Increase In Death Rate Research Articles

What are the Pathological Concerns and Limitations of Current Drug-coated Balloon Technology?

The use of endovascular therapy for peripheral artery disease and coronary artery disease has increased and spread worldwide and is considered as the foremost, guideline-based invasive treatment. Drug-coated balloons (DCBs) utilise anti-proliferative drugs similar to drug-eluting stents; however, the do not leave any permanent metallic scaffold. Excipients and drug formulations play a crucial role in innovative DCB technologies and allow for treatment of lesions where stents are not suitable. Although the significance of downstream embolic effects after DCB use remains uncertain, several preclinical studies suggest such side effects might pose safety concerns. Recently, a meta-analysis of randomised controlled trials of paclitaxel devices suggested an association between increased mortality and paclitaxel device use. Subsequently, unfavourable criticism of paclitaxel devices attracted much attention and gave rise to a discussion about the safety of such devices. In this review, we will focus on the novel DCB technologies from the standpoint of preclinical studies and clinical trials, as well as discuss current controversies regarding the increase in death rates from paclitaxel-coated DCBs versus control devices seen in a recent meta-analysis of randomised controlled clinical trials.

Incidence of Fall Accident in Suseong District of Daegu Metropolitan City, Republic of Korea

Background: Among the various types of injuries in the world, falls are one of the most important health problem related issues, especially for modern societies with aged populations. Korea, a country where industrialization and urbanization have made building structures and living spaces complex, has also been facing the emerging danger of falls. So, among the causes of death due to unintended injury accidents, falls are second reason of injury worldwide following traffic accidents. Falls are important causes in increase of morbidity rates, hospitalization rates, death rates and medical fees. Falls are not unfortunate accidents rather, they are preventable and predictable. Therefore, we needs to identify the incidence and causes of falls. Objectives The purposes of this study are to identify the incidence of fall accident in Suseong district of Daegu metropolitan city and to develop the evidence based fall accident program for Suseong district. Methods: In order to identify the incidence of falls of the citizens of Suseong district, authors analyzed the annual report on the causes of death statistics from the National Statistical Office and the injury data from Fire Station 119 Rescue Activity Daily Record. As well, in order to understand the current state of falls in households, an epidemiological survey was conducted to people from 1,977 households in Suseong district by home visited. The collected data were analyzed using SPSS WIN 17.0 based on the research objectives, and the frequency and percentages were investigated. Results: According to the data from the National Statistical Office, the death rate due to falls was 4.1 people (per 100,000 persons). In terms of age, elders aged 65 and over was the highest death rate with 17.0 out of 100,000 persons. In the injury transfer rate analyzed from rescue records of 119, accidents due to falls were highest with 2.3 cases out of 1,000 persons. In terms of age, elders aged 65 and over was the highest injury rate with 9.2 out of 1000 persons. After analyzing the injury causes of the citizens of Suseong district through household visits, the highest rate of falls was 43.7%, followed by traffic accidents (24.9%) and bump injuries (21.1%). Therefore, we were able to confirm once again that the fall prevention program is a very important program for improving the safety of citizens. Housework (29.4%) was the most common cause of falls. The most common places for falls were living rooms (22.6%), followed by restrooms and entrance. Conclusion: Mortality due to falls can be reduced through education, environmental improvements, and safety policies. It is necessary to conduct preventive education for elderly people who are vulnerable to falls, and to apply gymnastic exercises that can enhance balance and lower extremity muscle strength. In addition to, it is necessary to strengthen regulations on safety facilities at the senior community center. Therefore the government and related organizations should put fall prevention as the primary task and spread an effective evidence-based fall prevention program based on result of research.

Trends in adverse drug reaction-related hospitalisations over 13 years in New South Wales, Australia.

