Azithromycin and the risk of cardiovascular death Ray, Wayne A; Murray, Katherine T; Hall, Kathi ...
New England journal of medicine/The New England journal of medicine,
05/2012, Letnik:
366, Številka:
20
Journal Article
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Although several macrolide antibiotics are proarrhythmic and associated with an increased risk of sudden cardiac death, azithromycin is thought to have minimal cardiotoxicity. However, published ...reports of arrhythmias suggest that azithromycin may increase the risk of cardiovascular death.
We studied a Tennessee Medicaid cohort designed to detect an increased risk of death related to short-term cardiac effects of medication, excluding patients with serious noncardiovascular illness and person-time during and shortly after hospitalization. The cohort included patients who took azithromycin (347,795 prescriptions), propensity-score-matched persons who took no antibiotics (1,391,180 control periods), and patients who took amoxicillin (1,348,672 prescriptions), ciprofloxacin (264,626 prescriptions), or levofloxacin (193,906 prescriptions).
During 5 days of therapy, patients taking azithromycin, as compared with those who took no antibiotics, had an increased risk of cardiovascular death (hazard ratio, 2.88; 95% confidence interval CI, 1.79 to 4.63; P<0.001) and death from any cause (hazard ratio, 1.85; 95% CI, 1.25 to 2.75; P=0.002). Patients who took amoxicillin had no increase in the risk of death during this period. Relative to amoxicillin, azithromycin was associated with an increased risk of cardiovascular death (hazard ratio, 2.49; 95% CI, 1.38 to 4.50; P=0.002) and death from any cause (hazard ratio, 2.02; 95% CI, 1.24 to 3.30; P=0.005), with an estimated 47 additional cardiovascular deaths per 1 million courses; patients in the highest decile of risk for cardiovascular disease had an estimated 245 additional cardiovascular deaths per 1 million courses. The risk of cardiovascular death was significantly greater with azithromycin than with ciprofloxacin but did not differ significantly from that with levofloxacin.
During 5 days of azithromycin therapy, there was a small absolute increase in cardiovascular deaths, which was most pronounced among patients with a high baseline risk of cardiovascular disease. (Funded by the National Heart, Lung, and Blood Institute and the Agency for Healthcare Quality and Research Centers for Education and Research on Therapeutics.).
Abstract
We present measurements of the surface density of star formation, the star-forming clump luminosity function, and the clump size distribution function, for the lensed galaxy ...SGAS J111020.0+645950.8 at a redshift of
z
= 2.481. The physical size scales that we probe, radii
r
= 30–50 pc, are considerably smaller scales than have yet been studied at these redshifts. The star formation surface density we find within these small clumps is consistent with surface densities measured previously for other lensed galaxies at similar redshift. Twenty-two percent of the rest-frame ultraviolet light in this lensed galaxy arises from small clumps, with
pc. Within the range of overlap, the clump luminosity function measured for this lensed galaxy is remarkably similar to those of
galaxies. In this galaxy, star-forming regions smaller than 100 pc—physical scales not usually resolved at these redshifts by current telescopes—are important locations of star formation in the distant universe. If this galaxy is representative, this may contradict the theoretical picture in which the critical size scale for star formation in the distant universe is of the order of 1 kpc. Instead, our results suggest that current telescopes have not yet resolved the critical size scales of star-forming activity in galaxies over most of cosmic time.
Users of typical antipsychotic drugs have an increased risk of serious ventricular arrhythmias and sudden cardiac death. However, less is known regarding the cardiac safety of the atypical ...antipsychotic drugs, which have largely replaced the older agents in clinical practice.
We calculated the adjusted incidence of sudden cardiac death among current users of antipsychotic drugs in a retrospective cohort study of Medicaid enrollees in Tennessee. The primary analysis included 44,218 and 46,089 baseline users of single typical and atypical drugs, respectively, and 186,600 matched nonusers of antipsychotic drugs. To assess residual confounding related to factors associated with the use of antipsychotic drugs, we performed a secondary analysis of users of antipsychotic drugs who had no baseline diagnosis of schizophrenia or related psychoses and with whom nonusers were matched according to propensity score (i.e., the predicted probability that they would be users of antipsychotic drugs).
