RESUMEN
Mortality rates in our fracture liaison service ranged from 2.7% at year 1 to 14.8% at year 5 post-screening. Presentation with multiple simultaneous fractures at screening was associated with higher risk of death. This finding indicates the need for increased focus on this high-risk group. PURPOSE: To examine all-cause mortality rates in a provincial fracture liaison service (FLS) and the association between the index fracture type, particularly multiple simultaneous fractures, and the risk of death at follow-up. METHODS: This cohort study includes fragility fracture patients aged 50+, enrolled in a provincial FLS in Ontario, Canada, between 2007 and 2010. All-cause mortality was assessed using administrative data. Multivariable Cox proportional hazards model was used to examine the risk of death 5 years after screening. RESULTS: Crude mortality rates for 6543 fragility fracture patients were 2.7% at year 1, 5.6% at year 2, and 14.8% at year 5 after screening. After adjusting for age and sex, and relative to distal radius fracture, patients with multiple (simultaneous) fractures at screening had a higher risk of dying (HR = 1.8, 95%CI 1.3-2.4), followed by those with a hip fracture (HR = 1.5, 95%CI 1.3-1.8), a proximal humerus fracture (HR = 1.4, 95%CI 1.2-1.7), and other single fractures (HR = 1.4, 95%CI 1.1-1.7). Having an index ankle fracture was not associated with the risk of death over a distal radius fracture. As compared to the 50-65 age group, patients 66 years and older had a higher risk of death (for 66-70 age group: HR = 2.5, 95%CI 1.9-3.3; for 71-80: HR = 4.3, 95%CI 3.5-5.4; and for 81+: HR = 10.6, 95%CI 8.7-13.0). Females had a lower risk of death (HR = 0.5, 95%CI 0.5-0.6) than males. CONCLUSIONS: Presenting with multiple fractures was an indicator of higher risk of death relative to a distal radius fracture. This finding indicates the need for increased focus on this high-risk group.
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Fracturas Múltiples , Fracturas de Cadera , Fracturas Osteoporóticas , Anciano , Estudios de Cohortes , Femenino , Fracturas Múltiples/mortalidad , Fracturas de Cadera/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Ontario/epidemiología , Fracturas Osteoporóticas/etiología , Fracturas Osteoporóticas/mortalidad , Modelos de Riesgos Proporcionales , Factores de RiesgoRESUMEN
We examined the 5-year refracture rate of 6543 patients and found an overall rate of 9.7%. Adjusted analysis showed that presenting with multiple fractures was an indicator of a higher refracture risk; while presenting with an ankle fracture was associated with a lower refracture risk. INTRODUCTION: To examine refractures among patients screened in a province-wide fracture liaison service (FLS). METHODS: We assessed the 5-year refracture rate of fragility fracture patients aged 50+ who were screened at 37 FLS fracture clinics in Ontario, Canada. Refracture was defined as a new hip, pelvis, spine, distal radius, or proximal humerus fracture. Kaplan-Meier curves and Cox proportional hazards model adjusting for age, sex, and index fracture type were used to examine refracture rates. RESULTS: The 5-year refracture rate of 6543 patients was 9.7%. Those presenting with multiple fractures at baseline (i.e., two or more fractures occurring simultaneously) had the highest refracture rate of 19.6%. As compared to the 50-65 age group, refracture risk increased monotonically with age group (66-70 years: HR = 1.3, CI 95%, 1.0-1.7; 71-80 years: HR = 1.7, CI 1.4-2.1; 81+ years: HR = 3.0, CI 2.4-3.7). Relative to distal radius, presenting with multiple fractures at screening was associated with a higher risk of refracture (HR = 2.3 CI 1.6-3.1), while presenting with an ankle fracture was associated with a lower risk of refracture (HR = 0.7 CI 0.6-0.9). Sex was not a statistically significant predictor of refracture risk in this cohort (HR = 1.2, CI 1.0-1.5). CONCLUSIONS: One in ten patients in our cohort refractured within 5 years after baseline. Presenting with multiple fractures was an indicator of a higher refracture risk, while presenting with an ankle fracture was associated with a lower refracture risk. A more targeted FLS approach may be appropriate for patients at a higher refracture risk.
