[Predictive validity of selection process in medical school, a systematic review of the literature]. / Sélection des étudiants en médecine : facteurs prédictifs de réussite ; une revue systématique de la littérature.

CONTEXT: The number of applicants to medical school exceeds the number of places available, a situation that questions the effectiveness and relevance of medical student assessment and selection. OBJECTIVES: The objective of this review of the literature was to analyze in a systematic way the studies looking for an association between results of an admission procedure and a later evaluation of the characteristics of the students or the doctors that they became. DOCUMENTARY SOURCES (KEY WORDS AND LANGUAGE): MedLine, Web of Science and Cochrane Library. The articles written in English were selected. The keywords were: "medical school"; "student admissions"; "student selection"; "predictive validity"; "student performance"; "interview"; "MCAT" (Medical College Admission Test); "MMI" (Mini Mental Interview). RESULTS: Of the 1116 listed publications, 22 were analyzed. Criteria assessed at the admission (standardized written tests, evaluation of personality and social skills, academic evaluation, demographic characteristics) were confronted with the criteria measured during the follow-up (academic or clinical evaluations). The previous academic results and the standardized written tests seem associated to academic success in medical school. CONCLUSION: The actual selection methods used in our French medical universities are very different from those described in international literature. It is difficult to clearly define factors associated with success during student selection as there is a great diversity of cultures and methods involved.

Acquiring procedural skills in ICUs: a prospective multicenter study*.

OBJECTIVES: Providing appropriate training of procedural skills to residents while ensuring patient safety through trainee supervision is a difficult and constant challenge. We sought to determine how effective and safe procedural skill acquisition is in French ICUs and to identify failure and complication risk factors. DESIGN: Multicenter prospective observational study. Invasive procedures performed by residents were recorded during two consecutive semesters. SETTING: Eighty-four residents. SUBJECTS: Eighty-four residents. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Number of invasive procedures performed, failure and complication rates, supervision, and assistance provided. Five thousand six hundred seventeen procedures were prospectively studied: 1,007 tracheal intubations, 1,272 arterial and 2,586 central venous catheter insertions, 457 fiberoptic bronchoscopies, and 295 chest tube insertions. During the semesters, residents performed a median of 10 intubations, 14 arterial catheter insertions, and 26 central venous catheter insertions. Complication rates were low, similar to those in the literature: 8.6% desaturation and 7.4% esophageal placement during intubation; 0.4% and 2.3% pneumothorax with jugular and subclavian central venous catheter insertions, respectively. We identified risk factors for failure and complications. Higher rates of failure and complications for intubation were associated with residents with no or little previous experience (p < 0.001); failure of internal jugular vein catheterization was associated with left-side insertion (p = 0.005) and absence of mechanical ventilation (p = 0.007). Supervision and assistance were more frequent at the beginning of the semester and for intubation and chest tube insertion. Finally, residents had less access to fiberoptic bronchoscopy and chest tube insertion. CONCLUSION: Procedural skills acquisition by residents in the ICU appears feasible and safe with complication rates comparable to what has previously been reported. We identified specific procedures and situations associated with higher failure and complication rates that could require proactive training. Questions still remain regarding minimal numbers of procedures to attain competence and how best to provide procedural training.

Fluid challenge: tracking changes in cardiac output with blood pressure monitoring (invasive or non-invasive).

