What should be monitored? The past, present, and future of physiological monitoring

1990 ◽  
Vol 36 (8) ◽  
pp. 1536-1543 ◽  
Author(s):  
W C Shoemaker
Keyword(s):  
High Risk ◽  
Randomized Clinical Trials ◽  
Decision Rules ◽  
Vital Signs ◽  
Normal Function ◽  
Monitoring Systems ◽  
Predictive Index ◽  
Mortality And Morbidity ◽  
Therapeutic Goals ◽  
Hemodynamic Variables

Abstract The status of conventional monitoring by vital signs and present concepts of invasive monitoring with the balloon-tipped pulmonary artery (Swan-Ganz) catheter are reviewed. Survivors of high-risk general surgery were observed to have cardiac index (CI) values averaging 4.5 L/min.m2, oxygen delivery (DO2) greater than 600 mL/min.m2, and oxygen consumption (VO2) greater than 170 mL/min.m2. By contrast, those who subsequently died during their hospitalization maintained relatively normal CI, DO2, and VO2 values. However, in the immediate postoperative period, values for other hemodynamic variables were not greatly different for survivors and nonsurvivors or different from the normal range. A predictive index based on these observations predicted outcome correctly in 94% of the subjects in a subsequent prospective study. The use of survivor values as appropriate therapeutic goals was tested in prospective randomized clinical trials and was found to reduce mortality and morbidity significantly. Simultaneous invasive and noninvasive hemodynamic and oxygen-transport monitoring systems were evaluated in high-risk postoperative patients to describe unanticipated adverse circulatory events. Before the monitored event, about three-fourths of the patients exhibited normal function. At the nadir, cardiac functions decreased in about two-thirds, perfusion decreased in more than one-half, and paO2 fell in only one-fourth. Two-thirds recovered with increased cardiac function, more than one-half had improved perfusion, and paO2 increased in fewer than one-fifth of monitored events. These data provide an information base for criteria needed to develop therapeutic decision rules for noninvasive monitoring systems. When noninvasive data are continuously displayed early in the course of critical illness and high-risk conditions, therapy may be instituted early, while physiological deficits are still minimal and easily reversible.

scholarly journals A multi-center, adaptive, randomized, platform trial to evaluate the effect of repurposed medicines in outpatients with early coronavirus disease 2019 (COVID-19) and high-risk for complications: the TOGETHER master trial protocol

2021 ◽  
Vol 5 ◽  
pp. 117
Author(s):  
Gilmar Reis ◽  
Eduardo Augusto dos Santos Moreira Silva ◽  
Daniela Carla Medeiros Silva ◽  
Kristian Thorlund ◽  
Lehana Thabane ◽  
...  
Keyword(s):  
High Risk ◽  
Adaptive Design ◽  
Randomized Clinical Trials ◽  
Decision Rules ◽  
High Body Mass Index ◽  
Controlled Clinical Trial ◽  
Middle Income ◽  
External Evidence ◽  
Equal Chance ◽  
Repurposed Drugs

Background: Although vaccines are currently available for coronavirus disease 2019 (COVID-19), there remains a need for an effective and affordable outpatient treatment for early COVID-19. Multiple repurposed drugs have shown promise in treating COVID-19. We describe a master protocol that will assess the efficacy of different repurposed drugs as treatments for early COVID-19 among outpatients at a high risk for severe complications. Methods: The TOGETHER Trial is an international (currently in Brazil and Africa), multi-center platform adaptive randomized, placebo-controlled, clinical trial. Patients are included if they are at least 18 years of age, have a positive antigen test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and have an indication for high risk of disease severity, including co-morbidities, older age, or high body mass index. Eligible patients are randomized with equal chance to an investigational product (IP) or to placebo. The primary endpoint is hospitalization due to clinical worsening of COVID-19 or emergency room required observation for more than 6 hours up to 28 days after randomization. Key secondary endpoints include viral clearance, clinical improvement, hospitalization for any cause, mortality for any cause, and safety and tolerability of each IP. Scheduled interim analyses are conducted and reviewed by the Data and Safety Monitoring Committee (DSMC), who make recommendations on continuing or stopping each IP. The platform adaptive design go-no-go decision rules are extended to dynamically incorporate external evidence on COVID-19 interventions from ongoing independent randomized clinical trials. Discussion: Results from this trial will assist in the identification of therapeutics for COVID-19 that can easily be scaled in low- and middle-income settings. The novel methodological extension of the platform adaptive design to dynamically incorporate external evidence is one of the first of its kind and may provide highly valuable information for all COVID-19 trials going forward. Clinicaltrials.gov registration: NCT04727424 (27/01/2021)