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Fracturas Osteoporóticas/epidemiología , Fracturas Osteoporóticas/prevención & control , Distribución por Edad , Anciano , Anciano de 80 o más Años , Fracturas de Tobillo/epidemiología , Femenino , Estudios de Seguimiento , Fracturas Múltiples/epidemiología , Humanos , Estimación de Kaplan-Meier , Masculino , Tamizaje Masivo/organización & administración , Persona de Mediana Edad , Ontario/epidemiología , Recurrencia , Medición de Riesgo/métodos , Factores de Riesgo , Prevención Secundaria/organización & administración , Factores de TiempoAsunto(s)
COVID-19/epidemiología , Pandemias , Mejoramiento de la Calidad , Servicio de Cirugía en Hospital/estadística & datos numéricos , Servicio de Cirugía en Hospital/normas , Registros Electrónicos de Salud , Utilización de Instalaciones y Servicios , Humanos , SARS-CoV-2 , Reino Unido/epidemiología , Procedimientos Quirúrgicos Vasculares/normas , Procedimientos Quirúrgicos Vasculares/estadística & datos numéricosRESUMEN
BACKGROUND: Schizophrenia (SZ) and bipolar disorder (BD) have substantial negative impact on the quality of human life. Both, microRNA (miRNA) expression profiling in SZ and BD postmortem brains [and genome-wide association studies (GWAS)] have implicated miRNAs in disease etiology. Here, we aim to determine whether significant GWAS signals observed in the Psychiatric Genetic Consortium (PGC) are enriched for miRNAs. METHOD: A two-stage approach was used to determine whether association signals from PGC affect miRNAs: (i) statistical assessment of enrichment using a Simes test and sum of squares test (SST) and (ii) biological evidence that quantitative trait loci (eQTL) mapping to known miRNA genes affect their expression in an independent sample of 78 postmortem brains from the Stanley Medical Research Institute. RESULTS: A total of 2567 independent single nucleotide polymorphisms (SNPs) (R2 > 0.8) were mapped locally, within 1 Mb, to all known miRNAs (miRBase v. 21). We show robust enrichment for SZ- and BD-related SNPs with miRNAs using Simes (SZ: p ≤ 0.0023, BD: p ≤ 0.038), which remained significant after adjusting for background inflation in SZ (empirical p = 0.018) and approached significance in BD (empirical p = 0.07). At a false discovery rate of 10%, we identified a total of 32 eQTLs to influence miRNA expression; 11 of these overlapped with BD. CONCLUSIONS: Our approach of integrating PGC findings with eQTL results can be used to generate specific hypotheses regarding the role of miRNAs in SZ and BD.
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Trastorno Bipolar/genética , Esquizofrenia/genética , Autopsia , Encéfalo , Mapeo Cromosómico , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Humanos , MicroARNs/genética , Polimorfismo Genético , Sitios de Carácter CuantitativoRESUMEN
UNLABELLED: We completed a network meta-analysis of published papers to compare bisphosphonate gastrointestinal safety. We found that zoledronic acid had the highest chance of causing gastrointestinal adverse events. Etidronate had the highest chance of discontinuation due to an adverse event. No difference was found for serious adverse events. INTRODUCTION: Bisphosphonates are first-line treatment for osteoporosis. Gastrointestinal (GI) adverse events (AE) are the primary reason for non-adherence. Little is known about the comparative GI safety of bisphosphonates. PURPOSE: Leverage published clinical trial data to examine the comparative GI safety of bisphosphonates. METHODS: We completed a systematic review of all English-language clinical trials that assessed bisphosphonate safety and/or efficacy in primary osteoporosis through to 2012. Randomized, blinded, and controlled studies were eligible. The primary outcome was any GI-related AE. Subanalyses were completed for upper GI symptoms, serious GI, nausea, esophageal-related events, and discontinuation due to AE. A Bayesian-based network meta-analysis was completed to allow for indirect comparisons. Results were reported as the probability that a specific drug had the highest number of events. RESULTS: We identified 50 studies: 32 alendronate, 12 risedronate, 5 etidronate, and 7 zoledronic acid. Zoledronic acid had the highest probability of having the highest number of any GI AE (91%) and nausea (70%). Etidronate (70%) and zoledronic acid (28%) had the highest probability of having the greatest attrition due to AE. Etidronate had the highest probability (56%) of having the greatest number of upper GI symptoms among oral bisphosphonates. CONCLUSION: Zoledronic acid had the highest probability of causing the greatest number of GI AE, possibly related to nausea. These results question the assumption that annual zoledronic acid will translate into better adherence. Little difference was found between alendronate and risedronate for serious AE. More research into real-world implications of the comparative safety of bisphosphonates is needed.