PURPOSE: To assess whether invasive and non-invasive blood pressure (BP) monitoring allows the identification of patients who have responded to a fluid challenge, i.e., who have increased their cardiac output (CO). METHODS: Patients with signs of circulatory failure were prospectively included. Before and after a fluid challenge, CO and the mean of four intra-arterial and oscillometric brachial cuff BP measurements were collected. Fluid responsiveness was defined by an increase in CO ≥10 or ≥15% in case of regular rhythm or arrhythmia, respectively. RESULTS: In 130 patients, the correlation between a fluid-induced increase in pulse pressure (Δ500mlPP) and fluid-induced increase in CO was weak and was similar for invasive and non-invasive measurements of BP: r² = 0.31 and r² = 0.29, respectively (both p < 0.001). For the identification of responders, invasive Δ500mlPP was associated with an area under the receiver-operating curve (AUC) of 0.82 (0.74-0.88), similar (p = 0.80) to that of non-invasive Δ500mlPP [AUC of 0.81 (0.73-0.87)]. Outside large gray zones of inconclusive values (5-23% for invasive Δ500mlPP and 4-35% for non-invasive Δ500mlPP, involving 35 and 48% of patients, respectively), the detection of responsiveness or unresponsiveness to fluid was reliable. Cardiac arrhythmia did not impair the performance of invasive or non-invasive Δ500mlPP. Other BP-derived indices did not outperform Δ500mlPP. CONCLUSIONS: As evidenced by large gray zones, BP-derived indices poorly reflected fluid responsiveness. However, in our deeply sedated population, a high increase in invasive pulse pressure (>23%) or even in non-invasive pulse pressure (>35%) reliably detected a response to fluid. In the absence of a marked increase in pulse pressure (<4-5%), a response to fluid was unlikely.

Effect of eritoran, an antagonist of MD2-TLR4, on mortality in patients with severe sepsis: the ACCESS randomized trial.

IMPORTANCE: Eritoran is a synthetic lipid A antagonist that blocks lipopolysaccharide (LPS) from binding at the cell surface MD2-TLR4 receptor. LPS is a major component of the outer membrane of gram-negative bacteria and is a potent activator of the acute inflammatory response. OBJECTIVE: To determine if eritoran, a TLR4 antagonist, would significantly reduce sepsis-induced mortality. DESIGN, SETTING, AND PARTICIPANTS: We performed a randomized, double-blind, placebo-controlled, multinational phase 3 trial in 197 intensive care units. Patients were enrolled from June 2006 to September 2010 and final follow-up was completed in September 2011. INTERVENTIONS: Patients with severe sepsis (n = 1961) were randomized and treated within 12 hours of onset of first organ dysfunction in a 2:1 ratio with a 6-day course of either eritoran tetrasodium (105 mg total) or placebo, with n = 1304 and n = 657 patients, respectively. MAIN OUTCOME MEASURES: The primary end point was 28-day all-cause mortality. The secondary end points were all-cause mortality at 3, 6, and 12 months after beginning treatment. RESULTS: Baseline characteristics of the 2 study groups were similar. In the modified intent-to-treat analysis (randomized patients who received at least 1 dose) there was no significant difference in the primary end point of 28-day all-cause mortality with 28.1% (366/1304) in the eritoran group vs 26.9% (177/657) in the placebo group (P = .59; hazard ratio, 1.05; 95% CI, 0.88-1.26; difference in mortality rate, -1.1; 95% CI, -5.3 to 3.1) or in the key secondary end point of 1-year all-cause mortality with 44.1% (290/657) in the eritoran group vs 43.3% (565/1304) in the placebo group, Kaplan-Meier analysis of time to death by 1 year, P = .79 (hazard ratio, 0.98; 0.85-1.13). No significant differences were observed in any of the prespecified subgroups. Adverse events, including secondary infection rates, did not differ between study groups. CONCLUSIONS AND RELEVANCE: Among patients with severe sepsis, the use of eritoran, compared with placebo, did not result in reduced 28-day mortality. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00334828.

Acute kidney injury in the critically ill: is iodinated contrast medium really harmful?

