Objects drawn from haptic perception and vision-based spatial abilities.

Haptic perception is used in the anatomy laboratory with the handling of three-dimensional (3D) prosections, dissections, and synthetic models of anatomical structures. Vision-based spatial ability has been found to correlate with performance on tests of 3D anatomy knowledge in previous studies. The objective was to explore whether haptic-based spatial ability was correlated with vision-based spatial ability. Vision-based spatial ability was measured in a study group of 49 medical graduates with three separate tests: a redrawn Vandenberg and Kuse Mental Rotations Tests in two (MRT A) and three (MRT C) dimensions and a Surface Development Test (SDT). Haptic-based spatial ability was measured using 18 different objects constructed from 10 cubes glued together. Participants were asked to draw these objects from blind haptic perception, and drawings were scored by two independent judges. The maximum score was 24 for each of MRT A and MRT C, 60 for SDT, and 18 for the drawings. The drawing score based on haptic perception [median = 17 (lower quartile = 16, upper quartile = 18)] correlated with MRT A [14 (9, 17)], MRT C [9 (7, 12)] and SDT [44 (36, 52)] scores with a Spearman's rank correlation coefficient of 0.395 (p = 0.0049), 0.507 (p = 0.0002) and 0.606 (p < 0.0001), respectively. Spatial abilities assessed by vision-based tests were correlated with a drawing score based on haptic perception of objects. Future research should investigate the contribution of haptic-based and vision-based spatial abilities on learning 3D anatomy from physical models.

Mortality Risk Increases With Clustered Ventricular Arrhythmias in Patients With Implantable Cardioverter-Defibrillators.

OBJECTIVES: This study sought to examine the adverse prognosis associated with ventricular arrhythmia clusters that falls outside the current electrical storm definition. BACKGROUND: Electrical storm is most frequently defined as a cluster of ≥3 episodes of ventricular arrhythmia (VA) in a 24-h period. This definition has been associated with adverse cardiovascular outcomes and mortality, but the effect of lesser and greater clustering of arrhythmias has not been described. METHODS: Among all patients in the Resynchronization in Ambulatory Heart Failure trial, 14,515 implantable cardioverter-defibrillator-detected events with data available were rigorously adjudicated in blinded fashion. Arrhythmia incidence was examined for clustering, defined as 2 or more VA events occurring within 3 months. The prognostic importance of clustering was analyzed by varying the cluster length and number of events used to define a cluster. Mortality rates of groups with clustered arrhythmias were compared to patients with no arrhythmia or with unclustered arrhythmia. RESULTS: The trial included 1,764 patients, among whom 465 patients had two or more VA episodes within 3 months, whereas 406 had unclustered arrhythmias. Compared to patients with no arrhythmia, patients experiencing unclustered VA had increased risk of death (hazard ratio [HR]: 1.45; 95% confidence interval [CI]: 1.09 to 1.93; p = 0.011), whereas the risk was even higher in patients with clustered arrhythmia (HR: 2.68; 95% CI: 2.13 to 3.36; p < 0.0001). Mortality risk increased with higher VA burden (number of VAs in a cluster) and shorter cluster length. This was observed in all groups tested, including the cluster with the least VA burden in the longest cluster length tested (2 VA episodes occurring within 3 months) (mortality HR: 2.85; 95% CI: 1.95 to 4.17; p < 0.0001). Although clustered arrhythmias terminated with antitachycardia pacing were associated with increased mortality, clusters terminated with implantable cardioverter-defibrillator shocks were associated with still higher mortality risk. CONCLUSIONS: Significant adverse prognostic association of clustered VAs is observable with even 2 VA events within 3 months and increases with higher cluster density.

Cardiac Resynchronization Therapy Reduces Ventricular Arrhythmias in Primary but Not Secondary Prophylactic Implantable Cardioverter Defibrillator Patients: Insight From the Resynchronization in Ambulatory Heart Failure Trial.

