8. 2018SCCM 疼痛、激惹/镇静、谵妄、制动与睡眠干扰指南（PADIS）解读与实施
9. 2018SCCM 疼痛、激惹/镇静、谵妄、制动与睡眠干扰指南（PADIS）要目
12. NEJM 病例决策分享 ： ECMO 治疗ARDS
13.Josh Farkas 即将发布网络重症医学新书
1. ATS提前发表：来自纽约州的调查：强制执行脓毒症报告及Bundle降低脓毒症病死率 Mortality Changes Associated with Mandated Public Reporting for Sepsis: The Results of the New York State Initiative
Mitchell M Levy , Foster C Gesten , Gary S Phillips , Kathleen M. Terry , Christopher W Seymour , Hallie C Prescott , Marcus Friedrich , Theodore J. Iwashyna , Tiffany Osborn , and Stanley Lemeshow
Rationale: In 2013, the New York State Department of Health (NYSDOH) began an initiative to improve recognition and treatment of severe sepsis and septic shock. Objectives: This study examines protocol initiation, 3-hour and 6-hour sepsis bundle completion, and hospital mortality among adult patients with severe sepsis and septic shock. Methods: Cohort analysis of patients from 183 hospitals in New York State from April 1, 2014 to June 30, 2016 Participants: 113,380 cases submitted to NYSDOH of which 91,357 hospitalizations met study criteria. . Interventions: NYSDOH required all hospitals to submit and follow evidenced-informed protocols (including elements of 3- and 6-hour sepsis bundles-lactate measurement, early blood cultures and antibiotic administration, fluids and vasopressors) for identification and treatment of severe sepsis or septic shock (5). Measurements and main results: Compliance with elements of the sepsis bundles and risk-adjusted mortality. Of 91,357 patients, 74,293 (81.3%) had the sepsis protocol initiated. Among these individuals, 3-hour bundle compliance increased from 53.4% to 64.7% during the study period (p < 0.001)), while among those eligible for the 6-hour bundle (n = 35,307) compliance increased from 28.8% to 41.8% (p < 0.001). Risk-adjusted mortality decreased from 23.9% to 30.8% (p < 0.001) in patients among whom a sepsis protocol was initiated. Greater hospital compliance with 3-hour and 6-hour bundles was associated with shorter length of stay and lower risk-adjusted mortality. Conclusions: New York's statewide initiative increased compliance with sepsis-performance measures. Risk-adjusted sepsis mortality decreased during the initiative and was associated with increased hospital-level compliance.
评论：这是SSC指南最主要制定者之一Levy MM（另一位就是Dellinger）再次利用公共数据证实对SSC 3h和6hBundle执行依从性的增高可显著缩短住院日和校正后的病死率！
2. 快诱导插管造成甲状腺风暴Thyroid storm following rapid sequence intubation
Thyroid storm is a rare complication with an estimated incidence ranging from 0.61 to 0.76 cases per 100,000 people. Common causes include intrinsic hyperthyroidism, such as in Grave's disease, infection, surgery, severe emotional stress, and acute trauma to the thyroid gland. Without immediate treatment, mortality is seen in up to 30% of cases. Here, we report a case of a 46-year-old male who presented with a possible food impaction for the past 48 h. The patient developed extreme hypertension, tachycardia, and diaphoresis immediately following rapid sequence intubation (RSI), which, after further work-up, was due to thyroid storm.
3. 评论：开放吸氧确可恶化重症患者预后吗？ Is the Liberal Use of Oxygen Associated With Worse Outcomes Among Critically Ill Patients?