OBJECTIVES: To assess whether the use of iodinated contrast medium increases the incidence of acute kidney injury in ICU patients, compared with patients not receiving iodinated contrast medium. DESIGN: Prospective observational matched cohort study. SETTING: Two ICUs in two tertiary teaching hospitals. PATIENTS: A total of 380 adults were included (20% more than once), before an iodinated contrast medium infusion (contrast inclusions, n=307) or before an intrahospital transfer without iodinated contrast medium infusion (control inclusions, n=170). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among contrast inclusions, iodinated contrast medium-associated acute kidney injury occurred after 23 administrations (7.5%) according to the Acute Kidney Injury Network definition (stage≥1, over 48 hr). As expected, a broader definition (≥25% increase in serum creatinine over 72 hr) yielded a greater incidence (16%). In 146 pairs of contrast and control inclusions, matched on propensity for iodinated contrast medium infusion, the incidence of acute kidney injury was similar (absolute difference in incidence, 0%; 95% confidence interval, -5.2; 5.2%), Acute Kidney Injury Network definition). Hospital mortality was also similar in 71 contrast and 71 control patients included only once and matched the same way. Contrary to iodinated contrast medium infusion (odds ratio, 1.57; 95% confidence interval, 0.69-3.53), the Sequential Organ Failure Assessment score at inclusion (odds ratio, 1.18; 95% confidence interval, 1.07-1.31) and the number of other nephrotoxic agents (odds ratio, 1.38; 95% confidence interval, 1.03-1.85) were independent risk factors for acute kidney injury. CONCLUSIONS: The specific toxic effect of monomeric nonionic low-osmolar iodinated contrast medium in ICU patients with multiple renal aggressions seemed minimal. Severity of disease and the global nephrotoxic burden were risk factors for acute kidney injury, regardless of iodinated contrast medium infusion.

Safety and diagnostic yield of renal biopsy in the intensive care unit.

PURPOSE: Renal biopsy (RB) is occasionally performed in critically ill patients. The safety and impact of RB in this setting have not been reported. METHODS: A 10-year (2000-2009) retrospective multicentre study was conducted in ten French intensive care units (ICU) on patients who underwent RB during their management. Medical files were retrieved for data analysis. RESULTS: Seventy-seven patients underwent an RB of which 68 (88 %) were on a native kidney and 9 (12 %) on a transplanted kidney. Percutaneous ultrasound-guided RB was used in most cases (87 %). Fifty-seven per cent of the patients were on mechanical ventilation at the time of RB. RB-related complications occurred in 17 (22 %) patients, two were graded as severe (requirement for kidney embolization, eventually successful). In 35 (51 %) non-transplanted patients, RB established a specific diagnosis other than acute tubular necrosis (ATN), which was diagnosed in only 18 % of patients. In the remaining patients, only non-specific lesions were observed. Therapeutic modifications followed RB in 14 (21 %) non-transplanted patients. Presence of signs of systemic disease involving the renal tract, occurrence of renal failure before hospital admission, and absence of any factor usually associated with ATN significantly predicted the presence of a specific diagnosis at RB other than ATN. CONCLUSIONS: In this cohort, the contribution of RB to diagnosis and treatment was undeniable, but at the expense of frequent adverse events although most of them were not considered severe.

Hypoglycaemia: a little known effect of Venlafaxine overdose.

We report the case of a 39-year-old woman who presented with serotonin syndrome and hypoglycaemia likely due to intoxication with a very high dose of venlafaxine. This case of venlafaxine-associated hypoglycaemia was treated first by glucose perfusion, but despite large doses, hypoglycaemia recurred. Blood glucose normalized after injection of octreotide, eliminating the need for hypertonic glucose. Octreotide has been shown to decrease glucose requirements and the number of hypoglycaemic episodes in patients with sulfonylurea-induced hypoglycaemia but, to our knowledge, its ability to resolve hypoglycaemic episodes due to massive venlafaxine overdose has not yet been described.

Feasibility of right ventricular longitudinal systolic function evaluation with transthoracic echocardiographic indices derived from tricuspid annular motion: a preliminary study in acute respiratory distress syndrome.

