Early Evidence of Sepsis-Associated Hyperperfusion-A Study of Cerebral Blood Flow Measured With MRI Arterial Spin Labeling in Critically Ill Septic Patients and Control Subjects.

OBJECTIVES: Mechanisms underlying sepsis-associated encephalopathy remain unclear, but reduced cerebral blood flow, alone or in conjunction with altered autoregulation, is reported as a potential contributor. We compared cerebral blood flow of control subjects and vasopressor-dependent septic patients. DESIGN: Randomized crossover study. SETTING: MRI with arterial spin labeling. PATIENTS: Ten sedated septic patients on mechanical ventilation (four with controlled chronic hypertension) and 12 control subjects (six with controlled chronic hypertension) were enrolled. Mean ± SD ages were 61.4 ± 10.2 and 44.2 ± 12.8 years, respectively (p = 0.003). Mean Acute Physiology and Chronic Health Evaluation II score of septic patients at ICU admission was 27.7 ± 6.6. INTERVENTIONS: To assess the potential confounding effects of sedation and mean arterial pressure, we measured cerebral blood flow with and without sedation with propofol in control subjects and at a target mean arterial pressure of 65 mm Hg and greater than or equal to 75 mm Hg in septic patients. The sequence of sedation versus no sedation and mean arterial pressure targets were randomized. MEASUREMENTS AND MAIN RESULTS: In septic patients, cerebral blood flow measured at a mean arterial pressure target of 65 mm Hg (40.4 ± 10.9 mL/100 g/min) was not different from cerebral blood flow measured at a mean arterial pressure target of greater than or equal to 75 mm Hg (41.3 ± 9.8 mL/100 g/min; p = 0.65). In control subjects, we observed no difference in cerebral blood flow measured without and with sedation (24.8 ± 4.2 vs 24.9 ± 5.9 mL/100 g/min; p = 0.93). We found no interaction between chronic hypertension and the effect of sedation or mean arterial pressure targets. Cerebral blood flow measured in sedated septic patients (mean arterial pressure target 65 mm Hg) was 62% higher than in sedated control subjects (p = 0.001). CONCLUSIONS: In septic patients, cerebral blood flow was higher than in sedated control subjects and did not vary with mean arterial pressure targets. Further research is required to understand the clinical significance of cerebral hyperperfusion in septic patients on vasopressors and to reassess the neurologic effects of current mean arterial pressure targets in sepsis.

Knowledge Translation Strategy to Reduce the Use of Potentially Inappropriate Medications in Hospitalized Elderly Adults.

OBJECTIVES: To evaluate the effect of a knowledge translation (KT) strategy to reduce potentially inappropriate medication (PIM) use in hospitalized elderly adults. DESIGN: Segmented regression analysis of an interrupted time series. SETTING: Teaching hospital. PARTICIPANTS: Individuals aged 75 and older discharged from the hospital in 2013/14 (mean age 83.3, 54.5% female). INTERVENTION: The KT strategy comprises the distribution of educational materials, presentations by geriatricians, pharmacist-physician interventions based on alerts from a computerized alert system, and comprehensive geriatric assessments. MEASUREMENTS: Rate of PIM use (number of patient-days with use of at least one PIM/number of patient-days of hospitalization for individuals aged ≥75). RESULTS: For 8,622 patients with 14,071 admissions, a total of 145,061 patient-days were analyzed. One or more PIMs were prescribed on 28,776 (19.8%) patient-days; a higher rate was found for individuals aged 75 to 84 (24.0%) than for those aged 85 and older (14.4%) (P < .001), and in women (20.8%) than in men (18.6%) (P < .001). The drug classes most frequently accounting for the PIM were gastrointestinal agents (21%), antihistamines (18%), and antidepressants (17%). An absolute decrease of 3.5% (P < .001) of patient-days with at least one PIM was observed immediately after the intervention. CONCLUSION: A KT strategy resulted in decreased use of PIM in elderly adults in the hospital. Additional interventions will be implemented to maintain or further reduce PIM use.

