RESUMEN
PURPOSES: To compare the risk of anastomotic leak (AL) between Ethicon manual circular staplers (two-row) versus Medtronic EEA™ circular stapler with Tri-Staple™ technology (three-row) and between Medtronic EEA™ circular stapler with DST™ Series technology (two-row) versus Tri-Staple™ technology. METHODS: A retrospective cohort study was conducted in adult patients who underwent a left-sided colorectal surgery 2019-2022 in U.S. Premier Healthcare Database to assess the risk of AL within 30 days post-index procedure. The study devices were Ethicon manual circular staplers, Medtronic EEA™ circular stapler with DST™ technology, and Medtronic EEA™ circular stapler with Tri-Staple™ technology. RESULTS: Across 447 hospitals, the cumulative incidences (95% confidence intervals [CI]) of AL within 30 days post-index procedure were 7.78% (6.91-8.74%) among 8337 patients in the Ethicon manual circular stapler cohort, 7.54% (6.87-8.27%) among 7928 patients in the Medtronic EEA™ circular stapler with DST™ technology cohort, and 8.19% (6.57-10.07%) among 1306 patients in the Medtronic EEA™ circular stapler with Tri-Staple™ technology cohort. Comparative analyses revealed no difference comparing Ethicon manual circular staplers with Medtronic EEA™ circular staplers with Tri-Staple™ technology (risk ratio [RR], 0.72; 95% CI, 0.52-1.01) or comparing Medtronic EEA™ circular staplers with DST™ technology to Tri-Staple™ technology (RR, 0.75; 95% CI, 0.53-1.06). CONCLUSION: In this analysis of a large cohort of patients undergoing a left-sided colorectal surgery from a U.S. hospital database, the risk of AL observed with manual two-row circular staplers was similar to that seen with three-row devices. This study affirms the safety of manual two-row circular staplers in colorectal anastomosis.
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Fuga Anastomótica , Neoplasias Colorrectales , Adulto , Humanos , Fuga Anastomótica/etiología , Estudios de Cohortes , Engrapadoras Quirúrgicas/efectos adversos , Estudios Retrospectivos , Anastomosis Quirúrgica/efectos adversos , Neoplasias Colorrectales/cirugía , Grapado Quirúrgico/efectos adversosRESUMEN
In 2020, the European Commission up-classified metal cobalt as Class 1B Carcinogen (presumed to have carcinogenic potential) based primarily on data from rodent inhalation carcinogenicity studies. This up-classification requires an assessment under the Medical Device Regulations of cobalt cancer risk from medical devices. We performed a systematic review and meta-analysis to evaluate site-specific cancer risks with cobalt exposure from either total joint replacement (TJR) or occupational exposure (OC). Results were stratified by exposure type (OC or TJR), exposure level (metal-on-metal (MoM) or non-MoM), follow-up duration (latency period: <5, 5-10 or >10 years), and cancer incidence or mortality (detection bias assessment). From 30 studies (653,104 subjects, average 14.5 years follow-up), the association between TJR/OC and cancer risk was null for 22 of 27 cancer sites, negative for 3 sites, and positive for prostate cancer and myeloma. Significant heterogeneity and large estimate ranges were observed for many cancer sites. No significant increase in estimates was observed by exposure level or follow-up duration. The current evidence, including weak associations, heterogeneity across studies and no increased association with exposure level or follow-up duration, is insufficient to conclude that there exists an increased risk for people exposed to cobalt in TJR/OC of developing site-specific cancers.
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Cobalto/análisis , Prótesis Articulares/estadística & datos numéricos , Neoplasias/epidemiología , Exposición Profesional/análisis , Humanos , Medición de RiesgoRESUMEN
In 2020, the European Commission up-classified pure cobalt metal to a Category 1B hazard, based primarily on data from rodent inhalation carcinogenicity studies of metallic cobalt. The European Commission review did not evaluate cobalt-containing alloys in medical devices, which have very different properties vs. pure cobalt metal and did not include a systematic epidemiologic review. We performed a systematic review and meta-analysis of published, peer-reviewed epidemiologic studies evaluating the association between overall cancer risk and exposure to orthopedic implants containing cobalt alloys or cobalt particulates in occupational settings. Study-specific estimates were pooled using random-effects models. Analyses included 20 papers on orthopedic implants and 10 occupational cohort papers (~1 million individuals). The meta-analysis summary estimates (95% confidence intervals) for overall cancer risk were 1.00 (0.96-1.04) overall and 0.97 (0.94-1.00) among high-quality studies. Results were also similar in analyses stratified by type of exposure/data sources (occupational cohort, implant registry or database), comparators (general or implant population), cancer incidence or mortality, follow-up duration (latency period), and study precision. In conclusion, meta-analysis found no association between exposure to orthopedic implants containing cobalt alloys or cobalt particulates in occupational settings and overall cancer risk, including an analysis of studies directly comparing metal-on-metal vs. non-metal-on-metal implants.
