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BACKGROUND: It is unclear how the coronavirus disease 2019 (Covid-19) pandemic has affected multimorbidity incidence among those with one pre-existing chronic condition, as well as how vaccination could modify this association. AIM: To examine the association of Covid-19 infection with multimorbidity incidence among people with one pre-existing chronic condition, including those with prior vaccination. DESIGN: Nested case-control study. METHODS: We conducted a territory-wide nested case-control study with incidence density sampling using Hong Kong electronic health records from public healthcare facilities and mandatory Covid-19 reports. People with one listed chronic condition (based on a list of 30) who developed multimorbidity during 1 January 2020-15 November 2022 were selected as case participants and randomly matched with up to 10 people of the same age, sex and with the same first chronic condition without having developed multimorbidity at that point. Conditional logistic regression was used to estimate adjusted odds ratios (aORs) of multimorbidity. RESULTS: In total, 127â744 case participants were matched with 1â230â636 control participants. Adjusted analysis showed that there were 28%-increased odds of multimorbidity following Covid-19 [confidence interval (CI) 22% to 36%] but only 3% (non-significant) with prior full vaccination with BNT162b2 or CoronaVac (95% CI -2% to 7%). Similar associations were observed in men, women, older people aged 65 or more, and people aged 64 or younger. CONCLUSIONS: We found a significantly elevated risk of multimorbidity following a Covid-19 episode among people with one pre-existing chronic condition. Full vaccination significantly reduced this risk increase.
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COVID-19 , Masculino , Humanos , Feminino , Idoso , COVID-19/epidemiologia , COVID-19/prevenção & controle , Multimorbidade , Estudos de Casos e Controles , Vacina BNT162 , Doença CrônicaRESUMO
OBJECTIVE: This study is to evaluate if there is any difference in the balance between incidence of and remission from overweight/obesity in Hong Kong school-age children before and during the COVID-19 pandemic over three years. METHODS: This is a retrospective longitudinal study that involved children aged 6-16 years from a database of the School Physical Fitness Award Scheme. RESULTS: 2765 students were longitudinally followed up for two years. The prevalence of childhood overweight/obesity was increased between the 2019 and 2021 academic years (P < 0.001). During the COVID-19 pandemic, the rate of obesity remission significantly reduced by 7.9 % (P = 0.003), at a background of a plateau of obesity among children and adolescents. CONCLUSIONS: Our study provides evidence on the impact of school closure and home confinement as a standard infection control measure for the prevention of COVID-19, which are likely to break the balance between incidence of and remission from childhood obesity.
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COVID-19 , Obesidade Infantil , Adolescente , Humanos , Criança , Obesidade Infantil/epidemiologia , COVID-19/epidemiologia , COVID-19/prevenção & controle , Estudos Longitudinais , Estudos Retrospectivos , Hong Kong/epidemiologia , Pandemias , Sobrepeso/epidemiologiaRESUMO
INTRODUCTION: The number of poisoning cases involving attention deficit hyperactivity disorder (ADHD) medications has reportedly risen with their increased use. However, there is limited relevant evidence from Asia. We analysed the characteristics of poisoning events involving these medications in Hong Kong. METHODS: We retrieved data regarding ADHD medication-related poisoning cases from the Hong Kong Poison Information Centre and conducted a descriptive analysis of the demographic information and poisoning information including sources of cases, exposure reason, exposure location, and outcome. The HKPIC data were linked with the Hospital Authority Clinical Data Analysis and Reporting System (CDARS) via de-identified Accident and Emergency numbers of public hospitals to investigate clinical characteristics. We also retrieved ADHD medication prescription records from the CDARS, then compared trends between poisoning cases and ADHD medication use. RESULTS: We identified 72 poisoning cases involving ADHD medications between 2009 and 2019, of which approximately 70% occurred in the affected individual's residence; most were intentional poisoning events (65.3%). No statistically significant association was observed between ADHD medication prescription trends and poisoning events involving ADHD medications. Of the 66 cases (91.7%) successfully linked to CDARS, 40 (60.6%) occurred in individuals with ADHD (median age: 14 years); 26 (39.4%) occurred in individuals who lacked ADHD (median age: 33 years) but displayed higher rates of other mental disorders including depression and anxiety. CONCLUSION: No significant correlation was evident between ADHD medication prescriptions and poisoning events involving ADHD medications. However, medication management and caregiver education must be emphasised to prevent potential poisoning events.
