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RATIONALE & OBJECTIVE: Glomerulonephritis (GN) is a leading cause of chronic kidney disease (CKD). Major adverse cardiovascular events (MACE) are prolific in CKD. The risk of MACE in GN cohorts is multifactorial. We investigated the prognostic significance of routine cardiac biomarkers, Troponin I and N-terminal pro-BNP (NT-proBNP) in predicting MACE within 5 years of GN diagnosis. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Data were obtained from TriNetX, a global federated health research network of electronic health records (EHR). EXPOSURE OR PREDICTOR: Biomarker thresholds: Troponin I: 18 ng/L, NT-proBNP: 400 pg/mL. OUTCOMES: Primary outcome: Incidence of major adverse cardiovascular events (MACE). SECONDARY OUTCOME: was the risk for each individual component of the composite outcome. ANALYTICAL APPROACH: 1:1 propensity score matching using logistic regression. Cox proportional hazard models were used to assess the association of cardiac biomarkers with the primary and secondary outcomes, reported as Hazard Ratio (HR) and 95% confidence intervals (CI). Survival analysis was performed which estimates the probability of an outcome over a 5-year follow-up from the index event. RESULTS: Following PSM, 34,974 and 18,218 patients were analysed in the Troponin I and NTproBNP cohorts, respectively. In the Troponin I all cause GN cohort, 3,222 (9%) developed composite MACE outcome HR 1.79; (95% CI, 1.70, 1.88, p < 0.0001). In the NTproBNP GN cohort, 1,686 (9%) developed composite MACE outcome HR 1.99; (95% CI, 1.86, 2.14, p < 0.0001). LIMITATIONS: The data are derived from EHR for administrative purposes; therefore, there is the potential for data errors or missing data. CONCLUSIONS: In GN, routinely available cardiac biomarkers can predict incident MACE. The results suggest the clinical need for cardiovascular and mortality risk profiling in glomerular disease using a combination of clinical and laboratory variables.
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Biomarcadores , Enfermedades Cardiovasculares , Glomerulonefritis , Péptido Natriurético Encefálico , Fragmentos de Péptidos , Troponina I , Humanos , Masculino , Femenino , Biomarcadores/sangre , Troponina I/sangre , Glomerulonefritis/sangre , Glomerulonefritis/epidemiología , Glomerulonefritis/diagnóstico , Fragmentos de Péptidos/sangre , Persona de Mediana Edad , Estudios Retrospectivos , Péptido Natriurético Encefálico/sangre , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/mortalidad , Anciano , Bases de Datos Factuales , Adulto , Incidencia , Pronóstico , Estudios de Cohortes , Valor Predictivo de las PruebasRESUMEN
Aims: We compared the glycaemic and cardiorenal effects of combination therapy involving metformin, pioglitazone, sodium-glucose-linked-cotransporter-2 inhibitor (SGLT2i), and glucagon-like peptide-1 receptor agonist (GLP-1RA) versus a more conventional glucocentric treatment approach combining sulphonylureas (SU) and insulin from the point of type 2 diabetes (T2D) diagnosis. Methods: We performed a retrospective cohort study using the Global Collaborative Network in TriNetX. We included individuals prescribed metformin, pioglitazone, an SGLT2i, and a GLP-1 RA for at least 1-year duration, within 3 years of a T2D diagnosis, and compared with individuals prescribed insulin and a SU within the same temporal pattern. Individuals were followed up for 3 years. Results: We propensity score-matched (PSM) for 26 variables. A total of 1762 individuals were included in the final analysis (n = 881 per cohort). At 3-years, compared to the insulin/SU group, the metformin/pioglitazone/SGLT2i/GLP-1 RA group had a lower risk of heart failure (HR 0.34, 95% CI 0.13-0.87, p = 0.018), acute coronary syndrome (HR 0.29, 95% CI 0.12-0.67, p = 0.002), stroke (HR 0.17, 95% CI 0.06-0.49, p < 0.001), chronic kidney disease (HR 0.50, 95% CI 0.25-0.99, p = 0.042), and hospitalisation (HR 0.59, 95% CI 0.46-0.77, p < 0.001). Conclusions: In this real-world study, early, intensive polytherapy, targeting the distinct pathophysiological defects in T2D, is associated with significantly more favourable cardiorenal outcomes, compared to insulin and SU therapy.
