The tensions between evaluating treatments (learning) and just treating patients (doing) during the COVID-19 pandemic are described. The clinical research and practice communities are encouraged to ...support each other's imperatives, so that both can "learn from doing" in a more integrated patient care approach. Actions toward the realization of this goal are also proposed.
Randomized clinical trials (RCTs) have revolutionized medicine by providing evidence on the efficacy and safety of drugs, devices, and procedures. Today, more than 40,000 RCTs are reported annually, ...their quality continues to increase, and oversight mechanisms ensure adequate protection of participants. However, RCTs have at least 4 related problems: they are too expensive and difficult; their findings are too broad (average treatment effect not representative of benefit for any given individual) and too narrow (trial population and setting not representative of general practice); randomizing patients can make patients and physicians uncomfortable, especially when comparing different types of existing care; and there are often long delays before RCT results diffuse into practice. Here, Angus proposes ways that electronic health records and other "big data" can be integrated with randomized trial designs to leverage the strengths of both for research inferences, including conducting RCTs as freestanding enterprise.
Enhancing Recovery From Sepsis: A Review Prescott, Hallie C; Angus, Derek C
JAMA : the journal of the American Medical Association,
01/2018, Letnik:
319, Številka:
1
Journal Article
Recenzirano
IMPORTANCE: Survival from sepsis has improved in recent years, resulting in an increasing number of patients who have survived sepsis treatment. Current sepsis guidelines do not provide guidance on ...posthospital care or recovery. OBSERVATIONS: Each year, more than 19 million individuals develop sepsis, defined as a life-threatening acute organ dysfunction secondary to infection. Approximately 14 million survive to hospital discharge and their prognosis varies. Half of patients recover, one-third die during the following year, and one-sixth have severe persistent impairments. Impairments include development of an average of 1 to 2 new functional limitations (eg, inability to bathe or dress independently), a 3-fold increase in prevalence of moderate to severe cognitive impairment (from 6.1% before hospitalization to 16.7% after hospitalization), and a high prevalence of mental health problems, including anxiety (32% of patients who survive), depression (29%), or posttraumatic stress disorder (44%). About 40% of patients are rehospitalized within 90 days of discharge, often for conditions that are potentially treatable in the outpatient setting, such as infection (11.9%) and exacerbation of heart failure (5.5%). Compared with patients hospitalized for other diagnoses, those who survive sepsis (11.9%) are at increased risk of recurrent infection than matched patients (8.0%) matched patients (P < .001), acute renal failure (3.3% vs 1.2%, P < .001), and new cardiovascular events (adjusted hazard ratio HR range, 1.1-1.4). Reasons for deterioration of health after sepsis are multifactorial and include accelerated progression of preexisting chronic conditions, residual organ damage, and impaired immune function. Characteristics associated with complications after hospital discharge for sepsis treatment are not fully understood but include both poorer presepsis health status, characteristics of the acute septic episode (eg, severity of infection, host response to infection), and quality of hospital treatment (eg, timeliness of initial sepsis care, avoidance of treatment-related harms). Although there is a paucity of clinical trial evidence to support specific postdischarge rehabilitation treatment, experts recommend referral to physical therapy to improve exercise capacity, strength, and independent completion of activities of daily living. This recommendation is supported by an observational study involving 30 000 sepsis survivors that found that referral to rehabilitation within 90 days was associated with lower risk of 10-year mortality compared with propensity-matched controls (adjusted HR, 0.94; 95% CI, 0.92-0.97, P < .001). CONCLUSIONS AND RELEVANCE: In the months after hospital discharge for sepsis, management should focus on (1) identifying new physical, mental, and cognitive problems and referring for appropriate treatment, (2) reviewing and adjusting long-term medications, and (3) evaluating for treatable conditions that commonly result in hospitalization, such as infection, heart failure, renal failure, and aspiration. For patients with poor or declining health prior to sepsis who experience further deterioration after sepsis, it may be appropriate to focus on palliation of symptoms.
Angus talks about sepsis and its search for effective therapy. Sepsis is a broad term, with its roots in the writings of Hippocrates. At its heart is the concept of a patient fighting to survive a ...life-threatening infection. And it is die fight that is thought to he injurious. The invading pathogen can be directly toxic and destructive to tissue, but much of the pathology associated with sepsis is attributed to the host response. Host immune cells exposed to pathogen-associated molecular patterns, such as lipopolysaccharide, rapidly produce a broad array of cytokines, chernokines, and other proteins to sequester and eradicate invading pathogens.
