RESUMO
BACKGROUND: Prior trials suggest that intravenous racemic ketamine is a highly effective for treatment-resistant depression (TRD), but phase 3 trials of racemic ketamine are needed. AIMS: To assess the acute efficacy and safety of a 4-week course of subcutaneous racemic ketamine in participants with TRD. Trial registration: ACTRN12616001096448 at www.anzctr.org.au. METHOD: This phase 3, double-blind, randomised, active-controlled multicentre trial was conducted at seven mood disorders centres in Australia and New Zealand. Participants received twice-weekly subcutaneous racemic ketamine or midazolam for 4 weeks. Initially, the trial tested fixed-dose ketamine 0.5 mg/kg versus midazolam 0.025 mg/kg (cohort 1). Dosing was revised, after a Data Safety Monitoring Board recommendation, to flexible-dose ketamine 0.5-0.9 mg/kg or midazolam 0.025-0.045 mg/kg, with response-guided dosing increments (cohort 2). The primary outcome was remission (Montgomery-Åsberg Rating Scale for Depression score ≤10) at the end of week 4. RESULTS: The final analysis (those who received at least one treatment) comprised 68 in cohort 1 (fixed-dose), 106 in cohort 2 (flexible-dose). Ketamine was more efficacious than midazolam in cohort 2 (remission rate 19.6% v. 2.0%; OR = 12.1, 95% CI 2.1-69.2, P = 0.005), but not different in cohort 1 (remission rate 6.3% v. 8.8%; OR = 1.3, 95% CI 0.2-8.2, P = 0.76). Ketamine was well tolerated. Acute adverse effects (psychotomimetic, blood pressure increases) resolved within 2 h. CONCLUSIONS: Adequately dosed subcutaneous racemic ketamine was efficacious and safe in treating TRD over a 4-week treatment period. The subcutaneous route is practical and feasible.
Assuntos
Transtorno Depressivo Resistente a Tratamento , Ketamina , Humanos , Ketamina/efeitos adversos , Depressão , Midazolam/efeitos adversos , Austrália , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológicoRESUMO
BACKGROUND AND AIM: To determine risk factors for incident chronic kidney disease (CKD) in a large population-based cohort. METHODS: This prospective opt-in population-based cohort study is based on the 45 and Up Study, where New South Wales residents aged ≥45 years were randomly sampled from the Services Australia database and agreed to complete the 45 and Up Study baseline questionnaire and have their responses linked to their health data in routinely collected databases. The primary outcome was the development of incident CKD, defined as eGFR < 60 mL/min/1.73 m2 . CKD incidence was calculated using Poisson regression. Risk factors for incident CKD were assessed using Cox regression in multivariable models. RESULTS: In 39 574 participants who did not have CKD at enrolment, independent factors associated with developing CKD included: older age, regional residence (HR 1.38 (1.27-1.50) for outer regional vs major city), smoking (1.13 (1.00-1.27) for current smoker vs non-smoker), obesity (1.25 (1.16-1.35) for obese vs normal body mass index), diabetes mellitus (1.41 (1.33-1.50)), hypertension (1.53 (1.44-1.62)), coronary heart disease (1.13 (1.07-1.20)), depression/anxiety (1.16 (1.09-1.24)) and cancer (1.29 (1.20-1.39)). Migrants were less likely to develop CKD compared with people born in Australia (0.88 (0.83-0.94)). Gender, partner status and socioeconomic factors were not independently associated with developing CKD. CONCLUSIONS: This large population-based study found multiple modifiable and non-modifiable factors were independently associated with developing CKD. In the Australian setting, the risk of CKD was higher with regional residence. Differences according to socioeconomic status were predominantly explained by age, comorbidities and harmful health-related behaviours.
Assuntos
Insuficiência Renal Crônica , Idoso , Austrália/epidemiologia , Estudos de Coortes , Feminino , Taxa de Filtração Glomerular , Humanos , Incidência , Masculino , Obesidade/epidemiologia , Estudos Prospectivos , Insuficiência Renal Crônica/complicações , Fatores de RiscoRESUMO
BACKGROUND: The highest burden of chronic obstructive pulmonary disease (COPD) occurs in low- and middle-income countries. Low-cost oral medications, if effective, could enable affordable, accessible COPD treatment. METHODS: In this randomised, three-arm, double-blind, double-dummy, placebo-controlled study conducted in 37 centres in China, symptomatic patients with moderate to very severe COPD were randomised 1:1:1 to placebo twice daily plus placebo once daily, low-dose theophylline 100â mg twice daily plus placebo once daily or low-dose theophylline 100â mg twice daily plus low-dose oral prednisone 5â mg once daily for 48â weeks. The primary end-point was annualised exacerbation rate. RESULTS: 1670 subjects were randomised and 1242 completed the study (1142 with acceptable data at week 48). Subjects (75.7% male) had a mean age of 64.4â years, with mean±sd baseline post-bronchodilator forced expiratory volume in 1â s (FEV1) 1.1±0.4â L (42.2% predicted) and St George's Respiratory Questionnaire (SGRQ) score 45.8±20.1. There were negligible differences between annualised exacerbation rates across the three treatments: 0.89 (95% CI 0.78-1.02) on theophylline plus prednisone, 0.86 (95% CI 0.75-0.99) on theophylline plus placebo and 1.00 (95% CI 0.87-1.14) on placebo. The rate ratio for theophylline plus prednisone versus pooled theophylline plus placebo and placebo was 0.96 (95% CI 0.83-1.12), for theophylline plus placebo versus placebo was 0.87 (95% CI 0.73-1.03; p=0.101) and for theophylline plus prednisone versus placebo was 0.90 (95% CI 0.76-1.06; p=0.201). Secondary outcomes of hospitalisations, FEV1, SGRQ and COPD Assessment Test score showed no statistically significant difference between treatment arms. Serious adverse events other than exacerbations were <2% and did not differ between treatment arms. CONCLUSIONS: Low-dose theophylline alone or in combination with prednisone did not reduce exacerbation rates or clinically important secondary end-points compared with placebo.