4. 2018SSC指南Bundle：当指南“赶超”证据 The 2018 Surviving Sepsis Campaign’s Treatment Bundle: When Guidelines Outpace the Evidence Supporting Their Use
Inadvertent catastrophes often arise from good intentions. One recent medical care example of this phenomenon was the 2002 Centers for Medicare & Medicaid Services (CMS) National Hospital Quality Measure for the initial management of community-acquired pneumonia.1 This measure called for obtaining blood cultures and administering antibiotics within 4 hours of emergency department (ED) triage in patients being admitted with pneumonia, even if pneumonia was not clearly present on arrival. These metrics had little evidentiary basis but led to an institutional-fostered culture of overdiagnosis and overtreatment.2 Eventually, many recognized the downstream harms of antibiotic overuse and misuse,2 prompting the loss of the National Quality Forum measure endorsement and the measure’s subsequent removal as a CMS quality metric. Have we learned from this folly or does a new sepsis guideline promote similar time-based treatment strategies with little direct supporting evidence?
Although well intentioned, the current sepsis bundles and the potential penalties associated with noncompliance lay a heavy weight on ED care absent evidence that a net benefit will follow. The proposed Surviving Sepsis Campaign abbreviated bundle heightens the burden by further restricting the time allotted for the identification and treatment of patients with suspected sepsis, all without any evidence of benefit or knowledge of the logistic consequences or cost. A more thoughtful approach to both the identification and management of patients with sepsis is needed, one that engages all stakeholders and experts, including the emergency medicine clinicians who treat most patients hospitalized with sepsis and who will be responsible for implementing these recommendations. A better strategy will identify more meaningful time stamps, focus less on the exact volume of fluid administered, and concentrate on identifying the subgroup of septic patients who will benefit from timely, appropriate care while limiting the diagnostic noise and logistic burdens that come with oversensitive screening tools. Absent this reevaluation and reconstructing, we may look back on our current efforts with the same sense of embarrassment and regret once experienced with the pneumonia quality metric.
5. 尿液肌酐与重症患者远期与近期预后病死率 Urinary creatinine excretion is related to short-term and long-term mortality in critically ill patients
Purpose Patients with reduced muscle mass have a worse outcome, but muscle mass is difficult to quantify in the ICU. Urinary creatinine excretion (UCE) reflects muscle mass, but has not been studied in critically ill patients. We evaluated the relation of baseline UCE with short-term and long-term mortality in patients admitted to our ICU.
Methods Patients who stayed ≥ 24 h in the ICU with UCE measured within 3 days of admission were included. We excluded patients who developed acute kidney injury stage 3 during the first week of ICU stay. As muscle mass is considerably higher in men than women, we used sex-stratified UCE quintiles. We assessed the relation of UCE with both in-hospital mortality and long-term mortality.
Results From 37,283 patients, 6151 patients with 11,198 UCE measurements were included. Mean UCE was 54% higher in males compared to females. In-hospital mortality was 17%, while at 5-year follow-up, 1299 (25%) patients had died. After adjustment for age, sex, estimated glomerular filtration rate, body mass index, reason for admission and disease severity, patients in the lowest UCE quintile had an increased in-hospital mortality compared to the patients in the highest UCE quintile (OR 2.56, 95% CI 1.96–3.34). For long-term mortality, the highest risk was also observed for patients in the lowest UCE quintile (HR 2.32, 95% CI 1.89–2.85), independent of confounders.
Conclusions In ICU patients without severe renal dysfunction, low urinary creatinine excretion is associated with short-term and long-term mortality, independent of age, sex, renal function and disease characteristics, underscoring the role of muscle mass as risk factor for mortality and UCE as relevant biomarker.
6. ICM白皮书：利益冲突声明 White paper: statement on conflicts of interest
Introduction Conflicts of interest are a normal part of human social intercourse. They become problematic when there is a power differential between participants in the setting of relationships requiring a high degree of trust, as in healthcare. In this white paper we consider how these conflicts may be detected and mitigated.
Methods Following Medline search and reference chaining, we undertook a narrative review of the literature with iterative discussion.
Results Conflicts of interest may be financial, professional or personal, and may operate at the level of the individual or the organisation. Unmanaged, they become a source of bias which places the interests of the professional or the organisation before those of the patient. Reported with increasing frequency, conflicts damage trust, harm patients, and defraud the health system. We make 15 recommendations for minimising conflicts of interest.
