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This database study examines the association between glucagon-like peptide 1 agonists (eg, semaglutide, liraglutide) used for weight loss and reports of gastrointestinal adverse events.
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Fármacos Antiobesidad , Enfermedades Gastrointestinales , Receptor del Péptido 1 Similar al Glucagón , Sobrepeso , Pérdida de Peso , Humanos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Receptor del Péptido 1 Similar al Glucagón/agonistas , Péptidos Similares al Glucagón , Hipoglucemiantes/efectos adversos , Hipoglucemiantes/uso terapéutico , Liraglutida/efectos adversos , Liraglutida/uso terapéutico , Pérdida de Peso/efectos de los fármacos , Fármacos Antiobesidad/efectos adversos , Fármacos Antiobesidad/farmacología , Fármacos Antiobesidad/uso terapéutico , Sobrepeso/tratamiento farmacológico , Enfermedades Gastrointestinales/inducido químicamenteRESUMEN
This study examines the association of sublingual buprenorphine/naloxone and dental adverse events using the IQVIA health claims database.
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Analgésicos Opioides , Combinación Buprenorfina y Naloxona , Antagonistas de Narcóticos , Trastornos Relacionados con Opioides , Enfermedades Estomatognáticas , Humanos , Administración Sublingual , Analgésicos Opioides/administración & dosificación , Analgésicos Opioides/efectos adversos , Analgésicos Opioides/uso terapéutico , Combinación Buprenorfina y Naloxona/administración & dosificación , Combinación Buprenorfina y Naloxona/efectos adversos , Combinación Buprenorfina y Naloxona/uso terapéutico , Antagonistas de Narcóticos/administración & dosificación , Antagonistas de Narcóticos/efectos adversos , Antagonistas de Narcóticos/uso terapéutico , Trastornos Relacionados con Opioides/tratamiento farmacológico , Enfermedades Estomatognáticas/inducido químicamenteRESUMEN
AIMS: Recent epidemiologic studies have examined the risk of maculopathy with pentosan polysulfate sodium (PPS), a drug indicated for the treatment of interstitial cystitis. However, results have been contradictory. Thus, we quantified the risk of maculopathy with PPS with a focus on risk with duration of use. METHODS: We used a new user, retrospective cohort study with an active comparator. We created a cohort of mutually exclusive 6221 PPS users and 89 744 amitriptyline users, a tricyclic antidepressant also used for the treatment of pain secondary to interstitial cystitis. Subjects were selected from the PharMetrics Plus database (IQVIA, Durham, NC) from 2006 to 2020. Cohort members were followed to the first event of the study outcome (maculopathy) or end of enrolment. A Cox regression model was constructed to adjust for potential confounders. RESULTS: The mean follow-up was 3.0 years for PPS users and amitriptyline users. The adjusted hazard ratio (HR) for maculopathy in PPS users was 2.64 (95% confidence interval [CI]: 1.90-3.68). The HR for the sensitivity analysis that combined maculopathy and age-related macular degeneration (AMD) was 1.38 (95% CI: 1.16-1.65). A cumulative duration-response pattern was observed, with use greater than 3 years having a 9.5-fold risk of maculopathy (HR = 9.56, 95% CI: 3.60-25.37) compared to a 2.3-fold risk of maculopathy with use for 1 year or less (HR = 2.27, 95% CI: 1.50-3.43). The number needed to harm for the first 4 years of use was 250. CONCLUSIONS: The results of this study suggest an increased risk of maculopathy with PPS use, particularly with longer duration of use.
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Cistitis Intersticial , Degeneración Macular , Amitriptilina/efectos adversos , Cistitis Intersticial/inducido químicamente , Cistitis Intersticial/tratamiento farmacológico , Cistitis Intersticial/epidemiología , Humanos , Degeneración Macular/inducido químicamente , Degeneración Macular/tratamiento farmacológico , Degeneración Macular/epidemiología , Poliéster Pentosan Sulfúrico/efectos adversos , Estudios RetrospectivosRESUMEN
PURPOSE: Sympathetic ophthalmia (SO) is a rare, bilateral panuveitis that occurs following open globe injury (OGI), with a variable incidence reported in the literature. Our objective was to determine the incidence proportion and incidence rate of SO following OGI to help guide shared physician-patient decision making. DESIGN: Systematic review and meta-analysis. METHODS: A systematic literature search was performed using the MEDLINE, EMBASE, and Cochrane databases from inception to November 2020 for population-based studies on OGI and SO in adults and children. Two reviewers independently screened search results. Random-effects meta-analyses were performed to calculate the incidence proportion and incidence rate. The Risk Of Bias In Non-Randomized Studies - of Interventions (ROBINS-I) tool was used to assess the risk of bias. The study was registered on PROSPERO CRD42020198920. RESULTS: A total of 24 studies were utilized in the meta-analyses. After OGI, the estimated overall incidence proportion of SO was 0.19% (95% CI 0.14%-0.24%) and the incidence rate of SO was 33 per 100,000 person-years, (95% CI 19.61-56.64) with I2 of 13% and 72%, respectively. CONCLUSIONS: SO after OGI is rare. The estimated incidence proportion and incidence rate are useful when counselling patients regarding management options after OGI. Further studies are needed to examine the influence of age, the extent and location of trauma, timing of repair, and prophylactic eye removal on the incidence of SO.
