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1.
Age Ageing ; 50(1): 40-48, 2021 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-32986799

RESUMO

BACKGROUND: Frailty, increased vulnerability to physiological stressors, is associated with adverse outcomes. COVID-19 exhibits a more severe disease course in older, comorbid adults. Awareness of atypical presentations is critical to facilitate early identification. OBJECTIVE: To assess how frailty affects presenting COVID-19 symptoms in older adults. DESIGN: Observational cohort study of hospitalised older patients and self-report data for community-based older adults. SETTING: Admissions to St Thomas' Hospital, London with laboratory-confirmed COVID-19. Community-based data for older adults using the COVID Symptom Study mobile application. SUBJECTS: Hospital cohort: patients aged 65 and over (n = 322); unscheduled hospital admission between 1 March 2020 and 5 May 2020; COVID-19 confirmed by RT-PCR of nasopharyngeal swab. Community-based cohort: participants aged 65 and over enrolled in the COVID Symptom Study (n = 535); reported test-positive for COVID-19 from 24 March (application launch) to 8 May 2020. METHODS: Multivariable logistic regression analysis performed on age-matched samples from hospital and community-based cohorts to ascertain association of frailty with symptoms of confirmed COVID-19. RESULTS: Hospital cohort: significantly higher prevalence of probable delirium in the frail sample, with no difference in fever or cough. Community-based cohort: significantly higher prevalence of possible delirium in frailer, older adults and fatigue and shortness of breath. CONCLUSIONS: This is the first study demonstrating higher prevalence of probable delirium as a COVID-19 symptom in older adults with frailty compared to other older adults. This emphasises need for systematic frailty assessment and screening for delirium in acutely ill older patients in hospital and community settings. Clinicians should suspect COVID-19 in frail adults with delirium.


Assuntos
COVID-19 , Delírio , Fragilidade , Medição de Risco/métodos , SARS-CoV-2/isolamento & purificação , Idoso , COVID-19/epidemiologia , COVID-19/psicologia , COVID-19/terapia , Teste de Ácido Nucleico para COVID-19/métodos , Teste de Ácido Nucleico para COVID-19/estatística & dados numéricos , Estudos de Coortes , Delírio/diagnóstico , Delírio/epidemiologia , Delírio/etiologia , Feminino , Idoso Fragilizado , Fragilidade/diagnóstico , Fragilidade/epidemiologia , Fragilidade/etiologia , Avaliação Geriátrica/métodos , Hospitalização/estatística & dados numéricos , Humanos , Londres/epidemiologia , Masculino , Prevalência , Fatores de Risco
3.
J Sports Sci ; 33(13): 1396-402, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25573319

RESUMO

Few studies have characterised the immune response to exercise of different intensities and durations in women. In those that have, baseline hormone levels and training status were not always adequately controlled for. Here, leucocyte and cytokine profiles of 11 aerobically trained, eumenorrhoeic females (33 ± 5 years) in the early follicular phase of the menstrual cycle were characterised after 30-min exercise at 3 intensities: 90% lactate threshold (LT), LT, and 110% LT. Proposed cytokine response mediators were quantified: plasma lactate and basal oestradiol concentrations. Intensity-dependent increases occurred in total white blood cells and lymphocyte counts (P < 0.001). Elevated plasma IL-6 and IL-1ra concentrations post-exercise [F = 12.38, P < 0.01 and F = 7.65, P < 0.05, respectively] were not intensity-dependent, indicating that cytokine release may be better associated with exercise duration than intensity in trained women. Changes in plasma IL-1ra and basal oestradiol (ρ = -0.893, P < 0.01) were correlated at intensities above LT only. These findings suggest a role for plasma sex hormones in moderating the exercise-induced immune response in women. However, the associations observed did not account for the magnitude of the cytokine response observed, and future studies should explore contributions of other potential mediators following short-duration exercise.