The administration of supplemental oxygen is one of the world’s most used therapies and is a cornerstone of care in the intensive care unit (ICU). The primary rationale is to avoid hypoxemia in ...patients with, or at risk for, impaired pulmonary gas exchange. Oxygen is generally considered to be widely available (which may not be true in less developed countries), inexpensive, and very safe. Consequently, it is typically administered liberally with an upward titration of the fraction of inspired oxygen (F
io
2
) to achieve a high level of arterial oxygen saturation (e.g., >96%), with less attention on avoidance of excess use. . . .
Angus discusses the study by Buell et al which considers a potential situation, supplemental oxygen support for patients requiring mechanical ventilation in the intensive care unit (ICU). They ...conducted a secondary analysis of two large randomized clinical trials to estimate individual treatment effects using a machine learning model. The results showed significant heterogeneity of treatment effects, with some patients benefiting from conservative oxygen therapy while others benefited from liberal oxygen therapy. They suggest that if these results are true and generalizable, it could lead to a significant improvement in patient outcomes. However, they also acknowledge the limitations of the study, such as overfitting of data and the impossibility of directly observing individual treatment effects. He concludes by highlighting the need for further research and the development of practical bedside decision rules for personalized medicine.
Severe Sepsis and Septic Shock Angus, Derek C; van der Poll, Tom
The New England journal of medicine,
2013-Aug-29, Letnik:
369, Številka:
9
Journal Article
Recenzirano
Odprti dostop
Sepsis, a complex physiological and metabolic response to infection, is a common reason for admission to an intensive care unit. This review examines the basis, diagnosis, and current treatment of ...this disorder.
Sepsis is one of the oldest and most elusive syndromes in medicine. Hippocrates claimed that sepsis (σήψις) was the process by which flesh rots, swamps generate foul airs, and wounds fester.
1
Galen later considered sepsis a laudable event, necessary for wound healing.
2
With the confirmation of germ theory by Semmelweis, Pasteur, and others, sepsis was recast as a systemic infection, often described as “blood poisoning,” and assumed to be the result of the host's invasion by pathogenic organisms that then spread in the bloodstream. However, with the advent of modern antibiotics, germ theory did not fully explain the pathogenesis of . . .
Reducing the global burden of sepsis, a recognized global health challenge, requires comprehensive data on the incidence and mortality on a global scale.
To estimate the worldwide incidence and ...mortality of sepsis and identify knowledge gaps based on available evidence from observational studies.
We systematically searched 15 international citation databases for population-level estimates of sepsis incidence rates and fatality in adult populations using consensus criteria and published in the last 36 years.
The search yielded 1,553 reports from 1979 to 2015, of which 45 met our criteria. A total of 27 studies from seven high-income countries provided data for metaanalysis. For these countries, the population incidence rate was 288 (95% confidence interval CI, 215-386; τ = 0.55) for hospital-treated sepsis cases and 148 (95% CI, 98-226; τ = 0.99) for hospital-treated severe sepsis cases per 100,000 person-years. Restricted to the last decade, the incidence rate was 437 (95% CI, 334-571; τ = 0.38) for sepsis and 270 (95% CI, 176-412; τ = 0.60) for severe sepsis cases per 100,000 person-years. Hospital mortality was 17% for sepsis and 26% for severe sepsis during this period. There were no population-level sepsis incidence estimates from lower-income countries, which limits the prediction of global cases and deaths. However, a tentative extrapolation from high-income country data suggests global estimates of 31.5 million sepsis and 19.4 million severe sepsis cases, with potentially 5.3 million deaths annually.
Population-level epidemiologic data for sepsis are scarce and nonexistent for low- and middle-income countries. Our analyses underline the urgent need to implement global strategies to measure sepsis morbidity and mortality, particularly in low- and middle-income countries.
In a cluster-randomized trial conducted in five ICUs, a nurse-led family-support intervention did not affect surrogates’ scores for anxiety and depression 6 months after the patients’ ...hospitalization, but it improved surrogates’ ratings of the patient-centeredness of care.
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