O39 VTE risk in the general population: applying context to the impact of JAK inhibition

Rheumatology ◽  
2020 ◽  
Vol 59 (Supplement_2) ◽  
Author(s):  
Serena Baroncini ◽  
Mark Yates ◽  
Katie Bechman ◽  
Sanjeev Patel ◽  
Andrew Rutherford ◽  
...  

Abstract Background Trial data indicate an increased risk of VTE with JAK inhibition. The EMA and FDA have given regulatory advice for their use as a result. To understand the context of any association, we need to understand VTE risk in the background population. Our objective was to describe the changing epidemiology of VTE risk including a breakdown of DVT and PE in the general population in England, over a 20-year period. Methods We utilised hospital episodes statistics data to study all patients presenting for hospital care in England between 1 January 1998 and 31 December 2017. We identified VTE events using ICD10 codes I26.0, I26.9, I80.1, I80.2 and I80.3. To estimate annualised event rates, we used the number of finished consultant episodes for admitted care where the primary diagnosis was VTE for the numerator; the denominator was the whole population estimate, from the office for National Statistics, for the relevant year for England. Rates were calculated per 100,000 population, and the Cochrane Armitage test was used to evaluate statistical significance of trends over time. Linear regression allowed modelling of estimates over time, with model assumptions tested using residual versus fitted plots. To explore non-linearity, we used a cubic spline model. Results The average VTE rate across the 20 years was 127/100,000. VTE rates have increased over time, climbing from 108/100,000 in 1998, to 151/100,000 in 2017. The relative frequency of DVTs and PEs has changed over this time: in 1998 DVT was more frequent than PE (rates 68/100,000 and 40/100,000 respectively). By 2018 this ratio had reversed (DVT 52/100,000: PE 98/100,000). This change was statistically significant (p < 0.0001). DVT rates declined in a linear manner over time. PE rates increased with a non-linear pattern, with a sharp rise apparent between 2008 and 2010. Conclusion The inversion in the frequency of DVTs and PEs is consistent with previous findings using European data. One possible explanation is changing diagnostics (CTPA replacing V/Q), capturing previously subclinical PE events. Limitations include our ecologic design as well as lack of linkage to mortality records. The presumed VTE risk associated with JAK inhibition is small. It is plausible that future shifts in population wide patterns of VTE could obscure or amplify any effect attributable to JAK inhibitors. As longer-term observational data become available, it is crucial they are interpreted in the context of background population trends. Disclosures S. Baroncini: None. M. Yates: None. K. Bechman: None. S. Patel: None. A. Rutherford: None. A. Kleymann: None. J. Galloway: None.

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4869-4869
Author(s):  
Vivek Kumar ◽  
Sikander Ailawadhi ◽  
Leyla Bojanini ◽  
Aditya Mehta ◽  
Anshika Singh ◽  
...  