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Lesiones Oculares , Oftalmía Simpática , Adulto , Niño , Enucleación del Ojo , Lesiones Oculares/complicaciones , Lesiones Oculares/epidemiología , Humanos , Incidencia , Oftalmía Simpática/diagnóstico , Oftalmía Simpática/epidemiología , Oftalmía Simpática/etiologíaRESUMEN
BACKGROUND: Hormonal contraceptives (HCs) are a known risk factor for dry eye disease (DED), yet the relationship between HCs use and DED in women of child-bearing age remains debatable. The aim of this study was to determine the association between HCs and DED in females of reproductive age. METHODS: This was a retrospective cohort study using data from IQVIA's electronic medical record (IQVIA, USA). 4,871,504 women (age 15-45) between 2008 and 2018 were followed to the first diagnosis of DED as defined by an ICD-9/10 code. DED cases also required at least two prescriptions of cyclosporine or lifitegrast topical drops within 60 days of the first code. The date of the first code was designated as the index date. Regular HCs users needed to have at least two prescriptions in both the first year and second year prior to the index date. For each case, five controls were selected and matched to cases by age and follow-up time. A conditional logistic regression model was used to adjust for confounders of DED and to calculate odds ratios (ORs). RESULTS: HCs users were at a higher risk for DED than non-users. Regular users of HCs were more likely to develop DED (ORs = 2.73, 95% CI [2.21-3.73]) than irregular users. Those who used a greater number of HCs were at a higher risk for DED. CONCLUSIONS: This study indicates an increased risk of DED with HCs use in women of child-bearing age.
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Anticonceptivos , Síndromes de Ojo Seco , Adolescente , Adulto , Síndromes de Ojo Seco/inducido químicamente , Síndromes de Ojo Seco/diagnóstico , Síndromes de Ojo Seco/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Estudios Retrospectivos , Factores de Riesgo , Adulto JovenRESUMEN
INTRODUCTION: Acetylcholinesterase inhibitors (AChEIs) are commonly used to treat mild to moderate cases of Alzheimer disease (AD). To the best of our knowledge, there has been no study estimating the risk of bleeding and cardiovascular events in patients with non-hypertensive AD. Therefore, this study aimed to estimate the association between AChEIs and the risk of bleeding and cardiovascular ischemic events in patients with non-hypertensive AD. METHODS: A nested case-control study was conducted to estimate the risk of bleeding and ischemic events (angina, myocardial infarction [MI], and stroke) in patients with AD. This study was conducted using the UK Clinical Practice Research Datalink and Hospital Episode Statistics (HES) databases. The study cohort consisted of AD patients ≥65 years of age. The case groups included all AD subjects in the database who had a bleeding or ischemic event during the cohort follow-up. Four controls were selected for each case. Patients were classified as current users or past users based on a 60-day threshold of consuming the drug. Simple and multivariable conditional logistic regression analyses were used to calculate the adjusted odds ratio for bleeding events and cardiovascular events. RESULTS: We identified 507 cases and selected 2028 controls for the bleeding event cohort and 555 cases and 2220 controls for the ischemic event cohort. The adjusted odds ratio (OR) (95% confidence interval [CI]) for the association of AChEI use was 0.93 (0.75 to 1.16) for bleeding events, 2.58 (1.01 to 6.59) for angina, and 1.89 (1.07 to 3.33) for MI. Past users of AChEIs were also at increased risk of stroke (1.51 [1.00 to 2.27]). DISCUSSION: This is the first study assessing the risk of bleeding and cardiovascular events in patients with non-hypertensive AD. Our findings could be of great interest for clinicians and researchers working on AD.