scholarly journals A multi-center, adaptive, randomized, platform trial to evaluate the effect of repurposed medicines in outpatients with early coronavirus disease 2019 (COVID-19) and high-risk for complications: the TOGETHER master trial protocol

2021 ◽  
Vol 5 ◽  
pp. 117
Author(s):  
Gilmar Reis ◽  
Eduardo Augusto dos Santos Moreira Silva ◽  
Daniela Carla Medeiros Silva ◽  
Kristian Thorlund ◽  
Lehana Thabane ◽  
...  
Keyword(s):  
High Risk ◽  
Adaptive Design ◽  
Randomized Clinical Trials ◽  
Decision Rules ◽  
High Body Mass Index ◽  
Controlled Clinical Trial ◽  
Emergency Setting ◽  
External Evidence ◽  
Equal Chance ◽  
Repurposed Drugs

Background: There remains a need for an effective and affordable outpatient treatment for early COVID-19. Multiple repurposed drugs have shown promise in treating COVID-19. We describe a master protocol that will assess the efficacy of different repurposed drugs as treatments for early COVID-19 among outpatients at a high risk for severe complications. Methods: The TOGETHER Trial is a multi-center platform adaptive randomized, placebo-controlled, clinical trial. Patients are included if they are at least 18 years of age, have a positive antigen test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and have an indication for high risk of disease severity, including co-morbidities, older age, or high body mass index. Eligible patients are randomized with equal chance to an investigational product (IP) or to placebo.The primary endpoint is hospitalization defined as either retention in a COVID-19 emergency setting for greater than 6 hours or transfer to tertiary hospital due to COVID-19. Secondary outcomes include mortality, adverse events, adherence, and viral clearance. Scheduled interim analyses are conducted and reviewed by the Data and Safety Monitoring Committee (DSMC), who make recommendations on continuing or stopping each IP. The platform adaptive design go-no-go decision rules are extended to dynamically incorporate external evidence on COVID-19 interventions from ongoing independent randomized clinical trials. Discussion: Results from this trial will assist in the identification of therapeutics for the treatment of early diagnosed COVID-19. The novel methodological extension of the platform adaptive design to dynamically incorporate external evidence is one of the first of its kind and may provide highly valuable information for all COVID-19 trials going forward. Clinicaltrials.gov registration: NCT04727424 (27/01/2021)

Trends and forecasts of the global availability of food

2020 ◽  
Vol 16 (7) ◽  
pp. 1297-1316
Author(s):  
O.N. Terent'eva
Keyword(s):  
High Risk ◽  
Growth Rates ◽  
Statistical Data ◽  
Economic Security ◽  
Agricultural Products ◽  
Mortality And Morbidity ◽  
National Economic ◽  
Production Growth ◽  
Country Analysis ◽  
Cross Country

