Experience-based investigation and codesign of approaches to prevent and reduce Mental Health Act use (CO-PACT): a protocol

INTRODUCTION: The Independent Review of the Mental Health Act (MHA) in England and Wales confirmed increasing levels of compulsory detentions, especially for racialised communities. This research aims to: (a) understand the causes of and propose preventive opportunities to reduce the disproportionate use of the MHA, (b) use an adapted form of experience-based codesign (EBCD) to facilitate system-wide changes and (c) foreground the voices of service users at risk of detention to radically reform policy and implement new legislation to ensure the principles of equity are retained. METHODS AND ANALYSIS: This is a qualitative study, using a comparative case study design. This study is composed of five work packages; photovoice workshops will be conducted in eight local systems with service users and healthcare professionals separately (WP1); a series of three EBCD workshops in each local system to develop approaches that reduce detentions and improve the experience of people from racialised communities. This will inform a comparative analysis and national knowledge exchange workshop (WP2); an evaluation led by the patient and public involvement group to better understand what it is like for people to participate in photovoice, codesign and participatory research (WP3); an economic evaluation (WP4) and dissemination strategy (WP5). The impact of the involvement of patients and public will be independently evaluated. ETHICS AND DISSEMINATION: This study is sponsored by the University of Oxford and granted ethical approval from the NHS Research Ethics Committee and Health Research Authority (21/SC/0204). The outputs from this study will be shared through several local and national channels

Anticancer drug screening using invitro Cell Proliferation assay

Introduction: In this presentation cell proliferation methods and how they are related to screening for effective chemotherapy drugs will be reviewed. Cancer in its most basic form is the unchecked mass dividing of cells while normal apoptosis is not undertaken for various reasons, some of which that have yet to be discovered. By these means’ tumors form that inhibit the functions of the organs it is residing in and the effected cells may metastasize and spread throughout the body. For this reason, chemotherapy drugs must be assessed through introduction into working strains of cultured cancer cells that are then screened for effectiveness through a process called cell proliferation assays. Objective: The goal is to find the exact dosage for inhibiting the greatest number of Colorectal Cancer Cell (CRC) cells, strain HCT-116, while leaving other healthy cells unaffected as the methods are explained. Methods: Several methods exist for determining the resulting levels of proliferation of cells after drug administration such as: Molecular Targeted Therapies (MTT) and (Water Soluble Tetrazolium) WST-1 that uses a tetrazolium salt reagent on the cells before introducing the drug in question and then a colorimetric assay is used to determine the quantity of living cells remaining through assessing which retain the dye that is produced. Alamar BLUE is another experiment that uses redox reactions but substitutes the tetrazolium with resorufin, other options include Bromodeoxyuridine (BrdU) assay which analyzes the amount of a thymidine analog that is present post experiment after it has been absorbed by denatured DNA. Results: Once cell counts have been gathered, drugs of varying concentrations have been administered, and the assays are performed to gather the number of cells that continue to proliferate, tables and graphs reflecting such information may be drawn to find the Growth Inhibitory dose of 50% (GI 50) of the cells. Discussion: At the conclusion of these trials work will still need to be done to find how these drugs will be implemented in vivo. The next logical step is moving on to testing these therapies on animals to find strengths and weaknesses in live models. Conclusion: Through the course of testing 4 different chemotherapy drugs on HCT-116, MTT and other such cell proliferation assays are utilized in finding the correct dosages to elicit the desired response of inhibiting the growth of CRC cells. The process will begin from the first splitting of cell stock to acquire workable amounts of HCT-116, culturing this working stock, and passaging it as the quantity of cells become larger. The cell proliferation methods will be outlined along with the reasoning and theory behind them to include the materials utilized. The results will be discussed while also explaining how the results are to be properly evaluated. Finally, graphed analysis resulting in either GI 50 curves may be constructed to better tabulate what the varying concentrations effects resulted in. From here we continue to narrow our search to more finite concentrations that will yield better results in killing only the exact number of cells desired

Interpersonal violence in a deprived Scottish urban area with aggregations of physical health risks and psychiatric morbidity: an ecological study