Influence of Blood Pressure and Other Clinical Variables on Long-Term Mortality in a Cohort of Elderly Subjects with Type 2 Diabetes.

BACKGROUND: Diabetes mellitus and high blood pressure (HBP) are commonly associated conditions in the elderly population. An effect of treatments, biologic and anthropometric variables on long-term mortality is unknown in this population. OBJECTIVES: To determine the prevalence of HBP control in a sample of elderly patients with type 2 diabetes with office blood pressure (BP) readings and ambulatory blood pressure monitoring (ABPM) and evaluate the influence of BP, anthropometric and laboratory variables on long term mortality. METHODS: Cohort study in patients living at home in the area of Sherbrooke, ≥65 years old, receiving reimbursement for antidiabetic medication. The study included medical history, 2 sets of BP measurements, 2 24-hour urinary collections for microalbuminuria, 1 24-hour ABPM, blood level of creatinine and glycosylated hemoglobin. Charts were reanalyzed 8 years later for analysis of cardiovascular and total mortality cases. RESULTS: 198 patients were initially recruited. By history, 83% of the subjects had diagnoses and treatments for high blood pressure. In multivariate analysis, factors associated with an 8-year increased risk for cardiovascular mortality were creatinine ≥84 µmol/L, office seated systolic blood pressure ≤130 and diastolic BP ≤67.6 over 24 hours. Factors associated with total mortality were lower waist circumference, serum creatinine ≥84 and diastolic BP ≤67.6 over 24 hours. CONCLUSIONS: Lower systolic and diastolic BP (office and ABPM), lower waist circumference and higher creatinine values are associated with an increased mortality risk. This suggests that a lower BP, declining kidney function and frailty are factors associated with this observation.

A Pharmacist-Physician Intervention Model Using a Computerized Alert System to Reduce High-Risk Medication Use in Elderly Inpatients.

BACKGROUND: Prescription is a complex challenge facing clinicians caring for elderly inpatients. Potentially inappropriate medication (PIM) use frequently leads to adverse drug events and geriatric syndromes. Strategies to reduce PIM use are thus urgently needed. OBJECTIVES: The objectives of this study were to assess (1) the applicability of a pharmacist-physician intervention model to reduce the use of high-risk medications; and (2) the clinical relevance of the alerts generated by a computerized alert system (CAS). METHODS: The study was conducted in patients aged 65 years or older admitted to a teaching hospital between April and June 2014. In the intervention model, the pharmacist determined the clinical relevance of the Beers criteria-based CAS alerts, analyzed the patient's pharmacotherapy, and developed a geriatric pharmacotherapeutic plan to be discussed with the treating physician. The main outcome was the change rate, defined as the number of patient-days with a change in at least one medication out of the number of patient-days with a pharmacist intervention. RESULTS: The CAS identified at least one alert in 200 patient-days, i.e., 4.3% of screened patient-days. In 74.5% of those patient-days, at least one alert was judged to be clinically relevant. The change rate was 77.7%. The most frequent changes were drug discontinuation (42.4%) and dose reduction (29.1%). The inpatient geriatric consultation team was involved in only 24% of the hospitalizations with at least one change in medication. CONCLUSION: The intervention model reduced high-risk medication use in older inpatients. Most of the vulnerable inpatients identified by CAS alerts would not have otherwise had a geriatric medication review.

An interprofessional qualitative study of barriers and potential solutions for the safe use of insulin in the hospital setting.

