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World is fighting Covid-19 pandemic since beginning of the year 2020. To prevent spread of Covid-19 disease, sanitization of workplaces using sodium hypochlorite (NaOCl) disinfectant is one of the several precautionary steps that are followed currently. In this letter, I share an experience wherein regular spraying of NaOCl solution in metal forming section of an organization led to development of corrosion damage and rejection of a large number of aircraft structural components made of Al-2024 alloy sheet material.
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BACKGROUND: As people with intellectual disabilities (ID) are now living longer, they are more at risk of developing non-communicable diseases, including type 2 diabetes mellitus. However, understanding of factors associated with diabetes for targeted management and prevention strategies is limited. This study aimed to investigate prevalence of diabetes in adults (aged ≥18 years) with ID and its relationship with demographic, lifestyle, independence and health factors. METHOD: This was a cross-sectional analysis of interview data from 1091 adults with ID from the Leicestershire Learning Disability Register from 1 January 2010 to 31 December 2016. Logistic regression models were used to identify factors associated with diabetes in the study population. RESULTS: The study population did not have healthy lifestyles: just under half reported having lower physical activity levels than people without ID of a similar age; one-quarter consumed fizzy drinks daily; and 20% consumed five or more fruit and/or vegetables per day. Prevalence of carer/self-reported diabetes was 7.3% (95% confidence interval 5.9-9.0). After adjustment, diabetes was positively associated with South Asian ethnicity (P = 0.03) and older age groups (P < 0.001). Diabetes was less common in people living with family members (P = 0.02). We did not find a relationship between any of the lifestyle, independence and health factors investigated. CONCLUSIONS: A significant proportion of people with ID are living with diabetes. Diabetes management and prevention strategies should be tailored to individuals' complex needs and include consideration of lifestyle choices. Such strategies may want to focus on adults of South Asian ethnicity and people living in residential homes where prevalence appears to be higher.
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Diabetes Mellitus Tipo 2/epidemiologia , Nível de Saúde , Deficiência Intelectual/epidemiologia , Estilo de Vida , Características de Residência/estatística & dados numéricos , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Sistema de Registros , Fatores de Risco , Fatores Sexuais , Reino Unido/epidemiologia , Adulto JovemRESUMO
BACKGROUND: Multimorbidity [two or more conditions in addition to intellectual disability (ID)] is known to be more common among people with ID. However, the relationship between multimorbidity and lifestyle factors is currently unknown. The aim of this study was to determine the prevalence of multimorbidity in a population of adults with ID. We also aimed to identify risk factors, including lifestyle factors, for multimorbidity in this population. METHODS: This was a cross-sectional analysis using data from a diabetes screening study of 920 adults aged 18-74 years with ID living in Leicestershire, UK. We described comorbidities and the prevalence of multimorbidity in this population. We explored the relationship between multimorbidity and age, gender, ethnicity, severity of ID, socio-economic status, physical activity, sedentary behaviour, fruit and vegetable consumption and smoking status using multiple logistic regression. RESULTS: The prevalence of multimorbidity was 61.2% (95% CI 57.7-64.7). Multimorbidity was independently associated with being female (P < 0.001) and severe/profound ID (P = 0.004). Increasing age was of borderline significance (P = 0.06). Individuals who were physically inactive or sedentary were more likely to be multimorbid, independent of ability to walk, age, gender, severity of ID, ethnicity and socio-economic status (adjusted OR = 1.91; 95% CI 1.23-2.97; P = 0.004 and OR = 1.98; 95% CI 1.42-2.77; P < 0.001). After excluding probable life-long conditions (autism spectrum conditions, attention deficit hyperactivity disorders, epilepsy, cerebral palsy and other paralytic syndromes) as contributing comorbidities, the effect of sedentary behaviour, but not physical activity, remained (P = 0.004). We did not observe a relationship between multimorbidity, fruit and vegetable consumption and smoking status. CONCLUSIONS: Multimorbidity presents a significant burden to people with ID. Individuals who were physically inactive or sedentary were more likely to be multimorbid, but further work is recommended to explore the relationship between multimorbidity and lifestyle factors using standardised objective measures.