BACKGROUND: The RAFT (Resynchronization in Ambulatory Heart Failure Trial) demonstrated that cardiac resynchronization therapy (CRT) reduced both mortality and heart failure hospitalizations in patients with functional class II or III heart failure and widened QRS. We examined the influence of CRT on ventricular arrhythmias in patients with primary versus secondary prophylaxis defibrillator indications. METHODS AND RESULTS: All ventricular arrhythmias among RAFT study participants were downloaded and adjudicated by 2 blinded reviewers with an overreader for disagreements and committee review for remaining discrepancies. Incidence of ventricular arrhythmias among patients randomized to CRT-D versus implantable cardioverter defibrillator (ICD) were compared within the groups of patients treated for primary prophylaxis and for secondary prophylaxis. Of 1798 enrolled patients, 1764 had data available for adjudication and were included. Of these, 1531 patients were implanted for primary prophylaxis, while 233 patients were implanted for secondary prophylaxis; 884 patients were randomized to ICD and 880 to CRT-D. During 5953.6 patient-years of follow-up, there were 11 278 appropriate ICD detections of ventricular arrhythmias. In the primary prophylaxis group, CRT-D significantly reduced incidence ventricular arrhythmias in comparison to ICD (hazard ratio, 0.86; 95% confidence interval, 0.74-0.99; P=0.044). This effect was not seen in the secondary prophylaxis group (hazard ratio, 1.14; 95% confidence interval, 0.82-1.58; P=0.45). CRT-D was not associated with significant differences in overall ventricular arrhythmia burden in either group. CONCLUSIONS: CRT reduced the rate of onset of new ventricular arrhythmias detected by ICDs in patients without a history of prior ventricular arrhythmias. This effect was not observed among patients who had prior ventricular arrhythmias. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00251251.

Frequency and Outcomes of Postrandomization Atrial Tachyarrhythmias in the Resynchronization/Defibrillation in Ambulatory Heart Failure Trial.

BACKGROUND: Whether adding cardiac resynchronization therapy (CRT-D) to an implanted cardioverter-defibrillator alters the risk of atrial fibrillation or other atrial tachyarrhythmias (AF/AT), or if postimplantation AF/AT modulate the benefits of CRT-D, remain unknown. METHODS AND RESULTS: We studied 972 Resynchronization/Defibrillation in Ambulatory Heart Failure Trial (RAFT) participants without permanent AF, who were randomized to CRT-D (n=495) versus nonresynchronization defibrillator (implanted cardioverter-defibrillator; n=477) within the predefined stratum eligible for an atrial lead. Occurrence of postrandomization AF/AT was prospectively assessed, and Cox models were used to test the independent association between the postrandomization AF/AT and the RAFT primary composite outcome of all-cause mortality or hospitalization for heart failure. Over 41 (±19) months, postrandomization AF/AT occurred in 216 (45.3%) patients randomized to implanted cardioverter-defibrillator and 249 (50.3%) randomized to CRT-D. After adjusting for competing risk of death, randomization to CRT-D increased risk of postrandomization AF/AT (hazard ratio, 1.20; 95% confidence interval, 1.00-1.42; P=0.045). Postrandomization AF/AT, which remained paroxysmal in 69.5%, did not reduce biventricular pacing percentage. In adjusted models, postrandomization AF/AT was not associated with the primary outcome (hazard ratio, 1.04; 95% confidence interval, 0.84-1.30). However, AF/AT was associated with a borderline decreased risk of mortality (hazard ratio, 0.75; 95% confidence interval, 0.58-1.00) but increased risk of heart failure hospitalization (hazard ratio, 1.43; 95% confidence interval, 1.08-1.90). CONCLUSIONS: In RAFT, nearly half of the patients developed postrandomization AF/AT, and those randomized to CRT-D had borderline significant higher risk. Postrandomization AF/AT was associated with risk of heart failure hospitalization, but not with the primary composite outcome. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00251251.

Incidence, predictors, and procedural results of upgrade to resynchronization therapy: the RAFT upgrade substudy.