Adverse drug reactions (ADR) are severe problems in global public health, and result in high mortality and morbidity. Various trends of ADR-related hospitalisations have been studied in many countries, while estimates of the trends in Australia are limited. To examine trends in ADR-related hospitalisations in New South Wales (NSW). Data were extracted from the Admitted Patient Data Collection, a census of hospital separations in NSW. We estimated age-adjusted rates of ADR-related hospitalisation between 1 July 2001 and 30 June 2014 and rates by patient characteristics, main therapeutic medication groups and clinical condition groups that warranted the hospitalisation. We used the percentage change annualised estimator to evaluate rates over time. A total of 315 274 NSW residents admitted for urgent care of ADR was identified. The age-adjusted rates of ADR-related hospitalisations nearly doubled and increased by 5.8% (95% CI: 5.0-6.6%) per annum, with an in-hospital death rate increase of 2.4% (1.6-3.3%). Agranulocytosis (2.7%), nausea and vomiting (2.4%) and heart failure (2.4%) were the most common conditions that led to ADR-related hospitalisations over 13 years, with acute renal failure (1.4%) recently emerging as the leading adverse condition. Participants aged between 65 and 84 years accounted for nearly half of ADR hospitalisations (45.6%), with age-adjusted rate increasing from 103.9 in 2001-2002 to 189.0 per 100 000 NSW residents in 2013-2014. Anticoagulants (13.5%) were the most common medications contributing to ADR-related hospitalisation, followed by opioid analgesics (9.6%). ADR-related hospitalisation remains a population health burden, with significant increase over time. The findings call for continuing efforts to prevent ADR, especially among high-risk populations, such as older people.

Drug and Opioid-Involved Overdose Deaths - United States, 2013-2017.

The 63,632 drug overdose deaths in the United States in 2016 represented a 21.4% increase from 2015; two thirds of these deaths involved an opioid (1). From 2015 to 2016, drug overdose deaths increased in all drug categories examined; the largest increase occurred among deaths involving synthetic opioids other than methadone (synthetic opioids), which includes illicitly manufactured fentanyl (IMF) (1). Since 2013, driven largely by IMF, including fentanyl analogs (2-4), the current wave of the opioid overdose epidemic has been marked by increases in deaths involving synthetic opioids. IMF has contributed to increases in overdose deaths, with geographic differences reported (1). CDC examined state-level changes in death rates involving all drug overdoses in 50 states and the District of Columbia (DC) and those involving synthetic opioids in 20 states, during 2013-2017. In addition, changes in death rates from 2016 to 2017 involving all opioids and opioid subcategories,* were examined by demographics, county urbanization levels, and by 34 states and DC. Among 70,237 drug overdose deaths in 2017, 47,600 (67.8%) involved an opioid.† From 2013 to 2017, drug overdose death rates increased in 35 of 50 states and DC, and significant increases in death rates involving synthetic opioids occurred in 15 of 20 states, likely driven by IMF (2,3). From 2016 to 2017, overdose deaths involving all opioids and synthetic opioids increased, but deaths involving prescription opioids and heroin remained stable. The opioid overdose epidemic continues to worsen and evolve because of the continuing increase in deaths involving synthetic opioids. Provisional data from 2018 indicate potential improvements in some drug overdose indicators;§ however, analysis of final data from 2018 is necessary for confirmation. More timely and comprehensive surveillance data are essential to inform efforts to prevent and respond to opioid overdoses; intensified prevention and response measures are urgently needed to curb deaths involving prescription and illicit opioids, specifically IMF.

Rationalization of biological tests in cardiology department

Laboratory tests usually complete clinical examinations for diagnostic, prognostic and even therapeutical care. However, French doctors might too easily prescribe such examinations without knowing their cost. As a matter of fact, the prescription is sometimes excessive or unjustified. Cardiology is not an exception, with costly laboratory tests. To show that the relevance of each additional test prescription, in a cardiology department, allows a significant reduction of the examination volumes and costs, with no prejudicial effect on patients' care. Two consecutive 2-year periods, between November 1st 2011 and October 31st 2015, - before and after the development of a policy of rationalization of additional tests - were compared. All the patients admitted in our cardiology department during these periods were prospectively included.During 4 years, the volume and the cost of prescription of the most frequent laboratory tests were studied, considering successive half-year periods. After rationalizing, there was a significant reduction of prescription of the laboratory tests (CBC -72%, BNP -92%, troponin -82%, CRP -89%, liver test -87%, lipid status -80%, TSH -80%, p<0.01).No serious adverse events were reported and no death rate increase was noticed. Rationalizing allows a significant reduction of complementary examinations, with no additional risk for the patient.

