Effect of nurse practitioner and pharmacist counseling on inappropriate medication use in family practice

Objective

To measure the effect of nurse practitioner and pharmacist consultations on the appropriate use of medications by patients.

Design

We studied patients in the intervention arm of a randomized controlled trial. The main trial intervention was provision of multidisciplinary team care and the main outcome was quality and processes of care for chronic disease management.

Setting

Patients were recruited from a single publicly funded family health network practice of 8 family physicians and associated staff serving 10 000 patients in a rural area near Ottawa, Ont.

Participants

A total of 120 patients 50 years of age or older who were on the practice roster and who were considered by their family physicians to be at risk of experiencing adverse health outcomes.

Intervention

A pharmacist and 1 of 3 nurse practitioners visited each patient at his or her home, conducted a comprehensive medication review, and developed a tailored plan to optimize medication use. The plan was developed in consultation with the patient and the patient’s doctor. We assessed medication appropriateness at the study baseline and again 12 to 18 months later.

Main outcome measures

We used the medication appropriateness index to assess medication use. We examined associations between personal characteristics and inappropriate use at baseline and with improvements in medication use at the follow-up assessment. We recorded all drug problems encountered during the trial.

Results

At baseline, 27.2% of medications were inappropriate in some way and 77.7% of patients were receiving at least 1 medication that was inappropriate in some way. At the follow-up assessments these percentages had dropped to 8.9% and 38.6%, respectively (P < .001). Patient characteristics that were associated with receiving inappropriate medication at baseline were being older than 80 years of age (odds ratio [OR] = 5.00, 95% CI 1.19 to 20.50), receiving more than 4 medications (OR = 6.64, 95% CI 2.54 to 17.4), and not having a university-level education (OR = 4.55, 95% CI 1.69 to 12.50).

Conclusion

We observed large improvements in the appropriate use of medications during this trial. This might provide a mechanism to explain some of the reductions in mortality and morbidity observed in other trials of counseling and advice provided by pharmacists and nurses.

Trial registration number

{"type":"clinical-trial","attrs":{"text":"NCT00238836","term_id":"NCT00238836"}}NCT00238836 (ClinicalTrials.gov).     

Heme arginate improves reperfusion patterns after ischemia: a randomized, placebo-controlled trial in healthy male subjects

Background

Heme arginate can induce heme oxygenase-1 to protect tissue against ischemia-reperfusion injury. Blood oxygen level dependent (BOLD) functional magnetic resonance imaging measures changes in tissue oxygenation with a high spatial and temporal resolution. BOLD imaging was applied to test the effect of heme arginate on experimental ischemia reperfusion injury in the calf muscles.

Methods

A two period, controlled, observer blinded, crossover trial was performed in 12 healthy male subjects. Heme arginate (1 mg/kg body weight) or placebo were infused 24 h prior to a 20 min leg ischemia induced by a thigh cuff. 3 Tesla BOLD-imaging of the calf was performed and signal time courses from soleus, gastrocnemius and tibialis anterior muscle were available from 11 participants for technical reasons.

Results

Peak reactive hyperemia signal of the musculature was significantly increased and occurred earlier after heme arginate compared to placebo (106.2±0.6% at 175±16s vs. 104.5±0.6% at 221±19s; p = 0.025 for peak reperfusion and p = 0.012 for time to peak).

Conclusions

A single high dose of heme arginate improves reperfusion patterns during ischemia reperfusion injury in humans. BOLD sensitive, functional MRI is applicable for the assessment of experimental ischemia reperfusion injury in skeletal muscle.

Trial registration

ClinicalTrials: {"type":"clinical-trial","attrs":{"text":"NCT01461512","term_id":"NCT01461512"}}NCT01461512EudraCT: 2008-006967-35     

Clinical validation of a new thermodilution system for the assessment of cardiac output and volumetric parameters

Introduction

Transpulmonary thermodilution is used to measure cardiac output (CO), global end-diastolic volume (GEDV) and extravascular lung water (EVLW). A system has been introduced (VolumeView/EV1000™ system, Edwards Lifesciences, Irvine CA, USA) that employs a novel algorithm for the mathematical analysis of the thermodilution curve. Our aim was to evaluate the agreement of this method with the established PiCCO™ method (Pulsion Medical Systems SE, Munich, Germany, clinicaltrials.gov identifier: {"type":"clinical-trial","attrs":{"text":"NCT01405040","term_id":"NCT01405040"}}NCT01405040)

Methods

Seventy-two critically ill patients with clinical indication for advanced hemodynamic monitoring were included in this prospective, multicenter, observational study. During a 72-hour observation period, 443 sets of thermodilution measurements were performed with the new system. These measurements were electronically recorded, converted into an analog resistance signal and then re-analyzed by a PiCCO₂™ device (Pulsion Medical Systems SE).