RESUMEN
AIMS: We aimed to investigate the association between hormonal contraceptive (HC) use and the incidence of glaucoma in females of reproductive age with a focus on duration and type of HCs used. METHODS: A retrospective cohort study with a case-control analysis (nested case-control) was undertaken using data from IQVIA's electronic medical record (IQVIA, USA) from 2008 to 2018. Within a cohort of 4 871 504 women, cases of glaucoma or ocular hypertension were identified. Subjects were followed to the first diagnosis of glaucoma. Each glaucoma case was matched to four controls by age, body mass index and follow up time. The main outcome measure was the first diagnosis of glaucoma defined by the first ICD-9/10 code for glaucoma or ocular hypertension. RESULTS: Among 4 871 504 women identified, there were 2366 cases of glaucoma and 9464 controls. Regular users of hormonal contraceptives had an elevated risk of glaucoma compared to non-users with an adjusted incident rate ratio (aIRR) of 1.57 (95% CI: 1.29-1.92). Current users were of greatest risk (aIRR of 2.38, 95% CI: 1.81-3.13), whereas the aIRR among past users was 1.08 (95% CI: 0.82-1.43). The aIRR for glaucoma increased from 0.82 (95% CI: 0.70-0.95) among those with one or two prescriptions in the 2 years prior to the first diagnosis of glaucoma to 1.54 (95% CI: 1.32-1.81) among those with greater than four prescriptions. CONCLUSIONS: This nested case-control study demonstrated an elevated risk, albeit low, of glaucoma in females of reproductive age who use regular hormonal contraception. Future studies are needed to confirm these findings.
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Anticonceptivos Hormonales Orales , Glaucoma , Estudios de Casos y Controles , Estudios de Cohortes , Anticonceptivos Hormonales Orales/efectos adversos , Femenino , Glaucoma/inducido químicamente , Glaucoma/diagnóstico , Glaucoma/epidemiología , Humanos , Estudios RetrospectivosRESUMEN
BACKGROUND: Melanoma can be lethal if not detected early and treated. Early detection can be facilitated via skin self-examination (SSE) and as such, SSE is part of melanoma follow-up care for individuals with a prior history, who face a life-long risk of reoccurrence. The objective of the current study was to identify short- and long-term predictors of SSE among melanoma survivors to inform future prevention interventions in high-risk groups. METHOD: This is an observational study with longitudinal assessments conducted with adult melanoma patients in active follow-up care. PRIMARY OUTCOME MEASURES: Behavioral outcomes, comprehensive SSE (checking up to 5 body areas in the last 3 months) and optimal SSE (checking the entire body at least monthly in the last 3 months) were assessed at 3, 12, and 24 months post a dermatological educational session on skin cancer prevention. T tests and chi square analyses were used to examine changes in outcomes from 3 to 12 and 24 months. Linear and logistic regression models were used to examine the association between predictors and the primary outcomes. RESULTS: Comprehensive SSE did not decrease significantly from 3 (M = 2.7, SD = 1.1) to 12 (M = 2.6, SD = 1.2) and 24 months (M = 2.4, SD = 1.2) post the education session, with the stronger predictor at all timepoints being intentions to perform SSE. Optimal SSE was higher at 3 months (59%) compared to 12 (46%) and 24 months (34%), with key predictors including self-efficacy and intentions to perform SSE and male sex at 3 months post; self-efficacy and reliance on medical advice at 12 months; and (lower) education and self-efficacy at 24 months. CONCLUSIONS: The key findings of this study are that 1) survivors maintain SSE behaviour over time, but rates of SSE performed in agreement with medical recommendations are higher immediately post standard dermatological education (i.e. usual care) and decrease somewhat over a 24-month period; and 2) the strongest psycho-social predictors of SSE are intentions and self-efficacy to perform the behavior, which are highly modifiable, for example via motivational interviewing and goal setting health interventions.
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Melanoma/epidemiología , Autoexamen , Neoplasias Cutáneas/epidemiología , Anciano , Detección Precoz del Cáncer , Femenino , Humanos , Estudios Longitudinales , Masculino , Melanoma/diagnóstico , Persona de Mediana Edad , Estadificación de Neoplasias , Quebec/epidemiología , Autoeficacia , Índice de Severidad de la Enfermedad , Neoplasias Cutáneas/diagnósticoRESUMEN
BACKGROUND: Recent studies have linked fluoroquinolones (FQs) to cardiac adverse events, including aortic dissection and aneurysm. To date, whether FQs can increase the risk of aortic or mitral regurgitation has not been studied. OBJECTIVES: This disproportionality analysis and case-control study examined whether FQs increase the risk of aortic and mitral regurgitation. METHODS: Data from the U.S. Food and Drug Administration's adverse reporting system database was used to undertake a disproportionality analysis, and a random sample of 9,053,240 patients from the U.S. PharMetrics Plus database (IQVIA) was used for the matched nested case-control study. Current FQ exposure implied an active prescription at the index date or 30 days prior to the event date. Recent FQ exposure was defined as FQ use within days 31 to 60 and past within days 61 to 365 prior to the event date. Rate ratios (RRs) were compared to users of amoxicillin and azithromycin. Conditional logistic regression was used to compute RRs adjusting for confounders. RESULTS: The reported odds ratio for the disproportionality analysis was 1.45 (95% confidence interval [CI]: 1.20 to 1.77). A total of 12,505 cases and 125,020 control subjects were identified in the case-control study. The adjusted RRs for current users of FQ compared with amoxicillin and azithromycin users were 2.40 (95% CI: 1.82 to 3.16) and 1.75 (95% CI: 1.34 to 2.29), respectively. The adjusted RRs for recent and past FQ users when compared with amoxicillin were 1.47 (95% CI: 1.03 to 2.09) and 1.06 (95% CI: 0.91 to 1.21), respectively. CONCLUSIONS: These results show that the risk of aortic and mitral regurgitation is highest with current use followed by recent use. No risk was observed with past use of FQs. Future studies are necessary to confirm or refute these associations.
