External validation of the ISARIC 4C Mortality Score to predict in-hospital mortality among patients with COVID-19 in a Canadian intensive care unit: a single-centre historical cohort study.

PURPOSE: With uncertain prognostic utility of existing predictive scoring systems for COVID-19-related illness, the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) 4C Mortality Score was developed by the International Severe Acute Respiratory and Emerging Infection Consortium as a COVID-19 mortality prediction tool. We sought to externally validate this score among critically ill patients admitted to an intensive care unit (ICU) with COVID-19 and compare its discrimination characteristics to that of the Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores. METHODS: We enrolled all consecutive patients admitted with COVID-19-associated respiratory failure between 5 March 2020 and 5 March 2022 to our university-affiliated and intensivist-staffed ICU (Jewish General Hospital, Montreal, QC, Canada). After data abstraction, our primary outcome of in-hospital mortality was evaluated with an objective of determining the discriminative properties of the ISARIC 4C Mortality Score, using the area under the curve of a logistic regression model. RESULTS: A total of 429 patients were included, 102 (23.8%) of whom died in hospital. The receiver operator curve of the ISARIC 4C Mortality Score had an area under the curve of 0.762 (95% confidence interval [CI], 0.717 to 0.811), whereas those of the SOFA and APACHE II scores were 0.705 (95% CI, 0.648 to 0.761) and 0.722 (95% CI, 0.667 to 0.777), respectively. CONCLUSIONS: The ISARIC 4C Mortality Score is a tool that had a good predictive performance for in-hospital mortality in a cohort of patients with COVID-19 admitted to an ICU for respiratory failure. Our results suggest a good external validity of the 4C score when applied to a more severely ill population.

RéSUMé: OBJECTIF: Compte tenu de l'utilité pronostique incertaine des systèmes de notation prédictive existants pour les maladies liées à la COVID-19, le score de mortalité ISARIC 4C a été mis au point par l'International Severe Acute Respiratory and Emerging Infection Consortium en tant qu'outil de prédiction de la mortalité associée à la COVID-19. Nous avons cherché à valider en externe ce score chez les patient·es gravement malades atteint·es de COVID-19 admis·es dans une unité de soins intensifs (USI) et à comparer ses caractéristiques de discrimination à celles des scores APACHE II (Acute Physiology and Chronic Health Evaluation) et SOFA (Sequential Organ Failure Assessment). MéTHODE: Nous avons recruté toutes les personnes consécutives admises pour insuffisance respiratoire associée à la COVID-19 entre le 5 mars 2020 et le 5 mars 2022 dans notre unité de soins intensifs affiliée à l'université et dotée d'intensivistes (Hôpital général juif, Montréal, QC, Canada). Après l'abstraction des données, notre critère d'évaluation principal de mortalité à l'hôpital a été évalué dans le but de déterminer les propriétés discriminatives du score de mortalité ISARIC 4C, en utilisant la surface sous la courbe d'un modèle de régression logistique. RéSULTATS: Au total, 429 patient·es ont été inclus·es, dont 102 (23,8 %) sont décédé·es à l'hôpital. La fonction d'efficacité du récepteur (courbe ROC) du score de mortalité ISARIC 4C avait une surface sous la courbe de 0,762 (intervalle de confiance [IC] à 95 %, 0,717 à 0,811), tandis que celles des scores SOFA et APACHE II étaient de 0,705 (IC 95%, 0,648 à 0,761) et 0,722 (IC 95%, 0,667 à 0,777), respectivement. CONCLUSION: Le score de mortalité ISARIC 4C est un outil qui a affiché une bonne performance prédictive de la mortalité à l'hôpital dans une cohorte de patient·es atteint·es de COVID-19 admis·es dans une unité de soins intensifs pour insuffisance respiratoire. Nos résultats suggèrent une bonne validité externe du score 4C lorsqu'il est appliqué à une population plus gravement malade.

High-flow nasal oxygen as first-line therapy for COVID-19-associated hypoxemic respiratory failure: a single-centre historical cohort study.