BACKGROUND: The resynchronization-defibrillation for ambulatory heart failure trial (RAFT) study demonstrated that adding cardiac resynchronization therapy (CRT) in selected patients requiring de novo implantable cardiac defibrillators (ICD) reduced mortality as compared with ICD therapy alone, despite an increase in procedure-related adverse events. Data are lacking regarding the management of patients with ICD therapy who develop an indication for CRT upgrade. METHODS AND RESULTS: Participating RAFT centers provided data regarding de novo CRT-D (CRT with ICD) implant, upgrade to CRT-D during RAFT (study upgrade), and upgrade within 6 months after presentation of study results (substudy). Substudy centers enrolled 1346 (74.9%) patients in RAFT, including 644 de novo, 80 study upgrade, and 60 substudy CRT attempts. The success rate (initial plus repeat attempts) was 95.2% for de novo versus 96.3% for study upgrade and 90.0% for substudy CRT attempts (P=0.402). Acute complications occurred among 26.2% of de novo versus 18.8% of study upgrade and 3.4% of substudy CRT implantation attempts (P<0.001). The most common complication was left ventricular lead dislodgement. The principal reasons for not yet attempting upgrade in the substudy were patient preference (31.9%), New York Heart Association Class I (17.0%), and a QRS<150 ms (13.1%). CONCLUSIONS: Among a broad group of implant physicians, CRT upgrades were performed in patients with an ICD in situ with no difference in implant success rate and a reduced acute complication rate as compared with a de novo CRT implant. Decisions to upgrade were influenced by predictors of benefit in subgroup analyses of the RAFT study and other trials.

Spatial abilities of medical graduates and choice of residency programs.

Spatial abilities have been related in previous studies to three-dimensional (3D) anatomy knowledge and the performance in technical skills. The objective of this study was to relate spatial abilities to residency programs with different levels of content of 3D anatomy knowledge and technical skills. The hypothesis was that the choice of residency program is related to spatial abilities. A cohort of 210 medical graduates was enrolled in a prospective study in a 5-year experiment. Spatial abilities were measured with a redrawn Vandenberg and Kuse Mental Rotations Test (MRT) in two (MRTA) and three (MRTC) dimensions. Medical graduates were enrolled in Family Medicine (n = 76, 36.2%), Internal Medicine (64, 30.5%), Surgery (52, 24.8%), and Anesthesia (18, 8.6%). The assumption was that the level of 3D anatomy knowledge and technical skills content was higher in Surgery and Anesthesia compared to Family Medicine and Internal Medicine. Mean MRTA score of 12.4 (±SD 4.6), 12.0 (±4.3), 14.1 (±4.3), and 14.6 (±4.0) was obtained in Family Medicine, Internal Medicine, Surgery, and Anesthesia, respectively (P = 0.0176). Similarly, mean MRTC score of 8.0 (±4.4), 7.5 (±3.6), 8.5 (±3.9), and 7.9 (±4.1) was obtained (P = 0.5647). Although there was a tendency for lower MRTA score in Family Medicine and Internal Medicine compared to Surgery and Anesthesia, no statistically significant main effect of residency, year, sex, or the interactions were observed for the MRTA and MRTC. Studied sample of medical graduates was not found to choose their residency programs based on their innate spatial abilities.

Impact of cardiac resynchronization therapy on hospitalizations in the Resynchronization-Defibrillation for Ambulatory Heart Failure trial.

BACKGROUND: This study reports the impact of cardiac resynchronization therapy (CRT) on hospitalizations in patients randomized to implantable cardioverter-defibrillator (ICD) or ICD-CRT in the Resynchronization-Defibrillation for Ambulatory Heart Failure Trial (RAFT). METHODS AND RESULTS: Hospitalization rates and lengths of hospital stay were compared between the 2 groups. At the 18-month follow-up, the numbers of patients hospitalized for any cause were similar in the ICD (n=351, 38.8%) and ICD-CRT (n=331, 30.0%) groups. The number of patients hospitalized for heart failure was significantly lower in the ICD-CRT (n=101, 11.3%) compared with the ICD (n=141, 15.6%; P=0.003) group. The number of patients hospitalized for a device-related indication was similar in the ICD-CRT group (n=147, 16.4%) and ICD group (n=126, 13.9%; P=0.148). The total number of hospitalizations for any cause (n=1448 versus n=1553; P=0.042), any cardiovascular cause (n=667 versus n=790; P=0.017), and any heart failure cause (n=385 versus n=505; P<0.0001) was significantly lower in ICD-CRT group compared with the ICD group, whereas the number of hospitalizations for device-related causes was significantly higher in the ICD-CRT group compared with the ICD group (246 versus 159; P<0.001). Although the reduction in hospitalizations for heart failure in the CRT-ICD group was offset by an increased number of hospitalizations for device-related indications, the length of hospital stay for any cause was significantly shorter in the ICD-CRT group (8.83±13.30 days) compared with the ICD group (9.59±14.40 days; P=0.005). CONCLUSION: ICD-CRT therapy significantly reduces hospitalizations and total days in hospital in patients with New York Heart Association class II/III heart failure compared with ICD therapy despite increased admissions for device-related indications. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00251251.