INTRODUCTION: Assessment of right ventricular (RV) function in patients with acute respiratory distress syndrome (ARDS) remains challenging. Transthoracic echocardiographic (TTE) indices based on longitudinal systolic RV function are now considered as a reliable evaluation of RV function. We investigated feasibility of two methods in ARDS patients. METHODS: Prospective observational study. TTE was performed after 12-36 hours of mechanical ventilation. Feasibility of tricuspid annular motion (S(t) ), tricuspid annular plane systolic excursion (TAPSE) was compared to usual two-dimensional (2D) study: fractional area change (RV(FAC) ) and ratio of right to left ventricular end-diastolic area (RVEDA/LVEDA). RESULTS: Fifty patients were investigated, with TTE possible in all but two patients. Feasibility was 62% for RV(FAC), 72% for RVEDA/LVEDA, and 96% for TAPSE and S(t). RV dilatation (RVEDA/LVEDA ≥ 0.60) was found in 16 patients, including 4 patients with acute cor pulmonale. A longitudinal RV dysfunction (TAPSE < 12 mm or S(t) < 11.5 cm/sec) was suspected in 30% of patients. Relation between both longitudinal indices was modest (r(2) = 0.36, P < 0.001). TAPSE (but not S(t) ) was found poorly related to RV(FAC) (r(2) = 0.27, P = 0.03). Both indices were related to LV function (S(t) : r(2) = 0.27, TAPSE: r(2) = 0.17, both P < 0.05). CONCLUSION: Despite a superior feasibility than 2D study, our results suggest that both indices may not bring identical information to echo study. TAPSE may be more adapted to ICU use than S(t) . Both should be further investigated in terms of analysis of RV function and ventricular interdependence. Their relations with LV function may limit their use as sole markers of RV function in this population.

Randomized comparison of 2 protocols to prevent acquisition of methicillin-resistant Staphylococcus aureus: results of a 2-center study involving 500 patients.

OBJECTIVE: To compare an interventional protocol with a standard protocol for preventing the acquisition of methicillin-resistant Staphylococcus aureus (MRSA) in the intensive care unit (ICU). DESIGN: Prospective, randomized, controlled, parallel-group, nonblinded clinical trial. SETTING: Medical ICUs of 2 French university hospitals. PARTICIPANTS: Five hundred adults with an expected length of stay in the ICU greater than 48 hours. INTERVENTIONS: For the intervention group, the protocol required repeated MRSA screening, contact and droplet isolation precautions for patients at risk for MRSA at ICU admission and for MRSA-positive patients, and decontamination with nasal mupirocin and chlorhexidine body wash for MRSA-positive patients. For the standard group, the standard precautions protocol was used, and the results of repeated MRSA screening in the standard group were not communicated to investigators. MAIN OUTCOME MEASURE: MRSA acquisition rate in the ICU. An audit was conducted to assess compliance with hygiene and isolation precautions. RESULTS: In the intent-to-treat analysis ([Formula: see text]), the MRSA acquisition rate in the ICU was similar in the standard (13 [5.3%] of 243) and intervention (16 [6.5%] of 245) groups ([Formula: see text]). The audit showed that the overall compliance rate was 85.5% in the standard group and 84.1% in the intervention group ([Formula: see text]), although compliance was higher when isolation precautions were absent than when they were in place (88.2% vs 79.1%; [Formula: see text]). MRSA incidence rates were higher without isolation precautions (7.57‰) than with isolation precautions (2.36‰; [Formula: see text]). CONCLUSIONS: Individual allocation to MRSA screening, isolation precautions, and decontamination do not provide individual benefit in reducing MRSA acquisition, compared with standard precautions, although the collective risk was lower during the periods of isolation. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT00151606.

Relation between mean arterial pressure and renal function in the early phase of shock: a prospective, explorative cohort study.

INTRODUCTION: Because of disturbed renal autoregulation, patients experiencing hypotension-induced renal insult might need higher levels of mean arterial pressure (MAP) than the 65 mmHg recommended level in order to avoid the progression of acute kidney insufficiency (AKI). METHODS: In 217 patients with sustained hypotension, enrolled and followed prospectively, we compared the evolution of the mean arterial pressure (MAP) during the first 24 hours between patients who will show AKI 72 hours after inclusion (AKIh72) and patients who will not. AKIh72 was defined as the need of renal replacement therapy or "Injury" or "Failure" classes of the 5-stage RIFLE classification (Risk, Injury, Failure, Loss of kidney function, End-stage renal disease) for acute kidney insufficiency using the creatinine and urine output criteria. This comparison was performed in four different subgroups of patients according to the presence or not of AKI at the sixth hour after inclusion (AKIh6 as defined as a serum creatinine level above 1.5 times baseline value within the first six hours) and the presence or not of septic shock at inclusion.The ability of MAP averaged over H6 to H24 to predict AKIh72 was assessed by the area under the receiver operating characteristic curve (AUC) and compared between groups. RESULTS: The MAP averaged over H6 to H24 or over H12 to H24 was significantly lower in patients who showed AKIh72 than in those who did not, only in septic shock patients with AKIh6, whereas no link was found between MAP and AKIh72 in the three others subgroups of patients. In patients with septic shock plus AKIh6, MAP averaged over H6 to H24 or over H12 to H24 had an AUC of 0.83 (0.72 to 0.92) or 0.84 (0.72 to 0.92), respectively, to predict AKIh72 . In these patients, the best level of MAP to prevent AKIh72 was between 72 and 82 mmHg. CONCLUSIONS: MAP about 72 to 82 mmHg could be necessary to avoid acute kidney insufficiency in patients with septic shock and initial renal function impairment.

