Drug-induced torsades de pointes in an underserved urban population. Methadone: is there therapeutic equipoise?

BACKGROUND Although it has been well established that methadone use can result in prolonged QTc/torsades de pointes (TdP) and has been labeled as one of the main drugs that cause TdP, it is still prescribed indiscriminately, and several cases of methadone-associated TdP have been seen in our community. METHODS Our objective was to determine the associated factors for prolonged QTc and the development of torsades de pointes (TdP) in our underserved patient population. We found 12,550 ECGs with prolonged QTc between 2002 and 2013. Medical records were reviewed in order to identify precipitating factors for prolonged QTc and to detect incidence of TdP. RESULTS We identified 2735 patients with prolonged QTc who met the inclusion criteria. Of these, 89 (3%) experienced TdP. There was a greater prevalence of HIV infection in the TdP group (11.2 vs. 3.7%, p < 0.001). Furosemide, hydrochlorothiazide, selective serotonin reuptake inhibitors (SSRIs), amiodarone, ciprofloxacin, methadone, haloperidol, and azithromycin were the drugs most often associated with prolonged QTc (31, 8.2, 7.6, 7.1, 3.9, 3.4 and 3.3%, respectively). However, the agents most commonly associated with TdP were furosemide (39.3%), methadone (27%), SSRIs (19.1%), amiodarone (18%), and dofetilide (9%). The medications with statistical significance in the multivariate analysis for TdP development in descending order were as follows: ranolazine (odds ratios [OR] = 53.61, 95% confidence interval [CI] 5.4-524, p < 0.001), dofetilide (OR = 25, CI 6.47-103.16, p < 0.001), voriconazole (OR = 21.40, CI 3.24-124.25, p < 0.001), verapamil (OR = 10.98, CI 2.62-44.96, p < 0.001), sotalol (OR = 12.72, 1.95-82.81, p = 0.008), methadone (OR = 9.89, CI 4.05-24.15, p < 0.001), and SSRI (OR = 2.26, CI 1.10-5.96, p < 0.001). This multivariate analysis revealed that amiodarone and HIV infection were not implicated in TdP. CONCLUSION Methadone was by far the leading medication implicated in the development of TdP and an independent predictor in both univariate and multivariate analyses despite the fact that it was not the most common QT-prolonging medication in our population.

Stable oxygen and carbon isotope of foraminifera from DSDP Leg 90 sites

High-resolution oxygen and carbon isotope stratigraphy is presented for Miocene to early Pliocene sequences at three DSDP sites from the Lord Howe Rise, southwest Pacific, at water depths ranging from 1,300 to 2,000 m. Site 588 is located in the warm subtropics (~26°S), whereas Sites 590 and 591 are positioned in transitional (northern temperate) water masses (~31°S). Benthic foraminiferal oxygen and carbon isotope analyses were conducted on all sites; planktonic foraminiferal isotope data were generated for Site 590 only. Sample resolution in these sequences is on the order of 50,000 yr. or better. The chronological framework employed in this study is based largely upon ages assigned to Neogene calcareous nannoplankton boundaries. The benthic oxygen isotope record exhibits several major features during the Neogene. During most of the early Miocene, delta18O values were relatively low, reaching minimum values in the late early Miocene (19.5 to 16.5 Ma), and recording the climax of Neogene warmth. This was followed by a major increase in benthic delta18O values between ~16.5 and 13.5 Ma, which is interpreted as representing major, permanent accumulation of the East Antarctic ice sheet and cooling of bottom waters. During the 3 m.y. 18O enrichment, surface waters at these middle latitudes warmed between 16 and 14.5 Ma. During the remainder of the middle and late Miocene, benthic delta18O values exhibit distinct fluctuations, but the average value remained unchanged. The isotopic data show two distinct episodes of climatic cooling close to the middle/late Miocene boundary. The earliest of these events occurred between 12.5 and 11.5 Ma in the latest middle Miocene. The second cooling event occurred from 11 to 9 Ma, and is marked by some of the highest delta18O values of the entire Miocene. This was followed by relative warmth during the middle part of the late Miocene. The latest Miocene and earliest Pliocene (6.2 to 4.5 Ma) were marked by relatively high delta18O values, indicating increased cooling and glaciation. During the middle Pliocene, at about 3.4 Ma, a 0.4 per mil increase in benthic delta18O documents a net increase in average global ice volume and cooling of bottom waters. During this interval of increased glaciation, surface waters warmed by 2-3°C in southern middle-latitude regions. During the late Pliocene, between 2.6 and 2.4 Ma, a further increase in delta18O occurred; this has been interpreted by previous workers as heralding the onset of Northern Hemisphere glaciation. Surface-water warming in the middle latitudes occurred in association with major high-latitude glacial increases in the early middle Miocene (16-14 Ma), middle Pliocene (-3.5 Ma), and late Pliocene (~2.4 Ma). These intervals were also marked by increases in the vertical temperature gradient in the open ocean. Intersite correlation is enhanced by using carbon isotope stratigraphy. The great similarity of the delta13C time-series records within and between ocean basins and with water depth clearly indicates that changes in oceanwide average delta13C of [HCO3]- in seawater dominated the records, rather than local effects. Broad changes in the Neogene delta13C record were caused largely by transfer of organic carbon between continental and oceanic reservoirs. These transfers were caused by marine transgressions and regressions on the continental margins. The dominant feature of Neogene delta13C stratigraphy is a broad late early to early middle Miocene increase of about lâ between ~19 and 14.5 Ma. This trend occurred contemporaneously with a period of maximum coastal onlap (transgression) and maximum Neogene climatic warmth. The delta13C trend terminated during the expansion of the Antarctic ice sheet and associated marine regression. The latest Miocene carbon isotope shift (of up to - 0.75 per mil) at 6.2 Ma is clearly recorded in all sites examined and was followed by relatively low values during the remainder of the Neogene. This shift was caused by a glacioeustatic sealevel lowering that exposed continental margins via regression and ultimately increased the flux of organic carbon to the deep sea. An increase in delta13C values during the early Pliocene (~5 to 4 Ma) resulted from marine transgression during a time of global warmth.