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Diabetes Mellitus Tipo 2 , Quimioterapia Combinada , Receptor del Péptido 1 Similar al Glucagón , Hipoglucemiantes , Insulina , Metformina , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Compuestos de Sulfonilurea , Humanos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Femenino , Masculino , Hipoglucemiantes/uso terapéutico , Estudios Retrospectivos , Persona de Mediana Edad , Anciano , Metformina/uso terapéutico , Compuestos de Sulfonilurea/uso terapéutico , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Insulina/uso terapéutico , Receptor del Péptido 1 Similar al Glucagón/agonistas , Pioglitazona/uso terapéutico , Bases de Datos Factuales , Glucemia/metabolismo , Glucemia/efectos de los fármacos , Resultado del TratamientoRESUMEN
Purpose: To evaluate effects of aerobic and resistance exercises for cancer-related pain in adults with and surviving cancer. Secondary objectives were to a) evaluate the effect of exercise on fatigue, psychological function, physical function, b) assess fidelity to exercise. Design: A systematic search of MEDLINE, EMBASE, AMED, CINAHL and Cochrane Central Register of Controlled Trials was conducted to identify randomised controlled trials (RCTs) comparing aerobic and/or resistance exercise to control groups. The primary endpoint were changes in cancer-related pain intensity from baseline to post intervention. Meta-regression analysis evaluated predictors for heterogeneity between study findings. Tolerability was defined as reporting of exercise-induced adverse events while fidelity evaluated by reported intervention dropout. Results: Twenty-three RCTs including 1954 patients (age 58 ± 8.5 years; 78 % women); 1087 (56 %) and 867 (44 %) allocated to aerobic/resistance exercise therapy and control group, respectively. Exercise therapy was associated with small to moderate decreases in cancer-related pain compared to controls (SMD = 0.38, 95 % CI: 0.17, 0.58). Although there was significant heterogeneity between individual and pooled study effects (Q = 205.25, p < 0.0001), there was no publication bias. Meta-regression including supervision, age, duration and exercise type as moderators showed no significant differences in reported outcomes. Analysis of secondary outcomes revealed a moderate effect for improvements in physical function, fatigue and psychological symptoms. Conclusions: Aerobic and resistance exercises are tolerable and effective adjunct therapies to reduce cancer-related pain while also improving physical function, fatigue and mood. Future RCTs of dose, frequency, compliance and exercise type in specific cancer settings are required.
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AIMS/HYPOTHESIS: A protective role of sodium-glucose cotransporter 2 inhibitors (SGLT2is) and glucagon-like peptide 1 receptor agonists (GLP1-ra) in the development of diabetic retinopathy and diabetic macular oedema has been described in some recent studies, which may extend beyond glycaemic control. We aimed to review the clinical impact of SGLT2i and GLP1-ra therapy on the risk of diabetic retinopathy and diabetic macular oedema in individuals with type 2 diabetes taking insulin. METHODS: This is a retrospective cohort analysis of approximately two million people with type 2 diabetes receiving insulin across 97 healthcare organisations using a global federated health research network (TriNetX, Cambridge, USA). Two intervention cohorts (SGLT2i + insulin, n=176,409; GLP1-ra + insulin, n=207,034) were compared against a control cohort (insulin with no SGLT2i/GLP1-ra, n=1,922,312). Kaplan-Meier survival analysis was performed and estimated HRs were reported for each outcome. Propensity score was used to 1:1 match for age, sex, ischaemic heart disease, hypertension, microvascular complications, chronic kidney disease, HbA1c, BMI and use of pioglitazone, lipid modifying agents, antilipemic agents, ACE inhibitors, angiotensin II inhibitors and metformin. A sub-analysis comparing the two intervention cohorts was also performed. RESULTS: SGLT2i with insulin was associated with a reduced HR (95% CI) for diabetic macular oedema compared with the control cohort (0.835; 0.780, 0.893), while GLP1-ra with insulin demonstrated a lack of signal with no statistical significance to the HR (1.013; 0.960, 1.069). SGLT2i with insulin was not associated with a clinically significant increase in the risk of developing diabetic retinopathy (1.076; 1.027, 1.127), while GLP1-ra with insulin increased diabetic retinopathy risk (1.308; 1.261, 1.357). Compared with SGLT2i with insulin, GLP1-ra with insulin was associated with higher risk of diabetic retinopathy (1.205; 1.153, 1.259) and diabetic macular oedema (1.130; 1.056, 1.208). CONCLUSIONS/INTERPRETATION: Our study suggests that the combination of SGLT2i and insulin is associated with lower risk of developing diabetic macular oedema. However, the use of GLP1-ra was associated with an increased risk of diabetic retinopathy in individuals with type 2 diabetes also taking insulin. A comparative analysis showed favourable outcomes with SGLT2i and insulin in the development of diabetic macular oedema and diabetic retinopathy. RCTs using dedicated retinal imaging are required to determine the causal relationship with these therapies.
