisation has the capacity to operate the system to its full advantage. Responding to adverse event reports requires the availability of experts to analyse the incidents and to provide feedback in a timely fashion. A comprehensive strategy for national implementation must be in place including, but not limited to, presentations at national meetings, the provision of written information to all practitioners and the running of workshops, so that all stakeholders fully understand the purposes of adverse event reporting. Unless this is achieved, any system runs the risk of failure, or at the very least, limited usefulness.</p

Pharmacological levels of withaferin A (Withania somnifera) trigger clinically relevant anticancer effects specific to triple negative breast cancer cells

Withaferin A (WA) isolated from Withania somnifera (Ashwagandha) has recently become an attractive phytochemical under investigation in various preclinical studies for treatment of different cancer types. In the present study, a comparative pathway-based transcriptome analysis was applied in epithelial-like MCF-7 and triple negative mesenchymal MDA-MB-231 breast cancer cells exposed to different concentrations of WA which can be detected systemically in in vivo experiments. Whereas WA treatment demonstrated attenuation of multiple cancer hallmarks, the withanolide analogue Withanone (WN) did not exert any of the described effects at comparable concentrations. Pathway enrichment analysis revealed that WA targets specific cancer processes related to cell death, cell cycle and proliferation, which could be functionally validated by flow cytometry and real-time cell proliferation assays. WA also strongly decreased MDA-MB-231 invasion as determined by single-cell collagen invasion assay. This was further supported by decreased gene expression of extracellular matrix-degrading proteases (uPA, PLAT, ADAM8), cell adhesion molecules (integrins, laminins), pro-inflammatory mediators of the metastasis-promoting tumor microenvironment (TNFSF12, IL6, ANGPTL2, CSF1R) and concomitant increased expression of the validated breast cancer metastasis suppressor gene (BRMS1). In line with the transcriptional changes, nanomolar concentrations of WA significantly decreased protein levels and corresponding activity of uPA in MDA-MB-231 cell supernatant, further supporting its anti-metastatic properties. Finally, hierarchical clustering analysis of 84 chromatin writer-reader-eraser enzymes revealed that WA treatment of invasive mesenchymal MDA-MB-231 cells reprogrammed their transcription levels more similarly towards the pattern observed in non-invasive MCF-7 cells. In conclusion, taking into account that sub-cytotoxic concentrations of WA target multiple metastatic effectors in therapy-resistant triple negative breast cancer, WA-based therapeutic strategies targeting the uPA pathway hold promise for further (pre)clinical development to defeat aggressive metastatic breast cancer

Incidence of synchronous appendiceal neoplasm in patients with colorectal cancer and its clinical significance

<p>Abstract</p> <p>Background</p> <p>The aims of this study were to evaluate the incidence of synchronous appendiceal neoplasm in patients with colorectal cancer, and to determine its clinical significance.</p> <p>Methods</p> <p>Pathological reports and medical records were reviewed of patients with colorectal adenocarcinoma who underwent oncological resection of the tumor together with appendectomy at the Faculty of Medicine Siriraj Hospital, Mahidol University, Thailand between September 2000 and April 2008.</p> <p>Results</p> <p>This study included 293 patients with an average age of 62 years (range 19–95) and 51 percent were male. Of the patients studied, 228 (78 percent) had right hemicolectomy, whereas the others (22 percent) had surgery for left-sided colon cancer or rectal cancer. One patient (0.3 percent) had epithelial appendiceal neoplasm (mucinous cystadenoma) and 3 patients (1.0 percent) had metastatic colorectal cancer in the mesoappendix. However, the presence of synchronous appendiceal tumors and/or metastasis did not alter postoperative management, as these patients had received adjuvant therapy and were scheduled for surveillance program because of nodal involvement.</p> <p>Conclusion</p> <p>The incidence of synchronous primary appendiceal neoplasm and secondary (metastatic) appendiceal neoplasm in colorectal cancer patients was 0.3 and 1.0 percent, respectively. However, these findings did not change the postoperative clinical management.</p

Population Analysis of the Fusarium graminearum Species Complex from Wheat in China Show a Shift to More Aggressive Isolates