Subject. The stable supply of food to people is a cornerstone for the national economic security, while a lack of food or its expensiveness may undermine the economy, principles of power, and cause panics and wars. Malnutrition and hunger are critical indicators of the insufficient foods supply. Objectives. The article indicates which countries have high risk of hunger, and predicts its further movement. I also evaluate factual trends in the availability of food across countries. Methods. The study refers to statistical data in public domain, including the FAOSTAT. I apply methods of ranking, abstraction, prediction. Results. I performed the cross-country analysis and discovered that 117 countries demonstrated signs of malnutrition. The article sets forth a technique for splitting countries into five groups by level of hunger risk. The article compares data on hunger in the countries and consequences of mortality and morbidity. I ranked countries by key types of agricultural products and explained their production growth rates for a span of 18 years. I predicted how countries would be ranked in terms of hunger from 2030 to 2050, and found the extent to which the hunger risk will escalate in more flourishing countries. Conclusions and Relevance. Hunger and shortage of food seem invincible in the countries where people are hungry or very hungry. Sometimes it appears almost impossible for respective governments to solve the issue. Triggering the systemic hunger, such factors and premises are beyond control of starving countries. Hence, the international community should provide their support and aid to them.

scholarly journals Hypofractionated radiotherapy versus conventional radiotherapy in patients with intermediate- to high-risk localized prostate cancer: a meta-analysis of randomized controlled trials

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Wei Guo ◽  
Yun-Chuan Sun ◽  
Jian-Qiang Bi ◽  
Xin-Ying He ◽  
Li Xiao
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Adverse Events ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Localized Prostate Cancer ◽  
Hypofractionated Radiotherapy ◽  
Cancer Specific Survival ◽  
Conventional Radiotherapy ◽  
Results Of Treatment

Abstract Background Prostate cancer is one of the most common cancers in the world. The results of treatment after hypofractionated radiotherapy only have been reported from several small randomized clinical trials. Therefore, we conducted a meta-analysis to compare clinical outcomes of hypofractionated radiotherapy versus conventional radiotherapy in the treatment of intermediate- to high-risk localized prostate cancer. Methods Relevant studies were identified through searching related databases till August 2018. Hazard ratio (HR) or risk ratio (RR) with its corresponding 95% confidence interval (CI) was used as pooled statistics for all analyses. Results The meta-analysis results showed that overall survival (HR = 1.12, 95% CI: 0.93–1.35, p = 0.219) and prostate cancer-specific survival (HR = 1.29, 95% CI: 0.42–3.95, p = 0.661) were similar in two groups. The pooled data showed that biochemical failure was RR = 0.90, 95% CI: 0.76–1.07, p = 0.248. The incidence of acute adverse gastrointestinal events (grade ≥ 2) was higher in the hypofractionated radiotherapy (RR = 1.70, 95% CI: 1.12–2.56, p = 0.012); conversely, for late grade ≥ 2 gastrointestinal adverse events, a significant increase in the conventional radiotherapy was found (RR = 0.75, 95% CI: 0.61–0.91, p = 0.003). Acute (RR = 1.01, 95% CI: 0.89–1.15, p = 0.894) and late (RR = 0.98, 95% CI: 0.86–1.10, p = 0.692) genitourinary adverse events (grade ≥ 2) were similar for both treatment groups. Conclusion Results suggest that the efficacy and risk for adverse events are comparable for hypofractionated radiotherapy and conventional radiotherapy in the treatment of intermediate- to high-risk localized prostate cancer.

Development of a breast cancer-specific prognostic tool using CancerLinQ Discovery.

2021 ◽  
Vol 39 (28_suppl) ◽  
pp. 275-275
Author(s):  
Emily Miller Ray ◽  
Xinyi Zhang ◽  
Lisette Dunham ◽  
Xianming Tan ◽  
Jennifer Elston Lafata ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Logistic Regression ◽  
Metastatic Breast Cancer ◽  
High Risk ◽  
Performance Status ◽  
Vital Signs ◽  
Metastatic Breast ◽  
Clinical Use ◽  
Final Model ◽  
Prognostic Tool