Results

For CO, GEDV, and EVLW, the systems showed a high correlation (r² = 0.981, 0.926 and 0.971, respectively), minimal bias (0.2 L/minute, 29.4 ml and 36.8 ml), and a low percentage error (9.7%, 11.5% and 12.2%). Changes in CO, GEDV and EVLW were tracked with a high concordance between the two systems, with a traditional concordance for CO, GEDV, and EVLW of 98.5%, 95.1%, and 97.7% and a polar plot concordance of 100%, 99.8% and 99.8% for CO, GEDV, and EVLW, respectively. Radial limits of agreement for CO, GEDV and EVLW were 0.31 ml/minute, 81 ml and 40 ml, respectively. The precision of GEDV measurements was significantly better using the VolumeView™ algorithm compared to the PiCCO™ algorithm (0.033 (0.03) versus 0.040 (0.03; median (interquartile range), P = 0.000049).

Conclusions

For CO, GEDV, and EVLW, the agreement of both the individual measurements as well as measurements of change showed the interchangeability of the two methods. For the VolumeView method, the higher precision may indicate a more robust GEDV algorithm.

Trial registration

clinicaltrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01405040","term_id":"NCT01405040"}}NCT01405040.     

Early or late parenteral nutrition: ASPEN vs. ESPEN

Citation

Casaer MP, Mesotten D, Hermans G et al. Early versus late parenteral nutrition in critically ill adults. N Engl J Med. 2011;365: 506-517.

Background

Controversy exists about the timing of the initiation of parenteral nutrition (PN) in critically ill adults in whom caloric targets cannot be met by enteral nutrition (EN) alone.

Methods

Objective

To compare early-initiation of PN (European guidelines) with late-initiation (American and Canadian guidelines) in adults who are receiving insufficient enteral nutrition in the intensive care unit (ICU).

Design

Prospective, randomized, controlled, parallel-group, multicenter clinical trial.

Setting

Seven multidisciplinary ICUs in Belgium.

Subjects

All adults admitted to participating ICUs with a nutritional risk score of 3 or more who did not meet any exclusion criteria.

Intervention

After enrollment, 2312 patients were randomized to receive PN 48 hours after ICU admission (early-initiation) and 2328 patients were randomized to receive PN on day 8 (late-initiation group). Both groups received early EN using a standardized protocol. PN was continued until EN met 80% of calorific goals, or when oral nutrition was resumed. It was restarted if enteral or oral feeding fell below 50% of calculated calorific needs.

Outcomes

Primary end point was the duration of dependency on intensive care, defined as the number of intensive care days and time to discharge from the ICU.

Results

The median stay in the ICU was one day shorter for the late-initiation group (3 v. 4; p = 0.02). The late-initiation group had a relative increase, of 6.3%, in the likelihood of being discharged earlier, and alive, from the ICU (hazard ratio 1.06; 95% confidence interval [CI] 1.00-1,13; p = 0.04). Rates of death in the ICU and survival at 90 days were similar between the two groups. The late-initiation group, as compared to the early-initiation group, had fewer ICU infections (22.8% v. 26.2%; p = 0.008), less days of renal replacement therapy (7 days (interquartile range [IQR] 3-16) v. 10 days (IQR 5-23); p = 0.008) and fewer patients requiring more than 2 days of mechanical ventilation (36.3% v. 40.2%; p = 0.006).

Conclusions

Late-initiation of PN was associated with faster recovery and fewer complications, when compared with early-initiation.

Trial Registration

{"type":"clinical-trial","attrs":{"text":"NCT00512122","term_id":"NCT00512122"}}NCT00512122     

Extracorporeal cell therapy of septic shock patients with donor granulocytes: a pilot study

Introduction

Neutrophil granulocytes are the first defense line in bacterial infections. However, granulocytes are also responsible for severe local tissue impairment. In order to use donor granulocytes, but at the same time to avoid local side effects, we developed an extracorporeal immune support system. This first-in-man study investigated whether an extracorporeal plasma treatment with a granulocyte bioreactor is tolerable in patients with septic shock. A further intention was to find suitable efficacy end-points for subsequent controlled trials.

Methods

The trial was conducted as a prospective uncontrolled clinical phase I/II study with 28-day follow-up at three university hospital intensive care units. Ten consecutive patients (five men, five women, mean age 60.3 ± 13.9 standard deviation (SD) years) with septic shock with mean ICU entrance scores of Acute Physiology and Chronic Health Evaluation (APACHE) II of 29.9 ± 7.2 and of Simplified Acute Physiology Score (SAPS) II of 66.2 ± 19.5 were treated twice within 72 hours for a mean of 342 ± 64 minutes/treatment with an extracorporeal bioreactor containing 1.41 ± 0.43 × 10E10 granulocytes from healthy donors. On average, 9.8 ± 2.3 liters separated plasma were treated by the therapeutic donor cells. Patients were followed up for 28 days.