Conclusions Nationally funded open-access registries should be established to permit complete disclosure of financial, professional, and personal relationships with the potential for driving bias in research, clinical practice, or health management. Governance of disclosure should be the responsibility of employing organisations through annual staff appraisals, audited by national research integrity committees. Research fraud should incur suspension of the license to practice. Organisations should monitor staff perceptions of ethical climate to enhance awareness of staff behaviours and the potential for misconduct driven by academic pressures. Clear separation of advisory and voting roles is needed in best practice guideline panels. Professional societies and scientific journals should display conflict of interest policies for their own staff and officers as well as for speakers and authors. Undergraduates should not be exposed to pharmaceutical promotions masquerading as education. Undergraduate and postgraduate training programmes should include teaching about managing conflicts of interest and identifying research misconduct.
7. 2018SCCM疼痛、激惹/镇静、谵妄、制动与睡眠干扰指南（PADIS）的方法学创新 Methodologic Innovation in Creating Clinical Practice Guidelines: Insights From the 2018 Society of Critical Care Medicine Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption Guideline Effort
Objectives: To describe novel guideline development strategies created and implemented as part of the Society of Critical Care Medicine’s 2018 clinical practice guidelines for pain, agitation (sedation), delirium, immobility (rehabilitation/mobility), and sleep (disruption) in critically ill adults.
Design: We involved critical illness survivors from start to finish, used and expanded upon Grading of Recommendations, Assessment, Development and Evaluation methodology for making recommendations, identified evidence gaps, and developed communication strategies to mitigate challenges.
Setting/Subjects: Thirty-two experts from five countries, across five topic-specific sections; four methodologists, two medical librarians, four critical illness survivors, and two Society of Critical Care Medicine support staff.
Interventions: Unique approaches included the following: 1) critical illness survivor involvement to help ensure patient-centered questions and recommendations; 2) qualitative and semiquantitative approaches for developing descriptive statements; 3) operationalizing a three-step approach to generating final recommendations; and 4) systematic identification of evidence gaps.
Measurements and Main Results: Critical illness survivors contributed to prioritizing topics, questions, and outcomes, evidence interpretation, recommendation formulation, and article review to ensure that their values and preferences were considered in the guidelines. Qualitative and semiquantitative approaches supported formulating descriptive statements using comprehensive literature reviews, summaries, and large-group discussion. Experts (including the methodologists and guideline chairs) developed and refined guideline recommendations through monthly topic-specific section conference calls. Recommendations were precirculated to all members, presented to, and vetted by, most members at a live meeting. Final electronic voting provided links to all forest plots, evidence summaries, and “evidence to decision” frameworks. Written comments during voting captured dissenting views and were integrated into evidence to decision frameworks and the guideline article. Evidence gaps, reflecting clinical uncertainty in the literature, were identified during the evidence to decision process, live meeting, and voting and formally incorporated into all written recommendation rationales. Frequent scheduled “check-ins” mitigated communication gaps.
Conclusions: Our multifaceted, interdisciplinary approach and novel methodologic strategies can help inform the development of future critical care clinical practice guidelines.
8. 2018SCCM 疼痛、激惹/镇静、谵妄、制动与睡眠干扰指南（PADIS）解读与实施
Interpreting and Implementing the 2018 Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption Clinical Practice Guideline
The 2018 Clinical Practice Guideline for the Prevention and Management of Pain, Agitation (Sedation), Delirium, Immobility, and Sleep (Disruption) (PADIS) in adult patients in the ICU addresses new management challenges related to pain, agitation, and delirium and offers guidance on two additional topics—rehabilitation/mobility and sleep (1 , 2). The PADIS guidelines build on the 2013 Society of Critical Care Medicine (SCCM) PAD guidelines (3) and incorporate a number of methodological innovations, including critical illness survivor input from start to finish (4–6). The PADIS methods, with an emphasis on those approaches that are novel, are outlined in a separate methods article (7).