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Insuficiencia de la Válvula Aórtica/inducido químicamente , Fluoroquinolonas/efectos adversos , Insuficiencia de la Válvula Mitral/inducido químicamente , Administración Oral , Anciano , Estudios de Casos y Controles , Estudios Transversales , Femenino , Fluoroquinolonas/administración & dosificación , Humanos , Masculino , Persona de Mediana Edad , Medición de RiesgoRESUMEN
IMPORTANCE: Tumor necrosis factor inhibitors (TNFi) are widely used in the treatment of a variety of autoimmune diseases. A number of case reports have linked TNFi to neurologic adverse events including peripheral neuropathy (PN) in patients with rheumatic diseases. OBJECTIVES: To quantify the risk of peripheral neuropathy with TNFi in patients with rheumatic diseases. DESIGN: Nested-Case Control study within a cohort of patients with rheumatic diseases. SETTING: PharMetrics Plus™ health claims database from the United States. PARTICIPANTS: From a random sample of 9,053,240 subjects from the PharMetrics Plus™ database a cohort of patients with rheumatic diseases who had two physician visit codes for rheumatoid arthritis, ankylosing spondylitis and psoriasis in addition to a medication used in the treatment of each condition from 2006 to 2016 was created. EXPOSURE: We created different risk periods of current use (day 0-60), recent use (day 61-180) and past use (day 180-365) from the index date. MAIN OUTCOME MEASURES: New cases of PN were identified from the rheumatic disease cohort. Each case was matched to 10 controls by calendar time and age using density based sampling. Rate ratios (RRs) for new users of TNFi were computed using conditional logistic regression adjusting for gender, vitamin B12 deficiency, fluoroquinolone use, HIV, viral hepatitis, chronic renal failure and diabetes. RESULTS: Among a cohort of 61,570 patients with rheumatic diseases 1358 cases of PN and 13,580 corresponding controls were identified. The adjusted rate ratio (RR) of PN among recent users of TNFi was 1.14 (95% CI:0.90-1.43). The RR for past use of TNFi was 2.77 (95% CI:1.67-4.58). Past users who used three or more prescriptions had a higher risk of PN 3.49 (1.63-7.49). The RRs did not change when the risk of PN with TNFi was compared to those taking methotrexate and one additional disease modifying anti rheumatic drug (DMARD) for recent and past use (RRâ¯=â¯0.95 [95% CI:0.72-1.24] and RRâ¯=â¯2.30 (1.37-3.87), respectively). CONCLUSIONS: Patients with rheumatic diseases who are past users of TNFi are at higher risk of developing PN compared to those taking methotrexate and one additional DMARD.
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Antirreumáticos/efectos adversos , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Enfermedades Reumáticas/tratamiento farmacológico , Inhibidores del Factor de Necrosis Tumoral/efectos adversos , Adulto , Anciano , Antirreumáticos/uso terapéutico , Estudios de Casos y Controles , Bases de Datos Factuales , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Enfermedades del Sistema Nervioso Periférico/epidemiología , Riesgo , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico , Estados UnidosRESUMEN
BACKGROUND: Antidepressants are one of the most prescribed classes of medications. A number of case reports have linked these drugs to extrapyramidal symptoms (EPSs), but no large epidemiologic study to date has examined this association. We sought to quantify the association of EPSs with different antidepressants by undertaking a large pharmacoepidemiologic study. METHODS: A nested case-control study was conducted using a large health claims database in the United States from June 2006 to December 2015. Subjects with a diagnosis of primary Parkinson disease and those who received prescriptions of levodopa, ropinirole, pramipexole, domperidone, metoclopramide, entacapone, benztropine, selegiline, rasagiline, diphenhydramine, trihexyphenidyl, typical and atypical antipsychotics, and tricyclic antidepressants were excluded. Cases were followed to the first billing code for an extrapyramidal event or last date of enrollment in the cohort. For each case, 10 control subjects were matched by follow-up time, calendar time, and age through density-based sampling. Rate ratios were computed using conditional logistic regression adjusting for other covariates. RESULTS: We identified 3,838 subjects with EPSs compared with 38,380 age-matched control subjects. Rate ratios with respect to EPSs were as follows: duloxetine, 5.68 (95% confidence interval [CI], 4.29-7.53); mirtazapine, 3.78 (95% CI, 1.71-8.32); citalopram, 3.47 (95% CI, 2.68-4.50); escitalopram, 3.23 (95% CI, 2.44-4.26); paroxetine, 3.07 (95% CI, 2.15-4.40); sertraline, 2.57 (95% CI, 2.02-3.28); venlafaxine, 2.37 (95% CI, 1.71-3.29); bupropion, 2.31 (95% CI, 1.67-3.21); and fluoxetine, 2.03 (95% CI, 1.48-2.78). CONCLUSIONS: This observational study demonstrates a harmful association between the incidence of Parkinson disease or associated EPSs and use of the antidepressants duloxetine, mirtazapine, citalopram, escitalopram, paroxetine, sertraline, venlafaxine, bupropion, and fluoxetine.
