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BACKGROUND AND AIMS: A cardiovascular disease polygenic risk score (CVD-PRS) can stratify individuals into different categories of cardiovascular risk, but whether the addition of a CVD-PRS to clinical risk scores improves the identification of individuals at increased risk in a real-world clinical setting is unknown. METHODS: The Genetics and the Vascular Health Check Study (GENVASC) was embedded within the UK National Health Service Health Check (NHSHC) programme which invites individuals between 40-74 years of age without known CVD to attend an assessment in a UK general practice where CVD risk factors are measured and a CVD risk score (QRISK2) is calculated. Between 2012-2020, 44,141 individuals (55.7% females, 15.8% non-white) who attended an NHSHC in 147 participating practices across two counties in England were recruited and followed. When 195 individuals (cases) had suffered a major CVD event (CVD death, myocardial infarction or acute coronary syndrome, coronary revascularisation, stroke), 396 propensity-matched controls with a similar risk profile were identified, and a nested case-control genetic study undertaken to see if the addition of a CVD-PRS to QRISK2 in the form of an integrated risk tool (IRT) combined with QRISK2 would have identified more individuals at the time of their NHSHC as at high risk (QRISK2 10-year CVD risk of ≥10%), compared with QRISK2 alone. RESULTS: The distribution of the standardised CVD-PRS was significantly different in cases compared with controls (cases mean score .32; controls, -.18, P = 8.28×10-9). QRISK2 identified 61.5% (95% confidence interval [CI]: 54.3%-68.4%) of individuals who subsequently developed a major CVD event as being at high risk at their NHSHC, while the combination of QRISK2 and IRT identified 68.7% (95% CI: 61.7%-75.2%), a relative increase of 11.7% (P = 1×10-4). The odds ratio (OR) of being up-classified was 2.41 (95% CI: 1.03-5.64, P = .031) for cases compared with controls. In individuals aged 40-54 years, QRISK2 identified 26.0% (95% CI: 16.5%-37.6%) of those who developed a major CVD event, while the combination of QRISK2 and IRT identified 38.4% (95% CI: 27.2%-50.5%), indicating a stronger relative increase of 47.7% in the younger age group (P = .001). The combination of QRISK2 and IRT increased the proportion of additional cases identified similarly in women as in men, and in non-white ethnicities compared with white ethnicity. The findings were similar when the CVD-PRS was added to the atherosclerotic cardiovascular disease pooled cohort equations (ASCVD-PCE) or SCORE2 clinical scores. CONCLUSIONS: In a clinical setting, the addition of genetic information to clinical risk assessment significantly improved the identification of individuals who went on to have a major CVD event as being at high risk, especially among younger individuals. The findings provide important real-world evidence of the potential value of implementing a CVD-PRS into health systems.
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In this article, we will solve the Bagley-Torvik equation by employing integral transform method. Caputo fractional derivative operator is used in the modeling of the equation. The obtained solution is expressed in terms of generalized G function. Further, we will compare the obtained results with other available results in the literature to validate their usefulness. Furthermore, examples are included to highlight the control of the fractional parameters on he dynamics of the model. Moreover, we use this equation in modelling of real free oscillations of a one-degree-of-freedom mechanical system composed of a cart connected with the springs to the support and moving via linear rolling bearing block along a rail.
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BACKGROUND AND OBJECTIVES: A recent change in the diabetes Quality and Outcomes Framework (QOF) retired the mandatory testing of urinary ACR. We designed a study demonstrates the impact of this change in a primary healthcare setting. This is relevant as a significant proportion of the NHS budget is spent on managing microvascular and macrovascular complications that result from type 1 and 2 Diabetes mellitus. METHODS: Our cross-sectional study collected testing data for 482 patients in a primary care setting. Based on the results seen from the first set of data collection, an intervention was offered to the clinicians by way of clinical presentation that emphasised and refreshed the knowledge of the latest NICE guidelines on urine ACR collection. Subsequently, a second set of data collection was conducted to assess the success, if any, of changes implemented based on the intervention made RESULTS: Our study demonstrates the drastic decrease in uptake of ACR testing in the primary care setting that took place following the change in the diabetes QOF. CONCLUSION: The study highlights the need for the reintroduction of such a QOF measure to enable regular monitoring of early signs of nephropathy, thereby allow the timely commencement treatment as deemed appropriate. Furthermore, detecting the development of such complications in diabetic patients, in a timely manner, has the potential to reduce the financial footprint associated with treating the complications resulting from this condition.