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Transtorno do Deficit de Atenção com Hiperatividade , Estimulantes do Sistema Nervoso Central , Humanos , Adolescente , Adulto , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Estimulantes do Sistema Nervoso Central/uso terapêutico , Hong Kong/epidemiologia , Transtornos de Ansiedade/tratamento farmacológicoRESUMO
The COVID-19 pandemic led ADHD services to modify the clinical practice to reduce in-person contact as much as possible to minimise viral spread. This had far-reaching effects on day-to-day clinical practice as remote assessments were widely adopted. Despite the attenuation of the acute threat from COVID, many clinical services are retaining some remote practices. The lack of clear evidence-based guidance about the most appropriate way to conduct remote assessments meant that these changes were typically implemented in a localised, ad hoc, and un-coordinated way. Here, the European ADHD Guidelines Group (EAGG) discusses the strengths and weaknesses of remote assessment methods of children and adolescents with ADHD in a narrative review based on available data and expert opinions to highlight key recommendations for future studies and clinical practice. We conclude that going forward, despite remote working in clinical services functioning adequately during the pandemic, all required components of ADHD assessment should still be completed following national/international guidelines; however, the process may need adaptation. Social restrictions, including changes in education provision, can either mask or exacerbate features associated with ADHD and therefore assessment should carefully chart symptom profile and impairment prior to, as well as during an ongoing pandemic. While remote assessments are valuable in allowing clinical services to continue despite restrictions and may have benefits for routine care in the post-pandemic world, particular attention must be paid to those who may be at high risk but not be able to use/access remote technologies and prioritize these groups for conventional face-to-face assessments.
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Transtorno do Deficit de Atenção com Hiperatividade , COVID-19 , Humanos , Criança , Adolescente , Pandemias , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Transtorno do Deficit de Atenção com Hiperatividade/terapia , Atenção à SaúdeRESUMO
BACKGROUND: The risk of toxicity-related dose delays, with cancer treatment, should be included as part of pretreatment education and be considered by clinicians upon prescribing chemotherapy. An objective measure of individual risk could influence clinical decisions, such as escalation of standard supportive care and stratification of some patients, to receive proactive toxicity monitoring. PATIENTS AND METHODS: We developed a logistic regression prediction model (Delay-7) to assess the overall risk of a chemotherapy dose delay of 7 days for patients receiving first-line treatments for breast, colorectal and diffuse large B-cell lymphoma. Delay-7 included hospital treated, age at the start of chemotherapy, gender, ethnicity, body mass index, cancer diagnosis, chemotherapy regimen, colony stimulating factor use, first cycle dose modifications and baseline blood values. Baseline blood values included neutrophils, platelets, haemoglobin, creatinine and bilirubin. Shrinkage was used to adjust for overoptimism of predictor effects. For internal validation (of the full models in the development data) we computed the ability of the models to discriminate between those with and without poor outcomes (c-statistic), and the agreement between predicted and observed risk (calibration slope). Net benefit was used to understand the risk thresholds where the model would perform better than the 'treat all' or 'treat none' strategies. RESULTS: A total of 4604 patients were included in our study of whom 628 (13.6%) incurred a 7-day delay to the second cycle of chemotherapy. Delay-7 showed good discrimination and calibration, with c-statistic of 0.68 (95% confidence interval 0.66-0.7), following internal validation and calibration-in-the-large of -0.006. CONCLUSIONS: Delay-7 predicts a patient's individualised risk of a treatment-related delay at cycle two of treatment. The score can be used to stratify interventions to reduce the occurrence of treatment-related toxicity.