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Diabetes Mellitus Tipo 2 , Retinopatía Diabética , Receptor del Péptido 1 Similar al Glucagón , Edema Macular , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Humanos , Retinopatía Diabética/tratamiento farmacológico , Retinopatía Diabética/epidemiología , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/complicaciones , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Edema Macular/tratamiento farmacológico , Edema Macular/epidemiología , Masculino , Estudios Retrospectivos , Femenino , Persona de Mediana Edad , Anciano , Receptor del Péptido 1 Similar al Glucagón/agonistas , Hipoglucemiantes/uso terapéutico , Insulina/uso terapéuticoRESUMEN
BACKGROUND: Anti-vascular endothelial growth factor (anti-VEGF) therapy is commonly used intravitreally for diabetic proliferative retinopathy, but when used systemically for treating cancers, an excess of cardiovascular disease (CVD) events has been noted. The latter is of concern for people with diabetes, who are at higher risk of CVD. This study aims to explore the relationship between incident CVD and intravitreal anti-VEGF therapy in patients with diabetes, compared to other therapies, using a large real-world global federated dataset. METHODS: Data were analysed using TriNetX, a global electronic medical real-world ecosystem. The study included adults with diabetes and excluded those with a history of CVD prior to the time window of data extraction. Patients were categorised into two cohorts: anti-VEGF therapy or control cohort (laser or steroid therapies). The cohorts were 1:1 propensity score-matched for age, sex, ethnicity, body mass index, systolic blood pressure, HbA1c, and cardiovascular medications. Outcomes analysed at 1, 6 and 12 months were: (1) mortality; (2) acute myocardial infarction (MI); (3) cerebral infarction; and (4) heart failure. Relative risk analyses were performed using the built-in R statistical computing platform on TriNetX. RESULTS: In patients with diabetes (n = 2205; mean age 58.8 ± 15.8, Std diff 0.05; 56% male), anti-VEGF therapy was associated with a numerical but non-statistically significant increased CVD risk over 1, 6, and 12 months: Mortality over 1 month (RR 1; 95% CI 0.42, 2.40), 6 months (RR 1.46; 95% CI 0.72, 2.95) and 12 months (RR 1.41; 95% CI 0.88, 2.27). There was no excess of acute MI over 1 (RR n/a: not applicable; 0/0: 0 events in the anti-VEGF group/0 events in the control group), 6 and 12 months (RR n/a; 0/10 events); cerebral infarction over 1, 6 months (RR n/a; 0/0 events), and 12 months (RR n/a; 0/10); and heart failure over 1 month (RR n/a; 0/0 events), 6 months (RR 1; 95% CI 0.42, 2.40) and 12 months (RR 1; 95% CI 0.42, 2.34). CONCLUSIONS: There was no statistically significant risk of cardiovascular-related events in the short or medium term in patients with diabetes who received intravitreal anti-VEGF therapy, despite a small increase in the number of CVD events. Our study supports the real-world safety of intravitreal anti-VEGF therapy in patients with diabetes free of baseline CVD.
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BACKGROUND: Posttraumatic growth refers to positive psychological change following trauma. However, there is a need to better understand the experience of posttraumatic growth in the palliative care setting as well as the availability and efficacy of interventions that target this phenomenon. AIMS: To provide a review of the prevalence, characteristics and interventions involving posttraumatic growth in adults receiving palliative care and to collate recommendations for future development and utilisation of interventions promoting posttraumatic growth. DESIGN: We performed a systematic scoping review of studies investigating posttraumatic growth in palliative care settings using the Arksey and O'Malley six-step scoping review criteria. We used the PRISMA guidelines for scoping reviews. DATA SOURCES: Articles in all languages available on Ovid Medline [1946-2022], Embase [1947-2022], APA PsycINFO [1947-2022] and CINAHL [1981-2022] in November 2022. RESULTS: Of 2167 articles located, 17 were included for review. These reported that most people report low to moderate levels of posttraumatic growth with a decline towards end-of-life as distress and symptom burden increase. Associations include a relationship between posttraumatic growth, acceptance and greater quality-of-life. A limited number of interventions have been evaluated and found to foster posttraumatic growth and promote significant psychological growth. CONCLUSION: Posttraumatic growth is an emerging concept in palliative care where although the number of studies is small, early indications suggest that interventions fostering posttraumatic growth may contribute to improvements in psychological wellbeing in people receiving palliative care.
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Cuidados Paliativos , Crecimiento Psicológico Postraumático , Humanos , Cuidados Paliativos/psicología , Prevalencia , Calidad de Vida/psicología , Adulto , Femenino , Masculino , Persona de Mediana Edad , AncianoRESUMEN
BACKGROUND: Atrial fibrillation (AF) has consistently been associated with a higher risk of incident dementia. Observational evidence has suggested catheter ablation may be associated with a lower risk of dementia in patients with AF, but further research is needed. The objectives of this study were to use a global health research network to examine associations between catheter ablation, incident dementia and mortality in older adults with AF, and amongst subgroups by age, sex, co-morbidity status, and oral anticoagulant use. METHODS: The research network primarily included healthcare organizations in the United States. This network was searched on 28th September 2022 for patients aged ≥65 years with a diagnosis of AF received at least 5 years prior to the search date. Cox proportional hazard models were run on propensity-score matched cohorts. RESULTS: After propensity score matching, 20,746 participants (mean age 68 years; 59% male) were included in each cohort with and without catheter ablation. The cohorts were well balanced for age, sex, ethnicity, co-morbidities, and cardiovascular medications received. The risk of dementia was significantly lower in the catheter ablation cohort (Hazard Ratio 0.52, 95% confidence interval: 0.45-0.61). The catheter ablation cohort also had a lower risk of all-cause mortality (Hazard Ratio 0.58, 95% confidence interval: 0.55-0.61). These associations remained in subgroup analyses in individuals aged 65-79 years, ≥80 years, males, females, participants who received OACs during follow-up, participants with paroxysmal and non-paroxysmal AF, and participants with and without hypertension, diabetes mellitus, ischemic stroke, chronic kidney disease and heart failure, including heart failure with preserved ejection fraction and heart failure with reduced ejection fraction. CONCLUSION: The observed lower risk of dementia and mortality with catheter ablation could be an important consideration when determining appropriate patient-centered rhythm control strategies for patients with AF. Further studies including data on the success of ablation are required.