Assuntos
Exercício Físico/fisiologia , Fase Folicular/fisiologia , Proteína Antagonista do Receptor de Interleucina 1/sangue , Interleucina-10/sangue , Interleucina-6/sangue , Adulto , Estradiol/sangue , Feminino , Humanos , Ácido Láctico/sangue , Contagem de Linfócitos , Consumo de Oxigênio
4.
J Am Geriatr Soc ; 72(5): 1508-1524, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38241503

RESUMO

BACKGROUND: Multiple short delirium detection tools have been validated in research studies and implemented in routine care, but there has been little study of these tools in real-world conditions. This systematic review synthesized literature reporting completion rates and/or delirium positive score rates of detection tools in large clinical populations in general hospital settings. METHODS: PROSPERO (CRD42022385166). Medline, Embase, PsycINFO, CINAHL, and gray literature were searched from 1980 to December 31, 2022. Included studies or audit reports used a validated delirium detection tool performed directly with the patient as part of routine care in large clinical populations (n ≥ 1000) within a general acute hospital setting. Narrative synthesis was performed. RESULTS: Twenty-two research studies and four audit reports were included. Tools used alone or in combination were the Confusion Assessment Method (CAM), 4 'A's Test (4AT), Delirium Observation Screening Scale (DOSS), Brief CAM (bCAM), Nursing Delirium Screening Scale (NuDESC), and Intensive Care Delirium Screening Checklist (ICDSC). Populations and settings varied and tools were used at different stages and frequencies in the patient journey, including on admission only; inpatient, daily or more frequently; on admission and as inpatient; inpatient post-operatively. Tool completion rates ranged from 19% to 100%. Admission positive score rates ranged from: CAM 8%-51%; 4AT 13%-20%. Inpatient positive score rates ranged from: CAM 2%-20%, DOSS 6%-42%, and NuDESC 5-13%. Postoperative positive score rates were 21% and 28% (4AT). All but two studies had moderate-high risk of bias. CONCLUSIONS: This systematic review of delirium detection tool implementation in large acute patient populations found clinically important variability in tool completion rates, and in delirium positive score rates relative to expected delirium prevalence. This study highlights a need for greater reporting and analysis of relevant healthcare systems data. This is vital to advance understanding of effective delirium detection in routine care.


Assuntos
Delírio , Hospitais Gerais , Humanos , Lista de Checagem , Delírio/diagnóstico , Programas de Rastreamento/métodos
5.
Bone Jt Open ; 4(6): 447-456, 2023 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-37326476

RESUMO

Aims: Delirium is associated with adverse outcomes following hip fracture, but the prevalence and significance of delirium for the prognosis and ongoing rehabilitation needs of patients admitted from home is less well studied. Here, we analyzed relationships between delirium in patients admitted from home with 1) mortality; 2) total length of hospital stay; 3) need for post-acute inpatient rehabilitation; and 4) hospital readmission within 180 days. Methods: This observational study used routine clinical data in a consecutive sample of hip fracture patients aged ≥ 50 years admitted to a single large trauma centre during the COVID-19 pandemic between 1 March 2020 and 30 November 2021. Delirium was prospectively assessed as part of routine care by the 4 A's Test (4AT), with most assessments performed in the emergency department. Associations were determined using logistic regression adjusted for age, sex, Scottish Index of Multiple Deprivation quintile, COVID-19 infection within 30 days, and American Society of Anesthesiologists grade. Results: A total of 1,821 patients were admitted, with 1,383 (mean age 79.5 years; 72.1% female) directly from home. Overall, 87 patients (4.8%) were excluded due to missing 4AT scores. Delirium prevalence in the whole cohort was 26.5% (460/1,734): 14.1% (189/1,340) in the subgroup of patients admitted from home, and 68.8% (271/394) in the remaining patients (comprising care home residents and inpatients when fracture occurred). In patients admitted from home, delirium was associated with a 20-day longer total length of stay (p < 0.001). In multivariable analyses, delirium was associated with higher mortality at 180 days (odds ratio (OR) 1.69 (95% confidence interval (CI) 1.13 to 2.54); p = 0.013), requirement for post-acute inpatient rehabilitation (OR 2.80 (95% CI 1.97 to 3.96); p < 0.001), and readmission to hospital within 180 days (OR 1.79 (95% CI 1.02 to 3.15); p = 0.041). Conclusion: Delirium affects one in seven patients with a hip fracture admitted directly from home, and is associated with adverse outcomes in these patients. Delirium assessment and effective management should be a mandatory part of standard hip fracture care.