Results

Tolerance and technical safety during treatment, single organ functions pre/post treatment, and hospital survival were monitored. The extracorporeal treatments were well tolerated. During the treatments, the bacterial endotoxin concentration showed significant reduction. Furthermore, noradrenaline dosage could be significantly reduced while mean arterial pressure was stable. Also, C-reactive protein, procalcitonin, and human leukocyte antigen DR (HLA-DR) showed significant improvement. Four patients died in the hospital on days 6, 9, 18 and 40. Six patients could be discharged.

Conclusions

The extracorporeal treatment with donor granulocytes appeared to be well tolerated and showed promising efficacy results, encouraging further studies.

Trial registration

ClinicalTrials.gov Identifier: {"type":"clinical-trial","attrs":{"text":"NCT00818597","term_id":"NCT00818597"}}NCT00818597     

Argatroban versus Lepirudin in critically ill patients (ALicia): a randomized controlled trial

Introduction

Critically ill patients often require renal replacement therapy accompanied by thrombocytopenia. Thrombocytopenia during heparin anticoagulation may be due to heparin-induced thrombocytopenia with need for alternative anticoagulation. Therefore, we compared argatroban and lepirudin in critically ill surgical patients.

Methods

Following institutional review board approval and written informed consent, critically ill surgical patients more than or equal to 18 years with suspected heparin-induced thrombocytopenia, were randomly assigned to receive double-blind argatroban or lepirudin anticoagulation targeting an activated Partial Thromboplastin Time (aPTT) of 1.5 to 2 times baseline. In patients requiring continuous renal replacement therapy we compared the life-time of hemodialysis filters. We evaluated in all patients the incidence of bleeding and thrombembolic events.

Results

We identified 66 patients with suspected heparin-induced thrombocytopenia, including 28 requiring renal replacement therapy. Mean filter lifetimes did not differ between groups (argatroban 32 ± 25 hours (n = 12) versus lepirudin 27 ± 21 hours (n = 16), mean difference 5 hours, 95% CI −13 to 23, P = 0.227). Among all 66 patients, relevant bleeding occurred in four argatroban- versus eleven lepirudin-patients (OR 3.9, 95% CI 1.1 to 14.0, P = 0.040). In the argatroban-group, three thromboembolic events occurred compared to two in the lepirudin group (OR 0.7, 95% CI 0.1 to 4.4, P = 0.639). The incidence of confirmed heparin-induced thrombocytopenia was 23% (n = 15) in our study population.

Conclusions

This first randomized controlled double-blind trial comparing two direct thrombin inhibitors showed comparable effectiveness for renal replacement therapy, but suggests fewer bleeds in surgical patients with argatroban anticoagulation.

Trial registration

Clinical Trials.gov {"type":"clinical-trial","attrs":{"text":"NCT00798525","term_id":"NCT00798525"}}NCT00798525. Registered 25 November 2008

Electronic supplementary material

The online version of this article (doi:10.1186/s13054-014-0588-8) contains supplementary material, which is available to authorized users.     

Evaluation of an initiation protocol of 4 mg of warfarin for atrial fibrillation in the outpatient setting

Objective

To describe the efficacy and safety of an initiation algorithm for 4 mg of warfarin in ambulatory patients with atrial fibrillation.

Design

Prospectively planned retrospective chart review.

Setting

Centre for Family Medicine Family Health Team in Kitchener, Ont.

Participants

Ambulatory patients requiring anticoagulation for atrial fibrillation.

Interventions

Patients were prescribed 4 mg of warfarin to be taken once daily for 3 days. An international normalized ratio (INR) measured on the morning of the fourth day was used to predict the maintenance dose of warfarin. Subsequent INR measurements were obtained biweekly until patients reached their actual maintenance dose.

Main outcome measures

Number of INR values greater than or equal to 4.0 before the warfarin maintenance dose was achieved. Secondary outcome measures included thromboembolic and bleeding events, number of days required to reach therapeutic INR, and correlation between predicted and actual warfarin maintenance dose.

Results

Twenty-five patients were included in the study. The average age was 76.0 years (range 56.0 to 89.0), and 17 patients were women. The average CHADS₂ (congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, and stroke or transient ischemic attack) score was 2.0. Only 1 patient had an INR greater than 4.0 during the study period. The mean time to achieve a therapeutic INR was 11.0 days. The day 4 INR was moderately predictive of the maintenance dose (r² = 0.47). There were no adverse events that required medical attention during the study period.

Conclusion

In this pilot study, an initiation algorithm for 4 mg of warfarin was safe and achieved a therapeutic INR within a reasonable time frame in outpatients with atrial fibrillation.     

To JUPITER and beyond: Statins,inflammation, and primary prevention

Citation

Ridker PM, Danielson E, Fonseca FAH, Genest J, Gotto AM, Kastelein JJP, Koenig W, Libby P, Lorenzatti AJ, MacFadyen JG, Nordestgaard BG, Shepherd J, Willerson JT, Glynn RJ: Rosuvastatin to Prevent Vascular Events in Men and Women with Elevated C-Reactive Protein. NEJM 2008, 359: 2195-2207 [1].

