Search

Objectives: Rapid delivery of antibiotics is a cornerstone of sepsis therapy, although time targets for specific components of antibiotic delivery are unknown. We quantified time intervals comprising the task of antibiotic delivery and evaluated the association between interval delays and hospital mortality among patients treated in the emergency department for suspected sepsis.Design: Retrospective cohort.Setting: Twelve hospitals in Southeastern United States from 2014 to 2017.Patients: Twenty-four thousand ninety-three encounters among 20,026 adults with suspected sepsis in 12 emergency departments.Measurements and Main Results: We divided antibiotic administration into two intervals: time from emergency department triage to antibiotic order (recognition delay) and time from antibiotic order to infusion (administration delay). We used generalized linear mixed models to evaluate associations between these intervals and hospital mortality. Median time from emergency department triage to antibiotic administration was 3.4 hours (interquartile range, 2.0-6.0 hr), separated into a median recognition delay (time from emergency department triage to antibiotic order) of 2.7 hours(interquartile range, 1.5-4.7 hr) and median administration delay (time from antibiotic order to infusion) of 0.6 hours (0.3-1.2 hr). Adjusting for other risk factors, both recognition delay and administration delay were associated with mortality, but pairwise comparison with a no-delay reference group was not significant for up to 6 hours of recognition delay or up to 1.5 hours of administration delay.Conclusions: Both recognition delays and administration delays were associated with increased hospital mortality, but only for longer delays. These results suggest that both metrics may be important to measure and improve for patients with suspected sepsis but do not support targets less than 1 hour. [ABSTRACT FROM AUTHOR]

Background & Aims Drug induced liver injury ( DILI) is challenging because of the lack of biomarkers to predict mortality. Our aim was to describe miRNA changes in sera of subjects with acute idiosyncratic DILI and determine if levels of miRNAs were associated with 6 month mortality. Methods Clinical data and sera were collected from subjects enrolled in the Drug Induced Liver Injury Network prospective study. mi RNAs were isolated from serum obtained from 78 subjects within 2 weeks of acute DILI and followed up for 6 months or longer. mi RNAs were compared to 40 normal controls and 6 month survivors vs non-survivors. Results The mean age of the DILI cohort was 48 years, and 55% were female. Eleven (14.1%) subjects died, 10 within 6 months of DILI onset, 5 (45%) liver related. Lower levels of mi RNAs-122, -4463 and -4270 were associated with death within 6 months ( P<.05). None of the subjects with mi RNA-122 greater than the median value died within 6 months for a sensitivity of 100% and specificity of 57%. In subjects with a serum albumin <2.8 g/dL and miR-122<7.89 RFU the sensitivity, specificity, positive and negative predictive values for death within 6 months were 100%, 57%, 38% and 100% respectively. Conclusions Serum mi RNA-122 combined with albumin accurately identified subjects who died within 6 months of drug induced liver injury. If confirmed prospectively, mi RNA-122 and albumin may be useful in identifying patients at high risk for mortality or liver transplantation. [ABSTRACT FROM AUTHOR]

Recent reports of converging black and white breast cancer incidence rates have gained much attention, potentially foreshadowing a worsening of the black-white breast cancer mortality disparity. However, these incidence rates also reflect the sum of non-Hispanics and Hispanics that may mask important ethnicity-specific trends. We therefore assessed race- and ethnicity-specific breast cancer trends using the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) 13 Registries Database (1992-2014). Age-period-cohort models projected rates for 2015-2030. Results confirmed merging of age-standardized incidence rates for blacks and whites circa 2012, but not for non-Hispanic black (NHB) and non-Hispanic white (NHW) women. Incidence rates were highest for NHW women (n = 382 290), followed by NHB women (n = 51 074), and then Hispanic white women (n = 48 651). The sample size for Hispanic blacks was too small for analysis (n = 693). Notably, future incidence rates are expected to slowly increase (2015 through 2030) among NHW women (0.24% per year, 95% confidence interval [CI] = 0.17 to 0.32) and slowly decrease for NHB women (-0.14% per year, 95% CI = -0.15 to -0.13). A putative worsening of the black-white mortality disparity, therefore, seems unlikely. Ethnicity matters when assessing race-specific breast cancer incidence rates. [ABSTRACT FROM AUTHOR]

