The ratio of PACU length-of-stay to surgical duration: Practical observations.

BACKGROUND: Operating room (OR) and post-anesthesia care unit (PACU) activity are closely linked since the number, type, and sequence of surgeries influence subsequent PACU activity. We aimed to explore the relationship between duration-of-surgery (DOS) and PACU length-of-stay (LOS), the PACU-LOS:DOS ratio, since it is among the determinants of the number of PACU beds and nurse staffing required to insure efficient egress of patients from the OR. METHODS: PACU-LOS:DOS ratio was examined using retrospective data from a tertiary medical center's surgical information system (Phase 1) and prospectively collected data from a convenience sample of post-operative patients (Phase 2). RESULTS: Phase 1 included 17 047 patients, the majority (73%) with PACU-LOS:DOS ratios >1.0, indicating PACU-LOS longer than DOS. Median PACU-LOS was 117 minutes, median DOS was 80 minutes, and median PACU-LOS/DOS ratio was 1.5. PACU-LOS showed greater variability than DOS because of extended PACU stays. Phase 2 (n = 2054) confirmed Phase 1 results (median PACU-LOS/DOS ratio - 1.8). In both phases at a DOS of >130 minutes PACU-LOS/DOS ratio became <1.0. In 24% of Phase 2 patients PACU-LOS was prolonged because of administrative issues. Post-operative, more than pre- and intra-operative, measurements influenced PACU-LOS. CONCLUSIONS: The PACU-LOS/DOS ratio proved useful for demonstrating interactions between 2 central components of the surgical system. The many patients with PACU-LOS:DOS ratios >1.0 provides objective evidence for the number of PACU beds exceeding the number of ORs.

Using medical specialty and selection criteria clusters to study specialty selection by Israeli medical students.

BACKGROUND: During their final year of medical school, Israeli students must consider which specialty to choose for residency. Based on the vocational counseling literature we presumed that choices are made by selecting from a cluster of related specialties while considering professional and socio-economic issues. METHODS: Questionnaires distributed to final-year medical students at two Israeli medical schools ascertained inclinations toward various medical specialties and the importance of various selection criteria. Analysis focused on seven specialties where >20% of students reported they had positive inclinations. For each such specialty, the specialty and selection criteria query were compared using unpaired two-tailed Student's t-tests to determine differences between students with positive inclinations toward the specialty with those not so inclined. These data were placed in tables, with the significant differences highlighted to facilitate visual recognition of cluster patterns. RESULTS: Completed questionnaires were obtained from 317 of 455 students. Students often had positive inclinations toward more than one specialty (specialty clusters) associated with a group of selection criteria (selection criteria clusters). For example, interest in internal medicine was clustered with interest in internal medicine subspecialties, cardiology and research. Furthermore, there was a "reciprocal" aspect to some specialty cluster patterns. For example, those interested in internal medicine had little interest in surgical specialties. Selection criteria clusters revealed occupational interests and socio-environmental factors associated with the specialty clusters. For example, family medicine, which clustered with pediatrics and psychiatry, had a sub-cluster of: Bedside specialty with family orientation affording long-term patient care. Another sub-cluster was time for childrearing and family, only daytime work and outpatient care. Clusters also revealed students' perceptions that differed from expected: Cardiology is changing from a cognitive to a procedure-oriented subspecialty, clustering not only with internal medicine and its subspecialties but also with emergency medicine, surgical subspecialties and anesthesiology. CONCLUSIONS: The concept that career choice involves selecting from a cluster of related specialties provides information about the specialties students might be considering. Moreover, students are not only looking for individual aspects of a specialty, but for a package including clusters of socio-economic and occupational features. Practically, examining clusters can help in career counseling of medical students and assist residency program directors in marketing their specialties.

Do corticosteroids improve outcome for any critical illness?