Background

Increased levels of the inflammatory biomarker high-sensitivity C-reactive protein predict cardiovascular events. Since statins lower levels of high-sensitivity C-reactive protein as well as cholesterol, we hypothesized that people with elevated high-sensitivity C-reactive protein levels but without hyperlipidemia might benefit from statin treatment.

Methods

Objective

To investigate whether treatment with rosuvastatin, 20 mg daily, as compared to placebo, would decrease the rate of first major cardiovascular events.

Design

Randomized, double-blind, placebo-controlled, multicenter trial.

Setting

1315 sites in 26 countries.

Subjects

17,802 apparently healthy men and women with low-density lipoprotein (LDL) cholesterol levels of less than 130 mg per deciliter (3.4 mmol per liter) and high-sensitivity C-reactive protein levels of 2.0 mg per liter or higher.

Intervention

Subjects were randomly assigned to rosuvastatin, 20 mg daily, or placebo.

Outcomes

The primary outcome was the occurrence of a first major cardiovascular event, defined as myocardial infarction, stroke, arterial revascularization, hospitalization for unstable angina, or death from cardiovascular causes. Secondary endpoints included the components of the primary end point considered individually as well as death from any cause.

Results

The trial was stopped after a median follow-up of 1.9 years (maximum, 5.0). Rosuvastatin reduced LDL cholesterol levels by 50% and high-sensitivity C-reactive protein levels by 37%. The rates of the primary end point were 0.77 and 1.36 per 100 person-years of follow-up in the rosuvastatin and placebo groups, respectively (hazard ratio for rosuvastatin, 0.56; 95% confidence interval [CI], 0.46 to 0.69; P < 0.00001), with corresponding rates of 0.17 and 0.37 for myocardial infarction (hazard ratio, 0.46; 95% CI, 0.30 to 0.70; P = 0.0002), 0.18 and 0.34 for stroke (hazard ratio, 0.52; 95% CI, 0.34 to 0.79; P = 0.002), 0.41 and 0.77 for revascularization or unstable angina (hazard ratio, 0.53; 95% CI, 0.40 to 0.70; P < 0.00001), 0.45 and 0.85 for the combined end point of myocardial infarction, stroke, or death from cardiovascular causes (hazard ratio, 0.53; 95% CI, 0.40 to 0.69; P < 0.00001), and 1.00 and 1.25 for death from any cause (hazard ratio, 0.80; 95% CI, 0.67 to 0.97; P = 0.02). Consistent effects were observed in all subgroups evaluated. The rosuvastatin group did not have a significant increase in myopathy or cancer but did have a higher incidence of physician-reported diabetes.

Conclusions

In this trial of apparently healthy persons without hyperlipidemia but with elevated high-sensitivity C-reactive protein levels, rosuvastatin significantly reduced the incidence of major cardiovascular events. (ClinicalTrials.gov number, {"type":"clinical-trial","attrs":{"text":"NCT00239681","term_id":"NCT00239681"}}NCT00239681.)     

Neuroventilatory efficiency and extubation readiness in critically ill patients

Introduction

Based on the hypothesis that failure of weaning from mechanical ventilation is caused by respiratory demand exceeding the capacity of the respiratory muscles, we evaluated whether extubation failure could be characterized by increased respiratory drive and impaired efficiency to generate inspiratory pressure and ventilation.

Methods

Airway pressure, flow, volume, breathing frequency, and diaphragm electrical activity were measured in a heterogeneous group of patients deemed ready for a spontaneous breathing trial. Efficiency to convert neuromuscular activity into inspiratory pressure was calculated as the ratio of negative airway pressure and diaphragm electrical activity during an inspiratory occlusion. Efficiency to convert neuromuscular activity into volume was calculated as the ratio of the tidal volume to diaphragm electrical activity. All variables were obtained during a 30-minute spontaneous breathing trial on continuous positive airway pressure (CPAP) of 5 cm H₂O and compared between patients for whom extubation succeeded with those for whom either the spontaneous breathing trial failed or for those who passed, but then the extubation failed.

Results

Of 52 patients enrolled in the study, 35 (67.3%) were successfully extubated, and 17 (32.7%) were not. Patients for whom it failed had higher diaphragm electrical activity (48%; P < 0.001) and a lower efficiency to convert neuromuscular activity into inspiratory pressure and tidal volume (40% (P < 0.001) and 53% (P < 0.001)), respectively. Neuroventilatory efficiency demonstrated the greatest predictability for weaning success.

Conclusions

This study shows that a mixed group of critically ill patients for whom weaning fails have increased neural respiratory drive and impaired ability to convert neuromuscular activity into tidal ventilation, in part because of diaphragm weakness.

Trial Registration

Clinicaltrials.gov identifier NCT01065428. ©2012 Liu et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.     

Intra- and inter-individual variation of BIS-index? and Entropy? during controlled sedation with midazolam/remifentanil and dexmedetomidine/remifentanil in healthy volunteers: an interventional study

Introduction

We studied intra-individual and inter-individual variability of two online sedation monitors, BIS^® and Entropy^®, in volunteers under sedation.

