Pharmacogenetics-guided dalcetrapib therapy after an acute coronary syndrome: the dal-GenE trial.

AIMS: In a retrospective analysis of dal-Outcomes, the effect of dalcetrapib on cardiovascular events was influenced by an adenylate cyclase type 9 (ADCY9) gene polymorphism. The dal-GenE study was conducted to test this pharmacogenetic hypothesis. METHODS AND RESULTS: dal-GenE was a double-blind trial in patients with an acute coronary syndrome within 1-3 months and the AA genotype at variant rs1967309 in the ADCY9 gene. A total of 6147 patients were randomly assigned to receive dalcetrapib 600 mg or placebo daily. The primary endpoint was the time from randomization to first occurrence of cardiovascular death, resuscitated cardiac arrest, non-fatal myocardial infarction, or non-fatal stroke. After a median follow-up of 39.9 months, the primary endpoint occurred in 292 (9.5%) of 3071 patients in the dalcetrapib group and 327 (10.6%) of 3076 patients in the placebo group [hazard ratio 0.88; 95% confidence interval (CI) 0.75-1.03; P = 0.12]. The hazard ratios for the components of the primary endpoint were 0.79 (95% CI 0.65-0.96) for myocardial infarction, 0.92 (95% CI 0.64-1.33) for stroke, 1.21 (95% CI 0.91-1.60) for death from cardiovascular causes, and 2.33 (95% CI 0.60-9.02) for resuscitated cardiac arrest. In a pre-specified on-treatment sensitivity analysis, the primary endpoint event rate was 7.8% (236/3015) in the dalcetrapib group and 9.3% (282/3031) in the placebo group (hazard ratio 0.83; 95% CI 0.70-0.98). CONCLUSION: Dalcetrapib did not significantly reduce the risk of occurrence of the primary endpoint of ischaemic cardiovascular events at end of study. A new trial would be needed to test the pharmacogenetic hypothesis that dalcetrapib improves the prognosis of patients with the AA genotype. CLINICAL TRIAL REGISTRATION: Trial registration dal-GenE ClinicalTrials.gov Identifier: NCT02525939.

High Acoustic Impedance and Attenuation Backing for High-Frequency Focused P(VDF-TrFE)-Based Transducers.

Backing materials with tailored acoustic properties are beneficial for miniaturized ultrasonic transducer design. Whereas piezoelectric P(VDF-TrFE) films are common elements in high-frequency (>20 MHz) transducer design, their low coupling coefficient limits their sensitivity. Defining a suitable sensitivity-bandwidth trade-off for miniaturized high-frequency applications requires backings with impedances of >25 MRayl and strongly attenuating to account for miniaturized requirements. The motivation of this work is related to several medical applications such as small animal, skin or eye imaging. Simulations showed that increasing the acoustic impedance of the backing from 4.5 to 25 MRayl increases transducer sensitivity by 5 dB but decreases the bandwidth, which nevertheless remains high enough for the targeted applications. In this paper, porous sintered bronze material with spherically shaped grains, size-adapted for 25-30 MHz frequency, was impregnated with tin or epoxy resin to create multiphasic metallic backings. Microstructural characterizations of these new multiphasic composites showed that impregnation was incomplete and that a third air phase was present. The selected composites, sintered bronze-tin-air and sintered bronze-epoxy-air, at 5-35 MHz characterization, produced attenuation coefficients of 1.2 and >4 dB/mm/MHz and impedances of 32.4 and 26.4 MRayl, respectively. High-impedance composites were adopted as backing (thickness = 2 mm) to fabricate focused single-element P(VDF-TrFE)-based transducers (focal distance = 14 mm). The center frequency was 27 MHz, while the bandwidth at -6 dB was 65% for the sintered-bronze-tin-air-based transducer. We evaluated imaging performance using a pulse-echo system on a tungsten wire (diameter = 25 µm) phantom. Images confirmed the viability of integrating these backings in miniaturized transducers for imaging applications.

Efficacy and Safety of Low-Dose Colchicine after Myocardial Infarction.

