Frailty as a predictor of hospital length of stay after elective total joint replacements in elderly patients.

BACKGROUND: Total joint replacement procedures are increasing in number because of population aging and osteoarthritis development. Defined as a lack of physiological reserves and the inability to adequately respond to external stressors, frailty may be more common than expected in older patients with degenerative arthritis awaiting total joint replacements. The aim of the present study was to assess associations between frailty and adverse outcomes, frailty prevalence among elderly patients awaiting elective TJR, and agreement between 2 frailty screening instruments. METHODS: We undertook a prospective, observational, pilot study in our institution. We enrolled patients 65 years or older who were awaiting elective knee or hip replacement surgery and evaluated them in our preoperative clinic with planned postoperative hospital length of stay greater than 24 h. Patients were asked to grade their perceived well-being on the Clinical Frailty Scale and to answer questions on the FRAIL Scale. RESULTS: The Clinical Frailty Scale classified 40 patients (45.9%) as robust, 43 patients (49.4%) as prefrail and 4 patients (4.5%) as frail, while the FRAIL Scale categorized 12 patients (13.7%) as robust, 54 patients (62.0%) as prefrail, and 20 patients (22.9%) as frail. Robustness, ascertained on the Clinical Frailty Scale was, while the FRAIL Scale was not, significantly associated with shorter hospital length of stay and fewer discharges to the rehabilitation center. Both scales showed moderate mutual agreement. CONCLUSION: Screening for frailty identified between 5% and 10% of patients at risk of adverse outcomes. The Clinical Frailty Scale was, while the FRAIL scale was not, significantly associated with hospital length of stay and discharge to rehabilitation center in our cohort of total joint replacement patients.

A network meta-analysis of antibiotics for treatment of hospitalised patients with suspected or proven meticillin-resistant Staphylococcus aureus infection.

Infections due to meticillin-resistant Staphylococcus aureus (MRSA) pose a serious health risk. Novel methods for assessing comparative effectiveness and safety may provide valuable insights into therapeutic choices. We did a systematic review searching electronic databases including the archives of FDA/CDER and performed a Bayesian network meta-analysis to compare parenteral antibiotics used for treating hospitalised adults with complicated skin and soft-tissue infections (cSSTIs) or hospital-acquired or ventilator-associated pneumonia (HAP/VAP). Models were adjusted for clinical heterogeneity due to between-arm differences in the proportion of patients with diabetes (for cSSTI) and in those requiring mechanical ventilation (for pneumonia). Treatments were ranked on efficacy, defined as clinical success in the modified intention-to-treat population (MITT) and in the MITT population with MRSA at baseline (MRSA m-MITT), on all-cause mortality (in pneumonia only), and on serious adverse events and withdrawals due to adverse events. We identified 24 randomised controlled trials (17 for cSSTI and 10 for HAP/VAP) comparing one of six antibiotics with vancomycin. The network meta-analysis indicated that vancomycin ranked third (of six antibiotics) in cSSTI and second (of four) in pneumonia on both efficacy and safety. However, direct pairwise meta-analyses remained inconclusive as evidenced by the adjusted median odds ratios (ORs) and their 95% credible intervals. In cSSTI, linezolid and ceftaroline were non-significantly more effective than vancomycin. Linezolid ORs were 1.15 (0.74-1.71) and 1.01 (0.42-2.14) and ceftaroline ORs were 1.12 (0.78-1.64) and 1.59 (0.68-3.74) in the MITT and MRSA m-MITT populations, respectively. For HAP/VAP, linezolid was non-significantly better than vancomycin, with ORs of 1.05 (0.72-1.57) and 1.32 (0.71-2.48) in the MITT and MRSA m-MITT populations, respectively. We suspect performance and detection bias in cSSTI trials involving linezolid, but regression methods could not adjust for this potential bias. In these clinical trials, the preferred agents for treating serious MRSA infections were ceftaroline (for cSSTI, not studied in HAP/VAP) and linezolid. However, translation of these findings into practice should consider the small size of the evidence networks and the consequent uncertainty associated with the parameter estimates, the lack of evidence for ceftaroline in patients with severe renal impairment, and the lower internal validity of some of the linezolid trials.

Critically ill patients and end-of-life decision-making: the senior medical resident experience.

In order to improve the understanding of educational needs among residents caring for the critically ill, narrative accounts of 19 senior physician trainees participating in level of care decision-making were analyzed. In this multicentre qualitative study involving 9 university centers in Canada, in-depth interviews were conducted in either English or French, and the transcripts then underwent a hermeneutic phenomenological analysis. The resident was the central figure in the narrated incident, along with the patients' relatives and other attending physicians. The vast majority of interviews recounted negative experiences that involved delivering bad news to patients' families and managing difficult communications with them and with physician colleagues. Emotional distress and suffering were often part of their decision-making process. Narrating their experiences was viewed as a positive event. Data analysis uncovered 6 general themes that were organized into 2 categories, the first one grouping together themes related to interactions with the patients' families and the second comprising themes related to interactions with physician coworkers. The findings suggest that physician trainees' narratives are a rich source of data regarding what constitutes meaningful training experiences and what they learn from them. Educational approaches that incorporate the telling of stories would allow students to express their feelings, doubts, and opinions about their work experiences and could thus foster personal and emotional learning in critical care.