PURPOSE OF REVIEW: Corticosteroids have been widely administered in critically ill patients for various indications. Their clinical benefit is broadly investigated but remains controversial. The purpose of this review is to explore the use of corticosteroids in intensive care, their impact on patient outcome and to provide practical guidance for the use of corticosteroids in the ICU. RECENT FINDINGS: Critical illness is the result of significant tissue damage, due to cellular ischemia, trauma or infection, inducing a systemic inflammatory syndrome. Recent advances in the understanding of the immunologic and molecular mechanisms of inflammation support, in part, the conceptual use of corticosteroids as an adjunct immunomodulatory therapy. But use of corticosteroids carries the risk of severe adverse effects, partly because of their anti-infammatory effects. Recently, clinical research has focused on critical illness-related corticosteroid insufficiency and several trials investigated the role of corticosteroids therapy in septic and critically ill patients with severe systemic inflammation such as acute respiratory distress syndrome, severe community-acquired pneumonia and meningitis. Improved morbidity has been demonstrated in some studies but a clear benefit in term of mortality was not observed. SUMMARY: Critical illnesses stem from a group of heterogeneous medical conditions. Failure to target subgroups more likely to benefit from the use of corticosteroids may be one explanation for the largely disappointing results in clinical trials, thus, far.

The heat shock response in moss plants is regulated by specific calcium-permeable channels in the plasma membrane.

Land plants are prone to strong thermal variations and must therefore sense early moderate temperature increments to induce appropriate cellular defenses, such as molecular chaperones, in anticipation of upcoming noxious temperatures. To investigate how plants perceive mild changes in ambient temperature, we monitored in recombinant lines of the moss Physcomitrella patens the activation of a heat-inducible promoter, the integrity of a thermolabile enzyme, and the fluctuations of cytoplasmic calcium. Mild temperature increments, or isothermal treatments with membrane fluidizers or Hsp90 inhibitors, induced a heat shock response (HSR) that critically depended on a preceding Ca(2+) transient through the plasma membrane. Electrophysiological experiments revealed the presence of a Ca(2+)-permeable channel in the plasma membrane that is transiently activated by mild temperature increments or chemical perturbations of membrane fluidity. The amplitude of the Ca(2+) influx during the first minutes of a temperature stress modulated the intensity of the HSR, and Ca(2+) channel blockers prevented HSR and the onset of thermotolerance. Our data suggest that early sensing of mild temperature increments occurs at the plasma membrane of plant cells independently from cytosolic protein unfolding. The heat signal is translated into an effective HSR by way of a specific membrane-regulated Ca(2+) influx, leading to thermotolerance.

Hydrocortisone therapy for patients with septic shock.

BACKGROUND: Hydrocortisone is widely used in patients with septic shock even though a survival benefit has been reported only in patients who remained hypotensive after fluid and vasopressor resuscitation and whose plasma cortisol levels did not rise appropriately after the administration of corticotropin. METHODS: In this multicenter, randomized, double-blind, placebo-controlled trial, we assigned 251 patients to receive 50 mg of intravenous hydrocortisone and 248 patients to receive placebo every 6 hours for 5 days; the dose was then tapered during a 6-day period. At 28 days, the primary outcome was death among patients who did not have a response to a corticotropin test. RESULTS: Of the 499 patients in the study, 233 (46.7%) did not have a response to corticotropin (125 in the hydrocortisone group and 108 in the placebo group). At 28 days, there was no significant difference in mortality between patients in the two study groups who did not have a response to corticotropin (39.2% in the hydrocortisone group and 36.1% in the placebo group, P=0.69) or between those who had a response to corticotropin (28.8% in the hydrocortisone group and 28.7% in the placebo group, P=1.00). At 28 days, 86 of 251 patients in the hydrocortisone group (34.3%) and 78 of 248 patients in the placebo group (31.5%) had died (P=0.51). In the hydrocortisone group, shock was reversed more quickly than in the placebo group. However, there were more episodes of superinfection, including new sepsis and septic shock. CONCLUSIONS: Hydrocortisone did not improve survival or reversal of shock in patients with septic shock, either overall or in patients who did not have a response to corticotropin, although hydrocortisone hastened reversal of shock in patients in whom shock was reversed. (ClinicalTrials.gov number, NCT00147004.)

Utilization of the Public Health Ordinance to prevent nosocomial spread in a case of acute measles-associated psychosis.