The article discusses a study on the impact of left ventricular hypertrophy (LVH) in chronic obstructive pulmonary disease (COPD) patients by measurement of left ventricular dimensions by echocardiography. It cites an association between elevated left ventricular mass index with significantly increased risk of mortality in COPD patients thus requiring therapeutic interventions to address the modifiable risk factor in COPD patients.

Objectives: Heart failure (HF) is associated with high mortality and frequent hospitalizations. Disease management programs (DMPs) have a favorable impact on patients with HF. No data exist regarding the outcomes of patients discharged from such a program. Methods: We examined the outcome of patients with severe systolic HF who were discharged from a DMP following full clinical and echocardiographic recovery. Data were reviewed for mortality, emergency room visits, hospitalizations, medication adherence and left ventricular ejection fraction (EF). Results: At enrollment and discharge, the mean EF was 19 and 53%, respectively. At follow-up 46.2 months after discharge, 56% of patients had been to the emergency room, 34% were hospitalized a total of 41 times and 20% had died. In the patients who required hospitalization for HF, the mean EF upon rehospitalization had dropped to 23.4%. Conclusions: Many patients with initially severe systolic HF who had an almost full recovery in a multidisciplinary DMP had very poor outcomes once they were discharged from the program. It may be appropriate to revisit the practice of discharging patients from DMPs once they have reached a specific clinical target. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The article presents research on the impact of long-acting bronchodilator therapy and associated exposure to inhaled corticosteroids (ICS) on all-cause and cardiovascular mortality in patients with chronic obstructive pulmonary disease (COPD). Treatment of COPD with long-acting muscarinic antagonists (LAMA) and long-acting beta-agonists (LABA) is examined in this retrospective cohort study.

The article focuses on relevant information pertaining to lower respiratory tract infection (LRTI). An overview of LRTI is provided together with how it can be differentiated from pneumonia. Factors associated with respiratory infection-related mortality are presented along with the most common bacterial causes of LRTI and pneumonia. Guidelines covering investigations and assessment of severity are discussed together with considerations for management and prevention.

Presents information on a study which examined the ingestion of lead and nontoxic shotgun pellets by ducks in the Mississippi Flyway during the 1996 and 1997 hunting season. Comparison on the mortality rate of ducks that died from lead poisoning and non-toxic pellets; Details on the mandatory use of nontoxic pellets in the state; Results and discussion on the study findings.