Assuntos
Doença Pulmonar Obstrutiva Crônica , Teofilina , Corticosteroides/uso terapêutico , Broncodilatadores/uso terapêutico , China , Método Duplo-Cego , Feminino , Volume Expiratório Forçado , Humanos , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Teofilina/farmacologia , Teofilina/uso terapêuticoRESUMO
BACKGROUND: Growing evidence supports the benefits of eHealth interventions to increase patient engagement and improve outcomes for a range of conditions. However, ineffective program delivery and usage attrition limit exposure to these interventions and may reduce their effectiveness. OBJECTIVE: This study aims to evaluate the delivery fidelity of an eHealth intervention, describe use patterns, compare outcomes between low and high users, and identify mediating factors on intervention delivery and receipt. METHODS: This is a mixed methods study of an internet-based intervention being evaluated for effectiveness in a randomized controlled trial (RCT). The intervention comprised medication and cardiovascular disease (CVD) risk data uploaded from the primary care electronic health record (EHR); interactive, personalized CVD risk score estimation; goal setting and self-monitoring; an interactive social forum; and optional receipt of heart health messages. Fidelity was assessed over 12 months. Trial outcomes were compared between low and high users. Data sources included program delivery records, web log data, trial data, and thematic analysis of communication records. RESULTS: Most participants in the intervention group (451/486, 93%) had an initial training session conducted by telephone (413/447, 92.4% of participants trained), with a mean duration of 44 minutes (range 10-90 minutes). Staff conducted 98.45% (1776/1804) of the expected follow-ups, mostly by telephone or email. Of the 451 participants who commenced log-ins, 46.8% (211) were categorized as low users (defined as at least one log-in in 3 or fewer months of follow-up), 40.4% (182) were categorized as high users (at least one log-in in more than 3 months of follow-up), and 12.8% (58) were nonadopters (no log-ins after their training session). The mean log-in frequency was 3-4 per month in ongoing users. There was no significant difference between the groups in the primary trial outcome of adherence to guideline-recommended medications (P=.44). In unadjusted analyses, high users had significantly greater eHealth literacy scores (P=.003) and were more likely to meet recommended weekly targets for fruit (P=.03) and fish (P=.004) servings; however, the adjusted findings were not significant. Interactive screen use was highest for goal tracking and lowest for the chat forum. Screens with EHR-derived data held only an early interest for most users. Fidelity measures (reach, content, dose delivered, and dose received) were influenced by the facilitation strategies used by staff, invisible qualities of staff-participant communication, and participants' responsiveness to intervention attributes. CONCLUSIONS: A multifeature internet-based intervention was delivered with high fidelity to the RCT protocol and was regularly used by 40.4% (182/451) of users over 12 months. Higher log-in frequency as an indicator of greater intervention exposure was not associated with statistically significant improvements in eHealth literacy scores, lifestyle changes, or clinical outcomes. Attributes of the intervention and individualized support influenced initial and ongoing use.