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Aleaciones/química , Cobalto/análisis , Equipos y Suministros , Neoplasias/epidemiología , Exposición Profesional/análisis , Carcinogénesis , Humanos , Prótesis Articulares , Neoplasias/mortalidad , Medición de Riesgo , Titanio/análisisRESUMEN
In 2017, the European Union (EU) Committee for Risk Assessment (RAC) recommended the classification of metallic cobalt (Co) as Category 1B with respect to its carcinogenic and reproductive hazard potential and Category 2 for mutagenicity but did not evaluate the relevance of these classifications for patients exposed to Co-containing alloys (CoCA) used in medical devices. CoCA are inherently different materials from Co metal from a toxicological perspective and thus require a separate assessment. CoCA are biocompatible materials with a unique combination of properties including strength, durability, and a long history of safe use that make them uniquely suited for use in a wide-range of medical devices. Assessments were performed on relevant preclinical and clinical carcinogenicity and reproductive toxicity data for Co and CoCA to meet the requirements under the EU Medical Device Regulation triggered by the ECHA re-classification (adopted in October 2019 under the 14th Adaptation to Technical Progress to CLP) and to address their relevance to patient safety. The objective of this review is to present an integrated overview of these assessments, a benefit-risk assessment and an examination of potential alternative materials. The data support the conclusion that the exposure to CoCA in medical devices via clinically relevant routes does not represent a hazard for carcinogenicity or reproductive toxicity. Additionally, the risk for the adverse effects that are known to occur with elevated Co concentrations (e.g., cardiomyopathy) are very low for CoCA implant devices (infrequent reports often reflecting a unique catastrophic failure event out of millions of patients) and negligible for CoCA non-implant devices (not measurable/no case reports). In conclusion, the favorable benefit-risk profile also in relation to possible alternatives presented herein strongly support continued use of CoCA in medical devices.
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Aleaciones/química , Cobalto/análisis , Equipos y Suministros/normas , Enfermedades Genitales/epidemiología , Neoplasias/epidemiología , Carcinogénesis , Unión Europea , Humanos , Prótesis e Implantes/normas , Medición de Riesgo , Acero/análisisRESUMEN
Cobalt (Co) alloys have been used for over seven decades in a wide range of medical devices, including, but not limited to, hip and knee implants, surgical tools, and vascular stents, due to their favorable biocompatibility, durability, and mechanical properties. A recent regulatory hazard classification review by the European Chemicals Agency (ECHA) resulted in the classification of metallic Co as a Class 1B Carcinogen (presumed to have carcinogenic potential for humans), primarily based on inhalation rodent carcinogenicity studies with pure metallic Co. The ECHA review did not specifically consider the carcinogenicity hazard potential of forms or routes of Co that are relevant for medical devices. The purpose of this review is to present a comprehensive assessment of the available in vivo preclinical data on the carcinogenic hazard potential of exposure to Co-containing alloys (CoCA) in medical devices by relevant routes. In vivo data were reviewed from 33 preclinical studies that examined the impact of Co exposure on local and systemic tumor incidence in rats, mice, guinea pigs, and hamsters. Across these studies, there was no significant increase of local or systemic tumors in studies relevant for medical devices. Taken together, the relevant in vivo data led to the conclusion that CoCA in medical devices are not a carcinogenic hazard in available in vivo models. While specific patient and implant factors cannot be fully replicated using in vivo models, the available in vivo preclinical data support that CoCA in medical devices are unlikely a carcinogenic hazard to patients.
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Aleaciones/análisis , Cobalto/análisis , Equipos y Suministros , Aleaciones/administración & dosificación , Animales , Carcinogénesis , Cobalto/administración & dosificación , HumanosRESUMEN
INTRODUCTION: By providing real-time monitoring of catheter-tissue interface and for complications, intracardiac echocardiography (ICE) during catheter ablation for ventricular tachycardia (VT) may improve outcomes. To test this hypothesis, we compared 12-month readmission rates (all-cause, cardiovascular [CV]-related, and VT-related), repeat ablation, and complications among patients with VT with structural heart disease undergoing ablation with versus without ICE. METHODS AND RESULTS: Using the 2008-2017 IBM MarketScan Commercial and Medicare Supplemental databases, patients with a history of implantable cardioverter defibrillator/cardiac resynchronization therapy (ICD/CRT-D) who underwent VT ablation with and without ICE use were identified. Propensity matching was performed and regression analysis was used to compare outcomes. After matching, 1324 patients were identified (ICE: 662; non-ICE: 662). The rate of 12-month VT-related readmission (18.13% vs 22.51%; P < .05) and repeat VT ablation (14.35% vs 19.34%; P = .02) postindex discharge were lower among patients in the ICE group compared with the non-ICE group, with a 24% lower risk of 12-month VT-related readmission (odds ratio [OR], 0.76; 95% confidence interval [CI], 0.58-0.99) and a 30% lower risk of repeat ablation (OR, 0.70; 95% CI, 0.52-0.93) vs non-ICE group. The 12-month all-cause (44.56% vs 43.20%; P = .62) and CV-related readmissions (35.20% vs 32.93%; P = 0.38) and complication rates were not significantly different between the two groups. CONCLUSIONS: VT ablation using ICE was associated with a lower likelihood of 12-month VT-related readmission and repeat ablation compared with non-ICE patients.