275 Background: Oncologists often struggle to know which patients are near end of life to enable a timely transition to supportive care. We developed a breast cancer-specific prognostic tool, using electronic health record data from CancerLinQ Discovery (CLQD), to help identify patients at high risk of near-term death. We created multiple candidate models with varying thresholds for defining high risk that will be considered for future clinical use. Methods: We included patients with breast cancer diagnosed between 1/1/2000 to 6/1/2020 who had at least one encounter with vital signs and evidence of metastatic breast cancer (MBC). All encounters from 1/1/2000 to 7/5/2020 were included. We used multiple imputation (MI) to impute missing numeric variables and treated missing values as a new level for categorical variables. We sampled one encounter per patient and oversampled within 30 days of death, so that the event rate (death within 30 days of encounter) was about 10%. We randomly divided these patients into training (70%) and test datasets (30%). We evaluated candidate predictors of the event using logistic regression with forward variable selection. Candidate predictors included age, vital signs, laboratory values, performance status, pain score, time since chemotherapy, and ER/PR/HER2 receptor status, and change from baseline and change rate of numeric variables. We obtained a single final model by combining resulted logistic regression model from 10 MI training sets. We evaluated this final model on the MI test sets. We varied the alert threshold (i.e., high-risk proportion) from 5% to 40%. Results: We identified 9,270 patients, representing 586,801 encounters. Significant predictors of mortality were: increased age, decreased age at diagnosis, negative change in body mass index, low albumin, high ALP, high AST, high WBC, low sodium, high creatinine, worse performance status, low pulse oximetry, increased age with increased creatinine, high pain score with no opiates, increased pulse rate, unknown/missing PR, opiate use in past 3 months, and prior chemotherapy in past 1 year but not past 30 days. Candidate models had prediction accuracy of 70-89% and positive predictive value of 31-77%. Conclusions: Demographic and clinical variables can be used to predict risk of death within 30 days of a clinical encounter for patients with MBC. Next steps include selection of a preferred model for clinical use, balancing performance characteristics and acceptability, followed by implementation and evaluation of the prognostic tool in the clinic. Candidate models, varying by threshold or percentage of patients assumed to be at high risk, for the outcome of death within 30 days among patients with metastatic breast cancer.[Table: see text]

MO817ALDOSTERONE ANTAGONISTS FOR PATIENTS WITH CHRONIC KIDNEY DISEASE REQUIRING DIALYSIS

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Takeshi Hasegawa ◽  
Hiroki Nihiwaki ◽  
Erika Ota ◽  
William Levack ◽  
Hisashi Noma
Keyword(s):  
Chronic Kidney Disease ◽  
High Risk ◽  
Kidney Disease ◽  
Standard Care ◽  
Meta Analysis ◽  
Cardiovascular Death ◽  
Aldosterone Antagonists ◽  
Mortality And Morbidity ◽  
Risk Of Death ◽  
Increased Risk