A large number of Fusarium isolates was collected from blighted wheat spikes originating from 175 sampling sites, covering 15 provinces in China. Species and trichothecene chemotype determination by multilocus genotyping (MLGT) indicated that F. graminearum s. str. with the 15-acetyl deoxynivalenol (15ADON) chemotype and F. asiaticum with either the nivalenol (NIV) or the 3-acetyl deoxynivalenol (3ADON) chemotype were the dominant causal agents. Bayesian model-based clustering with allele data obtained with 12 variable number of tandem repeats (VNTR) markers, detected three genetic clusters that also show distinct chemotypes. High levels of population genetic differentiation and low levels of effective number of migrants were observed between these three clusters. Additional genotypic analyses revealed that F. graminearum s. str. and F. asiaticum are sympatric. In addition, composition analysis of these clusters indicated a biased gene flow from 3ADON to NIV producers in F. asiaticum. In phenotypic analyses, F. asiaticum that produce 3ADON revealed significant advantages over F. asiaticum that produce NIV in pathogenicity, growth rate, fecundity, conidial length, trichothecene accumulation and resistance to benzimidazole. These results suggest that natural selection drives the spread of a more vigorous, more toxigenic pathogen population which also shows higher levels of fungicide resistance

Multibudded tubules formed by COPII on artificial liposomes

COPII-coated vesicles form at the endoplasmic reticulum for cargo transport to the Golgi apparatus. We used in vitro reconstitution to examine the roles of the COPII scaffold in remodeling the shape of a lipid bilayer. Giant Unilamellar Vesicles were examined using fast confocal fluorescence and cryo-electron microscopy in order to avoid separation steps and minimize mechanical manipulation. COPII showed a preference for high curvature structures, but also sufficient flexibility for binding to low curvatures. The COPII proteins induced beads-on-a-string-like constricted tubules, similar to those previously observed in cells. We speculate about a mechanical pathway for vesicle fission from these multibudded COPII-coated tubules, considering the possibility that withdrawal of the Sar1 amphipathic helix upon GTP hydrolysis leads to lipid bilayer destabilization resulting in fission

The Framingham Heart Study 100K SNP genome-wide association study resource: overview of 17 phenotype working group reports

Background: The Framingham Heart Study (FHS), founded in 1948 to examine the epidemiology of cardiovascular disease, is among the most comprehensively characterized multi-generational studies in the world. Many collected phenotypes have substantial genetic contributors; yet most genetic determinants remain to be identified. Using single nucleotide polymorphisms (SNPs) from a 100K genome-wide scan, we examine the associations of common polymorphisms with phenotypic variation in this community-based cohort and provide a full-disclosure, web-based resource of results for future replication studies. Methods: Adult participants (n = 1345) of the largest 310 pedigrees in the FHS, many biologically related, were genotyped with the 100K Affymetrix GeneChip. These genotypes were used to assess their contribution to 987 phenotypes collected in FHS over 56 years of follow up, including: cardiovascular risk factors and biomarkers; subclinical and clinical cardiovascular disease; cancer and longevity traits; and traits in pulmonary, sleep, neurology, renal, and bone domains. We conducted genome-wide variance components linkage and population-based and family-based association tests. Results: The participants were white of European descent and from the FHS Original and Offspring Cohorts (examination 1 Offspring mean age 32 ± 9 years, 54% women). This overview summarizes the methods, selected findings and limitations of the results presented in the accompanying series of 17 manuscripts. The presented association results are based on 70,897 autosomal SNPs meeting the following criteria: minor allele frequency ≥ 10%, genotype call rate ≥ 80%, Hardy-Weinberg equilibrium p-value ≥ 0.001, and satisfying Mendelian consistency. Linkage analyses are based on 11,200 SNPs and short-tandem repeats. Results of phenotype-genotype linkages and associations for all autosomal SNPs are posted on the NCBI dbGaP website at http:// www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?id=phs000007. Conclusion: We have created a full-disclosure resource of results, posted on the dbGaP website, from a genome-wide association study in the FHS. Because we used three analytical approaches to examine the association and linkage of 987 phenotypes with thousands of SNPs, our results must be considered hypothesis-generating and need to be replicated. Results from the FHS 100K project with NCBI web posting provides a resource for investigators to identify high priority findings for replication.Molecular and Cellular Biolog

Common Variants at 10 Genomic Loci Influence Hemoglobin A(1C) Levels via Glycemic and Nonglycemic Pathways