PURPOSE: The optimal noninvasive modality for oxygenation support in COVID-19-associated hypoxemic respiratory failure and its association with healthcare worker infection remain uncertain. We report here our experience using high-flow nasal oxygen (HFNO) as the primary support mode for patients with COVID-19 in our institution. METHODS: We conducted a single-centre historical cohort study of all COVID-19 patients treated with HFNO for at least two hours in our university-affiliated and intensivist-staffed intensive care unit (Jewish General Hospital, Montreal, QC, Canada) between 27 August 2020 and 30 April 2021. We report their clinical characteristics and outcomes. Healthcare workers in our unit cared for these patients in single negative pressure rooms wearing KN95 or fit-tested N95 masks; they underwent mandatory symptomatic screening for COVID-19 infection, as well as a period of asymptomatic screening. RESULTS: One hundred and forty-two patients were analysed, with a median [interquartile range (IQR)] age of 66 [59-73] yr; 71% were male. Patients had a median [IQR] Sequential Organ Failure Assessment Score of 3 [2-3], median [IQR] oxygen saturation by pulse oximetry/fraction of inspired oxygen ratio of 120 [94-164], and a median [IQR] 4C score (a COVID-19-specific mortality score) of 12 [10-14]. Endotracheal intubation occurred in 48/142 (34%) patients, and overall hospital mortality was 16%. Barotrauma occurred in 21/142 (15%) patients. Among 27 symptomatic and 139 asymptomatic screening tests, there were no cases of HFNO-related COVID-19 transmission to healthcare workers. CONCLUSION: Our experience indicates that HFNO is an effective first-line therapy for hypoxemic respiratory failure in COVID-19 patients, and can be safely used without significant discernable infection risk to healthcare workers.

RéSUMé: OBJECTIF: La modalité non invasive optimale pour le soutien en oxygène lors d'insuffisance respiratoire hypoxémique liée à la COVID-19 et son association avec l'infection des travailleurs de la santé restent incertaines. Nous rapportons ici notre expérience avec l'utilisation de canules nasales à haut débit (CNHD) comme principale modalité de soutien pour les patients atteints de COVID-19 dans notre établissement. MéTHODE: Nous avons mené une étude de cohorte historique monocentrique de tous les patients atteints de COVID-19 traités par CNHD pendant au moins deux heures dans notre unité de soins intensifs affiliée à l'université et dotée d'intensivistes (Hôpital général juif, Montréal, QC, Canada) entre le 27 août 2020 et le 30 avril 2021. Nous rapportons leurs caractéristiques cliniques et leurs résultats. Les travailleurs de la santé de notre unité ont soigné ces patients dans des chambres individuelles à pression négative en portant des masques KN95 ou N95 ajustés; ils ont subi un dépistage symptomatique obligatoire de l'infection à la COVID-19, ainsi qu'un dépistage en période asymptomatique. RéSULTATS: Cent quarante-deux patients ont été analysés, avec un âge médian [écart interquartile (ÉIQ)] de 66 [59-73] ans; 71 % étaient des hommes. Les patients avaient un score SOFA (Sequential Organ Failure Assessment) médian [ÉIQ] de 3 [2, 3], un ratio médian [ÉIQ] de saturation en oxygène par oxymétrie de pouls/fraction d'oxygène inspiré de 120 [94-164], et un score 4C (un score de mortalité spécifique à la COVID-19) médian [ÉIQ] de 12 [10­14]. Dans l'ensemble, 48/142 patients (34 %) ont reçu une intubation endotrachéale, et la mortalité hospitalière globale était de 16 %. Un barotraumatisme est survenu chez 21/142 (15 %) patients. Parmi les 27 tests de dépistage symptomatiques et 139 tests asymptomatiques, aucun cas de transmission de COVID-19 liée aux CNHD aux travailleurs de la santé n'a été observé. CONCLUSION: Notre expérience indique que les CNHD constituent un traitement de première intention efficace pour l'insuffisance respiratoire hypoxémique chez les patients atteints de COVID-19 qui peut être utilisé en toute sécurité, sans risque d'infection significatif discernable pour les travailleurs de la santé.