Abstract Background and Aims Patients with chronic kidney disease (CKD) undergoing dialysis are at a particularly high risk of cardiovascular mortality and morbidity. This systematic review and meta-analysis aimed to evaluate the benefits and harms of aldosterone antagonists, both non-selective (spironolactone) and selective (eplerenone), in comparison to control (placebo or standard care) in patients with CKD requiring haemodialysis or peritoneal dialysis. Method We searched the Cochrane Kidney and Transplant Register of Studies up to 29 July 2019 using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register Search Portal and ClinicalTrials.gov. We included individual and cluster randomised controlled trials (RCTs), cross-over trials, and quasi-RCTs that compared aldosterone antagonists with placebo or standard care in patients with CKD requiring dialysis. We used a random-effects model meta-analysis to perform a quantitative synthesis of the data. We used the I2 statistic to measure heterogeneity among the trials in each analysis. We indicated summary estimates as a risk ratio (RR) for dichotomous outcomes with their 95% confidence interval (CI). We assessed the certainty of the evidence for each of the main outcomes using the GRADE (Grades of Recommendation, Assessment, Development, and Evaluation) approach. Results We included 16 trials (14 parallel RCTs and two cross-over trials) involving a total of 1,446 patients. Among included studies, 13 trials compared spironolactone to placebo or standard care and one trial compared eplerenone to a placebo. Most studies had an unclear or high risk of bias. Compared to control, aldosterone antagonists reduced the risk of all-cause death for patients with CKD requiring dialysis (9 trials, 1,119 patients: RR 0.45, 95% CI 0.30 to 0.67; moderate certainty of evidence). Aldosterone antagonist also decreased the risk of death due to cardiovascular disease (6 trials, 908 patients: RR 0.37, 95% CI 0.22 to 0.64; moderate certainty of evidence) and cardiovascular and cerebrovascular morbidity (3 trials, 328 patients: RR 0.38, 95% CI 0.18 to 0.76; moderate certainty of evidence). While aldosterone antagonists had an apparent increased risk of gynaecomastia compared with control (4 trials, 768 patients: RR 5.95, 95% CI 1.93 to 18.3; moderate certainty of evidence), the elevated risk of hyperkalaemia due to aldosterone antagonists was uncertain (9 trials, 981 patients: RR 1.41, 95% CI 0.72 to 2.78; low certainty of evidence). Conclusion Based on moderate certainty of the evidence, aldosterone antagonists could reduce the risk of all-cause and cardiovascular death and morbidity due to cardiovascular and cerebrovascular disease but increase the risk of gynaecomastia in patients with CKD requiring dialysis.

scholarly journals Follicular lymphoma: are we ready for a risk-adapted approach?

Hematology ◽  
2017 ◽  
Vol 2017 (1) ◽  
pp. 358-364 ◽  
Author(s):  
Brad S. Kahl
Keyword(s):  
High Risk ◽  
Follicular Lymphoma ◽  
Randomized Clinical Trials ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Predictive Biomarkers ◽  
Western Hemisphere ◽  
Ongoing Research ◽  
High Risk Patients ◽  
Risk Patients

Abstract Follicular lymphoma is the most common indolent non-Hodgkin lymphoma in the Western hemisphere. The natural history of FL appears to have been favorably impacted by the introduction of rituximab after randomized clinical trials demonstrated that the addition of rituximab to standard chemotherapy induction has improved the overall survival. Yet, the disease is biologically and clinically heterogeneous with wide variations in outcomes for individual patients. The ability to accurately risk-stratify patients and then tailor therapy to the individual is an area of ongoing research. Historically, tumor grade, tumor burden, and the FL international prognostic index (version 1 and version 2) have been used to distinguish low-risk from high-risk patients. Biologic factors such as mutations in key genes can identify patients at high risk for poor outcomes to first-line therapy (mutational status of 7 genes [EZH2, ARID1A, MEF2B, EP300, FOX01, CREBBP, and CARD11] with Follicular Lymphoma International Prognostic Index). More recently, the quality of the response to initial therapy, as measured by either PET imaging or by remission duration, has been show to identify individuals at high risk. However, several unmet needs remain, including a better ability to identify high-risk patients at diagnosis, the development of predictive biomarkers for targeted agents, and strategies to reduce the risk of transformation.

scholarly journals Pre-NELA vs NELA – has anything changed, or is it just an audit exercise?

2016 ◽  
Vol 98 (8) ◽  
pp. 554-559 ◽  
Author(s):  
M Mak ◽  
AR Hakeem ◽  
V Chitre
Keyword(s):  
Critical Care ◽  
High Risk ◽  
Uneventful Recovery ◽  
Emergency Laparotomy ◽  
Mortality And Morbidity ◽  
High Risk Patients ◽  
Possum Score ◽  
Operative Severity Score ◽  
Risk Patients ◽  
Set Up