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Linfoma Difuso de Grandes Células B , Tempo para o Tratamento , Humanos , Fatores de Risco , Modelos LogísticosRESUMO
BACKGROUND: Hypertension is a recognized risk factor for dementia. However, evidence for using antihypertensive agents to reduce the risk of Alzheimer's disease in people with hypertension is inconclusive. OBJECTIVE: To examine the association between antihypertensive agents and the incidence of Alzheimer's disease in adults with hypertension and normal cognition. DESIGN: We conducted a systemic review and performed meta-analyses using Ovid MEDLINE, Ovid Embase, Ovid PsycINFO, Web of science and Scopus, from inception to 18th February 2022. SETTING: Cohort and case-control studies. PARTICIPANTS: Adults ≥ 40 years with hypertension and normal cognition. INTERVENTION: Antihypertensive agents. MEASUREMENTS: We performed two separate meta-analyses, pooling the adjusted relative risk (RR) of non-antihypertensive comparator and antihypertensive comparator study design. RESULTS: We included nine studies, totalling 1,527,410 individuals. Meta-analysis of non-antihypertensive user comparator studies found that the use of antihypertensive agents is associated with a reduced risk of incident Alzheimer's disease (RR= 0.94, 95% CI 0.90-0.99; p=0.01). Meta-analysis of antihypertensive comparator studies found evidence that angiotensin II receptor blocker users are associated with a reduction in the risk of Alzheimer's disease compared to other antihypertensive agents (RR= 0.78, 95% CI 0.68-0.88; p< 0.001). CONCLUSION: Our review provides evidence that the use of antihypertensive agents is associated with a lower incidence of Alzheimer's disease. The use of angiotensin II receptor blockers may provide the most benefit among antihypertensive agents. Lowering raised blood pressure may not be the only mechanism for cognitive protection and further investigation of the effects of angiotensin II on cognition is indicated.
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Doença de Alzheimer , Hipertensão , Humanos , Anti-Hipertensivos/uso terapêutico , Doença de Alzheimer/epidemiologia , Doença de Alzheimer/prevenção & controle , Doença de Alzheimer/complicações , Angiotensina II , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Hipertensão/prevenção & controle , Antagonistas de Receptores de Angiotensina/uso terapêuticoRESUMO
BACKGROUND: We modeled the clinical course of a cohort of diffuse large B-cell lymphoma (DLBCL) patients with no prior cardiovascular diseases (CVDs) using a multistate modeling framework. PATIENTS AND METHODS: Data on 2600 patients with DLBCL diagnosed between 2000 and 2018 and had received chemotherapy with or without radiotherapy were obtained from a population-wide electronic health database of Hong Kong. We used the Markov illness-death model to quantify the impact of doxorubicin and various risk factors (therapeutic exposure, demographic, comorbidities, cardiovascular risk factors, and lifestyle factors which included smoking) on the clinical course of DLBCL (transitions into incident CVD, lymphoma death, and other causes of death). RESULTS: A total of 613 (23.6%) and 230 (8.8%) of 2600 subjects died of lymphoma and developed incident CVD, respectively. Median follow-up was 7.0 years (interquartile range 3.8-10.8 years). Older ages [hazard ratio (HR) for >75 versus ≤60 years 1.88; 95% confidence interval (CI) 1.25-2.82 and HR for 61-75 versus ≤60 years 1.60; 95% CI 1.12-2.30], hypertension (HR 4.92; 95% CI 2.61-9.26), diabetes (HR 1.43; 95% CI 1.09-1.87), and baseline use of aspirin (HR 5.30; 95% CI 3.93-7.16) were associated with an increased risk of incident CVD. In a subgroup of anticipated higher-risk patients (aged 61-75 years, smoked, had diabetes, and received doxorubicin), we found that they remained on average 7.9 (95% CI 7.2-8.8) years in the DLBCL state and 0.1 (95% CI 0.0-0.4) years in the CVD state, if they could be followed up for 10 years. The brief time in the CVD state is consistent with the high chance of death in patients who developed CVD. Other causes of death have overtaken DLBCL-related death after about 5 years. CONCLUSIONS: In this Asian population-based cohort, we found that incident CVDs can occur soon after DLBCL treatment and continued to occur throughout survivorship. Clinicians are advised to balance the risks and benefits of treatment choices to minimize the risk of CVD.
