Individualizing endpoints in randomized clinical trials to better inform individual patient care: the TARGET proposal

In practice, critical care practitioners individualize treatments and goals of care for each patient in light of that patient’s acute and chronic pathophysiology, as well as their beliefs and values. Yet critical care researchers routinely measure one endpoint for all patients during randomized clinical trials (RCTs), eschewing any such individualization. More recent methodology work has explored the possibility that enrollment criteria in RCTs can be individualized, as can data analysis plans. Here we propose that the specific endpoints of a RCT can be individualized—that is, different patients within a single RCT might have different secondary endpoints measured. If done rigorously and objectively, based on pre-randomization data, such individualization of endpoints may improve the bedside usefulness of information obtained during a RCT, while perhaps also improving the power and efficiency of any RCT. We discuss the theoretical underpinnings of this proposal in light of related innovations in RCT design such as sliding dichotomies. We discuss what a full elaboration of such individualization would require, and outline a pragmatic initial step towards the use of “individualized secondary endpoints” in a large RCT evaluating optimal enteral nutrition targets in the critically ill.Theodore J. Iwashyna and Adam M. Dean

Hospital Networks and the Dispersal of Hospital-Acquired Pathogens by Patient Transfer

Hospital-acquired infections (HAI) are often seen as preventable incidents that result from unsafe practices or poor hospital hygiene. This however ignores the fact that transmissibility is not only a property of the causative organisms but also of the hosts who can translocate bacteria when moving between hospitals. In an epidemiological sense, hospitals become connected through the patients they share. We here postulate that the degree of hospital connectedness crucially influences the rates of infections caused by hospital-acquired bacteria. To test this hypothesis, we mapped the movement of patients based on the UK-NHS Hospital Episode Statistics and observed that the proportion of patients admitted to a hospital after a recent episode in another hospital correlates with the hospital-specific incidence rate of MRSA bacteraemia as recorded by mandatory reporting. We observed a positive correlation between hospital connectedness and MRSA bacteraemia incidence rate that is significant for all financial years since 2001 except for 2008–09. All years combined, this correlation is positive and significantly different from zero (partial correlation coefficient r = 0.33 (0.28 to 0.38)). When comparing the referral pattern for English hospitals with referral patterns observed in the Netherlands, we predict that English hospitals more likely see a swifter and more sustained spread of HAIs. Our results indicate that hospitals cannot be viewed as individual units but rather should be viewed as connected elements of larger modular networks. Our findings stress the importance of cooperative effects that will have a bearing on the planning of health care systems, patient management and hospital infection control

Patient- and family-centered performance measures focused on actionable processes of care for persistent and chronic critical illness: protocol for a systematic review

Background: Approximately 5 to 10% of critically ill patients transition from acute critical illness to a state of persistent and in some cases chronic critical illness. These patients have unique and complex needs that require a change in the clinical management plan and overall goals of care to a focus on rehabilitation, symptom relief,discharge planning, and in some cases, end-of-life care. However, existing indicators and measures of care quality,and tools such as checklists, that foster implementation of best practices, may not be sufficiently inclusive in terms of actionable processes of care relevant to these patients. Therefore, the aim of this systematic review is to identify the processes of care, performance measures, quality indicators, and outcomes including reports of patient/family experience described in the current evidence base relevant to patients with persistent or chronic critical illness and their family members.Methods: Two authors will independently search from inception to November 2016: MEDLINE, Embase, CINAHL,Web of Science, the Cochrane Library, PROSPERO, the Joanna Briggs Institute and the International Clinical Trials Registry Platform. We will include all study designs except case series/reports o

Omega-3 supplementation in patients with sepsis: a systematic review and meta-analysis of randomized trials.

BACKGROUND: Nutritional supplementation of omega-3 fatty acids has been proposed to modulate the balance of pro- and anti-inflammatory mediators in sepsis. If proved to improve clinical outcomes in critically ill patients with sepsis, this intervention would be easy to implement. However, the cumulative evidence from several randomized clinical trials (RCTs) remains unclear. METHODS: We searched the Cochrane Library, MEDLINE, and EMBASE through December 2016 for RCTs on parenteral or enteral omega-3 supplementation in adult critically ill patients diagnosed with sepsis or septic shock. We analysed the included studies for mortality, intensive care unit (ICU) length of stay, and duration of mechanical ventilation, and used the Grading of Recommendations Assessment, Development and Evaluation approach to assess the quality of the evidence for each outcome. RESULTS: A total of 17 RCTs enrolling 1239 patients met our inclusion criteria. Omega-3 supplementation compared to no supplementation or placebo had no significant effect on mortality [relative risk (RR) 0.85; 95% confidence interval (CI) 0.71, 1.03; P = 0.10; I (2) = 0%; moderate quality], but significantly reduced ICU length of stay [mean difference (MD) -3.79 days; 95% CI -5.49, -2.09; P < 0.0001, I (2) = 82%; very low quality] and duration of mechanical ventilation (MD -2.27 days; 95% CI -4.27, -0.27; P = 0.03, I (2) = 60%; very low quality). However, sensitivity analyses challenged the robustness of these results. CONCLUSION: Omega-3 nutritional supplementation may reduce ICU length of stay and duration of mechanical ventilation without significantly affecting mortality, but the very low quality of overall evidence is insufficient to justify the routine use of omega-3 fatty acids in the management of sepsis

Perceived barriers to the regionalization of adult critical care in the United States: a qualitative preliminary study