BACKGROUND Following evidence suggestive of high mortality following emergency laparotomies, the National Emergency Laparotomy Audit (NELA) was set up, highlighting key standards in emergency service provision. Our aim was to compare our NHS trust’s adherence to these recommendations immediately prior to, and following, the launch of NELA, and to compare patient outcome. METHODS This was a retrospective study of patients who underwent an emergency laparotomy over the course of 6 months – 3 months either side of the initiation of NELA. RESULTS There were 44 patients before the initiation of NELA (pre-NELA, PN group) and 55 in the first 3 months of NELA (N group). We saw a significant increase in the proportion of patients whose decision to operate was made by the consultant: 75.0% in the PN group vs 100% in N group (subsequent data presented in this order) (P < 0.001). The presence of a consultant surgeon (75.0% vs 83.6%, P = 0.321) and anaesthetist (100.0% vs 90.9%, P = 0.064) in theatres were comparable in both groups. Risk stratification based on Portsmouth Physiological and Operative Severity Score for the enUmeration of Mortality and Morbidity (P-POSSUM) score showed no difference in high-risk patients in both groups (47.7% vs 36.4%, P = 0.306). With the NELA initiative, however, significantly more patients were admitted directly from theatres to the critical care unit, when compared with the pre-NELA period (9.1% vs 27.3%, P = 0.038). This also reflected a significant reduction in unexpected escalation to a higher level of care during this period (10.0% vs 0%, P = 0.036). Significantly more patients had uneventful recovery in the NELA period (52.3 vs 76.4%, P = 0.018), although there was no difference in 30-day mortality between the groups (2.3% vs 7.3%, P = 0.378). CONCLUSIONS This study demonstrated a greater degree of consultant involvement in the decision to operate during NELA. More high-risk patients have been identified preoperatively with diligent risk assessment and, hence, have been proactively admitted to critical care units following laparotomy, which may account for the significant reduction in unexpected escalation to level 2 or level 3 care and thus in overall better patient outcomes.

scholarly journals Toward economic evaluation of the value of vaccines and other health technologies in addressing AMR

2018 ◽  
Vol 115 (51) ◽  
pp. 12911-12919 ◽  
Author(s):  
J. P. Sevilla ◽  
David E. Bloom ◽  
Daniel Cadarette ◽  
Mark Jit ◽  
Marc Lipsitch
Keyword(s):  
Economic Value ◽  
Decision Rules ◽  
Health Sector ◽  
Economic Evaluations ◽  
General Point ◽  
Value For Money ◽  
Mortality And Morbidity ◽  
Health Technologies ◽  
General Terms ◽  
Future Work

We discuss the need to make economic evaluations of vaccines antimicrobial resistance (AMR)-sensitive and ways to do so. Such AMR-sensitive evaluations can play a role in value-for-money comparisons of different vaccines within a national immunization program, or in comparisons of vaccine-centric and non-vaccine-centric technologies within an anti-AMR program. In general terms, incremental cost-effectiveness ratios and rates of return and their associated decision rules are unaltered by consideration of AMR-related value. The decision metrics need to have their various health, cost, and socioeconomic terms disaggregated into resistance-related subcategories, which in turn have to be measured carefully before they are reaggregated. The fundamental scientific challenges lie primarily in quantifying the causal impact of health technologies on resistance-related health outcomes, and secondarily in ascertaining the economic value of those outcomes. We emphasize the importance of evaluating vaccines in the context of other potentially complementary and substitutable nonvaccine technologies. Complementarity implies that optimal spending on each set of interventions is positive, and substitutability implies that the ratio of spending will depend on relative value for money. We exemplify this general point through a qualitative discussion of the complementarities and (especially the) substitutability between pneumococcal conjugate vaccines and antimicrobial stewardship and between research and development (R&D) of a gonorrhea vaccine versus R&D of a gonorrhea antibiotic. We propose a roadmap for future work, which includes quantifying the causal effects of vaccination and other health technologies on short-term and long-term resistance-related outcomes, measuring the health-sector costs and broader socioeconomic consequences of resistance-related mortality and morbidity, and evaluating vaccines in the context of nonvaccine complements and substitutes.

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