Methods

Ten healthy volunteers were sedated in a stepwise manner with doses of either midazolam and remifentanil or dexmedetomidine and remifentanil. One week later the procedure was repeated with the remaining drug combination. The doses were adjusted to achieve three different sedation levels (Ramsay Scores 2, 3 and 4) and controlled by a computer-driven drug-delivery system to maintain stable plasma concentrations of the drugs. At each level of sedation, BIS^® and Entropy^® (response entropy and state entropy) values were recorded for 20 minutes. Baseline recordings were obtained before the sedative medications were administered.

Results

Both inter-individual and intra-individual variability increased as the sedation level deepened. Entropy^® values showed greater variability than BIS^® values, and the variability was greater during dexmedetomidine/remifentanil sedation than during midazolam/remifentanil sedation.

Conclusions

The large intra-individual and inter-individual variability of BIS^® and Entropy^® values in sedated volunteers makes the determination of sedation levels by processed electroencephalogram (EEG) variables impossible. Reports in the literature which draw conclusions based on processed EEG variables obtained from sedated intensive care unit (ICU) patients may be inaccurate due to this variability.

Trial registration

clinicaltrials.gov Nr. {"type":"clinical-trial","attrs":{"text":"NCT00641563","term_id":"NCT00641563"}}NCT00641563.     

Steroids in late ARDS?

Citation

Steinberg KP, Hudson LD, Goodman RB, Hough CL, Lanken PN, Hyzy R, Thompson BT, Ancukiewicz M: Efficacy and safety of corticosteroids for persistent acute respiratory distress syndrome. N Engl J Med 2006, 354:1671–1684 [1].

Background

Persistent acute respiratory distress syndrome (ARDS) is characterized by excessive fibroproliferation, ongoing inflammation, prolonged mechanical ventilation, and a substantial risk of death. Because previous reports suggested that corticosteroids may improve survival, the study authors performed a multicenter, randomized controlled trial of corticosteroids in patients with persistent ARDS.

Methods

Objective

To determine if low dose corticosteroids would improve survival among patients with persistent ARDS.

Design

Multicenter randomized controlled trial.

Setting

25 hospitals in the United States that were part of the ARDS Clinical Trials Network.

Subjects

180 mechanically ventilated patients with ARDS of at least seven days duration.

Intervention

Subjects were randomized to either intravenous methylprednisolone (steroid group) or placebo in a double-blind fashion. Those in the steroid group received 2 mg/kg loading dose followed by 0.5 mg/kg every 6 hours for 14 days, 0.5 mg/kg every 12 hours for 7 days, and then tapering of the dose over 2–4 days.

Measurements and main results

The primary end point was mortality at 60 days. Secondary end points included the number of ventilator-free days and organ-failure-free days, biochemical markers of inflammation and fibroproliferation, and infectious complications. At 60 days, the hospital mortality rate was 28.6 percent in the placebo group (95 percent confidence interval, 20.3 to 38.6 percent) and 29.2 percent in the methylprednisolone group (95 percent confidence interval, 20.8 to 39.4 percent; P = 1.0); at 180 days, the rates were 31.9 percent (95 percent confidence interval, 23.2 to 42.0 percent) and 31.5 percent (95 percent confidence interval, 22.8 to 41.7 percent; P = 1.0), respectively. Methylprednisolone was associated with significantly increased 60- and 180-day mortality rates among patients enrolled at least 14 days after the onset of ARDS. Methylprednisolone increased the number of ventilator-free and shock-free days during the first 28 days in association with an improvement in oxygenation, respiratory-system compliance, and blood pressure with fewer days of vasopressor therapy. As compared with placebo, methylprednisolone did not increase the rate of infectious complications but was associated with a higher rate of neuromuscular weakness.

Conclusion

These results do not support the routine use of methylprednisolone for persistent ARDS despite the improvement in cardiopulmonary physiology. In addition, starting methylprednisolone therapy more than two weeks after the onset of ARDS may increase the risk of death. (ClinicalTrials.gov number, {"type":"clinical-trial","attrs":{"text":"NCT00295269","term_id":"NCT00295269"}}NCT00295269.)     

High-flow nasal cannula oxygen versus non-invasive ventilation in patients with acute hypoxaemic respiratory failure undergoing flexible bronchoscopy - a prospective randomised trial

Introduction

Critically ill patients with respiratory failure undergoing bronchoscopy have an increased risk of hypoxaemia-related complications. Previous studies have shown that in awake, hypoxaemic patients non-invasive ventilation (NIV) is helpful in preventing gas exchange deterioration during bronchoscopy. An alternative and increasingly used means of oxygen delivery is its application via high-flow nasal cannula (HFNC). This study was conducted to compare HFNC with NIV in patients with acute hypoxaemic respiratory failure undergoing flexible bronchoscopy.

Methods

Prospective randomised trial randomising 40 critically ill patients with hypoxaemic respiratory failure to receive either NIV or HFNC during bronchoscopy in the intensive care unit.