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Fibrilación Atrial , Ablación por Catéter , Demencia , Insuficiencia Cardíaca , Femenino , Humanos , Masculino , Estados Unidos/epidemiología , Anciano , Fibrilación Atrial/complicaciones , Fibrilación Atrial/cirugía , Fibrilación Atrial/epidemiología , Comorbilidad , Demencia/complicacionesRESUMEN
PURPOSE: Suboptimal glucose control early in the diagnosis of type 2 diabetes (T2D) is strongly associated with subsequent morbidity and mortality, termed the 'glycaemic legacy'. Additionally, it is known that Asian and Black individuals are at increased risk of T2D, and its associated complications compared to their White counterparts. However, ethnicity does not currently feature in the treatment algorithm of T2D, unlike in other cardiovascular disease states such as hypertension. We therefore sought to evaluate the real-world impact of early intensive treatment with combination therapy on cardiorenal outcomes compared to standard treatment in T2D, with a focus on ethnicity. METHODS: We performed a retrospective cohort study of all patients aged 18 or over with T2D using the TriNetX platform. TriNetX is a global collaborative network providing access to real time, anonymised medical records. We included patients who were initiated with Metformin and an SGLT2i within one month of diagnosis of T2D and compared this cohort with individuals who received Metformin only for a period of at least 1 year. We evaluated cardiovascular and renal outcomes at three years and stratified by ethnicity. We excluded individuals with a personal history of an outcome of interest. FINDINGS: We identified 49,651 individuals with T2D who were treated with Metformin and an SGLT2i and 1,028,806 patients with T2D who were treated with Metformin alone. A total of 98,094 individuals were included in the core analysis. The Metformin only group had a greater risk of mortality (RR 1.44, [95% CI 1.34-1.55], P<0.0001), CKD (RR 1.10, [95% CI 1.04-1.16], P = 0.0004), diabetic nephropathy (RR 1.06, [95% CI 1.01-1.12], P = 0.0239), heart failure (RR 1.13, [95% CI 1.07-1.21], P < 0.0001) and hospitalisation (RR 1.24, [95% CI 1.21-1.27], P < 0.0001) compared to individuals treated with Metformin and SGLT2i. Black individuals had a reduced risk of mortality (RR 0.71, [95% CI 0.55-0.92], P = 0.0099) and IHD (RR 0.73, [95% CI 0.64-0.84], P < 0.0001) compared to White individuals. Asian individuals had a reduced risk of heart failure (RR 0.61, [95% CI 0.41-0.91], P = 0.0134) and hospitalisation (RR 0.76, [95% CI 0.66-0.87], P = 0.0001) compared to White individuals. IMPLICATIONS: Initial combination treatment within the first year of T2D diagnosis confers favourable cardio-metabolic outcomes when compared to standard therapy, even in patients without established cardiovascular disease. Black and Asian individuals in particular demonstrate a greater degree of benefit compared to White individuals. Further prospective studies with a focus on ethnicity are now required to validate these findings.
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Enfermedades Cardiovasculares , Diabetes Mellitus Tipo 2 , Insuficiencia Cardíaca , Metformina , Humanos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Metformina/uso terapéutico , Hipoglucemiantes/uso terapéutico , Etnicidad , Estudios Retrospectivos , Estudios ProspectivosRESUMEN
BACKGROUND: Although people living with cystic fibrosis (PwCF) often have some risk factors for cardiovascular disease, including diabetes and chronic inflammation, little is known about the long-term cardiac risk in this condition. We aimed to determine the characteristics, rates and outcomes for cardiac disease in CF. METHODS: We looked at rates and outcomes for cardiac disease in 5649 adult PwCF in the UK CF Registry and 6265 adult PwCF in TriNetX (a global federated database of electronic healthcare record data). We used propensity matching to compare risk of major adverse cardiac events (MACE) (myocardial infarction, left-sided heart failure and atrial fibrillation) in PwCF against matched non-CF comparators in the general population and other inflammatory diseases. RESULTS: PwCF had a high prevalence of diabetes but low rates of hypertension and obesity. Some cardiac risk factors (age, diabetes and hypertension) were associated with MACE, but relationships between disease-specific risk factors (lung function and intravenous antibiotic days) were also observed. In propensity score-matched analyses, PwCF had higher risk of MACE than matched general population comparators (hazard ratio (HR) 1.65, 95% CI 1.40-1.95; p<0.001) and an equivalent or higher relative risk compared with other inflammatory conditions considered "high risk" for cardiovascular disease, including systemic lupus erythematosus (HR 0.95, 95% CI 0.82-1.09; p=0.44), rheumatoid arthritis (HR 1.21, 95% CI 1.00-1.48; p<0.001) and HIV (HR 0.93, 95% CI 0.82-1.06; p=0.29). CONCLUSIONS: PwCF are at increased risk of adverse cardiac disease events. Future work should focus on defining determinants of cardiovascular risk such that appropriate risk stratification can be employed.