6.
Musculoskeletal Care ; 21(3): 786-796, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-36905636

RESUMO

PURPOSE: The primary aim was to evaluate the impact of COVID-19 on frailty in patients surviving a hip fracture. Secondary aims were to assess impact of COVID-19 on (i) length of stay (LoS) and post-discharge care needs, (ii) readmissions, and (iii) likelihood of returning to own home. METHODS: This propensity score-matched case-control study was conducted in a single centre between 01/03/20-30/11/21. A 'COVID-positive' group of 68 patients was matched to 141 'COVID-negative' patients. 'Index' and 'current' Clinical Frailty Scale (CFS) scores were assigned for frailty at admission and at follow-up. Data were extracted from validated records and included: demographics, injury factors, COVID-19 status, delirium status, discharge destination, and readmissions. For subgroup analysis controlling for vaccination availability, the periods 1 March 2020-30 November 2020 and 1 February 2021-30 November 2021 were considered pre-/post-vaccine periods. RESULTS: Median age was 83.0 years, 155/209 (74.2%) were female and median follow-up was 479 days (interquartile range [IQR] 311). There was an equivalent median increase in CFS in both groups (+1.00 [IQR 1.00-2.00, p = 0.472]). However, adjusted analysis demonstrated COVID-19 was independently associated with a greater magnitude change (Beta coefficient [ß] 0.27, 95% confidence interval [95% CI] 0.00-0.54, p = 0.05). COVID-19 in the post-vaccine availability period was associated with a smaller increase versus pre-vaccine (ß -0.64, 95% CI -1.20 to -0.09, p = 0.023). COVID-19 was independently associated with increased acute LoS (ß 4.40, 95% CI 0.22-8.58, p = 0.039), total LoS (ß 32.87, 95% CI 21.42-44.33, p < 0.001), readmissions (ß 0.71, 95% CI 0.04-1.38, p = 0.039), and a four-fold increased likelihood of pre-fracture home-dwelling patients failing to return home (odds ratio 4.52, 95% CI 2.08-10.34, p < 0.001). CONCLUSIONS: Hip fracture patients that survived a COVID-19 infection had increased frailty, longer LoS, more readmissions, and higher care needs. The health and social care burden is likely to be higher than prior to the COVID-19 pandemic. These findings should inform prognostication, discharge-planning, and service design to meet the needs of these patients.


Assuntos
COVID-19 , Fragilidade , Humanos , Feminino , Idoso de 80 Anos ou mais , Masculino , Fragilidade/epidemiologia , Fragilidade/complicações , COVID-19/epidemiologia , Estudos de Casos e Controles , Assistência ao Convalescente , Pandemias , Alta do Paciente , Estudos Retrospectivos
7.
J Clin Med ; 12(17)2023 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-37685625

RESUMO

The aims of this study were to assess whether completion of the emergency department (ED) Big 6 interventions (provision of pain relief, screening for delirium, early warning score (EWS) system, full blood investigation and electrocardiogram, intravenous fluids therapy, and pressure area care) in those presenting with an acute hip fracture were associated with mortality risk and length of acute hospital stay. A retrospective cohort study was undertaken. All patients aged ≥50 years that were admitted with a hip fracture via the ED at a single centre during a 42-month period were included. A total of 3613 patients (mean age 80.9; 71% female) were included. The mean follow up was 607 (range 240 to 1542) days. A total of 1180 (32.7%) patients had all six components completed. Pain relief (90.8%) was the most frequently completed component and pressure area assessment (57.6%) was the least. Completion of each of the individual Big 6 components, except for pressure areas assessment, were associated with a significantly (p ≤ 0.041) lower mortality risk at the 90-days, one-year and final follow-up. The completion of all components of the Big 6 was associated with a significantly (2.4 hours, p = 0.002) shorter time to theatre. Increasing number of Big 6 components completed were independently associated with a lower mortality risk: when all six were completed, the hazard ratio was 0.64 (95% CI 0.52 to 0.78, p < 0.001). Completion of an increasing number of Big 6 components was independently associated with shorter length of hospital stay and completion of all six was associated with a 2.3 (95% CI 0.9 to 3.8)-day shorter acute stay. The findings provide an evidence base to support the ongoing use of the Big 6 in the ED.