Assuntos
Doenças Cardiovasculares , Intervenção Baseada em Internet , Doenças Cardiovasculares/terapia , Registros Eletrônicos de Saúde , Humanos , Atenção Primária à Saúde , AutocuidadoRESUMO
BACKGROUND: Myocardial pathology is common in patients undergoing hemodialysis. To explore the effects of differing aspects of dialysis treatment on its evolution, we examined the impact of change in markers of volume status, hemodynamics and solute clearance on left ventricular (LV) parameters in a randomized trial of extended hours dialysis. METHODS AND RESULTS: A Clinical Trial of IntensiVE (ACTIVE) Dialysis randomized 200 patients undergoing hemodialysis to extended dialysis hours (≥ 24 hours/week) or standard hours (12-18 hours/week) for 12 months. In a prespecified substudy, 95 participants underwent cardiac magnetic resonance imaging (CMR) at baseline and at the study's end. Generalized linear regression was used to model the relationship between changes in LV parameters and markers of volume status (normalized ultrafiltration rate and total weekly interdialytic weight gain), hemodynamic changes (systolic and diastolic blood pressure) and solute control (urea clearance, dialysis hours and phosphate). Randomization to extended hours dialysis was not associated with change in any CMR parameter. Reduction in ultrafiltration rate was associated with reduction in LV mass index (Pâ¯=â¯0.049) and improved ejection fraction (Pâ¯=â¯0.024); reduction in systolic blood pressure was also associated with improvement in ejection fraction (Pâ¯=â¯0.045); reduction in interdialytic weight gain was associated with reduced stroke volume (Pâ¯=â¯0.038). There were no associations between change in urea clearance, phosphate or total hours per week and CMR parameters. CONCLUSIONS: Reduction in ultrafiltration rate and blood pressure are associated with improved myocardial parameters in hemodialysis recipients independently of solute clearance or dialysis time. These findings underscore the importance of fluid status and related parameters as potential treatment targets in this population.
Assuntos
Insuficiência Cardíaca , Falência Renal Crônica , Humanos , Hipertrofia Ventricular Esquerda , Falência Renal Crônica/terapia , Diálise Renal , Volume SistólicoRESUMO
BACKGROUND: Chronic Kidney Disease - Mineral and Bone Disorder (CKD-MBD) is a significant cause of morbidity among haemodialysis patients and is associated with pathological changes in phosphate, calcium and parathyroid hormone (PTH). In the ACTIVE Dialysis study, extended hours dialysis reduced serum phosphate but did not cause important changes in PTH or serum calcium. This secondary analysis aimed to determine if changes in associated therapies may have influenced these findings and to identify differences between patient subgroups. METHODS: The ACTIVE Dialysis study randomised 200 participants to extended hours haemodialysis (≥24 h/week) or conventional haemodialysis (≤18 h/week) for 12 months. Mean differences between treatment arms in serum phosphate, calcium and PTH; and among key subgroups (high vs. low baseline phosphate/PTH, region, time on dialysis, dialysis setting and frequency) were examined using mixed linear regression. RESULTS: Phosphate binder use was reduced with extended hours (- 0.83 tablets per day [95% CI -1.61, - 0.04; p = 0.04]), but no differences in type of phosphate binder, use of vitamin D, dose of cinacalcet or dialysate calcium were observed. In adjusted analysis, extended hours were associated with lower phosphate (- 0.219 mmol/L [- 0.314, - 0.124; P < 0.001]), higher calcium (0.046 mmol/L [0.007, 0.086; P = 0.021]) and no change in PTH (0.025 pmol/L [- 0.107, 0.157; P = 0.713]). The reduction in phosphate with extended hours was greater in those with higher baseline PTH and dialysing at home. CONCLUSION: Extended hours haemodialysis independently reduced serum phosphate levels with minimal change in serum calcium and PTH levels. With a few exceptions, these results were consistent across patient subgroups. TRIAL REGISTRATION: Clinicaltrials.gov NCT00649298 . Registered 1 April 2008.
Assuntos
Distúrbio Mineral e Ósseo na Doença Renal Crônica/sangue , Distúrbio Mineral e Ósseo na Doença Renal Crônica/epidemiologia , Diálise Renal/métodos , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/terapia , Adulto , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de TempoRESUMO
BACKGROUND: Pentoxifylline has been shown to increase haemoglobin levels in patients with chronic kidney disease (CKD) and erythropoietin-stimulating agent (ESA)-hyporesponsive anaemia in the Handling Erythropoietin Resistance with Oxpentifylline multicentre double-blind, randomized controlled trial. The present sub-study evaluated the effects of pentoxifylline on the iron-regulatory hormone hepcidin in patients with ESA-hyporesponsive CKD. METHODS: This sub-study included 13 patients in the pentoxifylline arm (400 mg daily) and 13 in the matched placebo arm. Hepcidin-25 was measured by ultra performance liquid chromatography/quadrupole time-of-flight mass spectrometry following isolation from patient serum. Serum hepcidin-25, serum iron biomarkers, haemoglobin and ESA dosage were compared within and between the two groups. RESULTS: Hepcidin-25 concentration at 4 months adjusted for baseline did not differ significantly in pentoxifylline versus placebo treated patients (adjusted mean difference (MD) -7.9 nmol, P = 0.114), although the difference between the groups mean translated into a >25% reduction of circulating hepcidin-25 due to pentoxifylline compared with the placebo baseline. In paired analysis, serum hepcidin-25 levels were significantly decreased at 4 months compared with baseline in the pentoxifylline group (-5.47 ± 2.27 nmol/l, P < 0.05) but not in the placebo group (2.82 ± 4.29 nmol/l, P = 0.24). Pentoxifylline did not significantly alter serum ferritin (MD 55.4 mcg/l), transferrin saturation (MD 4.04%), the dosage of ESA (MD -9.93 U/kg per week) or haemoglobin concentration (MD 5.75 g/l). CONCLUSION: The reduction of circulating hepcidin-25 due to pentoxifylline did not reach statistical significance; however, the magnitude of the difference suggests that pentoxifylline may be a clinically and biologically meaningful modulator of hepcidin-25 in dialysis of patients with ESA-hyporesponsive anaemia.