Differences in Genomic Patterns between African Americans and Whites with Acute Myeloid Leukemia

Differences in Genomic Patterns Between African Americans and Whites with Acute Myeloid LeukemiaAbstract ID: 114273Background:In the United States, racial disparities in acute myeloid leukemia (AML) include African Americans (AAs) presenting at an earlier age compared to whites (a median of 48 vs 55 years) and having worse outcomes, with a 12% increased risk of death. Differences persist in studies demonstrating similar induction and post-remission treatment, treatment intensity, and follow-up for AA and whites, controlling for access to health care. To determine if disease biology plays a role, we studied the genomic profile of AA and white patients (pts) with AML.Methods:Pts diagnosed with and treated for AML at Cleveland Clinic between 2001-2013 with next generation target sequencing (NGS) available and pts from the The Cancer Genome Atlas (TCGA) with NGS available were included. Genomic panels of 60 gene mutations that are commonly mutated in AML and other myeloid malignancies were sequenced. Cytogenetic risk classification was per CALBG/Alliance criteria. Functional molecular groups were classified as follows: cohesion, splicing, DNA methylation, transcription, chromatin modifications, receptor/kinases, RAS pathway, RNA helicase, and tumor suppressor (see Table 1). Baseline characteristics and mutation incidence were compared between racial cohorts using Wilcoxon rank sum and chi-square tests. Survival analyses used log-rank and Cox proportional hazards regression.Results:Of 320 pts analyzed, 25 (7.8%) were AA and 295 (92.2%) were whites. AAs were younger than whites at diagnosis (median age of 59 [range 25-80] vs 65 years [21-100], P=.03) but had similar sex distribution (52% male vs 53.6%, P=1.0), median WBC (5.91 vs 5.29, P=.73) and blast percentage (47 vs 39, P=.30). Among AA pts, 18 (75%) had intermediate-risk cytogenetics compared to 222 whites (76.6%); 6 (25%) had unfavorable cytogenetics compared to 68 whites (23.4%, P=1.0). Overall survival in AA vs whites was similar at a median of 10.6 (range .13-63) vs 14.6 months (range .03-114) (P = .50), and when controlling for cytogenetics and age (HR 1.05, 95% CI 0.60-1.85, P =.87).Overall, the most frequently mutated genes were NPM1 (seen in 74% of all pts), DNMT3A (63%), TET2 (50%), FLT3 (44%), RUNX1 (35%), ASXL1 (34%), IDH2 (27%), NRAS (25%), STAG2 (25%), IDH1 (23%), TP53 (23%), U2AF1 (21%). The median number of mutations per sample was 2 (range 0 - 15) and there was no difference between AA and whites (median 2 [range 0-6] vs 2 [0-15], P= 0.35). AA were more likely to have mutations in RAD21 (13 vs 2%, P=.019) and TP53 (20 vs 6%, P=.03), and less likely to present with TET2 (0 vs 17%, P=0.050). When mutations were grouped by function, mutations in genes for methylation were less common in AA (n=2, 15.4%) vs whites (n=78, 49.4%) (P=.038). No other differences were seen between groups when mutations were grouped by function, see Table 1.Stratified analysis by sex, comparing AA males to white males, revealed that the prevalence of RAD21 was higher in AA males (23 vs 2%, P<.001). TP53 was mutated in 23% of AA males vs 7.6% of white males (P=.166).Survival analyses, adjusting for age, estimated a 10-fold increase in death rate for AA with a RAD21 mutation compared to whites with a RAD21 mutation (HR 0.1, 95% CI 0.01-1.82, P=.12). Mutations in TP53 were associated with a non-significant survival difference in AA vs whites (HR 0.68, 95% CI 0.24-1.90, P=.46)Conclusion:AA pts with AML are younger at diagnosis compared to whites and more likely to have TP53 (consistent with previous studies showing higher rates of complex cytogenetics) and RAD21 mutations, but less likely to have TET2 mutations and methylation gene mutations. Some molecular abnormalities may be sex-specific. RAD21 is more common in AA males than white males and may contribute to excess death rates. These findings may help explain worse survival in AA and may suggest differential therapeutic efficacy. [Display omitted] DisclosuresNazha:MEI: Consultancy. Carraway:Agios: Consultancy, Speakers Bureau; Jazz: Speakers Bureau; Balaxa: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; FibroGen: Consultancy; Novartis: Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees. Gerds:Celgene: Consultancy; Apexx Oncology: Consultancy; Incyte: Consultancy; CTI Biopharma: Consultancy. Advani:Amgen: Research Funding; Pfizer: Honoraria, Research Funding; Glycomimetics: Consultancy; Novartis: Consultancy. Maciejewski:Ra Pharmaceuticals, Inc: Consultancy; Apellis Pharmaceuticals: Consultancy; Apellis Pharmaceuticals: Consultancy; Alexion Pharmaceuticals, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Ra Pharmaceuticals, Inc: Consultancy; Alexion Pharmaceuticals, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Sekeres:Celgene: Membership on an entity's Board of Directors or advisory committees; Opsona: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Opsona: Membership on an entity's Board of Directors or advisory committees.