Measles is a highly contagious disease. A 24 years old patient, recently exposed to measles (unvaccinated), presented in the emergency department with severe agitation, compatible with an acute psychotic episode, during the measles epidemic which spread in Israel in 2018-2019. Upon hospital admission, strict isolation was instructed, yet, without compliance, probably due to the patient's status. Measles diagnosis was promptly confirmed. As measles transmission was eminent, public health measures were employed through immediate implementation of the section 15 of the Public Health Ordinance, allowing for compulsory short-term isolation. The patient's condition improved within a few days and the measures were no longer necessary. This measles case occurred in the pre-Coronavirus disease 2019 (COVID-19) epidemic when use of a Public Health Ordinance was considered an extreme measure. This is in contrast to the current global use of Public Health laws to enforce strict quarantine and isolation on persons infected or potentially exposed to COVID-19. Nevertheless, minimizing infectious diseases transmission is a core function of public health law. Utilizing legal enforcement in circumstances of immediate public health hazard, such as nosocomial measles transmission, necessitates careful consideration. The integrative clinical and public health approach and prompt measures employed in this exceptional case, led to prevention of further infection spread.

Relocating to a New OR Suite: Practical Observations.

Operating room renovation projects usually involve updated technology and processes that can create challenges for administrative leaders (eg, maintaining a surgery schedule during a move) and require staff member adjustments. The perioperative team of a large tertiary care and trauma center relocated from a 35-year-old suite to a new suite, which required years of planning, months of training, and weeks of organizing. This article discusses the processes and observations that helped ensure a smooth transition to the new space. Early planning allowed time for leaders to make equipment decisions, develop and test new processes, and train staff members. The actual move required detailed planning, thorough execution, patience, and flexibility to ensure a safe transition. Perioperative leaders balanced operational needs with relocation plans to maintain patient and staff member safety. Open, multidisciplinary communication combined with staff member participation and buy-in contributed to an efficient, safe move at this facility.

Moderate Fever Cycles as a Potential Mechanism to Protect the Respiratory System in COVID-19 Patients.

Mortality in COVID-19 patients predominantly results from an acute respiratory distress syndrome (ARDS), in which lungs alveolar cells undergo programmed cell death. Mortality in a sepsis-induced ARDS rat model is reduced by adenovirus over-expression of the HSP70 chaperone. A natural rise of body temperature during mild fever can naturally accumulate high cellular levels of HSP70 that can arrest apoptosis and protect alveolar lung cells from inflammatory damages. However, beyond 1-2 h of fever, no HSP70 is being further produced and a decreased in body temperature required to the restore cell's ability to produce more HSP70 in a subsequent fever cycle. We suggest that antipyretics may be beneficial in COVID-19 patients subsequent to several hours of mild (<38.8°C) advantageous fever, allowing lung cells to accumulate protective HSP70 against damages from the inflammatory response to the virus SARS-CoV-2. With age, the ability to develop fever and accumulate HSP70 decreases. This could be ameliorated, when advisable to do so, by thermotherapies and/or physical training.

Role of small GTPases and alphavbeta5 integrin in Pseudomonas aeruginosa-induced increase in lung endothelial permeability.

Pseudomonas aeruginosa is an opportunistic pathogen that can cause severe pneumonia associated with airspace flooding with protein-rich edema in critically ill patients. The type III secretion system is a major virulence factor and contributes to dissemination of P. aeruginosa. However, it is still unknown which particular bacterial toxin and which cellular pathways are responsible for the increase in lung endothelial permeability induced by P. aeruginosa. Thus, the first objective of this study was to determine the mechanisms by which this species causes an increase in lung endothelial permeability. The results showed that ExoS and ExoT, two of the four known P. aeruginosa type III cytotoxins, were primarily responsible for bacterium-induced increases in protein permeability across the lung endothelium via an inhibition of Rac1 and an activation of the RhoA signaling pathway. In addition, inhibition of the alphavbeta5 integrin, a central regulator of lung vascular permeability, prevented these P. aeruginosa-mediated increases in albumin flux due to endothelial permeability. Finally, prior activation of the stress protein response or adenoviral gene transfer of the inducible heat shock protein Hsp72 also inhibited the damaging effects of P. aeruginosa on the barrier function of lung endothelium. Taken together, these results demonstrate the critical role of the RhoA/alphavbeta5 integrin pathway in mediating P. aeruginosa-induced lung vascular permeability. In addition, activation of the stress protein response with pharmacologic inhibitors of Hsp90 may protect lungs against P. aeruginosa-induced permeability changes.

