The postoperative bacteriuria score: a new way to predict nosocomial infection after prostate surgery.

OBJECTIVE: Urinary tract infections are the leading nosocomial urologic infections and may be a cause of added morbidity and costs, and sometimes sepsis. The aim of this study was to design a predictive score for these complications after prostate surgery. DESIGN: Multicenter prospective survey. SETTING: Eleven French urology centers. PATIENTS: All patients undergoing transurethral resection of prostate (TURP) during a 3-month period. RESULTS: The overall incidence of postoperative bacteriuria was 25.0% (95% confidence interval, 17.7%-29.5%). Almost all patients (95.7%) received antibiotic prophylaxis. A predictive postoperative bacteriuria score (POBS), with a 6-point scale of 0 to 5, was constructed on the basis of independent risk factors identified in multivariate analysis of a test sample of patients (n=135) and tested in a validation sample (n=73). Significantly more infections occurred in patients with a POBS of 2 or higher (87 [8%] vs 48 [50%]; P<.0001). With the test sample, this yielded a sensitivity of 77%, a specificity of 77%, a positive predictive value of 50%, a negative predictive value of 92%, and a global accuracy of 77%. CONCLUSIONS: POBS could be used to distinguish patients at risk of developing infection after TURP. This information might be useful for implementing selective prevention measures or for adjustment for differences in nosocomial infection rates when comparing data between urology centers.

Mortality attributable to nosocomial infections in the ICU.

Although a direct relationship between nosocomial infection and mortality in intensive care unit (ICU) patients has not always been demonstrated formally, it is possible to conclude that nosocomial infections increase the risk of death in critically ill patients. A more precise analysis indicates that: 1) this effect is highly probable for pneumonia, doubtful for bacteremia, and uncertain for urinary tract infection; 2) risk increases with duration of stay in the ICU; 3) bacterial etiology modifies the risk; and 4) this effect is stronger in less severely ill patients, probably because the severity of underlying disease remains the most significant factor.

Comparison of systematic versus selective screening for methicillin-resistant Staphylococcus aureus carriage in a high-risk dermatology ward.

OBJECTIVE: To compare two strategies for screening methicillin-resistant Staphylococcus aureus (MRSA) carriers in a high-risk dermatology ward: systematic screening of all admitted patients versus selective screening of patients at risk. DESIGN: The two strategies were applied prospectively during two consecutive periods. In period A (8.5 months), only patients transferred from other wards, or with a history of prior hospitalization, or presenting chronic wounds or disease with denuded skin were considered at high risk of MRSA carriage and sampled. In period B (7.5 months), all admitted patients were systematically screened. End-points were the number of patients having a MRSA-positive screening sample on admission during period B and having none of the risk factors used in period A, the rate of imported MRSA cases, and the rate of acquired cases. SETTING: A 1,032-bed university hospital with a 19-bed inpatient dermatology ward, a referral center for toxic epidermal necrolysis and severe extensive dermatoses. PATIENTS: The study included 729 dermatology inpatients (370 in period A and 359 in period B). RESULTS: During period A, screening samples were obtained on admission for 30% of patients (77% of the patients at risk) and identified 25 MRSA carriers. During period B, 90.5% of admitted patients were screened, and 26 MRSA carriers were detected on admission; all of these patients belonged to at least one predefined category at risk for carriage. Overall rates of imported and acquired cases were similar between the two periods (6.8% vs 7.5%, and 2.9% vs 2.4%, respectively). CONCLUSIONS: A screening strategy targeted to patients at risk of harboring MRSA has similar sensitivity and is more cost-effective than a strategy of systematic screening to identify MRSA carriers on admission.

Handwashing compliance in a French university hospital: new perspective with the introduction of hand-rubbing with a waterless alcohol-based solution.

The baseline compliance with handwashing in a French university hospital was as low as the compliance rates reported in other countries, i.e., less than 50%. By introducing the use of hand-rubbing with an alcoholic solution, as a substitution method for both handwashing with soap and handwashing with an antiseptic agent, we significantly improved hand-cleansing compliance. Despite these encouraging results, mainly due to the accessibility of these non-aqueous products, three major obstacles remain before a wide acceptance by healthcare workers: distrust in terms of efficacy, distrust in terms of skin tolerance and lack of knowledge on hand-cleansing indications.

