Abstract Transcatheter aortic valve implantation (TAVI) is a relatively new technology for the treatment of severe and symptomatic aortic valve stenosis. TAVI offers an alternative therapy for ...patients unable to be treated surgically because of contraindications or severe comorbidities. It is being rapidly dispersed in Canada, as it is worldwide. The objective of this article is to present our recommendations for the use of TAVI, based on a multidisciplinary evaluation of recently published evidence. We systematically searched and summarized published data (2008-2011) on benefits, risks, and cost-effectiveness of TAVI. We also examined ethical issues and organizational aspects of delivering the intervention. We discussed the soundness and applicability of our recommendations with clinical experts active in the field. The published TAVI results for high-risk and/or inoperable patients are promising in terms of survival, function, quality of life, and cost-effectiveness, although we noted large variability in the survival rates at 1 year and in the frequency of important adverse outcomes such as stroke. Until more data from randomized controlled trials and registries become available, prudence and discernment are necessary in the choice of patients most likely to benefit. Patients need to be well-informed about gaps in the evidence base. Our recommendations support the use of TAVI in the context of strict conditions with respect to patient eligibility, the patient selection process, organizational requirements, and the tracking of patient outcomes with a mandatory registry.
Background As surgical training is evolving and operative exposure is decreasing, new, effective, and experiential learning methods are needed to ensure surgical competency and patient safety. Video ...coaching is an emerging concept in surgery that needs further investigation. Design In this randomized controlled trial conducted at a single teaching hospital, participating residents were filmed performing a side-to-side intestinal anastomosis on cadaveric dog bowel for baseline assessment. The Surgical Video Coaching (SVC) group then participated in a one-on-one video playback coaching and debriefing session with a surgeon, during which constructive feedback was given. The control group went on with their normal clinical duties without coaching or debriefing. All participants were filmed making a second intestinal anastomosis. This was compared to their first anastomosis using a 7-category-validated technical skill global rating scale, the Objective Structured Assessment of Technical Skills. A single independent surgeon who did not participate in coaching or debriefing to the SVC group reviewed all videos. A satisfaction survey was then sent to the residents in the coaching group. Setting Department of Surgery, HôpitalMaisonneuve-Rosemont, tertiary teaching hospital affiliated to the University of Montreal, Canada. Participants General surgery residents from University of Montreal were recruited to take part in this trial. A total of 28 residents were randomized and completed the study. Results After intervention, the SVC group ( n = 14) significantly increased their Objective Structured Assessment of Technical Skills score (mean of differences 3.36, 1.09-5.63, p = 0.007) when compared to the control group ( n = 14) (mean of differences 0.29, p = 0.759). All residents agreed or strongly agreed that video coaching was a time-efficient teaching method. Conclusions Video coaching is an effective and efficient teaching intervention to improve surgical residents’ technical skills.
Objective To better describe the natural history, mode of inheritance, and the epidemiological and clinical features of isolated congenital asplenia, a rare and poorly understood primary ...immunodeficiency. Study design A French national retrospective survey was conducted in hospital pediatric departments. A definitive diagnosis of ICA was based on the presence of Howell-Jolly bodies, a lack of detectable spleen, and no detectable cardiovascular malformation. Results The study included 20 patients (12 males and 8 females) from 10 kindreds neither related to each other nor consanguineous. The diagnosis of ICA was certain in 13 cases (65%) and probable in 7 cases (35%). Ten index cases led to diagnosis of 10 additional cases in relatives. Five cases were sporadic and 15 were familial, suggesting autosomal dominant inheritance. Median age was 12 months at first infection (range, 2-516 months), 11 months at diagnosis of asplenia (range, 0-510 months), and 9.9 years at last follow-up (range, 0.7-52 years). Fifteen patients sustained 18 episodes of invasive bacterial infection, caused mainly by Streptococcus pneumoniae (61%). Outcomes were poor, with 9 patients (45%) dying from fulminant infection. Conclusions ICA is more common than was previously thought, with an autosomal dominant inheritance in at least some kindreds. Relatives of cases of ICA should be evaluated for ICA, as should children and young adults with invasive infection.
We describe the case of a 54-year-old woman admitted to the cardiology ward for the correction of radiation-induced aortic stenosis and coronary artery disease. After careful workup, she underwent ...surgical aortic valve replacement and aortocoronary bypass with venous grafts. This case demonstrates the late cardiovascular complications that can develop after radiation therapy for cancer, and the surgical complexity of these patients. Thorough workup is needed for the treatment of radiation-induced valvulopathy and coronary artery disease, as these patients are often poor surgical candidates with hostile chests. Multidisciplinary heart-team assessment is paramount, and consideration should be given to catheter-based approaches. RÉsumÉ: Nous décrivons le cas d’une femme de 54 ans admise en cardiologie pour la correction d’une sténose aortique radio-induite et une coronaropathie. Après un bilan minutieux, elle a subi un remplacement valvulaire aortique chirurgical et un pontage aortocoronarien à l’aide de greffons veineux. Ce cas démontre les complications cardiovasculaires tardives qui peuvent survenir après la radiothérapie administrée pour un cancer, et la complexité de l’intervention chirurgicale de ces patients. Un bilan complet est nécessaire avant le traitement de la valvulopathie radio-induite et de la coronaropathie, puisque ces patients sont souvent de mauvais candidats à l’intervention chirurgicale en raison de thorax « hostiles ». Il est primordial que l’équipe multidisciplinaire en cardiologie réalise l’évaluation et il faudrait envisager les approches par cathéter.