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Conservadores de la Densidad Ósea/efectos adversos , Difosfonatos/efectos adversos , Enfermedades Gastrointestinales/inducido químicamente , Osteoporosis/tratamiento farmacológico , Conservadores de la Densidad Ósea/uso terapéutico , Difosfonatos/uso terapéutico , Humanos , Imidazoles/efectos adversos , Náusea/inducido químicamente , Ensayos Clínicos Controlados Aleatorios como Asunto , Ácido ZoledrónicoRESUMEN
SUMMARY: Antihypertensive drugs are associated with an immediate increased falls risk in elderly patients which was significant during the first 14 days after receiving a thiazide diuretic, angiotensin-converting enzyme inhibitor, angiotensin II receptor blocker, calcium channel blocker, or beta-adrenergic blocker. Fall prevention strategies during this period may prevent fall-related injuries. INTRODUCTION: The purpose of this study is to evaluate if initiation of the common antihypertensive drugs is associated with the occurrence of falls. METHODS: This population-based self-controlled case series study used healthcare administrative databases to identify new users of antihypertensive drugs in the elderly aged 66 and older living in Ontario, Canada who suffered a fall from April 1, 2000 to March 31, 2009. The risk period was the first 45 days following antihypertensive therapy initiation, further subdivided into 0-14 and 15-44 days with control periods before and after treatment in a 450-day observation period. We calculated the relative incidence (incidence rate ratio, IRR), defined as the rate of falls in the risk period compared to falls rate in the control periods. RESULTS: Of the 543,572 new users of antihypertensive drugs among community-dwelling elderly, 8,893 experienced an injurious fall that required hospital care during the observation period. New users had a 69 % increased risk of having an injurious fall during the first 45 days following antihypertensive treatment (IRR = 1.69; 95 % CI, 1.57-1.81). This finding was consistent for thiazide diuretics, angiotensin-converting enzyme inhibitors, calcium channel blockers, and beta-adrenergic blockers but not angiotensin II receptor antagonists. There was also an increased falls risk during the first 14 days of antihypertensive drug initiation (IRR = 1.94; 95 % CI, 1.75-2.16), which was consistent for all antihypertensive drug classes. CONCLUSIONS: This study suggests that initiation of antihypertensive drugs is a risk factor for falls in the elderly. Fall prevention strategies during this period may reduce injuries.
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Accidentes por Caídas/estadística & datos numéricos , Antihipertensivos/efectos adversos , Heridas y Lesiones/etiología , Accidentes por Caídas/prevención & control , Anciano , Anciano de 80 o más Años , Bases de Datos Factuales , Prescripciones de Medicamentos , Femenino , Humanos , Incidencia , Masculino , Ontario/epidemiología , Medición de Riesgo/métodos , Heridas y Lesiones/epidemiología , Heridas y Lesiones/prevención & controlRESUMEN
AIMS: To examine temporal changes in progression to second-line therapies among older patients with diabetes newly treated with metformin. METHODS: We conducted a population-based study among residents of Ontario, Canada aged 66 years and older with diabetes newly treated with metformin monotherapy in 1997, 2000, 2003 or 2006. Each annual cohort was followed until progression to a second oral hypoglycaemic agent, insulin or until 31 December 2010. Time to progression to a second oral hypoglycaemic agent or insulin was compared across the cohorts. RESULTS: In the four annual cohorts, we identified a total of 46 104 people newly treated with metformin monotherapy. The median time to progression to any second diabetes therapy lengthened significantly over time, from 5.0 years in 1997 to 6.1 years in 2003 (P < 0.0001). Similarly, the time to progression to insulin lengthened over the study period (P = 0.03). Furthermore, the choice of second-line therapy changed over time. While 80.7% of new metformin users in 1997 progressed to glyburide therapy as second-line treatment, the corresponding figure by 2006 was only 45.1% as newer treatment options emerged. CONCLUSIONS: Although recent guidelines recommend aggressive intensification of oral therapy for patients with Type 2 diabetes, older Ontarians with diabetes who started metformin in 2006 remained on monotherapy for longer than those who started in 1997. Furthermore, although there is no consensus regarding a preferred second-line therapy, the introduction of new alternatives has led to greater variation in the selection of second-line therapies in this population.
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Glucemia/efectos de los fármacos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/administración & dosificación , Metformina/administración & dosificación , Anciano , Glucemia/metabolismo , Canadá/epidemiología , Estudios de Cohortes , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/epidemiología , Progresión de la Enfermedad , Esquema de Medicación , Femenino , Humanos , Masculino , Ontario/epidemiología , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
AIMS: To characterize temporal trends in the selection and timing of first-line pharmacotherapy among older patients with Type 2 diabetes. DESIGN AND METHODS: We studied five population-based cohorts every 3 years, from 1994 to 2006. In each of those years, we identified all subjects aged 66 years or older newly diagnosed with diabetes and determined the initial glucose-lowering drug and the time between diagnosis and drug initiation. We calculated the proportion of patients prescribed each agent and estimated time from diagnosis to initiation using Kaplan-Meier survival analysis. RESULTS: We identified a total of 64 368 eligible people who initiated drug therapy during the study period. From 1994 to 2006, first-line metformin use increased from 20.1 to 79.0%. Glyburide (glibenclamide) decreased from 71.1% of all first-line therapies in 1994 to 9.8% in 2006, while first-line use of insulin or combination therapy have changed little at approximately 5% each. No other medication exceeded 2% of first-line therapies. The median time from diagnosis to initiation of pharmacotherapy increased dramatically during the study period, from 1.8 years in 1994 to 4.6 years in 2006. CONCLUSIONS: Metformin has become the most commonly used initial medication for the treatment of diabetes. Although guidelines have evolved to recommend more aggressive initiation and intensification of pharmacotherapy, our results suggest that the time from diagnosis to initiation has increased substantially.