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Antidepresivos/efectos adversos , Enfermedades de los Ganglios Basales/inducido químicamente , Enfermedades de los Ganglios Basales/epidemiología , Bupropión/efectos adversos , Estudios de Casos y Controles , Citalopram/efectos adversos , Clorhidrato de Duloxetina/efectos adversos , Femenino , Fluoxetina/efectos adversos , Humanos , Masculino , Mianserina/efectos adversos , Mianserina/análogos & derivados , Persona de Mediana Edad , Mirtazapina , Paroxetina/efectos adversos , Farmacoepidemiología , Sertralina/efectos adversos , Estados Unidos/epidemiología , Clorhidrato de Venlafaxina/efectos adversosRESUMEN
PURPOSE: To examine the risk of persistent sexual dysfunction (PSD) with finasteride 1 mg. METHODS: We conducted a retrospective cohort study using the IMS U.S. health claims database. From an original cohort of 6,110,723 patients, we identified 1390 men who had stopped using finasteride 1 mg and 20,000 randomly selected age- and calendar time-matched users of omeprazole from 2006 to 2014. First PSD event was defined as (1) the first PSD diagnosis through the first International Classification for Diseases, Ninth Revision, Clinical Modification) code for sexual dysfunction and (2) use of a phosphodiesterase inhibitor (sildenafil, tadalafil, or vardenafil). RESULTS: In the primary analysis, we identified 1390 men taking finasteride 1 mg and 20,000 omeprazole users. The mean time to first PSD event after discontinuation of a finasteride 1 mg prescription was 391 days (SD, 357 days). The rate of PSD for finasteride 1 mg users and omeprazole users was 37.9 and 15.0 per 1000 person-years, respectively. For the primary analysis of sexual dysfunction, the adjusted hazard ratio (HR) comparing finasteride 1 mg users to omeprazole users was 1.62 (1.14-2.29). Adjusted HR in the secondary analysis comparing finasteride users to omeprazole users with respect to the first phosphodiesterase inhibitor was 2.73 (2.01-3.69). CONCLUSIONS: The risk of PSD in men who stopped finasteride 1 mg therapy was higher than that for omeprazole users. Patients who stopped finasteride therapy sought physician visits for sexual dysfunction up to 1 year after stopping finasteride.
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Inhibidores de 5-alfa-Reductasa/efectos adversos , Alopecia/tratamiento farmacológico , Finasterida/efectos adversos , Disfunciones Sexuales Fisiológicas/inducido químicamente , Inhibidores de 5-alfa-Reductasa/administración & dosificación , Adulto , Estudios de Cohortes , Finasterida/administración & dosificación , Humanos , Persona de Mediana Edad , Omeprazol/administración & dosificación , Omeprazol/efectos adversos , Estudios Retrospectivos , Disfunciones Sexuales Fisiológicas/epidemiología , Factores de TiempoRESUMEN
BACKGROUND: Hospitals treating patients with ST-elevation myocardial infarction (STEMI) may show good results with reperfusion treatment (fibrinolysis or primary percutaneous coronary intervention [PPCI]), but a comprehensive evaluation should factor in outcomes of patients with STEMI who do not receive reperfusion. We compared outcomes of patients receiving and not receiving reperfusion within a complete system of STEMI care by hospital type: PPCI centres, fibrinolysis centres, centres that only transfer for PPCI, and centres providing a mix of fibrinolysis and PPCI transfer. METHODS: All patients presenting to 82 Quebec hospitals with characteristic symptoms, a final diagnosis of acute myocardial infarction, and core-laboratory confirmed STEMI over two 6-month periods were studied. RESULTS: Of the total 3731 patients with STEMI, 2918 (78.2%) received reperfusion treatment (81% PPCI, 19% fibrinolysis); 813 (21.8%) did not. For reperfusion-treated patients, 30-day mortality was 5.4% in PPCI centres, 5.4% in fibrinolysis centres, 6.9% in transfer PPCI centres, and 6.0% in mixed centres (P = 0.55). For untreated patients, 30-day mortality was 15.7% (PPCI centres), 16.1% (fibrinolysis centres), 21.8% (transfer PPCI), and 24.6% (mixed) (P = 0.08). Adjusted mortality odds ratios for all patients were 1.00 (PPCI centres), 1.50 (95% CI: 0.97-2.32; fibrinolysis centres), 1.30 (0.95-1.78; transfer PPCI centres), and 1.58 (1.09-2.29; mixed centres). PPCI was within recommended delays in 35.4%, 11.9%, and 1.2% of PPCI, transfer, and mixed centres, respectively. CONCLUSIONS: Mixed centres had the highest crude and adjusted all-patient 30-day STEMI mortality. Relatively good outcomes of reperfusion-treated patients, despite long treatment delays, can misrepresent overall performance if untreated patients are not examined.