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Deficiência Intelectual/epidemiologia , Estilo de Vida , Multimorbidade , Adolescente , Adulto , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores Sexuais , Reino Unido/epidemiologia , Adulto JovemRESUMO
Background: We report on the development of the 'STOP Diabetes' education programme, a multi-component lifestyle behaviour change intervention for the prevention of type 2 diabetes and cardiovascular risk factors in adults with intellectual disabilities (ID). Methods: We combined qualitative stakeholder interviews with evidence reviews to develop the intervention, guided by the MRC Framework and informed by intervention mapping and two existing diabetes prevention programmes. We conducted two pilot cycles drawing on additional stakeholder interviews to inform and refine the intervention. Results: The STOP Diabetes education programme employed a theoretical framework, using sound learning and behavioural principles and concrete kinaesthetic methods, to provide the grounding for innovative games and activities to promote health behaviour change in adults with ID. Qualitative data also suggested that two educators and one support person delivering a programme of one carer session followed by seven 2.5-h sessions over 7 weeks was acceptable to service users, carers and educators and appeared to benefit the participants. Conclusions: The STOP Diabetes education programme was successfully developed and is suitable for a definitive randomized controlled trial.
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Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus Tipo 2/prevenção & controle , Comportamentos Relacionados com a Saúde , Educação em Saúde/métodos , Adulto , Atitude do Pessoal de Saúde , Atitude Frente a Saúde , Currículo , Diabetes Mellitus Tipo 2/psicologia , Pessoal de Saúde , Humanos , Deficiência Intelectual , Entrevistas como Assunto , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Desenvolvimento de Programas , Fatores de RiscoRESUMO
BACKGROUND: Adults with intellectual disabilities (ID) may be at increased risk of developing type 2 diabetes and cardiovascular disease, due to lifestyle factors, medications and other diagnosed conditions. Currently, there is lack of evidence on prevalence and prevention in this population. The aim of this study was to conduct a diabetes screening programme to determine prevalence of previously undiagnosed type 2 diabetes and impaired glucose regulation in people with ID. METHODS: Screening was conducted in a variety of community settings in Leicestershire, UK. Adults with ID were invited via: general practices; the Leicestershire Learning Disability Register; ID psychiatric services; and some people directly contacted the research team due to publicity about the study. Screening involved collection of anthropometric, biomedical and questionnaire data. Type 2 diabetes and impaired glucose regulation were defined according to (venous) fasting plasma glucose or HbA1c, following current World Health Organisation criteria. RESULTS: Nine hundred thirty adults (29% of those approached) participated. Mean age was 43 years, 58% were male and 16% of South Asian ethnicity. Most participants were either overweight or obese (68%). Diabetes status was successfully assessed for 675 (73%) participants: Nine (1.3%, 95% confidence interval 0.6 to 2.5) were found to have undiagnosed type 2 diabetes, and 35 (5.2%, 95% confidence interval 3.6 to 7.1) had impaired glucose regulation. Key factors associated with abnormal glucose regulation included the following: non-white ethnicity and a first degree family history of diabetes. CONCLUSIONS: Results from this large multi-ethnic cohort suggest a low prevalence of screen-detected (previously undiagnosed) type 2 diabetes and impaired glucose regulation in adults with ID. However, the high levels of overweight and obesity we found emphasise the need for targeted lifestyle prevention strategies, which are specifically tailored for the needs of people with ID.
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Diabetes Mellitus Tipo 2/epidemiologia , Intolerância à Glucose/epidemiologia , Deficiência Intelectual/epidemiologia , Sobrepeso/epidemiologia , Sistema de Registros , Adolescente , Adulto , Idoso , Comorbidade , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reino Unido/epidemiologia , Adulto JovemRESUMO
Detection of early colorectal cancer is expected to rise in light of national colorectal cancer screening programs. This The present review article delineates current endoscopic risk assessments, differentiating invasive from non-invasive neoplasia, for high likelihood of lymph node metastasis in early colorectal cancer, also termed high-risk early colorectal cancer, and endoscopic and surgical resection methods from a Western hemisphere perspective.