Left ventricular lead position and outcomes in the Resynchronization-Defibrillation for Ambulatory Heart Failure Trial (RAFT).

BACKGROUND: Conflicting data exist regarding the association between left ventricular (LV) lead position and benefit from cardiac resynchronization therapy. We evaluated the relationships between LV lead positions and the risk of death or hospitalization for heart failure (HF) in the cardiac resynchronization therapy arm of the Resynchronization-Defibrillation for Ambulatory Heart Failure Trial (RAFT). METHODS: LV lead position was categorized by site investigator (MD) and in a chest radiograph core laboratory (CXR) as "anterior," "lateral," or "posterior" in the short axis, and "basal," "mid," or "apical" in the long axis. Agreement between MD and CXR LV lead position classification was evaluated and the independent relationship between LV lead position and clinical outcome was assessed using Cox multivariable models. RESULTS: Agreement between MD and CXR LV lead position was poor (κ ≤ 0.26). Over 39 ± 20 months, 140 of 447 (31.3%) patients met the RAFT primary end point (death or HF hospitalization). In adjusted analyses, neither MD-determined nor CXR-determined anterior or apical LV lead position was significantly associated with the primary outcome. However, CXR-defined apical LV lead position was associated with a higher risk of HF hospitalization (hazard ratio, 1.99; P = 0.004). CONCLUSIONS: Poor agreement between implanting physician and core lab CXR-based categorizations of LV lead position was observed. Neither categorization method resulted in significant associations between apical or anterior LV lead position and the risk of the composite primary outcome of death or heart failure hospitalization. However, CXR-defined apical lead position was associated with increased risk of HF hospitalization.

Sex differences in spatial abilities of medical graduates entering residency programs.

Sex differences favoring males in spatial abilities have been known by cognitive psychologists for more than half a century. Spatial abilities have been related to three-dimensional anatomy knowledge and the performance in technical skills. The issue of sex differences in spatial abilities has not been addressed formally in the medical field. The objective of this study was to test an a priori hypothesis of sex differences in spatial abilities in a group of medical graduates entering their residency programs over a five-year period. A cohort of 214 medical graduates entering their specialist residency training programs was enrolled in a prospective study. Spatial abilities were measured with a redrawn Vandenberg and Kuse Mental Rotations Tests in two (MRTA) and three (MRTC) dimensions. Sex differences favoring males were identified in 131 (61.2%) female and 83 (38.8%) male medical graduates with the median (Q1, Q3) MRTA score [12 (8, 14) vs. 15 (12, 18), respectively; P < 0.0001] and MRTC score [7 (5, 9) vs. 9 (7, 12), respectively; P < 0.0001]. Sex differences in spatial abilities favoring males were demonstrated in the field of medical education, in a group of medical graduates entering their residency programs in a five-year experiment. Caution should be exerted in applying our group finding to individuals because a particular female may have higher spatial abilities and a particular male may have lower spatial abilities.

Sprint Fidelis lead fractures in patients with cardiac resynchronization therapy devices: insight from the Resynchronization/Defibrillation for Ambulatory Heart Failure (RAFT) study.

BACKGROUND: Using data from the Resynchronization/Defibrillation for Ambulatory Heart Failure (RAFT) study, we examined whether Fidelis lead failure was more common in patients with implantable cardioverter-defibrillators (ICDs) and cardiac resynchronization therapy (ICD-CRT) than in patients with an ICD only. METHODS AND RESULTS: All cases of patients who had a right ventricular defibrillation lead revision in the RAFT study were adjudicated for the presence of lead fracture. Criteria for fracture were at least 2 of the following: (1) Impedance rise (>50% or >500 Ω in 1 week), (2) short interval count >10 times per day or 300 times per month, or (3) inappropriate shock caused by noise, verified by stored electrogram. A total of 1798 patients were enrolled into the RAFT study, with a mean follow-up of 40±20 months. There were 818 patients (45.5%) who received a Fidelis lead at the original implantation, 405 with an ICD only and 413 with an ICD-CRT. There were 47 confirmed defibrillation lead fractures; 45 were Fidelis leads (5.5% of Fidelis leads). The overall rate of fracture in the ICD group was 3.2% compared with 7.8% in the ICD-CRT group (P=0.006; hazard ratio, 2.42; 95% confidence interval, 1.27-4.61). Significant correlates of lead fracture in this population were undergoing an ICD-CRT implantation and having ≥2 leads. CONCLUSIONS: In this analysis of the RAFT study, patients with an ICD-CRT were found to have a significantly higher fracture rate than patients with an ICD. This finding needs to be considered when these patients are assessed for possible lead revision at the time of an elective generator replacement.