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Ablación por Catéter , Ecocardiografía , Taquicardia Ventricular/cirugía , Potenciales de Acción , Adolescente , Adulto , Anciano , Ablación por Catéter/efectos adversos , Ablación por Catéter/mortalidad , Bases de Datos Factuales , Femenino , Frecuencia Cardíaca , Humanos , Masculino , Persona de Mediana Edad , Readmisión del Paciente , Valor Predictivo de las Pruebas , Medición de Riesgo , Factores de Riesgo , Taquicardia Ventricular/diagnóstico por imagen , Taquicardia Ventricular/mortalidad , Taquicardia Ventricular/fisiopatología , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
PURPOSE: In recent years, novel types of real-world evidence (RWE) have played a role in various decision-making processes relating to medicinal products, including regulatory approval, patient access, health technology assessment, safety monitoring, clinical use, and post-approval lifecycle management. We therefore reviewed the potential utility of RWE in the cycle of medicinal product benefit-risk (BR) assessment, communication/risk minimization and evaluation ("BRACE"). METHODS: A convenience sample of illustrative studies was drawn from the published literature and examined. Specifically, we examined the purpose for using RWE, the type of RWE used, its novelty and how it might be integrated with other data and activities of the BRACE cycle, and how it contributed to regulatory decision-making. RESULTS: Eight studies were selected with each illustrating a different activity in the BRACE cycle ranging from BR assessment in the preapproval setting, post-approval assessment of safety or effectiveness, communicating BR information to patients and healthcare professionals, and evaluating the effectiveness of risk minimization initiatives to support a positive BR balance. CONCLUSIONS: RWE has an important role in informing regulatory decision-making regarding the BR management of medicines. With increasing digitalization, facilitating data collection and stakeholder engagement in health, this role is only expected to expand in the future. To reach the full potential of RWE, both regulators and sponsors will need to be familiar with a range of existing and emerging methods for generating and analyzing such evidence appropriately and achieve convergence regarding how different types of RWE can best be used to inform BR management and decision-making.
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Comunicación , Preparaciones Farmacéuticas , Humanos , Proyectos de Investigación , Medición de RiesgoRESUMEN
PURPOSE: To facilitate surveillance and evaluate interventions addressing opioid-related overdoses, algorithms are needed for use in large health care databases to identify and differentiate community-occurring opioid-related overdoses from inpatient-occurring opioid-related overdose/oversedation. METHODS: Data were from Kaiser Permanente Northwest (KPNW), a large integrated health plan. We iteratively developed and evaluated an algorithm for electronically identifying inpatient overdose/oversedation in KPNW hospitals from 1 January 2008 to 31 December 2014. Chart audits assessed accuracy; data sources included administrative and clinical records. RESULTS: The best-performing algorithm used these rules: (1) Include events with opioids administered in an inpatient setting (including emergency department/urgent care) followed by naloxone administration within 275 hours of continuous inpatient stay; (2) exclude events with electroconvulsive therapy procedure codes; and (3) exclude events in which an opioid was administered prior to hospital discharge and followed by readmission with subsequent naloxone administration. Using this algorithm, we identified 870 suspect inpatient overdose/oversedation events and chart audited a random sample of 235. Of the random sample, 185 (78.7%) were deemed overdoses/oversedation, 37 (15.5%) were not, and 13 (5.5%) were possible cases. The number of hours between time of opioid and naloxone administration did not affect algorithm accuracy. When "possible" overdoses/oversedations were included with confirmed events, overall positive predictive value (PPV) was very good (PPV = 84.0%). Additionally, PPV was reasonable when evaluated specifically for hospital stays with emergency/urgent care admissions (PPV = 77.0%) and excellent for elective surgery admissions (PPV = 97.0%). CONCLUSIONS: Algorithm performance was reasonable for identifying inpatient overdose/oversedation with best performance among elective surgery patients.