Abstract Background: CLL is the most common leukemia diagnosis in adults and its treatment has undergone significant change from chemotherapy, to immunotherapy and now targeted kinase inhibitors, leading to improved overall survival (OS). With improving survivorship, SPMs can occur but an in-depth analysis of risks and trends of SPMs in CLL survivors is lacking. We performed a population-based analysis to evaluate this. Methods: Patients in the Surveillance, Epidemiology and End Results (SEER) database diagnosed with CLL between 1973-2015 were included. Due to variation in management techniques over time, the cohort was divided in four time periods: 1973-1982, 1983-1992, 1993-2002 and 2003-2015. We evaluated differences in risk for SPMs among CLL survivors compared to risk of individual malignancies expected in the general population during these time periods and studied the effect of demographics and time since CLL diagnosis. Results: Over a nearly 270,000 person-year follow up, 6,467 new SPMs were diagnosed with a standardized incidence ratio (SIR) of 1.2 (95% CI 1.17-1.23), which resulted in a 39 excess cancers per 10,000 population. The CLL survivors had a 20% overall increased risk of developing SPMs (excluding non-squamous skin cancer) compared to the general population. The risks for both solid (SIR 1.15 CI 95% 1.12-1.18) and hematological malignancies (SIR 1.61 95% CI 1.5-1.73) was higher than the expected in the general population. However, the risk for individual cancers was heterogeneous. The tumors associated with the highest risk were Hodgkin lymphoma (almost 8 times higher), Kaposi Sarcoma (4 times), non-epithelial skin cancers (4 times), salivary gland cancer (3 times) and acute lymphocytic leukemia (3 times). In contrast, tumors in the hepatobiliary system, female breast and female genital system were associated with a lower risk than the general population. The highest SIR across the study periods was observed in the younger population (ages 15-49). Although the risk increased in all ethnicities, it was statistically significant only in Caucasians. There was no gender-wise difference in SIR during any of the four time periods. A statistically significant increase in SIR was observed for both men and women from 1973-1982 to 2003-2015. This was mostly due to an increase in risk of hematological malignancies from 1.08 early in the study to 2.56 in the most recent study period. The SIR in solid tumors did not change significantly over time; in absolute terms, however, lung carcinoma contributed the most to the excess risk, followed by non-epithelial skin cancers and non-Hodgkin's lymphoma. The risk of developing a SPM was higher for the CLL survivors during most of the latency periods, but it was statistically significant during the 2-5 months and 12-59 months after diagnosis. A multivariate analysis was conducted to evaluate the impact of period of diagnosis on the development of SPMs among these patients. After adjusting for gender, ethnicity, radiation therapy, chemotherapy, and age at diagnosis of CLL, patients diagnosed with CLL in the most recent time period were at 45% higher risk of developing SPMs as compared to the patient diagnosed during 1973-1982 (Hazard ratio(HR) =1.45 95%CI:1.34-1.6, p<0.001). Moreover increased HRs were also observed for 1983-1992 and 1993-2002 time periods (Fig. 1) Conclusions: With improving therapeutics for cancer treatment, survivorship is improving as well and the risk of SPMs needs to be better understood and addressed. This is truer for CLL, where majority of patients have a favorable survival. The risk of SPMs was 20% higher in CLL survivors than in the general population and was most prominent in the survivors aged 15-49 years at the time of CLL diagnosis. The risk of individual malignancies may be heterogenous but there has been an increase in risk of SPMs over time, mainly due to an increase of secondary hematological malignancies in recent years. Active survivorship plans and long-term surveillance for SPMs is crucial for improved outcomes of patients with a history of CLL. Disclosures Ailawadhi: Janssen: Consultancy; Celgene: Consultancy; Amgen: Consultancy; Takeda: Consultancy; Pharmacyclics: Research Funding.


2012 ◽  
Vol 7 (1) ◽  
pp. 37
Author(s):  
Donald E Cutlip ◽  

Coronary artery disease in patients with diabetes is frequently a diffuse process with multivessel involvement and is associated with increased risk for myocardial infarction and death. The role of percutaneous coronary intervention (PCI) versus coronary artery bypass grafting (CABG) in patients with diabetes and multivessel disease who require revascularisation has been debated and remains uncertain. The debate has been continued mainly because of the question to what degree an increased risk for in-stent restenosis among patients with diabetes contributes to other late adverse outcomes. This article reviews outcomes from early trials of balloon angioplasty versus CABG through later trials of bare-metal stents versus CABG and more recent data with drug-eluting stents as the comparator. Although not all studies have been powered to show statistical significance, the results have been generally consistent with a mortality benefit for CABG versus PCI, despite differential risks for restenosis with the various PCI approaches. The review also considers the impact of mammary artery grafting of the left anterior descending artery and individual case selection on these results, and proposes an algorithm for selection of patients in whom PCI remains a reasonable strategy.


2019 ◽  
Vol 25 (29) ◽  
pp. 3098-3111 ◽  
Author(s):  
Luca Liberale ◽  
Giovanni G. Camici

Background: The ongoing demographical shift is leading to an unprecedented aging of the population. As a consequence, the prevalence of age-related diseases, such as atherosclerosis and its thrombotic complications is set to increase in the near future. Endothelial dysfunction and vascular stiffening characterize arterial aging and set the stage for the development of cardiovascular diseases. Atherosclerotic plaques evolve over time, the extent to which these changes might affect their stability and predispose to sudden complications remains to be determined. Recent advances in imaging technology will allow for longitudinal prospective studies following the progression of plaque burden aimed at better characterizing changes over time associated with plaque stability or rupture. Oxidative stress and inflammation, firmly established driving forces of age-related CV dysfunction, also play an important role in atherosclerotic plaque destabilization and rupture. Several genes involved in lifespan determination are known regulator of redox cellular balance and pre-clinical evidence underlines their pathophysiological roles in age-related cardiovascular dysfunction and atherosclerosis. Objective: The aim of this narrative review is to examine the impact of aging on arterial function and atherosclerotic plaque development. Furthermore, we report how molecular mechanisms of vascular aging might regulate age-related plaque modifications and how this may help to identify novel therapeutic targets to attenuate the increased risk of CV disease in elderly people.