Role for myeloid nuclear differentiation antigen in the regulation of neutrophil apoptosis during sepsis.

RATIONALE: Suppressed neutrophil apoptosis, a hallmark of sepsis, perpetuates inflammation and delays resolution. Myeloid nuclear differentiation antigen (MNDA) is expressed only in myeloid cells and has been implicated in cell differentiation; however, its function in mature neutrophils is not known. OBJECTIVES: We studied whether MNDA could contribute to regulation of apoptosis of neutrophils from healthy subjects and patients with sepsis, and investigated the impact of MNDA knockdown on apoptosis. METHODS: Human neutrophils were challenged with mediators of sepsis and neutrophils from patients with sepsis were cultured to investigate cleavage and cytoplasmic accumulation of MNDA. MNDA was knocked down in myeloid HL-60 cells to investigate development of apoptosis. MEASUREMENTS AND MAIN RESULTS: During constitutive apoptosis of human neutrophils, MNDA is cleaved by caspases and accumulated in the cytoplasm, where it promotes degradation of the antiapoptotic protein Mcl-1, thereby accelerating collapse of mitochondrial transmembrane potential. Culture of neutrophils with LPS, bacterial DNA, or platelet-activating factor prevented MNDA cleavage and cytoplasmic accumulation. MNDA knockdown with short hairpin RNA markedly attenuated Mcl-1 turnover and conferred resistance to stress-induced apoptosis in HL-60 cells. Neutrophils from patients with severe sepsis exhibited markedly suppressed apoptosis that was associated with impaired cytoplasmic MNDA accumulation, preservation of Mcl-1 expression, and mitochondrial transmembrane potential. Culture of neutrophils of healthy subjects with septic plasma delayed apoptosis and cytoplasmic MNDA accumulation. CONCLUSIONS: These results indicate that cytoplasmic accumulation of MNDA facilitates progression of apoptosis and suggest that impaired cytoplasmic MNDA accumulation contributes to delayed neutrophil apoptosis in patients with severe sepsis.

Protocolized intensive care unit management of analgesia, sedation, and delirium improves analgesia and subsyndromal delirium rates.

BACKGROUND: Sedatives and analgesics, in doses that alter consciousness in the intensive care unit (ICU), contribute to delirium and mortality. Pain, agitation, and delirium can be monitored in ICU patients. These symptoms were noted before (PRE) and after (POST) a protocol to alleviate undesirable symptoms. Analgesia and sedation levels, the incidence of coma, delirium, length of stay (LOS), discharge location, and mortality were then compared. We hypothesized that the likely reduction in iatrogenic coma would result in less delirium, because these 2 morbid conditions seem to be linked. METHODS: All patients were consecutively admitted to an ICU PRE-protocol (August 2003 to February 2004, 610 patients) and POST-protocol (April 2005 to November 2005, 604 patients). Between February 2004 and April 2005, we piloted and taught individualized nonpharmacologic strategies and titration of analgesics, sedatives, and antipsychotics based on sedation, analgesia, and delirium scores. We measured the following outcomes: coma, delirium, LOS, mortality, and discharge location. RESULTS: The POST group benefited from better analgesia, received less opiates (90.72 + or - 207.45 vs 22.93 + or - 40.36 morphine equivalents/d, P = <0.0001), and, despite comparable sedation, had shorter duration of mechanical ventilation. Medication-induced coma rates (18.1%vs 7.2%, P < 0.0001), ICU and hospital LOS, and dependency at discharge were lower in the POST-protocol group. Subsyndromal delirium was significantly reduced; delirium was similar. The 30-day mortality risk in the PRE cohort was 29.4% vs 22.9% in the POST cohort (log-rank test, P = 0.009). CONCLUSION: Educational initiatives incorporating systematic management protocols with nonpharmacologic measures and individualized titration of sedation, analgesia, and delirium therapies are associated with better outcomes.

Enteric absorption and pharmacokinetics of oseltamivir in critically ill patients with pandemic (H1N1) influenza.

BACKGROUND: Whether the enteric absorption of the neuraminidase inhibitor oseltamivir is impaired in critically ill patients is unknown. We documented the pharmacokinetic profile of oseltamivir in patients admitted to intensive care units (ICUs) with suspected or confirmed pandemic (H1N1) influenza. METHODS: We included 41 patients 18 years of age and older with suspected or confirmed pandemic (H1N1) influenza who were admitted for ventilatory support to nine ICUs in three cities in Canada and Spain. Using tandem mass spectrometry, we assessed plasma levels of oseltamivir free base and its active metabolite carboxylate at baseline (before gastric administration of the drug) and at 2, 4, 6, 9 and 12 hours after the fourth or later dose. RESULTS: Among the 36 patients who did not require dialysis, the median concentration of oseltamivir free base was 10.4 (interquartile range [IQR] 4.8-14.9) microg/L; the median concentration of the carboxylate metabolite was 404 (IQR 257-900) microg/L. The volume of distribution of the carboxylate metabolite did not increase with increasing body weight (R2=0.00, p=0.87). The rate of elimination of oseltamivir carboxylate was modestly correlated with estimations of creatinine clearance (R2=0.27, p<0.001). Drug clearance in the five patients who required continuous renal replacement therapy was about one-sixth that in the 36 patients with relatively normal renal function. INTERPRETATION: Oseltamivir was well absorbed enterically in critically ill patients admitted to the ICU with suspected or confirmed pandemic (H1N1) influenza. The dosage of 75 mg twice daily achieved plasma levels that were comparable to those in ambulatory patients and were far in excess of concentrations required to maximally inhibit neuraminidase activity of the virus. Adjustment of the dosage in patients with renal dysfunction requiring continuous renal replacement therapy is appropriate; adjustment for obesity does not appear to be necessary.