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Algoritmos , Analgésicos Opioides/envenenamiento , Sobredosis de Droga/epidemiología , Pacientes Internos , Bases de Datos Factuales/estadística & datos numéricos , Registros Electrónicos de Salud/estadística & datos numéricos , Servicio de Urgencia en Hospital/estadística & datos numéricos , Hospitalización , Humanos , Naloxona/administración & dosificación , Antagonistas de Narcóticos/administración & dosificación , Valor Predictivo de las PruebasRESUMEN
PURPOSE: To enhance automated methods for accurately identifying opioid-related overdoses and classifying types of overdose using electronic health record (EHR) databases. METHODS: We developed a natural language processing (NLP) software application to code clinical text documentation of overdose, including identification of intention for self-harm, substances involved, substance abuse, and error in medication usage. Using datasets balanced with cases of suspected overdose and records of individuals at elevated risk for overdose, we developed and validated the application using Kaiser Permanente Northwest data, then tested portability of the application using Kaiser Permanente Washington data. Datasets were chart-reviewed to provide a gold standard for comparison and evaluation of the automated method. RESULTS: The method performed well in identifying overdose (sensitivity = 0.80, specificity = 0.93), intentional overdose (sensitivity = 0.81, specificity = 0.98), and involvement of opioids (excluding heroin, sensitivity = 0.72, specificity = 0.96) and heroin (sensitivity = 0.84, specificity = 1.0). The method performed poorly at identifying adverse drug reactions and overdose due to patient error and fairly at identifying substance abuse in opioid-related unintentional overdose (sensitivity = 0.67, specificity = 0.96). Evaluation using validation datasets yielded significant reductions, in specificity and negative predictive values only, for many classifications mentioned above. However, these measures remained above 0.80, thus, performance observed during development was largely maintained during validation. Similar results were obtained when evaluating portability, although there was a significant reduction in sensitivity for unintentional overdose that was attributed to missing text clinical notes in the database. CONCLUSIONS: Methods that process text clinical notes show promise for improving accuracy and fidelity at identifying and classifying overdoses according to type using EHR data.
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Analgésicos Opioides/envenenamiento , Sobredosis de Droga/epidemiología , Procesamiento de Lenguaje Natural , Trastornos Relacionados con Opioides/complicaciones , Conjuntos de Datos como Asunto , Registros Electrónicos de Salud/estadística & datos numéricos , Heroína/envenenamiento , Humanos , Valor Predictivo de las Pruebas , Riesgo , Conducta Autodestructiva/epidemiología , Sensibilidad y Especificidad , WashingtónRESUMEN
PURPOSE: The study aims to develop and validate algorithms to identify and classify opioid overdoses using claims and other coded data, and clinical text extracted from electronic health records using natural language processing (NLP). METHODS: Primary data were derived from Kaiser Permanente Northwest (2008-2014), an integrated health care system (~n > 475 000 unique individuals per year). Data included International Classification of Diseases, Ninth Revision (ICD-9) codes for nonfatal diagnoses, International Classification of Diseases, Tenth Revision (ICD-10) codes for fatal events, clinical notes, and prescription medication records. We assessed sensitivity, specificity, positive predictive value, and negative predictive value for algorithms relative to medical chart review and conducted assessments of algorithm portability in Kaiser Permanente Washington, Tennessee State Medicaid, and Optum. RESULTS: Code-based algorithm performance was excellent for opioid-related overdoses (sensitivity = 97.2%, specificity = 84.6%) and classification of heroin-involved overdoses (sensitivity = 91.8%, specificity = 99.0%). Performance was acceptable for code-based suicide/suicide attempt classifications (sensitivity = 70.7%, specificity = 90.5%); sensitivity improved with NLP (sensitivity = 78.7%, specificity = 91.0%). Performance was acceptable for the code-based substance abuse-involved classification (sensitivity = 75.3%, specificity = 79.5%); sensitivity improved with the NLP-enhanced algorithm (sensitivity = 80.5%, specificity = 76.3%). The opioid-related overdose algorithm performed well across portability assessment sites, with sensitivity greater than 96% and specificity greater than 84%. Cross-site sensitivity for heroin-involved overdose was greater than 87%, specificity greater than or equal to 99%. CONCLUSIONS: Code-based algorithms developed to detect opioid-related overdoses and classify them according to heroin involvement perform well. Algorithms for classifying suicides/attempts and abuse-related opioid overdoses perform adequately for use for research, particularly given the complexity of classifying such overdoses. The NLP-enhanced algorithms for suicides/suicide attempts and abuse-related overdoses perform significantly better than code-based algorithms and are appropriate for use in settings that have data and capacity to use NLP.
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Analgésicos Opioides/envenenamiento , Sobredosis de Droga/epidemiología , Heroína/envenenamiento , Trastornos Relacionados con Opioides/complicaciones , Algoritmos , Sobredosis de Droga/clasificación , Registros Electrónicos de Salud/estadística & datos numéricos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Procesamiento de Lenguaje Natural , Sensibilidad y Especificidad , Suicidio/estadística & datos numéricos , Intento de Suicidio/estadística & datos numéricosRESUMEN
PURPOSE: The purpose of this study is to assess positive predictive value (PPV), relative to medical chart review, of International Classification of Diseases (ICD)-9/10 diagnostic codes for identifying opioid overdoses and poisonings. METHODS: Data were obtained from Kaiser Permanente Northwest and Northern California. Diagnostic data from electronic health records, submitted claims, and state death records from Oregon, Washington, and California were linked. Individual opioid-related poisoning codes (e.g., 965.xx and X42), and adverse effects of opioids codes (e.g., E935.xx) combined with diagnoses possibly indicative of overdoses (e.g., respiratory depression), were evaluated by comparison with chart audits. RESULTS: Opioid adverse effects codes had low PPV to detect overdoses (13.4%) as assessed in 127 charts and were not pursued. Instead, opioid poisoning codes were assessed in 2100 individuals who had those codes present in electronic health records in the period between the years 2008 and 2012. Of these, 10/2100 had no available information and 241/2100 were excluded potentially as anesthesia-related. Among the 1849 remaining individuals with opioid poisoning codes, 1495 events were accurately identified as opioid overdoses; 69 were miscodes or misidentified, and 285 were opioid adverse effects, not overdoses. Thus, PPV was 81%. Opioid adverse effects or overdoses were accurately identified in 1780 of 1849 events (96.3%). CONCLUSIONS: Opioid poisoning codes have a predictive value of 81% to identify opioid overdoses, suggesting ICD opioid poisoning codes can be used to monitor overdose rates and evaluate interventions to reduce overdose. Further research to assess sensitivity, specificity, and negative predictive value are ongoing. Copyright © 2017 John Wiley & Sons, Ltd.