Results

After the initiation of NIV and HFNC, oxygen levels were significantly higher in the NIV group compared to the HFNC group. Two patients were unable to proceed to bronchoscopy after the institution of HFNC due to progressive hypoxaemia. During bronchoscopy, one patient on HFNC deteriorated due to intravenous sedation requiring non-invasive ventilatory support. Bronchoscopy was well tolerated in all other patients. There were no significant differences between the two groups regarding heart rate, mean arterial pressure and respiratory rate. Three patients in the NIV group and one patient in the HFNC group were intubated within 24 hours after the end of bronchoscopy (P = 0.29).

Conclusions

The application of NIV was superior to HFNC with regard to oxygenation before, during and after bronchoscopy in patients with moderate to severe hypoxaemia. In patients with stable oxygenation under HFNC, subsequent bronchoscopy was well tolerated.

Trial registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01870765","term_id":"NCT01870765"}}NCT01870765. Registered 30 May 2013.     

Optimal Mode of clearance in critically ill patients with Acute Kidney Injury (OMAKI) - a pilot randomized controlled trial of hemofiltration versus hemodialysis: a Canadian Critical Care Trials Group project

Introduction

Among critically ill patients with acute kidney injury (AKI) needing continuous renal replacement therapy (CRRT), the effect of convective (via continuous venovenous hemofiltration [CVVH]) versus diffusive (via continuous venovenous hemodialysis [CVVHD]) solute clearance on clinical outcomes is unclear. Our objective was to evaluate the feasibility of comparing these two modes in a randomized trial.

Methods

This was a multicenter open-label parallel-group pilot randomized trial of CVVH versus CVVHD. Using concealed allocation, we randomized critically ill adults with AKI and hemodynamic instability to CVVH or CVVHD, with a prescribed small solute clearance of 35 mL/kg/hour in both arms. The primary outcome was trial feasibility, defined by randomization of >25% of eligible patients, delivery of >75% of the prescribed CRRT dose, and follow-up of >95% of patients to 60 days. A secondary analysis using a mixed-effects model examined the impact of therapy on illness severity, defined by sequential organ failure assessment (SOFA) score, over the first week.

Results

We randomized 78 patients (mean age 61.5 years; 39% women; 23% with chronic kidney disease; 82% with sepsis). Baseline SOFA scores (mean 15.9, SD 3.2) were similar between groups. We recruited 55% of eligible patients, delivered >80% of the prescribed dose in each arm, and achieved 100% follow-up. SOFA tended to decline more over the first week in CVVH recipients (-0.8, 95% CI -2.1, +0.5) driven by a reduction in vasopressor requirements. Mortality (54% CVVH; 55% CVVHD) and dialysis dependence in survivors (24% CVVH; 19% CVVHD) at 60 days were similar.

Conclusions

Our results suggest that a large trial comparing CVVH to CVVHD would be feasible. There is a trend toward improved vasopressor requirements among CVVH-treated patients over the first week of treatment.

Trial Registration

ClinicalTrials.gov: {"type":"clinical-trial","attrs":{"text":"NCT00675818","term_id":"NCT00675818"}}NCT00675818     

CORTICUS: The end of unconditional love for steroid use?

Citation

Sprung CL, Annane D, Keh D, Moreno R, Singer M, Freivogel K, Weiss YG, Benbenishty J, Kalenka A, Forst H, Laterre PF, Reinhart K, Cuthbertson BH, Payen D, Briegel J: Hydrocortisone therapy for patients with septic shock. N Engl J Med 2008, 358: 111–124 [1].

Background

Hydrocortisone is widely used in patients with septic shock, even though a survival benefit has been reported only in patients who remained hypotensive after fluid and vasopressor resuscitation and whose plasma cortisol levels did not rise appropriately after the administration of corticotropin.

Methods

Objective

To evaluate the efficacy and safety of low-dose hydrocortisone therapy in a broad population of patients with septic shock – in particular, patients who had had a response to a corticotropin test, in whom a benefit was unproven.

Design

Multi-center, prospective randomized, double-blind, placebo-controlled trial.

Setting

International study involving 52 intensive care units.

Subjects

499 patients 18 years or older with the diagnosis of septic shock.

Intervention

251 patients received 50 mg of intravenous hydrocortisone and 248 patients received placebo every 6 hours for 5 days; the dose was then tapered over a 6-day period. A short corticotropin test was performed from blood samples taken immediately before and 60 minutes after an intravenous administration of 250 mcg of cosyntropin prior to administration of hydrocortisone.

Outcomes

Primary outcome was the mortality rate at 28 days in patients who did not have a response to corticotropin. Secondary outcomes included 28-day mortality in corticotropin responders and in all patients; length of stay; reversal of organ failure; and rates of new infection, hypernatremia and hyperglycemia.