Background: Glasgow, Scotland, has previously shown exceptional levels of violence among young men, shows aggregations of health conditions, with shortened life expectancy. Health conditions can be both causes and consequences of violence, of shared community-level socio-economic risk factors, and can result from large-scale social forces beyond the control of populations with high levels of violence. The aim of the study was to provide an in depth understanding of the Public Health problem of violence among young adult men in Glasgow East. Method: Ecological investigation of violence and its associations with health conditions in areas of contrasting socioeconomic deprivation. National survey of 1916 British men aged 18–34 years, augmented by a sub-sample of 765 men in Glasgow East (GE). Participants completed questionnaires covering current physical and sexual health, psychiatric symptoms, substance misuse, lifestyle, and crime and violence. Results: The 5-year prevalence of violence was similar in both surveys but fights involving weapons (AOR 3.32, 95% CI 2.29–4.79), gang fights (AOR 2.30, 95% CI 1.77–2.98), and instrumental violence supporting criminal lifestyles were more common in GE, where 1 in 9 men had been in prison. Violent men in both samples reported poorer physical and sexual health and all types of psychiatric morbidity except depression, with multiple high-risk behaviours for both future poor health and violence. Associations between drug and alcohol dependence and violence in GE could not be entirely explained by deprivation

Reporting randomised trials of social and psychological interventions: the CONSORT-SPI 2018 Extension.

BACKGROUND: Randomised controlled trials (RCTs) are used to evaluate social and psychological interventions and inform policy decisions about them. Accurate, complete, and transparent reports of social and psychological intervention RCTs are essential for understanding their design, conduct, results, and the implications of the findings. However, the reporting of RCTs of social and psychological interventions remains suboptimal. The CONSORT Statement has improved the reporting of RCTs in biomedicine. A similar high-quality guideline is needed for the behavioural and social sciences. Our objective was to develop an official extension of the Consolidated Standards of Reporting Trials 2010 Statement (CONSORT 2010) for reporting RCTs of social and psychological interventions: CONSORT-SPI 2018. METHODS: We followed best practices in developing the reporting guideline extension. First, we conducted a systematic review of existing reporting guidelines. We then conducted an online Delphi process including 384 international participants. In March 2014, we held a 3-day consensus meeting of 31 experts to determine the content of a checklist specifically targeting social and psychological intervention RCTs. Experts discussed previous research and methodological issues of particular relevance to social and psychological intervention RCTs. They then voted on proposed modifications or extensions of items from CONSORT 2010. RESULTS: The CONSORT-SPI 2018 checklist extends 9 of the 25 items from CONSORT 2010: background and objectives, trial design, participants, interventions, statistical methods, participant flow, baseline data, outcomes and estimation, and funding. In addition, participants added a new item related to stakeholder involvement, and they modified aspects of the flow diagram related to participant recruitment and retention. CONCLUSIONS: Authors should use CONSORT-SPI 2018 to improve reporting of their social and psychological intervention RCTs. Journals should revise editorial policies and procedures to require use of reporting guidelines by authors and peer reviewers to produce manuscripts that allow readers to appraise study quality, evaluate the applicability of findings to their contexts, and replicate effective interventions

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Changes in health in England, with analysis by English regions and areas of deprivation, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013.

