Reply to: Concerns about estimating relative risk of death associated with convalescent plasma for COVID-19

Inflammation is the physiologic reaction to cellular and tissue damage caused by pathologic processes including trauma, infection, and ischemia. Effective inflammatory responses integrate molecular and cellular functions to prevent further tissue damage, initiate repair, and restore homeostasis, while futile or dysfunctional responses allow escalating injury, delay recovery, and may hasten death. Elevation of white blood cell count (WBC) and altered levels of other acute phase reactants are cardinal signs of inflammation, but the dynamics of these changes and their resolution are not established. Patient responses appear to vary dramatically with no clearly defined signs of good prognosis, leaving physicians reliant on qualitative interpretations of laboratory trends. We studied the human acute inflammatory response to trauma, ischemia, and infection by tracking the longitudinal dynamics of cellular and serum markers in hospitalized patients. Unexpectedly, we identified a conserved pattern of recovery defined by co-regulation of WBC and platelet (PLT) populations. Across all inflammatory conditions studied, recovering patients followed a consistent WBC-PLT trajectory shape that is well-approximated by exponential WBC decay and delayed linear PLT growth. This recovery trajectory shape may represent a fundamental archetype of human physiologic response at the cellular population scale, and provides a generic approach for identifying high-risk patients: 32x relative risk of adverse outcomes for cardiac surgery patients, 9x relative risk of death for COVID-19, and 5x relative risk of death for myocardial infarction.

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Geografias da Diabetes Mellitus em Portugal: Como as Condições do Contexto Influenciam o Risco de Morrer

Acta Médica Portuguesa ◽

10.20344/amp.4019 ◽

2014 ◽

Vol 27 (3) ◽

pp. 309 ◽

Cited By ~ 10

Author(s):

Paula Santana ◽

Cláudia Costa ◽

Adriana Loureiro ◽

João Raposo ◽

José Manuel Boavida

Keyword(s):

Diabetes Mellitus ◽

Relative Risk ◽

Rural Areas ◽

Public Health Problem ◽

Standardized Mortality Ratio ◽

Geographic Pattern ◽

Bayesian Hierarchical ◽

Risk Of Death ◽

Mortality Ratio ◽

Relative Risk Of Death

Introduction: Diabetes Mellitus is a public health problem that is on the increase throughout the world, including in Portugal. This paper aims to identify the changing geographic pattern of this cause of death in Portugal and its association with sociomaterial deprivation. Material and Methods: This is a transversal ecological study of the deaths by Diabetes Mellitus in Portuguese municipalities in three periods (1989-1993, 1999-2003 and 2006-2010). It uses a Bayesian hierarchical model in order to obtain a smooth standardized mortality ratio and the relative risk of death by Diabetes Mellitus associated to sociomaterial deprivation. Results: In 1989-1993, the highest smooth standardized mortality ratio values were found in coastal urban municipalities (80% of municipalities with smooth standardized mortality ratio ≥ 161, of which 60% are urban); in 2006-2010, the opposite was found, with the highest smooth standardized mortality ratio values occurring in rural areas in southern inland regions (76.9% of municipalities with smooth standardized mortality ratio ≥ 161, of which 69.2% are rural), particularly the Alentejo. The relative risk of death by Diabetes Mellitus increases with vulnerability associated to social and economic conditions in the area of residence, and is significant in the last two periods (relative risk: 1.00; IC95%: 0.98-1.02). Discussion: Diabetes Mellitus presents a geographic pattern marked by coastal-inland and urban-rural asymmetry. However, this has been altering over the last twenty years. 48% of the population reside in municipalities where the smooth standardized mortality ratio has increased in the last twenty years, particularly in the rural areas of inland Portugal. Conclusion: The highest smooth standardized mortality ratio are currently found in rural municipalities with the highest index of sociomaterial deprivation. Keywords: Demography; Diabetes Mellitus/epidemiology; Diabetes Mellitus/mortality; Portugal; Socioeconomic Factors.

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Antiepileptic drug use and mortality among community-dwelling persons with Alzheimer disease

Neurology ◽

10.1212/wnl.0000000000009435 ◽

2020 ◽

Vol 94 (20) ◽

pp. e2099-e2108 ◽

Cited By ~ 1

Author(s):

Tatyana Sarycheva ◽

Piia Lavikainen ◽

Heidi Taipale ◽

Jari Tiihonen ◽

Antti Tanskanen ◽

...