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Pólipos do Colo/patologia , Pólipos do Colo/cirurgia , Colonoscopia , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Colectomia , Neoplasias Colorretais/diagnóstico por imagem , Humanos , Mucosa Intestinal/patologia , Invasividade Neoplásica , Estadiamento de NeoplasiasRESUMO
BACKGROUND: Small bowel strictures are common in gastroenterology practice. We report diagnostic and therapeutic yield of double-balloon enteroscopy for small bowel strictures. METHODS: Retrospective study of 71 consecutive patients who were found to have small bowel stricture at the time of double-balloon enteroscopy. RESULTS: During double-balloon enteroscopy, stricture identification and tissue sampling were possible in all 71 cases. Surgical pathology reported aetiology as non-steroidal anti-inflammatory drugs (32%), non-specific (21%), Crohn's disease (21%), radiation-induced (9%), tumour (10%), anastomotic (4%), celiac disease (1%), and surgical adhesions (1%). Sixteen patients (23%) underwent balloon dilation. Sensitivity of abdominal computed-tomography and video-capsule endoscopy for strictures based on double balloon enteroscopy findings was 61% and 43%, respectively. CONCLUSION: Double-balloon enteroscopy was safe and effective to access small bowel stricture with direct visualization and tissue sampling or for therapeutic balloon dilation. Given low sensitivity with conventional computed-tomography and/or video-capsule endoscopy for small bowel stricture, double-balloon enteroscopy can be considered if clinical suspicion is high.
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Enteroscopia de Duplo Balão , Obstrução Intestinal/diagnóstico por imagem , Obstrução Intestinal/etiologia , Obstrução Intestinal/patologia , Idoso , Anti-Inflamatórios não Esteroides/efeitos adversos , Endoscopia por Cápsula , Doença de Crohn/complicações , Feminino , Florida , Humanos , Intestino Delgado/patologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Centros de Atenção Terciária , Tomografia Computadorizada por Raios XRESUMO
To understand transition to turbulence via 3D disturbance growth, we report here results obtained from the solution of Navier-Stokes equation (NSE) to reproduce experimental results obtained by minimizing background disturbances and imposing deterministic excitation inside the shear layer. A similar approach was adopted in Sengupta and Bhaumik [Phys. Rev. Lett. 107, 154501 (2011)], where a route of transition from receptivity to fully developed turbulent stage was explained for 2D flow in terms of the spatio-temporal wave-front (STWF). The STWF was identified as the unit process of 2D turbulence creation for low amplitude wall excitation. Theoretical prediction of STWF for boundary layer was established earlier in Sengupta, Rao, and Venkatasubbaiah [Phys. Rev. Lett. 96, 224504 (2006)] from the Orr-Sommerfeld equation as due to spatiotemporal instability. Here, the same unit process of the STWF during transition is shown to be present for 3D disturbance field from the solution of governing NSE.
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BACKGROUND: People with intellectual disability (ID) and epilepsy are more likely to die prematurely than the general population. A significant number of deaths in people with epilepsy may be potentially preventable through better seizure control, regular monitoring and raising awareness among patients and carers. The aim of this project was to study mortality from sudden unexpected death in epilepsy (SUDEP) in adults with ID. METHODS: All adults (≥20 years old) living in Leicester city, Leicestershire and Rutland, UK, with ID between 1993 and 2010 were identified using the Leicestershire Intellectual Disability Register database. People with and without ID who died during the same period were identified using death certificate data from the Office for National Statistics (ONS). Deaths from probable and definite SUDEP were identified. Additional information on adults with ID who had died from probable or definite SUDEP was obtained from case notes and post-mortem reports, where available. Cases of probable and definite SUDEP in adults with ID were compared with the general population using standardised mortality ratios (SMRs). RESULTS: A total of 898 adults with ID had died over the 18-year study period. Of these, 244 deaths (27%) occurred in people with ID who had a diagnosis of epilepsy. Twenty-six people with ID died from probable or definite SUDEP, which was the second most common cause of death among adults with ID and epilepsy. All-cause specific SMRs were 2.2 [95% confidence interval (CI): 2.0-2.4] and 2.8 (95% CI: 2.5-3.1) for men and women with ID respectively. SMRs were 3.2 (95% CI: 2.7-3.8) and 5.6 (95% CI: 4.6-6.7) for men and women with epilepsy and ID respectively. During the same study period, 83 adults without ID had died of probable or definite SUDEP. The SMRs for SUDEP in patients with ID were 37.6 for men (95% CI: 21.9-60.2) and 52.0 for women (95% CI: 23.8-98.8). We found that in the majority of ID cases there was little detailed documentation on the circumstances surrounding deaths, no communication with patients/carers about risk of SUDEP and an absence of post-mortem reports or carers' referral for bereavement counselling. CONCLUSION: The authors believe that a comprehensive risk management under a multiagency/multidisciplinary framework should be undertaken for all adults with ID and epilepsy in day-to-day clinical practice to reduce mortality in people with ID.