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Analgésicos Opioides/envenenamiento , Codificación Clínica , Sobredosis de Droga/epidemiología , Clasificación Internacional de Enfermedades , Adulto , California/epidemiología , Certificado de Defunción , Registros Electrónicos de Salud , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oregon/epidemiología , Valor Predictivo de las Pruebas , Sensibilidad y Especificidad , Washingtón/epidemiología , Adulto JovenRESUMEN
PURPOSE: An unintended consequence of extended-release (ER) and long-acting (LA) prescription opioids is that these formulations can be more attractive to abusers than immediate-release (IR) formulations. The US Food and Drug Administration recognized these risks and approved the ER/LA Opioid Analgesic Risk Evaluation and Mitigation Strategy (ER/LA REMS), which has a goal of reducing opioid misuse and abuse and their associated consequences. The primary objective of this analysis is to determine whether ER/LA REMS implementation was associated with decreased reports of misuse and abuse. METHODS: Data from the Researched Abuse, Diversion and Addiction-Related Surveillance (RADARS(R)) System Poison Center Program were utilized. Poison center cases are assigned a reason for exposure, a medical outcome, and a level of health care received. Rates adjusted for population and drug utilization were analyzed over time. RESULTS: RADARS System Poison Center Program data indicate a notable decrease in ER/LA opioid rates of intentional abuse and misuse as well as major medical outcomes or hospitalizations following implementation of the ER/LA REMS. CONCLUSIONS: While similar decreases were observed for the IR prescription opioid group, the decreasing rate for the ER/LA opioids exceeded the decreasing rates for the IR prescription opioids and was distinctly different than that for the prescription stimulants, indicating that the ER/LA REMS program may have had an additional effect on decreases in opioid abuse and intentional misuse beyond secular trends.
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Analgésicos Opioides/efectos adversos , Trastornos Relacionados con Opioides/epidemiología , Mal Uso de Medicamentos de Venta con Receta/tendencias , Evaluación y Mitigación de Riesgos , Adolescente , Adulto , Analgésicos Opioides/química , Niño , Preparaciones de Acción Retardada/efectos adversos , Preparaciones de Acción Retardada/química , Femenino , Humanos , Masculino , Persona de Mediana Edad , Trastornos Relacionados con Opioides/diagnóstico , Trastornos Relacionados con Opioides/prevención & control , Mal Uso de Medicamentos de Venta con Receta/prevención & control , Adulto JovenRESUMEN
Objective: Opioid abuse is a serious public health concern. In response, the Food and Drug Administration (FDA) determined that a risk evaluation and mitigation strategy (REMS) for extended-release and long-acting (ER/LA) opioids was necessary to ensure that the benefits of these analgesics continue to outweigh the risks. Key components of the REMS are training for prescribers through accredited continuing education (CE), and providing patient educational materials. Methods: The impact of this REMS has been assessed using diverse metrics including evaluation of prescriber and patient understanding of the risks associated with opioids; patient receipt and comprehension of the medication guide and patient counseling document; patient satisfaction with access to opioids; drug utilization and changes in prescribing patterns; and surveillance of ER/LA opioid misuse, abuse, overdose, addiction, and death. Results and Conclusions: The results of these assessments indicate that the increasing rates of opioid abuse, addiction, overdose, and death observed prior to implementation of the REMS have since leveled off or started to decline. However, these benefits cannot be attributed solely to the ER/LA opioid analgesics REMS since many other initiatives to prevent abuse occurred contemporaneously. These improvements occurred while preserving patient access to opioids as a large majority of patients surveyed expressed satisfaction with their access to opioids.