Mechanical ventilation patterns and trends over 20 years in an Israeli hospital system: policy ramifications.

BACKGROUND: Mechanical ventilation is a life supporting modality increasingly utilized when caring for severely ill patients. Its increasing use has extended the survival of the critically ill leading to increasing healthcare expenditures. We examined changes in the hospital-wide use of mechanical ventilation over 20 years (1997-2016) in two Israeli hospitals to determine whether there were specific patterns (e.g. seasonality, weekday vs. weekend) and trends (e.g. increases or decreases) among various hospital departments and units. METHODS: Retrospective analysis of prospectively collected data on all mechanically ventilated patients over 20-years in a two-hospital Israeli medical system was performed. Data were collected for each hospital unit caring for ventilated patients. Time-series analysis examined short and long-term trends, seasonality and intra-week variation. RESULTS: Over two decades overall ventilator-days increased from 11,164 (31 patients/day) in 1997 to 24,317 (67 patients/day) in 2016 mainly due to more patients ventilated on internal medicine wards (1997: 4 patients/day; 2016: 24 patients/day). The increases in other hospital areas did not approach the magnitude of the internal medicine wards increases. Ventilation on wards reflected the insufficient number of ICU beds in Israel. A detailed snapshot over 4 months of patients ventilated on internal medicine wards (n = 745) showed that they tended to be elderly (median age 75 years) and that 24% were ventilated for more than a week. Hospital-wide ventilation patterns were the weighted sum of the various individual patient units with the most noticeable pattern being peak winter prevalence on the internal medical wards and in the emergency department. This seasonality is not surprising, given the greater incidence of respiratory ailments in winter. CONCLUSIONS: Increased mechanical ventilation plus seasonality have budgetary, operational and staffing consequences for individual hospitals and the entire healthcare system. The Israeli healthcare leadership needs to plan and support expanding, equipping and staffing acute and chronic care units that are staffed by providers trained to care for such complex patients.

Enhanced expression of 70-kilodalton heat shock protein limits cell division in a sepsis-induced model of acute respiratory distress syndrome.

OBJECTIVE: Fibrotic changes are initiated early in acute respiratory distress syndrome. This may involve overproliferation of alveolar type II cells. In an animal model of acute respiratory distress syndrome, we have shown that the administration of an adenoviral vector overexpressing the 70-kd heat shock protein (AdHSP) limited pathophysiological changes. We hypothesized that this improvement may be modulated, in part, by an early AdHSP-induced attenuation of alveolar type II cell proliferation. DESIGN: Laboratory investigation. SETTING: Hadassah-Hebrew University and University of Pennsylvania animal laboratories. SUBJECTS: Sprague-Dawley Rats (250 g). INTERVENTIONS: Lung injury was induced in male Sprague-Dawley rats via cecal ligation and double puncture. At the time of cecal ligation and double puncture, we injected phosphate-buffered saline, AdHSP, or AdGFP (an adenoviral vector expressing the marker green fluorescent protein) into the trachea. Rats then received subcutaneous bromodeoxyuridine. In separate experiments, A549 cells were incubated with medium, AdHSP, or AdGFP. Some cells were also stimulated with tumor necrosis factor-alpha. After 48 hrs, cytosolic and nuclear proteins from rat lungs or cell cultures were isolated. These were subjected to immunoblotting, immunoprecipitation, electrophoretic mobility shift assay, fluorescent immunohistochemistry, and Northern blot analysis. MEASUREMENTS AND MAIN RESULTS: Alveolar type I cells were lost within 48 hrs of inducing acute respiratory distress syndrome. This was accompanied by alveolar type II cell proliferation. Treatment with AdHSP preserved alveolar type I cells and limited alveolar type II cell proliferation. Heat shock protein 70 prevented overexuberant cell division, in part, by inhibiting hyperphosphorylation of the regulatory retinoblastoma protein. This prevented retinoblastoma protein ubiquitination and degradation and, thus, stabilized the interaction of retinoblastoma protein with E2F1, a key cell division transcription factor. CONCLUSIONS: : Heat shock protein 70-induced attenuation of cell proliferation may be a useful strategy for limiting lung injury when treating acute respiratory distress syndrome if consistent in later time points.