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Doenças Cardiovasculares , Linfoma Difuso de Grandes Células B , Idoso , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/epidemiologia , Doxorrubicina/efeitos adversos , Humanos , Linfoma Difuso de Grandes Células B/complicações , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/epidemiologia , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , SobreviventesRESUMO
To determine denosumab's effectiveness for fracture prevention among postmenopausal women with osteoporosis in East Asia, the risk of fracture was compared between patients continuing denosumab therapy versus patients discontinuing denosumab after one dose. The real-world effectiveness was observed to be consistent with the efficacy demonstrated in the phase III trial. INTRODUCTION: After therapeutic efficacy is demonstrated for subjects in global clinical trials, real-world evidence may provide complementary knowledge of therapeutic effectiveness in a heterogeneous mix of patients seen in clinical practice. This retrospective cohort study was conducted to compare the fracture risk in real-world clinical care received in Taiwan and Hong Kong between a treatment cohort (patients receiving denosumab 60 mg subcutaneously every 6 months) versus an off-treatment cohort (patients discontinuing after 1 dose of denosumab, which has no known clinical benefit) among real-world postmenopausal women. METHODS: This study included 38,906 and 2,835 postmenopausal women receiving denosumab in Taiwan and Hong Kong, respectively. The primary endpoint was hip fracture, and secondary endpoints were clinical vertebral and nonvertebral fractures. Propensity-score-matched analysis, adjusting for known covariates, was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). The robustness of findings was evaluated with a series of sensitivity and quantitative bias analyses. RESULTS: In this study, 554 hip fractures were included in the primary Taiwan population analysis. The crude incidence rate was 0.9 per 100 person-years in the treatment cohort (n = 25,059) and 1.7 per 100 person-years in the off-treatment cohort (n = 13,847). After adjusting for prognostic differences between cohorts, denosumab reduced the risk of hip fractures by 38% (HR = 0.62, CI:0.52-0.75). Risk reductions of similar magnitude were observed for the secondary endpoints and for the analysis of the smaller Hong Kong population. CONCLUSION: The effectiveness of denosumab for fracture reduction among real-world postmenopausal women with osteoporosis was consistent with the efficacy demonstrated in a global clinical trial. REGISTRATION: EnCePP registration number: EUPAS26372; registration date: 12/11/2018.
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Conservadores da Densidade Óssea , Fraturas do Quadril , Osteoporose Pós-Menopausa , Osteoporose , Conservadores da Densidade Óssea/uso terapêutico , Denosumab/uso terapêutico , Feminino , Fraturas do Quadril/epidemiologia , Fraturas do Quadril/etiologia , Fraturas do Quadril/prevenção & controle , Humanos , Osteoporose/tratamento farmacológico , Osteoporose Pós-Menopausa/complicações , Osteoporose Pós-Menopausa/tratamento farmacológico , Osteoporose Pós-Menopausa/epidemiologia , Pós-Menopausa , Estudos RetrospectivosRESUMO
BACKGROUND: Previous studies have found contradicting results with regard to the use of antipsychotics during pregnancy and the risk of gestational diabetes mellitus (GDM). We aimed to evaluate the association between antipsychotic use in pregnancy and GDM. METHODS: A systematic literature search was conducted in PubMed, EMBASE, PsycINFO and Cochrane Library databases up to March 2019, for data from observational studies assessing the association between gestational antipsychotic use and GDM. Non-English studies, animal studies, case reports, conference abstracts, book chapters, reviews and summaries were excluded. The primary outcome was GDM. Estimates were pooled using a random effect model, with the I2 statistic used to estimate heterogeneity of results. Our study protocol was registered with PROSPERO number: CRD42018095014. RESULTS: In total 10 cohort studies met the inclusion criteria in our systematic review with 6642 exposed and 1 860 290 unexposed pregnancies. Six studies were included in the meta-analysis with a pooled adjusted relative risk of 1.24 overall [95% confidence interval (CI) 1.09-1.42]. The I2 result suggested low heterogeneity between studies (I2 = 6.7%, p = 0.373). CONCLUSION: We found that the use of antipsychotic medications during pregnancy is associated with an increased risk of GDM in mothers. However, the evidence is still insufficient, especially for specific drug classes. We recommend more studies to investigate this association for specific drug classes, dosages and comorbidities to help clinicians to manage the risk of GDM if initiation or continuation of antipsychotic prescriptions during pregnancy is needed.