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Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Humanos , Estudios Transversales , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/terapia , Diabetes Mellitus Tipo 2/complicaciones , Recolección de Datos , Atención Primaria de Salud , Albuminuria/diagnósticoRESUMEN
BACKGROUND: Randomised sham-controlled trials of cranial electrostimulation with the Alpha-Stim Anxiety Insomnia and Depression (AID) device have reported improved anxiety and depression symptoms; however, no adequately powered sham-controlled trials in major depression are available. We investigated whether active Alpha-Stim AID is superior to sham Alpha-Stim AID in terms of clinical effectiveness for depression symptoms in major depression. METHODS: The Alpha-Stim-D trial was a multicentre, parallel group, double-blind, randomised controlled trial, recruiting participants from 25 primary care centres in two regions in England, UK. Eligible participants were aged 16 years or older with a current diagnosis of primary major depression, a score of 10-19 on the nine-item Patient Health Questionnaire, and had been offered or prescribed and reported taking antidepressant medication for at least 6 weeks in the previous 3 months. Main exclusion criteria were contraindications to Alpha-Stim AID device use, having persistent suicidal ideation or self-harm, neurological conditions, a substance use disorder or dependence, an eating disorder, bipolar disorder, or non-affective psychosis, or receiving psychological treatment in the past 3 months. Eligible participants were randomly assigned (1:1, minimised by region, anxiety disorder, and antidepressant use) to 1 h daily use of active (100 µA) or sham Alpha-Stim AID treatment for 8 weeks. Randomisation was via an independent web-based system, with participants, outcome assessors, and data analyst masked to treatment assignment. The primary outcome was change from baseline in score on the 17-item Hamilton Depression Rating Scale (HDRS-17, GRID version) at 16 weeks after randomisation, with participants analysed by intention to treat (ITT; all randomly assigned participants). Safety was assessed in all randomly assigned participants. The trial is registered with the ISRCTN registry (ISRCTN11853110); status completed. FINDINGS: Between Sept 8, 2020, and Jan 14, 2022, 236 eligible participants were randomly assigned to active or sham Alpha-Stim AID (n=118 each). 156 (66%) participants were women, 77 (33%) were men, and three (1%) self-reported as other gender; 200 (85%) were White British or Irish; and the mean age was 38·0 years (SD 15·3; range 16-83). 102 (86%) participants in the active Alpha-Stim AID group and 98 (83%) in the sham group were followed up 16 weeks after randomisation. In the ITT population, mean change in GRID-HDRS-17 at 16 weeks was -5·9 (95% CI -7·1 to -4·8) in the active Alpha-Stim AID group and -6·5 (-7·7 to -5·4) in the sham group (mean change difference -0·6 [95% CI -1·0 to 2·2], p=0·46). Among the 236 participants, 17 adverse events were reported in 17 (7%) participants (nine [8%] participants in the active Alpha-Stim AID group; and eight [7%] participants in the sham group). One serious adverse event of suicidal ideation leading to hospitalisation was reported in the sham group, which was judged to be unrelated to the device. INTERPRETATION: Active Alpha-Stim AID was safe and acceptable, but no more clinically effective than sham Alpha-Stim AID in major depression. FUNDING: National Institute for Health Research Applied Research Collaboration East Midlands and Electromedical Products International.
