<p>  </p> <p><strong>Background: </strong></p> <p>Torsades de pointes (TdP) is a polymorphic ventricular tachycardia (VT) associated with heart rate-corrected QT interval (QTc) prolongation on the electrocardiogram (ECG). TdP can cause sudden cardiac arrest (SCA), a catastrophic outcome. The antiarrhythmic drugs dofetilide and sotalol can cause QTc prolongation and arrhythmias, as can more than 200 other medications available on global markets. Heart failure (HF) with reduced ejection fraction (HFrEF) is a risk factor for drug-induced TdP, and HFrEF heightens sensitivity to drug-induced QTc lengthening. However, ~55% of patients with HF have preserved, rather than reduced, ejection fraction. It remains unknown whether patients with HF with preserved ejection fraction (HFpEF) are at increased risk for drug-induced VT/SCA. Assessment of the risk of drug-induced VT/SCA in HFpEF patients is important, so that recommendations can be made regarding the safety of QTc-prolonging drugs and need for enhanced ECG monitoring in this population. </p> <p><strong>Objective:</strong></p> <p>In aim 1, we sought to determine the risk of VT and SCA associated with dofetilide and sotalol in patients with HFpEF. In aim 2, we were able to use QTc interval to determine the odds of dofetilide/sotalol-associated QT interval prolongation in patients with HFpEF. In Aim 3, we investigated the influence of HFpEF on VT and SCA associated with a broader group of drugs known to cause TdP (“known “TdP drugs”), as designated by the QT drugs list at www.crediblemeds.org. </p> <p><strong>Methods:</strong></p> <p>In aim 1, we used Medicare claims (2014-2016) and ICD-9/10 codes to identify patients taking the QT interval-prolonging drugs dofetilide or sotalol, which are used commonly in patients with HF and atrial fibrillation, as well as non-dofetilide or sotalol users among 3 groups: HFpEF, HFrEF, and no HF. Multinomial propensity score-matching was performed. Cochran–Mantel–Haenszel statistics and standardized differences were used to compare baseline characteristics. A generalized Cox proportional hazards model was used to estimate hazard ratios (HRs) and test the association of VT and SCA among dofetilide/sotalol users, HFpEF, HFrEF, and no HF.</p> <p>In Aim 2, the data source was electronic health records from the Indiana Network for Patient Care (February 2010 to May 2021). After removing patients with overlapping diagnoses of HFpEF and HFrEF, no diagnosis code, absence of QT interval records, and no validated record of using dofetilide or sotalol, we identified patients taking dofetilide or sotalol among three groups: HFrEF, HFpEF, and no HF. Cochran–Mantel–Haenszel statistics were used to compare baseline characteristics. QT interval prolongation was defined as heart rate-corrected QT (QTc) > 500 ms during dofetilide/sotalol therapy. Unadjusted odds ratios (OR) of QT interval prolongation were determined by univariate analysis, and adjusted ORs were determined by generalized estimating equations (GEE) with logit link to account for an individual cluster with different times of hospitalization and covariates.</p> <p>In aim 3, we used Medicare enrollment in fee-for-service medical and pharmacy benefits (2014 to 2016) and ICD-9/10 codes, we identified patients taking drugs known to cause torsades de pointes (TdP drugs; www.crediblemeds.org) and non-TdP drug users among three groups: HFrEF, HFpEF, and no HF. Multinomial propensity score-matching was performed to minimize baseline differences in covariates (patient demographics, comorbidities, health care utilization and drug history). Cochran–Mantel–Haenszel statistics and standardized differences were used to compare baseline characteristics. A generalized Cox proportional hazards model was used to estimate HRs and test the association of VT and SCA among TdP drug users with HFpEF, HFrEF, and no HF.</p> <p><strong>Results:</strong></p> <p>In Aim 1, VT and SCA occurred in 166 (10.68%) and 16 (1.03%), respectively, of 1,554 dofetilide/sotalol users with HFpEF, 543 (38.76%) and 40 (2.86%) of 1,401 dofetilide/sotalol users with HFrEF, and 245 (5.06%) and 13 (0.27%) of 4,839 dofetilide/sotalol users with no HF. The adjusted HR for VT in patients with HFrEF was 7.00 (95% CI 6.12-8.02) and in patients with HFpEF was 1.99 (1.71-2.32). The risk of VT associated with dofetilide/sotalol was increased across the overall study population (HR: 2.47 [1.89-3.23]). Use of dofetilide/sotalol increased the risk of VT in patients with HFrEF (HR: 1.53 [1.07-2.20]) and in those with HFpEF (HR: 2.34 [1.11-4.95]). However, while the overall risk of SCA was increased in patients with HFrEF (HR: 5.19 [4.10-6.57]) and HFpEF (HR: 2.53 [1.98-3.23]) compared to patients with no HF, dofetilide/sotalol use was not significantly associated with an increased risk of SCA.