Further deliberating the relationship between do-not-resuscitate and the increased risk of death

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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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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Impact of Delirium and Its Motor Subtypes on Stroke Outcomes

Stroke ◽

10.1161/strokeaha.120.026425 ◽

2021 ◽

Vol 52 (4) ◽

pp. 1322-1329

Author(s):

Ivã Taiuan Fialho Silva ◽

Pedro Assis Lopes ◽

Tiago Timotio Almeida ◽

Saint Clair Ramos ◽

Ana Teresa Caliman Fontes ◽

...

Keyword(s):

Functional Outcome ◽

Functional Dependence ◽

Confusion Assessment Method ◽

Assessment Method ◽

Modified Rankin Scale ◽

Stroke Patients ◽

Risk Of Death ◽

Increased Risk ◽

And Behavior ◽

The Relationship

Background and Purpose: Delirium is an acute and fluctuating impairment of attention, cognition, and behavior. Although common in stroke, studies that associate the clinical subtypes of delirium with functional outcome and death are lacking. We aimed to evaluate the influence of delirium occurrence and its different motor subtypes over stroke patients’ prognosis. Methods: Prospective cohort of stroke patients with symptom onset within 72 hours before research admission. Delirium was diagnosed by Confusion Assessment Method for the Intensive Care Unit, and its motor subtypes were defined according to the Richmond Agitation-Sedation Scale. The main outcome was functional dependence or death (modified Rankin Scale>2) at 90 days comparing: delirium versus no delirium patients; and between motor subtypes. Secondary outcomes included modified Rankin Scale score >2 at 30 days and 90-day-mortality. Results: Two hundred twenty-seven patients were enrolled. Delirium occurred in 71 patients (31.3%), with the hypoactive subtype as the most frequent, in 41 subjects (57.8%). Delirium was associated with increased risk of death and functional dependence at 30 and 90 days and higher 90-day mortality. Multivariate analysis showed delirium (odds ratio, 3.28 [95% CI, 1.17–9.22]) as independent predictor of modified Rankin Scale >2 at 90 days. Conclusions: Delirium is frequent in stroke patients in the acute phase. Its occurrence—specifically in mixed and hypoactive subtypes—seems to predict worse outcomes in this population. To our knowledge, this is the first study to prospectively investigate differences between delirium motor subtypes over functional outcome three months poststroke. Larger studies are needed to elucidate the relationship between motor subtypes of delirium and functional outcomes in the context of acute stroke.

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Prior lymphopenia is associated with mortality in primary care pneumonia: a cohort study

British Journal of General Practice ◽

10.3399/bjgp20x713981 ◽

2020 ◽

pp. bjgp20X713981

Author(s):

Fergus W Hamilton ◽

Rupert Payne ◽

David T Arnold

Keyword(s):

Primary Care ◽

Cohort Study ◽

Lymphocyte Count ◽

Cox Regression ◽

Practice Research ◽

Clinical Practice Research Datalink ◽

Risk Of Death ◽

Increased Risk ◽

One Year ◽

The Relationship

Abstract Background: Lymphopenia (reduced lymphocyte count) during infections such as pneumonia is common and is associated with increased mortality. Little is known about the relationship between lymphocyte count prior to developing infections and mortality risk. Aim: To identify whether patients with lymphopenia who develop pneumonia have increased risk of death. Design and Setting: A cohort study in the Clinical Practice Research Datalink (CPRD), linked to national death records. This database is representative of the UK population, and is extracted from routine records. Methods: Patients aged >50 years with a pneumonia diagnosis were included. We measured the relationship between lymphocyte count and mortality, using a time-to-event (multivariable Cox regression) approach, adjusted for age, sex, social factors, and potential causes of lymphopenia. Our primary analysis used the most recent test prior to pneumonia. The primary outcome was 28 day, all-cause mortality. Results: 40,909 participants with pneumonia were included from 1998 until 2019, with 28,556 having had a lymphocyte test prior to pneumonia (median time between test and diagnosis 677 days). When lymphocyte count was categorised (0-1×109/L, 1-2×109/L, 2-3×109/L, >3×109/L, never tested), both 28-day and one-year mortality varied significantly: 14%, 9.2%, 6.5%, 6.1% and 25% respectively for 28-day mortality, and 41%, 29%, 22%, 20% and 52% for one-year mortality. In multivariable Cox regression, lower lymphocyte count was consistently associated with increased hazard of death. Conclusion: Lymphopenia is an independent predictor of mortality in primary care pneumonia. Even low-normal lymphopenia (1-2×109/L) is associated with an increase in short- and long-term mortality compared with higher counts.