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Fibrosis Quística , Diabetes Mellitus , Cardiopatías , Hipertensión , Infarto del Miocardio , Adulto , Humanos , Estudios Retrospectivos , Fibrosis Quística/complicaciones , Fibrosis Quística/epidemiología , Prevalencia , Infarto del Miocardio/epidemiología , Factores de Riesgo , Diabetes Mellitus/epidemiologíaRESUMEN
AIMS/HYPOTHESIS: Insulin is the primary treatment for type 1 diabetes. However, alternative glucose-lowering therapies are used adjunctively, but importantly are off-label in type 1 diabetes. Little work has previously been undertaken to evaluate safety with long-term efficacy and cardio-renal benefits of such therapies. We sought to investigate the real-world impact of sodium-glucose cotransporter 2 inhibitor (SGLT2i) and glucagon-like peptide-1 receptor agonist (GLP-1 RA) therapy in individuals with type 1 diabetes in relation to effect on blood glucose levels, adverse events and cardio-renal outcomes. METHODS: We performed a retrospective cohort study of all patients aged 18 or over with type 1 diabetes on the TriNetX platform, a global collaborative network providing access to real-time, anonymised medical records. We included patients who had been treated with an SGLT2i or GLP-1 RA for at least 6 months and analysed the efficacy, safety and cardio-renal outcomes 5 years after initiation of therapy. RESULTS: We identified 196,691 individuals with type 1 diabetes, 13% of whom were treated with adjunctive glucose-lowering therapy in addition to insulin. Included in the core analysis were 1822 patients treated with a GLP-1 RA and 992 individuals treated with an SGLT2i. Both agents provided clinically meaningful reductions in HbA1c (-2.6 mmol/mol [-0.2%] with SGLT2i and -5.4 mmol/mol [-0.5%] with GLP-1 RA). The SGLT2i treated cohort showed preservation of eGFR over a 5-year period compared with the GLP-1 RA treated cohort (+3.5 ml/min per 1.73 m2 vs -7.2 ml/min per 1.73 m2, respectively), including patients with established chronic kidney disease (CKD). The SGLT2i treated cohort experienced higher rates of diabetic ketoacidosis (DKA) (RR 2.08 [95% CI 1.05, 4.12] p=0.0309) and urinary tract infection/pyelonephritis (RR 2.27 [95% CI 1.12, 4.55] p=0.019) compared with the GLP-1 RA treated cohort. However, the SGLT2i treated cohort were less likely to develop heart failure (RR 0.44 [95% CI 0.23, 0.83] p=0.0092), CKD (RR 0.49 [95% CI 0.28, 0.86] p=0.0118) and be hospitalised for any cause (RR 0.59 [95% CI 0.46, 0.76] p≤0.0001) when compared with the GLP-1 RA treated cohort. CONCLUSIONS/INTERPRETATION: Both SGLT2is and GLP-1 RAs have potential benefits as adjunctive agents in type 1 diabetes. SGLT2is provide cardio-renal benefits, despite an increase in the risk of DKA and urinary tract infection compared with GLP-1 RA therapy. Long-term evaluation of the efficacy and safety of these adjunctive therapies is required to guide their use in individuals with type 1 diabetes.
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Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Cetoacidosis Diabética , Insuficiencia Renal Crónica , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Humanos , Hipoglucemiantes/efectos adversos , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Estudios Retrospectivos , Insulina/uso terapéutico , Péptido 1 Similar al Glucagón/uso terapéutico , Péptido 1 Similar al Glucagón/agonistas , Glucosa , Receptor del Péptido 1 Similar al Glucagón/agonistasRESUMEN
AIM: To assess the relationship of sodium-glucose cotransporter-2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor analogues (GLP-1RA) and their combination (SGLT2i + GLP-1RA) with 5-year risk of all-cause mortality, hospitalization and cardiovascular/macrovascular disease in people with type 2 diabetes. MATERIALS AND METHODS: Retrospective cohort analysis of 2.2 million people with type 2 diabetes receiving insulin across 85 health care organizations using a global federated health research network. Three intervention cohorts (SGLT2i, GLP-1RA and SGLT2i + GLP-1RA) were compared against a control cohort (no SGLT2i/GLP-1RA). Propensity score matching for age, ischaemic heart disease, sex, hypertension, chronic kidney disease, heart failure and glycated haemoglobin was used to balance cohorts 1:1 (SGLT2i, n = 143 600; GLP-1RA, n = 186 841; SGLT-2i + GLP-1RA, n = 108 504). A sub-analysis comparing combination and monotherapy cohorts was also performed. RESULTS: The intervention cohorts showed a reduced hazard ratio (HR, 95% confidence interval) over 5 years compared with the control cohort for all-cause mortality (SGLT2i 0.49, 0.48-0.50; GLP-1RA 0.47, 0.46-0.48; combination 0.25, 0.24-0.26), hospitalization (0.73, 0.72-0.74; 0.69, 0.68-0.69; 0.60, 0.59-0.61) and acute myocardial infarct (0.75, 0.72-0.78; 0.70, 0.68-0.73; 0.63, 0.60-0.66), respectively. All other outcomes showed a significant risk reduction in favour of the intervention cohorts. The sub-analysis showed a significant risk reduction in all-cause mortality for combination therapy versus SGLT2i (0.53, 0.50-0.55) and GLP-1RA (0.56, 0.54-0.59). CONCLUSIONS: SGLT2i, GLP-1RAs or combination therapy confers mortality and cardiovascular protection in people with type 2 diabetes over 5 years. Combination therapy was associated with the greatest risk reduction in all-cause mortality versus a propensity matched control cohort. In addition, combination therapy offers a reduction in 5-year all-cause mortality when compared directly against either monotherapy.