</p> <p>In Aim 2, QTc prolongation associated with dofetilide/sotalol occurred in 51.2% of patients with HFpEF, 70.1% of patients with HFrEF, and 29.4% of patients with no HF. After adjusting for age, sex, race, serum potassium and magnesium concentrations, kidney function, concomitant drug therapy, and comorbid conditions, the adjusted odds of having QTc interval larger than 500ms during the hospital stay were 5.23 [3.15-8.67] for HFrEF and 1.98 [1.17-3.33] for HFpEF with no HF as the reference group. </p> <p>In Aim 3, of 23,910 known TdP drug users with HFrEF, VT and SCA occurred in 4,263 (17.8%) and 493 (2.1%) patients, respectively. In comparison, among 31,359 known TdP drug users with HFpEF, VT and SCA occurred in 1,570 (5.0%) and 340 (1.1%) patients. VT and SCA occurred in 3,154 (0.8%) and 528 (0.1%) of 384,824 known TdP drug users without HF. The overall HR of both VT and SCA was increased in patients with HFrEF (HR: 7.18 [6.13-8.40])  and in those with HFpEF (HR: 2.09 [1.80-2.42]). The risk of VT associated with known TdP drugs was increased across the overall population (HR: 1.34 [1.20-1.51]). Use of known TdP drugs significantly increased the risk of VT and SCA in patients with HFrEF (HR: 1.34 [1.07-1.67]), but not in patients with HFpEF.</p> <p><strong>Conclusion:</strong></p> <p>HFpEF may exhibit an enhanced response to drug-associated VT, and is associated with a higher risk of drug-associated QTc interval prolongation. Further study is needed to identify methods to minimize this risk for patients with HFpEF requiring therapy with dofetilide, sotalol, or drugs known to cause TdP. </p>

As reformas orientadas para o mercado realizadas no Brasil e no Equador a partir da década de 1980 e de 1990 diminuíram os gastos públicos e os recursos humanos das organizações nacionais de patrimônio cultural. Para suprir a demanda por tais recursos, surgiu, na arena política do patrimônio cultural, o agente financeiro internacional. Nesse contexto, esta dissertação busca compreender a relação de poder e as formas como são feitas as escolhas políticas entre os órgãos de patrimônio nacionais e a instituição multilateral que financia diversas políticas públicas culturais. Para tanto, partiu-se da experiência de dois países latino-americanos, o Brasil e o Equador, analisando em que medida os órgãos nacionais desobrigaram-se da realização das políticas públicas para o setor, sofrendo ingerência dos organismos financeiros internacionais. Estabeleceu-se como objeto de estudo três organizações o Banco Interamericano de Desenvolvimento (BID), o Instituto do Patrimônio Histórico e Artístico Nacional (IPHAN), no Brasil, e o Instituto Nacional de Patrimonio Cultural (Instituto de Patrimônio Cultural) (INPC), no Equador e recorreu-se à pesquisa bibliográfica, documental e de campo, bem como a entrevistas com gestores dos órgãos estudados. Confirmou-se a hipótese de que o processo de enfraquecimento das instituições nacionais de patrimônio cultural contribuiu decisivamente para que se retirasse, progressivamente, o poder de decidir, executar e avaliar políticas públicas de preservação do patrimônio cultural dos domínios do Estado. Entretanto, não se confirmou que as decisões se transferiram para organismos internacionais, mas sim para a iniciativa privada, buscando tornar os órgãos nacionais voltados àquele fim meros chanceladores de decisões tomadas fora deles. Verificou-se, ainda, que o processo de desmonte das instituições nacionais de patrimônio cultural brasileira e equatoriana se reverteu nos últimos anos com os governos dos presidentes Luis Inácio Lula da Silva e Rafael Corrêa, repercutindo, inclusive, na condução das políticas públicas financiadas pelo BID para o setor. / The market-oriented reforms carried out in Brazil and Ecuador from the 1980s and 1990s diminished the public expenses and the human resources in the national organizations of cultural heritage. In order to meet the demand for those resources, the international financial agent has come up in the arena of cultural heritage policy. In this context, this thesis aims at understanding the power relation between the national heritage organs and the multilateral institution, which supports several policies of cultural heritage, as well as the ways they choose their policies. To do so, starting with the experiences from two Latin American countries, Brazil and Ecuador, an analysis was held in order to determine to what extent the national organs relieved themselves of accomplishing the public policies for the sector, which caused them to undergo interference by the international financial organs. As the object of study, three organizations were chosen: the Inter-American Development Bank (IDB), the Instituto do Patrimônio Histórico e Artístico Nacional (National Institute of Artistic and Historical Heritage) (IPHAN), in Brazil, and the Instituto Nacional de Patrimonio Cultural (National Institute of Cultural Heritage) (INPC), in Ecuador. The research has used related literature, documentary and field research, as well as interviews with the managers of the organs in study. The hypothesis confirmed was that the process of weakening of the national institutions of cultural heritage has contributed decisively to deprive, progressively, the power to decide, implement and evaluate public policies for the preservation of cultural heritage of the State domains. However, it has not been proved that the decisions had been transferred to international organs; rather, to the public initiative, seeking to turn the national organs focused on preservation of heritage into mere chancellors of the decisions made apart from them. It has also been observed that the process of dismantling the Brazilian and Ecuadorian national institutions of cultural heritage was reversed in the last years during the government of Luis Inácio Lula da Silva and Rafael Corrêa, echoing, also, in the conduct of public policies for the sector sponsored by the IDB.

