To describe the burden, epidemiology and outcomes of co-infections and superinfections occurring in hospitalized patients with coronavirus disease 2019 (COVID-19).
We performed an observational ...cohort study of all consecutive patients admitted for ≥48 hours to the Hospital Clinic of Barcelona for COVID-19 (28 February to 22 April 2020) who were discharged or dead. We describe demographic, epidemiologic, laboratory and microbiologic results, as well as outcome data retrieved from electronic health records.
Of a total of 989 consecutive patients with COVID-19, 72 (7.2%) had 88 other microbiologically confirmed infections: 74 were bacterial, seven fungal and seven viral. Community-acquired co-infection at COVID-19 diagnosis was uncommon (31/989, 3.1%) and mainly caused by Streptococcus pneumoniae and Staphylococcus aureus. A total of 51 hospital-acquired bacterial superinfections, mostly caused by Pseudomonas aeruginosa and Escherichia coli, were diagnosed in 43 patients (4.7%), with a mean (SD) time from hospital admission to superinfection diagnosis of 10.6 (6.6) days. Overall mortality was 9.8% (97/989). Patients with community-acquired co-infections and hospital-acquired superinfections had worse outcomes.
Co-infection at COVID-19 diagnosis is uncommon. Few patients developed superinfections during hospitalization. These findings are different compared to those of other viral pandemics. As it relates to hospitalized patients with COVID-19, such findings could prove essential in defining the role of empiric antimicrobial therapy or stewardship strategies.
IMPORTANCE: Infectious diseases are mostly preventable but still pose a public health threat in the United States, where estimates of infectious diseases mortality are not available at the county ...level. OBJECTIVE: To estimate age-standardized mortality rates and trends by county from 1980 to 2014 from lower respiratory infections, diarrheal diseases, HIV/AIDS, meningitis, hepatitis, and tuberculosis. DESIGN AND SETTING: This study used deidentified death records from the National Center for Health Statistics (NCHS) and population counts from the US Census Bureau, NCHS, and the Human Mortality Database. Validated small-area estimation models were applied to these data to estimate county-level infectious disease mortality rates. EXPOSURES: County of residence. MAIN OUTCOMES AND MEASURES: Age-standardized mortality rates of lower respiratory infections, diarrheal diseases, HIV/AIDS, meningitis, hepatitis, and tuberculosis by county, year, and sex. RESULTS: Between 1980 and 2014, there were 4 081 546 deaths due to infectious diseases recorded in the United States. In 2014, a total of 113 650 (95% uncertainty interval UI, 108 764-117 942) deaths or a rate of 34.10 (95% UI, 32.63-35.38) deaths per 100 000 persons were due to infectious diseases in the United States compared to a total of 72 220 (95% UI, 69 887-74 712) deaths or a rate of 41.95 (95% UI, 40.52-43.42) deaths per 100 000 persons in 1980, an overall decrease of 18.73% (95% UI, 14.95%-23.33%). Lower respiratory infections were the leading cause of infectious diseases mortality in 2014 accounting for 26.87 (95% UI, 25.79-28.05) deaths per 100 000 persons (78.80% of total infectious diseases deaths). There were substantial differences among counties in death rates from all infectious diseases. Lower respiratory infection had the largest absolute mortality inequality among counties (difference between the 10th and 90th percentile of the distribution, 24.5 deaths per 100 000 persons). However, HIV/AIDS had the highest relative mortality inequality between counties (10.0 as the ratio of mortality rate in the 90th and 10th percentile of the distribution). Mortality from meningitis and tuberculosis decreased over the study period in all US counties. However, diarrheal diseases were the only cause of infectious diseases mortality to increase from 2000 to 2014, reaching a rate of 2.41 (95% UI, 0.86-2.67) deaths per 100 000 persons, with many counties of high mortality extending from Missouri to the northeastern region of the United States. CONCLUSIONS AND RELEVANCE: Between 1980 and 2014, there were declines in mortality from most categories of infectious diseases, with large differences among US counties. However, over this time there was an increase in mortality for diarrheal diseases.