Critically ill patients with 2009 influenza A(H1N1) infection in Canada.

CONTEXT: Between March and July 2009, the largest number of confirmed cases of 2009 influenza A(H1N1) infection occurred in North America. OBJECTIVE: To describe characteristics, treatment, and outcomes of critically ill patients in Canada with 2009 influenza A(H1N1) infection. DESIGN, SETTING, AND PATIENTS: A prospective observational study of 168 critically ill patients with 2009 influenza A(H1N1) infection in 38 adult and pediatric intensive care units (ICUs) in Canada between April 16 and August 12, 2009. MAIN OUTCOME MEASURES: The primary outcome measures were 28-day and 90-day mortality. Secondary outcomes included frequency and duration of mechanical ventilation and duration of ICU stay. RESULTS: Critical illness occurred in 215 patients with confirmed (n = 162), probable (n = 6), or suspected (n = 47) community-acquired 2009 influenza A(H1N1) infection. Among the 168 patients with confirmed or probable 2009 influenza A(H1N1), the mean (SD) age was 32.3 (21.4) years; 113 were female (67.3%) and 50 were children (29.8%). Overall mortality among critically ill patients at 28 days was 14.3% (95% confidence interval, 9.5%-20.7%). There were 43 patients who were aboriginal Canadians (25.6%). The median time from symptom onset to hospital admission was 4 days (interquartile range [IQR], 2-7 days) and from hospitalization to ICU admission was 1 day (IQR, 0-2 days). Shock and nonpulmonary acute organ dysfunction was common (Sequential Organ Failure Assessment mean [SD] score of 6.8 [3.6] on day 1). Neuraminidase inhibitors were administered to 152 patients (90.5%). All patients were severely hypoxemic (mean [SD] ratio of Pao(2) to fraction of inspired oxygen [Fio(2)] of 147 [128] mm Hg) at ICU admission. Mechanical ventilation was received by 136 patients (81.0%). The median duration of ventilation was 12 days (IQR, 6-20 days) and ICU stay was 12 days (IQR, 5-20 days). Lung rescue therapies included neuromuscular blockade (28% of patients), inhaled nitric oxide (13.7%), high-frequency oscillatory ventilation (11.9%), extracorporeal membrane oxygenation (4.2%), and prone positioning ventilation (3.0%). Overall mortality among critically ill patients at 90 days was 17.3% (95% confidence interval, 12.0%-24.0%; n = 29). CONCLUSION: Critical illness due to 2009 influenza A(H1N1) in Canada occurred rapidly after hospital admission, often in young adults, and was associated with severe hypoxemia, multisystem organ failure, a requirement for prolonged mechanical ventilation, and the frequent use of rescue therapies.

Residents' end-of-life decision making with adult hospitalized patients: a review of the literature.

PURPOSE: The authors performed a structured literature review to understand residents' experiences with end-of-life (EOL) decision making with adult hospitalized patients, specifically regarding decisions to withhold or withdraw advanced life-support measures. METHOD: An Ovid-based strategy was used to search Medline, ERIC, PsychINFO, and CINHAL databases for articles published between 1966 and February 2005, combining the domains of "resuscitation orders," "decision making," and "internship and residency." All quantitative and qualitative studies examining residents' EOL decision making with adult hospitalized patients were included. The authors developed and applied a scoring system for relevance and quality, performed data abstraction and quality assessment independently and in duplicate, then met to collate findings and identify factors in residents' EOL decision making. RESULTS: The searches yielded 884 articles, of which 26 were included. Variable methodologies precluded meta-analysis. In these studies, residents felt unprepared to handle patient EOL decision making, although exposure to EOL discussions helped them gain confidence. Residents' attitudes, skills, and knowledge were key determinants of whether EOL decisions were addressed. Many misinterpreted the terms "DNR" and "futility." Residents' understanding of the patient EOL decision-making process could be extremely variable, and their do-not-resuscitate discussions suboptimal. Residents' lived practice experience of the patient EOL decision-making process was often at odds with what they were taught in formal curricula. CONCLUSIONS: Educational strategies aimed at changing residents' knowledge, skills and attitude should address the hidden curriculum for the patient EOL decision-making process that is part of the experienced culture of every day practice. Future studies of this experienced culture would inform specific educational interventions.