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Enfermedades Cardiovasculares , Diabetes Mellitus Tipo 2 , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Simportadores , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Inhibidores del Cotransportador de Sodio-Glucosa 2/farmacología , Hipoglucemiantes/uso terapéutico , Hipoglucemiantes/farmacología , Receptor del Péptido 1 Similar al Glucagón/agonistas , Estudios Retrospectivos , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/prevención & control , Glucosa , SodioRESUMEN
AIMS: There is conflicting evidence on whether the type of atrial fibrillation (AF) is associated with risk of cardiovascular events, including acute myocardial infarction (MI) and ischemic stroke. The aim of the present study was to investigate whether the risk of MI and ischemic stroke differs between individuals with first-diagnosed paroxysmal vs. non-paroxysmal AF treated with anticoagulants. METHODS AND RESULTS: De-identified electronic medical records from the TriNetX federated research network were used. Individuals with a new diagnosis of paroxysmal AF who had no evidence of other types of AF in their records were 1:1 propensity score-matched with individuals with non-paroxysmal AF, defined as persistent or chronic AF, who had no evidence of other types of AF in their records. All patients were followed for three years for the outcomes of MI and ischemic stroke. Cox proportional hazard models were used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs). In the propensity-matched cohort, among 24 848 well-matched AF individuals [mean age 74.4 ± 10.4; 10 101 (40.6%) female], 410 (1.7%) were diagnosed with acute MI and 875 (3.5%) with ischemic stroke during the three-year follow-up. Individuals with paroxysmal AF had significantly higher risk of acute MI (HR: 1.65, 95%CI: 1.35-2.01) compared to those with non-paroxysmal AF. First diagnosed paroxysmal AF was associated with higher risk of non-ST elevation MI (nSTEMI) (HR: 1.89, 95%CI: 1.44-2.46). No significant association was observed between the type of AF and risk of ischemic stroke (HR: 1.09, 95%CI: 0.95-1.25). CONCLUSION: Patients with first-diagnosed paroxysmal AF had higher risk of acute MI compared to individuals with non-paroxysmal AF, attributed to the higher risk of nSTEMI among patients with first-diagnosed paroxysmal AF. There was no significant association between type of AF and risk of ischemic stroke.
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Fibrilación Atrial , Accidente Cerebrovascular Isquémico , Infarto del Miocardio , Infarto del Miocardio sin Elevación del ST , Accidente Cerebrovascular , Humanos , Femenino , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Masculino , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/epidemiología , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/etiología , Infarto del Miocardio sin Elevación del ST/complicaciones , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/epidemiología , Infarto del Miocardio/complicaciones , Anticoagulantes/efectos adversos , Factores de RiesgoRESUMEN
Neuropathic pain in people with spinal cord injury is thought to be due to altered central neuronal activity. A novel therapeutic intervention using virtual reality (VR) head-mounted devices was investigated in this study for pain relief. Given the potential links to neuronal activity, the aim of the current study was to determine whether use of VR was associated with corresponding changes in electroencephalography (EEG) patterns linked to the presence of neuropathic pain. Using a within-subject, randomised cross-over pilot trial, we compared EEG activity for three conditions: no task eyes open state, 2D screen task and 3D VR task. We found an increase in delta activity in frontal regions for 3D VR with a decrease in theta activity. There was also a consistent decrease in relative alpha band (8-12 Hz) and an increase in low gamma (30-45 Hz) power during 2D screen and 3D VR corresponding, with reduced self-reported pain. Using the nonlinear and non-oscillatory method of extracting fractal dimensions, we found increases in brain complexity during 2D screen and 3D VR. We successfully classified the 3D VR condition from 2D screen and eyes opened no task conditions with an overall accuracy of 80.3%. The findings in this study have implications for using VR applications as a therapeutic intervention for neuropathic pain in people with spinal cord injury.
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Neuralgia , Traumatismos de la Médula Espinal , Terapia de Exposición Mediante Realidad Virtual , Realidad Virtual , Electroencefalografía , Humanos , Neuralgia/terapiaRESUMEN
CONTEXT: Pain management in palliative care remains inadequate; the development of innovative therapeutic options is needed. OBJECTIVES: To determine the feasibility and preliminary effectiveness for larger randomised controlled trials of 3D head-mounted (HMD) virtual reality (VR) for managing cancer pain (CP) in adults. METHODS: Thirteen people receiving palliative care participated in a single-session randomised cross-over trial, after which they completed a qualitative semi-structured interview. We also compared the effects of 3D HMD VR and 2D screen applications on CP intensity and levels of perceived presence. Feasibility was assessed with recruitment, completion rates and time required to recruit target sample. RESULTS: Although recruitment was slow, completion rate was high (93%). Participants reported that the intervention was acceptable and caused few side effects. Although participants reported significantly reduced CP intensity after 3D HMD VR (1.9 ± 1.8, P = .003) and 2D screen applications (1.5 ± 1.6, P = .007), no significant differences were found between interventions (-.38 ± 1.2, 95% CI: -1.1-.29, P = .23). Participants reported significantly higher levels of presence with the 3D HMD VR compared to 2D screen (60.7 ± SD 12.4 versus 34.3 ± SD 17.1, mean 95% CI: 16.4-40.7, P = .001). Increased presence was associated with significantly lower pain intensity (mean 95% CI: -.04--0.01, P = 0.02). CONCLUSIONS: Our preliminary findings support growing evidence that both 3D and 2D virtual applications provide pain relief for people receiving palliative care. Given the relative lack of cybersickness and increasing access to portable VR, we suggest that larger clinical studies are warranted.