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Política de Salud/legislación & jurisprudencia , Trastornos Relacionados con Opioides/prevención & control , Evaluación de Procesos y Resultados en Atención de Salud , Analgésicos Opioides/uso terapéutico , Educación Médica Continua/métodos , Humanos , Educación del Paciente como Asunto/métodos , Pautas de la Práctica en Medicina , Estados Unidos , United States Food and Drug AdministrationRESUMEN
PURPOSE: Optimizing a therapeutic product's benefit-risk profile is an on-going process throughout the product's life cycle. Different, yet related, benefit-risk assessment strategies and frameworks are being developed by various regulatory agencies, industry groups, and stakeholders. This paper summarizes current best practices and discusses the role of the pharmacoepidemiologist in these activities, taking a life-cycle approach to integrated Benefit-Risk Assessment, Communication, and Evaluation (BRACE). METHODS: A review of the medical and regulatory literature was performed for the following steps involved in therapeutic benefit-risk optimization: benefit-risk evidence generation; data integration and analysis; decision making; regulatory and policy decision making; benefit-risk communication and risk minimization; and evaluation. Feedback from International Society for Pharmacoepidemiology members was solicited on the role of the pharmacoepidemiologist. The case example of natalizumab is provided to illustrate the cyclic nature of the benefit-risk optimization process. RESULTS: No single, globally adopted benefit-risk assessment process exists. The BRACE heuristic offers a way to clarify research needs and to promote best practices in a cyclic and integrated manner and highlight the critical importance of cross-disciplinary input. Its approach focuses on the integration of BRACE activities for risk minimization and optimization of the benefit-risk profile. CONCLUSION: The activities defined in the BRACE heuristic contribute to the optimization of the benefit-risk profile of therapeutic products in the clinical world at both the patient and population health level. With interdisciplinary collaboration, pharmacoepidemiologists are well suited for bringing in methodology expertise, relevant research, and public health perspectives into the BRACE process.
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Comunicación , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Medicamentos bajo Prescripción/economía , Análisis Costo-Beneficio , Salud Global , Humanos , Farmacoepidemiología , Medicamentos bajo Prescripción/efectos adversos , Medición de RiesgoRESUMEN
PURPOSE: Abuse of opioid analgesics for their psychoactive effects is associated with a large number of fatalities. The effect of making opioid tablets harder to crush/dissolve on opioid-related fatalities has not been assessed. The objective of this study was to assess the impact of introducing extended-release oxycodone (ERO [OxyContin(®) ]) tablets containing physicochemical barriers to crushing/dissolving (reformulated ERO) on deaths reported to the manufacturer. METHODS: All spontaneous adverse event reports of death in the US reported to the manufacturer between 3Q2009 and 3Q2013 involving ERO were used. The mean numbers of deaths/quarter in the 3 years after reformulated ERO introduction were compared with the year before. Changes in the slope of trends in deaths were assessed using spline regression. Comparison groups consisted of non-fatal reports involving ERO and fatality reports involving ER morphine. RESULTS: Reports of death decreased 82% (95% CI: -89, -73) from the year before to the third year after (131 to 23 deaths per year) reformulation; overdose death reports decreased 87% (95% CI: -93, -78) and overdose deaths with mention of abuse-related behavior decreased 86% (95% CI:-92, -75). In contrast, non-fatal ERO reports did not decrease post-reformulation, and reported ER morphine fatalities remained unchanged. The ratio of ERO fatalities to all oxycodone fatalities decreased from 21% to 8% in the year pre-reformulation to the second year post-reformulation. CONCLUSIONS: These findings, when considered in the context of previously published studies using other surveillance systems, suggest that the abuse-deterrent characteristics of reformulated ERO have decreased the fatalities associated with its misuse/abuse. © 2014 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons, Ltd.
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Química Farmacéutica/normas , Mortalidad/tendencias , Oxicodona/química , Adolescente , Adulto , Anciano , Química Farmacéutica/tendencias , Niño , Sistemas de Administración de Bases de Datos , Preparaciones de Acción Retardada , Formas de Dosificación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oxicodona/administración & dosificación , Estados UnidosRESUMEN
BACKGROUND: Reformulating opioid analgesics to deter abuse is one approach toward improving their benefit-risk balance. To assess sentiment and attempts to defeat these products among difficult-to-reach populations of prescription drug abusers, evaluation of posts on Internet forums regarding reformulated products may be useful. A reformulated version of OxyContin (extended-release oxycodone) with physicochemical properties to deter abuse presented an opportunity to evaluate posts about the reformulation in online discussions. OBJECTIVE: The objective of this study was to use messages on Internet forums to evaluate reactions to the introduction of reformulated OxyContin and to identify methods aimed to defeat the abuse-deterrent properties of the product. METHODS: Posts collected from 7 forums between January 1, 2008 and September 30, 2013 were evaluated before and after the introduction of reformulated OxyContin on August 9, 2010. A quantitative evaluation of discussion levels across the study period and a qualitative coding of post content for OxyContin and 2 comparators for the 26 month period before and after OxyContin reformulation were conducted. Product endorsement was estimated for each product before and after reformulation as the ratio of endorsing-to-discouraging posts (ERo). Post-to-preintroduction period changes in ERos (ie, ratio of ERos) for each product were also calculated. Additionally, post content related to recipes for defeating reformulated OxyContin were evaluated from August 9, 2010 through September 2013. RESULTS: Over the study period, 45,936 posts related to OxyContin, 18,685 to Vicodin (hydrocodone), and 23,863 to Dilaudid (hydromorphone) were identified. The proportion of OxyContin-related posts fluctuated between 6.35 and 8.25 posts per 1000 posts before the reformulation, increased to 10.76 in Q3 2010 when reformulated OxyContin was introduced, and decreased from 9.14 in Q4 2010 to 3.46 in Q3 2013 in the period following the reformulation. The sentiment profile for OxyContin changed following reformulation; the post-to-preintroduction change in the ERo indicated reformulated OxyContin was discouraged significantly more than the original formulation (ratio of ERos=0.43, P<.001). A total of 37 recipes for circumventing the abuse-deterrent characteristics of reformulated OxyContin were observed; 32 were deemed feasible (ie, able to abuse). The frequency of posts reporting abuse of reformulated OxyContin via these recipes was low and decreased over time. Among the 5677 posts mentioning reformulated OxyContin, 825 posts discussed recipes and 498 reported abuse of reformulated OxyContin by such recipes (41 reported injecting and 128 reported snorting). CONCLUSIONS: After introduction of physicochemical properties to deter abuse, changes in discussion of OxyContin on forums occurred reflected by a reduction in discussion levels and endorsing content. Despite discussion of recipes, there is a relatively small proportion of reported abuse of reformulated OxyContin via recipes, particularly by injecting or snorting routes. Analysis of Internet discussion is a valuable tool for monitoring the impact of abuse-deterrent formulations.
