Association between admission haematocrit and mortality among men with acute ischaemic stroke

ObjectiveAnaemia is associated with higher mortality among patients with non-stroke cardiovascular conditions; less is known regarding the relationship between anaemia and mortality among patients with acute ischaemic stroke.MethodsMedical records were abstracted for n=3965 veterans from 131 Veterans Health Administration facilities who were admitted with ischaemic stroke in fiscal year 2007. Haematocrit values within 24 hours of admission were classified as ≤27%, 28%–32%, 33%–37%, 38%–42%, 43%–47% or ≥48%. Multivariate logistic regression was used to examine the relationship between anaemia and in-hospital, 30-day, 6-month and 1-year mortality, adjusting for age, medical comorbidities, modified Acute Physiology and Chronic Health Evaluation-III and stroke severity. Impact factors were calculated to standardise comparisons between haematocrit tier and other covariates.ResultsAmong n=3750 patients included in the analysis, the haematocrit values were ≤27% in 2.1% (n=78), 28%–32% in 6.2% (n=234), 33%–37% in 17.9% (n=670), 38%–42% in 36.4% (n=1366), 43%–47% in 28.2% (n=1059) and ≥48% in 9.1% (n=343). Patients with haematocrit ≤27%, compared with patients in the 38%–42% range, were more likely to have died across all follow-up intervals, with statistically significant adjusted ORs (aORs) ranging from 2.5 to 3.5. Patients with polycythaemia (ie, haematocrit ≥48%) were at increased risk of in-hospital mortality (aOR=2.9; 95% CI 1.4 to 6.0), compared with patients with mid-range admission haematocrits. Pronounced differences between patients receiving and not receiving blood transfusion limited our ability to perform a propensity analysis. Impact factors in the 1-year mortality model were 0.46 (severe anaemia), 0.06 (cancer) and 0.018 (heart disease).ConclusionsAnaemia is independently associated with an increased risk of death throughout the first year post stroke; high haematocrit is associated with early poststroke mortality. Severe anaemia is associated with 1-year mortality to a greater degree than cancer or heart disease. These data cannot address the question of whether interventions targeting anaemia might improve patient outcomes.

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Associations between stopping prescriptions for opioids, length of opioid treatment, and overdose or suicide deaths in US veterans: observational evaluation

BMJ ◽

10.1136/bmj.m283 ◽

2020 ◽

pp. m283 ◽

Cited By ~ 12

Author(s):

Elizabeth M Oliva ◽

Thomas Bowe ◽

Ajay Manhapra ◽

Stefan Kertesz ◽

Jennifer M Hah ◽

...

Keyword(s):

Opioid Analgesic ◽

Veterans Health Administration ◽

Fiscal Year ◽

Veterans Health ◽

Health Administration ◽

Opioid Treatment ◽

Risk Of Death ◽

Length Of Treatment ◽

Increased Risk ◽

Stopping Treatment

Abstract Objective To examine the associations between stopping treatment with opioids, length of treatment, and death from overdose or suicide in the Veterans Health Administration. Design Observational evaluation. Setting Veterans Health Administration. Participants 1 394 102 patients in the Veterans Health Administration with an outpatient prescription for an opioid analgesic from fiscal year 2013 to the end of fiscal year 2014 (1 October 2012 to 30 September 2014). Main outcome measures A multivariable Cox non-proportional hazards regression model examined death from overdose or suicide, with the interaction of time varying opioid cessation by length of treatment (≤30, 31-90, 91-400, and >400 days) as the main covariates. Stopping treatment with opioids was measured as the time when a patient was estimated to have no prescription for opioids, up to the end of the next fiscal year (2014) or the patient’s death. Results 2887 deaths from overdose or suicide were found. The incidence of stopping opioid treatment was 57.4% (n = 799 668) overall, and based on length of opioid treatment was 32.0% (≤30 days), 8.7% (31-90 days), 22.7% (91-400 days), and 36.6% (>400 days). The interaction between stopping treatment with opioids and length of treatment was significant (P<0.001); stopping treatment was associated with an increased risk of death from overdose or suicide regardless of the length of treatment, with the risk increasing the longer patients were treated. Hazard ratios for patients who stopped opioid treatment (with reference values for all other covariates) were 1.67 (≤30 days), 2.80 (31-90 days), 3.95 (91-400 days), and 6.77 (>400 days). Descriptive life table data suggested that death rates for overdose or suicide increased immediately after starting or stopping treatment with opioids, with the incidence decreasing over about three to 12 months. Conclusions Patients were at greater risk of death from overdose or suicide after stopping opioid treatment, with an increase in the risk the longer patients had been treated before stopping. Descriptive data suggested that starting treatment with opioids was also a risk period. Strategies to mitigate the risk in these periods are not currently a focus of guidelines for long term use of opioids. The associations observed cannot be assumed to be causal; the context in which opioid prescriptions were started and stopped might contribute to risk and was not investigated. Safer prescribing of opioids should take a broader view on patient safety and mitigate the risk from the patient’s perspective. Factors to address are those that place patients at risk for overdose or suicide after beginning and stopping opioid treatment, especially in the first three months.