BACKGROUND: Experimental and clinical evidence supports the role of inflammation in atherosclerosis and its complications. Colchicine is an orally administered, potent antiinflammatory medication that is indicated for the treatment of gout and pericarditis. METHODS: We performed a randomized, double-blind trial involving patients recruited within 30 days after a myocardial infarction. The patients were randomly assigned to receive either low-dose colchicine (0.5 mg once daily) or placebo. The primary efficacy end point was a composite of death from cardiovascular causes, resuscitated cardiac arrest, myocardial infarction, stroke, or urgent hospitalization for angina leading to coronary revascularization. The components of the primary end point and safety were also assessed. RESULTS: A total of 4745 patients were enrolled; 2366 patients were assigned to the colchicine group, and 2379 to the placebo group. Patients were followed for a median of 22.6 months. The primary end point occurred in 5.5% of the patients in the colchicine group, as compared with 7.1% of those in the placebo group (hazard ratio, 0.77; 95% confidence interval [CI], 0.61 to 0.96; P = 0.02). The hazard ratios were 0.84 (95% CI, 0.46 to 1.52) for death from cardiovascular causes, 0.83 (95% CI, 0.25 to 2.73) for resuscitated cardiac arrest, 0.91 (95% CI, 0.68 to 1.21) for myocardial infarction, 0.26 (95% CI, 0.10 to 0.70) for stroke, and 0.50 (95% CI, 0.31 to 0.81) for urgent hospitalization for angina leading to coronary revascularization. Diarrhea was reported in 9.7% of the patients in the colchicine group and in 8.9% of those in the placebo group (P = 0.35). Pneumonia was reported as a serious adverse event in 0.9% of the patients in the colchicine group and in 0.4% of those in the placebo group (P = 0.03). CONCLUSIONS: Among patients with a recent myocardial infarction, colchicine at a dose of 0.5 mg daily led to a significantly lower risk of ischemic cardiovascular events than placebo. (Funded by the Government of Quebec and others; COLCOT ClinicalTrials.gov number, NCT02551094.).

Endometrial carcinoma molecular subtype correlates with the presence of lymph node metastases.

BACKGROUND: The role of lymph node assessment/dissection (LND) in endometrial cancer (EC) has been debated for decades, with significant practice variation between centers. Molecular classification of EC provides prognostic information and can be accurately performed on preoperative endometrial biopsies. We assessed the association between molecular subtype and lymph node metastases (LNM) in order to determine if this tool could be used to stratify surgical decision making. METHODS: All EC patients undergoing primary staging surgery with planned complete pelvic +/- para-aortic LND from a single institution in the 2015 calendar year were identified, with clinicopathological and outcome data assessed in the context of retrospectively assigned molecular classification. RESULTS: 172 patients were included. Molecular classification of the total cohort showed 21 POLEmut (12.2%), 47 MMRd (27.3%), 74 NSMP (43.1%), and 30 p53abn (17.4%) ECs. Complete pelvic +/- para-aortic LND was performed in 171 of 172 patients, and LNM were found in 31/171 (18.1%). This included macrometastases (19/31), micrometastases (5/31), and isolated tumour cells (ITCs) (7/31). LNM were pelvic only in 83.9%, and pelvic plus para-aortic in 16.1%. There were no isolated para-aortic LNM. Molecular subtype was significantly associated with LNM (p = 0.004). There was a strong association between the presence of LNM and p53abn EC (nodal involvement in 44.8% of cases), with LNM detected in 14.2% of POLEmut, 14.9% of MMRd, and 10.8% of NSMP EC. On multivariate analysis, molecular subtype and preoperative CA 125 > 25 were significantly associated with LNM (p = 0.021 and p = 0.022 respectively) but preoperative grade and histotype were not (p = 0.24). CONCLUSION: EC molecular subtype is significantly associated with the presence of LNM. As molecular classification can be obtained on preoperative diagnostic specimens, this information can be used to guide surgical treatment planning and may reduce the cost and morbidity of unnecessary lymph node staging in EC care.

[18F]FDG-PET CT for the evaluation of native valve endocarditis.