8.
J Infect ; 87(6): 506-515, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37777159

RESUMO

BACKGROUND: Booster COVID-19 vaccines have shown efficacy in clinical trials and effectiveness in real-world data against symptomatic and severe illness. However, some people still become infected with SARS-CoV-2 following a third (booster) vaccination. This study describes the characteristics of SARS-CoV-2 illness following a third vaccination and assesses the risk of progression to symptomatic disease in SARS-CoV-2 infected individuals with time since vaccination. METHODS: This prospective, community-based, case-control study used data from UK-based, adult (≥18 years) users of the COVID Symptom Study mobile application, self-reporting a first positive COVID-19 test between June 1, 2021 and April 1, 2022. To describe the characteristics of SARS-CoV-2 illness following a third vaccination, we selected cases and controls who had received a third and second dose of monovalent vaccination against COVID-19, respectively, and reported a first positive SARS-CoV-2 test at least 7 days after most recent vaccination. Cases and controls were matched (1:1) based on age, sex, BMI, time between first vaccination and infection, and week of testing. We used logistic regression models (adjusted for age, sex, BMI, level of social deprivation and frailty) to analyse associations of disease severity, overall disease duration, and individual symptoms with booster vaccination status. To assess for potential waning of vaccine effectiveness, we compared disease severity, duration, and symptom profiles of individuals testing positive within 3 months of most recent vaccination (reference group) to profiles of individuals infected between 3 and 4, 4-5, and 5-6 months, for both third and second dose. All analyses were stratified by time period, based on the predominant SARS-CoV-2 variant at time of infection (Delta: June 1, 2021-27 Nov, 2021; Omicron: 20 Dec, 2021-Apr 1, 2022). FINDINGS: During the study period, 50,162 (Delta period) and 162,041 (Omicron) participants reported a positive SARS-CoV-2 test. During the Delta period, infection following three vaccination doses was associated with lower odds of long COVID (symptoms≥ 4 weeks) (OR=0.83, CI[0.50-1.36], p < 0.0001), hospitalisation (OR=0.55, CI[0.39-0.75], p < 0.0001) and severe symptoms (OR=0.36, CI[0.27-0.49], p < 0.0001), and higher odds of asymptomatic infection (OR=3.45, CI[2.86-4.16], p < 0.0001), compared to infection following only two vaccination doses. During the Omicron period, infection following three vaccination doses was associated with lower odds of severe symptoms (OR=0.48, CI[0.42-0.55], p < 0.0001). During the Delta period, infected individuals were less likely to report almost all individual symptoms after a third vaccination. During the Omicron period, individuals were less likely to report most symptoms after a third vaccination, except for upper respiratory symptoms e.g. sneezing (OR=1.40, CI[1.18-1.35], p < 0.0001), runny nose (OR=1.26, CI[1.18-1.35], p < 0.0001), sore throat (OR=1.17, CI[1.10-1.25], p < 0.0001), and hoarse voice (OR=1.13, CI[1.06-1.21], p < 0.0001), which were more likely to be reported. There was evidence of reduced vaccine effectiveness during both Delta and Omicron periods in those infected more than 3 months after their most recent vaccination, with increased reporting of severe symptoms, long duration illness, and most individual symptoms. INTERPRETATION: This study suggests that a third dose of monovalent vaccine may reduce symptoms, severity and duration of SARS-CoV-2 infection following vaccination. For Omicron variants, the third vaccination appears to reduce overall symptom burden but may increase upper respiratory symptoms, potentially due to immunological priming. There is evidence of waning vaccine effectiveness against progression to symptomatic and severe disease and long COVID after three months. Our findings support ongoing booster vaccination promotion amongst individuals at high risk from COVID-19, to reduce severe symptoms and duration of illness, and health system burden. Disseminating knowledge on expected symptoms following booster vaccination may encourage vaccine uptake.