Assuntos
Anemia/tratamento farmacológico , Darbepoetina alfa/uso terapêutico , Resistência a Medicamentos , Eritropoese/efeitos dos fármacos , Hematínicos/uso terapêutico , Hepcidinas/sangue , Pentoxifilina/uso terapêutico , Insuficiência Renal Crônica/terapia , Idoso , Idoso de 80 Anos ou mais , Anemia/sangue , Anemia/diagnóstico , Biomarcadores/sangue , Darbepoetina alfa/efeitos adversos , Método Duplo-Cego , Feminino , Hematínicos/efeitos adversos , Hemoglobinas/metabolismo , Humanos , Ferro/sangue , Masculino , Pessoa de Meia-Idade , Pentoxifilina/efeitos adversos , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/diagnóstico , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: ß-Blocking agents reduce cardiovascular mortality in patients with heart disease, but their potential benefit in dialysis patients is unclear. We aimed to determine the feasibility of a randomized controlled trial (RCT). STUDY DESIGN: Pilot RCT. SETTING & PARTICIPANTS: Patients who received dialysis for 3 or more months and were 50 years or older (or ≥18 years with diabetes or cardiovascular disease) were recruited from 11 sites in Australia and New Zealand. We aimed to recruit 150 participants. INTERVENTION: After a 6-week run-in with the ß-blocker carvedilol, we randomly assigned participants to treatment with carvedilol or placebo for 12 months. OUTCOMES & MEASUREMENTS: The prespecified primary outcome was the proportion of participants who tolerated carvedilol, 6.25mg, twice daily during the run-in period. After randomization, we report participant withdrawal and the incidence of intradialytic hypotension (IDH). RESULTS: Of 1,443 patients screened, 354 were eligible, 91 consented, and 72 entered the run-in stage. 49 of 72 run-in participants (68%; 95% CI, 57%-79%) achieved the primary outcome. 5 of the 23 withdrawals from run-in were attributable to bradycardia or hypotension. After randomization, 10 of 26 allocated to carvedilol and 4 of 23 allocated to placebo withdrew. 4 participants randomly assigned to carvedilol withdrew because of bradycardia or hypotension. Overall, there were 4 IDH events per 100 hemodialysis sessions; in participants allocated to carvedilol versus placebo, respectively, there were 7 versus 2 IDH events per 100 hemodialysis sessions (P=0.1) in the 2 weeks immediately following a dose increase and 4 versus 3 IDH events per 100 hemodialysis sessions after no dose increase (P=0.7). LIMITATIONS: Unable to recruit planned sample size. CONCLUSIONS: Recruiting patients receiving dialysis to an RCT of ß-blocker versus placebo will prove challenging. Possible solutions include international collaboration and exploring novel trial designs such as a registry-based RCT.
Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Carbazóis/uso terapêutico , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , Falência Renal Crônica/complicações , Falência Renal Crônica/terapia , Propanolaminas/uso terapêutico , Diálise Renal , Idoso , Carvedilol , Método Duplo-Cego , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
AIM: The Fish oils and Aspirin in Vascular access OUtcomes in REnal Disease (FAVOURED) trial investigated whether 3 months of omega-3 polyunsaturated fatty acids, either alone or in combination with aspirin, will effectively reduce primary access failure of de novo arteriovenous fistulae. This report presents the baseline characteristics of all study participants, examines whether study protocol amendments successfully increased recruitment of a broader and more representative haemodialysis cohort, including patients already receiving aspirin, and contrasts Malaysian participants with those from Australia, New Zealand and the United Kingdom (UK). METHOD: This international, randomized, double-blind, placebo-controlled trial included patients older than 19 years with stage 4 or 5 chronic kidney disease currently receiving, or planned within 12 months to receive haemodialysis. RESULTS: Participants (n = 568) were overweight (28.6 ± 7.3 kg/m(2) ), relatively young (54.8 ± 14.3 years), and predominantly male (63%) with a high prevalence of diabetes mellitus (46%) but low rate of ischaemic heart disease (8%). Sixty one percent were planned for lower arm arteriovenous fistula creation. Malaysian participants (n = 156) were younger (51.8 ± 13.6 years vs 57.1 ± 14.2 years, P < 0.001) with a higher prevalence of diabetes mellitus (65% vs 43%, P < 0.001), but less ischaemic heart disease (5% vs 14%, P < 0.01) compared with the combined Australian, New Zealand and UK cohort (n = 228). Protocol modifications allowing for inclusion of patients receiving aspirin increased the prevalence of co-morbidities compared with the original cohort. CONCLUSIONS: The FAVOURED study participants, while mostly similar to patients in contemporary national registry reports and comparable recent clinical trials, were on average younger and had less ischaemic heart disease. These differences were reduced as a consequence of including patients already receiving aspirin.