Background Echinocandins (ECH) are recommended first-line for initial therapy (IT) of candidemia (CD) over fluconazole (FLU) due to their broad spectrum of activity. This recommendation was made prior to widespread implementation of rapid diagnostic testing (RDT), allowing prompt species identification and targeted therapy. The objective of this study was to compare clinical outcomes in patients with CD caused by FLU-susceptible species who received either FLU or ECH as IT. Methods This was a multicenter, retrospective cohort study of adults with CD caused by C. albicans , C. tropicalis , or C. parapsilosis. Patients who received FLU or ECH as IT for at least 48 hours from May 2012 to October 2018 were included. Patients who died within 48 hours of first positive blood culture were excluded. The primary endpoint was the rate of clinical failure (persistent CD for >72 hours, recurrent infection within 30 days, change in therapy, and all-cause mortality within 30 days). Secondary endpoints included 90-day all-cause mortality and time to culture clearance. A subgroup analysis in critically ill patients was conducted. Results Of the 371 patients evaluated, 128 met criteria for inclusion, 57 received FLU and 71 received ECH. Patients in the ECH group had a higher incidence of sepsis at the time of first positive blood culture (45.1% vs. 19.3%, P = 0.002). A line-associated source was more common in the ECH group (56.3%) vs. urinary source in the FLU group (21.1%). C. albicans was most common in both groups (63%). Clinical failure was similar in the FLU and ECH groups (38.6% vs. 35.2%, P = 0.69). 90-day mortality and time to culture clearance (1.6 vs. 1.5 days, P = 0.63) did not yield significant differences. In the subgroup analysis of critically ill patients, there was a trend suggesting higher rate of failure in patients who received FLU vs. an ECH (60.9% vs. 47.7%, P = 0.31), though underpowered to detect such a difference. Length of stay (LOS) was shorter in patients who received FLU (12 vs. 18 days, P = 0.018). Conclusion FLU as IT for FLU-susceptible CD may be a reasonable option in non-critically ill patients in the setting of RDT. This may lead to shorter LOS given the availability of an oral formulation. Additional prospective studies are needed to validate these conclusions. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background Options for treatment of carbapenem-resistant Enterobacteriaceae (CRE) infections were historically limited to antibiotics with limited efficacy and significant toxicities. Ceftazidime/avibactam (CA) and meropenem/vaborbactam (MV) are superior to older regimens; however, a direct comparison of the agents is lacking. This study compared clinical outcomes including recurrence of infection and emergence of drug resistance in patients who received CA vs. MV for CRE infections. Methods This was a multicenter, retrospective cohort study of adults with CRE infections who received CA or MV for ≥72 hours from February 2015 to October 2018. Patients with localized urinary tract infection were excluded. The primary endpoint was clinical success (30-day survival, resolution of signs and symptoms of infection, sterilization of blood cultures within 7 days in patients with bacteremia, absence of recurrent infection). Secondary endpoints included 30- and 90-day mortality, adverse events (AE), recurrent CRE infection within 90 days, and development of resistance in patients with recurrent infection. We conducted a post hoc subgroup analysis in patients with recurrence to compare development of resistance in those who received CA monotherapy, CA combination therapy, and MV monotherapy. Results 131 patients were included (CA: 105 patients, MV: 26 patients), 40% had bacteremia. No statistical difference in clinical success was observed between groups (62% vs. 69%, respectively, P = 0.49). Patients in the CA arm received combination therapy more often than patients in the MV arm (61% vs. 15%, P < 0.01). No difference in 30- and 90-day mortality resulted among groups, but numerically higher rates of AE were observed in the CA group (38% vs. 23%, P = 0.17). In patients with recurrent infection, development of resistance occurred more often with CA monotherapy, though not statistically significant (Table 1). One case of MV resistance was observed in a patient who had received 4 prior courses of MV, but this episode was outside of the study period. Conclusion Clinical success was similar between the groups despite MV being used more often as monotherapy. Development of resistance and rates of AE were higher in the CA group compared with MV therapy. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background: Reduction of premature mortality is a UN Sustainable Development Goal. Unlike other high-income countries, age-adjusted mortality in the USA plateaued in 2010 and increased slightly in 2015, possibly because of rising premature mortality. We aimed to analyse trends in mortality in the USA between 1999 and 2014 in people aged 25-64 years by age group, sex, and race and ethnicity, and to identify specific causes of death underlying the temporal trends.Methods: For this analysis, we used cause-of-death and demographic data from death certificates from the US National Center for Health Statistics, and population estimates from the US Census Bureau. We estimated annual percentage changes in mortality using age-period-cohort models. Age-standardised excess deaths were estimated for 2000 to 2014 as observed deaths minus expected deaths (estimated from 1999 mortality rates).Findings: Between 1999 and 2014, premature mortality increased in white individuals and in American Indians and Alaska Natives. Increases were highest in women and those aged 25-30 years. Among 30-year-olds, annual mortality increases were 2·3% (95% CI 2·1-2·4) for white women, 0·6% (0·5-0·7) for white men, and 4·3% (3·5-5·0) and 1·9% (1·3-2·5), respectively, for American Indian and Alaska Native women and men. These increases were mainly attributable to accidental deaths (primarily drug poisonings), chronic liver disease and cirrhosis, and suicide. Among individuals aged 25-49 years, an estimated 111 000 excess premature deaths occurred in white individuals and 6600 in American Indians and Alaska Natives during 2000-14. By contrast, premature mortality decreased substantially across all age groups in Hispanic individuals (up to 3·2% per year), black individuals (up to 3·9% per year), and Asians and Pacific Islanders (up to 2·6% per year), mainly because of declines in HIV, cancer, and heart disease deaths, resulting in an estimated 112 000 fewer deaths in Hispanic individuals, 311 000 fewer deaths in black individuals, and 34 000 fewer deaths in Asians and Pacific Islanders aged 25-64 years. During 2011-14, American Indians and Alaska Natives had the highest premature mortality, followed by black individuals.Interpretation: Important public health successes, including HIV treatment and smoking cessation, have contributed to declining premature mortality in Hispanic individuals, black individuals, and Asians and Pacific Islanders. However, this progress has largely been negated in young and middle-aged (25-49 years) white individuals, and American Indians and Alaska Natives, primarily because of potentially avoidable causes such as drug poisonings, suicide, and chronic liver disease and cirrhosis. The magnitude of annual mortality increases in the USA is extremely unusual in high-income countries, and a rapid public health response is needed to avert further premature deaths.Funding: US National Cancer Institute Intramural Research Program. [ABSTRACT FROM AUTHOR]