BACKGROUND: We examined the use of [18F]FDG-PET/CT for the diagnosis of native valve endocarditis (NVE). METHODS: PET/CT images in patients with suspected NVE were retrospectively reviewed independently by two experienced physicians blinded to all clinical information. The gold standard consisted of surgical findings, when available, or the modified Duke criteria. RESULTS: Fifty four subjects were included, 31 (57%) with a diagnosis of NVE. [18F]FDG-PET/CT correctly identified 21/31 (67.7%) subjects, yielding a sensitivity and specificity of 68% (95% CI 49-83%) and 100% (95% CI 85-100%), respectively. The sensitivity and specificity of the modified Duke criteria were 48% and 74%, respectively. Positive and negative predictive values of PET were 100% (95% CI 84-100%) and 70% (95% CI 51-84%), respectively. Modifying the Duke criteria to include [18F]FDG-PET positivity as a major criterion increased sensitivity to 77% without affecting specificity and led to the correct reclassification of 8/18 (44.4%) subjects from Possible IE to Definite IE. CONCLUSION: The addition of a positive [18F]FDG-PET/CT as a major criterion in the modified Duke Criteria improved performance of the criteria for the diagnosis of NVE, particularly in those subjects with Possible IE.

Five-Year Experience in the Surgical Treatment of Endometrial Cancer: Comparing Laparotomy with Robotic and Minimally Invasive Hysterectomy.

OBJECTIVES: To compare surgical and oncological outcomes in the treatment of endometrial cancer between laparotomy and minimally invasive surgery. The secondary objective was to determine which MIS approach was the most beneficial. METHODS: This was a single-centre retrospective review of all endometrial cancer surgeries performed between November 1, 2012 and October 31, 2017 in a gynaecologic oncology unit of a university hospital. Descriptive statistics were used to compare histopathologic results and oncological outcomes, and Kaplan-Meier estimates were used to compare survival. RESULTS: A total of 735 cases were reviewed. The majority of patients (77%) underwent either laparotomy (35%) or robotic-assisted hysterectomy (42%); the remaining patients underwent total laparoscopic hysterectomy (12%) or a laparoscopic-assisted vaginal hysterectomy (8.7%). There was a statistically significant overall survival benefit (P = 0.02), a shorter hospital stay (P < 0.0001), and fewer early surgical complications (<30 d; P = 0.0002), as well as a survival benefit in elderly patients (>70 y) in the robotic-assisted hysterectomy group (P = 0.043) than the laparotomy group. Operating time was shorter in the laparotomy group (P < 0.0001). Recurrence rates in stage 1 low-risk disease were similar between groups. CONCLUSION: Minimally invasive surgical approaches, particularly robotic surgery, do not compromise oncologic outcomes, especially for early-stage low-risk disease. In addition, these approaches are associated with fewer early surgical complications and shorter hospital stay, with significantly more same-day discharges. Overall survival and survival in a subgroup of elderly patients were significantly better in the robotic-assisted hysterectomy group.

Low BRCA1 and BRCA2 Germline Mutation Rates in a French-Canadian Population with a Diagnosis of Epithelial Tubo-Ovarian Carcinoma.

OBJECTIVE: Universal genetic testing has become increasingly important in the management of epithelial tubo-ovarian and peritoneal carcinoma. Worldwide, reported incidences of deleterious BRCA mutations vary between 12% and 15%. We sought to evaluate the incidence in our population, given its specific genetic background (French-Canadian ancestry). METHOD: Mainstream genetic testing was implemented in our service in May 2017 and offered to all patients with epithelial tubo-ovarian or peritoneal carcinomas, except mucinous and borderline tumours. Data were prospectively collected in a database and retrospectively analyzed. RESULTS: We tested 222 patients in our centre, of whom 183 (82.4%) had high-grade serous carcinoma (HGSC). Overall, 139 patients had no identified mutation (62.6%). Deleterious BRCA1 and BRCA2 mutations were found in 12 patients (5.4%): 6 had BRCA1, and 6 BRCA2 mutations; 11 of these patients had HGSC. Other non-BRCA mutations (ATM, RAD51C, RAD51D, BRIP1, CDH1, MRE11, MSH6, MUTYH, PALB2, and PMS2) were observed in an additional 20 patients (9.0%), of whom 18 had HGSC. A total of 63 different variants of unknown significance (VUS) were found, of which 4 were in the BRCA1 and BRCA2 genes. Deleterious mutations were not identified in clear cell carcinomas, and only 1 was found in low-grade serous carcinoma. CONCLUSION: In our French-Canadian population, the incidence of deleterious germline BRCA mutations was surprisingly low at 5.4%-less than half that reported in the literature. This may affect patient response to poly (ADP-ribose) polymerase (PARP) inhibitor (PARPi) therapy. Mainstream genetic testing was successfully implemented in our service and facilitated access to genetic testing in our patient population.