Assuntos
Derivação Arteriovenosa Cirúrgica , Aspirina/administração & dosagem , Ácidos Docosa-Hexaenoicos/administração & dosagem , Ácido Eicosapentaenoico/administração & dosagem , Fibrinolíticos/administração & dosagem , Oclusão de Enxerto Vascular/prevenção & controle , Diálise Renal , Insuficiência Renal Crônica/terapia , Trombose/prevenção & controle , Adulto , Idoso , Derivação Arteriovenosa Cirúrgica/efeitos adversos , Austrália/epidemiologia , Comorbidade , Método Duplo-Cego , Combinação de Medicamentos , Feminino , Oclusão de Enxerto Vascular/diagnóstico , Oclusão de Enxerto Vascular/epidemiologia , Oclusão de Enxerto Vascular/fisiopatologia , Humanos , Malásia/epidemiologia , Masculino , Pessoa de Meia-Idade , Nova Zelândia/epidemiologia , Prevalência , Insuficiência Renal Crônica/diagnóstico , Fatores de Risco , Índice de Gravidade de Doença , Trombose/diagnóstico , Trombose/epidemiologia , Trombose/fisiopatologia , Fatores de Tempo , Resultado do Tratamento , Reino Unido/epidemiologia , Grau de Desobstrução Vascular/efeitos dos fármacosRESUMO
BACKGROUND: Erythropoiesis-stimulating agent (ESA)-hyporesponsive anemia is common in chronic kidney disease (CKD). Pentoxifylline shows promise as a treatment for ESA-hyporesponsive anemia, but has not been rigorously evaluated. STUDY DESIGN: Multicenter, double-blind, randomized, controlled trial. SETTING & PARTICIPANTS: 53 adult patients with CKD stage 4 or 5 (including dialysis) and ESA-hyporesponsive anemia (hemoglobin≤120g/L and ESA resistance index [calculated as weight-adjusted weekly ESA dose in IU/kg/wk divided by hemoglobin concentration in g/L]≥1.0IU/kg/wk/g/L for erythropoietin-treated patients and ≥0.005µg/kg/wk/g/L for darbepoetin-treated patients). INTERVENTIONS: Pentoxifylline (400mg/d; n=26) or matching placebo (control; n=27) for 4 months. PRIMARY OUTCOME: ESA resistance index at 4 months; secondary outcomes: hemoglobin concentration, ESA dose, blood transfusion requirement, serum ferritin level and transferrin saturation, C-reactive protein level, adverse events, quality of life, and health economics. RESULTS: There was no statistically significant difference in ESA resistance index between the pentoxifylline and control groups (adjusted mean difference, -0.39 [95%CI, -0.89 to 0.10] IU/kg/wk/g/L; P=0.1). Pentoxifylline significantly increased hemoglobin concentration relative to the control group (adjusted mean difference, 7.6 [95%CI, 1.7-13.5] g/L; P=0.01). There was no difference in ESA dose between groups (-20.8 [95%CI, -67.2 to 25.7] IU/kg/wk; P=0.4). No differences in blood transfusion requirements, adverse events, or quality of life were observed between groups. Pentoxifylline cost A$88.05 (US $82.94) per person over the trial and produced mean savings in ESA cost of A$1,332 (US $1,255). The overall economic impact over the trial period was a saving of A$1,244 (US $1,172) per person for the pentoxifylline group compared with controls. LIMITATIONS: Sample size smaller than planned due to slow recruitment. CONCLUSIONS: Pentoxifylline did not significantly modify ESA hyporesponsiveness, but increased hemoglobin concentration. Further studies are warranted to determine whether pentoxifylline therapy represents a safe strategy for increasing hemoglobin levels in patients with CKD with ESA-hyporesponsive anemia.