Outcomes and clinical practice in patients with COVID-19 admitted to the intensive care unit in Montréal, Canada: a descriptive analysis.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic is responsible for millions of infections worldwide, and a substantial number of these patients will be admitted to the intensive care unit (ICU). Our objective was to describe the characteristics, outcomes and management of critically ill patients with COVID-19 pneumonia at a single designated pandemic centre in Montréal, Canada. METHODS: A descriptive analysis was performed on consecutive critically ill patients with COVID-19 pneumonia admitted to the ICU at the Jewish General Hospital, a designated pandemic centre in Montréal, between Mar. 5 and May 21, 2020. Complete follow-up data corresponding to death or discharge from hospital health records were included to Aug. 4, 2020. We summarized baseline characteristics, management and outcomes, including mortality. RESULTS: A total of 106 patients were included in this study. Twenty-one patients (19.8%) died during their hospital stay, and the ICU mortality was 17.0% (18/106); all patients were discharged home or died, except for 4 patients (2 awaiting a rehabilitation bed and 2 awaiting long-term care). Twelve of 65 patients (18.5%) requiring mechanical ventilation died. Prone positioning was used in 29 patients (27.4%), including in 10 patients who were spontaneously breathing; no patient was placed on extracorporeal membrane oxygenation. High-flow nasal cannula was used in 51 patients (48.1%). Acute kidney injury was the most common complication, seen in 20 patients (18.9%), and 12 patients (11.3%) required renal replacement therapy. A total of 53 patients (50.0%) received corticosteroids. INTERPRETATION: Our cohort of critically ill patients with COVID-19 had lower mortality than that previously described in other jurisdictions. These findings may help guide critical care decision-making in similar health care systems in further COVID-19 surges.

Early reversible acute kidney injury is associated with improved survival in septic shock.

INTRODUCTION: The fact that acute kidney injury (AKI) is associated with worse clinical outcomes forms the basis of most AKI prognostic scoring systems. However, early reversibility of renal dysfunction in acute illness is not considered in such systems. We sought to determine whether early (≤24 hours after shock documentation) reversibility of AKI was independently associated with in-hospital mortality in septic shock. METHODS: Patient information was derived from an international database of septic shock cases from 28 different institutions in Canada, the United States and Saudi Arabia. Data from a final cohort of 5443 patients admitted with septic shock between Jan 1996 and Dec 2009 was analyzed. The following 4 definitions were used in regards to AKI status: (1) reversible AKI = AKI of any RIFLE severity prevalent at shock diagnosis or incident at 6 hours post-diagnosis that reverses by 24 hours, (2) persistent AKI = AKI prevalent at shock diagnosis and persisting during the entire 24 hours post-shock diagnosis, (3) new AKI = AKI incident between 6 and 24 hours post-shock diagnosis, and (4) improved AKI = AKI prevalent at shock diagnosis or incident at 6 hours post followed by improvement of AKI severity across at least one RIFLE category over the first 24 hours. Cox proportional hazards were used to determine the association between AKI status and in-hospital mortality. RESULTS: During the first 24 hours, reversible AKI occurred in 13.0%, persistent AKI in 54.9%, new AKI in 11.7%, and no AKI in 22.4%. In adjusted analyses, reversible AKI was associated with improved survival (HR, 0.64; 95% CI, 0.53-0.77) compared to no AKI (referent), persistent AKI (HR, 0.99; 95% CI, 0.88-1.11), and new AKI (HR, 1.41; 95% CI, 1.22-1.62). Improved AKI occurred in 19.1% with improvement across any RIFLE category associated with a significant decrease in mortality (HR, 0.53; 95% CI, 0.45-0.63). More rapid antimicrobial administration, lower Acute Physiology and Chronic Health Evaluation II score, lower age, and a smaller number of failed organs (excluding renal) on the day of shock as well as community-acquired infection were independently associated with reversible AKI. CONCLUSION: In septic shock, reversible AKI within the first 24 hours of admission confers a survival benefit compared to no, new, or persistent AKI. Prognostic AKI classification schemes should consider integration of early AKI reversibility into the scoring system.

Antihypertensive agents acting on the renin-angiotensin system and the risk of sepsis.