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Causas de Morte , Morte Súbita/epidemiologia , Epilepsia/mortalidade , Deficiência Intelectual/mortalidade , Adulto , Estudos de Coortes , Comorbidade , Inglaterra , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valores de Referência , Fatores de Risco , Fatores Sexuais , Adulto JovemRESUMO
BACKGROUND: In the general population there are statistically significant urban-rural differences in the rate of common mental disorders. In people with intellectual disability (ID) no study has attempted to address this issue. AIMS: To compare the prevalence of mental illness, autism spectrum disorder (ASD) and behaviour disorder in people with ID living in urban areas with those living in rural areas. METHODS: Cross-sectional study of 2713 individuals registered with an ID service. Participants were assigned to urban or rural groups using the Department for Environment Food and Rural Affairs rural/urban local authority classification for their district. The main outcome variable was a clinical diagnosis of mental illness, ASD and behaviour disorder. Differences between diagnoses of mental illness in urban and rural areas were evaluated using the chi-squared test for the difference in two independent proportions. RESULTS: No differences were observed between gender, age and level of ID of service users based on their place of residence. But more people from an ethnic minority background were living in urban areas than rural areas. No differences were observed in the overall prevalence of mental illness by place of residence. However, the results showed that ASD was more common in people living in rural areas. CONCLUSIONS: We found these results surprising and at odds with the majority of studies carried out in the general population and propose several reasons for the differences found. We believe that the results and further studies in this area will help inform health service provision for those with ID who live in different geographical areas.
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Transtornos Mentais/epidemiologia , População Rural/estatística & dados numéricos , População Urbana/estatística & dados numéricos , Adulto , Síndrome de Asperger/epidemiologia , Síndrome de Asperger/psicologia , Transtorno Autístico/epidemiologia , Transtorno Autístico/psicologia , Comorbidade , Estudos Transversais , Feminino , Humanos , Deficiência Intelectual/epidemiologia , Deficiência Intelectual/psicologia , Masculino , Transtornos Mentais/psicologia , Pessoa de Meia-Idade , Prevalência , Reino Unido/epidemiologia , Adulto JovemRESUMO
Deterministic route to turbulence creation in 2D wall boundary layer is shown here by solving full Navier-Stokes equation by dispersion relation preserving (DRP) numerical methods for flow over a flat plate excited by wall and free stream excitations. Present results show the transition caused by wall excitation is predominantly due to nonlinear growth of the spatiotemporal wave front, even in the presence of Tollmien-Schlichting (TS) waves. The existence and linear mechanism of creating the spatiotemporal wave front was established in Sengupta, Rao and Venkatasubbaiah [Phys. Rev. Lett. 96, 224504 (2006)] via the solution of Orr-Sommerfeld equation. Effects of spatiotemporal front(s) in the nonlinear phase of disturbance evolution have been documented by Sengupta and Bhaumik [Phys. Rev. Lett. 107, 154501 (2011)], where a flow is taken from the receptivity stage to the fully developed 2D turbulent state exhibiting a k(-3) energy spectrum by solving the Navier-Stokes equation without any artifice. The details of this mechanism are presented here for the first time, along with another problem of forced excitation of the boundary layer by convecting free stream vortices. Thus, the excitations considered here are for a zero pressure gradient (ZPG) boundary layer by (i) monochromatic time-harmonic wall excitation and (ii) free stream excitation by convecting train of vortices at a constant height. The latter case demonstrates neither monochromatic TS wave, nor the spatiotemporal wave front, yet both the cases eventually show the presence of k(-3) energy spectrum, which has been shown experimentally for atmospheric dynamics in Nastrom, Gage and Jasperson [Nature 310, 36 (1984)]. Transition by a nonlinear mechanism of the Navier-Stokes equation leading to k(-3) energy spectrum in the inertial subrange is the typical characteristic feature of all 2D turbulent flows. Reproduction of the spectrum noted in atmospheric data (showing dominance of the k(-3) spectrum over the k(-5/3) spectrum in Nastrom et al.) in laboratory scale indicates universality of this spectrum for all 2D turbulent flows. Creation of universal features of 2D turbulence by a deterministic route has been established here for the first time by solving the Navier-Stokes equation without any modeling, as has been reported earlier in the literature by other researchers.