Keyword(s):

Relative Risk ◽

Alzheimer Disease ◽

Antiepileptic Drug ◽

Cognitive Disorder ◽

Careful Consideration ◽

Community Dwelling ◽

Risk Of Death ◽

Vulnerable Patients ◽

Relative Risk Of Death ◽

First 90 Days

ObjectiveTo evaluate the risk of death in relation to incident antiepileptic drug (AED) use compared with nonuse in people with Alzheimer disease (AD) through the assessment in terms of duration of use, specific drugs, and main causes of death.MethodsThe MEDALZ (Medication Use and Alzheimer Disease) cohort study includes all Finnish persons who received a clinically verified AD diagnosis (n = 70,718) in 2005–2011. Incident AED users were identified with 1-year washout period. For each incident AED user (n = 5,638), 1 nonuser was matched according to sex, age, and time since AD diagnosis. Analyses were conducted with Cox proportional regression models and inverse probability of treatment weighting (IPTW).ResultsNearly 50% discontinued AEDs within 6 months. Compared with nonusers, AED users had an increased relative risk of death (IPTW hazard ratio [HR], 1.23; 95% confidence interval [CI], 1.12–1.36). This was mainly due to deaths from dementia (IPTW HR, 1.62; 95% CI, 1.42–1.86). There was no difference in cardiovascular and cerebrovascular deaths (IPTW HR, 0.98; 95% CI, 0.67–1.44). The overall mortality was highest during the first 90 days of AED use (IPTW HR, 2.40; 95% CI, 1.91–3.03). Among users of older AEDs, relative risk of death was greater compared to users of newer AEDs (IPTW HR, 1.79; 95% CI, 1.52–2.16).ConclusionIn older vulnerable patients with a cognitive disorder, careful consideration of AED initiation and close adverse events monitoring are needed.

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Decline of the relative risk of death associated with low employment grade at older age: the impact of age related differences in smoking, blood pressure and plasma cholesterol

Journal of Epidemiology & Community Health ◽

10.1136/jech.55.1.24 ◽

2001 ◽

Vol 55 (1) ◽

pp. 24-28 ◽

Cited By ~ 6

Author(s):

P J M.-v. de Mheen

Keyword(s):

Blood Pressure ◽

Relative Risk ◽

Plasma Cholesterol ◽

Older Age ◽

Risk Of Death ◽

Age Related ◽

Relative Risk Of Death ◽

The Impact

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Concerns about estimating relative risk of death associated with convalescent plasma for COVID-19

Nature Medicine ◽

10.1038/s41591-021-01638-6 ◽

2022 ◽

Author(s):

Michael J. Joyner ◽

Nigel S. Paneth ◽

Jonathon W. Senefeld ◽

DeLisa Fairweather ◽

Katelyn A. Bruno ◽

...

Keyword(s):

Relative Risk ◽

Risk Of Death ◽

Relative Risk Of Death

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Controlled trials of rG-CSF and CD11b-directed MAb during hyperoxia and E. coli pneumonia in rats

Journal of Applied Physiology ◽

10.1152/jappl.1996.80.6.2066 ◽

1996 ◽

Vol 80 (6) ◽

pp. 2066-2076 ◽

Cited By ~ 49

Author(s):

B. D. Freeman ◽

R. Correa ◽

W. Karzai ◽

C. Natanson ◽

M. Patterson ◽

...

Keyword(s):

Relative Risk ◽

Lung Injury ◽

Neutrophil Function ◽

Lung Damage ◽

E Coli ◽

Risk Of Death ◽

Pathophysiological Role ◽

O2 Concentration ◽

Hyperoxic Lung Injury ◽

Relative Risk Of Death

We studied the effects of inhibiting and augmenting neutrophil function by using an immunocompetent rat model of infectious and hyperoxic lung injury. After intrabronchial Escherichia coli challenge at all fractional inspired O2 (FIO2) values studied (FIO2 = 0.21, 0.60, and 0.95) and after lethal O2 exposure alone (FIO2 = 0.90), lung injury, as measured by histological and physiological changes, was reduced by a CD11b/CD18-directed monoclonal antibody (MAb 1B6, P < 0.05 vs. controls) but was increased by recombinant granulocyte colony-stimulating factor (rG-CSF; P < 0.05 vs. control; MAb 1B6 vs. rG-CSF, P < 0.004). Pulmonary neutrophil counts were reduced by MAb 1B6 (P < 0.04) and increased by rG-CSF (P < 0.0004) compared with control animals. However, despite antibiotics, MAb 1B6 and rG-CSF both significantly increased the relative risk of death, independent of O2 concentration, during E. coli pneumonia (1.74 [symbol: see text] 1.20 and 2.39 [symbol: see text] 1.19, respectively, each P < 0.01). During lethal hyperoxia, MAb 1B6 increased the relative risk of death (1.76 [symbol: see text] 1.28, P < 0.16), whereas rG-CSF had no effect on survival (0.97 [symbol: see text] 1.28, P = 0.89). Thus inhibition of neutrophil function attenuated and enhancement worsened lung injury in response to infectious and hyperoxic challenges, supporting a pathophysiological role of the neutrophil in these processes. However, it is problematic that MAb 1B6 therapy, despite preventing lung damage, ultimately worsened host defenses and survival. Furthermore, rG-CSF also adversely affected survival during infectious lung injury, demonstrating the inherent risks of inhibiting or augmenting neutrophil function in an immunocompetent host during infection.