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Prognostic significance of international normalised ratio and prothrombin time in Chinese acute ischaemic stroke patients

Postgraduate Medical Journal ◽

10.1136/postgradmedj-2021-141204 ◽

2022 ◽

pp. postgradmedj-2021-141204

Author(s):

Shoujiang You ◽

Qiao Han ◽

Xiaofeng Dong ◽

Chongke Zhong ◽

Huaping Du ◽

...

Keyword(s):

Logistic Regression ◽

Ischaemic Stroke ◽

Prothrombin Time ◽

Hospital Discharge ◽

Acute Ischaemic Stroke ◽

Regression Models ◽

Logistic Regression Models ◽

Risk Of Death ◽

Increased Risk ◽

International Normalised Ratio

BackgroundWe investigated the association between international normalised ratio (INR) and prothrombin time (PT) levels on hospital admission and in-hospital outcomes in acute ischaemic stroke (AIS) patients.MethodsA total of 3175 AIS patients enrolled from December 2013 to May 2014 across 22 hospitals in Suzhou city were included. We divided patients into four groups according to their level of admission INR: (<0.92), Q2 (0.92–0.98), Q3 (0.98–1.04) and Q4 (≥1.04) and PT. Logistic regression models were used to estimate the effect of INR and PT on death or major disability (modified Rankin Scale score (mRS)>3), death and major disability (mRS scores 4–5) separately on discharge in AIS patients.ResultsHaving an INR level in the highest quartile (Q4) was associated with an increased risk of death or major disability (OR 1.69; 95% CI 1.23 to 2.31; P-trend=0.001), death (OR, 2.64; 95% CI 1.12 to 6.19; P-trend=0.002) and major disability on discharge (OR, 1.56; 95% CI 1.13 to 2.15; P-trend=0.008) in comparison to Q1 after adjusting for potential covariates. Moreover, in multivariable logistic regression models, having a PT level in the highest quartile also significantly increased the risk of death (OR, 2.38; 95% CI 1.06 to 5.32; P-trend=0.006) but not death or major disability (P-trend=0.240), major disability (P-trend=0.606) on discharge.ConclusionsHigh INR at admission was independently associated with death or major disability, death and major disability at hospital discharge in AIS patients and increased PT was also associated with death at hospital discharge.

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Gastrointestinal bleeding during acute ischaemic stroke hospitalisation increases the risk of stroke recurrence

Stroke and Vascular Neurology ◽

10.1136/svn-2019-000314 ◽

2020 ◽

Vol 5 (2) ◽

pp. 116-120

Author(s):

Wanliang Du ◽

Xingquan Zhao ◽

Yilong Wang ◽

Yuesong Pan ◽

Gaifen Liu ◽

...

Keyword(s):