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Trastorno Depresivo Mayor , Adulto , Femenino , Humanos , Masculino , Antidepresivos , Depresión , Trastorno Depresivo Mayor/terapia , Trastorno Depresivo Mayor/psicología , Método Doble Ciego , Inglaterra , Atención Primaria de Salud , Resultado del Tratamiento , Adolescente , Adulto Joven , Persona de Mediana Edad , Anciano , Anciano de 80 o más AñosRESUMEN
OBJECTIVE: The aim of the study was to assess the clinical effectiveness of the national cardiovascular disease (CVD) prevention programme-National Health Service Health Check (NHSHC) in reduction of CVD risk. DESIGN: Prospective cohort study. SETTING: 147 primary care practices in Leicestershire and Northamptonshire in England, UK. PARTICIPANTS: 27 888 individuals undergoing NHSHC with a minimum of 18 months of follow-up data. OUTCOME MEASURES: The primary outcomes were NHSHC attributed detection of CVD risk factors, prescription of medications, changes in values of individual risk factors and frequency of follow-up. RESULTS: At recruitment, 18% of participants had high CVD risk (10%-20% 10-year risk) and 4% very high CVD risk (>20% 10-year risk). New diagnoses or hypertension (HTN) was made in 2.3% participants, hypercholesterolaemia in 0.25% and diabetes mellitus in 0.9%. New prescription of stains and antihypertensive medications was observed in 5.4% and 5.4% of participants, respectively. Total cholesterol was decreased on average by 0.38 mmol/L (95% CI -0.34 to -0.41) and 1.71 mmol/L (-1.48 to -1.94) in patients with initial cholesterol >5 mmol/L and >7.5 mmol/L, respectively. Systolic blood pressure was decreased on average by 2.9 mm Hg (-2.3 to -3.7), 15.7 mm Hg (-14.1 to -17.5) and 33.4 mm Hg (-29.4 to -37.7), in patients with grade 1, 2 and 3 HTN, respectively. About one out of three patients with increased CVD risk had no record of follow-up or treatment. CONCLUSIONS: Majority of patients identified with increased CVD risk through the NHSHC were followed up and received effective clinical interventions. However, one-third of high CVD risk patients had no follow-up and therefore did not receive any treatment. Our study highlights areas of focus which could improve the effectiveness of the programme. TRIAL REGISTRATION NUMBER: NCT04417387.
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Enfermedades Cardiovasculares , Hipertensión , Humanos , Colesterol , Hipertensión/tratamiento farmacológico , Estudios Prospectivos , Factores de Riesgo , Medicina Estatal , Resultado del TratamientoRESUMEN
BACKGROUND: Major depression is the second leading cause of years lost to disability worldwide and is a leading contributor to suicide. However, first-line antidepressants are only fully effective for 33%, and only 40% of those offered psychological treatment attend for two sessions or more. Views gained from patients and primary care professionals are that greater treatment uptake might be achieved if people with depression could be offered alternative and more accessible treatment options. Although there is evidence that the Alpha-Stim Anxiety Insomnia and Depression (AID) device is safe and effective for anxiety and depression symptoms in people with anxiety disorders, there is much less evidence of efficacy in major depression without anxiety. This study investigates the effectiveness of the Alpha-Stim AID device, a cranial electrotherapy stimulation (CES) treatment that people can safely use independently at home. The device provides CES which has been shown to increase alpha oscillatory brain activity, associated with relaxation. METHODS: The aim of this study is to investigate the clinical and cost-effectiveness of Alpha-Stim AID in treatment-seeking patients (aged 16 years upwards) with moderate to moderately severe depressive symptoms in primary care. The study is a multi-centre parallel-group, double-blind, non-commercial, randomised controlled superiority trial. The primary objective of the study is to examine the clinical efficacy of active daily use of 8 weeks of Alpha-Stim AID versus sham Alpha-Stim AID on depression symptoms at 16 weeks (8 weeks after the end of treatment) in people with moderate severity depression. The primary outcome is the 17-item Hamilton Depression Rating Scale at 16 weeks. All trial and treatment procedures are carried out remotely using videoconferencing, telephone and postal delivery considering the COVID-19 pandemic restrictions. DISCUSSION: This study is investigating whether participants using the Alpha-Stim AID device display a reduction in depressive symptoms that can be maintained over 8 weeks post-treatment. The findings will help to determine whether Alpha-Stim AID should be recommended, including being made available in the NHS for patients with depressive symptoms. TRIAL REGISTRATION: ISRTCN ISRCTN11853110 . Registered on 14 August 2020.