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Dolor en Cáncer , Neoplasias , Realidad Virtual , Adulto , Dolor en Cáncer/terapia , Estudios Cruzados , Estudios de Factibilidad , Humanos , Neoplasias/complicaciones , Neoplasias/terapia , Cuidados PaliativosRESUMEN
OBJECTIVE: Although virtual reality is shown to have short-term analgesic effects in acute pain settings, its long-term efficacy in chronic pain conditions has not been established. This scoping review aims to provide a summary of virtual reality approaches explored in chronic primary and secondary pain conditions as defined by the International Association for the Study of Pain. METHODS: A systematic literature search in Ovid PubMed and Ovid Embase was conducted between January 5 and January 10, 2021, with the use of the Arksey and O'Malley six-step scoping review criteria. Articles were searched via search terms and keywords relating to International Classification of Diseases-defined primary and secondary chronic pain conditions, virtual reality, virtual illusion, distraction, and effects on levels of pain. RESULTS: Of the 2,118 articles located, 44 were included, which covered a range of primary and secondary chronic pain conditions and used a variety of different computer screen and headset protocols, including gaming, mindfulness, exercise, relaxation, and proprioceptive skills. CONCLUSIONS: Studies show virtual reality to be an effective analgesic intervention for people with chronic pain. Given user satisfaction, a lack of side effects such as cybersickness, and relief of comorbid symptoms, virtual reality has potential as a worthwhile adjunct to chronic pain management programs, thus enabling patients to take control of their symptoms.
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Dolor Agudo , Dolor Crónico , Terapia de Exposición Mediante Realidad Virtual , Realidad Virtual , Dolor Crónico/tratamiento farmacológico , Ejercicio Físico , Humanos , Terapia de Exposición Mediante Realidad Virtual/métodosRESUMEN
OBJECTIVE: Musculoskeletal pain is a significant contributor to the global disease burden. Management of musculoskeletal pain where a neuropathic component is present can be challenging. This study evaluated the internal structure of the Patient-Reported Outcome Measures Information System (PROMIS) pain quality scales, explored the prevalence of neuropathic and nociceptive pain, and identified health demographics and behaviors related to musculoskeletal pain presentations. METHODS: Patients presenting to the Victoria University Osteopathy Clinic (Melbourne, Vic., Australia) were invited to complete a health demographics and behaviors questionnaire, and the PROMIS Neuropathic (NeuroPQ) and Nociceptive (NociPQ) pain quality scales, before their initial consultation. Descriptive, inferential, and correlation statistics were used to evaluate the PROMIS scales, health demographics, and behaviors. Mokken scale analysis was used to evaluate the internal structure and dimensionality of the NeuroPQ and NociPQ scales. RESULTS: Three hundred eighty-three (N=383) patients completed the measures. Mokken scaling suggested the PROMIS scales demonstrated acceptable internal structure and were unidimensional. Over 22% of patients demonstrated cutoff scores above 50, suggesting a substantive neuropathic pain component to their musculoskeletal presentation. Patients who reported cigarette smoking, not being born in Australia or not speaking English at home, demonstrated higher NeuroPQ scores. Females demonstrated significantly higher NociPQ scores than males. Pain intensity demonstrated small to medium correlations with NeuroPQ and NociPQ scores. DISCUSSION: This study provides support for the use of the NeuroPQ and NociPQ scales in musculoskeletal pain patients. Associations with health demographics and behaviors were identified, and patients typically experienced a combination of neuropathic and nociceptive pain.
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Dolor Musculoesquelético , Dolor Nociceptivo , Femenino , Humanos , Sistemas de Información , Masculino , Dolor Musculoesquelético/epidemiología , Dolor Nociceptivo/epidemiología , Medición de Resultados Informados por el Paciente , Encuestas y CuestionariosRESUMEN
PURPOSE: Building well-performing machine learning (ML) models in health care has always been exigent because of the data-sharing concerns, yet ML approaches often require larger training samples than is afforded by one institution. This paper explores several federated learning implementations by applying them in both a simulated environment and an actual implementation using electronic health record data from two academic medical centers on a Microsoft Azure Cloud Databricks platform. MATERIALS AND METHODS: Using two separate cloud tenants, ML models were created, trained, and exchanged from one institution to another via a GitHub repository. Federated learning processes were applied to both artificial neural networks (ANNs) and logistic regression (LR) models on the horizontal data sets that are varying in count and availability. Incremental and cyclic federated learning models have been tested in simulation and real environments. RESULTS: The cyclically trained ANN showed a 3% increase in performance, a significant improvement across most attempts (P < .05). Single weight neural network models showed improvement in some cases. However, LR models did not show much improvement after federated learning processes. The specific process that improved the performance differed based on the ML model and how federated learning was implemented. Moreover, we have confirmed that the order of the institutions during the training did influence the overall performance increase. CONCLUSION: Unlike previous studies, our work has shown the implementation and effectiveness of federated learning processes beyond simulation. Additionally, we have identified different federated learning models that have achieved statistically significant performances. More work is needed to achieve effective federated learning processes in biomedicine, while preserving the security and privacy of the data.