AIMS: In response to safety concerns from two large randomized controlled trials, we investigated whether the use of telmisartan, an angiotensin receptor blocker (ARB), ARBs as a class and angiotensin-converting enzyme inhibitors (ACEIs) increase the risk of sepsis, sepsis-associated mortality and renal failure in hypertensive patients. METHODS: We performed a nested case-control study from a retrospective cohort of adults with hypertension from the UK General Practice Research Database diagnosed between 1 January 2000 and 30 June 2009. All subjects hospitalized with sepsis during follow-up were matched for age, sex, practice and duration of follow-up with 10 control subjects. Exposure was defined as current use of antihypertensive drugs. RESULTS: From the cohort of 550 436 hypertensive patients, 1965 were hospitalized with sepsis during follow-up (rate 6.9 per 10 000 per year), of whom 824 died and 346 developed acute renal failure within 30 days. Compared with use of ß-blockers, calcium-channel blockers or diuretics, use of ARBs, including telmisartan, was not associated with an elevated risk of sepsis (relative risk 1.09; 95% confidence interval 0.83-1.43); but use ACEIs was (relative risk 1.65; 95% confidence interval 1.42-1.93). Users of ARBs, ß-blockers, calcium-channel blockers or diuretics, but not users of ACEIs, had lower rates of hospitalization for sepsis compared with untreated hypertensive patients. Findings were similar for sepsis-related 30 day mortality and renal failure. CONCLUSIONS: Hypertensive patients treated with ARBs, including telmisartan, do not appear to be at increased risk of sepsis or sepsis-related 30 day mortality or renal failure. On the contrary, users of ACEIs may have an increased risk.

Activated protein C and septic shock: a propensity-matched cohort study*.

BACKGROUND: Septic shock is a highly inflammatory and procoagulant state associated with significant mortality. In a single randomized controlled trial, recombinant human activated protein C (drotrecogin alfa) reduced mortality in patients with severe sepsis at high risk of death. Further clinical trials, including a recently completed trial in patients with septic shock, failed to reproduce these results. OBJECTIVE: To evaluate the effectiveness of recombinant human activated protein C on mortality in a cohort of patients with septic shock and to explore possible reasons for inconsistent results in previous studies. DESIGN: Retrospective, 2:1 propensity-matched, multicenter cohort study. SETTING: Twenty-nine academic and community intensive care units in three countries. PATIENTS: Seven thousand three hundred ninety-two adult patients diagnosed with septic shock, of which 349 received recombinant human activated protein C within 48 hrs of intensive care unit admission between 1997 and 2007. MEASUREMENTS AND MAIN RESULTS: Our primary outcomes were mortality over 30 days and mortality stratified by Acute Physiology and Chronic Health Evaluation II quartile. Using a propensity-matched Cox proportional hazard model, we observed a 6.1% absolute reduction in 30-day mortality associated with the use of recombinant human activated protein C (108/311 [34.7%] vs. 254/622 [40.8%], hazard ratio 0.72, 95% confidence interval 0.52-1.00, p = .05) and noted consistent reductions in mortality among Acute Physiology and Chronic Health Evaluation II quartiles. A time to event analysis showed that the time to appropriate antimicrobials after documented hypotension decreased for each year of study (p = .003), a finding that was congruent with a decrease in annual mortality over the study period (odds ratio 0.96 per year [95% confidence interval 0.93-0.99], p = .003). CONCLUSIONS: In this retrospective, propensity-matched, multicenter cohort study of patients with septic shock, early use of recombinant human activated protein C was associated with reduced mortality. Improvements in general quality of care such as speed of antimicrobial delivery leading to decreasing mortality of patients with septic shock may have contributed to the null results of the recently completed trial of recombinant human activated protein C in patients with septic shock.

Antimicrobial therapeutic determinants of outcomes from septic shock among patients with cirrhosis.