OBJECTIVE: Insulin is regularly used in hospitalized patients for glycemic control but is associated with significant risks. The goals of this study were to describe the strengths and weaknesses of a university health centre in the safe use of insulin, to collect improvement proposals from health professionals involved in the management of insulin therapy and to assess inpatient glycemic control. METHODS: This is a qualitative study. Physicians, nurses and pharmacists practising at the Centre Hospitalier Universitaire de Sherbrooke (CHUS) for at least 2 years were invited to join focus groups on safe insulin treatment. Themes up for discussion were roles of professionals in insulin therapy, problems encountered, solutions put forward and strengths of the hospital. The Quality Hyperglycemia Score (QHS) was assessed using an existing cohort of inpatients who were prescribed insulin. RESULTS: A total of 5 focus groups were held in February and March of 2012, involving 31 healthcare professional participants. Several groups pointed out the same problems, namely, lack of access to useful information for optimal management of insulin therapy and lack of communication among personnel on different work shifts. Results of the QHS suggest room for improvement in blood glucose control at our institution. CONCLUSION: These focus groups allowed better identification of the management problems related to the use of insulin in our health institution and possible interventions to solve them. The QHS will be reassessed to measure quality of inpatient glycemic control over time.

Students' self-explanations while solving unfamiliar cases: the role of biomedical knowledge.

OBJECTIVE: General guidelines for teaching clinical reasoning have received much attention, despite a paucity of instructional approaches with demonstrated effectiveness. As suggested in a recent experimental study, self-explanation while solving clinical cases may be an effective strategy to foster reasoning in clinical clerks dealing with less familiar cases. However, the mechanisms that mediate this benefit have not been specifically investigated. The aim of this study was to explore the types of knowledge used by students when solving familiar and less familiar clinical cases with self-explanation. METHODS: In a previous study, 36 third-year medical students diagnosed familiar and less familiar clinical cases either by engaging in self-explanation or not. Based on an analysis of previously collected data, the present study compared the content of self-explanation protocols generated by seven randomly selected students while solving four familiar and four less familiar cases. In total, 56 verbal protocols (28 familiar and 28 less familiar) were segmented and coded using the following categories: paraphrases, biomedical inferences, clinical inferences, monitoring statements and errors. RESULTS: Students provided more self-explanation segments from less familiar cases (M = 275.29) than from familiar cases (M = 248.71, p = 0.046). They provided significantly more paraphrases (p = 0.001) and made more errors (p = 0.008). A significant interaction was found between familiarity and the type of inferences (biomedical versus clinical, p = 0.016). When self-explaining less familiar cases, students provided significantly more biomedical inferences than familiar cases. CONCLUSIONS: Lack of familiarity with a case seems to stimulate medical students to engage in more extensive thinking during self-explanation. Less familiar cases seem to activate students' biomedical knowledge, which in turn helps them to create new links between biomedical and clinical knowledge, and eventually construct a more coherent mental representation of diseases. This may clarify the previously found positive effect that self-explanation has on the diagnosis of unfamiliar cases.

The influence of medical students' self-explanations on diagnostic performance.

CONTEXT: Skill in clinical reasoning is a highly valued attribute of doctors, but instructional approaches to foster medical students' clinical reasoning skills remain scarce. Self-explanation is an instructional procedure, the positive effects of which on learning have been demonstrated in a variety of domains, but which remain largely unexplored in medical education. OBJECTIVES: The purpose of this study was to investigate the effects of self-explanation on students' learning of clinical reasoning during clerkships and to examine whether these effects are affected by topic familiarity. METHODS: An experimental study with a training phase and an assessment phase was conducted with 36 Year 3 medical students, randomly assigned to one of two groups. In the training phase, students solved 12 clinical cases (four cases on a less familiar topic; four on a more familiar topic; four on filler topics), either generating self-explanations (n = 18) or not (n = 18). The self-explanations were generated after minimal instructions and no feedback was provided to students. One week later, in the assessment phase, students were requested to diagnose 12 different, more difficult cases, similarly distributed among the same more familiar topic, less familiar topic and filler topics, and their diagnostic performance was assessed. RESULTS: In the training phase the performance of the two groups did not differ. However, in the assessment phase 1 week later, a significant interaction was found between self-explanation and case topic familiarity (F(1,34) = 6.18, p < 0.05). Students in the self-explanation condition, compared with those in the control condition, demonstrated better diagnostic performance on subsequent clinical cases, but this effect emerged only for cases concerning the less familiar topic. CONCLUSIONS: The present study shows the beneficial influence of generating self-explanations when dealing with less familiar clinical contexts. Generating self-explanations without feedback resulted in better diagnostic performance than in the control group at 1 week after the intervention.