<p>Abstract</p> <p>Background</p> <p>Regionalization of adult critical care services may improve outcomes for critically ill patients. We sought to develop a framework for understanding clinician attitudes toward regionalization and potential barriers to developing a tiered, regionalized system of care in the United States.</p> <p>Methods</p> <p>We performed a qualitative study using semi-structured interviews of critical care stakeholders in the United States, including physicians, nurses and hospital administrators. Stakeholders were identified from a stratified-random sample of United States general medical and surgical hospitals. Key barriers and potential solutions were identified by performing content analysis of the interview transcriptions.</p> <p>Results</p> <p>We interviewed 30 stakeholders from 24 different hospitals, representing a broad range of hospital locations and sizes. Key barriers to regionalization included personal and economic strain on families, loss of autonomy on the part of referring physicians and hospitals, loss of revenue on the part of referring physicians and hospitals, the potential to worsen outcomes at small hospitals by limiting services, and the potential to overwhelm large hospitals. Improving communication between destination and source hospitals, provider education, instituting voluntary objective criteria to become a designated referral center, and mechanisms to feed back patients and revenue to source hospitals were identified as potential solutions to some of these barriers.</p> <p>Conclusion</p> <p>Regionalization efforts will be met with significant conceptual and structural barriers. These data provide a foundation for future research and can be used to inform policy decisions regarding the design and implementation of a regionalized system of critical care.</p

Failure to complete adjuvant chemotherapy is associated with adverse survival in stage III colon cancer patients

Two recent North American studies have shown that completion of 5-fluorouracil (5FU)-based adjuvant chemotherapy is a major prognostic factor for the survival of elderly stage III colon cancer patients. The aim of the present study was to confirm this finding in a population-based series from Australia. The study cohort comprised 851 stage III colon cancer patients treated by surgery alone and 461 who initiated the Mayo chemotherapy regime. One-third of patients who initiated chemotherapy failed to complete more than three cycles of treatment. Independent predictors for failure to complete were treatment in district or rural hospitals, low socioeconomic index and treatment by a low-volume surgeon. Patients who failed to complete chemotherapy showed worse cancer-specific survival compared not only to those who completed treatment (HR=2.24; 95% confidence interval (CI) (1.66–3.03), P<0.001) but also to those treated by surgery alone (HR=1.37; 95% CI (1.09–1.72), P=0.008). The current and previous studies demonstrate the importance of completing adjuvant 5-FU-based chemotherapy for colon cancer. Further prospective studies are required to identify better the physiological and socioeconomic factors responsible for failure to complete chemotherapy so that appropriate improvements in health service delivery can be made

Key mechanisms by which post-ICU activities can improve in-ICU care: results of the international THRIVE collaboratives

Objective: To identify the key mechanisms that clinicians perceive improve care in the intensive care unit (ICU), as a result of their involvement in post-ICU programs. Methods: Qualitative inquiry via focus groups and interviews with members of the Society of Critical Care Medicine’s THRIVE collaborative sites (follow-up clinics and peer support). Framework analysis was used to synthesize and interpret the data. Results: Five key mechanisms were identified as drivers of improvement back into the ICU: (1) identifying otherwise unseen targets for ICU quality improvement or education programs—new ideas for quality improvement were generated and greater attention paid to detail in clinical care. (2) Creating a new role for survivors in the ICU—former patients and family members adopted an advocacy or peer volunteer role. (3) Inviting critical care providers to the post-ICU program to educate, sensitize, and motivate them—clinician peers and trainees were invited to attend as a helpful learning strategy to gain insights into post-ICU care requirements. (4) Changing clinician’s own understanding of patient experience—there appeared to be a direct individual benefit from working in post-ICU programs. (5) Improving morale and meaningfulness of ICU work—this was achieved by closing the feedback loop to ICU clinicians regarding patient and family outcomes. Conclusions: The follow-up of patients and families in post-ICU care settings is perceived to improve care within the ICU via five key mechanisms. Further research is required in this novel area

Enablers and Barriers to Implementing ICU Follow-Up Clinics and Peer Support Groups Following Critical Illness: The Thrive Collaboratives

OBJECTIVES: Data are lacking regarding implementation of novel strategies such as follow-up clinics and peer support groups, to reduce the burden of postintensive care syndrome. We sought to discover enablers that helped hospital-based clinicians establish post-ICU clinics and peer support programs, and identify barriers that challenged them. DESIGN: Qualitative inquiry. The Consolidated Framework for Implementation Research was used to organize and analyze data. SETTING: Two learning collaboratives (ICU follow-up clinics and peer support groups), representing 21 sites, across three continents. SUBJECTS: Clinicians from 21 sites. MEASUREMENT AND MAIN RESULTS: Ten enablers and nine barriers to implementation of "ICU follow-up clinics" were described. A key enabler to generate support for clinics was providing insight into the human experience of survivorship, to obtain interest from hospital administrators. Significant barriers included patient and family lack of access to clinics and clinic funding. Nine enablers and five barriers to the implementation of "peer support groups" were identified. Key enablers included developing infrastructure to support successful operationalization of this complex intervention, flexibility about when peer support should be offered, belonging to the international learning collaborative. Significant barriers related to limited attendance by patients and families due to challenges in creating awareness, and uncertainty about who might be appropriate to attend and target in advertising. CONCLUSIONS: Several enablers and barriers to implementing ICU follow-up clinics and peer support groups should be taken into account and leveraged to improve ICU recovery. Among the most important enablers are motivated clinician leaders who persist to find a path forward despite obstacles