UNLABELLED: It is unclear whether practice-related aspects of antimicrobial therapy contribute to the high mortality from septic shock among patients with cirrhosis. We examined the relationship between aspects of initial empiric antimicrobial therapy and mortality in patients with cirrhosis and septic shock. This was a nested cohort study within a large retrospective database of septic shock from 28 medical centers in Canada, the United States, and Saudi Arabia by the Cooperative Antimicrobial Therapy of Septic Shock Database Research Group between 1996 and 2008. We examined the impact of initial empiric antimicrobial therapeutic variables on the hospital mortality of patients with cirrhosis and septic shock. Among 635 patients with cirrhosis and septic shock, the hospital mortality was 75.6%. Inappropriate initial empiric antimicrobial therapy was administered in 155 (24.4%) patients. The median time to appropriate antimicrobial administration was 7.3 hours (interquartile range, 3.2-18.3 hours). The use of inappropriate initial antimicrobials was associated with increased mortality (adjusted odds ratio [aOR], 9.5; 95% confidence interval [CI], 4.3-20.7], as was the delay in appropriate antimicrobials (aOR for each 1 hour increase, 1.1; 95% CI, 1.1-1.2). Among patients with eligible bacterial septic shock, a single rather than two or more appropriate antimicrobials was used in 226 (72.9%) patients and was also associated with higher mortality (aOR, 1.8; 95% CI, 1.0-3.3). These findings were consistent across various clinically relevant subgroups. CONCLUSION: In patients with cirrhosis and septic shock, inappropriate and delayed appropriate initial empiric antimicrobial therapy is associated with increased mortality. Monotherapy of bacterial septic shock is also associated with increased mortality. The process of selection and implementation of empiric antimicrobial therapy in this high-risk group should be restructured.

Non-steroidal anti-inflammatory drugs and the risk of Clostridium difficile-associated disease.

AIM: Several case reports have linked diclofenac, a non-steroidal anti-inflammatory drug (NSAID), with Clostridium difficile associated disease (CDAD). We assessed whether NSAID use in general, and diclofenac use in particular, is associated with an increased risk of CDAD. METHODS: We used the United Kingdom's General Practice Research Database (GPRD) to conduct a population-based case-control study. All cases of CDAD occurring between 1994 and 2005 were identified and were matched to 10 controls each. Conditional logistic regression was used to estimate the odds ratio of CDAD associated with current NSAID use, adjusting for covariates. RESULTS: We identified 1360 CDAD cases and 13 072 controls. We found an increased risk of CDAD associated with diclofenac (adjusted odds ratio (RR) 1.35, 95% confidence interval (CI) 1.10, 1.67). We did not observe an increased risk of CDAD with use of any other NSAID. No dose-response for diclofenac exposure was found. When we analyzed only patients who were not hospitalized in the year before the index date, we found diclofenac to have a similar effect on CDAD risk (adjusted RR 1.43, 95% CI 1.11, 1.84). CONCLUSION: Diclofenac use is associated with a modest increase in the risk of CDAD. In patients at risk of CDAD, other NSAIDs could be prescribed.

The relationship between inotrope exposure, six-hour postoperative physiological variables, hospital mortality and renal dysfunction in patients undergoing cardiac surgery.

INTRODUCTION: Acute haemodynamic complications are common after cardiac surgery and optimal perioperative use of inotropic agents, typically guided by haemodynamic variables, remains controversial. The aim of this study was to examine the relationship of inotrope use to hospital mortality and renal dysfunction. MATERIAL AND METHODS: A retrospective cohort study of 1,326 cardiac surgery patients was carried out at two university-affiliated ICUs. Multivariable logistic regression analysis and propensity matching were performed to evaluate whether inotrope exposure was independently associated with mortality and renal dysfunction. RESULTS: Patients exposed to inotropes had a higher mortality rate than those not exposed. After adjusting for differences in Parsonnet score, left ventricular ejection fraction, perioperative intraaortic balloon pump use, bypass time, reoperation and cardiac index, inotrope exposure appeared to be independently associated with increased hospital mortality (adjusted odds ratio (OR) 2.3, 95% confidence interval (95% CI) 1.2 to 4.5) and renal dysfunction (adjusted OR 2.7, 95% CI 1.5 to 4.6). A propensity score-matched analysis similarly demonstrated that death and renal dysfunction were significantly more likely to occur in patients exposed to inotropes (P = 0.01). CONCLUSIONS: Postoperative inotrope exposure was independently associated with worse outcomes in this cohort study. Further research is needed to better elucidate the appropriate use of inotropes in cardiac surgery.

Risk factors for mortality following emergency colectomy for fulminant Clostridium difficile infection.