BACKGROUND: In the Global Burden of Disease Study 2013 (GBD 2013), knowledge about health and its determinants has been integrated into a comparable framework to inform health policy. Outputs of this analysis are relevant to current policy questions in England and elsewhere, particularly on health inequalities. We use GBD 2013 data on mortality and causes of death, and disease and injury incidence and prevalence to analyse the burden of disease and injury in England as a whole, in English regions, and within each English region by deprivation quintile. We also assess disease and injury burden in England attributable to potentially preventable risk factors. England and the English regions are compared with the remaining constituent countries of the UK and with comparable countries in the European Union (EU) and beyond. METHODS: We extracted data from the GBD 2013 to compare mortality, causes of death, years of life lost (YLLs), years lived with a disability (YLDs), and disability-adjusted life-years (DALYs) in England, the UK, and 18 other countries (the first 15 EU members [apart from the UK] and Australia, Canada, Norway, and the USA [EU15+]). We extended elements of the analysis to English regions, and subregional areas defined by deprivation quintile (deprivation areas). We used data split by the nine English regions (corresponding to the European boundaries of the Nomenclature for Territorial Statistics level 1 [NUTS 1] regions), and by quintile groups within each English region according to deprivation, thereby making 45 regional deprivation areas. Deprivation quintiles were defined by area of residence ranked at national level by Index of Multiple Deprivation score, 2010. Burden due to various risk factors is described for England using new GBD methodology to estimate independent and overlapping attributable risk for five tiers of behavioural, metabolic, and environmental risk factors. We present results for 306 causes and 2337 sequelae, and 79 risks or risk clusters. FINDINGS: Between 1990 and 2013, life expectancy from birth in England increased by 5·4 years (95% uncertainty interval 5·0-5·8) from 75·9 years (75·9-76·0) to 81·3 years (80·9-81·7); gains were greater for men than for women. Rates of age-standardised YLLs reduced by 41·1% (38·3-43·6), whereas DALYs were reduced by 23·8% (20·9-27·1), and YLDs by 1·4% (0·1-2·8). For these measures, England ranked better than the UK and the EU15+ means. Between 1990 and 2013, the range in life expectancy among 45 regional deprivation areas remained 8·2 years for men and decreased from 7·2 years in 1990 to 6·9 years in 2013 for women. In 2013, the leading cause of YLLs was ischaemic heart disease, and the leading cause of DALYs was low back and neck pain. Known risk factors accounted for 39·6% (37·7-41·7) of DALYs; leading behavioural risk factors were suboptimal diet (10·8% [9·1-12·7]) and tobacco (10·7% [9·4-12·0]). INTERPRETATION: Health in England is improving although substantial opportunities exist for further reductions in the burden of preventable disease. The gap in mortality rates between men and women has reduced, but marked health inequalities between the least deprived and most deprived areas remain. Declines in mortality have not been matched by similar declines in morbidity, resulting in people living longer with diseases. Health policies must therefore address the causes of ill health as well as those of premature mortality. Systematic action locally and nationally is needed to reduce risk exposures, support healthy behaviours, alleviate the severity of chronic disabling disorders, and mitigate the effects of socioeconomic deprivation. FUNDING: Bill & Melinda Gates Foundation and Public Health England.Bill & Melinda Gates Foundation; Public Health EnglandThis is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/S0140-6736(15)00195-

A simple synthesis of 5-spirobarbituric acids and transformations of spirocyclopropanobarbiturates to 5-substituted barbiturates

247-251The reactions of barbituric acid and its 1,3-dimethyl derivative with 1,2-dibromoethane, 1,4-dibromobutane, 1,5-dibromopentane and 1,2-bis[bromomethyl] benzene in DMF-K2CO3 (base), TBAHSO4 (catalyst) provide 5-spirobarbiturates as major products along with other products. The 5,7-dimethyl-5,7-diaza-spiro[2.5]octane-4,6,8-trione undergoes ring opening with -CN, -SR and Br2 to provide 5-substituted barbiturates

A facile synthesis of 5-acylbarbituric acids under microwave irradiations

1105-1108N-Monosubstituted and N,N’-disubstituted barbituric acids on treatment with benzoic anhydride/acetic anhydride under microwave irradiations without using any solvent provide a convenient methodology for the synthesis of 5-benzoyl/ acylbarbituric acids in moderate to high yields

Reactions of 5-benzoyl-/5-carbaldehyde- /5-(3-phenyl-acryloyl)- 6-hydroxy-1H-pyrimidin- 2,4-diones with amines: Anti-cancer and metal sequestering properties

291-296Reactions of 5-benzoyl- / 5-carbaldehyde- / 5-(3-phenyl-acryloyl)-6-hydroxy-1H- pyrimidine-2,4-diones and diamines result in the formation of corresponding enamines. Appreciable anti-cancer activities of compounds 2, 5, 6 and 8 at various cell lines of 59 human tumor cell panels have been observed. UV spectral studies of these compounds in solution with Cu(OAc)₂ and FeCl₃ indicate their interactions with Cu⁺² and Fe⁺³ ions