Ischaemic Stroke ◽

Acute Ischaemic Stroke ◽

Patient Characteristics ◽

Recurrence Risk ◽

Stroke Recurrence ◽

Gi Bleeding ◽

Stroke Registry ◽

Risk Of Death ◽

Increased Risk ◽

Death And Loss

ObjectiveGastrointestinal (GI) bleeding in patients who had a stroke is strongly associated with a higher risk of death and loss of independence. However, it is unknown whether GI bleeding increases risk for recurrence of stroke. In this study, we assess the potential relationship between GI bleeding and stroke recurrence in patients within 12 months of an acute ischaemic stroke (AIS), using the China National Stroke Registry (CNSR).MethodsThis study included 22 216 patients who had an ischaemic stroke included in the CNSR from 2007 to 2008. We analysed baseline patient characteristics, GI bleeding and outcomes of patients who had an AIS, specifically stroke recurrence at 3, 6 and 12 months. We used multivariable logistic regression to evaluate a possible association between GI bleeding and stroke recurrence.ResultsOf the 12 415 patients included in our study, 12.3%, 15.5% and 17.7% had a stroke recurrence at 3, 6 and 12 months, respectively. GI bleeding was an independent stroke recurrence risk factor in patients after ischaemic stroke at 3 months (adjusted OR 1.481, 95% CI 1.118 to 1.962), 6 months (adjusted OR 1.448, 95% CI 1.106 to 1.896) and 12 months (adjusted OR 1.350; 95% CI 1.034 to 1.763).ConclusionGI bleeding was associated with the increased risk of stroke recurrence after an AIS.

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Treatment of Diffuse Large B-Cell Lymphoma (DLBCL) Patients (pts) Age 80 and Older: Analysis of the Veterans Health Administration (VHA) National Database

Blood ◽

10.1182/blood.v120.21.968.968 ◽

2012 ◽

Vol 120 (21) ◽

pp. 968-968

Author(s):

Kenneth R. Carson ◽

Ryan Lynch ◽

Peter Riedell ◽

Ryan P. Roop ◽

Arun Ganti ◽

...

Keyword(s):

Elderly Population ◽

Performance Status ◽

B Cell Lymphoma ◽

National Database ◽

Veterans Health ◽

Health Administration ◽

Very Elderly ◽

Risk Of Death ◽

Increased Risk ◽

The Relationship

Abstract Abstract 968 Introduction: The incidence of DLBCL increases with age and the population ≥80 is the fastest growing segment of the elderly population. Optimal treatment of these very elderly DLBCL pts remains unclear. While chemo-immunotherapy can be curative, benefits of treatment must be balanced against toxicities in older, frail pts. Previous studies have suggested that doxorubicin treatment is associated with better survival in the very elderly population, though only on univariate analyses. To better understand the relationship between treatment and survival in pts ≥80, we performed a retrospective analysis of veterans to examine the relationship between treatment and overall survival (OS). Methods: We identified 523 DLBCL pts ≥80 diagnosed between 1998 and 2008 in the VHA Central Cancer Registry. We excluded pts with primary cutaneous or central nervous system DLBCL and pts treated with unknown agents outside the VHA. Data on stage, LDH, co-morbidities, date of death, treatment and supportive care medications were obtained for each pt. Treatment related mortality (TRM) was defined as death in the 30 days following any cycle of therapy. OS was defined as time from diagnosis to death. ECOG Performance Status (PS) at diagnosis was either obtained from pt charts or assessed from physician, nursing, and physical therapy notes available for each patient. Results: Of the 476 pts that met inclusion criteria, 193 received at least one dose of doxorubicin therapy (DT), 92 were treated without doxorubicin (non-DT) and 191 received no system therapy (NST). Median OS times were 30.2 months, 12.3 months, and 1.9 months in the DT, non-DT, and NST groups, respectively (Log-rank p<0.001). Baseline characteristics of 285 treated patients presented in Table 1. Among the 273 pts in whom treatment dates were available, 48 (18%) experienced TRM. Of these 48 deaths, 32 (67%) were associated with the first treatment cycle. On multivariate analysis, rituximab significantly reduced the risk of death (HR .62, CI .44 - .87), while GCSF use demonstrated a trend towards decreased death (HR .76, CI .57 – 1.03). Comorbidities (HR 1.1, CI 1.02 – 1.19) and PS were associated with increased risk of death. PS of 2–4 was associated with a marked increased risk of death within the first 45 days after diagnosis (HR 19.7, CI 2.6– 146) and a lesser risk after 45 days (HR 1.9, CI 1.4 –2.6). After controlling for other variables, doxorubicin use was no longer significantly associated with OS (HR .87, CI .64 – 1.17), suggesting the OS difference noted between the DT and non-DT groups was primarily due to differences in baseline patient characteristics. Conclusions: While we acknowledge the limitations of analyses of observational data, the observed 18% rate of TRM (compared to historical TRM rates of 4–6% seen in trials of R-CHOP) suggests that standard treatment paradigms are too toxic for many patients in this age group. The lack of association between doxorubicin and OS calls into question the importance of this drug in this patient population. In the absence of better risk stratification, treatment with less toxic regimens- either through attenuated doses or different drugs- may be appropriate in this population. Disclosures: Carson: Genentech: Consultancy, Honoraria, Speakers Bureau. Nabhan:Genentech: Research Funding, Speakers Bureau.