Author(s):  
Manuel Fröhlich ◽  
Abiodun Williams

The Conclusion returns to the guiding questions introduced in the Introduction, looking at the way in which the book’s chapters answered them. As such, it identifies recurring themes, experiences, structures, motives, and trends over time. By summarizing the result of the chapters’ research into the interaction between the Secretaries-General and the Security Council, some lessons are identified on the changing calculus of appointments, the conditions and relevance of the international context, the impact of different personalities in that interaction, the changes in agenda and composition of the Council as well as different formats of interaction and different challenges to be met in the realm of peace and security, administration, and reform, as well as concepts and norms. Taken together, they also illustrate the potential and limitations of UN executive action.


2020 ◽  
Vol 41 (S1) ◽  
pp. s258-s259
Author(s):  
James Harrigan ◽  
Ebbing Lautenbach ◽  
Emily Reesey ◽  
Magda Wernovsky ◽  
Pam Tolomeo ◽  
...  

Background: Clinically diagnosed ventilator-associated pneumonia (VAP) is common in the long-term acute-care hospital (LTACH) setting and may contribute to adverse ventilator-associated events (VAEs). Pseudomonas aeruginosa is a common causative organism of VAP. We evaluated the impact of respiratory P. aeruginosa colonization and bacterial community dominance, both diagnosed and undiagnosed, on subsequent P. aeruginosa VAP and VAE events during long-term acute care. Methods: We enrolled 83 patients on LTACH admission for ventilator weaning, performed longitudinal sampling of endotracheal aspirates followed by 16S rRNA gene sequencing (Illumina HiSeq), and bacterial community profiling (QIIME2). Statistical analysis was performed with R and Stan; mixed-effects models were fit to relate the abundance of respiratory Psa on admission to clinically diagnosed VAP and VAE events. Results: Of the 83 patients included, 12 were diagnosed with P. aeruginosa pneumonia during the 14 days prior to LTACH admission (known P. aeruginosa), and 22 additional patients received anti–P. aeruginosa antibiotics within 48 hours of admission (suspected P. aeruginosa); 49 patients had no known or suspected P. aeruginosa (unknown P. aeruginosa). Among the known P. aeruginosa group, all 12 patients had P. aeruginosa detectable by 16S sequencing, with elevated admission P. aeruginosa proportional abundance (median, 0.97; IQR, 0.33–1). Among the suspected P. aeruginosa group, all 22 patients had P. aeruginosa detectable by 16S sequencing, with a wide range of admission P. aeruginosa proportional abundance (median, 0.0088; IQR, 0.00012–0.31). Of the 49 patients in the unknown group, 47 also had detectable respiratory Psa, and many had high P. aeruginosa proportional abundance at admission (median, 0.014; IQR, 0.00025–0.52). Incident P. aeruginosa VAP was observed within 30 days in 4 of the known P. aeruginosa patients (33.3%), 5 of the suspected P. aeruginosa patients (22.7%), and 8 of the unknown P. aeruginosa patients (16.3%). VAE was observed within 30 days in 1 of the known P. aeruginosa patients (8.3%), 2 of the suspected P. aeruginosa patients (9.1%), and 1 of the unknown P. aeruginosa patients (2%). Admission P. aeruginosa abundance was positively associated with VAP and VAE risk in all groups, but the association only achieved statistical significance in the unknown group (type S error <0.002 for 30-day VAP and <0.011 for 30-day VAE). Conclusions: We identified a high prevalence of unrecognized respiratory P. aeruginosa colonization among patients admitted to LTACH for weaning from mechanical ventilation. The admission P. aeruginosa proportional abundance was strongly associated with increased risk of incident P. aeruginosa VAP among these patients.Funding: NoneDisclosures: None


2021 ◽  
Vol 108 (Supplement_6) ◽  
Author(s):  

Abstract Introduction Compared to the general population, in the postoperative period, surgical patients are both at increased risk of SARS-CoV-2 infection and increased mortality in the event of SARS-CoV-2 infection. This study modelled the impact of preoperative vaccination of patients aged ≥70 years having elective inpatient surgery. Method The primary outcome was the number needed to treat (NNT) to prevent one death over one year following SARS-CoV-2 vaccination. Postoperative SARS-CoV-2 incidence and adjusted mortality risk difference for SARS-CoV-2 infection were estimated from the prospective GlobalSurg-CovidSurg Week study (90,146 elective surgery patients across 1,595 hospitals in 115 countries), were used to estimate lives saved by vaccination in the first 30 postoperative days. SARS-CoV-2 case and death registration data from the Office for National Statistics was used to estimate NNTs for the general population. Best and worst-case scenarios were used to describe uncertainty around estimates. Results Among patients aged ≥70 years undergoing any type of surgery, NNT was estimated to be 332 (best case: 213; worst case: 690). NNT was lower in the cancer surgery subgroup (245 [150-545]). This was more favourable than the NNT for vaccination of the general population aged ≥70 (588 [403-1032]). Globally, vaccinating elective surgery patients aged ≥70 years preoperatively was projected to save 27,356 lives in one year compared to vaccinating the same patients after surgery. Conclusions Preoperative pathways should be set up for the vaccination of patients aged ≥70. In settings with limited vaccine availability, elective cancer surgery patients should be prioritised for vaccination.