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Glucemia/efectos de los fármacos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Insulina/uso terapéutico , Metformina/uso terapéutico , Tiempo de Tratamiento , Anciano , Glucemia/metabolismo , Estudios de Cohortes , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/mortalidad , Progresión de la Enfermedad , Esquema de Medicación , Práctica Clínica Basada en la Evidencia , Femenino , Humanos , Hipoglucemiantes/administración & dosificación , Insulina/administración & dosificación , Estimación de Kaplan-Meier , Masculino , Metformina/administración & dosificación , Selección de Paciente , Guías de Práctica Clínica como Asunto , Resultado del TratamientoRESUMEN
UNLABELLED: We studied new users of oral bisphosphonates and found that less than half persisted with therapy for 2 years, and interruptions in use were common. During a median observation period of 4.7 years, 10% of patients filled only a single prescription, 37% switched therapies and median cumulative exposure was 2.2 years. INTRODUCTION: We sought to describe bisphosphonate prescribing, persistence and cumulative exposure among seniors in Ontario, Canada. METHODS: We used Ontario Drug Benefit pharmacy claims to identify residents aged ≥ 66 years who initiated oral bisphosphonate therapy between April 1996 and March 2009. The first date of bisphosphonate dispensing was considered the index date. Persistence with therapy was defined as continuous treatment with no interruption exceeding 60 days. We examined persistence with therapy and the number of extended gaps (>60 days) between prescriptions over time periods ranging from 1 to 9 years. We also identified the proportion of patients filling only a single prescription and switching to a different bisphosphonate, and calculated the median days of exposure irrespective of gaps in therapy. RESULTS: A total of 451,113 eligible new bisphosphonate users were identified: mean age = 75.6 years (SD = 6.9), 84% female, and median follow-up length = 4.7 years. Persistence with therapy declined from 63% at 1 year to 46% at 2 years and 12% at 9 years. Among those with at least 5 years of follow-up (n = 213,029), 61% had one or more extended gaps in bisphosphonate therapy. Overall, 10% of patients filled only a single prescription, 37% switched to a different bisphosphonate and the median exposure was 2.2 years. CONCLUSION: Less than half of patients persisted with bisphosphonate therapy for 2 years and interruptions in therapy were common, with most patients experiencing two or more >60-day gaps in therapy. Interventions are needed to improve persistence with bisphosphonate therapy and reduce the frequency of gaps in treatment.
Asunto(s)
Conservadores de la Densidad Ósea/administración & dosificación , Difosfonatos/administración & dosificación , Cumplimiento de la Medicación/estadística & datos numéricos , Osteoporosis/tratamiento farmacológico , Pautas de la Práctica en Medicina/estadística & datos numéricos , Administración Oral , Anciano , Anciano de 80 o más Años , Conservadores de la Densidad Ósea/uso terapéutico , Difosfonatos/uso terapéutico , Prescripciones de Medicamentos/estadística & datos numéricos , Sustitución de Medicamentos/estadística & datos numéricos , Femenino , Estudios de Seguimiento , Humanos , Masculino , Ontario , Osteoporosis/psicología , Osteoporosis Posmenopáusica/tratamiento farmacológico , Osteoporosis Posmenopáusica/psicología , Factores de TiempoRESUMEN
AIMS: Sulphonylureas promote insulin release by inhibiting pancreatic potassium channels. Older sulphonylureas such as glyburide (glibenclamide), but not newer ones such as gliclazide, antagonize similar channels in myocardium, interfering with the protective effects of ischaemic preconditioning. Whether this imparts a higher risk of adverse cardiac events is unknown. METHODS: We conducted a population-based cohort study of patients aged 66 years and older who were hospitalized for acute myocardial infarction or who underwent percutaneous coronary intervention between 1 April 2007 and 31 March 2010 while receiving either glyburide or gliclazide. We used a high-dimensional propensity score matching process to ensure similarity of glyburide- and gliclazide-treated patients. The primary outcome was a composite of death or hospitalization for myocardial infarction or heart failure. RESULTS: During the 2-year study period, we matched 1690 patients treated with glyburide to 984 patients treated with gliclazide at the time of hospitalization for acute myocardial infarction or percutaneous coronary intervention. We found no difference in the risk of the composite outcome among patients receiving glyburide (adjusted hazard ratio 1.01; 95% CI 0.86-1.18). We found similar results in secondary analyses of each outcome individually, and in two supplementary analyses (haemorrhage and pneumonia) in which we anticipated no difference between the two patient groups. CONCLUSIONS: Among older patients hospitalized for acute myocardial infarction or percutaneous coronary intervention, treatment with glyburide is not associated with an increased risk of future adverse cardiovascular events relative to gliclazide, suggesting that the effect of glyburide on ischaemic preconditioning is of little clinical relevance.