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Mortality Risk by Functional Status and Health-related Quality of Life in Patients with Rheumatoid Arthritis

The Journal of Rheumatology ◽

10.3899/jrheum.110491 ◽

2011 ◽

Vol 39 (1) ◽

pp. 54-59 ◽

Cited By ~ 31

Author(s):

KALEB MICHAUD ◽

MONTSERRAT VERA-LLONCH ◽

GERRY OSTER

Keyword(s):

Rheumatoid Arthritis ◽

Health Status ◽

Mortality Risk ◽

Prediction Accuracy ◽

Risk Of Death ◽

Increased Risk ◽

Sf 36 ◽

Relationship Of ◽

Prospective Longitudinal ◽

The Relationship

Objective.Patients with rheumatoid arthritis (RA) are at increased risk of death. Modern RA therapy has been shown to improve health status, but the relationship of such improvements to mortality risk is unknown. We assessed the relationship between health status and all-cause mortality in patients with RA, using the Health Assessment Questionnaire (HAQ) and the Medical Outcomes Study Short Form-36 questionnaire (SF-36) physical and mental component summary scores (PCS, MCS).Methods.Subjects (n = 10,319) were selected from the National Data Bank for Rheumatic Diseases, a prospective longitudinal observational US study with semiannual assessments of HAQ, PCS, and MCS. Risk of death up to 7 years through 2006 was obtained from the US National Death Index. Relationship of HAQ, PCS, and MCS to mortality was assessed using Cox regression models; prediction accuracy was compared using Harrell’s concordance coefficient (C).Results.Over 64,888 patient-years of followup, there were 1317 deaths. Poorer baseline health status was associated with greater mortality risk. Adjusting for age, sex, and baseline PCS and MCS, declines in PCS and HAQ were associated with higher risk of death. HAQ improvement was associated with reduced mortality risk from 6 months through 3 years; a similar relationship was not observed for PCS or MCS improvement. Controlling for baseline values, change in PCS or HAQ did not improve prediction accuracy.Conclusion.The HAQ and the SF-36 PCS are similarly and strongly associated with mortality risk in patients with RA. Change in these measures over time does not appear to add to predictive accuracy over baseline levels.

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Fall-related Injuries Mediate the Relationship between Self-Reported Hearing Loss and Mortality in Middle-Aged and Older Adults

The Journals of Gerontology Series A ◽

10.1093/gerona/glab123 ◽

2021 ◽

Author(s):

Dongjuan Xu ◽

Melissa D Newell ◽

Alexander L Francis

Keyword(s):

Older Adults ◽

Hearing Loss ◽

Structural Equation ◽

Equation Modeling ◽

Middle Aged ◽

Risk Of Death ◽

Risk Of Injury ◽

Increased Risk ◽

The Relationship ◽

Hearing Problems

Abstract Background Hearing loss is associated with a greater risk of death in older adults. This relationship has been attributed to an increased risk of injury, particularly due to falling, in individuals with hearing loss. However, the link between hearing loss and mortality across the lifespan is less clear. Methods We used structural equation modeling and mediation analysis to investigate the relationship between hearing loss, falling, injury, and mortality across the adult lifespan in public-use data from the National Health Interview Survey and the National Death Index. We examined 1) the association between self-reported hearing problems and later mortality, 2) the associations between self-reported hearing problems and the risk of injury and degree and type of injury, 3) the mediating role of falling and injury in the association between self-reported hearing problems and mortality, and 4) whether these relationships differ in young (18-39), middle-aged (40-59) and older (60+) age groups. Results In all three age ranges, those reporting hearing problems were more likely to fall, were more likely to sustain an injury, and were more likely to sustain a serious injury, than those not reporting hearing problems. While there was no significant association between hearing loss and mortality in the youngest category, there was for middle-aged and older participants and for both fall-related injury was a significant mediator in this relationship. Conclusions Fall-related injury mediates the relationship between hearing loss and mortality for middle-aged as well as older adults, suggesting a need for further research into mechanisms and remediation.

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RV Pacing Percentage

European Heart Journal ◽

10.1093/ehjci/ehaa946.0785 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

Y.M Cha ◽

M.D Metzl ◽

R.C Canby ◽

E.M Fruechte ◽

M Duggal ◽

...