Cardiac resynchronization therapy in patients with permanent atrial fibrillation: results from the Resynchronization for Ambulatory Heart Failure Trial (RAFT).

BACKGROUND: Cardiac resynchronization (CRT) prolongs survival in patients with systolic heart failure and QRS prolongation. However, most trials excluded patients with permanent atrial fibrillation. METHODS AND RESULTS: The Resynchronization for Ambulatory Heart Failure Trial (RAFT) randomized patients to an implantable cardioverter defibrillator (ICD) or ICD+CRT, stratified by the presence of permanent atrial fibrillation. Patients with permanent atrial fibrillation were randomized to CRT-ICD (n=114) or ICD (n=115). Patients receiving a CRT-ICD were similar to those receiving an ICD: age (71.6±7.3 versus 70.4±7.7 years), left ventricular ejection fraction (22.9±5.3% versus 22.3±5.1%), and QRS duration (151.0±23.6 versus 153.4±24.7 ms). There was no difference in the primary outcome of death or heart failure hospitalization between those assigned to CRT-ICD versus ICD (hazard ratio, 0.96; 95% CI, 0.65-1.41; P=0.82). Cardiovascular death was similar between treatment arms (hazard ratio, 0.97; 95% CI, 0.55-1.71; P=0.91); however, there was a trend for fewer heart failure hospitalizations with CRT-ICD (hazard ratio, 0.58; 95% CI, 0.38-1.01; P=0.052). The change in 6-minute hall walk duration between baseline and 12 months was not different between treatment arms (CRT-ICD: 19±84 m versus ICD: 16±76 m; P=0.88). Patients treated with CRT-ICD showed a trend for a greater improvement in Minnesota Living with Heart Failure score between baseline and 6 months (CRT-ICD: 41±21 to 31±21; ICD: 33±20 to 28±20; P=0.057). CONCLUSIONS: Patients with permanent atrial fibrillation who are otherwise CRT candidates appear to gain minimal benefit from CRT-ICD compared with a standard ICD.

Cardiac resynchronization therapy: a meta-analysis of randomized controlled trials.

BACKGROUND: Studies of cardiac resynchronization therapy in addition to an implantable cardioverter defibrillator in patients with mild to moderate congestive heart failure had not been shown to reduce mortality until the recent RAFT trial (Resynchronization/Defibrillation for Ambulatory Heart Failure Trial). We performed a meta-analysis including the RAFT trial to determine the effect of cardiac resynchronization therapy with or without an implantable defibrillator on mortality. METHODS: We searched electronic databases and other sources for reports of randomized trials using a parallel or crossover design. We included studies involving patients with heart failure receiving optimal medical therapy that compared cardiac resynchronization therapy with optimal medical therapy alone, or cardiac resynchronization therapy plus an implantable defibrillator with a standard implantable defibrillator. The primary outcome was mortality. The optimum information size was considered to assess the minimum amount of information required in the literature to reach reliable conclusions about cardiac resynchronization therapy. RESULTS: Of 3071 reports identified, 12 studies (n = 7538) were included in our meta-analysis. Compared with optimal medical therapy alone, cardiac resynchronization therapy plus optimal medical therapy significantly reduced mortality (relative risk [RR] 0.73, 95% confidence interval [CI] 0.62-0.85). Compared with an implantable defibrillator alone, cardiac resynchronization therapy plus an implantable defibrillator significantly reduced mortality (RR 0.83, 95% CI 0.72-0.96). This last finding remained significant among patients with New York Heart Association (NYHA) class I or II disease (RR 0.80, 95% CI 0.67-0.96) but not among those with class III or IV disease (RR 0.84, 95% CI 0.69-1.07). Analysis of the optimum information size showed that the sequential monitoring boundary was crossed, which suggests no need for further clinical trials. INTERPRETATION: The cumulative evidence is now conclusive that the addition of cardiac resynchronization to optimal medical therapy or defibrillator therapy significantly reduces mortality among patients with heart failure.