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Angioplastia Coronaria con Balón/efectos adversos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Angiopatías Diabéticas/tratamiento farmacológico , Gliclazida/administración & dosificación , Gliburida/administración & dosificación , Infarto del Miocardio/tratamiento farmacológico , Compuestos de Sulfonilurea/administración & dosificación , Anciano , Estudios de Cohortes , Diabetes Mellitus Tipo 2/mortalidad , Diabetes Mellitus Tipo 2/fisiopatología , Angiopatías Diabéticas/mortalidad , Angiopatías Diabéticas/fisiopatología , Femenino , Estudios de Seguimiento , Gliclazida/efectos adversos , Gliburida/efectos adversos , Humanos , Incidencia , Precondicionamiento Isquémico , Masculino , Infarto del Miocardio/mortalidad , Infarto del Miocardio/fisiopatología , Miocardio , Ontario/epidemiología , Factores de Riesgo , Compuestos de Sulfonilurea/efectos adversos , Resultado del TratamientoRESUMEN
AIM: The safety and efficacy of laparoscopic surgery for colon cancer is well established but its uptake in the province has not been previously explored. We report an investigation of the trends of open and laparoscopic surgery for colon cancer in Ontario, Canada. METHOD: A retrospective cross-sectional time-series analysis examining population-based rates of elective surgery for colon cancer among 10.5 million adults in Ontario was conducted from 1 April 2002 to 31 March 2009. Databases were linked to assess quarterly elective procedure rates over time. RESULTS: During the study period, 3950 laparoscopic and 13 048 open elective colon cancer operations were performed in Ontario. The overall quarterly rate of colon cancer surgery remained stable at an average of 5.8 per 100000 population (P=0.10). From the first and last quarter, the rate of laparoscopic operations increased nearly threefold from 0.8 to 2.2 per 100000 population with a notable increase after 2005 (P<0.01). In contrast, open surgery decreased by more than 30% from 5.3 to 3.5 per 100 000 population (P<0.01). If current trends continue, the projected proportion of laparoscopic colon operations is estimated to reach 41% by 2015. Patients receiving open surgery had a significantly higher preoperative comorbidity (Charlson comorbidity score≥3) than those having laparoscopy (47.8%vs 39.1%, standardized difference 0.26). CONCLUSION: Trends in Ontario of laparoscopic colon cancer surgery show an increase between 2002 and 2009, but the incidence remains lower than for open surgery.
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Colectomía/tendencias , Neoplasias del Colon/cirugía , Procedimientos Quirúrgicos Electivos/tendencias , Laparoscopía/tendencias , Adulto , Anciano , Anciano de 80 o más Años , Colectomía/métodos , Colectomía/estadística & datos numéricos , Estudios Transversales , Procedimientos Quirúrgicos Electivos/métodos , Procedimientos Quirúrgicos Electivos/estadística & datos numéricos , Femenino , Humanos , Laparoscopía/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Ontario , Estudios RetrospectivosRESUMEN
AIM: The safety and efficacy of laparoscopic surgery for colon cancer have been demonstrated in large, multicentre clinical trials. The study aimed to determine the use of laparoscopic surgery for rectal cancer in Ontario over a 7-year period. METHOD: We conducted a retrospective study examining rates of elective rectal cancer surgery among 10.5 million adults in Ontario, Canada, from 1 April 2002 to 31 March 2009. We linked the Canadian Institute for Health Information Discharge Abstract Database, the Registered Persons Database and the database of the Ontario Cancer Registry to assess procedures used over the period. Data on demographics were collected. Trends were assessed using time series analysis. RESULTS: Over the 7-year period, 8189 open and 1079 laparoscopic elective operations for rectal cancer were identified. The annual rate of laparoscopic rectal cancer procedures increased from 0.60 per 100,000 population in 2003 to 2.24 per 100,000 population in 2008 (P < 0.01). Laparoscopic patients were similar to open with respect to age (66.5 ± 11.8 vs 66.2 ± 12.1 years; standardized difference 0.02), gender (63.2%vs 59.4%; standardized difference 0.08), Charlson Comorbidity Index score (standardized difference < 0.1) and socioeconomic status (standardized difference < 0.1). CONCLUSION: Laparoscopic rectal cancer surgery rates are increasing in Ontario. Ongoing research regarding the long-term safety and effectiveness of the laparoscopic approach for rectal cancer surgeries may lead to greater increases in its utilization.
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Procedimientos Quirúrgicos Electivos/tendencias , Laparoscopía/tendencias , Neoplasias del Recto/cirugía , Anciano , Femenino , Humanos , Laparoscopía/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Ontario , Estudios RetrospectivosRESUMEN
AIMS: It is uncertain whether meta-analyses lead to changes in prescribing practices. We studied trends in the prescribing of glucose-lowering therapy before and after the publication of a meta-analysis suggesting harm from rosiglitazone. METHODS: We examined the prescription records of all residents of Ontario, Canada, aged > or = 66 years. For each week between January and December 2007, we identified new users of five categories of glucose-lowering medications: rosiglitazone, pioglitazone, metformin, glibenclamide (glyburide) and insulin. The effect of the meta-analysis was assessed using interventional autoregressive integrated moving-average models. RESULTS: Following the release of the meta-analysis, there was a sudden decline in new users of rosiglitazone (P = 0.01), mirrored by a nearly identical but transient increase in new users of pioglitazone (P < 0.001). There was also a net decline in new users of thiazolidinediones as a class (P < 0.001). The number of new users of other glucose-lowering medications did not change. CONCLUSIONS: A highly-publicized meta-analysis regarding rosiglitazone's potential harms led to an abrupt decline in new users of the drug, as well as a transient surge in new use of pioglitazone.