Medical students' perceptions of a career in family medicine.

BACKGROUND: In Israel, there is a shortage of family medicine (FM) specialists that is occasioned by a shortage of students pursuing a FM career. METHODS: A questionnaire, based on methods adapted from marketing research, was used to provide insight into the medical specialty selection process. It was distributed to 6th-year medical students from two Israeli medical schools. RESULTS: A response rate of 66% resulted in collecting 218 completed questionnaires. Nineteen of the students reported that they were interested in FM, 68% of them were women. When compared to students not interested in FM, the selection criteria of students interested in FM reflected greater interest in a bedside specialty which provides direct long-term patient care. These latter students were also more interested in a controllable lifestyle that allowed time to be with family and children and working outside the hospital especially during the daytime. These selection criteria aligned with their perceptions of FM, which they perceived as providing them with a controllable lifestyle, allowing them to work limited hours with time for family and having a reasonable income to lifestyle ratio. The students not interested in FM, agreed with those interested in FM, that the specialty affords a controllable lifestyle and the ability to work limited hours Yet, students not interested in FM more often perceived FM as being a boring specialty and less often perceived it as providing a reasonable income to lifestyle ratio. Additionally, students not interested in FM rated the selection criteria, academic opportunities and a prestigious specialty, more highly than did students interested in FM. However, they perceived FM as neither being prestigious nor as affording academic opportunities CONCLUSION: This study enriches our understanding of the younger generation's attitudes towards FM and thus provides administrators, department chairs and residency program directors with objective information regarding selection criteria and the students' perceptions of FM. We identified the disconnect between the selection criteria profiles and the perceptions of FM of students not inclined to pursue a residency in FM. This allowed for recommendations on how to possibly make FM more attractive to some of these students.

Adenoviral transfer of HSP-70 into pulmonary epithelium ameliorates experimental acute respiratory distress syndrome.

The acute respiratory distress syndrome (ARDS) provokes three pathologic processes: unchecked inflammation, interstitial/alveolar protein accumulation, and destruction of pulmonary epithelial cells. The highly conserved heat shock protein HSP-70 can limit all three responses but is not appropriately expressed in the lungs after cecal ligation and double puncture (2CLP), a clinically relevant model of ARDS. We hypothesize that restoring expression of HSP-70 using adenovirus-mediated gene therapy will limit pulmonary pathology following 2CLP. We administered a vector containing the porcine HSP-70 cDNA driven by a CMV promoter (AdHSP) into the lungs of rats subjected to 2CLP or sham operation. Administration of AdHSP after either sham operation or 2CLP increased HSP-70 protein expression in lung tissue, as determined by immunohistochemistry and Western blot hybridization. Administration of AdHSP significantly attenuated interstitial and alveolar edema and protein exudation and dramatically decreased neutrophil accumulation, relative to a control adenovirus. CLP-associated mortality at 48 hours was reduced by half. Modulation of HSP-70 production reduces pathologic changes and may improve outcome in experimental ARDS.

Simian virus 40 vectors for pulmonary gene therapy.

BACKGROUND: Sepsis remains the leading cause of death in critically ill patients. One of the primary organs affected by sepsis is the lung, presenting as the Acute Respiratory Distress Syndrome (ARDS). Organ damage in sepsis involves an alteration in gene expression, making gene transfer a potential therapeutic modality. This work examines the feasibility of applying simian virus 40 (SV40) vectors for pulmonary gene therapy. METHODS: Sepsis-induced ARDS was established by cecal ligation double puncture (2CLP). SV40 vectors carrying the luciferase reporter gene (SV/luc) were administered intratracheally immediately after sepsis induction. Sham operated (SO) as well as 2CLP rats given intratracheal PBS or adenovirus expressing luciferase served as controls. Luc transduction was evaluated by in vivo light detection, immunoassay and luciferase mRNA detection by RT-PCR in tissue harvested from septic rats. Vector abundance and distribution into alveolar cells was evaluated using immunostaining for the SV40 VP1 capsid protein as well as by double staining for VP1 and for the surfactant protein C (proSP-C). Immunostaining for T-lymphocytes was used to evaluate the cellular immune response induced by the vector. RESULTS: Luc expression measured by in vivo light detection correlated with immunoassay from lung tissue harvested from the same rats. Moreover, our results showed vector presence in type II alveolar cells. The vector did not induce significant cellular immune response. CONCLUSION: In the present study we have demonstrated efficient uptake and expression of an SV40 vector in the lungs of animals with sepsis-induced ARDS. These vectors appear to be capable of in vivo transduction of alveolar type II cells and may thus become a future therapeutic tool.