KRAS mutations are detected in 20% to 30% of NSCLC. However, KRAS mutation subtypes may differently influence the outcome of patients with advanced NSCLC.
In the Biomarkers France study, 4894 KRAS ...mutations (26.2%) were detected in 4634 patients from the 17,664 enrolled patients with NSCLC. Survival and treatment data on noncurative stage III to IV NSCLC were available for 901 patients. First- and second-line treatment effects on progression-free survival and overall survival were analyzed according to the KRAS mutations subtype.
Over 95% of patients with KRAS mutation were smokers or former smokers who were white (99.5%), presenting with adenocarcinoma (82.5%). The most common KRAS mutation subtype was G12C (374 patients; 41.5%), followed by G12V (168; 18.6%), G12D (131; 14.5%), G12A (62; 6.9%), G13C (45; 5.0%), G13D (31; 3.4%), and others (10; 1%). Approximately 21% of patients had transition mutation and 68.2% had a transversion mutation. G12D and transition mutations were predominant in never-smokers. The median overall survival for patients with KRAS-mutated NSCLC was 8.1 months (95% confidence interval CI: 7.5–9.5), without any differences according to the different KRAS subtypes mutations. The median progression-free survival was 4.6 months (95% CI: 4.2–5.1) for first-line treatment and 4.8 months (95% CI: 4.3–6.8) for second-line treatment, without any differences according to the different KRAS subtypes mutations.
KRAS mutation subtypes influenced neither treatment responses nor outcomes. The KRAS G12C mutation was detected in 41.5% of patients, who are now eligible for potent and specific G12C inhibitors.
Abstract Left ventricular assist devices (LVADs) are used in chronic end-stage heart failure as “bridge to transplantation” (BTT) and, more recently, for transplant-ineligible patients as ...“destination therapy” (DT). We reviewed the evidence on clinical effects and cost-effectiveness of 2 types of continuous-flow LVADs (HeartMate II HM II and HeartWare), for BTT and DT patients. We systematically searched the scientific literature (January 2008-June 2012) and identified 14 clinical studies (approximately 2900 HM II and approximately 200 HeartWare patients), and 3 economic evaluations (HM II) using simulation models. Data were, however, limited to 2-3 studies per outcome. We made policy recommendations on the basis of our systematic review. Although complications after implantation are frequent, LVAD therapy is often highly effective across transplantation eligibility status and device, with 1-year survival reaching 86% for BTT and 78% for DT (compared with 25% for medical therapy). Neither BTT nor DT currently meet traditional cost-effectiveness limits in models using historical data, although BTT is standard practice for a limited number of patients in many regions. We found that BTT and DT as implantation strategies tend to be no longer mutually exclusive. We conclude that evidence is sufficient to support LVAD use, regardless of transplantation eligibility status, as long as patients are carefully selected and program infrastructure and budget are adequate. However, evidence gaps, limitations in economic models, and the lack of Canadian data point to the importance of mandatory, systematic monitoring of LVAD use and outcomes.
Time in range (TIR) goals are rarely met in children with type 1 diabetes, except at the cost of increased hypoglycaemia episodes. Our objective was to evaluate the safety and efficiency of the ...Diabeloop DBL4K (Diabeloop, Grenoble, France) hybrid closed-loop system in prepubescent children.
We did a multicentre, open-label, randomised, controlled, non-inferiority, two-session crossover study in the paediatric endocrinology departments of three university hospitals in France and Belgium. Eligible participants were aged 6–12 years with type 1 diabetes for at least 1 year, glycated haemoglobin A1C 9% (75 mmol/mol) or less, and insulin pump treatment for at least 3 months. Participants were randomly assigned (1:1) to a closed-loop device or sensor-augmented pump (open loop) therapy. Randomisation was by a permuted block randomisation scheme, using an interactive web-based response system, and was stratified on centre (block size 6). The assessed closed-loop device, the Diabeloop for Kids DBL4K hybrid closed-loop system, is an automated blood glucose regulation system composed of a handset, insulin pump, and continuous glucose monitor. The open-loop system is defined as a sensor-augmented pump therapy composed of the usual insulin pump used by the patient and a continuous glucose monitor. A 72-h in-patient period was followed by a 6-week home phase. After a 1-week washout period, the participants crossed over to the other device. The primary outcome, assessed in the intention-to-treat population, was the mean proportion of time spent in hypoglycaemia (3·9 mmol/L <70 mg/dL) during the hospital phase, with a non-inferiority margin of –2·5% (absolute value). Safety was assessed in the intention-to-treat population on a per-protocol basis. This study was registered with ClinicalTrials.gov, NCT03671915.