Opioid Use Is NOT Associated with in-Hospital Mortality Among Patients with Sickle CELL Disease in the United States: Findings from the National Inpatient Sample

BackgroundVaso-occlusive pain crises account for the majority of hospitalizations in patients with sickle cell disease (SCD), and opioids are the mainstay of chronic pain control in SCD. However, a marked increase in opioid-related overdoses and deaths in the United States (US) - ‘the US opioid epidemic’ - has been documented since 2000. We sought to: i) examine temporal trends in hospitalization rates and in-hospital mortality rates among adults with SCD since the onset of the US opioid epidemic, and ii) compare in-hospital mortality rates for SCD with the rates of opioid prescription-related deaths in the non-SCD general population since the onset of the US opioid epidemic.MethodsWe obtained data from the National Inpatient Sample from 1998 through 2013. We identified hospitalizations for patients with sickle cell disease using discharge diagnoses (ICD-9-CM) codes 282.41, 282.42, 282.60, 282.61, 282.62, 282.63, 282.64, 282.68, and 282.69. We examined hospitalization and in-hospital mortality rates and trends for the entire sample of SCD patients, as well as by the following age groups: 0-17 years, 18-44 years, 45-64 years, and ≥65 years. We also examined in-hospital mortality hospitalization trends by U.S Census Bureau regions viz: Northeast, Midwest, South, and West. Survey weights were applied in estimating the population-based hospitalization rates. We utilized annual mid-year population figures provided by the US Census Bureau as the reference population for each year. Survey analysis and trend analyses were performed with Stata 14.2®(StataCorp, College Station, TX), and Joinpoint Regression Program 4.2.02® (National Cancer Institute), respectively.ResultsThere were 1,755,220 hospitalizations among SCD patients in the US from 1998 to 2013. Hospitalization rates for SCD patients initially declined annually by 9.9% (95% CI: 4.0, 15.5) from 39/100,000 persons in 1998 to 27/100,000 persons in 2002, but no significant temporal trends were noted from 2002 to 2013 (figure 1).However, among young adults with SCD (18-44 years), there was a significant annual increase in hospitalization rates by 3.8% (95% CI: 2.4%, 5.2) from 43/100,000 persons in 2002 to 71/100,000 persons in 2013. Elderly SCD patients (≥65 years) also had a significant annual increase in hospitalization rates by 6.5% (95% CI: 2.9%, 10.2%) from 2.7/100,000 persons in 1998 to 5.4/100,000 persons in 2013. The only region with a significant increase in SCD hospitalization rate was the South with an annual increase of 3.5% (95% CI: 0.6, 6.4) from 2001 through 2011.There was no significant increase in-hospital SCD mortality, in contrast to the 350% increase in non-SCD opioid prescription-related death rates in the US from 1999 through 2013 (figure 2).ConclusionHospitalization rates are rising among most age-groups of adults with SCD. The reasons for this finding are unclear but the rising rates may reflect the fragmentation of care for SCD in adults as well as age-related increases in pain-related comorbidities and SCD complications as SCD patients live longer. However, there has been no associated increase in-hospital SCD mortality, supporting extant data which suggest that the rate of opioid-related deaths in SCD is low, and the use of opioids for pain control may be considered relatively safe in the SCD population. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

De-unionization and Drug Death Rates

Drug death rates in the United States have risen dramatically in recent years, sparking urgent discussions about causes. Most of these discussions have centered on supply-side issues, such as doctors overprescribing pain killers. However, there is increasing recognition of the need to go beyond proximate causes and to consider larger social forces that bear on the demand for pain-relieving drugs. Informed by sociological research linking labor unions to community health, we empirically examined the relationship between union density and drug death rates for the years 1999 to 2016. We found that states experiencing greater declines in unionization also tended to experience greater increases in drug deaths. Estimates from our fixed-effects models suggested that a one standard deviation decrease in union density was associated with a 42 percent increase in drug death rates over the period. Although the incorporation of a variety of statistical controls reduced this association, it remained negative and significant. Beyond variation in the availability of substances to misuse, our findings underscore the importance of considering institutional decline and broader social conditions as deeply relevant for contemporary drug death trends.