Population pharmacokinetics of ceftriaxone in critically ill septic patients: a reappraisal.

AIMS: To investigate the population pharmacokinetics of ceftriaxone in critically ill patients suffering from sepsis, severe sepsis or septic shock. METHODS: Blood samples were collected at preselected times in 54 adult patients suffering from sepsis, severe sepsis or septic shock in order to determine ceftriaxone concentrations using high-performance liquid chromatography-ultraviolet detection. The pharmacokinetics of ceftriaxone were assessed on two separate occasions for each patient: on the second day of ceftriaxone therapy and 48 h after catecholamine withdrawal in patients with septic shock, or on the fifth day in patients with sepsis. The population pharmacokinetics of ceftriaxone were studied using nonlinear mixed effects modelling. RESULTS: The population estimates (interindividual variability; coefficient of variation) for ceftriaxone pharmacokinetics were: a clearance of 0.88 l h(-1) (49%), a mean half-life of 9.6 h (range 0.83-28.6 h) and a total volume of distribution of 19.5 l (range 6.48-35.2 l). The total volume of distribution was higher than that generally found in healthy individuals and increased with the severity of sepsis. However, the only covariate influencing the ceftriaxone pharmacokinetics was creatinine clearance. Dosage simulations showed that the risk of ceftriaxone concentrations dropping below the minimum inhibitory concentration threshold was low. CONCLUSIONS: Despite the wide interpatient variability of ceftriaxone pharmacokinetic parameters, our results revealed that increasing the ceftriaxone dosage when treating critically ill patients is unnecessary. The risk of ceftriaxone concentrations dropping below the minimum inhibitory concentration threshold is limited to patients with high glomerular filtration rates or infections with high minimum inhibitory concentration pathogens (>1 mg l(-1)).

Recombinant tissue factor pathway inhibitor in severe community-acquired pneumonia: a randomized trial.

RATIONALE: Severe community-acquired pneumonia (sCAP) is a leading cause of death worldwide. Adjunctive therapies for sCAP are needed to further improve outcome. A systemic inhibitor of coagulation, tifacogin (recombinant human tissue factor pathway inhibitor) seemed to provide mortality benefit in the sCAP subgroup of a previous sepsis trial. OBJECTIVES: Evaluate the impact of adjunctive tifacogin on mortality in patients with sCAP. METHODS: A multicenter, randomized, placebo-controlled, double-blind, three-arm study was conducted from July 2005 to June 2008 at 188 centers in North and South America, Europe, South Africa, Asia, Australia, and New Zealand. Adults with sCAP were randomized to receive a continuous intravenous infusion of tifacogin 0.025 mg/kg/h, tifacogin 0.075 mg/kg/h, or matching placebo over 96 hours. MEASUREMENTS AND MAIN RESULTS: Severity-adjusted 28-day all-cause mortality. Of 2,138 randomized patients, 946, 238, and 918 received tifacogin 0.025 mg/kg/h, tifacogin 0.075 mg/kg/h, and placebo, respectively. Tifacogin 0.075 mg/kg/h was discontinued after the first interim analysis according to prespecified futility criterion. The 28-day all-cause mortality rates were similar between the 0.025 mg/kg/h (18%) and placebo groups (17.9%) (P = 0.56). Greater reduction in prothrombin fragment 1+2 and thrombin antithrombin complexes levels relative to baseline throughout the first 96 hours was found with tifacogin 0.025 mg/kg/h than with placebo. The incidence of adverse events and serious adverse events were comparable between the tifacogin 0.025 mg/kg/h and placebo groups. CONCLUSIONS: Tifacogin showed no mortality benefit in patients with sCAP despite evidence of biologic activity.