Results

Of the 499 patients in the study, 233 (46.7%) did not have a response to corticotropin (125 in the hydrocortisone group and 108 in the placebo group). At 28 days, there was no significant difference in mortality between patients in the two study groups who did not have a response to corticotropin (39.2% in the hydrocortisone group and 36.1% in the placebo group, P = 0.69) or in patients who had a response to corticotropin (28.8% in the hydrocortisone group and 28.7% in the placebo group, P = 1.00). Mortality at 28 days included 86 of 251 patients in the hydrocortisone group (34.3%) and 78 of 248 patients in the placebo group (31.5%) (P = 0.51). Shock reversal was quicker in the hydrocortisone group compared to the placebo group. However, there were more episodes of super infection, including new sepsis and septic shock in the hydrocortisone group.

Conclusion

Hydrocortisone did not improve survival in patients with septic shock, either overall or in patients who did not have a response to corticotropin. However, hydrocortisone hastened reversal of shock in all study patients.

Trial Registration

(ClinicalTrials.gov number, {"type":"clinical-trial","attrs":{"text":"NCT00147004","term_id":"NCT00147004"}}NCT00147004.)     

Methods for a study of Anticipatory and Preventive multidisciplinary Team Care in a family practice

BACKGROUND

T o examine the methodology used to evaluate whether focusing the work of nurse practitioners and a pharmacist on frail and at-risk patients would improve the quality of care for such patients.

DESIGN

Evaluation of methodology of a randomized controlled trial including analysis of quantitative and qualitative data over time and analysis of cost-effectiveness.

SETTING

A single practice in a rural area near Ottawa, Ont.

PARTICIPANTS

A total of 241 frail patients, aged 50 years and older, at risk of experiencing adverse health outcomes.

INTERVENTION

At-risk patients were randomly assigned to receive Anticipatory and Preventive Team Care (from their family physicians, 1 of 3 nurse practitioners, and a pharmacist) or usual care.

MAIN OUTCOME MEASURES

The principal outcome for the study was the quality of care for chronic disease management. Secondary outcomes included other quality of care measures and evaluation of the program process and its cost-effectiveness. This article examines the effectiveness of the methodology used. Quantitative data from surveys, administrative databases, and medical records were supplemented with qualitative information from interviews, focus groups, work logs, and study notes.

CONCLUSION

Three factors limit our ability to fully demonstrate the potential effects of this team structure. For reasons outside our control, the intervention duration was shorter than intended; the practice’s physical layout did not facilitate interactions between the care providers; and contamination of the intervention effect into the control arm cannot be excluded. The study used a randomized design, relied on a multifaceted approach to evaluating its effects, and used several sources of data.

TRIAL REGISTRATION NUMBER

{"type":"clinical-trial","attrs":{"text":"NCT00238836","term_id":"NCT00238836"}}NCT00238836 (CONSORT).     

Randomized trial comparing daily interruption of sedation and nursing-implemented sedation algorithm in medical intensive care unit patients

Introduction

Daily interruption of sedation (DIS) and sedation algorithms (SAs) have been shown to decrease mechanical ventilation (MV) duration. We conducted a randomized study comparing these strategies.

Methods

Mechanically ventilated adults 18 years old or older in the medical intensive care unit (ICU) were randomly assigned to DIS or SA. Exclusion criteria were severe neurocognitive dysfunction, administration of neuromuscular blockers, and tracheostomy. Study endpoints were total MV duration and 28-day ventilator-free survival.

Results

The study was terminated prematurely after 74 patients were enrolled (DIS 36 and SA 38). The two groups had similar age, gender, racial distribution, Acute Physiology and Chronic Health Evaluation II score, and reason for MV. The Data Safety Monitoring Board convened after DIS patients were found to have higher hospital mortality; however, no causal connection between DIS and increased mortality was identified. Interim analysis demonstrated a significant difference in primary endpoint, and study termination was recommended. The DIS group had longer total duration of MV (median 6.7 versus 3.9 days; P = 0.0003), slower improvement of Sequential Organ Failure Assessment over time (0.70 versus 0.23 units per day; P = 0.025), longer ICU length of stay (15 versus 8 days; P < 0.0001), and longer hospital length of stay (23 versus 12 days; P = 0.01).

Conclusion

In our cohort of patients, the use of SA was associated with reduced duration of MV and lengths of stay compared with DIS. Based on these results, DIS may not be appropriate in all mechanically ventilated patients.

Trial registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00205517","term_id":"NCT00205517"}}NCT00205517.     

Monitoring of international normalized ratios: Comparison of community nurses with family physicians

Objective

To determine whether community-based, nurse-led monitoring of the international normalized ratio (INR) in patients requiring long-term warfarin therapy was comparable to traditional physician monitoring.

Design

A retrospective cohort analysis of patients taking long-term warfarin therapy.

Setting

The study used data gathered from 3 family medicine clinics in a primary care network in Edmonton, Alta.

Participants

Medical records of patients currently taking warfarin were examined.

Intervention

Implementation of nurse-led monitoring in a primary care network in place of standard family physician INR monitoring.