Assuntos
COVID-19 , Adulto , Humanos , Estudos de Casos e Controles , COVID-19/diagnóstico , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Síndrome de COVID-19 Pós-Aguda , Estudos Prospectivos , SARS-CoV-2 , Vacinação , Masculino , Feminino
9.
J Gerontol A Biol Sci Med Sci ; 77(9): 1890-1897, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34609487

RESUMO

BACKGROUND: Aging affects immunity, potentially altering fever response to infection. We assess effects of biological variables on basal temperature, and during COVID-19 infection, proposing an updated temperature threshold for older adults ≥65 years. METHODS: Participants were from 4 cohorts: 1 089 unaffected adult TwinsUK volunteers; 520 adults with emergency admission to a London hospital with RT-PCR confirmed SARS-CoV-2 infection; 757 adults with emergency admission to a Birmingham hospital with RT-PCR confirmed SARS-CoV-2 infection and 3 972 adult community-based COVID Symptom Study participants self-reporting a positive RT-PCR test. Heritability was assessed using saturated and univariate ACE models; mixed-effect and multivariable linear regression examined associations between temperature, age, sex, and body mass index (BMI); multivariable logistic regression examined associations between fever (≥37.8°C) and age; receiver operating characteristic (ROC) analysis was used to identify temperature threshold for adults ≥ 65 years. RESULTS: Among unaffected volunteers, lower BMI (p = .001), and increasing age (p < .001) was associated with lower basal temperature. Basal temperature showed a heritability of 47% (95% confidence interval 18%-57%). In COVID-19+ participants, increasing age was associated with lower temperatures in Birmingham and community-based cohorts (p < .001). For each additional year of age, participants were 1% less likely to demonstrate a fever ≥37.8°C (OR 0.99; p < .001). Combining healthy and COVID-19+ participants, a temperature of 37.4°C in adults ≥65 years had similar sensitivity and specificity to 37.8°C in adults <65 years for discriminating infection. CONCLUSIONS: Aging affects temperature in health and acute infection, with significant heritability, indicating genetic factors contribute to temperature regulation. Our observations suggest a lower threshold (37.4°C/97.3°F) for identifying fever in older adults ≥65 years.


Assuntos
COVID-19 , Idoso , Índice de Massa Corporal , COVID-19/epidemiologia , COVID-19/genética , Estudos de Coortes , Humanos , SARS-CoV-2/genética , Temperatura
10.
Lancet Infect Dis ; 22(1): 43-55, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34480857