Spatial abilities in an elective course of applied anatomy after a problem-based learning curriculum.

A concern on the level of anatomy knowledge reached after a problem-based learning curriculum has been documented in the literature. Spatial anatomy, arguably the highest level in anatomy knowledge, has been related to spatial abilities. Our first objective was to test the hypothesis that residents are interested in a course of applied anatomy after a problem-based learning curriculum. Our second objective was to test the hypothesis that the interest of residents is driven by innate higher spatial abilities. Fifty-nine residents were invited to take an elective applied anatomy course in a prospective study. Spatial abilities were measured with a redrawn Vandenberg and Kuse Mental Rotations Test in two (MRT A) and three (MRT C) dimensions. A need for a greater knowledge in anatomy was expressed by 25 residents after a problem-based learning curriculum. MRT A and C scores obtained by those choosing (n = 25) and not choosing (n = 34) applied anatomy was not different (P = 0.46 and P = 0.38, respectively). Percentage of residents in each residency program choosing applied anatomy was different [23 vs. 31 vs. 100 vs. 100% in Family Medicine, Internal Medicine, Surgery, and Anesthesia, respectively; P < 0.0001]. The interest of residents in applied anatomy was not driven by innate higher spatial abilities. Our applied anatomy course was chosen by many residents because of training needs rather than innate spatial abilities. Future research will need to assess the relationship of individual differences in spatial abilities to learning spatial anatomy.

Effect of a liberal versus restrictive transfusion strategy on mortality in patients with moderate to severe head injury.

OBJECTIVE: To compare a restrictive versus a liberal transfusion strategy in patients with moderate to severe closed head injury following multiple trauma in 13 Canadian intensive care units (ICUs). METHODS: This is a subgroup analysis of a multicenter randomized controlled clinical trial involving sixty-seven critically ill patients from the Transfusion Requirements in the Critical Care trial who sustained a closed head injury. Patients had a hemoglobin concentration less than 9.0 g/dL within 72 hours of admission to the ICU. Patients were randomized to a restrictive allogeneic red blood cell transfusion strategy (hemoglobin 7.0 g/dL and maintained between 7.0 and 9.0 g/dL) or a liberal strategy (hemoglobin 10.0 g/dL and maintained between 10.0 and 12.0 g/dL). RESULTS: Baseline characteristics in the restrictive ( n = 29) and the liberal ( n = 38) transfusion groups were comparable. Average hemoglobin concentrations and red blood cell units transfused per patient were significantly lower in the restrictive compared to the liberal group. The 30-day all-cause mortality rates in the restrictive group were 17% as compared to 13% in the liberal group (risk difference 4.1 with 95% confidence interval [CI], 13.4 to 21.5, p = 0.64). Presence of multiple organ dysfunction (12.1 +/- 6.4 versus 10.6 +/- 6.3, p = 0.35) and changes in multiple organ dysfunction from baseline scores adjusted for death (4.5 +/- 6.2 versus 3.4 +/- 6.2, p = 0.49) were similar between the restrictive and liberal transfusion groups, respectively. Median length of stay in ICU (10 days, interquartile range 5 to 21 days versus 8 days, interquartile range 5 to 11 days, p = 0.26) and hospital (27 days, interquartile range 14 to 39 days versus 30.5 days, interquartile range 17 to 47 days, p = 0.72) were similar between the restrictive and liberal transfusion groups. CONCLUSIONS: We were unable to detect significant improvements in mortality with a liberal as compared to restrictive transfusion strategy in critically ill trauma victims with moderate to severe head injury.

Sequential response-adapted induction and consolidation regimens idarubicin/cytarabine and mitoxantrone/etoposide in adult acute myelogenous leukemia: 10 year follow-up of a study by the Canadian Leukemia Studies Group.