Current users of typical and of atypical antipsychotic drugs had higher rates of sudden cardiac death than did nonusers of antipsychotic drugs, with adjusted incidence-rate ratios of 1.99 (95% confidence interval CI, 1.68 to 2.34) and 2.26 (95% CI, 1.88 to 2.72), respectively. The incidence-rate ratio for users of atypical antipsychotic drugs as compared with users of typical antipsychotic drugs was 1.14 (95% CI, 0.93 to 1.39). Former users of antipsychotic drugs had no significantly increased risk (incidence-rate ratio, 1.13; 95% CI, 0.98 to 1.30). For both classes of drugs, the risk for current users increased significantly with an increasing dose. Among users of typical antipsychotic drugs, the incidence-rate ratios increased from 1.31 (95% CI, 0.97 to 1.77) for those taking low doses to 2.42 (95% CI, 1.91 to 3.06) for those taking high doses (P<0.001). Among users of atypical agents, the incidence-rate ratios increased from 1.59 (95% CI, 1 .03 to 2.46) for those taking low doses to 2.86 (95% CI, 2.25 to 3.65) for those taking high doses (P=0.01). The findings were similar in the cohort that was matched for propensity score.
Current users of typical and of atypical antipsychotic drugs had a similar, dose-related increased risk of sudden cardiac death.
Indications for measurement of NOAC serum levels might include: ▪Measurement of drug levels in patients undergoing urgent surgical procedures. ▪Uncovering accumulation of potentially toxic drug ...levels in patients with CKD or those undergoing dialysis. ▪Detection of potential drug–drug interactions to guide dose adjustment. ▪Evaluation of drug absorption in severely obese patients (body mass index >35 or weight >120 kg) ▪Assessment of patient adherence. 4.3 Interruption and Bridging Anticoagulation Recommendations for Interruption and Bridging AnticoagulationReferenced studies that support new or modified recommendations are summarized in Online Data Supplement 3.CORLOERecommendationsIC Bridging therapy with unfractionated heparin or low-molecular-weight heparin is recommended for patients with AF and a mechanical heart valve undergoing procedures that require interruption of warfarin. Stroke rates are higher in patients with MI and AF than in those without AF (3.1% for those with AF versus 1.3% for those in sinus rhythm) (S7.4-11). ...AF is an independent predictor of poor long-term outcome in patients with ACS (S7.4-13, S7.4-14). Of the patients treated with triple therapy for 1 month in the Bern PCI Registry, 60% were treated with a current-generation drug-eluting stent. 7.12 Device Detection of AF and Atrial Flutter (New) Recommendations for Device Detection of AF and Atrial FlutterReferenced studies that support new recommendations are summarized in Online Data Supplement 9.CORLOERecommendationsIB-NR In patients with cardiac implantable electronic devices (pacemakers or implanted cardioverter-defibrillators), the presence of recorded atrial high-rate episodes (AHREs) should prompt further evaluation to document clinically relevant AF to guide treatment decisions (S7.12-1–S7.12-5).IIaB-R In patients with cryptogenic stroke (i.e., stroke of unknown cause) in whom external ambulatory monitoring is inconclusive, implantation of a cardiac monitor (loop recorder) is reasonable to optimize detection of silent AF (S7.12-6). Presidents and Staff American College of Cardiology C. Michael Valentine, MD, FACC, President Timothy W. Attebery, DSc, MBA, FACHE, Chief Executive Officer William J. Oetgen, MD, MBA, FACC, FACP, Executive Vice President, Science, Education, Quality, and Publishing MaryAnne Elma, MPH, Senior Director, Science, Education, Quality, and Publishing Amelia Scholtz, PhD, Publications Manager, Science, Education, Quality, and Publishing American College of Cardiology/American Heart