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Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/efectos adversos , Tiazolidinedionas/efectos adversos , Anciano , Anciano de 80 o más Años , Humanos , Metaanálisis como Asunto , RosiglitazonaRESUMEN
OBJECTIVES: To examine the effectiveness of an antimicrobial stewardship programme on utilization and cost of antimicrobials in leukaemia patients in Canada. METHODS: We conducted a multisite retrospective observational time series study from 2005 to 2013. We implemented academic detailing as the intervention of an antimicrobial stewardship programme in leukaemia units at a hospital, piloted February-July 2010, then fully implemented December 2010-March 2013, with no intervention in August-November 2010. Internal control was the same hospital's allogeneic haematopoietic stem-cell transplantation unit. External control was the combined leukaemia-haematopoietic stem-cell transplantation unit at another hospital. Primary outcome was antimicrobial utilization (antibiotics and antifungals) in defined daily dose per 100 patient-days (PD). Secondary outcomes were antimicrobial cost (Canadian dollars per PD); cost and utilization by drug class; length of stay; 30-day inpatient mortality; and nosocomial Clostridium difficile infection. We used autoregressive integrated moving average models to evaluate the impact of the intervention on outcomes. RESULTS: The intervention group included 1006 patients before implementation and 335 during full implementation. Correspondingly, internal control had 723 and 264 patients, external control 1395 and 864 patients. Antimicrobial utilization decreased significantly in the intervention group (p <0.01, 278 vs. 247 defined daily dose per 100 PD), increased in external control (p = 0.02, 237.4 vs. 268.9 defined daily dose per 100 PD) and remained stable in internal control (p = 0.66). Antimicrobial cost decreased in the intervention group (p = 0.03; $154.59 per PD vs. $128.93 per PD), increased in external control (p = 0.01; $109.4 per PD vs. $135.97 per PD) but was stable in internal control (p = 0.27). Mortality, length of stay and nosocomial C. difficile rate in intervention group remained stable. CONCLUSIONS: The antimicrobial stewardship programme reduced antimicrobial use in leukaemia patients without affecting inpatient mortality and length of stay.
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Antiinfecciosos/economía , Programas de Optimización del Uso de los Antimicrobianos/estadística & datos numéricos , Infección Hospitalaria/epidemiología , Costos de los Medicamentos , Leucemia/epidemiología , Adulto , Anciano , Antiinfecciosos/uso terapéutico , Programas de Optimización del Uso de los Antimicrobianos/economía , Programas de Optimización del Uso de los Antimicrobianos/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Canadá/epidemiología , Infección Hospitalaria/tratamiento farmacológico , Infección Hospitalaria/etiología , Costos de los Medicamentos/estadística & datos numéricos , Femenino , Humanos , Leucemia/complicaciones , Leucemia/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Vigilancia en Salud Pública , Estudios RetrospectivosRESUMEN
RATIONALE: Targeted temperature management (TTM) improves survival with good neurological outcome after out-of-hospital cardiac arrest (OHCA), but is delivered inconsistently and often with delay. OBJECTIVE: To determine if prehospital cooling by paramedics leads to higher rates of 'successful TTM', defined as achieving a target temperature of 32-34°C within 6h of hospital arrival. METHODS: Pragmatic RCT comparing prehospital cooling (surface ice packs, cold saline infusion, wristband reminders) initiated 5min after return of spontaneous circulation (ROSC) versus usual resuscitation and transport. The primary outcome was rate of 'successful TTM'; secondary outcomes were rates of applying TTM in hospital, survival with good neurological outcome, pulmonary edema in emergency department, and re-arrest during transport. RESULTS: 585 patients were randomized to receive prehospital cooling (n=279) or control (n=306). Prehospital cooling did not increase rates of 'successful TTM' (30% vs 25%; RR, 1.17; 95% confidence interval [CI] 0.91-1.52; p=0.22), but increased rates of applying TTM in hospital (68% vs 56%; RR, 1.21; 95%CI 1.07-1.37; p=0.003). Survival with good neurological outcome (29% vs 26%; RR, 1.13, 95%CI 0.87-1.47; p=0.37) was similar. Prehospital cooling was not associated with re-arrest during transport (7.5% vs 8.2%; RR, 0.94; 95%CI 0.54-1.63; p=0.83) but was associated with decreased incidence of pulmonary edema in emergency department (12% vs 18%; RR, 0.66; 95%CI 0.44-0.99; p=0.04). CONCLUSIONS: Prehospital cooling initiated 5min after ROSC did not increase rates of achieving a target temperature of 32-34°C within 6h of hospital arrival but was safe and increased application of TTM in hospital.