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Fibrinolíticos/uso terapéutico , Intervención Coronaria Percutánea , Infarto del Miocardio con Elevación del ST/mortalidad , Infarto del Miocardio con Elevación del ST/terapia , Femenino , Hospitales/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Transferencia de Pacientes/estadística & datos numéricos , Intervención Coronaria Percutánea/estadística & datos numéricos , Quebec/epidemiologíaRESUMEN
The majority of diffuse large B-cell lymphoma (DLBCL) tumors contain mutations in histone-modifying enzymes (HMEs), indicating a potential therapeutic benefit of histone deacetylase inhibitors (HDIs), and preclinical data suggest that HDIs augment the effect of rituximab. In this randomized phase 2 study, we evaluated the response rate and toxicity of panobinostat, a pan-HDI administered 30 mg orally 3 times weekly, with or without rituximab, in 40 patients with relapsed or refractory de novo (n = 27) or transformed (n = 13) DLBCL. Candidate genes and whole exomes were sequenced in relapse tumor biopsies to search for molecular correlates, and these data were used to quantify circulating tumor DNA (ctDNA) in serial plasma samples. Eleven of 40 patients (28%) responded to panobinostat (95% confidence interval [CI] 14.6-43.9) and rituximab did not increase responses. The median duration of response was 14.5 months (95% CI 9.4 to "not reached"). At time of data censoring, 6 of 11 patients had not progressed. Of the genes tested for mutations, only those in MEF2B were significantly associated with response. We detected ctDNA in at least 1 plasma sample from 96% of tested patients. A significant increase in ctDNA at day 15 relative to baseline was strongly associated with lack of response (sensitivity 71.4%, specificity 100%). We conclude that panobinostat induces very durable responses in some patients with relapsed DLBCL, and early responses can be predicted by mutations in MEF2B or a significant change in ctDNA level at 15 days after treatment initiation. This clinical trial was registered at www.ClinicalTrials.gov (#NCT01238692).
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Ácidos Hidroxámicos/administración & dosificación , Indoles/administración & dosificación , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Rituximab/administración & dosificación , Adulto , Anciano , ADN de Neoplasias/sangre , ADN de Neoplasias/genética , Femenino , Humanos , Linfoma de Células B Grandes Difuso/sangre , Linfoma de Células B Grandes Difuso/genética , Factores de Transcripción MEF2/sangre , Factores de Transcripción MEF2/genética , Masculino , Persona de Mediana Edad , Mutación , Proteínas de Neoplasias/sangre , Proteínas de Neoplasias/genética , Panobinostat , RecurrenciaRESUMEN
Patients with chronic obstructive pulmonary disease (COPD) have higher incidence and prevalence of other chronic inflammatory diseases, including inflammatory bowel disease (IBD). We assessed whether IBD onset increases mortality risk in patients with COPD or asthma-associated COPD.Two population-based cohorts of COPD and asthma-COPD subjects were identified using the administrative health databases in Québec, Canada, 1990-2007. Death records were retrieved from the death certificate registry. Cox proportional hazards models were used to assess the impact of newly developed IBD on mortality risk.The COPD and asthma-COPD cohorts included 273â208 and 26â575 patients, respectively, of which 697 and 119 developed IBD. IBD increased the risk of all-cause mortality in both COPD (hazard ratio 1.23, 95% CI 1.09-1.4) and asthma-COPD (hazard ratio 1.65, 95% CI 1.23-2.22). In asthma-COPD patients, IBD increased the risk of mortality from respiratory conditions (hazard ratio 2.18, 95% CI 1.31-3.64); in COPD patients, IBD increased the risk of death from digestive conditions (hazard ratio 4.45, 95% CI 2.39-8.30).IBD is a risk factor for mortality in patients with pre-existing COPD or asthma-COPD. IBD increased mortality by respiratory and digestive conditions in patients with asthma-COPD and COPD, respectively.