Ordonnances des roys de France de la troisième race, recueillies par ordre chronologique.

Index B: Table chronologique des ordonnances des rois de France de la troisième race jusqu'au règne de Louis XII inclusivement, suivie d'une table alphabétique pour en faciliter l'usage, par J. M. Pardessus ... . Paris, Imprimerie royale, 1847. 2 p. l., viii, 607 p. 40 cm.

Ioannis Cantacuzeni ... Contra Mahometicam fidem Christiana [et] orthodoxa assertio, graece conscripta ante annos fere ducentos, nunc uero latinitate donata /

Contiene según consta en port., con port. y pag. propias: Kata eis ton sarakenon haireseos Apologiai D. Tou autou Kata tou Moameou logoi D. ... Christianae religionis acerrimi propugnatoris D. Ioannis Cantacuzeni ... contra Saracenorum haeresim, pro christiana religione apologiae IIII. Eiusdem contra Mahometem Orationes IIII

Ioannis Cantacuzeni eximperatoris Historiarum libri IV : graece et latine /

Covers mostly the years 1320-1356.

Machumetis Saracenorum principis, eiusque successorum vitae, doctrina, ac ipse Alcoran, ... quae ante annos CCCC, ... D. Petrus abbas Cluniacensis, per uiros eruditos [Robertum Retenensem, [et] Hermannum Dalmatam] ... ex Arabica lingua in Latinam transferri curauit. ... His adiunctae sunt Confutationes multoru[m], [et] quidem ... authorum, Arabum, Graecorum,[et] Latinoru[m], unà cum... Philippi Melanchthonis praemonitione ... Adiuncti sunt etiam De Turcarum, siue Sarracenorum ... origine, ac rebus gestis, a DCCCC annis ad nostra usq[ue] tempora, libelli aliquot ... Haec omnia in unum uolumen redacta sunt, opera [et] studio Theodori Bibliandri, ...

Contiene con portada y paginación propias: Confutationes legis mahumeticae, quam uocant alcoranum ... : adiecta quoq[ue] est Lodouici Viuis ... De Mahumete [et] Alcorano eius Censura, ex Libris ipsius De Veritate fidei christiana decerpta ... Item Ioannis Cantacuzeni ... Contra Mahometic[m] fidem chistiana [et] orthodoxa assertio, quatuor libris comprehensa, [et] per Rodolphum Gualtherum ... in latinum ... conuersa.

[La medicina ocupa con razón , desde tiempos antiguos, un lugar distinguido entre las ciencias] : Discurso leido en la Universidad Central en la solemne investidura de doctor en la Facultad de Medicina /

Mode of access: Internet.

Auisos de Parnaso / de Traiano Bocalini ... ; primera y segunda centuria ; traducidos de lengua toscana en española por Fernando Perez de Sousa ...

Mode of access: Internet.

Medulla theologiae moralis : in duos tomos distributa /

Mode of access: Internet.

La pala d'altare di Iacobello e Pier Paolo dalle Masegne nella chiesa di S. Francesco in Bologna /

"Documenti"--P. [27]-50.

Por um beijo : um acto em verso /

Mode of access: Internet.

Tratado de patología externa y medicina operatoria /

Mode of access: Internet.

Historia topográfica, química y médica de La Puda de Monserrat, precedida de algunas generalidades de hidrología general y balnearia /

Mode of access: Internet.

Ioannis Cantacuzeni eximperatoris historiarum libri IV. Graece et latine.

Mode of access: Internet.