PURPOSE: The Canadian Leukemia Studies Group (CLSG) sought to test the safety and efficacy of response-adapted, non-cross resistant chemotherapy in de novo acute myeloid leukemia (AML). The combinations of idarubicin 12 mg/m(2)/d on days 1 - 3 and Ara-C (200 mg/m(2)/d) on days 1 - 7 (IDAC) followed by mitoxantrone 10 mg/m(2)/day, and etoposide 100 mg/m(2)/day, on days 1 - 5 (NOVE) were used according to patient response to induction and consolidation. PATIENTS AND METHODS: In this multi-centre open-label phase II study, 140 patients up to age 80 were given induction with IDAC. Patients were entered between March 1993 and August 1995. If patients had persistent blasts at day 14 or on recovery, they were given NOVE. As consolidation, patients achieving complete remission (CR) with IDAC were given 1 further cycle of IDAC and 1 cycle of NOVE. Patients achieving CR after NOVE were given 2 further cycles of NOVE. RESULTS: 76% of all patients achieved remission after IDAC +/- NOVE, 81% in patients aged < or =60 years and 67% in patients aged >60. Overall, induction mortality was 11% and toxicity was similar to other cooperative group studies. Median follow-up was 104.0 months with 95% CI: (100.0, 105.2). Median overall survival (OS) in responding patients < or =60 was not reached: of the 79 responders < or =60, 35 died. The median disease free survival (DFS) in these responding patients was 22.7 (14.9, na) months. Median OS and DFS in responding patients >60 was 10.0 (7.3, 15.2) months and 7.5 (6.2, 15.2) months, respectively. CONCLUSION: The results of this trial are very encouraging and suggest that there may be long-term benefit to this method. On the basis of these results, a randomized phase III trial has been performed.

Shelter-based managed alcohol administration to chronically homeless people addicted to alcohol.

BACKGROUND: People who are homeless and chronically alcoholic have increased health problems, use of emergency services and police contact, with a low likelihood of rehabilitation. Harm reduction is a policy to decrease the adverse consequences of substance use without requiring abstinence. The shelter-based Managed Alcohol Project (MAP) was created to deliver health care to homeless adults with alcoholism and to minimize harm; its effect upon consumption of alcohol and use of crisis services is described as proof of principle. METHODS: Subjects enrolled in MAP were dispensed alcohol on an hourly basis. Hospital charts were reviewed for all emergency department (ED) visits and admissions during the 3 years before and up to 2 years after program enrollment, and the police database was accessed for all encounters during the same periods. The results of blood tests were analyzed for trends. A questionnaire was administered to MAP participants and staff about alcohol use, health and activities of daily living before and during the program. Direct program costs were also recorded. RESULTS: Seventeen adults with an average age of 51 years and a mean duration of alcoholism of 35 years were enrolled in MAP for an average of 16 months. Their monthly mean group total of ED visits decreased from 13.5 to 8 (p = 0.004); police encounters, from 18.1 to 8.8 (p = 0.018). Changes in blood test findings were nonsignificant. All program participants reported less alcohol consumption during MAP, and subjects and staff alike reported improved hygiene, compliance with medical care and health. INTERPRETATION: A managed alcohol program for homeless people with chronic alcoholism can stabilize alcohol intake and significantly decrease ED visits and police encounters.

Prostaglandin E vaginal gel to treat dystocia in spontaneous labour: a multicentre randomised placebo-controlled trial.

OBJECTIVE: To test the safety and efficacy of prostaglandin E(2) (PgE(2)) as a treatment for dystocia in spontaneous labour. DESIGN: Randomised, double-blind, placebo-controlled trial. SETTING: Multicentre study in nine university-affiliated hospitals in Canada. Population Three hundred and thiry-two nulliparous women with spontaneous labour at term. METHODS: Women who had progressed < 2 cm of cervical dilation in the 4 hours following the diagnosis of labour were randomly assigned to receive a single dose of either 1 mg (n= 112) or 2 mg (n= 111) PgE(2) vaginal gel or placebo gel (n= 109). MAIN OUTCOME MEASURES: The primary outcome was resolution of dystocia, defined as a change in cervical dilatation of >0.5 cm per hour in the 6 hours following gel administration. Secondary outcomes were progress of labour, uterine hyperstimulation (more than five contractions in 10 minutes or a contraction lasting more than 2 minutes), use of oxytocin, method of delivery, maternal and neonatal morbidity. RESULTS: Dystocia resolved more often after PgE(2) 1 mg (49%), RR 1.53 (95% CI 1.1, 2.1) and PgE(2) 2 mg (49%), RR 1.5 (CI 1.1, 2.1), compared with placebo (32%). Hyperstimulation was increased after PgE(2) 2 mg treatment (15%), RR 5.6 (95% CI 1.7, 18), but not after PgE(2) 1 mg (5.4%), RR 1.9 (CI 0.50, 7.6) when compared with placebo (2.8%). There was an increase in caesarean sections performed in the second stage of labour in the PgE(2) groups versus placebo. There were no differences in measures of maternal or neonatal morbidity. CONCLUSION: A single 1-mg dose of PgE(2) vaginal gel is more effective than placebo in resolving dystocia, without increasing uterine hyperstimulation, but may be associated with an increase in the incidence of second stage caesarean section.