PURPOSE: This study evaluated risk factors for mortality after emergency colectomy for fulminant Clostridium difficile infection. METHODS: Retrospective study of 130 cases of Clostridium difficile infection that required a colectomy between 1994 and 2007 in four hospitals of Quebec, Canada. Primary outcome was 30-day mortality. RESULTS: Twenty-five cases underwent colectomy in 1994 to 2002, 41 in 2003, 40 in 2004, and 24 in 2005 to 2007. Common indications were septic shock (41 percent) and nonresponse to medical treatment (39 percent). Overall, 30-day mortality was 37 percent. Mortality increased with age but was not influenced by comorbidities burden. Mortality correlated with preoperative lactate (< or =2.1 mmol/L: 26 percent; 2.2-4.9 mmol/L: 52 percent; > or =5.0 mmol/L: 75 percent, P < 0.001), leukocytosis (<20.0 x 10(9)/L: 32 percent; 20.0-49.9 x 10(9)/L: 33 percent; > or =50.0 x 10(9)/L: 73 percent, P = 0.008), albumin (> or =25 g/L: 19 percent; 15-24 g/L: 38 percent; <15 g/L: 52 percent, P = 0.04) and renal failure. In multivariate analysis, risk factors for mortality were age (per year, adjusted odds ratio: 1.03, 95 percent confidence interval: 1.00-1.06), preoperative lactate greater than or equal to 5.0 mmol/L (adjusted odds ratio: 10.32, 95 percent confidence interval: 2.59-41.1), leukocytosis greater than or equal to 50.0 x10(9)/L (adjusted odds ratio: 3.68, 95 percent confidence interval: 0.92-14.8) and albumin less than 15 g/L (adjusted odds ratio, 6.57, 95 percent confidence interval: 1.31-33.1). CONCLUSIONS: Incidence of Clostridium difficile infection-related emergency colectomies increased 20-fold during the epidemic. Postoperative mortality can be predicted by simple laboratory parameters. Three-fourths of patients with leukocytosis greater or equal to 50.0 x10(9)/L or lactate greater or equal to 5.0 mmol/L died. When possible, emergency colectomy should be performed earlier.

Acute kidney injury in septic shock: clinical outcomes and impact of duration of hypotension prior to initiation of antimicrobial therapy.

OBJECTIVE: To describe the incidence and outcomes associated with early acute kidney injury (AKI) in septic shock and explore the association between duration from hypotension onset to effective antimicrobial therapy and AKI. DESIGN: Retrospective cohort study. SUBJECTS: A total of 4,532 adult patients with septic shock from 1989 to 2005. SETTING: Intensive care units of 22 academic and community hospitals in Canada, the United States and Saudi Arabia. MEASUREMENTS AND MAIN RESULTS: In total, 64.4% of patients with septic shock developed early AKI (i.e., within 24 h after onset of hypotension). By RIFLE criteria, 16.3% had risk, 29.4% had injury and 18.7% had failure. AKI patients were older, more likely female, with more co-morbid disease and greater severity of illness. Of 3,373 patients (74.4%) with hypotension prior to receiving effective antimicrobial therapy, the median (IQR) time from hypotension onset to antimicrobial therapy was 5.5 h (2.0-13.3). Patients with AKI were more likely to have longer delays to receiving antimicrobial therapy compared to those with no AKI [6.0 (2.3-15.3) h for AKI vs. 4.3 (1.5-10.8) h for no AKI, P < 0.0001). A longer duration to antimicrobial therapy was also associated an increase in odds of AKI [odds ratio (OR) 1.14, 95% CI 1.10-1.20, P < 0.001, per hour (log-transformed) delay]. AKI was associated with significantly higher odds of death in both ICU (OR 1.73, 95% CI 1.60-1.9, P < 0.0001) and hospital (OR 1.62, 95% CI, 1.5-1.7, P < 0.0001). By Cox proportional hazards analysis, including propensity score-adjustment, each RIFLE category was independently associated with a greater hazard ratio for death (risk 1.31; injury 1.45; failure 1.56). CONCLUSION: Early AKI is common in septic shock. Delays to appropriate antimicrobial therapy may contribute to significant increases in the incidence of AKI. Survival was considerably lower for septic shock associated with early AKI, with increasing severity of AKI, and with increasing delays to appropriate antimicrobial therapy.