High-grade endometrial carcinoma limited to the endometrium or a polyp: is adjuvant treatment necessary?

OBJECTIVE: High-grade endometrial carcinoma limited to the endometrium or a polyp is a rare clinical entity. Currently there is no consensus on standard treatment. Thus, the goal of this study was to evaluate the clinical outcomes of patients with type II endometrial carcinoma without myometrial infiltration or limited to a polyp. METHODS: We retrospectively identified type II endometrial carcinoma (FIGO endometrioid grade 3, serous, clear cell, mixed and carcinosarcoma) with spread limited to the endometrium or a polyp from April 2013 to November 2017. Medical records were reviewed for the following information: age at diagnosis, patient characteristics, type of surgery, histology, stage according to FIGO 2009 classification, adjuvant treatments, and site of recurrence. Descriptive statistics and the Kaplan-Meier estimate were used for analysis. RESULTS: A total of 25 patients with a type II stage IA adenocarcinoma were included. All were surgically staged with total hysterectomy, salpingo-oophorectomy, and lymph nodes assessment. The median age at diagnosis was 69 years. All patients had either disease limited to the endometrium (60%) or a polyp (40%). Only four patients had lymphovascular space invasion (16%). The median follow-up was 44 (range 2-67) months. Six patients (24%) received vault brachytherapy only and all others received no adjuvant treatment after surgery (n=19, 76%). Three patients (12%) experienced recurrences at 15, 21, and 55 months after surgery. Following systemic treatment all are alive and disease-free. The 3-year progression-free survival and overall survival were 91% and 100%, respectively. CONCLUSION: Expectant management with surveillance alone following surgery appears to be safe for patients with high-grade endometrial carcinoma limited to a polyp or the endometrium without myometrial invasion.

An in-home rehabilitation program for the treatment of urinary incontinence symptoms in endometrial cancer survivors: a single-case experimental design study.

INTRODUCTION AND HYPOTHESIS: There is a high prevalence of urinary incontinence among endometrial cancer survivors. They are also known to present with pelvic floor muscle alterations. Evidence on the effects of conservative interventions for the management of UI is scarce. This study aims at verifying the effects of an in-home rehabilitation program, including the use of a mobile technology, to reduce UI severity in endometrial cancer survivors. METHODS: This study used a single-case experimental design with replications. Primary outcome for UI severity was the pad test, and secondary outcomes were the ICIQ-UI SF questionnaire and 3-day bladder diary. Pelvic floor muscle function was assessed using 2D-transperineal ultrasound and intravaginal dynamometry. Adherence was documented using mobile technology and an exercise log. Visual and non-parametric analyses of longitudinal data were conducted. RESULTS: Results show a reduction in UI severity for 87.5% of participants, with a significant relative treatment effect of moderate size (RTE: 0.30). Significant small relative treatment effects were found for the quick contraction and endurance dynamometric tests. CONCLUSION: This study provides new evidence that endometrial cancer survivors can improve the severity of their UI following an in-home rehabilitation program, including the use of a mobile technology. This mode of delivery has the potential to address a gap in access to pelvic floor physiotherapy services for survivors of EC living in rural and remote communities.

Does management of lipid lowering differ between specialists and primary care: Insights from GOAL Canada.