OBJECTIVE Glycated hemoglobin (HbA1c), used to monitor and diagnose diabetes, is influenced by average glycemia over a 2- to 3-month period. Genetic factors affecting expression, turnover, and abnormal glycation of hemoglobin could also be associated with increased levels of HbA1c. We aimed to identify such genetic factors and investigate the extent to which they influence diabetes classification based on HbA1c levels. RESEARCH DESIGN AND METHODS We studied associations with HbA1c in up to 46,368 nondiabetic adults of European descent from 23 genome-wide association studies (GWAS) and 8 cohorts with de novo genotyped single nucleotide polymorphisms (SNPs). We combined studies using inverse-variance meta-analysis and tested mediation by glycemia using conditional analyses. We estimated the global effect of HbA1c loci using a multilocus risk score, and used net reclassification to estimate genetic effects on diabetes screening. RESULTS Ten loci reached genome-wide significant association with HbA1c, including six new loci near FN3K (lead SNP/P value, rs1046896/P = 1.6 × 10−26), HFE (rs1800562/P = 2.6 × 10−20), TMPRSS6 (rs855791/P = 2.7 × 10−14), ANK1 (rs4737009/P = 6.1 × 10−12), SPTA1 (rs2779116/P = 2.8 × 10−9) and ATP11A/TUBGCP3 (rs7998202/P = 5.2 × 10−9), and four known HbA1c loci: HK1 (rs16926246/P = 3.1 × 10−54), MTNR1B (rs1387153/P = 4.0 × 10−11), GCK (rs1799884/P = 1.5 × 10−20) and G6PC2/ABCB11 (rs552976/P = 8.2 × 10−18). We show that associations with HbA1c are partly a function of hyperglycemia associated with 3 of the 10 loci (GCK, G6PC2 and MTNR1B). The seven nonglycemic loci accounted for a 0.19 (% HbA1c) difference between the extreme 10% tails of the risk score, and would reclassify ∼2% of a general white population screened for diabetes with HbA1c. CONCLUSIONS GWAS identified 10 genetic loci reproducibly associated with HbA1c. Six are novel and seven map to loci where rarer variants cause hereditary anemias and iron storage disorders. Common variants at these loci likely influence HbA1c levels via erythrocyte biology, and confer a small but detectable reclassification of diabetes diagnosis by HbA1c

General practitioners' attitudes and preparedness towards Clinical Decision Support in e-Prescribing (CDS-eP) adoption in the West of Ireland: a cross sectional study

Background: Electronic clinical decision support (CDS) is increasingly establishing its role in evidence-based clinical practice. Considerable evidence supports its enhancement of efficiency in e-Prescribing, but some controversy remains. This study evaluated the practicality and identified the perceived benefits of, and barriers to, its future adoption in the West of Ireland. Methods: This cross sectional study was carried out by means of a 27-part questionnaire sent to 262 registered general practitioners in Counties Galway, Mayo and Roscommon. The survey domains encompassed general information of individual's practice, current use of CDS and the practitioner's attitudes towards adoption of CDS-eP. Descriptive and inferential analyses were performed to analyse the data collected. Results: The overall response rate was 37%. Nearly 92% of respondents employed electronic medical records in their practice. The majority acknowledged the value of electronic CDS in improving prescribing quality (71%) and reducing prescribing errors (84%). Despite a high degree of unfamiliarity (73%), the practitioners were open to the use of CDS-eP (94%) and willing to invest greater resources for its implementation (62%). Lack of a strategic implementation plan (78%) is the main perceived barrier to the incorporation of CDS-eP into clinical practice, followed by i) lack of financial incentives (70%), ii) lack of standardized product software (61%), iii) high sensitivity of drug-drug interaction or medication allergy markers (46%), iv) concern about overriding physicians' prescribing decisions(44%) and v) lack of convincing evidence on the systems' effectiveness (22%). Conclusions: Despite favourable attitudes towards the adoption of CDS-eP, multiple perceived barriers impede its incorporation into clinical practice. These merit further exploration, taking into consideration the structure of the Irish primary health care system, before CDS-eP can be recommended for routine clinical use in the West of Ireland.Healthcare Informatics Society of Ireland (HISI) research bursary 2007-2009Deposited by bulk impor

Acquisition of a Unique Onshore/Offshore Geophysical and Geochemical Dataset in the Northern Malawi (Nyasa) Rift

The Study of Extension and maGmatism in Malawi aNd Tanzania (SEGMeNT) project acquired a comprehensive suite of geophysical and geochemical datasets across the northern Malawi (Nyasa) rift in the East Africa rift system. Onshore/offshore active and passive seismic data, long‐period and wideband magnetotelluric data, continuous Global Positioning System data, and geochemical samples were acquired between 2012 and 2016. This combination of data is intended to elucidate the sedimentary, crustal, and upper‐mantle architecture of the rift, patterns of active deformation, and the origin and age of rift‐related magmatism. A unique component of our program was the acquisition of seismic data in Lake Malawi, including seismic reflection, onshore/offshore wide‐angle seismic reflection/refraction, and broadband seismic data from lake‐bottom seismometers, a towed streamer, and a large towed air‐gun source