Influence of the severity of illness measured by the Simplified Acute Physiology Score (SAPS) on occurrence of nosocomial infections in ICU patients.

To evaluate the ability of the Simplified Acute Physiology Score (SAPS) to predict the occurrence of hospital-acquired infections in intensive care unit (ICU) patients, we conducted a cohort study in an eight-bed combined ICU. From January 1991 to December 1992, 690 patients were admitted in the ICU and 656 stayed at least 48 h. Patients' severity of illness was estimated within the first 24 h of the ICU stay using the SAPS. Nosocomial infection rates were compared between the high SAPS group (> 10 points) and the low SAPS group (< or = 10 points), with the cut-off point chosen according to a ROC curve. One hundred (15.2%) patients developed hospital-acquired infections during their ICU stay. The mean SAPS of infected patients was significantly higher than the mean SAPS of noninfected patients (15.4 +/- 4.3 vs. 12.0 +/- 5.9 points, P < 0.0001). Significantly more infections occurred in the patients with a SAPS > 10 points (20.9% vs. 5.1%, P < 0.0001). Sensitivity, specificity, positive and negative predictive values for a SAPS > 10 points were 88, 40, 21, and 95%, respectively. Our results suggest that 95% of patients at low risk for developing hospital-acquired infections could be identified on admission with the use of severity scoring systems such as SAPS < or = 10 points.

Misuse of gloves: the foundation for poor compliance with hand hygiene and potential for microbial transmission?

Improvement in hand hygiene compliance is important for reducing cross-infection by micro-organisms. The objective of this prospective observational study was to measure how the improper use of gloves limits compliance to hand hygiene and exposes patient's to infection. The study was conducted in five wards (three intensive care units and two medical wards) in a French university hospital. Staff-patient and staff-environment contacts were observed in 120 healthcare workers caring for patients colonized or infected with pathogenic bacteria. Hand hygiene was not undertaken due to improper gloving in 64.4% (95%CI, 64.1% to 65.1%) of instances. Possible microbial transmission might have occurred in 18.3% (95%CI, 17.8% to 18.8%) of all contacts because used gloves were not removed before performing care activities that necessitated strict aseptic precautions. Failure to change or remove contaminated gloves was a major component in the poor compliance with hand hygiene and carried a high-risk of microbial transmission. Improving hand hygiene compliance will require changing healthcare workers behaviour towards glove use.

[Prevention of acquired pneumonia during artificial ventilation (excluding the use of anti-infectious agents)]. / Moyens de prévention des pneumopathies acquises lors de la ventilation artificielle (à l'exclusion de l'utilisation des anti-infectieux).

Nosocomial pneumonia remains a serious complication which occurs in patients who are artificially ventilated; as neither frequency nor important sequelae have altered recently inspite of the progress which has been achieved both with diagnosis and treatment. Preventative measures ought to be developed and realistically assessed before their introduction. Today it is indispensable to measure the impact of these measures, whether they have been previously or recently proposed by therapeutic trials. The current techniques proposed to prevent the appearance of nosocomial pneumonia are integrated in the usual conventional group of measures in the struggle against nosocomial infection which rests predominantly on standard approaches to hospital hygiene. These may be more specifically directed at good practical measures for the care of the ventilated patient. Regular toilet to the digestive and respiratory pathway, care of the ventilator material, absence of the changing of ventilation tubing during the stay. A certain number of measures are specifically suggested to prevent pneumonias: they have been imperfectly evaluated in clinical practice and remain controversial. Thus selective decontamination of the digestive system has not been dealt with her but also the sitting position, the utilisation of turning or oscillating beds, the continuous aspiration of oropharyngeal secretions or the use of Sucralfate as a means of prevention stress ulcers. Today, and until a complete evaluation of different techniques, the prevention of acquired pneumopathy during artificial ventilation rests above all on extremely simple measures; these cost little and are essentially meticulous care of the upper respiratory and digestive apparatus, to tracheal aspiration and physiotherapy which assure effective drainage and secretions, the use of the semi-sitting position, a well positioned gastric tube, in other words, basic care of the ventilated patient of a very good quality.

Contamination of healthcare workers' hands with Clostridium difficile spores after caring for patients with C. difficile infection.