Association Katherine A. Sheehan, PhD, Director, Guideline Strategy and Operations Abdul R. Abdullah, MD, Senior Manager, Guideline Science Thomas S. D. Getchius, Manager, Guideline Science Zainab Shipchandler, MPH, Associate Guideline Advisor American Heart Association Ivor J. Benjamin, MD, President Nancy Brown, Chief Executive Officer Rose Marie Robertson, MD, FAHA, Chief Science and Medicine Officer Gayle R. Whitman, PhD, RN, FAHA, FAAN, Senior Vice President, Office of Science Operations Anne Leonard, MPH, RN, CCRC, FAHA, Senior Science and Medicine Advisor, Office of Science Operations Jody Hundley, Production and Operations Manager, Scientific Publications, Office of Science OperationsAppendix 1 Author Relationships With Industry and Other Entities (Relevant)—2019 AHA/ACC/HRS Focused Update of the 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation (July 2018) Appendix 2 Abbreviated Reviewer Relationships With Industry and Other Entities—2019 AHA/ACC/HRS Focused Update of the 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation (August 2018)∗ Table 1 Applying Class of Recommendation and Level of Evidence to Clinical Strategies, Interventions, Treatments, or Diagnostic Testing in Patient Care* (Updated August 2015)
Long-acting opioids increase the risk of unintentional overdose deaths but also may increase mortality from cardiorespiratory and other causes.
To compare all-cause mortality for patients with ...chronic noncancer pain who were prescribed either long-acting opioids or alternative medications for moderate to severe chronic pain.
Retrospective cohort study between 1999 and 2012 of Tennessee Medicaid patients with chronic noncancer pain and no evidence of palliative or end-of-life care.
Propensity score-matched new episodes of prescribed therapy for long-acting opioids or either analgesic anticonvulsants or low-dose cyclic antidepressants (control medications).
Total and cause-specific mortality as determined from death certificates. Adjusted hazard ratios (HRs) and risk differences (difference in incidence of death) were calculated for long-acting opioid therapy vs control medication.
There were 22,912 new episodes of prescribed therapy for both long-acting opioids and control medications (mean SD age, 48 11 years; 60% women). The long-acting opioid group was followed up for a mean 176 days and had 185 deaths and the control treatment group was followed up for a mean 128 days and had 87 deaths. The HR for total mortality was 1.64 (95% CI, 1.26-2.12) with a risk difference of 68.5 excess deaths (95% CI, 28.2-120.7) per 10,000 person-years. Increased risk was due to out-of-hospital deaths (154 long-acting opioid, 60 control deaths; HR, 1.90; 95% CI, 1.40-2.58; risk difference, 67.1; 95% CI, 30.1-117.3) excess deaths per 10,000 person-years. For out-of-hospital deaths other than unintentional overdose (120 long-acting opioid, 53 control deaths), the HR was 1.72 (95% CI, 1.24-2.39) with a risk difference of 47.4 excess deaths (95% CI, 15.7-91.4) per 10,000 person-years. The HR for cardiovascular deaths (79 long-acting opioid, 36 control deaths) was 1.65 (95% CI, 1.10-2.46) with a risk difference of 28.9 excess deaths (95% CI, 4.6-65.3) per 10,000 person-years. The HR during the first 30 days of therapy (53 long-acting opioid, 13 control deaths) was 4.16 (95% CI, 2.27-7.63) with a risk difference of 200 excess deaths (95% CI, 80-420) per 10,000 person-years.
Prescription of long-acting opioids for chronic noncancer pain, compared with anticonvulsants or cyclic antidepressants, was associated with a significantly increased risk of all-cause mortality, including deaths from causes other than overdose, with a modest absolute risk difference. These findings should be considered when evaluating harms and benefits of treatment.