2020 ◽  
Vol 29 ◽  
Author(s):  
M. Strand ◽  
R. Zhang ◽  
L. M. Thornton ◽  
A. Birgegård ◽  
B. M. D'Onofrio ◽  
...  

Abstract Aims Compared to the general population, adoptees are more often referred to specialist psychiatric treatment, exhibit increased risk of suicide and display more symptoms of attention-deficit/hyperactivity-disorder. However, little is known about the impact of being an adoptee on the risk of developing an eating disorder. The aim of the present study was to assess whether international adoptees have a higher risk for eating disorders than native Swedes. Methods In the present retrospective cohort study, data from the Swedish total population registers on individuals born between 1979 and 2005 were used to assess whether international adoptees residing in Sweden (n = 25 287) have a higher risk for anorexia nervosa (AN) and other eating disorders (OED) than non-adoptees with Swedish-born parents from the general population (n = 2 046 835). The patterns of these results were compared to those for major depressive disorder (MDD), obsessive-compulsive disorder (OCD), and anxiety disorders to determine whether any observed effects were unique to eating disorders or reflected a more general impact on mental health outcomes. Results A survival analysis adjusting for relevant demographic covariates revealed an elevated risk of all examined psychiatric disorders in international adoptees: hazard ratios (95% confidence intervals) are 1.21 (1.04–1.41) for AN, 1.60 (1.44–1.79) for OED, 1.90 (1.81–2.00) for MDD, 1.25 (1.09–1.44) for OCD, and 1.69 (1.60–1.78) for anxiety disorders. Conclusions Elevated risk of eating disorders as well as of MDD, OCD, and anxiety disorders was found in international adoptees. A parallel pattern between AN and OCD was observed, which both display less elevated rates than the other diagnoses. A considerable number of biological, environmental, and societal factors have been suggested to explain the observed differences in mental health between adoptees and non-adoptees, but they remain primarily theoretical.


Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 760-760
Author(s):  
Tanya Wildes ◽  
Suhong Luo ◽  
Graham A Colditz ◽  
Kenneth R. Carson