Patterns of antibiotic use and risk of hospital admission because of Clostridium difficile infection.

BACKGROUND: Previous observations have indicated that infection with Clostridium difficile occurs almost exclusively after exposure to antibiotics, but more recent observations have suggested that prior antibiotic exposure may be less frequent among cases of community-acquired disease. METHODS: We used 2 linked health databases to perform a matched, nested case-control study of elderly patients admitted to hospital with community-acquired C. difficile infection. For each of 836 cases among people 65 years of age or older, we selected 10 controls. We determined the proportion of cases that occurred without prior antibiotic exposure and estimated the risk related to exposure to different antibiotics and the duration of increased risk. RESULTS: Of the 836 cases, 442 (52.9%) had no exposure to antibiotics in the 45-day period before the index date, and 382 (45.7%) had no exposure in the 90-day period before the index date. Antibiotic exposure was associated with a rate ratio (RR) of 10.6 (95% confidence interval [CI] 8.9-12.8). Clindamycin (RR 31.8, 95% CI 17.6-57.6), cephalosporins (RR 14.9, 95% CI 10.9-20.3) and gatifloxacin (RR 16.7, 95% CI 8.3-33.6) were associated with the highest risk. The RR for C. difficile infection associated with antibiotic exposure declined from 15.4 (95% CI 12.2-19.3) by about 20 days after exposure to 3.2 (95% CI 2.0-5.0) after 45 days. Use of a proton pump inhibitor was associated with increased risk (RR 1.6, 95% CI 1.3-2.0), as were concurrent diagnoses of inflammatory bowel disease (RR 4.1, 95% CI 2.6-6.6), irritable bowel syndrome (RR 3.4, 95% CI 2.3-5.0) and renal failure (RR 1.7, 95% CI 1.2-2.2). INTERPRETATION: Community-acquired C. difficile infection occurred in a substantial proportion of individuals with no recent exposure to antibiotics. Among patients who had been exposed to antibiotics, the risk declined markedly by 45 days after discontinuation of use.

Antimicrobial drugs and community-acquired Clostridium difficile-associated disease, UK.

In a population-based case-control study of community acquired Clostridium difficile-associated disease (CDAD), we matched 1,233 cases to 12,330 controls. CDAD risk increased 3-fold with use of any antimicrobial agent and 6-fold with use of fluoroquinolones. Prior use of antimicrobial agents did not affect risk for CDAD after 6 months.

Antimicrobial drugs and community-acquired methicillin-resistant Staphylococcus aureus, United Kingdom.

We report results of a case-control study of the association between receipt of antimicrobial agents and diagnosis of community-acquired methicillin-resistant Staphylococcus aureus (MRSA) in the United Kingdom. Eligible adults, selected from the General Practice Research Database, had no previous diagnosis of MRSA, no hospitalization in the past 2 years, and > or = 2 years of follow-up recorded in the database. For 2000-2004, we identified 1,981 MRSA case-patients and 19,779 matched control-patients. The odds ratios (ORs) and 95% confidence intervals (CIs) of MRSA diagnosis for patients who were prescribed 1, 2-3, or > or = 4 antimicrobial drugs were 1.57 (CI 1.36-1.80), 2.46 (CI 2.15-2.83), and 6.24 (CI 5.43-7.17), respectively. Risk for community-acquired MRSA increased with number of antimicrobial drug prescriptions, appeared to vary according to antimicrobial drug classes prescribed the previous year, and was highest for quinolones (OR 3.37, CI 2.80-4.09) and macrolides (OR 2.50, CI 2.14-2.91).

Proton pump inhibitor use and risk of community-acquired Clostridium difficile-associated disease defined by prescription for oral vancomycin therapy.