As reformas orientadas para o mercado realizadas no Brasil e no Equador a partir da década de 1980 e de 1990 diminuíram os gastos públicos e os recursos humanos das organizações nacionais de patrimônio cultural. Para suprir a demanda por tais recursos, surgiu, na arena política do patrimônio cultural, o agente financeiro internacional. Nesse contexto, esta dissertação busca compreender a relação de poder e as formas como são feitas as escolhas políticas entre os órgãos de patrimônio nacionais e a instituição multilateral que financia diversas políticas públicas culturais. Para tanto, partiu-se da experiência de dois países latino-americanos, o Brasil e o Equador, analisando em que medida os órgãos nacionais desobrigaram-se da realização das políticas públicas para o setor, sofrendo ingerência dos organismos financeiros internacionais. Estabeleceu-se como objeto de estudo três organizações o Banco Interamericano de Desenvolvimento (BID), o Instituto do Patrimônio Histórico e Artístico Nacional (IPHAN), no Brasil, e o Instituto Nacional de Patrimonio Cultural (Instituto de Patrimônio Cultural) (INPC), no Equador e recorreu-se à pesquisa bibliográfica, documental e de campo, bem como a entrevistas com gestores dos órgãos estudados. Confirmou-se a hipótese de que o processo de enfraquecimento das instituições nacionais de patrimônio cultural contribuiu decisivamente para que se retirasse, progressivamente, o poder de decidir, executar e avaliar políticas públicas de preservação do patrimônio cultural dos domínios do Estado. Entretanto, não se confirmou que as decisões se transferiram para organismos internacionais, mas sim para a iniciativa privada, buscando tornar os órgãos nacionais voltados àquele fim meros chanceladores de decisões tomadas fora deles. Verificou-se, ainda, que o processo de desmonte das instituições nacionais de patrimônio cultural brasileira e equatoriana se reverteu nos últimos anos com os governos dos presidentes Luis Inácio Lula da Silva e Rafael Corrêa, repercutindo, inclusive, na condução das políticas públicas financiadas pelo BID para o setor. / The market-oriented reforms carried out in Brazil and Ecuador from the 1980s and 1990s diminished the public expenses and the human resources in the national organizations of cultural heritage. In order to meet the demand for those resources, the international financial agent has come up in the arena of cultural heritage policy. In this context, this thesis aims at understanding the power relation between the national heritage organs and the multilateral institution, which supports several policies of cultural heritage, as well as the ways they choose their policies. To do so, starting with the experiences from two Latin American countries, Brazil and Ecuador, an analysis was held in order to determine to what extent the national organs relieved themselves of accomplishing the public policies for the sector, which caused them to undergo interference by the international financial organs. As the object of study, three organizations were chosen: the Inter-American Development Bank (IDB), the Instituto do Patrimônio Histórico e Artístico Nacional (National Institute of Artistic and Historical Heritage) (IPHAN), in Brazil, and the Instituto Nacional de Patrimonio Cultural (National Institute of Cultural Heritage) (INPC), in Ecuador. The research has used related literature, documentary and field research, as well as interviews with the managers of the organs in study. The hypothesis confirmed was that the process of weakening of the national institutions of cultural heritage has contributed decisively to deprive, progressively, the power to decide, implement and evaluate public policies for the preservation of cultural heritage of the State domains. However, it has not been proved that the decisions had been transferred to international organs; rather, to the public initiative, seeking to turn the national organs focused on preservation of heritage into mere chancellors of the decisions made apart from them. It has also been observed that the process of dismantling the Brazilian and Ecuadorian national institutions of cultural heritage was reversed in the last years during the government of Luis Inácio Lula da Silva and Rafael Corrêa, echoing, also, in the conduct of public policies for the sector sponsored by the IDB.

Indiana University-Purdue University Indianapolis (IUPUI) / In 2009, Indianapolis Emergency Medical Service (I-EMS, formerly Wishard Ambulance Service) launched an electronic medical record system within their ambulances and started to exchange patient data with the Indiana Network for Patient Care (INPC). This unique system allows EMS personnel in an ambulance to get important medical information prior to the patient’s arrival to the accepting hospital from incident scene. In this retrospective cohort study, we found EMS personnel made 3,021 patient data requests (14%) of 21,215 EMS transports during a one-year period, with a “success” match rate of 46%, and a match “failure” rate of 17%. The three major factors for causing match “failure” were (1) ZIP code 55%, (2) Patient Name 22%, and (3) Birth Date 12%. This study shows that the ZIP code is not a robust identifier in the patient identification process and Non-ZIP code identifiers may be a better choice due to inaccuracies and changes of the ZIP code in a patient’s record.