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Servicios Médicos de Urgencia/métodos , Hipotermia Inducida/métodos , Hielo , Paro Cardíaco Extrahospitalario/terapia , Cloruro de Sodio/administración & dosificación , Anciano , Anciano de 80 o más Años , Temperatura Corporal , Reanimación Cardiopulmonar , Frío , Femenino , Humanos , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Paro Cardíaco Extrahospitalario/mortalidad , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Some of the benefit of statins for the prevention of cardiovascular disease may be due to their antithrombotic properties. Little is known about the effect of these drugs on the development of deep vein thrombosis. MATERIALS AND METHODS: We conducted a retrospective cohort study over an 8-year period by linking Ontario provincial health care administrative databases covering more than 1.4 million Ontario residents aged 65 years or older. We excluded those with a documented history of atherosclerosis, venous thromboembolism, or cancer within 36 months prior to study enrollment, as well as those prescribed warfarin sodium within 12 months before enrollment. In the primary cohort, we evaluated the subsequent risk of deep vein thrombosis (DVT) among men and women prescribed thyroid replacement therapy, nonstatin lipid-lowering agents, or statins. A second cohort of women only was evaluated in a similar fashion, but estrogen use was added as a third comparison drug group. RESULTS: There were 125 862 men and women in the primary cohort. After adjusting for age; sex; prior hospitalization; newly diagnosed cancer; or prescribed aspirin, warfarin, or estrogen, statin users (n = 77 993) had an associated decreased risk of DVT relative to those prescribed thyroid replacement therapy (n = 35 978) (adjusted hazard ratio [HR], 0.78; 95% confidence interval [CI], 0.69-0.87). Compared with thyroid replacement therapy, users of nonstatin lipid-lowering agents (n = 11 891) did not seem to be at lower risk for deep vein thrombosis (HR, 0.97; 95% CI, 0.79-1.18). In the secondary cohort of 89 508 women, after adjusting for age, prior hospitalization, newly diagnosed cancer, or prescribed aspirin or warfarin, estrogen users (n = 29 165) had an associated increased risk for DVT compared with those receiving thyroid replacement therapy (n = 22 118) (HR, 1.16; 95% CI, 1.01-1.33), while statin users had an associated decreased risk (HR, 0.68; 95% CI, 0.59-0.79). Nonstatin lipid-lowering agents (n = 5155) were not associated with a reduced risk of DVT compared with thyroid replacement therapy (HR, 0.84; 95% CI, 0.63-1.12). CONCLUSION: Among selected individuals aged 65 years or older, statins were associated with a 22% relative risk reduction in the risk of DVT. A randomized clinical trial is needed to evaluate the efficacy of statins for the primary and secondary prevention of DVT.
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Anticolesterolemiantes/uso terapéutico , Lovastatina/uso terapéutico , Trombosis de la Vena/prevención & control , Anciano , Estudios de Cohortes , Estrógenos/uso terapéutico , Femenino , Humanos , Masculino , Análisis Multivariante , Estudios Retrospectivos , Factores de Riesgo , Hormonas Tiroideas/uso terapéuticoRESUMEN
OBJECTIVE: The authors assessed changes over time in antidepressant utilization among elderly subjects regarding the prevalence of antidepressant users, shifts in prescription patterns, and related financial implications. METHOD: The authors conducted a population-based study of more than 1.4 million Ontario residents aged 65 years or older. Cross-sectional data regarding annual antidepressant utilization were obtained from administrative databases for 1993 to 1997. Time series analysis was used to assess trends over time and to make future projections. RESULTS: The proportion of antidepressant users increased from 9.3% of the elderly population in 1993 to 11.5% in 1997. Prescriptions for selective serotonin reuptake inhibitors (SSRIs) accounted for 9.6% of antidepressant prescriptions dispensed in the first 30 days of 1993 and 45.1% of those dispensed by the last 30 days of 1997 and were projected to increase to approximately 56% by the end of 2000. Prescriptions for tricyclic antidepressants fell from 79.0% in the first 30 days of 1993 to 43.1% by the last 30 days of 1997 and were projected to decline to approximately 28% by the end of 2000. Annual antidepressant costs (in Canadian dollars) increased by 150%, from $10.8 million in 1993 to $27.0 million in 1997. Population shifts and an increase in the prevalence of antidepressant users accounted for at least 20% of this increase, whereas the prescribing transition from tricyclic antidepressants to SSRIs accounted for at least 61% of the increase. CONCLUSIONS: The introduction of SSRIs has had a substantial financial impact at the drug utilization level. Future research should address the appropriate balancing of the cost of newer agents versus their ostensible advantages.