Clinical Applications in Alzheimer's Disease

This paper is focused to reflect the changes in burn mortality and events leading to fatal burn injuries.Two national community-based cross sectional health and injury surveys were done in Bangladesh during 2003 and 2016. Similar methodology had been followed in both the surveys. Multistage cluster sampling method considering probability-proportional-to-size strategy was used in both the surveys to obtain the desired sample. A pretested semi-structured questionnaire was deployed to identify causes of mortality and morbidity among the population. Verbal autopsy method was used to ascertain the cause of death.An estimated 5000 deaths occurred during 2002 due to burn, whereas, around 9000 deaths were caused by burn in 2015 reflected by the death rates 3.5 and 5.7 per 100,000 population in respective years. This study found an increase in death rates in all age groups from 2002 to 2015. Electrocution caused the highest burn deaths in this country, especially among males and in rural areas. The death toll by this particular mechanism has increased by more than two folds within a decade. The place of occurrence of fatal burn injuries has also shifted from home to the outside of the home especially in the agricultural fields.Burn death is an emerging cause of injury deaths in Bangladesh. Further researches are required to explore the epidemiology of electrocution deaths in Bangladesh and design effective interventions.

ISY7-2 - Key roles of immune-check inhibitors for first- and second line treatment for advanced NSCLC

Early development of anti-PD-1/PD-L1 in advanced NSCLC demonstrated long lasting responses translating into long term survival for approximately 15% of patients. Five phase III studies including mainly unselected patients compared anti-PD-1/PD-L1 as single agent with docetaxel in 2nd line setting. Four studies showed a significant OS benefit, doubling 2-year survival rates and a better tolerance profile with around 10% grade 3-4 immune-related adverse events. The lack of PFS improvement and an increase in the early death rates in one trial underscored the need for a better patients selection. PD-L1 expression appears as an enrichment factor correlated with the probability of response and the magnitude of OS benefit. The development of pembrolizumab has established more than 50% of tumor cells expressing PD-L1 as the best cutoff for a high probability of response. Other predictive biomarkers are under investigation, notably the tumor mutational burden. In 1st line setting, the Keynote 024 trial compared pembrolizumab to platinum-based doublet in tumors with high PD-L1 expression and demonstrated a large OS benefit with 30 months median survival compared to 14.2 months in the control arm despite a cross over in 62% of patients, establishing pembrolizumab as the new standard of care for these patients. The 2nd lead combined anti-CTLA4 and anti-PD1/PD-L1 with an announcement of a significant PFS benefit for ipilimumab-nivolumab combination compared to 1st line chemotherapy in case of TMB > 10 mutations/Mb. The 3rd lead in 1st line setting assessed in unselected patients combinations of cytotoxic chemotherapy and anti-PD-1/PD-L1. The addition of atezolizumab to carboplatin-paclitaxel-bevacizumab provided a significant PFS improvement while the combination of pembrolizumab to a platinum-pemetrexed regimen improved both PFS and OS. These new combinations will change the NSCLC treatment algorithm, underscoring the need of predictive biomarkers for patients selection.

Mortality due to cirrhosis and liver cancer in the United States, 1999-2016: observational study

ObjectiveTo describe liver disease related mortality in the United States during 1999-2016 by age group, sex, race, cause of liver disease, and geographic region.DesignObservational cohort study.SettingDeath certificate data from the...

Age exerts a continuous effect in the outcomes of Asian breast cancer patients treated with breast-conserving therapy