BACKGROUND: The association between the use of proton pump inhibitors and the risk of Clostridium difficile-associated disease (CDAD) is controversial. In this study we re-examined a previously reported association between the use of proton pump inhibitors and the development of community-acquired CDAD, this time using an alternative case definition of the disease. METHODS: We performed a case-control study of community-acquired CDAD using a United Kingdom clinical research database. Patients receiving oral vancomycin therapy were identified as having CDAD, the only indication for this drug. Each case subject was matched with up to 10 control subjects. Neither the cases nor the controls had been admitted to hospital in the year before the date of the vancomycin prescription (index date). Conditional logistic regression analysis was used to adjust for key covariates. RESULTS: We identified 317 cases of community-acquired CDAD treated with oral vancomycin therapy and 3167 matched control subjects. Exposure to a proton pump inhibitor in the 90 days before the index date was associated with an increased risk of CDAD (odds ratio [OR] 3.5, 95% confidence interval [CI] 2.3-5.2). Antibiotic exposure in the 90 days before the index date was also a significant risk factor for community-acquired CDAD (OR 8.2, 95% CI 6.1- 11.0), even though 45% of the case subjects had not received a prescription for an antibiotic during that period. Certain comorbidities, in particular renal failure, inflammatory bowel disease and malignant disease, as well as prior methicillin-resistant Staphylococcus aureus infection, were also associated with an increased risk. INTERPRETATION: Proton pump inhibitor use was associated with an increased risk of community-acquired CDAD, when cases were defined by receipt of prescription for oral vancomycin therapy. Prior antibiotic exposure was also a significant risk factor, but a significant proportion of the patients with community-acquired CDAD had no such exposure.

Is there a role for mask continuous positive airway pressure in acute respiratory failure due to COPD? Lessons from a retrospective audit of 3 different cohorts.

Exacerbations of COPD that result in acute respiratory failure requiring intubation and mechanical ventilation have high morbidity and mortality. This study is a retrospective observational study that compared the outcomes of 237 patients with COPD and acute respiratory failure requiring intensive care unit (ICU) admission according to modality of initial therapy: mask continuous positive airway pressure (CPAP), medical therapy, or intubation. Of the patients treated with CPAP initially, only 16% failed and required intubation compared with 62% of those treated medically (p = 0.001). The median length of ICU stay was 5 days in those treated with CPAP, compared with 7 days for those medically treated, and 8.5 days for intubated patients (p = 0.001). When compared with mask CPAP, and after adjusting for potentially confounding differences, mortality was significantly higher if patients were initially intubated (adjusted odds ratios [OR] 15.7; 95% confidence interval [CI] 4.2, 59) or given medical therapy (OR 5.1; CI 1.2, 20.8). In COPD patients with acute respiratory failure, initial treatment with mask CPAP was associated with significantly better outcomes than other treatment modalities, even after adjusting for potentially confounding differences in disease severity.

Hemodilution and surgical hemostasis contribute significantly to transfusion requirements in patients undergoing coronary artery bypass.

OBJECTIVE: We sought to determine the incidence of and risk factors for the development of low intraoperative hematocrit levels and of excessive postoperative bleeding in patients undergoing coronary artery bypass grafting, whether the risk factors are the same, and their effect on blood product transfusions. METHODS: We performed a prospective cohort study of 613 adult patients who underwent coronary artery bypass grafting in 3 tertiary, university-affiliated hospitals during the period from October 1, 2000, to March 31, 2001. RESULTS: Low intraoperative hematocrit levels (<19%) were found in 131 (24%) patients who had operations performed with extracorporeal circulation compared with in 3 (4%) patients with operations performed off pump. In multivariate analysis this was associated with older age, female sex, lower preoperative hemoglobin levels, lower body surface area, longer duration on bypass, and use of higher total volumes with more hydroxyethyl starch in the circuit. Low intraoperative hematocrit levels did not predict excessive postoperative hemorrhage (>1 L of mediastinal drainage in the first 12 hours). This occurred in 26% (n = 140) of patients undergoing on-pump operations and in 25% of patients undergoing off-pump operations and in multivariate analysis was associated with male sex, longer pump times, not receiving aprotinin, and operations performed by certain surgeons but not with total circuit or hydroxyethyl starch volume. CONCLUSIONS: We observed that the risk factors for the development of a low intraoperative hematocrit level and excessive postoperative bleeding differed. Our results suggest that decreasing these outcomes in patients undergoing cardiac surgery requires a comprehensive approach, including limiting hemodilution, particularly in female subjects with lower preoperative hemoglobin levels, and careful attention to surgical hemostasis.