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Antidepresivos/uso terapéutico , Anciano , Antidepresivos/administración & dosificación , Antidepresivos/economía , Antidepresivos Tricíclicos/administración & dosificación , Antidepresivos Tricíclicos/economía , Antidepresivos Tricíclicos/uso terapéutico , Canadá/epidemiología , Estudios Transversales , Trastorno Depresivo/tratamiento farmacológico , Trastorno Depresivo/epidemiología , Trastorno Depresivo/psicología , Costos de los Medicamentos/estadística & datos numéricos , Prescripciones de Medicamentos/estadística & datos numéricos , Utilización de Medicamentos/tendencias , Femenino , Predicción , Humanos , Masculino , Inhibidores de la Monoaminooxidasa/administración & dosificación , Inhibidores de la Monoaminooxidasa/economía , Inhibidores de la Monoaminooxidasa/uso terapéutico , Ontario/epidemiología , Inhibidores Selectivos de la Recaptación de Serotonina/administración & dosificación , Inhibidores Selectivos de la Recaptación de Serotonina/economía , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéuticoRESUMEN
STUDY OBJECTIVE: To determine whether a reservoir nasal cannula (RNC) (Oxymizer) provides an arterial hemoglobin oxygen saturation as measured by pulse oximetry (SpO2) equivalent to that provided by the standard nasal cannula (SNC) during sleep in hypoxemic patients with COPD while reducing oxygen flow requirement and cost. DESIGN: The study took place in a sleep laboratory for three nights, with the first night for acclimatization to the new sleeping environment. In a repeated-measures design, on the second and third nights, subjects used the SNC for one night and the RNC on another night. The order in which they received the two devices was counterbalanced. SUBJECTS: The subjects were patients with COPD who had a stable PaO2 of 55 mm Hg or less or had a value of 56 to 59 mm Hg with evidence of cor pulmonale or polycythemia (or both) and an FEV1/FVC of less than 70 percent. INTERVENTIONS: A pulse oximeter was used to measure SpO2. An arterial blood gas measurement was taken on each night while the patients with COPD were receiving oxygen therapy via the assigned device. An EEG machine was used to record measurements of electro-oculography, chin electromyography (EMG), anterior tibialis EMG and EEG. MEASUREMENTS AND MAIN RESULTS: There was a statistically significant difference between mean SpO2 during sleep (RNC, 91 percent; SNC, 93 percent; F = 7.89; p = 0.01). Nocturnal SpO2 was less than 90 percent for 24.2 percent of the time with the RNC and for 17.5 percent of the time with the SNC (F = 5.41; p = 0.03), but there was no significant difference in the amount of time that SpO2 was less than 85 percent. Compared to the SNC, in 4 of 26 patients with COPD, the RNC performed better; in 12 patients with COPD, the RNC performed the same, and in 10 patients with COPD the RNC performed worse during sleep. Sleep parameters were not significantly different between the two devices. CONCLUSIONS: The difference of 2 percent in mean SpO2 is within the range of SpO2 measurement error. Therefore, the two devices are equally effective when the sample is considered as a whole. Nighttime oximetry is necessary prior to prescription, since nighttime efficacy of the RNC cannot be predicted on the basis of daytime pulse oximetry.
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Enfermedades Pulmonares Obstructivas/terapia , Terapia por Inhalación de Oxígeno/instrumentación , Oxígeno/sangre , Sueño , Anciano , Hemoglobinas/análisis , Humanos , Intubación/instrumentación , Enfermedades Pulmonares Obstructivas/sangre , Masculino , Persona de Mediana Edad , Nariz , OximetríaRESUMEN
OBJECTIVE: To assess the prevalence of antidepressant use with respect to age, gender, and time during a 5-year period from 1993 to 1997. DESIGN: A retrospective, population-based study in which data regarding a cross-sectional series of annual antidepressant use were obtained from administrative claims and census databases for more than 1.4 million older persons during calendar years 1993 through 1997. PARTICIPANTS: All residents of Ontario aged 65 or older. MAIN OUTCOME MEASURES: Changes in the prevalence of antidepressant users as a function of age group, gender, and time. RESULTS: A general, positive, linear trend in the prevalence of antidepressant users with increasing age group was consistently detected regardless of gender and year assessed (P < .001 for both genders and all years). The age-adjusted relative risk of women being dispensed an antidepressant relative to men was significantly higher during each year but seemed to decrease slightly over time: 1.74 (95% CI, 1.72-1.76) in 1993 and 1.65 (95% CI, 1.63-1.67) in 1997. The multiple linear regression model revealed significant relationships between the prevalence of antidepressant users and increasing age group, female gender, and increasing year of assessment (P < .001 for each variable). The prevalence was observed to range from a low of 5.6% in 65 to 69-year-old men in 1993 to a high of 17.2% among 85 to 89-year-old women in 1997. CONCLUSIONS: Our findings reveal that the prevalence of antidepressant users is dynamic and is significantly and independently associated with age, gender, and time of assessment.