BACKGROUND: We studied whether significant differences in care gaps exist between specialists and primary care physicians (PCPs). METHODS: GOAL Canada enrolled patients with CVD or familial hypercholesterolemia (FH) and LDL-C > 2.0 mmol/L despite maximally tolerated statin therapy. During follow-up, physicians received online reminders of treatment recommendations based on Canadian Guidelines. RESULTS: A total of 177 physicians (58% PCPs) enrolled 2009 patients; approximately half of the patients were enrolled by each physician group. Patients enrolled by specialists were slightly older (mean age 63 years vs 62), female (45% vs 40%), Caucasian (77% vs 65%), and had a slightly higher systolic pressure and lower heart rate. Patients enrolled by specialists had less frequent history of FH, diabetes, hypertension, chronic kidney disease and liver disease but more frequent history of coronary artery disease, atrial fibrillation and premature family history of CVD. There was no significant baseline difference in LDL-C, HDL-C or non-HDL-C, although total cholesterol and triglycerides were slightly higher in patients managed by PCPs. At baseline, PCPs were more likely to use statins (80% vs 73%, P = .0002) and other therapies such as niacin or fibrate (10% vs 6%, P = .0006) but similar use of ezetimibe (24% vs 27%, P = .15). At the end of follow-up, specialists used less statins (70% vs 77%, P = .0005) and other therapies (6% vs 10%, P = .007) but more ezetimibe (45% vs 38%, P = .01) and the same frequency of PCSK9i (28% vs 27%, P = .65). The proportion of patients achieving the recommended LDL-C level of 2.0 mmol/L or below (primary endpoint) was similar at last available visit between specialists and PCPs (44% vs 42%, P = .32). CONCLUSION: Despite minor differences in the clinical profile of their patients, both PCPs and specialists actively participate in the management of lipid-lowering therapy in high-risk CVD patients and experience similar challenges and care gaps.

Time-to-treatment initiation of colchicine and cardiovascular outcomes after myocardial infarction in the Colchicine Cardiovascular Outcomes Trial (COLCOT).

AIMS: The COLchicine Cardiovascular Outcomes Trial (COLCOT) demonstrated the benefits of targeting inflammation after myocardial infarction (MI). We aimed to determine whether time-to-treatment initiation (TTI) influences the beneficial impact of colchicine. METHODS AND RESULTS: In COLCOT, patients were randomly assigned to receive colchicine or placebo within 30 days post-MI. Time-to-treatment initiation was defined as the length of time between the index MI and the initiation of study medication. The primary efficacy endpoint was a composite of cardiovascular death, resuscitated cardiac arrest, MI, stroke, or urgent hospitalization for angina requiring coronary revascularization. The relationship between endpoints and various TTI (<3, 4-7 and >8 days) was examined using multivariable Cox regression models. Amongst the 4661 patients included in this analysis, there were 1193, 720, and 2748 patients, respectively, in the three TTI strata. After a median follow-up of 22.7 months, there was a significant reduction in the incidence of the primary endpoint for patients in whom colchicine was initiated < Day 3 compared with placebo [hazard ratios (HR) = 0.52, 95% confidence intervals (CI) 0.32-0.84], in contrast to patients in whom colchicine was initiated between Days 4 and 7 (HR = 0.96, 95% CI 0.53-1.75) or > Day 8 (HR = 0.82, 95% CI 0.61-1.11). The beneficial effects of early initiation of colchicine were also demonstrated for urgent hospitalization for angina requiring revascularization (HR = 0.35), all coronary revascularization (HR = 0.63), and the composite of cardiovascular death, resuscitated cardiac arrest, MI, or stroke (HR = 0.55, all P < 0.05). CONCLUSION: Patients benefit from early, in-hospital initiation of colchicine after MI. TRIAL REGISTRATION: COLCOT ClinicalTrials.gov number, NCT02551094.

Cardiovascular Efficacy and Safety of Bococizumab in High-Risk Patients.