BackgroundAsians are diagnosed with breast cancer at a younger age than Caucasians are. We studied the effect of age on locoregional recurrence and the survival of Asian breast cancer patients treated with breast-conserving therapy.MethodsMedical records of 2492 patients treated with breast-conserving therapy between 1989 and 2012 were reviewed. The Kaplan–Meier method was used to estimate locoregional recurrence, breast cancer-free survival, and breast cancer-specific survival rates. These rates were then compared using log-rank tests. Outcomes and age were modeled by Cox proportional hazards. Fractional polynomials were then used to test for non-linear relationships between age and outcomes.ResultsPatients ≤ 40 years old were more likely to have locoregional recurrence than were older patients (Hazard ratio [HR] = 2.32, P < 0.001). Locoregional recurrence rates decreased year-on-year by 4% for patients with luminal-type breast cancers, compared with 8% for those with triple-negative cancers. Similarly, breast cancer-free survival rates increased year-on-year by 4% versus 8% for luminal-type and triple-negative cancers, respectively. Breast cancer-specific survival rates increased with age by 5% year-on-year. Both breast cancer-free survival and breast cancer-specific survival rates in patients with luminal cancers exhibited a non-linear (“L-shaped”) relationship—where decreasing age at presentation was associated with escalating risks of relapse and death. The influence of age on overall survival was confounded by competing non-cancer deaths in older women, resulting in a “U-shaped” relationship.ConclusionsYoung Asian breast cancer patients have a continuous year-on-year increase in rates of disease relapse and cancer deaths compared with older patients with no apparent threshold.

Changes in burn mortality in Bangladesh: Findings from Bangladesh Health and Injury Survey (BHIS) 2003 and 2016

PurposeThis paper is focused to reflect the changes in burn mortality and events leading to fatal burn injuries. MethodsTwo national community-based cross sectional health and injury surveys were done in Bangladesh during 2003 and 2016. Similar methodology had been followed in both the surveys. Multistage cluster sampling method considering probability-proportional-to-size strategy was used in both the surveys to obtain the desired sample. A pretested semi-structured questionnaire was deployed to identify causes of mortality and morbidity among the population. Verbal autopsy method was used to ascertain the cause of death. ResultsAn estimated 5000 deaths occurred during 2002 due to burn, whereas, around 9000 deaths were caused by burn in 2015 reflected by the death rates 3.5 and 5.7 per 100,000 population in respective years. This study found an increase in death rates in all age groups from 2002 to 2015. Electrocution caused the highest burn deaths in this country, especially among males and in rural areas. The death toll by this particular mechanism has increased by more than two folds within a decade. The place of occurrence of fatal burn injuries has also shifted from home to the outside of the home especially in the agricultural fields. ConclusionBurn death is an emerging cause of injury deaths in Bangladesh. Further researches are required to explore the epidemiology of electrocution deaths in Bangladesh and design effective interventions.

Systematic Review and Meta-analysis of Outcomes of Patients With Subsegmental Pulmonary Embolism With and Without Anticoagulation Treatment.

This systematic review addresses the controversy over the decision to anticoagulate patients with subsegmental pulmonary embolism (SSPE). We searched Ovid MEDLINE, PubMed, Embase, the Cochrane Library, Scopus, Web of Science, ClinicalTrials.gov, Google Scholar, and bibliographies in March 2017. Two authors reviewed and retained papers with symptomatic patients who underwent computerized tomographic pulmonary angiography and had sufficient information to determine SSPE; decision to treat (or not) with systemic anticoagulation; and outcomes of bleeding, venous thromboembolism (VTE) recurrence, and death. Papers were assessed for selection and publication bias and heterogeneity, with Eggers and the inconsistency indexes (I2 ). From 1,512 papers screened, we included 14 studies comprising 15,563 patients for full-length review and analysis. Pooled data demonstrated I2 =99% with an Eggers p<0.001, suggesting significant publication bias. The pooled prevalence of SSPE was 4.6% (95% confidence interval [CI]=1.8%-8.5%). The frequency of bleeding in SSPE patients treated with anticoagulation (n=589) was 8.1% (95% CI=2.8%-15.8%), with no available bleeding data in untreated patients (n=126). The frequency of VTE recurrence within 90 days was 5.3% (95% CI=1.6%-10.9%) for treated versus 3.9% (95% CI=4.8%-13.4%) for untreated, while the frequency of death was 2.1% (95% CI=3.4%-5.2%) for treated versus 3.0% (95% CI=2.8%-8.6%) for untreated. This systematic review highlights the lack of any clinical trial to make a clear inference about harm or benefit of anticoagulation for SSPE. Comparison of pooled data from uncontrolled outcome studies shows no increase in VTE recurrence or death rates for patients who were not anticoagulated. These data suggest clinical equipoise for decision to anticoagulate or not anticoagulate patients with SSPE. However, this inference is limited by small numbers, imprecision, and the lack of a controlled clinical trial.