9. 2018SCCM 疼痛、激惹/镇静、谵妄、制动与睡眠干扰指南（PADIS）要目 Executive Summary: Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the ICU
Clinical practice guidelines are published and promoted, often by professional societies, because they provide a current and transparently analyzed review of relevant research and are written with the aim to guide clinical practice. The 2018 Pain, Agitation/sedation, Delirium, Immobility (rehabilitation/mobilization), and Sleep (disruption) (PADIS) guidelines (1) first 1) builds on this mission by updating the 2013 PAD guidelines (2); 2) by adding two inextricably related clinical care topics (immobility and sleep); 3) by including patients as collaborators and coauthors; and 4) by inviting panelists from high-income countries as an early step toward incorporating more diverse practices and expertise from the global critical care community.
Readers will find rationales for 37 recommendations (derived from actionable Patient Intervention Comparison Outcome questions), two good practice statements, and 32 statements (derived from nonactionable, descriptive questions for which the Grading of Recommendations Assessment, Development and Evaluation methodology was not used) across the five guideline sections. Only two of the 37 recommendations are strong; most are conditional. Compared with a strong recommendation (most desirable to clinicians), conditional recommendations apply to most, but not all critically ill adults, and are made when evidence is conflicting, low quality, insufficient and/or applicable to just one patient subgroup, and/or when potential benefits require weighing almost equal risks. The supplemental digital figures and tables linked to the full guideline provide background on how the questions were established, profiles of the evidence, the “evidence to decision” tables used to develop recommendations, and voting results. We also describe the evidence gaps that prevented us from fully addressing all clinical priority questions.
10. 创新抗流感药物Xofluza治疗成人与青少年流感 Baloxavir Marboxil for Uncomplicated Influenza in Adults and Adolescents
BACKGROUND Baloxavir marboxil is a selective inhibitor of influenza cap-dependent endonuclease. It has shown therapeutic activity in preclinical models of influenza A and B virus infections, including strains resistant to current antiviral agents.
METHODS We conducted two randomized, double-blind, controlled trials involving otherwise healthy outpatients with acute uncomplicated influenza. After a dose-ranging (10 to 40 mg) placebo-controlled trial, we undertook a placebo- and oseltamivir-controlled trial of single, weight-based doses of baloxavir (40 or 80 mg) in patients 12 to 64 years of age during the 2016–2017 season. The dose of oseltamivir was 75 mg twice daily for 5 days. The primary efficacy end point was the time to alleviation of influenza symptoms in the intention-to-treat infected population.
RESULTS In the phase 2 trial, the median time to alleviation of influenza symptoms was 23.4 to 28.2 hours shorter in the baloxavir groups than in the placebo group (P<0.05). In the phase 3 trial, the intention-to-treat infected population included 1064 patients; 84.8 to 88.1% of patients in each group had influenza A(H3N2) infection. The median time to alleviation of symptoms was 53.7 hours (95% confidence interval [CI], 49.5 to 58.5) with baloxavir, as compared with 80.2 hours (95% CI, 72.6 to 87.1) with placebo (P<0.001). The time to alleviation of symptoms was similar with baloxavir and oseltamivir. Baloxavir was associated with greater reductions in viral load 1 day after initiation of the regimen than placebo or oseltamivir. Adverse events were reported in 20.7% of baloxavir recipients, 24.6% of placebo recipients, and 24.8% of oseltamivir recipients. The emergence of polymerase acidic protein variants with I38T/M/F substitutions conferring reduced susceptibility to baloxavir occurred in 2.2% and 9.7% of baloxavir recipients in the phase 2 trial and phase 3 trial, respectively.
CONCLUSIONS Single-dose baloxavir was without evident safety concerns, was superior to placebo in alleviating influenza symptoms, and was superior to both oseltamivir and placebo in reducing the viral load 1 day after initiation of the trial regimen in patients with uncomplicated influenza. Evidence for the development of decreased susceptibility to baloxavir after treatment was also observed. (Funded by Shionogi; JapicCTI number, 153090, and CAPSTONE-1 ClinicalTrials.gov number, NCT02954354.)