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Antipsicóticos/efeitos adversos , Diabetes Gestacional/induzido quimicamente , Diabetes Gestacional/epidemiologia , Antipsicóticos/uso terapêutico , Feminino , Humanos , Transtornos Mentais/tratamento farmacológico , Gravidez , Fatores de RiscoRESUMO
AIM: Current guideline recommends insulin as fourth-line glucose-lowering medications. However, treatment effects of sodium glucose co-transporter-2 inhibitors (SGLT2i) on the risk of complications are uncertain. This study examines risks of all-cause mortality, cardiovascular diseases (CVD) and end-stage renal diseases (ESRD) in type 2 diabetes mellitus (T2DM) patients on triple oral glucose-lowering medications initiating SGLT2i, insulin or other oral medications. METHODS: A population-based retrospective cohort of patients with T2DM between 2006-2017 was extracted from Hong Kong Hospital Authority database. Patients who were initiated a fourth-line therapy with SGLT2i, insulin or other oral medications were included. Hazard ratios (HRs) for all-cause mortality, CVD and ESRD were assessed using Cox proportional hazard models. RESULTS: Over a median follow-up period of 18.5 months with 63,122 person-years, SGLT2i and insulin group had the lowest and highest incidence rate of all-cause mortality, CVD and ESRD (1.06, 0.65 and 0.61 vs 4.25, 5.58 and 4.39/100 person-years), respectively. Initiating SGLT2i as fourth-line medication had more benefits on CVD, in particular coronary heart disease and stroke. Insulin users had higher risks of CVD (HR=8.04, 95%CI=3.06-21.12) than SGLT2i users. SGLT2i was associated with insignificant reduction in ESRD (HR=4.62, 95%CI=0.73-29.09) and all-cause mortality (HR=3.06, 95%CI=0.75-12.45), and HF (HR=2.99, 95%CI=0.37-24.42) among patients without established HF. CONCLUSION: Among T2DM patients initiating fourth-line therapy, SGLT2i users had significant benefits in lowering risk of CVD, and potential benefits in lowering risks of ESRD and all-cause mortality. SGLT2i was the preferred fourth-line glucose-lowering medication least likely to be associated with complication risks.
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Diabetes Mellitus Tipo 2 , Inibidores do Transportador 2 de Sódio-Glicose , Doenças Cardiovasculares/epidemiologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Humanos , Falência Renal Crônica/epidemiologia , Mortalidade , Medição de Risco , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversosRESUMO
The coronavirus disease 2019 (COVID-19) pandemic has resulted in millions of patients infected worldwide and indirectly affecting even more individuals through disruption of daily living. Long-term adverse outcomes have been reported with similar diseases from other coronaviruses, namely Middle East Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS). Emerging evidence suggests that COVID-19 adversely affects different systems in the human body. This review summarizes the current evidence on the short-term adverse health outcomes and assesses the risk of potential long-term adverse outcomes of COVID-19. Major adverse outcomes were found to affect different body systems: immune system (including but not limited to Guillain-Barré syndrome and paediatric inflammatory multisystem syndrome), respiratory system (lung fibrosis and pulmonary thromboembolism), cardiovascular system (cardiomyopathy and coagulopathy), neurological system (sensory dysfunction and stroke), as well as cutaneous and gastrointestinal manifestations, impaired hepatic and renal function. Mental health in patients with COVID-19 was also found to be adversely affected. The burden of caring for COVID-19 survivors is likely to be huge. Therefore, it is important for policy makers to develop comprehensive strategies in providing resources and capacity in the healthcare system. Future epidemiological studies are needed to further investigate the long-term impact on COVID-19 survivors.
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Betacoronavirus , Infecções por Coronavirus/complicações , Infecções por Coronavirus/epidemiologia , Avaliação de Resultados da Assistência ao Paciente , Pneumonia Viral/complicações , Pneumonia Viral/epidemiologia , Betacoronavirus/imunologia , COVID-19 , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Interações Hospedeiro-Patógeno/imunologia , Humanos , Especificidade de Órgãos , Pandemias , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , SARS-CoV-2 , Fatores de TempoRESUMO
INTRODUCTION: As the first approved oral kinase inhibitor, tofacitinib is effective and well-tolerated, but more expensive than conventional treatments for uncontrolled rheumatoid arthritis. Public formulary listing typically exerts a positive impact on the uptake of new drugs. We aimed to assess the budgetary impact of introducing tofacitinib into the Hospital Authority Drug Formulary as a fully subsidised drug in Hong Kong. METHODS: We applied a population-based budget impact model to trace the number of eligible patients receiving biologics or tofacitinib treatment, then estimated the 5-year healthcare expenditure on rheumatoid arthritis treatments, with or without tofacitinib (2017-2021). We used linear regression to estimate the number of target patients and compound annual growth rate to estimate market share. Competing treatments included abatacept, adalimumab, certolizumab pegol, etanercept, golimumab, infliximab, and tofacitinib. Retail price was used for drug costs, valued in Hong Kong dollars (HK$) in 2017 and discounted at 4% per year. RESULTS: The annual treatment cost of tofacitinib was HK$74 214 per patient, and the costs of biologics ranged from HK$64 350 to HK$115 700. Without tofacitinib, the annual government health expenditures for rheumatoid arthritis treatment were estimated to increase from HK$147.9 million (2017) to HK$190.6 million (2021). The introduction of tofacitinib to the formulary would reduce healthcare expenditures by 17.3% to 20.3% per year, with cumulative savings of HK$192.8 million; this change was estimated to provide consistent savings (HK$66.4 million to HK$196.8 million) in all tested scenarios. CONCLUSION: Introduction of tofacitinib to the formulary will provide 5-year savings, given the current drug price and patient volume.