OBJECTIVE: We determined the percentage of healthcare workers' (HCWs') hands contaminated with Clostridium difficile spores after caring for patients with C. difficile infection (CDI) and risk factors associated with contamination. DESIGN: Prospective study. SETTING: A French university hospital. METHODS: We compared the hand contamination rate among HCWs caring for patients with CDI (exposed group; n = 66) with that among an unexposed group (n = 44). Spores of C. difficile were recovered from the hands of HCWs after rubbing their fingers and palms in alcohol shortly after patient care. Associations between hand contamination and HCW category, type (patient or environment), and risk level (high or low risk) of HCW contacts and their respective duration as well as use of gloves were analyzed by bivariate and multivariate analysis. RESULTS: C. difficile spores were detected on 24% of HCWs' hands in the exposed group and on 0% in the unexposed group (P < .001). In the exposed group, logistic regression, which adjusted for high-risk contact (ie, exposure to fecal soiling), contact with the environment, and contact with or without use of gloves, revealed that high-risk contact (adjusted odds ratio [aOR] per 1 contact increment, 2.78; 95% confidence interval [CI], 1.42-5.45; P = .003) and at least 1 contact without use of gloves (aOR, 6.26; 95% CI, 1.27-30.78; P = .02) were independently associated with HCW hand contamination by C. difficile spores. CONCLUSIONS: Nearly one-quarter of HCWs have hands contaminated with C. difficile spores after routine care of patients with CDI. Hand contamination is positively associated with exposure to fecal soiling and lack of glove use.

Effect of time to onset on clinical features and prognosis of post-sternotomy mediastinitis.

Incubation time affects the clinical features and outcome of many nosocomial infections. However, its role in the setting of post-sternotomy mediastinitis (PSM) has not been specifically studied. The present study aimed to evaluate the impact of time to onset of PSM on the clinical presentation and outcomes of patients. Hospital records of 197 patients who developed PSM over a 10-year period and were treated by closed drainage using Redon catheters were reviewed retrospectively. Follow-up was complete for all included patients (median of 19 months); 98 patients developed early-onset PSM (time from initial operation to PSM <14 days) and 99 patients had late-onset PSM (≥14 days). Patients with late-onset PSM had a higher rate of internal thoracic artery harvest and mediastinal re-exploration after initial operation. Patients with early-onset PSM presented more frequently with septic shock. Microbiological findings differed between early- and late-onset PSM by a higher incidence of Enterococcus species in the former and of Staphylococcus aureus in the latter. Overall mortality reached 34% (n = 66). Rates of superinfection, treatment failure, mediastinitis-related death, mortality at 1 year and overall mortality were all significantly higher in patients with early-onset PSM. Multiple regression procedures identified early-onset PSM as a significant and independent risk factor for both 1-year (OR 2.40; 95% CI 1.12-5.11) and overall (OR 2.11; 95% 1.26-3.53) mortality. In conclusion, the results obtained in the present study support the distinction between early- and late-onset PSM with different clinical and pathophysiological features. Early-onset PSM is associated with a significantly higher morbidity and mortality compared to late-onset PSM.

Clinical impact of a real-time PCR assay for rapid identification of Staphylococcus aureus and determination of methicillin resistance from positive blood cultures.

The full identification and susceptibility profile of staphylococci from positive blood cultures (BCs) generally takes 24-48 h using phenotypic methods. The aim of this prospective study was to evaluate the clinical impact of a real-time PCR strategy for rapid identification of staphylococci and determination of methicillin resistance directly from positive BCs. During a 12-month period, 250 episodes of positive BCs with organism morphology resembling staphylococci were enrolled. Two strategies were compared: conventional (n = 128) using standard phenotypic methods or rapid (n = 122) using a real-time PCR assay that is able to detect specific genes of Staphylococcus aureus (nuc and sa442) and the encoding gene for methicillin resistance (mecA). Overall, 97 episodes (39%) were clinical-significant bloodstream infections. The prevalence of methicillin resistance of S. aureus was 24%. A favorable outcome (defined as clinical cure with resolution of signs and no evidence of recurrence or relapse at 12 weeks follow-up) was observed in similar proportions of episodes with (58%) or without (60%) PCR testing (p 0.8). In multivariate analyses, age and infection due to methicillin-susceptible S. aureus (adjusted OR 0.96, 95% CI 0.93-0.99; and adjusted OR 3.11, 95% CI 1.12-8.65, respectively) were the unique factors independently associated with a favorable outcome. Among the 153 episodes of contaminated BCs, similar proportions received unjustified antibiotic therapy (PCR strategy: 17%, conventional testing: 10%; p 0.33). In a setting with a moderate level of methicillin-resistant S. aureus and relatively high contamination of BCs, real-time PCR testing was not beneficial compared to conventional methods.