Iatrogenic events contributing to ICU admission: a prospective study.

OBJECTIVE: To determine the incidence, risk factors, severity, and preventability of iatrogenic events (IEs) as a cause of intensive care unit (ICU) admission. DESIGN: Comparison of patients admitted or not for IE. IE was diagnosed after assessing independently predefined criteria. SETTING: The ICU of a teaching hospital. PATIENTS: All patients consecutively admitted over 6 months. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Characteristics of patients, supportive treatments, length of stay, and outcomes were recorded. For patients admitted for IE, cause, origin, and preventability of IE were assessed by consensus. Of 528 patients, 103 (19.5%) were admitted for IE. Their Simplified Acute Physiology Score (SAPS) II was higher (41.2 +/- 22.6 versus 31.4 +/- 18.6), as was their Logistic Organ Dysfunction (LOD) score. Surgical admissions and admission for shock were more frequent. The main risk factors were age, underlying disease, low Mac Cabe or Knaus score, number of physicians treating the patient, number of drugs prescribed, and other hospitalization within 1 month. Length of stay was higher (11.1 days versus 7.9 days, 0.5-6.0, p = 0.02). Catecholamine drugs, blood transfusion, and parenteral nutrition were more frequently required in the IE group. ICU mortality was 15.5% in the IE group and 11.3% in the group without IEs [not significant (ns) after adjustment]. IE was considered as probably preventable in 73.8% of cases. CONCLUSION: Of admissions to the ICU, 19.5% resulted from IE, with high proportion of shock, leading to greater need for invasive treatments and longer stay in the ICU. Most cases of IE seemed preventable.

Influence of jet nebulization and oxygen delivery on the fraction of inspired oxygen: an experimental model.

BACKGROUND: The fraction of inspired oxygen (FiO(2)) during oxygen-driven jet nebulization is unknown. In the case of air-driven jet nebulization, oxygen is often added through a nasal device, and again, the FiO(2) is unknown. The aim of this experimental study was to measure FiO(2) during oxygen- and air-driven jet nebulization, oxygen being added through a nasal device, and to compare the values observed with those measured during standard oxygen therapy. METHODS: An endotracheal tube was inserted into the distal tracheal extremity of a cadaveric head and neck specimen and connected to a pump, simulating different respiratory patterns. FiO(2) was measured using an electrochemical oxygen analyzer under different nebulization and oxygen delivery conditions. Variables were compared using canonical analysis and analysis of simple and multiple variance. RESULTS: FiO(2) was significantly influenced by the mode of oxygen delivery (p = 0.001). The highest FiO(2) was observed when oxygen was delivered via a nasopharyngeal catheter associated with air-driven jet nebulization. For oxygen flow rates of 12 and 15 L/min, a nasal cannula combined with air-driven jet nebulization resulted in a similar FiO(2). The FiO(2) was significantly lower in the case of oxygen-driven jet nebulization. The FiO(2) decreased with increasing respiratory rate (p < 0.001) and tidal volume (p < 0.001). CONCLUSIONS: Oxygen delivery through a nasal device during air-driven jet nebulization significantly increases the FiO(2), whereas oxygen-driven jet nebulization dramatically decreases FiO(2) compared with standard oxygen therapy.

[Acute lithium intoxications, review of the literature and cases study]. / Intoxications aiguës au lithium : revue de la littérature et étude de cas cliniques.

The efficacy of lithium in the prevention of bipolar disorders is now well established. However, acute lithium intoxications still occur, often after suicide attempts. Symptoms are often different from one patient to the other, and long lasting neurologic sequelae may happen. Active treatments are available, notably haemodialysis, which increase lithium clearance dramatically. We report cases quoted in the department of intensive care of Tours University Hospital over the last three years and compared them with the literature. Lithium level and treatment of these intoxications were analysed. Although new medicines are available for the treatment of bipolar disorders, lithium is still an important drug in this disease, therefore, the prescribers have to be aware of the consequences of acute lithium intoxications.