Cortisol changes among patients with septic shock and the relationship to ICU and hospital stay.

OBJECTIVE: To evaluate adrenal function in patients with severe sepsis or septic shock. DESIGN: A prospective study of unstimulated and high-dose ACTH stimulated cortisol levels on days 1 and 2 following ICU admission and day 28 or last day of hospitalization (herein day 28). SETTING: General intensive care unit. PATIENTS: 34 septic patients. INTERVENTIONS: On days 1, 2, and 28 of sepsis unstimulated and ACTH stimulated cortisol levels were evaluated. End-points were length of ICU and hospital stay and 28 day all cause mortality. MEASUREMENTS AND RESULTS: Eight patients on days 1 and 2 had criteria of adrenal insufficiency defined as unstimulated cortisol levels less than 15 microg/dl. Patients with unstimulated cortisol levels less than 15 microg/dl on day 1 or change of 9 microg/dl or less had longer ICU stays. Patients with unstimulated cortisol levels less than 15 microg/dl on day 1 also demonstrated longer hospital stay. On day 1 regression analysis revealed that unstimulated cortisol levels had a significant inverse correlation with length of ICU and hospital stay. The proportional change between unstimulated cortisol and post-ACTH cortisol (Delta%) is a new modality; the higher this Delta% value, the longer is the patient's ICU and hospital stay. A significant positive correlation was found in survivors when comparing unstimulated cortisol vs. day 28 changes. CONCLUSIONS: The present study highlights the wide range of cortisol levels among patients with sepsis. We observed a difference in cortisol response pattern between survivors and nonsurvivors on day 28. The proportional change between unstimulated cortisol and post-ACTH cortisol was used as a method to evaluate the relative change in cortisol levels between patients.

Clinical review: the Israeli experience: conventional terrorism and critical care.

Over the past four years there have been 93 multiple-casualty terrorist attacks in Israel, 33 of them in Jerusalem. The Hadassah-Hebrew University Medical Center is the only Level I trauma center in Jerusalem and has therefore gained important experience in caring for critically injured patients. To do so we have developed a highly flexible operational system for managing the general intensive care unit (GICU). The focus of this review will be on the organizational steps needed to provide operational flexibility, emphasizing the importance of forward deployment of intensive care unit personnel to the trauma bay and emergency room and the existence of a chain of command to limit chaos. A retrospective review of the hospital's response to multiple-casualty terror incidents occurring between 1 October 2000 and 1 September 2004 was performed. Information was assembled from the medical center's trauma registry and from GICU patient admission and discharge records. Patients are described with regard to the severity and type of injury. The organizational work within intensive care is described. Finally, specific issues related to the diagnosis and management of lung, brain, orthopedic and abdominal injuries, caused by bomb blast events associated with shrapnel, are described. This review emphasizes the importance of a multidisciplinary team approach in caring for these patients.

Genome-wide association study of survival from sepsis due to pneumonia: an observational cohort study.