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Asma/complicaciones , Enfermedades Inflamatorias del Intestino/complicaciones , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Enfermedad Pulmonar Obstructiva Crónica/mortalidad , Anciano , Asma/mortalidad , Estudios de Cohortes , Comorbilidad , Bases de Datos Factuales , Femenino , Humanos , Incidencia , Inflamación/complicaciones , Inflamación/mortalidad , Enfermedades Inflamatorias del Intestino/mortalidad , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Quebec , Sistema de Registros , Factores de RiesgoRESUMEN
AIM: To characterize the most common causes and risk factors of maternal mortality in the USA and observe trends over the past 9 years. METHODS: We carried out a population-based retrospective cohort study using data from the Health Care Cost and Utilization Project, Nationwide Inpatient Sample. Women who were pregnant between 2003 and 2011 were identified. Baseline characteristics of pregnant women who died and those who lived were measured. ICD-9 codes for each cause of death were examined by up to three independent reviewers. Causes of death were categorized into the nine most common subgroups and trends were examined by tertiles of the period 2003-2011. RESULTS: During this 9-year period, there were approximately 7 million births and 1102 maternal deaths, for an overall incidence of 14.2 per 100 000 births. Primary causes of maternal death included sepsis (20.6%), cardiac disease (17.8%), hemorrhage (16.2%), venous thromboembolism (15.2%), and hypertensive disorders (9.4%). During the study period, there was a significant decrease in the frequency of sepsis from 33.2% to 10.0% and a non-significant decrease in venous thromboembolism from 19.1% to 12.9%. There were increases noted in all other groups, notably in terms of hemorrhage from 8.2% to 22.0% and hypertensive disorders from 2.1% to 16.4%. CONCLUSION: Maternal mortality remains a rare event. Although sepsis was the overall predominant cause of mortality during the study period, frequency declined over time and it was surpassed by hemorrhage and hypertensive disorders as the leading causes of maternal mortality.
Asunto(s)
Mortalidad Materna , Complicaciones del Embarazo/mortalidad , Adulto , Femenino , Humanos , Hipertensión Inducida en el Embarazo/mortalidad , Incidencia , Embarazo , Estudios Retrospectivos , Factores de Riesgo , Sepsis/mortalidad , Estados Unidos , Adulto JovenRESUMEN
Patients with ST-elevation myocardial infarction (STEMI) who die in hospital before inpatient admission are generally not included in clinical studies and registries, and the clinical profiles of patients who die earlier versus later are not well defined. We aimed to characterize all patients with STEMI who arrived at emergency departments in the province of Quebec (Canada) based on inpatient admission status and when they died. All patients who presented with symptoms and core laboratory-confirmed STEMI or left bundle branch block during 6 months in 82 hospitals in Quebec were included. Death certificates were used to identify nonadmitted deaths. Of the 2017 patients with STEMI, 340 (16.9%) died within 1 year. Of the latter, 63 (18.5%) were nonadmitted deaths (group A), 179 (52.6%) were deaths after admission but within 30 days (group B), and 98 (28.8%) were deaths after 30 days to 1 year (group C). Group A was younger and most often hemodynamically unstable, followed for both features by B then C. Earliest presentation from symptom onset and most frequent ambulance use were found in group A, followed by B, then C. Presenting electrocardiogram (ECG) features were most severe in A, then B, then C (more arrhythmias, more anterior STEMI, more leads with ST elevation, and higher ST elevation). Patients who died earliest had the least frequency of previous myocardial infarction, coronary revascularization, vascular disease, and heart failure, and the least noncardiac co-morbidity. In conclusion, patients with STEMI dying in hospital before inpatient admission contributed substantially to overall STEMI mortality. Although dying patients who presented earlier had severer presenting clinical profiles, they were paradoxically younger and had less co-morbidity. Previous co-morbidities may favor adaptive protective mechanisms on initial presentation with STEMI.