Abstract Abstract 760 Introduction: The incidence of multiple myeloma (MM) increases with age, and the prognosis worsens. Comorbidities increase in prevalence with age, yet little is known about the impact of comorbid medical conditions on outcomes in MM. Methods: In a retrospectively-assembled cohort study, all patients with MM diagnosed between 1998 and 2009 at a Veterans' Administration (VA) hospital were identified in the VA central cancer registry. Patients who received no treatment within 6 months of diagnosis were excluded, eliminating those with smoldering myeloma or who received supportive care only. Comorbidities were ascertained from ICD-9 codes present prior to the diagnosis of MM, and categorized using the Romano adaptation of the Charlson Comorbidity Index (CCI). The independent effects of age, race and comorbidities were examined using Cox proportional hazards modeling. The impact of individual comorbidities on survival was also examined, controlling for age and race. Results: A total of 2,968 patients were identified. The median age was 69 (range 27–92). The vast majority of patients (98%) were male; 28.6% of the patients were black. The median Charlson Comorbidity Index score was 2 (range 0–13). The frequencies of selected comorbidities were: diabetes (31%), renal impairment (23.8%), cardiovascular comorbidities (38.8%) and pulmonary (26.6%). The median overall survival (OS) for the entire cohort was 28.6 months at a median follow up of 26.8 months (range 0–137 months). On multivariate analysis, age was significantly associated with mortality [Hazard Ratio (HR) 1.03 per year (95% confidence intervals (CI) 1.03–1.04), p<0.0001]. Race was not significantly associated with survival [HR 0.99 (95% CI 0.90–1.09), p=0.81]. The median OS, adjusted for age and race, was 36.5 months for patients with no comorbidities, 33.9 months for patients with a CCI score of 1–2, 25.6 months for patients with a CCI score of 3–4 and 20.2 months for patients with a CCI score ≥5. The impact of comorbidities on survival violated the proportional hazards assumption, with a cut-point at 1 year, indicating that the influence of comorbidities varied over time. Relative to those with no comorbidities, the HR for death among those with a CCI score 1–2 was 1.20 (0.97–1.48) in the first year, and 1.03 (95% CI 0.89–1.18) subsequent to the first year; among those with a CCI score 3–4, the HR for death was 1.67 (95% CI 1.34–2.08) in the first year and 1.23 (95% CI 1.05–1.45) subsequently; among those with a CCI score ≥5, the risk of death in the first year doubled [HR 2.15 (95% CI 1.73–2.67)] and was increased 40% subsequently [HR 1.42 (95% CI 1.19–1.69)]. Individual prevalent comorbidities were then examined. Cardiovascular disease, renal impairment, and pulmonary disease were all significantly associated with mortality. In the first year after diagnosis, cardiovascular disease was associated with a 55% increase in mortality [HR 1.55 (95% CI 1.35–1.78)] while, subsequent to the first year, the risk was only increased about 20% [HR 1.19 (95% CI 1.07–1.39)]. The impact of renal impairment and pulmonary impairment did not vary over time; both were associated with a 25% increased risk of death [renal impairment HR 1.26 (95% CI 1.14–1.38); pulmonary disease HR 1.24 (95% CI 1.13–1.37)]. Diabetes was not associated with survival (HR 1.02, p=0.64) after controlling for age, race and cardiovascular, pulmonary or renal impairment. Conclusion: Age and comorbidities are independently associated with increased risk of mortality in MM. The influence of comorbidities varies over time, with the greatest impact noted in the first year after diagnosis of MM among those with a CCI score ≥3 and with cardiovascular disease. Further study is needed to determine whether this increased early mortality is related to increased risk of toxicity of therapy, inadequate MM therapy or both. Disclosures: No relevant conflicts of interest to declare.


2017 ◽  
Vol 34 (1) ◽  
pp. 48-54 ◽  
Author(s):  
Stefano Busani ◽  
Giulia Serafini ◽  
Elena Mantovani ◽  
Claudia Venturelli ◽  
Maddalena Giannella ◽  
...  

Background: Patients with septic shock by multidrug resistant (MDR) microorganism maybe considered a specific population of critical patients at very high risk of death in whom the effects of standard sepsis treatment has never been assessed. The objective of this retrospective analysis was to evaluate the risk factors for 30-day mortality and the impact of sepsis management in patients with septic shock caused by MDR bacteria. Methods: Patients with septic shock by MDR bacteria admitted to the mixed intensive care unit (ICU) of Modena University Hospital during a 6-year period were studied. The clinical and microbiological characteristics and sepsis treatments provided were analyzed and compared between survivors (S) and nonsurvivors (NS) at 30 days after septic shock appearance. Results: Ninety-four patients were studied. All therapeutic interventions applied to patients during their ICU stay did not show statistical significance between S and NS groups, except for administration of immunoglobulin M (IgM) preparation which were provided more frequently in S group ( P < .05). At the multivariate adjusted analysis, preexisting cancer (odds ratio [OR] = 2.965) and Acinetobacter baumannii infections (OR = 3.197) were independently correlated with an increased risk of 30-day mortality, whereas treatment with IgM preparation was protective (OR = 0.283). Conclusions: This retrospective study showed that in patients with septic shock caused by MDR bacteria, history of cancer and infection sustained by A baumannii increase the risk of mortality and that standard sepsis treatments do not seem to provide any protective effect. Adjunctive therapy with IgM preparation seems to be beneficial, but further appropriate studies are needed to confirm the results observed.


2013 ◽  
Vol 14 (2) ◽  
pp. 70-74
Author(s):  
Catherine Jury ◽  
Nicoli Nattrass

Background. While household support is an important component of effective care and treatment in HIV/AIDS, there are few insights from Southern Africa into how household support arrangements change over time for patients starting antiretroviral therapy (ART).Objective. We hypothesised that patients initiating ART are more likely to be living with family, especially their mothers, compared with the general population, but that over time these differences disappear.Methods. A panel survey of ART patients was matched by age, gender and education to a comparison sample drawn from adults in Khayelitsha, Cape Town.Results. The results show that there is a substantial potential burden of care on the families of patients starting ART, particularly mothers, and that the use of ART appears to reduce this burden over time. But, even after their health is restored, ART patients are significantly less likely to have a resident sexual partner and more likely to be living in single-person households than their counterparts in the general population.


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