相关知识：今年2月，由盐野义制药（Shionogi）研发的新型抗流感药物Xofluza（Baloxavir marboxil，曾用名：S-033188）得到了加速批准，在日本上市。Xofluza是一款创新的Cap依赖型核酸内切酶抑制剂，也是世上少数可以抑制流感病毒增殖的新药。它能针对流感病毒复制的关键环节，抑制它从宿主细胞中获得宿主mRNA 5′端的CAP结构，从而抑制流感病毒自身mRNA的转录。由于宿主细胞内不存在有类似机制的蛋白酶，这一药物理论上不会对宿主细胞产生影响。
11. 冠脉CT与5年心梗风险 Coronary CT Angiography and 5-Year Risk of Myocardial Infarction
BACKGROUND Although coronary computed tomographic angiography (CTA) improves diagnostic certainty in the assessment of patients with stable chest pain, its effect on 5-year clinical outcomes is unknown.
METHODS In an open-label, multicenter, parallel-group trial, we randomly assigned 4146 patients with stable chest pain who had been referred to a cardiology clinic for evaluation to standard care plus CTA (2073 patients) or to standard care alone (2073 patients). Investigations, treatments, and clinical outcomes were assessed over 3 to 7 years of follow-up. The primary end point was death from coronary heart disease or nonfatal myocardial infarction at 5 years.
RESULTS The median duration of follow-up was 4.8 years, which yielded 20,254 patient-years of follow-up. The 5-year rate of the primary end point was lower in the CTA group than in the standard-care group (2.3% [48 patients] vs. 3.9% [81 patients]; hazard ratio, 0.59; 95% confidence interval [CI], 0.41 to 0.84; P=0.004). Although the rates of invasive coronary angiography and coronary revascularization were higher in the CTA group than in the standard-care group in the first few months of follow-up, overall rates were similar at 5 years: invasive coronary angiography was performed in 491 patients in the CTA group and in 502 patients in the standard-care group (hazard ratio, 1.00; 95% CI, 0.88 to 1.13), and coronary revascularization was performed in 279 patients in the CTA group and in 267 in the standard-care group (hazard ratio, 1.07; 95% CI, 0.91 to 1.27). However, more preventive therapies were initiated in patients in the CTA group (odds ratio, 1.40; 95% CI, 1.19 to 1.65), as were more antianginal therapies (odds ratio, 1.27; 95% CI, 1.05 to 1.54). There were no significant between-group differences in the rates of cardiovascular or noncardiovascular deaths or deaths from any cause.
CONCLUSIONS In this trial, the use of CTA in addition to standard care in patients with stable chest pain resulted in a significantly lower rate of death from coronary heart disease or nonfatal myocardial infarction at 5 years than standard care alone, without resulting in a significantly higher rate of coronary angiography or coronary revascularization. (Funded by the Scottish Government Chief Scientist Office and others; SCOT-HEART ClinicalTrials.gov number, NCT01149590.)
12. NEJM 病例决策分享 ： ECMO 治疗ARDS Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome
Mr. Jackson is a 36-year-old man whom you are caring for in the intensive care unit (ICU). Before this hospitalization, he was healthy and took no medications. He has never smoked, and he drinks three or four beers every week. A week ago, a couple of coworkers in his office had respiratory illnesses, and a day later, he started having fever, chills, cough, and generalized weakness. Two nights ago, he presented to the emergency department with confusion and rapidly progressive dyspnea; urgent endotracheal intubation was performed because of acute respiratory failure. Testing for influenza virus A was positive.
13.Josh Farkas 即将发布网络重症医学新书
freely available to anyone, anywhere, anytime
optimized for smartphones, facilitating on-the-fly use
robust peer review provided by any reader
updated in real time based on peer review, new evidence, and new opinions
seamless links to references and other online resources
embedded graphics, tweets, and videos
accompanying podcasts that highlight key points of each chapter
ability to search the book for any word (easier than a traditional index)
no conflicts of interest (unlike many traditional multi-author textbooks)
its own twitter account, of course
After two years of writing, the rough draft is mapped out. I am now going to review the book with an emphasis on late-breaking evidence, releasing the chapters as I go. Chapters will be released out of order to avoid topic fatigue. The book contains ~150 chapters which will be unrolled over 2-3 years.
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