Assuntos
Anemia , Eritropoese/efeitos dos fármacos , Eritropoetina , Pentoxifilina , Insuficiência Renal Crônica , Adulto , Idoso , Anemia/sangue , Anemia/tratamento farmacológico , Anemia/etiologia , Redução de Custos , Método Duplo-Cego , Monitoramento de Medicamentos/métodos , Resistência a Medicamentos/efeitos dos fármacos , Sinergismo Farmacológico , Eritropoetina/administração & dosagem , Eritropoetina/efeitos adversos , Fármacos Hematológicos/administração & dosagem , Fármacos Hematológicos/efeitos adversos , Hemoglobinas/análise , Humanos , Pessoa de Meia-Idade , Pentoxifilina/administração & dosagem , Pentoxifilina/efeitos adversos , Qualidade de Vida , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/economia , Insuficiência Renal Crônica/psicologia , Vasodilatadores/administração & dosagem , Vasodilatadores/efeitos adversosAssuntos
Insuficiência Cardíaca , Miocárdio Atordoado , Ventrículos do Coração , Humanos , Diálise Renal , SístoleRESUMO
BACKGROUND: It has been well-established, both by population genetics theory and direct observation in many organisms, that increased genetic diversity provides a survival advantage. However, given the limitations of both sample size and genome-wide metrics, this hypothesis has not been comprehensively tested in human populations. Moreover, the presence of numerous segregating small effect alleles that influence traits that directly impact health directly raises the question as to whether global measures of genomic variation are themselves associated with human health and disease. RESULTS: We performed a meta-analysis of 17 cohorts followed prospectively, with a combined sample size of 46,716 individuals, including a total of 15,234 deaths. We find a significant association between increased heterozygosity and survival (P = 0.03). We estimate that within a single population, every standard deviation of heterozygosity an individual has over the mean decreases that person's risk of death by 1.57%. CONCLUSIONS: This effect was consistent between European and African ancestry cohorts, men and women, and major causes of death (cancer and cardiovascular disease), demonstrating the broad positive impact of genomic diversity on human survival.
Assuntos
Polimorfismo de Nucleotídeo Único , Estudo de Associação Genômica Ampla , Heterozigoto , Humanos , Mortalidade , Modelos de Riscos ProporcionaisRESUMO
AIMS: The aim of this study was to determine the comparative effectiveness and safety of direct oral anticoagulants (DOACs) and warfarin in adults with atrial fibrillation (AF) by level of kidney function. METHODS AND RESULTS: We pooled findings from five retrospective cohorts (2011-18) across Australia and Canada of adults with; a new dispensation for a DOAC or warfarin, an AF diagnosis, and a measure of baseline estimated glomerular filtration rate (eGFR). The outcomes of interest, within 1 year from the cohort entry date, were: (1) the composite of all-cause death, first hospitalization for ischaemic stroke, or transient ischaemic attack (effectiveness), and (2) first hospitalization for major bleeding defined as an intracranial, upper or lower gastrointestinal, or other bleeding (safety). Cox models were used to examine the association of a DOAC vs. warfarin with outcomes, after 1:1 matching via a propensity score. Kidney function was categorized as eGFR ≥60, 45-59, 30-44, and <30 mL/min/1.73 m2. A total of 74 542 patients were included in the matched analysis. DOAC initiation was associated with greater or similar effectiveness compared with warfarin initiation across all eGFR categories [pooled HRs (95% CIs) for eGFR categories: 0.74(0.69-0.79), 0.76(0.54-1.07), 0.68(0.61-0.75) and 0.86(0.76-0.98)], respectively. DOAC initiation was associated with lower or similar risk of major bleeding than warfarin initiation [pooled HRs (95% CIs): 0.75(0.65-0.86), 0.81(0.65-1.01), 0.82(0.66-1.02), and 0.71(0.52-0.99), respectively). Associations between DOAC initiation, compared with warfarin initiation, and study outcomes were not modified by eGFR category. CONCLUSION: DOAC use, compared with warfarin use, was associated with a lower or similar risk of all-cause death, ischaemic stroke, and transient ischaemic attack and also a lower or similar risk of major bleeding across all levels of kidney function.
Assuntos
Fibrilação Atrial , Isquemia Encefálica , Ataque Isquêmico Transitório , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Adulto , Varfarina/uso terapêutico , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/diagnóstico , Ataque Isquêmico Transitório/complicações , Anticoagulantes/efeitos adversos , Estudos Retrospectivos , Isquemia Encefálica/complicações , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Hemorragia/induzido quimicamente , Hemorragia/epidemiologia , AVC Isquêmico/complicações , RimRESUMO