Comparison of the efficacy of a hydrogen peroxide dry-mist disinfection system and sodium hypochlorite solution for eradication of Clostridium difficile spores.

OBJECTIVE: To compare a hydrogen peroxide dry-mist system and a 0.5% hypochlorite solution with respect to their ability to disinfect Clostridium difficile-contaminated surfaces in vitro and in situ. DESIGN: Prospective, randomized, before-after trial. SETTING: Two French hospitals affected by C. difficile. INTERVENTION: In situ efficacy of disinfectants was assessed in rooms that had housed patients with C. difficile infection. A prospective study was performed at 2 hospitals that involved randomization of disinfection processes. When a patient with C. difficile infection was discharged, environmental contamination in the patient's room was evaluated before and after disinfection. Environmental surfaces were sampled for C. difficile by use of moistened swabs; swab samples were cultured on selective plates and in broth. Both disinfectants were tested in vitro with a spore-carrier test; in this test, 2 types of material, vinyl polychloride (representative of the room's floor) and laminate (representative of the room's furniture), were experimentally contaminated with spores from 3 C. difficile strains, including the epidemic clone ribotype 027-North American pulsed-field gel electrophoresis type 1. RESULTS: There were 748 surface samples collected (360 from rooms treated with hydrogen peroxide and 388 from rooms treated with hypochlorite). Before disinfection, 46 (24%) of 194 samples obtained in the rooms randomized to hypochlorite treatment and 34 (19%) of 180 samples obtained in the rooms randomized to hydrogen peroxide treatment showed environmental contamination. After disinfection, 23 (12%) of 194 samples from hypochlorite-treated rooms and 4 (2%) of 180 samples from hydrogen peroxide treated rooms showed environmental contamination, a decrease in contamination of 50% after hypochlorite decontamination and 91% after hydrogen peroxide decontamination (P < .005). The in vitro activity of 0.5% hypochlorite was time dependent. The mean (+/-SD) reduction in initial log(10) bacterial count was 4.32 +/- 0.35 log(10) colony-forming units after 10 minutes of exposure to hypochlorite and 4.18 +/- 0.8 log(10) colony-forming units after 1 cycle of hydrogen peroxide decontamination. CONCLUSION: In situ experiments indicate that the hydrogen peroxide dry-mist disinfection system is significantly more effective than 0.5% sodium hypochlorite solution at eradicating C. difficile spores and might represent a new alternative for disinfecting the rooms of patients with C. difficile infection.

Prevention of nosocomial infections in acute respiratory failure patients.

Patients with acute respiratory failure are predisposed to acquire nosocomial infection primarily because they may need ventilatory support, usually invasive mechanical ventilation. The presence of an endotracheal tube impairs natural defences of the respiratory tract and favours airways colonisation and lung infection. Cross transmission of microorganisms may also occur via contaminated hands of healthcare workers that manipulate invasive devices. Thus, avoiding the endotracheal tube and increasing hand hygiene compliance are major measures to prevent ventilator-associated pneumonia. The use of noninvasive ventilation has been shown to reduce the incidence of nosocomial infections and should be used whenever possible. Using hand rubbing with waterless alcohol-based products evidenced higher efficacy to reduce hand contamination as compared to conventional hand washing with soap. Due to its rapid activity and ease of access, hand rubbing constitutes a promising avenue for improving hand hygiene compliance and thus reducing cross infection.

Development of a Web-based clinical information system for surveillance of multiresistant organisms and nosocomial infections.

To optimize the surveillance and control of infections at our hospital, we have developed a clinical information system (CIS) linked to a server providing three kinds of patient-oriented data reports: 1/an automated alert for multiresistant bacteria from a data-driven mechanism; 2/the relevant data for surveillance of hospital-acquired infections; 3/some clinical and educational data for antibiotic prescribing. The new CIS is a Web-based one and now integrated to the Hospital Information System (HIS). In a close collaboration with the experts, we have, first, specified the relevant information for each report. Then, we have linked the system to those HIS DBs containing this information. Finally we have developed a well-secured intranet Web site, on which the concerned practitioners can instantaneously review the latest alerts and/or the summarized/detailed reports. The preliminary results shows that the system is reliable in medical practice and the response time is satisfying.