Benzodiazepine hypnotics and the related nonbenzodiazepine hypnotics (z-drugs) are among the most frequently prescribed medications for older adults. Both can depress respiration, which could have ...fatal cardiorespiratory effects, particularly among patients with concurrent opioid use. Trazodone, frequently prescribed in low doses for insomnia, has minimal respiratory effects, and, consequently, may be a safer hypnotic for older patients. Thus, for patients beginning treatment with benzodiazepine hypnotics or z-drugs, we compared deaths during periods of current hypnotic use, without or with concurrent opioids, to those for comparable patients receiving trazodone in doses up to 100 mg. The retrospective cohort study in the United States included 400,924 Medicare beneficiaries 65 years of age or older without severe illness or evidence of substance use disorder initiating study hypnotic therapy from January 2014 through September 2015. Study endpoints were out-of-hospital (primary) and total mortality. Hazard ratios (HRs) were adjusted for demographic characteristics, psychiatric and neurologic disorders, cardiovascular and renal conditions, respiratory diseases, pain-related diagnoses and medications, measures of frailty, and medical care utilization in a time-dependent propensity score-stratified analysis. Patients without concurrent opioids had 32,388 person-years of current use, 260 (8.0/1,000 person-years) out-of-hospital and 418 (12.9/1,000) total deaths for benzodiazepines; 26,497 person-years,150 (5.7/1,000) out-of-hospital and 227 (8.6/1,000) total deaths for z-drugs; and 16,177 person-years,156 (9.6/1,000) out-of-hospital and 256 (15.8/1,000) total deaths for trazodone. Out-of-hospital and total mortality for benzodiazepines (respective HRs: 0.99 95% confidence interval, 0.81 to 1.22, p = 0.954 and 0.95 0.82 to 1.14, p = 0.513 and z-drugs (HRs: 0.96 0.76 to 1.23, p = 0.767 and 0.87 0.72 to 1.05, p = 0.153) did not differ significantly from that for trazodone. Patients with concurrent opioids had 4,278 person-years of current use, 90 (21.0/1,000) out-of-hospital and 127 (29.7/1,000) total deaths for benzodiazepines; 3,541 person-years, 40 (11.3/1,000) out-of-hospital and 64 (18.1/1,000) total deaths for z-drugs; and 2,347 person-years, 19 (8.1/1,000) out-of-hospital and 36 (15.3/1,000) total deaths for trazodone. Out-of-hospital and total mortality for benzodiazepines (HRs: 3.02 1.83 to 4.97, p < 0.001 and 2.21 1.52 to 3.20, p < 0.001) and z-drugs (HRs: 1.98 1.14 to 3.44, p = 0.015 and 1.65 1.09 to 2.49, p = 0.018) were significantly increased relative to trazodone; findings were similar with exclusion of overdose deaths or restriction to those with cardiovascular causes. Limitations included composition of the study cohort and potential confounding by unmeasured variables. In US Medicare beneficiaries 65 years of age or older without concurrent opioids who initiated treatment with benzodiazepine hypnotics, z-drugs, or low-dose trazodone, study hypnotics were not associated with mortality. With concurrent opioids, benzodiazepines and z-drugs were associated with increased out-of-hospital and total mortality. These findings indicate that the dangers of benzodiazepine-opioid coadministration go beyond the documented association with overdose death and suggest that in combination with opioids, the z-drugs may be more hazardous than previously thought.
Abstract
Using the combined resolving power of the
Hubble Space Telescope
and gravitational lensing, we resolve star-forming structures in a
galaxy on scales much smaller than the usual kiloparsec ...diffraction limit of
HST
. SGAS J111020.0+645950.8 is a clumpy, star-forming galaxy lensed by the galaxy cluster SDSS J1110+6459 at
, with a total magnification
across the entire arc. We use a hybrid parametric/non-parametric strong lensing mass model to compute the deflection and magnification of this giant arc, reconstruct the light distribution of the lensed galaxy in the source plane, and resolve the star formation into two dozen clumps. We develop a forward-modeling technique to model each clump in the source plane. We ray-trace the model to the image plane, convolve with the instrumental point-spread function (PSF), and compare with the GALFIT model of the clumps in the image plane, which decomposes clump structure from more extended emission. This technique has the advantage, over ray-tracing, of accounting for the asymmetric lensing shear of the galaxy in the image plane and the instrument PSF. At this resolution, we can begin to study star formation on a clump-by-clump basis, toward the goal of understanding feedback mechanisms and the buildup of exponential disks at high redshift.
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