Rationale & Objective: The benefit-risk profile of rivaroxaban versus warfarin for atrial fibrillation (AF) in patients with chronic kidney disease is uncertain. We compared rivaroxaban with warfarin across the range of kidney function in adults with AF. Study Design: Multicenter retrospective cohort. Setting & Participants: Adults with AF and a measure of estimated glomerular filtration rate (eGFR); using administrative data from 5 jurisdictions across Australia and Canada (2011-2018). Kidney function was categorized as eGFR ≥60, 45-59, 30-44, and <30 mL/min/1.73 m2. Patients receiving dialysis and kidney transplant recipients were excluded. Exposures: New dispensation of either rivaroxaban or warfarin. Outcomes: Composite (1) effectiveness outcome (all-cause death, ischemic stroke, or transient ischemic attack) and (2) major bleeding events (intracranial, gastrointestinal, or other) at 1 year. Analytical Approach: Cox proportional hazards models accounting for propensity score matching were performed independently in each jurisdiction and then pooled using random-effects meta-analysis. Results: 55,568 patients (27,784 rivaroxaban-warfarin user matched pairs; mean age 74 years, 46% female, 33.5% with eGFR <60 mL/min/1.73 m2) experienced a total of 4,733 (8.5%) effectiveness and 1,144 (2.0%) bleeding events. Compared to warfarin, rivaroxaban was associated with greater or similar effectiveness across a broad range of kidney function (pooled HRs of 0.72 [95% CI, 0.66-0.78], 0.78 [95% CI, 0.58-1.06], 0.70 [95% CI, 0.57-0.87], and 0.78 [95% CI, 0.62-0.99]) for eGFR ≥60, 45-59, 30-44, and <30 mL/min/1.73 m2, respectively). Rivaroxaban was also associated with similar risk of major bleeding across all eGFR categories (pooled HRs of 0.75 [95% CI, 0.56-1.00], 1.01 [95% CI, 0.79-1.30], 0.87 [95% CI, 0.66-1.15], and 0.63 [95% CI, 0.37-1.09], respectively). Limitations: Unmeasured treatment selection bias and residual confounding. Conclusions: In adults with AF, rivaroxaban compared with warfarin was associated with lower or similar risk of all-cause death, ischemic stroke and transient ischemic attack and similar risk of bleeding across a broad range of kidney function. Plain-Language Summary: This real-world study involved a large cohort of 55,568 adults with atrial fibrillation from 5 jurisdictions across Australia and Canada. It showed that the favorable safety (bleeding) and effectiveness (stroke or death) profile of rivaroxaban compared with warfarin was consistent across different levels of kidney function. This study adds important safety data on the use of rivaroxaban in patients with reduced kidney function, including those with estimated glomerular filtration rate <30 mL/min/1.73 m2 in whom the risks and benefits of rivaroxaban use is most uncertain. Overall, the study supports the use of rivaroxaban as a safe and effective alternative to warfarin for atrial fibrillation across differing levels of kidney function.
Assuntos
Ácidos Graxos Ômega-3 , Óleos de Peixe , Derivação Arteriovenosa Cirúrgica , Aspirina , Humanos , NefropatiasRESUMO
Non-attendance to dermatology outpatient appointments is a risk factor for poorer patient outcomes. The culturally and linguistically diverse (CALD) communities in Australia have been identified as at risk of poorer health outcomes, but there is a paucity of data assessing patient factors that may increase outpatient non-attendance. To investigate this, we performed a retrospective cross-sectional study of dermatology appointments from patients attending a tertiary, referral public hospital located in one of Australia's most racially and ethnically diverse communities. Patients within the 18-45 years age bracket were 61% more likely not to attend when compared with older age groups. Those born in Oceania, Middle East Asia, and surprisingly Australia were more likely to miss an appointment, whilst those born in East and Southeast Asia were more likely to attend. Those who spoke Arabic at home were more likely not to attend, whilst those who spoke Vietnamese at home were more likely to attend. This study sheds further light on health disparities in non-attendance and emphasizes the importance of not collectively amalgamating all groups of the CALD community.
Assuntos
Dermatologia , Idoso , Agendamento de Consultas , Estudos Transversais , Etnicidade , Humanos , Pacientes Ambulatoriais , Estudos RetrospectivosRESUMO
BACKGROUND AND OBJECTIVES: The burden of chronic obstructive pulmonary disease (COPD) disproportionately affects patients in low to middle-income countries. Although the Theophylline and Steroids in COPD Study (TASCS) showed no clinical benefit from administering low-dose theophylline and prednisone in COPD patients compared to placebo, it was hypothesized that those with elevated blood eosinophil counts would receive clinical benefit from the intervention. METHODS: This was a post-hoc analysis of the TASCS dataset - a double-blinded, placebo-controlled trial conducted in patients with moderate-severe COPD in China. Participants were allocated 1:1:1 to low-dose oral theophylline (100mg bd) and prednisone (5mg qd; PrT), theophylline (100mg bd) and prednisone-matched placebo (TP), or double-matched placebo (DP) groups and followed-up for 48 weeks. A baseline count of ≥300 eosinophils/µL blood was categorized as elevated/eosinophilic, and the primary outcome was the annualized moderate-severe exacerbation rate. RESULTS: Of 1487 participants eligible for analysis, 325 (22%) were eosinophilic. These participants were predominantly male (82%), had a mean (SD) age of 64 (±8) years and a predicted forced expiratory volume in 1s (FEV1) of 43% (±16). The annualized moderate-severe exacerbation rate was significantly higher in the PrT group compared to the pooled results of the TP and DP groups (incidence rate ratio = 1.6; ([95% CI 1.06-1.76]) p = 0.016). Changes in spirometry values and reported disease impact scores (St. George's Respiratory Questionnaire and COPD Assessment Test) at week 48 were not significantly different between groups. CONCLUSION: Combination low-dose theophylline and prednisone was associated with a significant increase in the annual moderate-severe exacerbation rate in participants with a blood eosinophil count ≥300 cells/µL compared to placebo.