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Opioid-dependent error processing

Journal of Opioid Management ◽

10.5055/jom.2011.0085 ◽

2017 ◽

Vol 7 (6) ◽

pp. 443-449

Author(s):

James Fellows-Smith, MBBS, MMedSc, MRCPsych, FRANZCP, FAchAM

Keyword(s):

Relative Risk ◽

Methadone Treatment ◽

Error Processing ◽

Opioid Overdose ◽

Community Based ◽

Risk Of Death ◽

Oral Naltrexone ◽

Naltrexone Treatment ◽

Relative Risk Of Death ◽

Methadone Program

Objective: To evaluate error processing in contrasting opioid treatment samples by finding the relative risk of fatal dosing errors leading to opioid overdose in a controlled cohort of detoxified patients with opioid dependence.Methods: Data linkage was performed between the Western Australian deaths register and recorded admissions to the Perth Naltrexone Clinic and community-based methadone program. Death register and corresponding data of coronial findings for all the patients who were treated with rapid opioid detoxification under sedation and oral naltrexone were compared with corresponding data for all the patients who were prescribed methadone over a 2-year period.Results: Data for naltrexone-treated patients (n = 1,097) and community-based methadone-treated patients (n = 2,520) showed mortality rates to be 2.6 percent per year for naltrexone treatment when compared with 0.7 percent for methadone treatment (p 0.001). This was due to 4.3 times the relative risk of death from opioid toxicity for naltrexone-treated patients (p 0.001).Conclusions: Naltrexone increases vulnerability to overdose as enhanced opioid effects following neuroanatomical blockade can reverse behavioral tolerance and lead to greater fatal dosing errors on reinstatement of opioid dependence.

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Effects and Relative Factors of Adjunctive Chinese Medicine Therapy on Survival of Hepatocellular Carcinoma Patients: A Retrospective Cohort Study in Taiwan

Integrative Cancer Therapies ◽

10.1177/1534735420915275 ◽

2020 ◽

Vol 19 ◽

pp. 153473542091527

Author(s):

Yu-Pei Liao ◽

Pei-Tseng Kung ◽

Yueh-Hsin Wang ◽

Yeong-Ruey Chu ◽

Shung-Te Kao ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Relative Risk ◽

Survival Rate ◽

Chinese Medicine ◽

Western Medicine ◽

Early Stage Disease ◽

Risk Of Death ◽

Study Results ◽

Relative Risk Of Death ◽

Relative Factors

Some patients with cancer use adjunctive Chinese medicine, which might improve the quality of life. This study aims to investigate the effects and relative factors of adjunctive Chinese medicine on survival of hepatocellular carcinoma patients at different stages. The study population was 23 581 newly diagnosed hepatocellular carcinoma patients and received surgery from 2004 to 2010 in Taiwan. After propensity score matching with a ratio of 1:10, this study included 1339 hepatocellular carcinoma patients who used adjunctive Chinese medicine and 13 390 hepatocellular carcinoma patients who used only Western medicine treatment. All patients were observed until the end of 2012. Kaplan-Meier method and Cox proportional hazards model was applied to find the relative risk of death between these 2 groups. The study results show that the relative risk of death was lower for patients with adjunctive Chinese medicine treatment than patients with only Western medicine treatment (hazard ratio = 0.68; 95% confidence interval = 0.62-0.74). The survival rates of patients with adjunctive Chinese medicine or Western medicine treatment were as follows: 1-year survival rate: 83% versus 72%; 3-year survival rate: 53% versus 44%; and 5-year survival rate: 40% versus 31%. The factors associated with survival of hepatocellular carcinoma patients included treatment, demographic characteristics, cancer stage, health status, physician characteristics, and characteristics of primary medical institution. Moreover, stage I and stage II hepatocellular carcinoma patients had better survival outcome than stage III patients by using adjunctive Chinese medicine therapy. The effect of adjunctive Chinese medicine was better on early-stage disease.

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