The regulation of combined treatment-induced cell death with recombinant TRAIL and bortezomib through TRAIL signaling in TRAIL-resistant cells

BackgroundMultiple trials have attempted to demonstrate the effective induction of cell death in TRAIL-resistant cancer cells, including using a combined treatment of recombinant TRAIL and various proteasome inhibitors. These studies have yielded limited success, as the mechanism of cell death is currently unidentified. Understanding this mechanism’s driving forces may facilitate the induction of cell death in TRAIL-resistant cancer cells.MethodsThree kinds of recombinant soluble TRAIL proteins were treated into TRAIL-resistant cells and TRAIL-susceptible cells, with or without bortezomib, to compare their respective abilities to induce cell death. Recombinant TRAIL was treated with bortezomib to investigate whether this combination treatment could induce tumor regression in a mouse syngeneic tumor model. To understand the mechanism of combined treatment-induced cell death, cells were analyzed by flow cytometry and the effects of various cell death inhibitors on cell death rates were examined.ResultsILz:rhTRAIL, a recombinant human TRAIL containing isoleucine zipper hexamerization domain, showed the highest cell death inducing ability both in single treatment and in combination treatment with bortezomib. In both TRAIL-resistant and TRAIL-susceptible cells treated with the combination treatment, an increase in cell death rates was dependent upon both the dose of TRAIL and its intrinsic properties. When a syngeneic mouse tumor model was treated with the combination of ILz:rhTRAIL and bortezomib, significant tumor regression was seen as a result of the effective induction of cancer cell death. The combination treatment-induced cell death was both inhibited by TRAIL blocking antibody and caspase-dependent. However, it was not inhibited by various ER stress inhibitors and autophagy inhibitors.ConclusionsThe combination treatment with ILz:rhTRAIL and bortezomib was able to induce cell death in both TRAIL-susceptible and TRAIL-resistant cancer cells through the intracellular TRAIL signaling pathway. The efficiency of cell death was dependent on the properties of TRAIL under the environment provided by bortezomib. The combination treatment-induced cell death was not regulated by bortezomib-induced ER stress response or by autophagy.

The Epidemiology of Unintentional and Violence-Related Injury Morbidity and Mortality among Children and Adolescents in the United States.

Injuries and violence among young people have a substantial emotional, physical, and economic toll on society. Understanding the epidemiology of this public health problem can guide prevention efforts, help identify and reduce risk factors, and promote protective factors. We examined fatal and nonfatal unintentional injuries, injuries intentionally inflicted by other (i.e., assaults and homicides) among children ages 0–19, and intentionally self-inflicted injuries (i.e., self-harm and suicides) among children ages 10–19. We accessed deaths (1999–2015) and visits to emergency departments (2001–2015) for these age groups through the Centers for Disease Control and Prevention’s (CDC) Web-based Injury Statistics Query and Reporting System (WISQARS), and examined trends and differences by age, sex, race/ethnicity, rural/urban status, and injury mechanism. Almost 13,000 children and adolescents age 0–19 years died in 2015 from injury and violence compared to over 17,000 in 1999. While the overall number of deaths has decreased over time, there were increases in death rates among certain age groups for some categories of unintentional injury and for suicides. The leading causes of injury varied by age group. Our results indicate that efforts to reduce injuries to children and adolescents should consider cause, intent, age, sex, race, and regional factors to assure that prevention resources are directed at those at greatest risk.

The Association of Recently Diagnosed Diabetes and Long-term Diabetes With Survival in Pancreatic Cancer Patients: A Pooled Analysis.

It is unclear whether long-standing diabetes or new-onset pancreatogenic diabetes contributes to poor prognosis in patients with pancreatic ductal adenocarcinoma (PDAC). We investigated the influence of diabetes diagnosed shortly before PDAC and long-term diabetes on overall survival in 2792 PDAC patients who had participated in 3 PDAC case-control studies in the Pancreatic Cancer Case-Control Consortium. There were 300 patients with long-term diabetes of more than 3 years' duration (11%) and 418 patients with recently diagnosed diabetes of 3-year duration or less (15%). We performed Cox regression to determine the association of long-term diabetes and recently diagnosed diabetes with overall survival, adjusting for study site, age, sex, race, stage of disease, surgery, chemotherapy, smoking history, and body mass index at diagnosis. In the overall population, neither long-term diabetes (hazard ratio [HR], 1.10; 95% confidence interval [CI], 0.97-1.26) nor recently diagnosed diabetes (HR, 1.06; 95% CI, 0.94-1.18) was associated with shorter survival. When stratified by stage of disease, long-term diabetes was associated with 42% increase in rate of death in persons with resectable PDAC (HR, 1.42; 95% CI, 1.13-1.78), whereas it was not associated with survival in PDAC patients with more advanced disease. Long-term diabetes was associated with increased rate of death in patients with resectable PDAC.