Assuntos
Doença Pulmonar Obstrutiva Crônica , Teofilina , Idoso , Broncodilatadores , Método Duplo-Cego , Eosinófilos , Feminino , Volume Expiratório Forçado , Humanos , Masculino , Pessoa de Meia-Idade , Prednisona/efeitos adversos , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Teofilina/efeitos adversosRESUMO
Digital health applications (apps) have the potential to improve health behaviors and outcomes. We aimed to examine the effectiveness of a consumer web-based app linked to primary care electronic health records (EHRs). CONNECT was a multicenter randomized controlled trial involving patients with or at risk of cardiovascular disease (CVD) recruited from primary care (Clinical Trial registration ACTRN12613000715774). Intervention participants received an interactive app which was pre-populated and refreshed with EHR risk factor data, diagnoses and, medications. Interactive risk calculators, motivational messages and lifestyle goal tracking were also included. Control group received usual health care. Primary outcome was adherence to guideline-recommended medications (≥80% of days covered for blood pressure (BP) and statin medications). Secondary outcomes included attainment of risk factor targets and eHealth literacy. In total, 934 patients were recruited; mean age 67.6 (±8.1) years. At 12 months, the proportion with >80% days covered with recommended medicines was low overall and there was no difference between the groups (32.8% vs. 29.9%; relative risk [RR] 1.07 [95% CI, 0.88-1.20] p = 0.49). There was borderline improvement in the proportion meeting BP and LDL targets in intervention vs. control (17.1% vs. 12.1% RR 1.40 [95% CI, 0.97-2.03] p = 0.07). The intervention was associated with increased attainment of physical activity targets (87.0% intervention vs. 79.7% control, p = 0.02) and e-health literacy scores (72.6% intervention vs. 64.0% control, p = 0.02). In conclusion, a consumer app integrated with primary health care EHRs was not effective in increasing medication adherence. Borderline improvements in risk factors and modest behavior changes were observed.
RESUMO
BACKGROUND AND OBJECTIVES: This study investigated the effect of management - including home medicines reviews and chronic disease management plans funded through the Medicare Benefits Schedule - on self-reported medication non-adherence. METHOD: An observational cohort study including 244 individuals with an exacerbation of chronic illness enrolled into the Care Navigation randomised controlled trial of integrated care. Non-adherence was measured using the Morisky-Greene-Levine self-reported adherence tool. RESULTS: The cohort comprised an equal number of older men and women with, on average, three chronic diseases, receiving between five and 10 unique medications each month and visiting a general practitioner (GP) more than 50 times in the year prior to completing the questionnaire. Forty per cent reported non-adherence, which was greater in males (relative risk [RR]: 1.73; 95% confidence interval [CI]: 1.25, 2.54) and in patients reporting a recent fall (RR 1.40; 95% CI: 1.02, 1.89). GP-initiated chronic disease management programs did not influence adherence. DISCUSSION: Despite almost weekly contact with GPs, two in five patients were non-adherent. Better methods of encouraging adherence are needed.
Assuntos
Doença Crônica/psicologia , Adesão à Medicação/estatística & dados numéricos , Idoso , Austrália , Estudos de Coortes , Feminino , Humanos , Masculino , Adesão à Medicação/psicologia , Pessoa de Meia-Idade , Isolamento Social/psicologiaRESUMO
BACKGROUND: The HONEYPOT trial failed to establish the superiority of exit-site application of Medihoney compared with nasal mupirocin prophylaxis for the prevention of peritonitis in peritoneal dialysis (PD) patients. This study aimed to assess the representativeness of the patients in the HONEYPOT trial to the Australian and New Zealand PD population. METHODS: This study compared baseline characteristics of the 371 PD patients in the HONEYPOT trial with those of 6,085 PD patients recorded on the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry. RESULTS: Compared with the PD population, the HONEYPOT sample was older (standardized difference [d] = 0.19, p = 0.003), more likely to be treated with automated PD (d = 0.58, p < 0.001), had higher residual renal function (d = 0.26, p < 0.001) and a higher proportion of participants with end-stage kidney disease due to polycystic kidney disease (d = 0.17) and lower proportion due to diabetes (d = -0.17) and glomerulonephritis (d = -0.18) (p < 0.001), and lower proportions of indigenous people (d = -0.17, p < 0.001), current smokers (d = -0.10, p < 0.001), and people with prior histories of hemodialysis (d = -0.16, p < 0.001), diabetes mellitus (d = -0.18, p < 0.001), and coronary artery disease (d = -0.15, p < 0.001). CONCLUSIONS: HONEYPOT trial participants tended to be healthier than the Australian and New Zealand PD patient population. Although the differences between the groups were generally modest, it is possible that their cumulative effect may have had some impact on external generalizability, which is not an uncommon occurrence in clinical trials.