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Analgésicos Opioides/administración & dosificación , Internet , Trastornos Relacionados con Opioides/prevención & control , Oxicodona/administración & dosificación , Acetaminofén , Química Farmacéutica , Combinación de Medicamentos , Humanos , Hidrocodona , Hidromorfona , Oxicodona/química , Medios de Comunicación SocialesRESUMEN
Radiofrequency ablation (RFA) using the CARTO 3D mapping system is a common approach for pulmonary vein isolation to treat atrial fibrillation (AF). Linkage between CARTO procedural data and patients' electronical health records (EHR) provides an opportunity to identify the ablation-related parameters that would predict AF recurrence. The objective of this study is to assess the incremental accuracy of RFA procedural data to predict post-ablation AF recurrence using machine learning model. Procedural data generated during RFA procedure were downloaded from CARTONET and linked to deidentified Mercy Health EHR data. Data were divided into train (70%) and test (30%) data for model development and validation. Automate machine learning (AutoML) was used to predict 1 year AF recurrence, defined as a composite of repeat ablation, electrical cardioversion, and AF hospitalization. At first, AutoML model only included Patients' demographic and clinical characteristics. Second, an AutoML model with procedural variables and demographical/clinical variables was developed. Area under receiver operating characteristic curve (AUROC) and net reclassification improvement (NRI) were used to compare model performances using test data. Among 306 patients, 67 (21.9%) patients experienced 1-year AF recurrence. AUROC increased from 0.66 to 0.78 after adding procedural data in the AutoML model based on test data. For patients with AF recurrence, NRI was 32% for model with procedural data. Nine of 10 important predictive features were CARTO procedural data. From CARTO procedural data, patients with lower contact force in right inferior site, long ablation duration, and low number of left inferior and right roof lesions had a higher risk of AF recurrence. Patients with persistent AF were more likely to have AF recurrence. The machine learning model with procedural data better predicted 1-year AF recurrence than the model without procedural data. The model could be used for identification of patients with high risk of AF recurrence post ablation.
Asunto(s)
Técnicas de Ablación , Fibrilación Atrial , Ablación por Catéter , Venas Pulmonares , Ablación por Radiofrecuencia , Humanos , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/cirugía , Resultado del Tratamiento , Factores de Tiempo , Ablación por Catéter/métodos , Recurrencia , Venas Pulmonares/cirugíaRESUMEN
Background: Local impedance drop in cardiac tissue during catheter ablation may be a valuable measure to guide atrial fibrillation (AF) ablation procedures for greater effectiveness. Objective: The study sought to assess whether local impedance drop during catheter ablation to treat AF predicts 1-year AF recurrence and what threshold of impedance drop is most predictive. Methods: We identified patients with AF undergoing catheter ablation in the Mercy healthcare system. We downloaded AF ablation procedural data recorded by the CARTO system from a cloud-based analytical tool (CARTONET) and linked them to individual patient electronic health records. Average impedance drops in anatomical region of right and left pulmonary veins were calculated. Effectiveness was measured by a composite outcome of repeat ablation, AF rehospitalization, direct current cardioversion, or initialization of a new antiarrhythmic drug post-blanking period. The association between impedance drop and 1-year AF recurrence was assessed by logistic regression adjusting for demographics, clinical, and ablation characteristics. Bootstrapping was used to determine the most predictive threshold for impedance drop based on the Youden index. Results: Among 242 patients, 23.6% (n = 57) experienced 1-year AF recurrence. Patients in the lower third vs upper third of average impedance drop had a 5.9-fold (95% confidence interval [CI] 1.81-21.8) higher risk of recurrence (37.0% vs 12.5%). The threshold of 7.2 Ω (95% CI 5.75-7.7 Ω) impedance drop best predicted AF recurrence, with sensitivity of 0.73 and positive predictive value of 0.33. Patients with impedance drop ≤7.2 Ω had 3.5-fold (95% CI 1.39-9.50) higher risk of recurrence than patients with impedance drop >7.2 Ω, and there was no statistical difference in adverse events between the 2 groups of patients. Sensitivity analysis on right and left wide antral circumferential ablation impedance drop was consistent. Conclusion: Average impedance drop is a strong predictor of clinical success in reducing AF recurrence but as a single criterion for predicting recurrence only reached 73% sensitivity and 33% positive predictive value.