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Successful thrombolysis in essential thrombocythemia-related acute ischaemic stroke

BMJ Case Reports ◽

10.1136/bcr-2021-242925 ◽

2021 ◽

Vol 14 (5) ◽

pp. e242925

Author(s):

Ishita Desai ◽

Ashutosh Tiwari ◽

Mritunjai Kumar Singh ◽

Niraj Kumar

Keyword(s):

Ischaemic Stroke ◽

Essential Thrombocythemia ◽

Acute Ischaemic Stroke ◽

Jak2 V617f ◽

Preliminary Evidence ◽

Sudden Onset ◽

Left Ventricular ◽

Interesting Case ◽

Increased Risk ◽

Successful Thrombolysis

Essential thrombocythemia (ET)-related acute ischaemic stroke (AIS) may account for approximately 0.25%–0.5% of all ischaemic strokes. If left undiagnosed and untreated, patients with ET carry an increased risk of recurrent thrombosis involving major organs including the brain. We report an interesting case of a 67-year-old man, who was successfully thrombolysed for AIS resulting from ET. He presented with sudden onset of left-sided hemiparesis with a left-ventricular clot. His subsequent investigations including positive JAK2 V617F mutation confirmed the diagnosis of ET. He made a significant recovery with thrombolysis, anticoagulation, antiplatelet and hydroxyurea. A fear of post-thrombolytic haemorrhagic complications appears the major reason for the lack of reports of thrombolysis in ET-related AIS. Although the diagnosis of ET was confirmed on subsequent investigations, successful thrombolysis in our case provides preliminary evidence that ET-related AIS cases can undergo successful thrombolysis using tenecteplase. To date, ours is only the second case of ET-related AIS being thrombolysed.

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6074Cardiorespiratory fitness, socioeconomic status and mortality in middle-aged men: a population-based prospective cohort study

European Heart Journal ◽

10.1093/eurheartj/ehz746.0122 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

S Y Jae ◽

S Kurl ◽

B A Franklin ◽

J Choo ◽

H J Kim ◽

...

Keyword(s):

Socioeconomic Status ◽

Heart Disease ◽

Density Lipoprotein ◽

Population Based ◽

Lipoprotein Cholesterol ◽

Low Ses ◽

Risk Of Death ◽

Increased Risk ◽

Material Standard Of Living ◽

Cvd Mortality

Abstract Background Although both low socioeconomic status (SES) and poor cardiorespiratory fitness (CRF) are associated with increased chronic disease and a heightened risk of death, it remains unclear whether moderate-to-high levels of CRF confer survival benefits in low SES populations. Purpose The present study evaluated the hypothesis that SES and CRF predict all-cause mortality (ACM), cardiovascular disease (CVD) mortality and sudden cardiac death (SCD), and that moderate-to-high levels of CRF may attenuate the associations between low SES and adverse cardiovascular outcomes. Methods This prospective study was based on a population-based sample of 2,368 men aged 42 to 61 years, who were followed in the Kuopio Ischemic Heart Disease cohort. CRF was directly measured by peak oxygen uptake (VO2peak) during progressive exercise testing to volitional fatigue. SES was characterized using self-reported questionnaires via combined measures of income, education, occupation, occupational prestige, material standard of living, and housing conditions. CRF and SES were divided into tertiles, and 4 combined groups (Fit-high SES, Fit-low SES, Unfit-high SES, and Unfit-low SES) based on the median values of CRF and SES. Results During a 25 year median follow-up (interquartile ranges: 18–27 years), 1116 ACM, 512 CVD mortality and 221 SCD events occurred. After adjusting for potential confounders (age, smoking, alcohol, body mass index, systolic blood pressure, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, glucose, diabetes, hypertensive medication, family history of coronary heart disease, and physical activity), the lowest levels of SES were at significantly increased risk for ACM (hazard ratio (HR) 1.49, 95% Confidence Interval (CI): 1.30–1.71), CVD mortality (HR 1.38, 1.13–1.69) and SCD (HR 1.34, 0.97–1.84). In contrast, higher levels of CRF were associated with lower risks of ACM (HR 0.56, 0.46–0.67), CVD mortality (HR 0.53, 0.40–0.71) and SCD (HR 0.53, 0.34–0.83). In combined associations of SES and CRF with mortality, unfit-low SES had significantly higher risks of ACM (HR 2.12, 1.75–2.57), CVD mortality (HR 2.20, 1.64–2.94) and SCD (HR 2.95, 1.79–4.86), but fit-low SES was not associated with a heightened risk of cardiovascular mortality or SCD (CVD mortality, 1.03, 0.73–1.46; SCD, 1.54, 0.87–2.72) as compared with their fit-high SES counterparts (reference). Conclusion Our findings indicate that both SES and CRF are independently associated with the risk of death; however, moderate-to-high levels of CRF appear to attenuate the risk of CVD mortality and SCD in low SES men. These unique data have important implications for public health interventions designed to enhance survival in underserved population cohorts.