Leptomeningeal disease (LMD) is a common complication from solid tumor malignancies with a poor prognosis and limited treatment options. We present a single arm Phase II study of 18 patients with LMD ...receiving combined ipilimumab and nivolumab until progression or unacceptable toxicity (NCT02939300). The primary end point is overall survival at 3 months (OS3). Secondary end points include toxicity, cumulative time-to-progression at 3 months, and progression-free survival. A Simon two-stage design is used to compare a null hypothesis OS3 of 18% against an alternative of 44%. Median follow up based on patients still alive is 8.0 months (range: 0.5 to 15.9 months). The study has met its primary endpoint as 8 of 18 (OS3 0.44; 90% CI: 0.24 to 0.66) patients are alive at three months. One third of patients have experienced one (or more) grade-3 or higher adverse events. Two patients have discontinued protocol treatment due to unacceptable toxicity (hepatitis and colitis, respectively). The most frequent adverse events include fatigue (N = 7), nausea (N = 6), fever (N = 6), anorexia (N = 6) and rash (N = 6). Combined ipilimumab and nivolumab has an acceptable safety profile and demonstrates promising activity in LMD patients. Larger, multicenter clinical trials are needed to validate these results.
To analyze the long-term survival and tumor control outcomes after stereotactic body radiotherapy (SBRT) for metastases limited in number and extent.
We prospectively analyzed the long-term overall ...survival (OS) and cancer control outcomes of 121 patients with five or fewer clinically detectable metastases, from any primary site, metastatic to one to three organ sites, and treated with SBRT. Freedom from widespread distant metastasis (FFDM) was defined as metastatic disease not amenable to local therapy (i.e., resection or SBRT). Prognostic variables were assessed using log-rank and Cox regression analyses.
For breast cancer patients, the median follow-up was 4.5 years (7.1 years for 16 of 39 patients alive at the last follow-up visit). The 2-year OS, FFDM, and local control (LC) rate was 74%, 52%, and 87%, respectively. The 6-year OS, FFDM, and LC rate was 47%, 36%, and 87%, respectively. From the multivariate analyses, the variables of bone metastases (p = .057) and one vs. more than one metastasis (p = .055) were associated with a fourfold and threefold reduced hazard of death, respectively. None of the 17 bone lesions from breast cancer recurred after SBRT vs. 10 of 68 lesions from other organs that recurred (p = .095). For patients with nonbreast cancers, the median follow-up was 1.7 years (7.3 years for 7 of 82 patients alive at the last follow-up visit). The 2-year OS, FFDM, and LC rate was 39%, 28%, and 74%, respectively. The 6-year OS, FFDM, and LC rate was 9%, 13%, and 65%, respectively. For nonbreast cancers, a greater SBRT target volume was significantly adverse for OS (p = .012) and lesion LC (p < .0001). Patients whose metastatic lesions, before SBRT, demonstrated radiographic progression after systemic therapy experienced significantly worse OS compared with patients with stable or regressing disease.
Select patients with limited metastases treated with SBRT are long-term survivors. Future research should address the therapeutic benefit of SBRT for these patients.
OBJECTIVE:To update national population-level pregnancy-related mortality estimates and examine characteristics and causes of pregnancy-related deaths in the United States during 2011–2013.
...METHODS:We conducted an observational study using population-based data from the Pregnancy Mortality Surveillance System to calculate pregnancy-related mortality ratios by year, age group, and race–ethnicity groups. We explored 10 cause-of-death categories by pregnancy outcome during 2011–2013 and compared their distribution with those in our earlier reports since 1987.
RESULTS:The 2011–2013 pregnancy-related mortality ratio was 17.0 deaths per 100,000 live births. Pregnancy-related mortality ratios increased with maternal age, and racial–ethnic disparities persisted with non-Hispanic black women having a 3.4 times higher mortality ratio than non-Hispanic white women. Among causes of pregnancy-related deaths, the following groups contributed more than 10%cardiovascular conditions ranked first (15.5%) followed by other medical conditions often reflecting pre-existing illnesses (14.5%), infection (12.7%), hemorrhage (11.4%), and cardiomyopathy (11.0%). Relative to the most recent report of Pregnancy Mortality Surveillance System data for 2006–2010, the distribution of cause-of-death categories did not change considerably. However, compared with serial reports before 2006–2010, the contribution of hemorrhage, hypertensive disorders of pregnancy, and anesthesia complications declined, whereas that of cardiovascular and other medical conditions increased (population-level percentage comparison).
CONCLUSION:The pregnancy-related mortality ratio and the distribution of the main causes of pregnancy-related mortality have been relatively stable in recent years.
National health-system hospitals of Lombardy faced a heavy burden of admissions for acute respiratory distress syndromes associated with coronavirus disease (COVID-19). Data on patients of European ...origin affected by COVID-19 are limited.