The Epidemic of Despair Among White Americans: Trends in the Leading Causes of Premature Death, 1999-2015.

To evaluate trends in premature death rates by cause of death, age, race, and urbanization level in the United States. We calculated cause-specific death rates using the Compressed Mortality File, National Center for Health Statistics data for adults aged 25 to 64 years in 2 time periods: 1999 to 2001 and 2013 to 2015. We defined 48 subpopulations by 10-year age groups, race/ethnicity, and county urbanization level (large urban, suburban, small or medium metropolitan, and rural). The age-adjusted premature death rates for all adults declined by 8% between 1999 to 2001 and 2013 to 2015, with decreases in 39 of the 48 subpopulations. Most decreases in death rates were attributable to HIV, cardiovascular disease, and cancer. All 9 subpopulations with increased death rates were non-Hispanic Whites, largely outside large urban areas. Most increases in death rates were attributable to suicide, poisoning, and liver disease. The unfavorable recent trends in premature death rate among non-Hispanic Whites outside large urban areas were primarily caused by self-destructive health behaviors likely related to underlying social and economic factors in these communities.

Trends in heroin and pharmaceutical opioid overdose deaths in Australia

BackgroundThere has been international concern over the rise in fatal pharmaceutical opioid overdose rates, driven by increased opioid analgesic prescribing. The current study aimed to examine trends in opioid overdose deaths by: 1) opioid type (heroin and pharmaceutical opioids); and 2) age, gender, and intent of the death assigned by the coroner. MethodsAnalysis of data from the National Coronial Information System (NCIS) of opioid overdose deaths occurring between 2001 and 2012. ResultsDeaths occurred predominantly (98%) among Australians aged 15–74 years. Approximately two-thirds of the decedents (68%) were male. The heroin overdose death rate remains unchanged over the period; these were more likely to occur among males. Pharmaceutical opioid overdose deaths increased during the study period (from 21.9 per million population in 2001–36.2), and in 2012 they occurred at 2.5 times the incident rate of heroin overdose deaths. Increases in pharmaceutical opioid deaths were largely driven by accidental overdoses. They were more likely to occur among males than females, and highest among Australians aged 45–54 years. Rates of fentanyl deaths in particular showed an increase over the study period (from a very small number at the beginning of the period) but in 2012 rates of morphine deaths were higher than those for oxycodone, fentanyl and tramadol. ConclusionsGiven the increase in rates of pharmaceutical opioid overdose deaths, it is imperative to implement strategies to reduce pharmaceutical opioid-related mortality, including more restrictive prescribing practices and increasing access to treatment for opioid dependence.

Geographic Variation in Opioid and Heroin Involved Drug Poisoning Mortality Rates

An important barrier to formulating effective policies to address the rapid rise in U.S. fatal overdoses is that the specific drugs involved are frequently not identified on death certificates. This analysis supplies improved estimates of state opioid and heroin involved drug fatality rates in 2014, and changes from 2008 to 2014. Reported mortality rates were calculated directly from death certificates and compared to corrected rates that imputed drug involvement when no drug was specified. The analysis took place during 2016-2017. Nationally, corrected opioid and heroin involved mortality rates were 24% and 22% greater than reported rates. The differences varied across states, with particularly large effects in Pennsylvania, Indiana, and Louisiana. Growth in corrected opioid mortality rates, from 2008 to 2014, were virtually the same as reported increases (2.5 deaths per 100,000 people) whereas changes in corrected heroin death rates exceeded reported increases (2.7 vs 2.3 per 100,000). Without corrections, opioid mortality rate changes were considerably understated in Pennsylvania, Indiana, New Jersey, and Arizona, but dramatically overestimated in South Carolina, New Mexico, Ohio, Connecticut, Florida, and Kentucky. Increases in heroin death rates were understated in most states, and by large amounts in Pennsylvania, Indiana, New Jersey, Louisiana, and Alabama. The correction procedures developed here supply a more accurate understanding of geographic differences in drug poisonings and supply important information to policymakers attempting to reduce or slow the increase in fatal drug overdoses.