[Evaluation of circadian variation of blood pressure by ambulatory blood pressure monitoring in an elderly diabetic population with or without orthostatic hypotension]. / Évaluation des variations circadiennes de la tension artérielle par monitorage ambulatoire de la pression artérielle dans une population âgée diabétique atteinte ou non d'hypotension orthostatique.

Orthostatic hypotension is frequently observed in the elderly population and has been previously identified as a significant risk factor for increased mortality. The link between this condition and increased mortality could be due to an abnormal circadian pattern of blood pressure. The absence of a physiological nocturnal decrease in blood pressure is termed the non-dipping pattern. This abnormality is relatively frequent in elderly people suffering from orthostatic hypotension, but its prevalence in the diabetic geriatric population is unknown. The purpose of this study is to compare blood pressure profiles on ambulatory blood pressure monitoring (ABPM) in a sample of elderly diabetic subjects suffering from orthostatic hypotension with those without postural hypotension. One hundred and ninety-eight patients were recruited by mail. The presence or absence of orthostatic hypotension was determined. They all subsequently underwent ABPM. One hundred and thirty-one of our subjects (68%) suffered from orthostatic hypotension; of these, 76% had a non-dipping pattern on ABPM, compared with 74% of the subjects not suffering from orthostatic hypotension (P = NS). This study thus demonstrates the high prevalence of orthostatic hypotension in an elderly diabetic population. On the other hand, we could not demonstrate a correlation between the non-dipping pattern and the presence of orthostatic hypotension. This is in contrast with previous work done in a non-diabetic elderly population. Further studies are needed to determine the effect of diabetes on blood pressure.

Characteristics and short-term prognosis of perioperative myocardial infarction in patients undergoing noncardiac surgery: a cohort study.

BACKGROUND: Each year, millions of patients worldwide have a perioperative myocardial infarction (MI) after noncardiac surgery. OBJECTIVE: To examine the characteristics and short-term outcome of perioperative MI. DESIGN: Cohort study. (ClinicalTrials.gov registration number: NCT00182039) SETTING: 190 centers in 23 countries. PATIENTS: 8351 patients included in the POISE (PeriOperative ISchemic Evaluation) trial. MEASUREMENTS: Four cardiac biomarker or enzyme assays were measured within 3 days of surgery. The definition of perioperative MI included either autopsy findings of acute MI or an elevated level of a cardiac biomarker or enzyme and at least 1 of the following defining features: ischemic symptoms, development of pathologic Q waves, ischemic changes on electrocardiography, coronary artery intervention, or cardiac imaging evidence of MI. RESULTS: Within 30 days of random assignment, 415 patients (5.0%) had a perioperative MI. Most MIs (74.1%) occurred within 48 hours of surgery; 65.3% of patients did not experience ischemic symptoms. The 30-day mortality rate was 11.6% (48 of 415 patients) among patients who had a perioperative MI and 2.2% (178 of 7936 patients) among those who did not (P < 0.001). Among patients with a perioperative MI, mortality rates were elevated and similar between those with (9.7%; adjusted odds ratio, 4.76 [95% CI, 2.68 to 8.43]) and without (12.5%; adjusted odds ratio, 4.00 [CI, 2.65 to 6.06]) ischemic symptoms. LIMITATION: Cardiac markers were measured only until day 3 after surgery, and additional asymptomatic MIs may have been missed. CONCLUSION: Most patients with a perioperative MI will not experience ischemic symptoms. Data suggest that routine monitoring of troponin levels in at-risk patients is needed after surgery to detect most MIs, which have an equally poor prognosis regardless of whether they are symptomatic or asymptomatic.