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Gene-directed enzyme prodrug therapy (GDEPT) is a promising and emerging strategy that attempts to limit the systemic toxicity inherent to cancer chemotherapy by means of tumor-targeted delivery and expression of an exogenous gene whose product converts nontoxic prodrug(s) into activated cytotoxic agent(s). The bacterial nitroreductase (NTR) enzyme, coupled with its substrate prodrug 5-(azaridin-1-yl)-2,4-dinitrobenzamide (CB1954), is a promising GDEPT strategy that has reached clinical trials. However, no strategy exists to visually monitor and quantitatively evaluate the therapeutic efficacy of NTR/CB1954 prodrug therapy in cells and imaging in living animals. As the success of any GDEPT is dependent upon the efficiency of transgene expression in vivo, we developed a safe, sensitive and reproducible noninvasive imaging method to monitor NTR transgene expression that would allow quantitative assessment of both therapeutic efficacy and diagnostic outcome of NTR/CB1954 prodrug therapy in the future. Here, we investigate the use of a novel fluorescent imaging dye CytoCy5S (a Cy5-labeled quenched substrate of NTR enzyme) on various cancer cell lines in vitro and in NTR-transfected tumor-bearing animals in vivo. CytoCy5S-labeled cells become fluorescent at 'red-shifted' wavelengths (638 nm) when reduced by cellular NTR enzyme and remains trapped within the cells for extended periods of time. The conversion and entrapment was dynamically recorded using a time-lapsed microscopy. Systemic and intratumoral delivery of CytoCy5S to NTR-expressing tumors in animals indicated steady and reproducible signals even 16 h after delivery (P<0.001). This is the first study to address visual monitoring and quantitative evaluation of NTR activity in small animals using CytoCy5S, and establishes the capability of NTR to function as an imageable reporter gene.
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Aziridinas/metabolismo , Imagem Molecular , Nitrorredutases/genética , Nitrorredutases/metabolismo , Pró-Fármacos/metabolismo , Animais , Aziridinas/uso terapêutico , Linhagem Celular , Ativação Enzimática/genética , Expressão Gênica , Ordem dos Genes , Vetores Genéticos , Humanos , Mucosa Intestinal/metabolismo , Intestinos/microbiologia , Cinética , Metagenoma/genética , Camundongos , Camundongos Nus , Neoplasias/tratamento farmacológico , Neoplasias/enzimologia , Neoplasias/genética , Pró-Fármacos/uso terapêutico , Transfecção , Transplante HeterólogoRESUMO
The traditional viewpoint of fluid flow considers the transition to turbulence to occur by the secondary and nonlinear instability of wave packets, which have been created experimentally by localized harmonic excitation. The boundary layer has been shown theoretically to support spatiotemporal growing wave fronts by Sengupta, Rao, and Venkatasubbaiah [Phys. Rev. Lett. 96, 224504 (2006)] by a linear mechanism, which is shown here to grow continuously, causing the transition to turbulence. Here, we track spatiotemporal wave fronts to a nonlinear turbulent state by solving the full 2D Navier-Stokes equation, without any limiting assumptions. Thus, this is the only demonstration of deterministic disturbances evolving from a receptivity stage to the full turbulent flow. This is despite the prevalent competing conjectures of the event being three-dimensional and/or stochastic in nature.
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BACKGROUND: Antipsychotics are perceived to be over-used in the management of behavioural problems in people with an intellectual disability (ID). Published guidelines have set good practice standards for the use of these drugs for behavioural indications. We sought to identify the range of indications for which antipsychotic drugs are prescribed in people with ID and to audit clinical practice against the standards. METHOD: Data were collected from the clinical records of individuals with ID who were under the care of mental health services in the UK, and prescribed an antipsychotic drug. RESULTS: The sample comprised 2319 patients from 39 clinical services. Twenty-seven per cent of the patients had a diagnosis of a psychotic illness (ICD-10 F20-29) and 27% an affective illness (ICD-10 F30-39). The proportion who did not have a psychiatric diagnosis ranged from 6% of those with borderline/mild ID to 21% of those with severe/profound ID. Overall, the most common indications for prescribing an antipsychotic drug were comorbid psychotic illness, anxiety and agitation, and a range of behavioural disturbances. The prevalence of use of antipsychotic drugs to manage challenging behaviour in the absence of concomitant mental illness increased with the severity of ID and accounted for almost half of prescriptions in those with severe/profound ID. Adherence to the audit standards related to documentation of clinical indications and review of efficacy was high. Side effect monitoring was less assiduous. CONCLUSIONS: In clinical practice, most prescriptions for antipsychotic drugs in people with ID are consistent with the evidence base and the overall quality of prescribing practice, as measured against recognised standards, is good, although in some patients potentially remedial side effects may not be detected and treated.