RESUMEN
INTRODUCTION: Racial and ethnic disparities in orthopaedic surgery are well documented. However, the extent to which these persist in fracture care is unknown. This study sought to assess racial disparities in the postoperative surgical and medical management of patients after diaphyseal tibia fracture fixation. METHODS: Patients with surgically treated tibial shaft fractures from October 1, 2015, to December 31, 2020, were identified in the MarketScan® Medicaid Database. Exclusion criteria included concurrent fractures or amputation. Outcomes included 2-year postoperative complications, reoperation rates, and filled prescriptions. Surgically-treated Black and White cohorts were propensity-score matched using nearest-neighbor matching on patient demographics, comorbidities, fracture pattern and severity, and fixation type. Chi-square tests and survival analyses (Kaplan-Meier and Cox proportional hazard models) were conducted. RESULTS: 5,472 patients were included, 2,209 Black and 3,263 White patients. After matching, 2,209 were retained in each cohort. No significant differences in complication rates were observed in the matched Black vs White cohorts. Rates of reoperation, however, were significantly lower in Black as compared to White patients (28.5 % vs. 35.5 % rate, risk difference = 7.0 % (95 % confidence interval (CI): 4.2 % to 9.7 %)). Implant removal was also significantly lower in Black (17.9 %) vs. White (25.1 %) patients (Risk difference = 7.2 %, (95 %CI: 4.8 % to 9.6 %)). The adjusted hazard ratio comparing the reoperation rate in Black versus White patients was 0.77 (95 %CI: 0.69-0.82, p < 0.0001). Significantly lower proportions of Black vs White patients filled at least one prescription for benzodiazepine, antidepressants, strong opiates, or antibiotics at every time point post-index. DISCUSSION: Fewer resources were used in post-operative management after surgical treatment of tibial shaft fractures for Black versus White Medicaid-insured patients. These results may be reflective of the undertreatment of complications after tibia fracture surgery for Black patients and highlight the need for further interventions to address racial disparities in trauma care.
Asunto(s)
Disparidades en Atención de Salud , Medicaid , Complicaciones Posoperatorias , Fracturas de la Tibia , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Negro o Afroamericano/estadística & datos numéricos , Fijación de Fractura/estadística & datos numéricos , Fijación de Fractura/métodos , Fijación Interna de Fracturas , Disparidades en Atención de Salud/estadística & datos numéricos , Disparidades en Atención de Salud/etnología , Medicaid/estadística & datos numéricos , Cuidados Posoperatorios , Complicaciones Posoperatorias/epidemiología , Reoperación/estadística & datos numéricos , Estudios Retrospectivos , Fracturas de la Tibia/cirugía , Estados Unidos/epidemiología , Blanco/estadística & datos numéricosRESUMEN
OBJECTIVES: To analyze US commercial insurance payments associated with COVID-19 as a function of severity and duration of disease. STUDY DESIGN: Retrospective database analysis. METHODS: Patients with COVID-19 between April 1, 2020, and June 30, 2021, in the Merative MarketScan Commercial database were identified and stratified as having asymptomatic, mild, moderate (with and without lower respiratory disease), or severe/critical (S/C) disease based on the severity of the acute COVID-19 infection. Duration of disease (DOD) was estimated for all patients. Patients with DOD longer than 12 weeks were defined as having post-COVID-19 condition (PCC). Outcomes were all-cause payments (ACP) and disease-specific payments (DSP) for the entire DOD. Variables included demographic and comorbidities at the time of acute disease. Adjusted payments by disease severity were estimated using generalized linear models (γ distribution with log link). RESULTS: A total of 738,339 patients were included (374,401 asymptomatic, 156,220 mild, 180,213 moderate, and 27,505 S/C cases). DSP increased from $217 (95% CI, $214-221) for asymptomatic cases to $2744 (95% CI, $2678-$2811) for moderate cases with lower respiratory disease and $28,250 (95% CI, $26,963-$29,538) for S/C cases. ACP increased from $505 (95% CI, $497-$512) for asymptomatic cases to $46,538 (95% CI, $44,096-$48,979) for S/C cases. The DSP and ACP further increased by $50,736 (95% CI, $45,337-$56,136) and $94,839 (95% CI, $88,029-$101,649), respectively, in S/C cases with PCC vs a DOD of fewer than 4 weeks. CONCLUSIONS: COVID-19 payments for S/C cases were more than 10-fold greater than those of moderate cases and further increased by nearly $95,000 in S/C cases with PCC vs a DOD of fewer than 4 weeks.