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COVID-19 , Trastorno Depresivo Mayor , Terapia por Estimulación Eléctrica , Adolescente , COVID-19/terapia , Análisis Costo-Beneficio , Depresión/tratamiento farmacológico , Depresión/terapia , Trastorno Depresivo Mayor/terapia , Humanos , Pandemias , Atención Primaria de SaludRESUMEN
INTRODUCTION: As the therapeutic options in the management of type 2 diabetes increase, there is an increase confusion among health care professionals, thus leading to the phenomenon of therapeutic inertia. This is the failure to escalate or de-escalate treatment when the clinical need for this is required. It has been studied extensively in various settings, however, it has never been reported in any studies focusing solely on primary care physicians with an interest in diabetes. This group is increasingly becoming the focus of managing complex diabetes care in the community, albeit with the support from specialists. METHODS: In this retrospective audit, we assessed the prevalence of the phenomenon of therapeutic inertia amongst primary care physicians with an interest in diabetes in UK. We also assessed the predictive abilities of various patient level characteristics on therapeutic inertia amongst this group of clinicians. RESULTS: Out of the 240 patients reported on, therapeutic inertia was judged to have occurred in 53 (22.1%) of patients. The full model containing all the selected variables was not statistically significant, p=0.59. So the model was not able to distinguish between situations in which therapeutic inertia occurred and when it did not occur. None of the patient level characteristics on its own was predictive of therapeutic inertia. CONCLUSION: Therapeutic inertia was present only in about a fifth of patient patients with diabetes being managed by primary care physicians with an interest in diabetes.
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Actitud del Personal de Salud , Glucemia/efectos de los fármacos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Médicos Generales/psicología , Adhesión a Directriz , Conocimientos, Actitudes y Práctica en Salud , Hipoglucemiantes/administración & dosificación , Guías de Práctica Clínica como Asunto , Pautas de la Práctica en Medicina , Atención Primaria de Salud , Anciano , Biomarcadores/sangre , Glucemia/metabolismo , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/diagnóstico , Femenino , Médicos Generales/normas , Hemoglobina Glucada/metabolismo , Adhesión a Directriz/normas , Humanos , Hipoglucemiantes/efectos adversos , Masculino , Auditoría Médica , Persona de Mediana Edad , Guías de Práctica Clínica como Asunto/normas , Pautas de la Práctica en Medicina/normas , Atención Primaria de Salud/normas , Estudios Retrospectivos , Factores de Riesgo , Reino UnidoRESUMEN
Using nasopharyngeal carriage as a marker of vaccine impact, pneumococcal colonization and its relation to invasive disease were examined in children, their parents, and older adults in the United Kingdom following introduction of 7-valent pneumococcal conjugate vaccine (PCV7) and prior to 13-valent pneumococcal conjugate vaccine (PCV13).A cross-sectional observational study was conducted, collecting nasopharyngeal swabs from children aged 25 to 55 months who had previously received 3 doses of PCV7, their parents, and adults aged ≥65 years. Pneumococcal serotyping was conducted according to World Health Organization guidelines with nontypeable isolates further analyzed by molecular serotyping. A national invasive disease surveillance program was conducted throughout the corresponding period.Pneumococcus was isolated from 47% of children, 9% of parents, and 2.2% of older adults. For these groups, the percentage of serotypes covered by PCV7 were 1.5%, 0.0%, and 15.4%, with a further 20.1%, 44.4%, and 7.7% coverage added by those in PCV13. In each group, the percentage of disease due to serotypes covered by PCV7 were 1.0%, 7.4% and 5.1% with a further 65.3%, 42.1%, and 61.4% attributed to those in PCV13.The prevalence of carriage is the highest in children, with direct vaccine impact exemplified by low carriage and disease prevalence of PCV7 serotypes in vaccinated children, whereas the indirect effects of herd protection are implied by similar observations in unvaccinated parents and older adults.
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Nasofaringe/microbiología , Infecciones Neumocócicas/prevención & control , Streptococcus pneumoniae/aislamiento & purificación , Vacunas Conjugadas/farmacología , Adulto , Anciano , Preescolar , Estudios Transversales , Femenino , Humanos , Masculino , Nasofaringe/efectos de los fármacos , Serogrupo , Streptococcus pneumoniae/genéticaRESUMEN
Diabetes is highly prevalent and serious chronic debilitating disease and reported to be the fourth main cause of death in Europe. Despite extensive evidence of benefits of tight glycemic control, large proportions of people with diabetes do not achieve target glycemic control. One major reason for this is clinical inertia which is "recognising the problem but failure to act" by health care professionals in primary care. The key issues in the management of people with T2DM include early detection of problems, realistic goal setting, improved patient adherence, better knowledge and understanding of pharmacotherapeutic treatment options and prompt intervention. Health care professionals must need to overcome clinical inertia and need to intensify therapy in an appropriate and timely manner.