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Association between fasting blood glucose and outcomes and mortality in acute ischaemic stroke patients with diabetes mellitus: a retrospective observational study in Wuhan, China

BMJ Open ◽

10.1136/bmjopen-2020-037291 ◽

2020 ◽

Vol 10 (6) ◽

pp. e037291

Author(s):

Tao Yao ◽

Yanqiang Zhan ◽

Jing Shen ◽

Lu Xu ◽

Bo Peng ◽

...

Keyword(s):

Diabetes Mellitus ◽

Blood Glucose ◽

Ischaemic Stroke ◽

Acute Ischaemic Stroke ◽

Fasting Blood Glucose ◽

Chinese Patients ◽

Stroke Severity ◽

Unfavourable Outcome ◽

Cox Regression Analysis ◽

Risk Of Death

ObjectiveTo evaluate the predictive value of fasting blood glucose (FBG) on unfavourable outcomes and mortality in diabetes mellitus (DM) patients after acute ischaemic stroke (AIS).Study designA hospital-based observational cohort study was conducted. Clinical data, including sex, age, body mass index, vascular risk factors and systolic/diastolic blood pressure, were routinely collected. National Institutes of Health Stroke Scale score was used to assess stroke severity on admission. FBG was determined on the first day after fasting for at least 8 hours. The modified Rankin Scale was used to assess functional outcome at 90 days: 3–6, unfavourable outcome and 6, death.SettingRenmin Hospital of Wuhan University, Wuhan, China.ParticipantsPatients who had AIS with DM, who were consecutively admitted within 24 hours of onset from January 2018 to June 2019.ResultsFor the 568 patients, the median age was 65 years (IQR, 55–74 years). There were 377 (66.4%) men. The median FBG values were 7.37 mmol/L (IQR, 5.99–10.10 mmol/L), and the median glycated haemoglobin (HbA1c) values were 6.6 (IQR, 5.8–8.3). Multivariable logistic and Cox regression analysis of confounding factors showed that FBG at the time of admission was an independent predictor of unfavourable outcome (OR, 1.25 (1.14–1.37); p<0.0001) and mortality (HR, 1.10 (1.03–1.15); p<0.05) at 90 days after onset. Time to death was analysed by Kaplan-Meier curves based on FBG quartiles. The risk of death in the two highest quartile groups (FBG, 7.38–10.10 mmol/L; FBG, ≥10.11 mmol/L) was significantly higher than that in the two lowest quartile groups (FBG, ≤6.00 mmol/L; FBG, 6.01–7.37 mmol/L; p<0.0001).ConclusionsHigher FBG levels are associated with unfavourable outcomes and mortality in Chinese patients who had AIS with DM. Our data contribute to the knowledge regarding the relationship between FBG and prognosis in patients with DM who had AIS.

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Using the General Social Survey – National Death Index cohort to study the relationship between neighbourhood fear and mortality in the USA

BMJ Open ◽

10.1136/bmjopen-2019-030330 ◽

2019 ◽

Vol 9 (11) ◽

pp. e030330

Author(s):

Erin Grinshteyn ◽

Peter Muennig ◽

Roman Pabayo

Keyword(s):