All consecutive patients aged ≥18 years, coming from North-East of Milan's province and admitted at San Raffaele Hospital with COVID-19, between February 25th and March 24th, were reported, all patients were followed for at least one month. Clinical and radiological features at admission and predictors of clinical outcomes were evaluated.
Of the 500 patients admitted to the Emergency Unit, 410 patients were hospitalized and analyzed: median age was 65 (IQR 56–75) years, and the majority of patients were males (72.9%). Median (IQR) days from COVID-19 symptoms onset was 8 (5–11) days. At hospital admission, fever (≥ 37.5 °C) was present in 67.5% of patients. Median oxygen saturation (SpO2) was 93% (range 60–99), with median PaO2/FiO2 ratio, 267 (IQR 184–314). Median Radiographic Assessment of Lung Edema (RALE) score was 9 (IQR 4–16). More than half of the patients (56.3%) had comorbidities, with hypertension, coronary heart disease, diabetes and chronic kidney failure being the most common. The probability of overall survival at day 28 was 66%. Multivariable analysis showed older age, coronary artery disease, cancer, low lymphocyte count and high RALE score as factors independently associated with an increased risk of mortality.
In a large cohort of COVID-19 patients of European origin, main risk factors for mortality were older age, comorbidities, low lymphocyte count and high RALE.
This comparison of outcomes of allogeneic hematopoietic stem-cell transplantation in 1993–1997 and 2003–2007 shows that although patients had a somewhat poorer overall prognosis in the more recent ...period, the rate of death not preceded by relapse, the risk of relapse, and overall mortality decreased.
Infections, graft-versus-host disease (GVHD), and liver, kidney, and pulmonary complications have been associated with high mortality after allogeneic hematopoietic-cell transplantation since the introduction of this procedure 40 years ago.
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Changes in practice have decreased organ toxicity,
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and improved prevention and treatment strategies have decreased the severity of acute GVHD.
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The control of infectious complications has improved since the development of molecular methods for the detection of viral and fungal infections, the use of preemptive treatments, the introduction of new antifungal agents, and the prevention of nosocomial infection.
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To examine the hypothesis that changes in the care of . . .
Transcatheter aortic valve implantation was developed to provide a therapeutic option for patients considered to be ineligible for, and to mitigate mortality and morbidity associated with, high-risk ...surgical aortic valve replacement.
The Edwards SAPIEN Aortic Bioprosthesis European Outcome (SOURCE) Registry was designed to assess initial post commercial clinical transcatheter aortic valve implantation results of the Edwards SAPIEN valve in consecutive patients in Europe. Cohort 1 consists of 1038 patients enrolled at 32 centers. One-year outcomes are presented. Patients with the transapical approach (n=575) suffered more comorbidities than transfemoral patients (n=463) with a significantly higher logistic EuroSCORE (29% versus 25.8%; P=0.007). These groups are different; therefore, outcomes cannot be directly compared. Total Kaplan Meier 1-year survival was 76.1% overall, 72.1% for transapical and 81.1% for transfemoral patients, and 73.5% of surviving patients were in New York Heart Association (NYHA) class I or II at 1 year. Combined transapical and transfemoral causes of death were cardiac in 25.1%, noncardiac in 49.2%, and unknown in 25.7%. Pulmonary complications (23.9%), renal failure (12.5%), cancer (11.4%), and stroke (10.2%) were the most frequent noncardiac causes of death. Multivariable analysis identified logistic EuroSCORE, renal disease, liver disease, and smoking as variables with the highest hazard ratios for 1-year mortality whereas carotid artery stenosis, hyperlipidemia, and hypertension were associated with lower mortality.
The SOURCE Registry is the largest consecutively enrolled registry for transcatheter aortic valve implantation procedures. It demonstrates that with new transcatheter aortic techniques excellent 1-year survival in high-risk and inoperable patients is achievable and provides a benchmark against which future transcatheter aortic valve implantation cohorts and devices can be measured.