Is a restrictive transfusion strategy safe for resuscitated and critically ill trauma patients?

BACKGROUND: An analysis from the prospective multicenter randomized controlled trial (Transfusion Requirements in Critical Care Trial) compared the use of restrictive and liberal transfusion strategies with resuscitated critically ill trauma patients. METHODS: Critically ill trauma patients with a hemoglobin concentration less than 90 g/L within 72 hours of admission to the intensive care unit were randomized to a restrictive (hemoglobin concentration, 70 g/L) or liberal (hemoglobin concentration, 100 g/L) red blood cell transfusion strategy. RESULTS: The baseline characteristics in the restrictive (n = 100) and liberal (n = 103) transfusion groups were comparable. The average hemoglobin concentrations (82.7 +/- 6.2 g/L vs. 104.3 +/- 12.2 g/L; p < 0.0001) and the red blood cell units transfused per patient (2.3 +/- 4.4 vs. 5.4 +/- 4.3; p < 0.0001) were significantly lower in the restrictive group than in the liberal group. The 30-day all-cause mortality rates in the restrictive group were 10%, as compared with 9% in the liberal group (p = 0.81). The presence of multiple organ dysfunction (9.2 +/- 6.3 vs. 9.0 +/- 6.0; p = 0.81), the changes in multiple organ dysfunction from baseline scores adjusted for death (1.2 +/- 6.1 vs. 1.9 +/- 5.7; p = 0.44), and the length of stay in the intensive care unit (9.8 +/- 8.1 vs. 10.2 +/- 8.7 days; p = 0.73) and hospital (31.4 +/- 17.1 vs. 33.7 +/- 17.7 days; p = 0.34) also were similar between the restrictive and liberal transfusion groups. CONCLUSIONS: A restrictive red blood cell transfusion strategy appears to be safe for critically ill multiple-trauma patients. A randomized controlled trial would provide the appropriate level of evidence with regard to the daily use of blood in this population of patients.

Outpatient oral prednisone after emergency treatment of chronic obstructive pulmonary disease.

BACKGROUND: In this randomized, double-blind, placebo-controlled trial, we studied the effectiveness of prednisone in reducing the risk of relapse after outpatient exacerbations of chronic obstructive pulmonary disease (COPD). METHODS: We enrolled 147 patients who were being discharged from the emergency department after an exacerbation of COPD and randomly assigned them to 10 days of treatment with 40 mg of oral prednisone once daily or identical-appearing placebo. All patients received oral antibiotics for 10 days, plus inhaled bronchodilators. The primary end point was relapse, defined as an unscheduled visit to a physician's office or a return to the emergency department because of worsening dyspnea, within 30 days after randomization. RESULTS: The overall rate of relapse at 30 days was lower in the prednisone group than in the placebo group (27 percent vs. 43 percent, P=0.05), and the time to relapse was prolonged in those taking prednisone (P=0.04). After 10 days of therapy, patients in the prednisone group had greater improvements in forced expiratory volume in one second than did patients in the placebo group (mean [+/-SD] increase from base line, 34+/-42 percent vs. 15+/-31 percent; P=0.007). Patients in the prednisone group also had significant improvements in dyspnea, as measured by the transitional dyspnea index (P=0.04) and by the dyspnea domain of the Chronic Respiratory Disease Index Questionnaire (P=0.02), but not in health-related quality of life (P=0.14). CONCLUSIONS: Outpatient treatment with oral prednisone offers a small advantage over placebo in treating patients who are discharged from the emergency department with an exacerbation of COPD.