Fear Of Crime ◽

General Social Survey ◽

National Death Index ◽

Social Survey ◽

Time To Death ◽

Risk Of Death ◽

Increased Risk ◽

Adjusted Model ◽

The Relationship

ObjectivesFear of crime is associated with adverse mental health outcomes and reduced social interaction independent of crime. Because mental health and social interactions are associated with poor physical health, fear of crime may also be associated with death. The main objective is to determine whether neighbourhood fear is associated with time to death.Setting and participantsData from the 1978–2008 General Social Survey were linked to mortality data using the National Death Index (GSS-NDI) (n=20 297).MethodsGSS-NDI data were analysed to assess the relationship between fear of crime at baseline and time to death among adults after removing violent deaths. Fear was measured by asking respondents if they were afraid to walk alone at night within a mile of their home. Crude and adjusted HRs were calculated using survival analysis to calculate time to death. Analyses were stratified by sex.ResultsAmong those who responded that they were fearful of walking in their neighbourhood at night, there was a 6% increased risk of death during follow-up in the adjusted model though this was not significant (HR=1.06, 95% CI 0.99 to 1.13). In the fully adjusted models examining risk of mortality stratified by sex, findings were significant among men but not women. Among men, in the adjusted model, there was an 8% increased risk of death during follow-up among those who experienced fear at baseline in comparison with those who did not experience fear (HR=1.08, 95% CI 1.02 to 1.14).ConclusionsResearch has recently begun examining fear as a public health issue. With an identified relationship with mortality among men, this is a potential public health problem that must be examined more fully.

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P1802Management and outcomes of infective endocarditis in adults with congenital heart disease

European Heart Journal ◽

10.1093/eurheartj/ehz748.0554 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

R Ly ◽

D Lebeaux ◽

F Pontnau ◽

F Compain ◽

B Gaye ◽

...

Keyword(s):

Congenital Heart Disease ◽

Heart Disease ◽

Infective Endocarditis ◽

Congenital Heart ◽

Hospital Death ◽

Oral Streptococci ◽

Mortality And Morbidity ◽

Risk Of Death ◽

Duke Criteria ◽

Increased Risk

Abstract Background Causes, epidemiology and microbiology of infective endocarditis (IE) have evolved in recent decades. Although novel tools for the diagnosis and therapeutic strategies have emerged, mortality and morbidity remain high. These trends may particularly concern the growing population of adults with congenital heart disease (CHD) who are at increased risk for IE. Purpose We aimed to characterize IE in CHD patients and describe management and outcome in this setting. We also sought to determine the risk factors associated with in-hospital death in CHD patients. Methods From January 2000 to June 2018, 666 consecutive episodes of IE in adults were recorded in our center. Among them, 143 concerned CHD, including 5 implantable cardiac electronic devices-lead infections, all managed by an IE team including CHD specialists. Cases were classified according to modified Duke criteria. Results CHD patients were significantly younger (37 years IQR [26–52]), with a more common history of cardiac reoperations (numbers of sternotomies≥2 in 35.7%) and infective endocarditis (19.7%, p<0.01) compared to non-CHD patients. There were more infections of valve-containing prosthetics (44% vs. 30%, p<0.04), and the right heart side (41.5%, p<0.01) in CHD patients. Forty-nine percent of them had a simple CHD, 12.7% a moderate, and 36.4% a complex. A predisposing event could be identified in only 34% of cases. Oral streptococci/Streptococci bovis and Staphylococcus aureus were the most frequently microorganisms isolated (32.4% and 20.4%, respectively). Surgery was performed in 90 episodes (62%), and was selected in emergency (<24h) in 61% (figure 1). In-hospital mortality was 12.7% and was directly related to IE in 10/18 cases. CHD patients had a significant lower risk of death compared to non-CHD patients (OR=0.47, p=0.026, p<0.01), even after adjustment for age, and the infected heart side. On multivariate analysis the complexity of CHD (if simple CHD: OR=0.07 IQR [0.01 to 0.44], p<0.01) and the white blood cell count (OR=1.18 IQR [1.04 to 1.33], p=0.01) were the strongest predictive factors of in-hospital death in the CHD group. Conclusions Mortality associated with IE in CHD patients is lower than in acquired heart disease. The multidisciplinary approach by IE team and CHD specialists may have improved management and outcome in this setting. However, risk for death remains high in complex lesions. Larger prospective studies on IE in adults with CHD are needed to develop guidelines in these complex patients.