Summary Background Young people's health has emerged as a neglected yet pressing issue in global development. Changing patterns of young people's health have the potential to undermine future ...population health as well as global economic development unless timely and effective strategies are put into place. We report the past, present, and anticipated burden of disease in young people aged 10–24 years from 1990 to 2013 using data on mortality, disability, injuries, and health risk factors. Methods The Global Burden of Disease Study 2013 (GBD 2013) includes annual assessments for 188 countries from 1990 to 2013, covering 306 diseases and injuries, 1233 sequelae, and 79 risk factors. We used the comparative risk assessment approach to assess how much of the burden of disease reported in a given year can be attributed to past exposure to a risk. We estimated attributable burden by comparing observed health outcomes with those that would have been observed if an alternative or counterfactual level of exposure had occurred in the past. We applied the same method to previous years to allow comparisons from 1990 to 2013. We cross-tabulated the quantiles of disability-adjusted life-years (DALYs) by quintiles of DALYs annual increase from 1990 to 2013 to show rates of DALYs increase by burden. We used the GBD 2013 hierarchy of causes that organises 306 diseases and injuries into four levels of classification. Level one distinguishes three broad categories: first, communicable, maternal, neonatal, and nutritional disorders; second, non-communicable diseases; and third, injuries. Level two has 21 mutually exclusive and collectively exhaustive categories, level three has 163 categories, and level four has 254 categories. Findings The leading causes of death in 2013 for young people aged 10–14 years were HIV/AIDS, road injuries, and drowning (25·2%), whereas transport injuries were the leading cause of death for ages 15–19 years (14·2%) and 20–24 years (15·6%). Maternal disorders were the highest cause of death for young women aged 20–24 years (17·1%) and the fourth highest for girls aged 15–19 years (11·5%) in 2013. Unsafe sex as a risk factor for DALYs increased from the 13th rank to the second for both sexes aged 15–19 years from 1990 to 2013. Alcohol misuse was the highest risk factor for DALYs (7·0% overall, 10·5% for males, and 2·7% for females) for young people aged 20–24 years, whereas drug use accounted for 2·7% (3·3% for males and 2·0% for females). The contribution of risk factors varied between and within countries. For example, for ages 20–24 years, drug use was highest in Qatar and accounted for 4·9% of DALYs, followed by 4·8% in the United Arab Emirates, whereas alcohol use was highest in Russia and accounted for 21·4%, followed by 21·0% in Belarus. Alcohol accounted for 9·0% (ranging from 4·2% in Hong Kong to 11·3% in Shandong) in China and 11·6% (ranging from 10·1% in Aguascalientes to 14·9% in Chihuahua) of DALYs in Mexico for young people aged 20–24 years. Alcohol and drug use in those aged 10–24 years had an annual rate of change of >1·0% from 1990 to 2013 and accounted for more than 3·1% of DALYs. Interpretation Our findings call for increased efforts to improve health and reduce the burden of disease and risks for diseases in later life in young people. Moreover, because of the large variations between countries in risks and burden, a global approach to improve health during this important period of life will fail unless the particularities of each country are taken into account. Finally, our results call for a strategy to overcome the financial and technical barriers to adequately capture young people's health risk factors and their determinants in health information systems. Funding Bill & Melinda Gates Foundation.
EUROCARE-3 analysed the survival of 1815584 adult cancer patients diagnosed from 1990 to 1994 in 22 European countries. The results are reported in tables, one per cancer site, coded according to the ...International Classification of Diseases (ICD)-9 classification. The main findings of the tables are summarised and commented on in this article. For most solid cancers, wide differences in survival between different European populations were found, as also reported by EUROCARE-1 and EUROCARE-2, despite a remarkable (10%) overall increase in cancer survival from 1985 to 1994. Survival was highest in northern Europe (Sweden, Norway, Finland and Iceland), and fairly good in central–southern Europe (France, Switzerland, Austria and Spain). Survival was particularly low in eastern Europe, low in Denmark and the UK, and fairly low in Portugal and Malta. The mix of tumour stage at diagnosis explains much of the survival differences for cancers of the digestive tract, female reproductive system, breast, thyroid, and also skin melanoma. For tumours of the urinary tract and prostate, the differences were explained mainly by differences in diagnostic criteria and procedures. The case mix by anatomic subsite largely explains differences in survival for head and neck cancers. For oesophagus, pancreas, liver and brain cancer, with poor prognoses, survival differences were limited. Tumours, for which highly effective treatments are available, such as testicular cancer, Hodgkin’s lymphoma and some haematological malignancies, had fairly uniform survival across Europe. Survival for all tumours combined (an indicator of the overall cancer care performance of a nation’s health system) was better in young than old patients, and better in women than men. The affluence of countries influenced overall cancer survival through the availability of adequate diagnostic and treatment procedures, and screening programmes.