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Artrite Reumatoide/economia , Produtos Biológicos/economia , Custos de Cuidados de Saúde/estatística & dados numéricos , Piperidinas/economia , Inibidores de Proteínas Quinases/economia , Pirimidinas/economia , Pirróis/economia , Artrite Reumatoide/tratamento farmacológico , Custos de Cuidados de Saúde/tendências , Hong Kong , Hospitais Públicos , Humanos , Modelos Lineares , Piperidinas/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas/uso terapêutico , Pirróis/uso terapêuticoRESUMO
BACKGROUND: While accelerated ageing is recognised among individuals with Down syndrome (DS), the trajectory of their bone health across adulthood remains poorly understood. METHODS: This study aimed to determine the age-related loss of bone mineral density (BMD) of the lumbar spine in 128 adults with DS aged 18 to 54 years compared with 723 counterparts without DS. RESULTS: Men and women with DS had lower level of BMD than counterparts without DS across age groups. Magnitude of decrement in BMD as reflected in the z-scores was similar between younger and older men with DS. Older women with DS, on the contrary, showed greater decrement in older ages especially in their fourth decade of life. Osteopenia and osteoporosis as defined using age-specific and gender-specific T-scores affected greater number of men with DS (38% and 25%) than women (17% and 17%) aged 40-49 years. CONCLUSIONS: Findings supported adults with DS, especially men, to have early bone mineral testing.
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Senilidade Prematura/diagnóstico por imagem , Densidade Óssea , Doenças Ósseas Metabólicas/diagnóstico por imagem , Síndrome de Down/diagnóstico por imagem , Absorciometria de Fóton , Adolescente , Adulto , Senilidade Prematura/complicações , Doenças Ósseas Metabólicas/etiologia , Síndrome de Down/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoporose/diagnóstico por imagem , Osteoporose/etiologia , Fatores Sexuais , Adulto JovemAssuntos
Hidrato de Cloral/administração & dosagem , Dexmedetomidina/administração & dosagem , Hipnóticos e Sedativos/administração & dosagem , Tomografia Computadorizada por Raios X/métodos , Administração Intranasal , Administração Oral , Pré-Escolar , Hidrato de Cloral/efeitos adversos , Dexmedetomidina/efeitos adversos , Método Duplo-Cego , Humanos , Hipnóticos e Sedativos/efeitos adversos , LactenteRESUMO
BACKGROUND: Intranasal dexmedetomidine produces safe, effective sedation in children and adults. It may be administered by drops from a syringe or by nasal mucosal atomisation (MAD NasalTM). METHODS: This prospective, three-period, crossover, double-blind study compared the pharmacokinetic (PK) and pharmacodynamic (PD) profile of i.v. administration with these two different modes of administration. In each session each subject received 1 µg kg-1 dexmedetomidine, either i.v., intranasal with the atomiser or intranasal by drops. Dexmedetomidine plasma concentration and Ramsay sedation score were used for PK/PD modelling by NONMEM. RESULTS: The i.v. route had a significantly faster onset (15 min, 95% CI 15-20 min) compared to intranasal routes by atomiser (47.5 min, 95% CI 25-135 min), and by drops (60 min, 95%CI 30-75 min), (P<0.001). There was no significant difference in sedation duration across the three treatment groups (P=0.88) nor in the median onset time between the two modes of intranasal administration (P=0.94). A 2-compartment disposition model, with transit intranasal absorption and clearance driven by cardiac output using the well-stirred liver model, was the final PK model. Intranasal bioavailability was estimated to be 40.6% (95% CI 34.7-54.4%) and 40.7% (95% CI 36.5-53.2%) for atomisation and drops respectively. Sedation score was modelled via a sigmoidal Emax model driven by an effect compartment. The effect compartment had an equilibration half time 3.3 (95% CI 1.8-4.7) min-1, and the EC50 was estimated to be 903 (95% CI 450-2344) pg ml-1. CONCLUSIONS: There is no difference in bioavailability with atomisation or nasal drops. A similar degree of sedation can be achieved by either method. CLINICAL TRIAL REGISTRATION: HKUCTR-1617.