Appropriate use of restricted antimicrobial agents in hospitals: the importance of empirical therapy and assisted re-evaluation.

We evaluated the appropriateness of use of restricted antimicrobial agents in the context of a newly implemented order form and delivery system for restricted antimicrobial agents, using sequential prospective audits of prescriptions. Four antimicrobial agents were selected: glycopeptides (61 prescriptions), ciprofloxacin (42), piperacillin-tazobactam (42) and imipenem- cilastatin (47). The justification and adequacy of the antibiotic or combination used, reassessment of therapy and duration of treatment were appraised with reference to the clinical situation and hospital's guidelines. Of the 192 prescriptions, 30 (16%) were empirical therapy, 95 (49%) empirical and secondarily documented and 67 (35%) initially documented therapy. Overall, 73% of prescriptions conformed to guidelines, but the adequacy varied from 93% for vancomycin to only 38% for ciprofloxacin. Of 83/157 initially inadequate prescriptions, 42 (51%) were switched according to guidelines, but only 14% of ciprofloxacin prescriptions were adapted later. An intervention audit with counselling on ciprofloxacin usage increased this rate to 75%. Although implementation of the guidelines resulted in a marked reduction in overall antimicrobial costs, inappropriate antibiotic usage may persist for some drugs despite restricted access. These results emphasize the need for combined interventions using education and expert counselling, targeted to classes of antibiotic for which inappropriate usage is most common.

Risk factors and outcome of nosocomial infections: results of a matched case-control study of ICU patients.

Intensive-care-unit (ICU) patients are at risk for both acquiring nosocomial infection and dying, and require a high level of therapy whether infection occurs or not. The objective of the present study was to precisely define the interrelationships between underlying disease, severity of illness, therapeutic activity, and nosocomial infections in ICU patients, and their respective influences on these patients' outcome. In a 10-bed medical ICU, we conducted a case-control study with matching for initial severity of illness, with daily monitoring of severity of illness and therapeutic activity scores, and with analysis of the contribution of nosocomial infections to patients' outcomes. Forty-one cases of patients who developed nosocomial infections during a 1-yr period were paired with 41 controls without nosocomial infection according to three criteria: age (+/- 5 yr), Acute Physiology and Chronic Health Evaluation II (APACHE II) score (+/- 5 points), and duration of exposure to risk. Successful matching was achieved for 118 of 123 (96%) variables. Neurologic failure on the third day after ICU admission was the sole independent risk factor for nosocomial infection (adjusted odds ratio [OR]: 1.34; 95% confidence interval [CI]: 1.09 to 1.64; p = 0.007). Unlike control patients, case patients showed no clinical improvement and required a high level of therapeutic activity between ICU admission and the day of infection. Mortality attributable to nosocomial infection was 44%. Excess length of stay and duration of antibiotic treatment attributable to nosocomial infection were 14 d and 10 d, respectively. Attributable therapeutic activity as measured with the Therapeutic Intervention Scoring System (TISS) and Omega score was 368 and 233 points, respectively. Such consequences were observed in patients who developed multiple infections. These findings suggest that a persistent high level of therapeutic activity and persistent impaired consciousness are risk factors for nosocomial infections in ICU patients. These infections are responsible for excess mortality, prolongation of stay, and excess therapeutic activity resulting in important cost overruns for health-care systems.

Selective screening of carriers for control of methicillin-resistant Staphylococcus aureus (MRSA) in high-risk hospital areas with a high level of endemic MRSA.

Screening for methicillin-resistant Staphylococcus aureus (MRSA) carriage in patients at risk was evaluated as part of a control program in a 26-bed medical intensive care unit (ICU) of a university hospital with a high level of endemic MRSA. Control measures included isolation and barrier precautions, skin decolonization with chlorhexidine of patients from whom MRSA was recovered, and mupirocin treatment of nasal carriers of MRSA. Of 3,686 patients admitted during a 4-year period, 44% were screened, which occurred during admission for 38%; MRSA was recovered from 293 patients (8%). There were 150 imported cases and 143 ICU-acquired cases, of which 51% and 45%, respectively, were first identified through screening. Nasal swab cultures identified 84% of MRSA carriers. The incidence of all ICU-acquired cases and of acquired colonization or infection decreased from 5.8% and 5.6% to 2.6% and 1.4% (P = .002 and P < .001), respectively, whereas that of imported cases remained unchanged (range, 3.8% to 4.3%; P = .8). Selective screening for nasal carriage during admission to high-risk areas may contribute to identification of a substantial proportion of cases of MRSA and to early implementation of effective control measures.