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Antipsicóticos/uso terapêutico , Transtornos de Deficit da Atenção e do Comportamento Disruptivo/tratamento farmacológico , Deficiência Intelectual/tratamento farmacológico , Transtornos Mentais/tratamento farmacológico , Serviços de Saúde Mental/estatística & dados numéricos , Adolescente , Adulto , Idoso , Transtornos de Deficit da Atenção e do Comportamento Disruptivo/epidemiologia , Comorbidade , Medicina Baseada em Evidências/normas , Medicina Baseada em Evidências/estatística & dados numéricos , Feminino , Humanos , Deficiência Intelectual/epidemiologia , Masculino , Transtornos Mentais/epidemiologia , Serviços de Saúde Mental/normas , Pessoa de Meia-Idade , Padrões de Prática Médica/normas , Padrões de Prática Médica/estatística & dados numéricos , Reino Unido/epidemiologia , Adulto JovemRESUMO
BACKGROUND: Aggressive challenging behaviour in people with intellectual disability (ID) is frequently treated with antipsychotic drugs, despite a limited evidence base. METHOD: A multi-centre randomised controlled trial was undertaken to investigate the efficacy, adverse effects and costs of two commonly prescribed antipsychotic drugs (risperidone and haloperidol) and placebo. RESULTS: The trial faced significant problems in recruitment. The intent was to recruit 120 patients over 2 years in three centres and to use a validated aggression scale (Modified Overt Aggression Scale) score as the primary outcome. Despite doubling the period of recruitment, only 86 patients were ultimately recruited. CONCLUSIONS: Variation in beliefs over the efficacy of drug treatment, difficulties within multidisciplinary teams and perceived ethical concerns over medication trials in this population all contributed to poor recruitment. Where appropriate to the research question cluster randomised trials represent an ethically and logistically feasible alternative to individually randomised trials.
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Agressão/efeitos dos fármacos , Antipsicóticos/uso terapêutico , Haloperidol/uso terapêutico , Deficiência Intelectual/tratamento farmacológico , Seleção de Pacientes , Risperidona/uso terapêutico , Transtornos do Comportamento Social/tratamento farmacológico , Adulto , Antipsicóticos/efeitos adversos , Relação Dose-Resposta a Droga , Método Duplo-Cego , Medicina Baseada em Evidências , Feminino , Haloperidol/efeitos adversos , Humanos , Deficiência Intelectual/psicologia , Masculino , Determinação da Personalidade/estatística & dados numéricos , Psicometria , Queensland , Risperidona/efeitos adversos , Transtornos do Comportamento Social/psicologia , Resultado do Tratamento , Reino UnidoRESUMO
Methylation of lysine residues of histones is associated with functionally distinct regions of chromatin, and, therefore, is an important epigenetic mark. Over the past few years, several enzymes that catalyze this covalent modification on different lysine residues of histones have been discovered. Intriguingly, histone lysine methylation has also been shown to be cross-regulated by histone ubiquitination or the enzymes that catalyze this modification. These covalent modifications and their cross-talks play important roles in regulation of gene expression, heterochromatin formation, genome stability, and cancer. Thus, there has been a very rapid progress within past several years towards elucidating the molecular basis of histone lysine methylation and ubiquitination, and their aberrations in human diseases. Here, we discuss these covalent modifications with their cross-regulation and roles in controlling gene expression and stability.