Keyword(s):

Real World ◽

Cox Regression ◽

Funding Source ◽

Private Company ◽

Risk Of Death ◽

Kaplan Meier ◽

Increased Risk ◽

Rv Pacing ◽

First 90 Days ◽

The Relationship

Abstract Introduction Chronic right ventricular pacing (RVP) has been associated with dyssynchrony, leading to increased mortality. However, there have been discrepancies in previous reports in the effect of RVP levels. Objective To sub-stratify mortality risk by age for different RVP level groups within a large real-world ICD cohort. Methods Optum® de-identified electronic health records were linked to the Medtronic Carelink data to identify dual chamber ICD recipients (2007–2017). RVP level was based on median daily pacing during the first 90 days post-implant and categorized either into groups with a cutoff of 40%, or with groups of 0–9%, 10–19%, 20–29%, 30–39%, 40–49%, and 50–100%. The endpoint was death more than 90 days post-implant. Kaplan-Meier survival curves, log-rank tests, and Cox regression were used to analyze the relationship between RVP and risk of death. Results Among 14,832 ICD patients (median age 67; 74.0% male), there were 2,602 deaths within 10 years after implant. In unadjusted comparisons, high RVP (>40%) increased the risk of death relative to low RVP (≤40%) (p<0.001). This effect remained significant in older cohort (≥67 years old at implant) (p<0.001), but not in younger cohort (<67 years old) (p=0.955) (Figure). After controlling for age, gender, pacing mode, MI, SCA, HF hospitalization, diabetes, and renal dysfunction, similar or increased risk was associated with higher pacing groups relative to the 0–9% pacing group in the older cohort, but not in the younger cohort. Conclusions Our data from a large contemporaneous real-world source suggests that older age or characteristics associated with age make patients more sensitive to chronic RVP effects. These results help reconcile differences observed in prior studies. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Medtronic, Inc.

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Increased Risk of Death in Patients With Do-Not-Resuscitate Orders

Medical Care ◽

10.1097/00005650-199908000-00003 ◽

1999 ◽

Vol 37 (8) ◽

pp. 727-737 ◽

Cited By ~ 78

Author(s):

Laura B. Shepardson ◽

Stuart J. Youngner ◽

Theodore Speroff ◽

Gary E. Rosenthal

Keyword(s):

Do Not Resuscitate ◽

Risk Of Death ◽

Increased Risk ◽

Do Not Resuscitate Orders

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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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Treatment of intracerebral hemorrhage: From specific interventions to bundles of care

International Journal of Stroke ◽

10.1177/1747493020964663 ◽

2020 ◽

Vol 15 (9) ◽

pp. 945-953

Author(s):

Adrian R Parry-Jones ◽

Tom J Moullaali ◽

Wendy C Ziai

Keyword(s):

Intracerebral Hemorrhage ◽

Vitamin K ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Phase Iii ◽

Hematoma Expansion ◽

Care Bundle ◽

Do Not Resuscitate ◽

Risk Of Death ◽

Increased Risk

Intracerebral hemorrhage (ICH) represents a major, global, unmet health need with few treatments. A significant minority of ICH patients present taking an anticoagulant; both vitamin-K antagonists and increasingly direct oral anticoagulants. Anticoagulants are associated with an increased risk of hematoma expansion, and rapid reversal reduces this risk and may improve outcome. Vitamin-K antagonists are reversed with prothrombin complex concentrate, dabigatran with idarucizumab, and anti-Xa agents with PCC or andexanet alfa, where available. Blood pressure lowering may reduce hematoma growth and improve clinical outcomes and careful (avoiding reductions ≥60 mm Hg within 1 h), targeted (as low as 120–130 mm Hg), and sustained (minimizing variability) treatment during the first 24 h may be optimal for achieving better functional outcomes in mild-to-moderate severity acute ICH. Surgery for ICH may include hematoma evacuation and external ventricular drainage to treat hydrocephalus. No large, well-conducted phase III trial of surgery in ICH has so far shown overall benefit, but meta-analyses report an increased likelihood of good functional outcome and lower risk of death with surgery, compared to medical treatment only. Expert supportive care on a stroke unit or critical care unit improves outcomes. Early prognostication is difficult, and early do-not-resuscitate orders or withdrawal of active care should be used judiciously in the first 24–48 h of care. Implementation of acute ICH care can be challenging, and using a care bundle approach, with regular monitoring of data and improvement of care processes can ensure consistent and optimal care for all patients.

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