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The Risk of Day 100 Mortality Following Umbilical Cord Blood Transplantation Is Significantly Higher in Patients Who Do Not Achieve An ANC of 100 by Day +16 Post Transplant

Blood ◽

10.1182/blood.v118.21.3033.3033 ◽

2011 ◽

Vol 118 (21) ◽

pp. 3033-3033 ◽

Cited By ~ 1

Author(s):

Ann Dahlberg ◽

Filippo Milano ◽

Ted A. Gooley ◽

Colleen Delaney

Keyword(s):

Cord Blood ◽

Severe Neutropenia ◽

Research Protocol ◽

Post Transplant ◽

Risk Of Death ◽

Cord Blood Transplant ◽

Number Of Patients ◽

Increased Risk ◽

Conditioning Regimens ◽

The Relationship

Abstract Abstract 3033 Background: Cord blood transplant (CBT) recipients have higher infection-related morbidity and mortality than recipients of other stem cells sources following allogeneic transplant due to delayed hematopoietic recovery and immune reconstitution. Even in recipients of myeloablative (MA) double cord blood transplant (dCBT), time to engraftment (defined as the first of two consecutive days with an absolute neutrophil count (ANC) ≥ 500/μl) is delayed more than three weeks resulting in higher rates of infection in the first 100 days post-transplant. However, a better understanding of the relationship between duration of neutropenia and risk of early transplant related mortality is needed to assess the clinical impact of methodologies aimed at reducing neutropenia post transplant. Previously, the relationship between severe neutropenia (ANC ≤ 100/μl) and risk of death was evaluated for allogeneic bone marrow transplant recipients using proportional hazards models and demonstrated a significantly increased risk for those with severe neutropenia at day 15 or beyond following transplantation (Offner et al, Blood, 1996; 88(10): 4058–62). Here we use a similar model to determine how duration of severe neutropenia relates to risk of death following CBT. Methods: All patients (n=137) who received a CBT on a research protocol at a single institution from 2006–2010 were eligible. On each day from day 0 to day +100, surviving patients were divided into those with ANC ≤ 100/μl and those with ANC >100/μl and the number of patients who died by day +100 determined for each group. Hazard ratios (HR) with 95% confidence intervals for day +100 mortality were then calculated for day post-CBT with the HR representing the risk of day +100 death among those with ANC ≤ 100/μl relative to those with ANC >100/μl for each day. Results: Of the 137 patients who received a CBT on a research protocol, 99 patients (72%) received MA conditioning regimens and 38 patients (28%) received reduced-intensity conditioning regimens (RIC). Twenty-two patients (16%) received a single cord blood unit while the remainder received dCBT. As the overall results and trends observed for patients receiving MA or RIC regimens were similar, only the combined results are presented. Thirty-one patients (23%) died before day +100. Causes of death were primary graft failure (17), infection (7), disease relapse (5), multi-organ failure (1), and leukoencephalopathy (1). The median time to engraftment was the same (20 days) for those with death before day+100 (9–39 days) as those alive at day+100 (6–69 days). The hazard ratio for day 100 mortality by day post-CBT was significantly higher for patients with ANC ≤ 100/μl beginning on day +16 and remained so through day +50, at which point the number of patients with ANC ≤ 100/μl was small and thus the calculations were no longer significant. The HRs for each day post-CBT from day 0 to day +50 are plotted in Figure 1 along with their 95% upper and lower confidence intervals. From the graphical plot of these HRs, one can identify date ranges (days 0–12, days 13–23, days 24–40, days 41–100) where the HRs are roughly equivalent with a clear increase in HR in the next date range. Modeling ANC ≤ 100/μl as a time-dependent covariate, we calculated HRs for each of these date ranges and found a significantly increased risk of day 100 mortality for days 12–23 (HR=2.96, p=0.01), days 24–40 (HR=5.53, p=0.0004), and days 41–100 (HR=14.59, p<0.0001) for patients with ANC ≤ 100/μl. The HR was 1.16 (0.49–2.76, p=0.73) for days 0–12; however, some of these patients had initial autologous recovery following RIC regimens and poor outcomes. Conclusions: Our study demonstrates that severe neutropenia, defined as ANC ≤ 100, poses a significant increased risk of day 100 mortality for recipients of CBT as early as 12–23 days post-CBT. Importantly, this patient cohort was transplanted in the modern era of aggressive supportive care, including use of newer antimicrobials. However, despite this, severe neutropenia remains a significant risk factor for day 100 mortality in recipients of CBT. Interestingly, median time to engraftment (ANC ≥ 500/μl) was the same for those with death before day+100 as those alive at day+100 suggesting that time to ANC of 100 may be a better predictor of early death following CBT. Thus, strategies that result in more rapid myeloid recovery (to an ANC of 100) remain essential for recipients of CBT. Disclosures: No relevant conflicts of interest to declare.

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