RESUMO

BACKGROUND: COVID-19 vaccines show excellent efficacy in clinical trials and effectiveness in real-world data, but some people still become infected with SARS-CoV-2 after vaccination. This study aimed to identify risk factors for post-vaccination SARS-CoV-2 infection and describe the characteristics of post-vaccination illness. METHODS: This prospective, community-based, nested, case-control study used self-reported data (eg, on demographics, geographical location, health risk factors, and COVID-19 test results, symptoms, and vaccinations) from UK-based, adult (≥18 years) users of the COVID Symptom Study mobile phone app. For the risk factor analysis, cases had received a first or second dose of a COVID-19 vaccine between Dec 8, 2020, and July 4, 2021; had either a positive COVID-19 test at least 14 days after their first vaccination (but before their second; cases 1) or a positive test at least 7 days after their second vaccination (cases 2); and had no positive test before vaccination. Two control groups were selected (who also had not tested positive for SARS-CoV-2 before vaccination): users reporting a negative test at least 14 days after their first vaccination but before their second (controls 1) and users reporting a negative test at least 7 days after their second vaccination (controls 2). Controls 1 and controls 2 were matched (1:1) with cases 1 and cases 2, respectively, by the date of the post-vaccination test, health-care worker status, and sex. In the disease profile analysis, we sub-selected participants from cases 1 and cases 2 who had used the app for at least 14 consecutive days after testing positive for SARS-CoV-2 (cases 3 and cases 4, respectively). Controls 3 and controls 4 were unvaccinated participants reporting a positive SARS-CoV-2 test who had used the app for at least 14 consecutive days after the test, and were matched (1:1) with cases 3 and 4, respectively, by the date of the positive test, health-care worker status, sex, body-mass index (BMI), and age. We used univariate logistic regression models (adjusted for age, BMI, and sex) to analyse the associations between risk factors and post-vaccination infection, and the associations of individual symptoms, overall disease duration, and disease severity with vaccination status. FINDINGS: Between Dec 8, 2020, and July 4, 2021, 1 240 009 COVID Symptom Study app users reported a first vaccine dose, of whom 6030 (0·5%) subsequently tested positive for SARS-CoV-2 (cases 1), and 971 504 reported a second dose, of whom 2370 (0·2%) subsequently tested positive for SARS-CoV-2 (cases 2). In the risk factor analysis, frailty was associated with post-vaccination infection in older adults (≥60 years) after their first vaccine dose (odds ratio [OR] 1·93, 95% CI 1·50-2·48; p<0·0001), and individuals living in highly deprived areas had increased odds of post-vaccination infection following their first vaccine dose (OR 1·11, 95% CI 1·01-1·23; p=0·039). Individuals without obesity (BMI <30 kg/m2) had lower odds of infection following their first vaccine dose (OR 0·84, 95% CI 0·75-0·94; p=0·0030). For the disease profile analysis, 3825 users from cases 1 were included in cases 3 and 906 users from cases 2 were included in cases 4. Vaccination (compared with no vaccination) was associated with reduced odds of hospitalisation or having more than five symptoms in the first week of illness following the first or second dose, and long-duration (≥28 days) symptoms following the second dose. Almost all symptoms were reported less frequently in infected vaccinated individuals than in infected unvaccinated individuals, and vaccinated participants were more likely to be completely asymptomatic, especially if they were 60 years or older. INTERPRETATION: To minimise SARS-CoV-2 infection, at-risk populations must be targeted in efforts to boost vaccine effectiveness and infection control measures. Our findings might support caution around relaxing physical distancing and other personal protective measures in the post-vaccination era, particularly around frail older adults and individuals living in more deprived areas, even if these individuals are vaccinated, and might have implications for strategies such as booster vaccinations. FUNDING: ZOE, the UK Government Department of Health and Social Care, the Wellcome Trust, the UK Engineering and Physical Sciences Research Council, UK Research and Innovation London Medical Imaging and Artificial Intelligence Centre for Value Based Healthcare, the UK National Institute for Health Research, the UK Medical Research Council, the British Heart Foundation, and the Alzheimer's Society.


Assuntos
COVID-19/epidemiologia , Aplicativos Móveis/estatística & dados numéricos , Vacinação/estatística & dados numéricos , Eficácia de Vacinas , Adulto , Idoso , COVID-19/prevenção & controle , Teste para COVID-19/estatística & dados numéricos , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Autorrelato , Reino Unido/epidemiologia , Adulto Jovem
11.
Nat Med ; 27(4): 626-631, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33692530

RESUMO

Reports of long-lasting coronavirus disease 2019 (COVID-19) symptoms, the so-called 'long COVID', are rising but little is known about prevalence, risk factors or whether it is possible to predict a protracted course early in the disease. We analyzed data from 4,182 incident cases of COVID-19 in which individuals self-reported their symptoms prospectively in the COVID Symptom Study app1. A total of 558 (13.3%) participants reported symptoms lasting ≥28 days, 189 (4.5%) for ≥8 weeks and 95 (2.3%) for ≥12 weeks. Long COVID was characterized by symptoms of fatigue, headache, dyspnea and anosmia and was more likely with increasing age and body mass index and female sex. Experiencing more than five symptoms during the first week of illness was associated with long COVID (odds ratio = 3.53 (2.76-4.50)). A simple model to distinguish between short COVID and long COVID at 7 days (total sample size, n = 2,149) showed an area under the curve of the receiver operating characteristic curve of 76%, with replication in an independent sample of 2,472 individuals who were positive for severe acute respiratory syndrome coronavirus 2. This model could be used to identify individuals at risk of long COVID for trials of prevention or treatment and to plan education and rehabilitation services.