This section presents comments on the article "Racial Disparities in Cancer Survival Among Randomized Clinical Trials of the Southwest Oncology Group," by Albain et al. The authors mention the researchers' assertion that African American patients with breast or other sex-specific cancers have lower survival rates compared with white patients. They pointed out the importance of access to quality cancer care in cancer-specific and all-cause mortality.

Background Based on the early results of the Placement of Aortic Transcatheter Valves (PARTNER) trial, transcatheter aortic valve replacement (TAVR) is an accepted treatment for patients with severe aortic stenosis who are not suitable for surgery. However, little information is available about the late clinical outcomes in such patients. Methods We did this randomised controlled trial at 21 experienced valve centres in Canada, Germany, and the USA. We enrolled patients with severe symptomatic inoperable aortic stenosis and randomly assigned (1:1) them to transfemoral TAVR or to standard treatment, which often included balloon aortic valvuloplasty. Patients and their treating physicians were not masked to treatment allocation. The randomisation was done centrally, and sites learned of the assignment only after a patient had been screened, consented, and entered into the database. The primary outcome of the trial was all-cause mortality at 1 year in the intention-to-treat population, here we present the prespecified findings after 5 years. This study is registered with ClinicalTrials.gov, number NCT00530894. Findings We screened 3015 patients, of whom 358 were enrolled (mean age 83 years, Society of Thoracic Surgeons Predicted Risk of Mortality 11·7%, 54% female). 179 were assigned to TAVR treatment and 179 were assigned to standard treatment. 20 patients crossed over from the standard treatment group and ten withdrew from study, leaving only six patients at 5 years, of whom five had aortic valve replacement treatment outside of the study. The risk of all-cause mortality at 5 years was 71·8% in the TAVR group versus 93·6% in the standard treatment group (hazard ratio 0·50, 95% CI 0·39–0·65; p<0·0001). At 5 years, 42 (86%) of 49 survivors in the TAVR group had New York Heart Association class 1 or 2 symptoms compared with three (60%) of five in the standard treatment group. Echocardiography after TAVR showed durable haemodynamic benefit (aortic valve area 1·52 cm2 at 5 years, mean gradient 10·6 mm Hg at 5 years), with no evidence of structural valve deterioration. Interpretation TAVR is more beneficial than standard treatment for treatment of inoperable aortic stenosis. TAVR should be strongly considered for patients who are not surgical candidates for aortic valve replacement to improve their survival and functional status. Appropriate selection of patients will help to maximise the benefit of TAVR and reduce mortality from severe comorbidities. INSET: Research in context.. [ABSTRACT FROM AUTHOR]