Between May 6 and Dec 23, 2019, we included 21 participants (closed loop then open loop, n=10; open loop then closed loop, n=11). The proportion of time spent in hypoglycaemia was significantly lower with the closed-loop system than the open-loop system in both groups (2·04% 95% CI 0·44 to 3·64 vs 7·06% 5·46 to 8·66; non-inferiority one-sided p<0·0001). No severe ketoacidosis, nor severe hyoglycaemic events or fatal adverse events occurred. All 25 adverse events (18 with the closed-loop system, seven with the open-loop system) were related to the treatment.
The closed-loop Diabeloop system decreased hypoglycaemic episodes and provided good metabolic control in prepubescent children with type 1 diabetes, under real-life conditions. This finding supports the safe use of closed-loop technology in this paediatric population.
Diabeloop.
For the French translation of the abstract see Supplementary Materials section.
Minimum inhibitory concentrations (MICs) of the antifungal agent voriconazole were determined using the Etest
® and compared with those of amphotericin B, itraconazole and fluconazole using 1986 ...clinical isolates of
Candida spp. Voriconazole MICs were also compared with those of amphotericin B and itraconazole using 391 clinical isolates of
Aspergillus spp. Voriconazole was found to have more potent activity and lower MIC values than amphotericin B, itraconazole and fluconazole against
C. albicans,
C. tropicalis,
C. parapsilosis and
C. kefyr. Against
C. glabrata and
C. krusei, voriconazole was more active than either of the other two azole antifungals but had similar activity to amphotericin B. For species of
Aspergillus, MIC values of voriconazole were lower than those of amphotericin B and itraconazole against
A. fumigatus and
A. flavus, and were similar to those of amphotericin B against
A. niger. Against
A. terreus, MIC values for voriconazole and itraconazole were similar.
A. terreus is known to be resistant to amphotericin B, and this was reflected in higher MIC values compared with those of voriconazole and itraconazole. Voriconazole therefore compares very favourably with other antifungal agents against a large number of clinical isolates of
Candida and
Aspergillus spp.
Objective To study the effectiveness of dimethylglycine (DMG) on oxygen consumption (VO2) in children with Saguenay-Lac-Saint-Jean cytochrome-c oxidase (SLSJ-COX) deficiency (OMIM 220111). Study ...design In a crossover randomized double-blind clinical trial, 5 children with SLSJ-COX deficiency, who were stable and old enough to comply with VO2 measurement, were treated with placebo or DMG for 3 days, and with the alternate treatment after a 2-week washout period. VO2 was measured by indirect calorimetry before and after treatment. Dietary caloric intake was calculated for 3 days before each measurement. Mean caloric intakes per day were 1562 and 1342 kcal·m−2 before and during placebo, 1336 and 1380 before and during DMG, respectively. Results DMG was well tolerated and, in all cases, resulted in markedly increased blood DMG levels (617 + 203 mmol·L−1), versus 0 to 2 mmol·L−1 without treatment. Mean VO2 was lower after administration of either DMG (–1 ± 3 mL·min−1·m−2) or placebo (−6 ± 4), but neither difference was statistically significant. There was no detectable effect of DMG treatment on blood levels of lactate, pyruvate, bicarbonate, or pH. VO2 values of patients (range, 101-135 mL·min−1·m−2) were lower than published norms (150-160 mL·min−1·m−2). Conclusion This study suggests that treatment with DMG does not substantially change VO2 in children with SLSJ-COX deficiency. (J Pediatr 2003;142:62-6)
Minimum inhibitory concentrations (MICs) of the antifungal agent voriconazole were determined using the Etest super(registeredsign) and compared with those of amphotericin B, itraconazole and ...fluconazole using 1986 clinical isolates of Candida spp. Voriconazole MICs were also compared with those of amphotericin B and itraconazole using 391 clinical isolates of Aspergillus spp. Voriconazole was found to have more potent activity and lower MIC values than amphotericin B, itraconazole and fluconazole against C. albicans, C. tropicalis, C. parapsilosis and C. kefyr. Against C. glabrata and C. krusei, voriconazole was more active than either of the other two azole antifungals but had similar activity to amphotericin B. For species of Aspergillus, MIC values of voriconazole were lower than those of amphotericin B and itraconazole against A. fumigatus and A. flavus, and were similar to those of amphotericin B against A. niger. Against A. terreus, MIC values for voriconazole and itraconazole were similar. A. terreus is known to be resistant to amphotericin B, and this was reflected in higher MIC values compared with those of voriconazole and itraconazole. Voriconazole therefore compares very favourably with other antifungal agents against a large number of clinical isolates of Candida and Aspergillus spp.
PDF