Assuntos
COVID-19/complicações , SARS-CoV-2 , Adulto , Fatores Etários , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Fatores de Tempo
12.
Int J Nephrol Renovasc Dis ; 11: 137-148, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29695925

RESUMO

IgA nephropathy (IgAN) is the most common form of primary glomerulonephritis worldwide, exhibiting a variable clinical and pathological course and significantly contributing to the global burden of chronic kidney disease and end-stage renal disease. Current standards of care focus on optimization of antihypertensive and antiproteinuric therapies (typically renin- angiotensin system blockade) to reduce disease progression. Much recent attention has focused on whether additional immunosuppression confers better outcomes than supportive management alone, and indeed, several trials have demonstrated renoprotective effects following the use of oral corticosteroids. However, results have been inconsistent, and perceived benefits must be balanced against risks and adverse effects associated with generalized immunosuppression, as highlighted by the high-profile STOP-IgAN and TESTING clinical trials. Recent translational research in vitro and animal models of IgAN have generated greater insight into potential therapeutic targets for this complex autoimmune disease. Deeper understanding of the roles of the mucosal immune barrier, complement activation and deposition, T-cell dependent and independent mechanisms of B cell activation, and of the deposition and downstream inflammatory signaling pathways of nephritogenic polymeric IgA1 complexes (e.g., signaling of immune receptors via spleen tyrosine kinase) has formed the rationale for the development of novel agents and clinical trials of more targeted therapies. However, translating findings into clinical practice is challenging, with many immunopathological features of IgAN specific to humans. Recent comprehensive reviews outline current understanding of mechanisms of IgAN as well as ongoing and future clinical trials; it is not our aim to replicate this here. Instead, we take a mechanistic approach to current treatment strategies, outlining advantages and limitations of each before exploring ongoing research with potential translation into future targeted therapies for this complex disease.

14.
JRSM Open ; 5(2): 2042533313517692, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25057373

RESUMO

OBJECTIVES: To (1) evaluate educational needs of clinical students at Al-Quds University Medical School in the West Bank; (2) address these needs where possible using synchronous distance learning, with clinicians in Oxford providing case-based tutorials to undergraduates in the West Bank via an online platform (WizIQ) and (3) assess the impact of this education. DESIGN: Review of online OxPal Medlink database for tutorials held between March 2012 and April 2013. Needs assessment and evaluation of student and tutor experiences through online questionnaires, focus groups and semi-structured interviews. SETTING: Oxford University Hospitals, Oxford, UK, and Al-Quds University Medical School, Abu Dies, Palestine. PARTICIPANTS: Doctors at Oxford University Hospitals and fourth-, fifth- and sixth-year medical students and faculty members at Al-Quds Medical School. MAIN OUTCOME MEASURES: Number of tutorials, student participation, student-rated satisfaction and qualitative feedback from tutors and students. RESULTS: Students demonstrated strong theoretical knowledge but struggled to apply this in presentation-based scenarios. Between March 2012 and April 2013, 90 tutorials were delivered to 60 students. Feedback: >95% respondents rated tutorials as 'Excellent' or 'Good' and 'Very' or 'Fairly' relevant to their future practice in Palestine. Students reported the programme had modified their approach to patients but requested better synchronization with concurrent attachments and clarification of learning outcomes. CONCLUSIONS: OxPal Medlink is a novel, web-based distance-learning partnership designed to overcome some of the challenges to local medical education in the occupied Palestinian territories. Evaluation of the first year indicates teaching is relevant to local practice and of high quality. This approach may have the potential to strengthen local capacity for medical education.

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