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Histonas/metabolismo , Histonas/fisiologia , Reparo do DNA , Regulação da Expressão Gênica , Metilação , Estabilidade Proteica , Receptor Cross-Talk , UbiquitinaçãoRESUMO
OBJECTIVE(S): To assess the effects and cost-effectiveness of haloperidol, risperidone and placebo on aggressive challenging behaviour in adults with intellectual disability. DESIGN: A double-blind randomised controlled trial of two drugs and placebo administered in flexible dosage, with full, independent assessments of aggressive and aberrant behaviour, global improvement, carer burden, quality of life and adverse drug effects at baseline, 4, 12 and 26 weeks, and comparison of total care costs in the 6 months before and after randomisation. At 12 weeks, patients were given the option of leaving the trial or continuing until 26 weeks. Assessments of observed aggression were also carried out with key workers at weekly intervals throughout the trial. SETTING: Patients were recruited from all those being treated by intellectual disability services in eight sites in England, one in Wales and one in Queensland, Australia. PARTICIPANTS: Patients from all severity levels of intellectual disability; recruitment was extended to include those who may have been treated with neuroleptic drugs in the past. EXCLUSION CRITERIA: treatment with depot neuroleptics/another form of injected neuroleptic medication within the last 3 months; continuous oral neuroleptic medication within the last week; those under a section of the Mental Health Act 1983 or Queensland Mental Health Act 2000. INTERVENTIONS: Randomisation to treatment with haloperidol (a typical neuroleptic drug), risperidone (an atypical neuroleptic drug) or placebo using a permuted blocks procedure. Dosages were: haloperidol 1.25-5.0 mg daily; risperidone 0.5-2.0 mg daily. MAIN OUTCOME MEASURES: Primary: reduction in aggressive episodes between baseline and 4 weeks using Modified Overt Aggression Scale. Secondary: Aberrant Behaviour Checklist; Uplift/Burden Scale; 40-item Quality of Life Questionnaire; Udvalg for Kliniske Undersøgelser scale; Clinical Global Impressions scale. Economic costs recorded using a modified version of Client Service Receipt Inventory for 6 months before and after randomisation. RESULTS: There were considerable difficulties in recruitment because of ethical and consent doubts. Twenty-two clinicians recruited a total of 86 patients. Mean daily dosages were 1.07 mg rising to 1.78 mg for risperidone and 2.54 mg rising to 2.94 mg for haloperidol. Aggression declined dramatically with all three treatments by 4 weeks, with placebo showing the greatest reduction (79%, versus 57% for combined drugs) (p = 0.06). Placebo-treated patients showed no evidence of inferior response in comparison to patients receiving neuroleptic drugs. An additional study found that clinicians who had not participated in clinical trials before were less likely to recruit. Mean total cost of accommodation, services, informal care and treatment over the 6 months of the trial was 16,336 pounds for placebo, 17,626 pounds for haloperidol and 18,954 pounds for risperidone. CONCLUSIONS: There were no significant important benefits conferred by treatment with risperidone or haloperidol, and treatment with these drugs was not cost-effective. While neuroleptic drugs may be of value in the treatment of aggressive behaviour in some patients with intellectual disability, the underlying pathology needs to be evaluated before these are given. The specific diagnostic indications for such treatment require further investigation. Prescription of low doses of neuroleptic drugs in intellectual disability on the grounds of greater responsiveness and greater liability to adverse effects also needs to be re-examined.
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Agressão/efeitos dos fármacos , Antipsicóticos/uso terapêutico , Haloperidol/uso terapêutico , Pessoas com Deficiência Mental , Risperidona/uso terapêutico , Adolescente , Adulto , Idoso , Agressão/psicologia , Antipsicóticos/administração & dosagem , Antipsicóticos/farmacologia , Análise Custo-Benefício , Relação Dose-Resposta a Droga , Inglaterra , Feminino , Haloperidol/administração & dosagem , Haloperidol/farmacologia , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Placebos , Risperidona/administração & dosagem , Risperidona/farmacologia , Índice de Gravidade de Doença , Adulto JovemRESUMO
BACKGROUND: Aggressive challenging behaviour is common in adults with intellectual disability (ID) in long-term care facilities. The government's commitment to the closure of all facilities in England has led to concerns over how to manage this behaviour in the community. The aim of this study was to assess changes in aggressive challenging behaviour and psychotropic drug use in adults with ID following resettlement using a person-centred approach. METHOD: The Modified Overt Aggression Scale was administered to carers of 49 adults with ID prior to discharge from a long-stay hospital and 6 months and 1 year after community resettlement. RESULTS: All areas of aggressive challenging behaviour reduced significantly between baseline and 6 months following resettlement (P < 0.001). This reduction remained (but did not decrease further) at 1-year follow-up. CONCLUSIONS: Further work is needed to evaluate the role of environmental setting on aggressive challenging behaviour in adults with ID.