Characteristics and short-term prognosis of perioperative myocardialinfarction in patients undergoing noncardiac surgery a cohort study

BACKGROUND: Each year, millions of patients worldwide have a perioperative myocardial infarction (MI) after noncardiac surgery.OBJECTIVE: To examine the characteristics and short-term outcome of perioperative MI.DESIGN: Cohort study. (ClinicalTrials.gov registration number: NCT00182039)SETTING: 190 centers in 23 countries.PATIENTS: 8351 patients included in the POISE (PeriOperative ISchemic Evaluation) trial.MEASUREMENTS: Four cardiac biomarker or enzyme assays were measured within 3 days of surgery. The definition of perioperative MI included either autopsy findings of acute MI or an elevated level of a cardiac biomarker or enzyme and at least 1 of the following defining features: ischemic symptoms, development of pathologic Q waves, ischemic changes on electrocardiography, coronary artery intervention, or cardiac imaging evidence of MI.RESULTS: Within 30 days of random assignment, 415 patients (5.0%) had a perioperative MI. Most MIs (74.1%) occurred within 48 hours of surgery; 65.3% of patients did not experience ischemic symptoms. The 30-day mortality rate was 11.6% (48 of 415 patients) among patients who had a perioperative MI and 2.2% (178 of 7936 patients) among those who did not (P < 0.001). Among patients with a perioperative MI, mortality rates were elevated and similar between those with (9.7%; adjusted odds ratio, 4.76 [95% CI, 2.68 to 8.43]) and without (12.5%; adjusted odds ratio, 4.00 [CI, 2.65 to 6.06]) ischemic symptoms.LIMITATION: Cardiac markers were measured only until day 3 after surgery, and additional asymptomatic MIs may have been missed.CONCLUSION: Most patients with a perioperative MI will not experience ischemic symptoms. Data suggest that routine monitoring of troponin levels in at-risk patients is needed after surgery to detect most MIs, which have an equally poor prognosis regardless of whether they are symptomatic or asymptomatic.

Lung atelectasis secondary to massive esophageal dilation in a patient with scleroderma.

Esophageal dilation is a rare complication of scleroderma and CREST syndrome. A case of atelectasis secondary to right inferior bronchus compression by a massively dilated esophagus is described. The authors are unaware of any previous cases of atelectasis secondary to esophageal dilation in scleroderma.

A single-nucleotide polymorphism of alanine to threonine at position 163 of the human angiotensin II type 1 receptor impairs Losartan affinity.

BACKGROUND AND OBJECTIVE: AT1 is the principal receptor for angiotensin II (AngII), which regulates blood pressure and osmotic homeostasis. Earlier studies have shown that position 163 interacts with the antihypertensive nonpeptide antagonist, Losartan. A recently discovered polymorphism found in humans (rs12721226) coding for residue 163 led us to determine whether this polymorphism would affect Losartan antihypertensive therapies. The pharmacological properties of the A163T hAT1 variant are described. METHOD AND RESULTS: The A163T hAT1 mutation was evaluated by testing its affinity by dose displacement of AngII analogs in COS-7 cells expressing either wild-type hAT1 or the A163T hAT1. The expressions of the receptors were evaluated by saturation binding and the efficacies were assessed by measuring the 3H-inositol phosphate production. The results showed that the A163T hAT1 receptor is comparable with the affinity, expression, and efficacy of native hAT1 towards peptide ligands. The affinities were also tested with nonpeptide antagonists Losartan, L-158 809, valsartan, telmisartan, irbesartan, candesartan, and EXP3174. Losartan and EXP3174 displayed a 7-fold loss in affinity towards A163T hAT1. The ability of Losartan to inhibit AngII-induced inositol triphosphate production also confirmed a loss in efficacy. Molecular modeling showed a higher steric and hydrophilic hindrance of the A163T hAT1-Losartan complex. CONCLUSION: The polymorphism that codes for the A163T hAT1 variant results in a receptor with normal physiological properties toward the endogenous hormone. However, the significant reduction in affinity to Losartan and its active metabolite, EXP3174, could significantly impair the clinical effectiveness of an antihypertensive therapy using Losartan with patients bearing the A163T polymorphism.

Pneumococcal vaccination and risk of myocardial infarction.