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Nube Computacional , Difusión de la Información , Privacidad , Humanos , Aprendizaje Automático , Redes Neurales de la ComputaciónRESUMEN
Context: Virtual and augmented imagery are emerging technologies with potential to reduce the severity and impact of neuropathic pain in people with spinal cord injury (SCI).Objective: We aimed to identify and discuss studies using virtual and augmented reality applications for the management of neuropathic pain in people with spinal cord injury.Methods (data sources, data extraction): A systematic literature search was conducted using PRISMA scoping review guidelines. Articles were searched in PubMed, Embase and Web of Science databases using search terms relating to SCI, virtual and augmented reality and neuropathic pain. With no strong evidence for visual imagery in the treatment of pain in SCI patients, we selected exploratory, feasibility and more rigorous methodologies such as randomized controlled trials and case-control studies. We only selected studies evaluating the effects of visual imagery on neuropathic pain at or below the spinal cord injury level.Results: Of 60 articles located, we included nine articles involving 207 participants. All studies were exploratory using head-mounted devices or 3D and 2D screens with virtual walking or limb movement imagery. Outcomes included pain sensitivity, motor function and body ownership. Eight of the nine studies reported significant reductions in neuropathic pain intensity. However, given small sample sizes in all studies, results may be unreliable.Conclusion: Although the number of studies and individual sample sizes are small, these initial findings are promising. Given the limited options available for the effective treatment of neuropathic SCI pain and early evidence of efficacy, they provide valuable incentive for further research.
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Neuralgia , Traumatismos de la Médula Espinal , Terapia de Exposición Mediante Realidad Virtual , Realidad Virtual , Humanos , Neuralgia/etiología , Neuralgia/terapia , Traumatismos de la Médula Espinal/complicaciones , CaminataRESUMEN
STUDY DESIGN: Within-subject, randomised cross-over trial. OBJECTIVES: To determine whether a commercially available 3D head-mounted (HMD) virtual reality (VR) device results in significant reductions in neuropathic pain compared to using a 2D screen device in people with spinal cord injury (SCI). SETTING: Greenwich Hospital, Sydney, Australia. METHODS: Sixteen men with established SCI and chronic neuropathic pain participated in a single-session randomised cross-over trial. We compared the effects of 3D HMD VR and a 2D screen application on SCI neuropathic pain intensity and levels of perceived presence. RESULTS: Participants reported significantly lower pain intensity after 3D HMD VR compared to 2D screen application (1.9 ± SD 1.8 versus 3.4 ± SD 1.6, mean 95% CI: 1.5, P < 0.0001). Participants reported significantly higher perceived levels of presence with the 3D HMD VR compared to 2D screen of (49.6 ± SD 8.9 versus 32.8 ± SD 11.1, mean 95% CI: 16.6, P < 0.0001). Increased perceived presence was associated with significantly lower pain intensity regardless of randomised sequencing of the two conditions (mean 95% CI: 0.06, P = 0.005). Effect size for pain reduction using 3D HMD VR was 0.80. CONCLUSIONS: We suggest that 3D HMD VR may provide neuropathic pain relief for people with SCI. Given the lack of cybersickness and ease of access, we propose that immersive VR could be a helpful adjunct to current pharmacotherapy. Further research is required to show that VR can be effective for more long-term reductions in SCI pain.
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Neuralgia , Traumatismos de la Médula Espinal , Realidad Virtual , Estudios Cruzados , Humanos , Masculino , Neuralgia/etiología , Neuralgia/terapia , Proyectos Piloto , Traumatismos de la Médula Espinal/complicacionesRESUMEN
BACKGROUND: Pain has been identified as a global health issue with substantial effects on individuals and society. Health professionals managing pain complaints must have appropriate knowledge of pain neurophysiology, and attitudes and beliefs towards pain management that align with current practice guidelines. OBJECTIVES: Evaluate Australian osteopaths' current level of knowledge of pain neurophysiology and their beliefs and attitudes towards pain, and explore associations with demographic variables. METHOD: Australian osteopaths drawn from a nationally representative practice-based research network received the questionnaire. The questionnaire included demographic information, Neurophysiology of Pain Questionnaire (NPQ), Pain Attitudes and Beliefs Scale for Physiotherapists (PABS-PT) and the Attitudes to Back Pain Scale in Musculoskeletal Practitioners (ABS-mp). RESULTS: Complete responses were received from 211 osteopaths (21.3% response rate). The mean total NPQ score was equivalent to 72.2% correct responses. The PABS-PT Biomedical scale mean score was 38.8 ( ±9.1, α = 0.81) and the Biopsychosocial scale was 22.3 ( ±3.3, α = 0.38). ABS-mp mean factor scores suggest osteopaths support psychological approaches (22.1, ±3.3, α = 0.71) but endorsed more treatment sessions for those with back pain (15.9, ±4.7, α = 0.71). Trivial correlations between measures and most demographic variables were observed. Osteopaths who undertook further studies in pain had higher mean NPQ scores, with moderate negative correlations with a lower PABS-PT Biomedical subscale score (ρ = -0.45, p < 0.01). CONCLUSIONS: Australian osteopaths demonstrate a range of pain neurophysiology knowledge, and beliefs and attitudes towards pain. The findings support the positive impact of professional development for improving pain knowledge in this population.