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Dexmedetomidina/farmacologia , Hipnóticos e Sedativos/farmacologia , Administração Intranasal , Administração Intravenosa , Adulto , Estudos Cross-Over , Dexmedetomidina/administração & dosagem , Dexmedetomidina/farmacocinética , Método Duplo-Cego , Feminino , Humanos , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/farmacocinética , Masculino , Estudos ProspectivosRESUMO
Essentials Bleeding is a common cause of hospital admission and readmission in oral anticoagulant users. Patients with dabigatran and warfarin were included to assess hospital admission risk. Dabigatran users had a higher risk of 30-day readmission with bleeding than warfarin users. Close monitoring following hospital discharge for dabigatran-related bleeding is warranted. SUMMARY: Background Reducing 30-day hospital readmission is a policy priority worldwide. Warfarin-related bleeding is among the most common cause of hospital admissions as a result of adverse drug events. Compared with warfarin, dabigatran achieves a full anticoagulation effect more quickly following its initiation; hence it may lead to early-onset bleeds. Objectives To compare the incidence of bleeding-related hospital admissions and 30-day readmissions with dabigatran vs. warfarin in patients with non-valvular atrial fibrillation (NVAF). Methods This was a retrospective cohort study using a population-wide database managed by the Hong Kong Hospital Authority. Patients newly diagnosed with NVAF from 2010 through to 2014 and prescribed dabigatran or warfarin were 1:1 matched by propensity score. The incidence rate of hospital admission with bleeding (a composite of gastrointestinal bleeding, intracranial hemorrhage and bleeding at other sites) was assessed. Results Among the 51 946 patients with NVAF, 8309 users of dabigatran or warfarin were identified, with 5160 patients matched by propensity score. The incidence of first hospitalized bleeding did not differ significantly between groups (incidence rate ratio, 0.92; 95% confidence interval [CI], 0.66-1.28). Among patients who were continuously prescribed their initial anticoagulants upon discharge, dabigatran use was associated with a higher risk of 30-day readmission with bleeding over warfarin (adjusted hazard ratio, 2.87; 95%CI, 1.10-7.43). Conclusion When compared with warfarin, dabigatran was associated with a comparable incidence of first hospital admission but a higher risk of 30-day redmission with respect to bleeding. Close early monitoring of patients initiated on dabigatran following hospital discharge for bleeding is warranted.
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Anticoagulantes/efeitos adversos , Antitrombinas/efeitos adversos , Fibrilação Atrial/tratamento farmacológico , Coagulação Sanguínea/efeitos dos fármacos , Dabigatrana/efeitos adversos , Hemorragia/induzido quimicamente , Readmissão do Paciente , Varfarina/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/sangue , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/epidemiologia , Bases de Dados Factuais , Feminino , Hemorragia/diagnóstico , Hemorragia/epidemiologia , Hemorragia/terapia , Hong Kong/epidemiologia , Humanos , Incidência , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Razão de Chances , Pontuação de Propensão , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
Acanthosis Nigricans (AN) is a common finding in adolescents with obesity. Little is known about its relevance for cardiovascular (CVS) risk, in particular arterial stiffening. We investigated associations between AN, conventional markers of CVS risk and carotid-radial pulse wave velocity (PWV) in a community sample of adolescents with obesity aged 12-19 recruited to an obesity trial. AN was present in 63% of subjects and 43% had severe grading. Presence of AN and severe AN were associated with z-score of body mass index (BMIz). Presence of AN (but not severity) was associated with abnormal or fasting hyperinsulinaemia but not after adjustment for BMIz. PWV data were available for 147 (84% of participants). Severe-grade AN was associated with PWV (co-efficient 0.51, 95% CI 0.13-0.89, P=0.01) but not when adjusted for BMIz, ethnic grouping and age. In our study presence and severity of AN offered little additional information on CVS risk beyond the degree of obesity itself. The relevance of AN for CVS risk should be interpreted with caution.