Assuntos
Agressão/psicologia , Deficiência Intelectual/psicologia , Transtornos do Comportamento Social/psicologia , Adulto , Idoso , Agressão/efeitos dos fármacos , Antipsicóticos/efeitos adversos , Antipsicóticos/uso terapêutico , Comorbidade , Desinstitucionalização , Inglaterra , Feminino , Seguimentos , Lares para Grupos , Humanos , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/reabilitação , Inteligência , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Comportamento Autodestrutivo/diagnóstico , Comportamento Autodestrutivo/psicologia , Comportamento Autodestrutivo/reabilitação , Transtornos do Comportamento Social/diagnóstico , Transtornos do Comportamento Social/reabilitação , Meio SocialRESUMO
BACKGROUND: UK policies aim to facilitate access to general psychiatric services for adults with intellectual disability (ID). If this is to be achieved, it is important to have a clear idea of the characteristics and proportion of people with ID who currently access specialist psychiatric services and the nature and extent of psychiatric disorders in this population. METHODS: A cross-sectional study was carried out on all adults with ID using specialist services in Leicestershire and Rutland, UK, between 2001 and 2006. Characteristics of individuals seen by psychiatric services and the nature and prevalence of psychiatric disorders were investigated. RESULTS: Of 2711 adults identified, 1244 (45.9%) accessed specialist psychiatric services at least once during the study period. Individuals attending psychiatric services were more likely to be older and to live in residential settings; they were less likely to be south Asian or to have mild/moderate ID. The prevalence of psychiatric disorders among the total study population was 33.8%; the most common disorders were behaviour disorder (19.8%) and autistic spectrum disorders (8.8%). Epilepsy was highly prevalent (60.8%) among those attending psychiatric services without a mental health diagnosis. Behaviour disorders and autistic spectrum disorders were more common in men and in adults with severe/profound ID, whereas schizophrenia and organic disorders were more common in women and in adults with mild/moderate ID. Depression was also more common in women with ID. CONCLUSIONS: Psychiatric disorders and specialist health problems are common among adults with ID and the profile of psychiatric disorders differs from that found in general psychiatry. Close collaboration between general and specialist service providers is needed if the current move towards use of general psychiatric services in this population is to be achieved. The measures should include a clear care pathway for people with ID and mental health problems to facilitate the smooth transfer of patients between specialist and generic mental health services and arrangements for joint working where input from both services is required. The commissioning framework for such processes should be in place with appropriate pooling of resources.
Assuntos
Deficiência Intelectual/epidemiologia , Transtornos Mentais/epidemiologia , Serviços de Saúde Mental/estatística & dados numéricos , Adulto , Distribuição por Idade , Comorbidade , Estudos Transversais , Feminino , Humanos , Deficiência Intelectual/psicologia , Masculino , Transtornos Mentais/psicologia , Transtornos Mentais/terapia , Pessoa de Meia-Idade , Prevalência , Características de Residência , Índice de Gravidade de Doença , Distribuição por Sexo , Reino Unido/epidemiologia , Adulto JovemRESUMO
BACKGROUND: Previous studies of weight problems in adults with intellectual disability (ID) have generally been small or selective and given conflicting results. The objectives of our large-scale study were to identify inequalities in weight problems between adults with ID and the general adult population, and to investigate factors associated with obesity and underweight within the ID population. METHODS: We undertook a population-based prevalence study of 1119 adults with ID aged 20 and over on the Leicestershire Learning Disability Register who participated in a programme of universal health checks and home interviews with their carers. We performed a cross-sectional analysis of the register data and compared the observed and expected prevalences of body mass index categories in the ID and general populations using indirect standardisation for age. We used logistic regression to evaluate the association of a range of probable demographic, physical, mental and skills attributes with obesity and underweight. RESULTS: In those aged 25 and over, the standardised morbidity ratio (SMR) for obesity was 0.80 (95% CI 0.64-1.00) in men and 1.48 (95% CI 1.23-1.77) in women. The SMR for underweight was 8.44 (95% CI 6.52-10.82) in men and 2.35 (95% CI 1.72-3.19) in women. Among those aged 20 and over, crude prevalences were 20.7% for obesity, 28.0% for overweight, 32.7% for normal weight and 18.6% for underweight. Obesity was associated with living independently/with family, ability to feed/drink unaided, being female, hypertension, Down syndrome and the absence of cerebral palsy. Underweight was associated with younger age, absence of Down syndrome and not taking medication. CONCLUSION: Obesity in women and underweight in both men and women was more common in adults with ID than in the general population after controlling for differences in the age distributions between the two populations. The associated factors suggest opportunities for targeting high-risk groups within the ID population for lifestyle and behaviour modification.