Main outcome measures

The degree of INR control before and after the implementation of nurse-run INR monitoring was assessed. The average proportion of time spent outside of therapeutic INR ranges, as well as the average number of days between successive INR readings, was calculated and compared. The degree of control placed patients into either a good-control group (out of range ≤ 25% of the time) or a moderate-control group (out of range > 25% of the time) and these groups were compared.

Results

Before nurse monitoring, INR values were out of range 20.4% of the time; after nurse monitoring they were out of range 19.2% of the time (P = .115); the time between sequential INR readings also did not differ before and after implementation of nurse monitoring (23.9 vs 21.6 days, P = .789).

Conclusion

Nurse-led monitoring of INR is as effective as traditional physician monitoring. Advantages of nurse-led monitoring might include freeing family physicians to see more patients or to spend less time at work. It might also represent potential cost savings.     

Intensive insulin therapy in the medical ICU – not so sweet?

Citation

Van den Berghe G, Wilmer A, Hermans G, Meersseman W, Wouters PJ, Milants I, Van Wijngaerden E, Bobbaers H, Bouillon R: Intensive insulin therapy in the medical ICU. N.Engl.J.Med 2006; 354: 449-61 [1].

Background

Intensive insulin therapy reduces morbidity and mortality in patients in surgical intensive care units (ICUs), but its role in patients in medical ICUs is unknown.

Methods

Objective

To investigate the efficacy of intensive insulin therapy in medical ICU patients.

Design

Prospective, randomized, controlled trial

Setting

Medical ICU in Leuven, Belgium.

Subjects

1200 medical ICU patients anticipated to need intensive care for at least three days.

Intervention

On admission, patients were randomly assigned to strict normalization of blood glucose levels (80 to 110 mg per deciliter [4.4 to 6.1 mmol per liter]) with the use of insulin infusion or to conventional therapy (insulin administered when the blood glucose level exceeded 215 mg per deciliter [12 mmol per liter], with the infusion tapered when the level fell below 180 mg per deciliter [10 mmol per liter]).

Measurements and main results

There was a history of diabetes in 16.9 percent of the patients. In the intention-to-treat analysis of 1200 patients, intensive insulin therapy reduced blood glucose levels but did not significantly reduce in-hospital mortality (40.0 percent in the conventional-treatment group vs. 37.3 percent in the intensive-treatment group, P = 0.33). However, morbidity was significantly reduced by the prevention of newly acquired kidney injury, accelerated weaning from mechanical ventilation, and accelerated discharge from the ICU and the hospital. Although length of stay in the ICU could not be predicted on admission, among 433 patients who stayed in the ICU for less than three days, mortality was greater among those receiving intensive insulin therapy. In contrast, among 767 patients who stayed in the ICU for three or more days, inhospital mortality in the 386 who received intensive insulin therapy was reduced from 52.5 to 43.0 percent (P = 0.009) and morbidity was also reduced.

Conclusion

Intensive insulin therapy significantly reduced morbidity but not mortality among all patients in the medical ICU. Although the risk of subsequent death and disease was reduced in patients treated for three or more days, these patients could not be identified before therapy. Further studies are needed to confirm these preliminary data. (ClinicalTrials.gov number, {"type":"clinical-trial","attrs":{"text":"NCT00115479","term_id":"NCT00115479"}}NCT00115479).     

Nutrition intervention for migraine: a randomized crossover trial

Background

Limited evidence suggests that dietary interventions may offer a promising approach for migraine. The purpose of this study was to determine the effects of a low-fat plant-based diet intervention on migraine severity and frequency.

Methods

Forty-two adult migraine sufferers were recruited from the general community in Washington, DC, and divided randomly into two groups. This 36-week crossover study included two treatments: dietary instruction and placebo supplement. Each treatment period was 16 weeks, with a 4-week washout between. During the diet period, a low-fat vegan diet was prescribed for 4 weeks, after which an elimination diet was used. Participants were assessed at the beginning, midpoint, and end of each period. Significance was determined using student’s t-tests.

Results

Worst headache pain in last 2 weeks, as measured by visual analog scale, was initially 6.4/10 cm (SD 2.1 cm), and declined 2.1 cm during the diet period and 0.7 cm during the supplement period (p=0.03). Average headache intensity (0–10 scale) was initially 4.2 (SD 1.4) per week, and this declined by 1.0 during the diet period and by 0.5 during the supplement period (p=0.20). Average headache frequency was initially 2.3 (SD 1.8) per week, and this declined by 0.3 during the diet period and by 0.4 during the supplement period (p=0.61). The Patient’s Global Impression of Change showed greater improvement in pain during the diet period (p<0.001).

Conclusions

These results suggest that a nutritional approach may be a useful part of migraine treatment, but that methodologic issues necessitate further research.

Trial registration

Clinicaltrials.gov, {"type":"clinical-trial","attrs":{"text":"NCT01699009","term_id":"NCT01699009"}}NCT01699009 and {"type":"clinical-trial","attrs":{"text":"NCT01547494","term_id":"NCT01547494"}}NCT01547494.