Association of noninvasive ventilation with nosocomial infections and survival in critically ill patients.

CONTEXT: Invasive life-support techniques are a major risk factor for nosocomial infection. Noninvasive ventilation (NIV) can be used to avoid endotracheal intubation and may reduce morbidity among patients in intensive care units (ICUs). OBJECTIVE: To determine whether the use of NIV is associated with decreased risk of nosocomial infections and improved survival in everyday clinical practice among patients with acute exacerbation of chronic obstructive pulmonary disease (COPD) or hypercapnic cardiogenic pulmonary edema (CPE). DESIGN AND SETTING: Matched case-control study conducted in the medical ICU of a French university hospital from January 1996 through March 1998. PATIENTS: Fifty patients with acute exacerbation of COPD or severe CPE who were treated with NIV for at least 2 hours and 50 patients treated with mechanical ventilation between 1993 and 1998 (controls), matched on diagnosis, Simplified Acute Physiology Score II, Logistic Organ Dysfunction score, age, and no contraindication to NIV. MAIN OUTCOME MEASURES: Rates of nosocomial infections, antibiotic use, lengths of ventilatory support and of ICU stay, ICU mortality, compared between cases and controls. RESULTS: Rates of nosocomial infections and of nosocomial pneumonia were significantly lower in patients who received NIV than those treated with mechanical ventilation (18% vs 60% and 8% vs 22%; P<.001 and P =.04, respectively). Similarly, the daily risk of acquiring an infection (19 vs 39 episodes per 1000 patient-days; P =.05), proportion of patients receiving antibiotics for nosocomial infection (8% vs 26%; P =.01), mean (SD) duration of ventilation (6 [6] vs 10 [12] days; P =.01), mean (SD) length of ICU stay (9 [7] vs 15 [14] days; P =.02), and crude mortality (4% vs 26%; P =.002) were all lower among patients who received NIV than those treated with mechanical ventilation. CONCLUSIONS: Use of NIV instead of mechanical ventilation is associated with a lower risk of nosocomial infections, less antibiotic use, shorter length of ICU stay, and lower mortality. JAMA. 2000;284:2361-2367.

Predictors of mortality in acute respiratory distress syndrome. Focus On the role of right heart catheterization.

Right heart catheterization (RHC) has been suspected of increasing mortality. The acute respiratory distress syndrome (ARDS) is a frequent reason for RHC. We designed a retrospective cohort study of 119 consecutive ARDS patients admitted to two medical intensive care units of tertiary care hospitals in which two different approaches are used for hemodynamic monitoring: RHC on demand (Henri Mondor Hospital [HM]) and no use of RHC (Ambroise Paré Hospital [AP]). The study tried to identify risk factors for death, and to assess the influence of RHC, with adjustment for the intensity of hemodynamic support as a confounding factor, using 98 patients in whom the delay between onset of ARDS, use of vasopressors, and RHC did not exceed 48 h. Several variables, including septic shock, cause of ARDS, Simplified Acute Physiology Score (SAPS) II, use of epinephrine/norepinephrine, and presence of RHC were entered into a logistic regression model to evaluate their independent prognostic roles. Mortality was different at HM and AP (36 of 55 patients [65.5%] versus 16 of 43 patients [37.2%], p < 0.005), and 29 of the 35 RHC-monitored patients died (82.8%), as compared with 23 of 63 patients (36.5%) treated without RHC (p < 0.0001). However, administration of epinephrine/norepinephrine and a nonpulmonary cause of ARDS were each independently associated with death. It is only when administration of vasopressors was omitted from the model that RHC, septic shock, and SAPS II became independent predictors of mortality. These results suggest that: (1) the use of vasopressors, but not of RHC, represents an important prognostic factor; and (2) not taking into account the use of these drugs may be misleading when assessing the influence of RHC on outcome.