BACKGROUND: Based on promising results from laboratory studies, we hypothesized that pneumococcal vaccination would protect patients from myocardial infarction. METHODS: We conducted a hospital-based case-control study that included patients considered to be at risk of myocardial infarction. We used health databases to obtain hospital diagnoses and vaccination status. We compared patients who had been admitted for treatment of myocardial infarction with patients admitted to a surgical department in the same hospital for a reason other than myocardial infarction between 1997 and 2003. RESULTS: We found a total of 43 209 patients who were at risk; of these, we matched 999 cases and 3996 controls according to age, sex and year of hospital admission. Cases were less likely than controls to have been vaccinated (adjusted odds ratio [OR] 0.53, 95% confidence interval [CI] 0.40-0.70). This putative protective role of the vaccine was not observed for patients who had received the vaccine up to 1 year before myocardial infarction (adjusted OR 0.85, 95% CI 0.54-1.33). In contrast, if vaccination had occurred 2 years or more before the hospital admission, the association was stronger (adjusted OR 0.33, 95% CI 0.20-0.46). INTERPRETATION: Pneumococcal vaccination was associated with a decrease of more than 50% in the rate myocardial infarction 2 years after exposure. If confirmed, this association should generate interest in exploring the putative mechanisms and may offer another reason to promote pneumococcal vaccination.

One giant leap for mankind? A cost-utility analysis of abolishing the law of gravity.

BACKGROUND: Canada's Neo Rhino Party, a joke political party created in 2006 as a successor to the Parti Rhinocéros, is planning a new regulation to repeal the law of gravity, which could have an important impact on diseases attributable to gravity on earth. METHODS: We sought to estimate the number of quality-adjusted life-years that would be saved if the proposed regulation is passed and determine the cost-effectiveness of adapting Boris Volfson's antigravity machine for use on earth. We performed an economic analysis using a hidden Markov model. RESULTS: Our results suggest that a microgravity environment would save over 2 million quality-adjusted life-years. The cost for every quality-adjusted life-year saved is estimated to be $328. INTERPRETATION: Microgravity is the solution to the health care crisis in Canada. In addition, using technological, statistical and medical jargon gives us the opportunity to defy the laws of physics, mathematics and medicine.

Emergence of fluoroquinolones as the predominant risk factor for Clostridium difficile-associated diarrhea: a cohort study during an epidemic in Quebec.

BACKGROUND: Since 2002, an epidemic of Clostridium difficile-associated-diarrhea (CDAD) associated with a high case-fatality rate has involved >30 hospitals in the province of Quebec, Canada. In 2003, a total of 55% of patients with CDAD at our hospital had received fluoroquinolones in the preceding 2 months. It has been suggested that massive use of proton pump inhibitors might have facilitated this epidemic. METHODS: To delineate the risk of CDAD associated with specific classes of antibiotics and whether this is modulated by concomitant use of proton pump inhibitors and other drugs altering gastric acidity or gastrointestinal motility, we conducted a retrospective cohort study of patients hospitalized in a teaching hospital in Sherbrooke, Canada, during the period of January 2003 through June 2004. We obtained data on 7421 episodes of care corresponding to 5619 individuals. Patients were observed until they either developed CDAD or died or for 60 days after discharge from the hospital. Adjusted hazard ratios (AHRs) were calculated using Cox regression. RESULTS: CDAD occurred in 293 patients. Fluoroquinolones were the antibiotics most strongly associated with CDAD (AHR, 3.44; 95% confidence interval [CI], 2.65-4.47). Almost one-fourth of all inpatients received quinolones, for which the population-attributable fraction of CDAD was 35.9%. All 3 generations of cephalosporins, macrolides, clindamycin, and intravenous beta-lactam/beta-lactamase inhibitors were intermediate-risk antibiotics, with similar AHRs (1.56-1.89). Proton pump inhibitors (AHR, 1.00, 95% CI, 0.79-1.28) were not associated with CDAD. CONCLUSIONS: Administration of fluoroquinolones emerged as the most important risk factor for CDAD in Quebec during an epidemic caused by a hypervirulent strain of C. difficile.