BACKGROUND: Sepsis continues to be a major cause of death, disability, and health-care expenditure worldwide. Despite evidence suggesting that host genetics can influence sepsis outcomes, no specific loci have yet been convincingly replicated. The aim of this study was to identify genetic variants that influence sepsis survival. METHODS: We did a genome-wide association study in three independent cohorts of white adult patients admitted to intensive care units with sepsis, severe sepsis, or septic shock (as defined by the International Consensus Criteria) due to pneumonia or intra-abdominal infection (cohorts 1-3, n=2534 patients). The primary outcome was 28 day survival. Results for the cohort of patients with sepsis due to pneumonia were combined in a meta-analysis of 1553 patients from all three cohorts, of whom 359 died within 28 days of admission to the intensive-care unit. The most significantly associated single nucleotide polymorphisms (SNPs) were genotyped in a further 538 white patients with sepsis due to pneumonia (cohort 4), of whom 106 died. FINDINGS: In the genome-wide meta-analysis of three independent pneumonia cohorts (cohorts 1-3), common variants in the FER gene were strongly associated with survival (p=9·7 × 10(-8)). Further genotyping of the top associated SNP (rs4957796) in the additional cohort (cohort 4) resulted in a combined p value of 5·6 × 10(-8) (odds ratio 0·56, 95% CI 0·45-0·69). In a time-to-event analysis, each allele reduced the mortality over 28 days by 44% (hazard ratio for death 0·56, 95% CI 0·45-0·69; likelihood ratio test p=3·4 × 10(-9), after adjustment for age and stratification by cohort). Mortality was 9·5% in patients carrying the CC genotype, 15·2% in those carrying the TC genotype, and 25·3% in those carrying the TT genotype. No significant genetic associations were identified when patients with sepsis due to pneumonia and intra-abdominal infection were combined. INTERPRETATION: We have identified common variants in the FER gene that associate with a reduced risk of death from sepsis due to pneumonia. The FER gene and associated molecular pathways are potential novel targets for therapy or prevention and candidates for the development of biomarkers for risk stratification. FUNDING: European Commission and the Wellcome Trust.

Intensive care outflow limitation--frequency, etiology, and impact.

OBJECTIVE: To assess the frequency, causes, and effect of unsuccessful discharge decisions from the ICU. SETTING: An 11-bed general intensive care unit of a 750-bed urban university hospital, tertiary referral center and level one trauma center. DESIGN: A prospective, observational study. PATIENTS: All ICU patients judged appropriate for discharge by the ICU attending physician. MEASUREMENTS AND RESULTS: A total of 856 attempted discharges in 706 patients were analyzed over 16 months. Of these, 703 (82%) were successful within 24 hours. Of the remaining 153 unsuccessful discharges, 51 (33%) were deferred because of medical deterioration, 32 (21%) at the request of the ward physicians or nurses and 70 (46%) because of administrative difficulties (lack of ward bed space or disagreement over admitting service). When compared to patients successfully discharged on the first attempt, those whose discharge was deferred had a significantly longer ICU admission prior to the first discharge attempt (median 4d v 3d, P =.009), and a higher proportion required intermediate care (48% v 26%, P <.001). Both these factors were independently associated with unsuccessful discharge in a logistic regression analysis (OR 1.04, 95%CI 1.02, 1.06, P =.0001, OR 2.05 95%CI 1.30, 3.26, P =.002, respectively). Deferred discharges accounted for 153 days of ICU care (2.6% of the total) and were associated with ICU overflow on 118 days (2% of all ICU days). CONCLUSION: ICU outflow limitation occurs in up to 1 in 6 discharges. It can be due to medical deterioration, level of care issues or administrative problems, and may lead to inefficient use of ICU resources.

Medical students' and interns' interest in orthopedic surgery: the gender factor.

OBJECTIVE: There is an extremely small proportion of female medical students choosing to specialize in orthopedic surgery. The aim of the study was to assess medical students' and interns' interests and perceptions of orthopedic surgery and explore why women are not interested in orthopedic surgery. SETTING: Questionnaires were distributed to final-year medical students and interns assessing their interests and perception of orthopedic surgery. PARTICIPANTS: Final-year medical students and interns. RESULTS: Responses were obtained from 317 students and 199 interns. Among the medical students, 15% were interested in orthopedic surgery, but only 2% were women. Both male and female students perceived orthopedics as an "action"-packed, procedure-based profession, providing instant gratification, time in the operating room, high income, and the option for private practice. Female medical students considered it boring. Among interns, 11% were interested in orthopedic surgery; however, only 2% were women. When compared with the interns who were not interested in orthopedic surgery, a greater number of the interns interested in orthopedic surgery rated time with family and a procedure-intensive profession as important. Female students and interns were also interested in other surgical fields. CONCLUSIONS: The increasing majority of women among medical students will reshape the future of physician workforce by dictating changes in workforce participation, working conditions, and intercollegial relationships. Orthopedic surgery will need to adapt to these realities.