Asunto(s)
Electrocardiografía , Servicios Médicos de Urgencia/estadística & datos numéricos , Infarto del Miocardio/mortalidad , Admisión del Paciente/estadística & datos numéricos , Sistema de Registros , Anciano , Causas de Muerte/tendencias , Femenino , Estudios de Seguimiento , Mortalidad Hospitalaria/tendencias , Humanos , Masculino , Infarto del Miocardio/diagnóstico , Quebec/epidemiología , Estudios Retrospectivos , Factores de TiempoRESUMEN
BACKGROUND: Immunomodulatory medications in patients with inflammatory bowel disease (IBD) have been associated with an increased risk of developing certain malignancies. The aim of this study was to evaluate the risk of melanoma, nonmelanoma skin cancer, colorectal cancer and lymphoma associated with immunomodulators and biologics in patients with IBD. METHODS: A nested case-control study was carried out using the provincial health insurance database of Québec, Canada (RAMQ/MedECHO). RESULTS: A total of 41,176 patients with IBD were identified of whom 19,582 patients were eligible for inclusion in the study. Treatment with thiopurine for more than 5 years was associated with a significantly increased risk of nonmelanoma skin cancer (odds ratio: 1.78; 95% confidence interval, 1.25-2.54). Immunomodulator treatment was not associated with an increased risk of non-Hodgkin's lymphoma (odds ratio: 0.87; 95% confidence interval, 0.53-1.41). Neither immunomodulators nor anti-TNF-α agents were associated with an increased risk of melanoma or colorectal cancer. CONCLUSIONS: In a large provincial IBD cohort, treatment with immunomodulators for more than 5 years was associated with an increased risk of non-melanoma skin cancer, whereas the risk of lymphoma, melanoma, and colorectal cancer was not increased. No association was found between the risk of the evaluated malignancies and anti-TNF-α medications.
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Productos Biológicos/efectos adversos , Neoplasias Colorrectales/inducido químicamente , Bases de Datos Factuales , Inmunosupresores/efectos adversos , Enfermedades Inflamatorias del Intestino/complicaciones , Linfoma/inducido químicamente , Neoplasias Cutáneas/inducido químicamente , Adulto , Estudios de Casos y Controles , Neoplasias Colorrectales/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Seguro de Salud , Linfoma/epidemiología , Masculino , Pronóstico , Quebec/epidemiología , Factores de Riesgo , Neoplasias Cutáneas/epidemiologíaRESUMEN
AIM: Maternal sepsis is one of the leading causes of maternal mortality around the world. The aim of this study was to estimate the incidence and mortality rate of sepsis, and the associated risk factors for their development during pregnancy, labor, delivery and the post-partum period. METHODS: We conducted a population-based cohort study consisting of 5 million births that occurred in the USA. Data were obtained from the Healthcare Cost and Utilization Project-Nationwide Inpatient Sample (HCUP-NIS) database from 1998 to 2008. Logistic regression was used to calculate the adjusted odds ratio and corresponding 95% confidence intervals (95%CI) for sepsis development and sepsis-related death during admission for delivery. RESULTS: The overall incidence of maternal sepsis was 29.4 per 100 000 births (95%CI: 28.0-30.9) with a sepsis case fatality rate of 4.4 per 100 births (95%CI: 3.5-5.6). Both the incidence of maternal sepsis and sepsis-related death rate have increased over the last decade. Women who are black, older than 35 years and who smoke were more likely to experience maternal sepsis. An association was also found between maternal sepsis and diabetes mellitus, cardiovascular disease, eclampsia, preterm birth, hysterectomy, puerperal infection, post-partum hemorrhage, transfusion and chorioamnionitis. CONCLUSIONS: Mortality from maternal sepsis during labor and delivery is an increasing and important problem in westernized countries. Initiatives aimed at improving early recognition and effective management may help reduce the occurrence and outcomes of maternal sepsis at time of labor and delivery.
Asunto(s)
Sepsis/mortalidad , Adulto , Corioamnionitis , Estudios de Cohortes , Parto Obstétrico , Femenino , Humanos , Incidencia , Trabajo de Parto , Embarazo , Infección Puerperal , Estudios Retrospectivos , Factores de Riesgo , Sepsis/epidemiología , Sepsis/etiologíaRESUMEN
BACKGROUND: Recent attention has been focused on the relationship between carcinoembryonic antigen (CEA) and pathological complete response (pCR), without consensus regarding its predictive value. This study aims to examine the association between CEA and pCR. METHODS: We conducted a retrospective review of a prospectively maintained database of all patients who underwent primary rectal cancer resection after neo-adjuvant chemoradiotherapy (nCRT). Patients were divided into two groups, pCR or no-pCR, based on final pathology. CEA levels were measured at the initial visit with the surgeon/oncologist and post-completion of nCRT. RESULTS: One hundred and forty-one patients underwent primary rectal cancer resections after nCRT. Nineteen patients (13.5 %) achieved pCR, while 122 (86.5 %) had no-pCR. Pre-nCRT CEA levels were not significantly different between groups (2.75 vs 4.5 µg/L, p = 0.65). However, post-nCRT CEA levels were significantly lower in patients with pCR (1.7 vs 2.4 µg/L, p < 0.01). On multivariate logistic regression analyses, low post-nCRT CEA level was an independent predictor of pCR (OR 1.74, CI 1.06, 3.81) and normalization of CEA from an initially elevated level was a highly significant predictor of pCR (OR 64.8, CI 2.53, 18,371). CONCLUSION: Low post-nCRT CEA is an independent predictor of pCR, and normalization of CEA post-nCRT is a strong predictor of pCR.