BACKGROUND: Bococizumab is a humanized monoclonal antibody that inhibits proprotein convertase subtilisin-kexin type 9 (PCSK9) and reduces levels of low-density lipoprotein (LDL) cholesterol. We sought to evaluate the efficacy of bococizumab in patients at high cardiovascular risk. METHODS: In two parallel, multinational trials with different entry criteria for LDL cholesterol levels, we randomly assigned the 27,438 patients in the combined trials to receive bococizumab (at a dose of 150 mg) subcutaneously every 2 weeks or placebo. The primary end point was nonfatal myocardial infarction, nonfatal stroke, hospitalization for unstable angina requiring urgent revascularization, or cardiovascular death; 93% of the patients were receiving statin therapy at baseline. The trials were stopped early after the sponsor elected to discontinue the development of bococizumab owing in part to the development of high rates of antidrug antibodies, as seen in data from other studies in the program. The median follow-up was 10 months. RESULTS: At 14 weeks, patients in the combined trials had a mean change from baseline in LDL cholesterol levels of -56.0% in the bococizumab group and +2.9% in the placebo group, for a between-group difference of -59.0 percentage points (P<0.001) and a median reduction from baseline of 64.2% (P<0.001). In the lower-risk, shorter-duration trial (in which the patients had a baseline LDL cholesterol level of ≥70 mg per deciliter [1.8 mmol per liter] and the median follow-up was 7 months), major cardiovascular events occurred in 173 patients each in the bococizumab group and the placebo group (hazard ratio, 0.99; 95% confidence interval [CI], 0.80 to 1.22; P=0.94). In the higher-risk, longer-duration trial (in which the patients had a baseline LDL cholesterol level of ≥100 mg per deciliter [2.6 mmol per liter] and the median follow-up was 12 months), major cardiovascular events occurred in 179 and 224 patients, respectively (hazard ratio, 0.79; 95% CI, 0.65 to 0.97; P=0.02). The hazard ratio for the primary end point in the combined trials was 0.88 (95% CI, 0.76 to 1.02; P=0.08). Injection-site reactions were more common in the bococizumab group than in the placebo group (10.4% vs. 1.3%, P<0.001). CONCLUSIONS: In two randomized trials comparing the PCSK9 inhibitor bococizumab with placebo, bococizumab had no benefit with respect to major adverse cardiovascular events in the trial involving lower-risk patients but did have a significant benefit in the trial involving higher-risk patients. (Funded by Pfizer; SPIRE-1 and SPIRE-2 ClinicalTrials.gov numbers, NCT01975376 and NCT01975389 .).

Development of a 3D functional assay and identification of biomarkers, predictive for response of high-grade serous ovarian cancer (HGSOC) patients to poly-ADP ribose polymerase inhibitors (PARPis): targeted therapy.

BACKGROUND: Poly(ADP-ribose) polymerase inhibitors (PARPis) specifically target homologous recombination deficiency (HRD) cells and display good therapeutic effect in women with advanced-stage BRCA1/2-mutated breast and epithelial ovarian cancer (EOC). However, about 50% of high grade serous ovarian cancers (HGSOC) present with HRD due to epigenetic BRCA1 inactivation, as well as genetic/epigenetic inactivation(s) of other HR genes, a feature known as "BRCAness". Therefore, there is a potential for extending the use of PARPis to these patients if HR status can be identified. METHODS: We have developed a 3D (spheroid) functional assay to assess the sensitivity of two PARPis (niraparib and olaparib) in ascites-derived primary cell cultures (AsPCs) from HGSOC patients. A method for AsPCs preparation was established based on a matrix (agarose), allowing for easy isolation and successive propagation of monolayer and 3D AsPCs. Based on this method, we performed cytotoxicity assays on 42 AsPCs grown both as monolayers and spheroids. RESULTS: The response to PARPis treatment in monolayer AsPCs, was significantly higher, compared to 3D AsPCs, as 88% and 52% of the monolayer AsPCs displayed sensitivity to niraparib and olaparib respectively, while 66% of the 3D AsPCs were sensitive to niraparib and 38% to olaparib, the latter being more consistent with previous estimates of HRD (40%-60%) in EOC. Moreover, niraparib displayed a significantly stronger cytotoxic effect in both in 3D and monolayer AsPCs, which was confirmed by consecutive analyses of the HR pathway activity (γH2AX foci formation) in PARPis-sensitive and resistant AsPCs. Global gene expression comparison of 6 PARPi-resistant and 6 PARPi-sensitive 3D AsPCs was indicative for the predominant downregulation of numerous genes and networks with previously demonstrated roles in EOC chemoresistance, suggesting that the PARPis-sensitive AsPCs could display enhanced sensitivity to other chemotherapeutic drugs, commonly applied in cancer management. Microarray data validation identified 24 potential gene biomarkers associated with PARPis sensitivity. The differential expression of 7 selected biomarkers was consecutively confirmed by immunohistochemistry in matched EOC tumor samples. CONCLUSION: The application of this assay and the potential biomarkers with possible predictive significance to PARPis therapy of EOC patients now need testing in the setting of a clinical trial.

Tc-99m-pyrophosphate scintigraphy for the diagnosis of ATTR cardiac amyloidosis: Comparison of quantitative and semi-quantitative approaches.

BACKGROUND: ATTR cardiac amyloidosis (CA) can be diagnosed with Tc-99m-PYP scintigraphy. There are two recommended interpretative approaches: the quantitative heart-to-contralateral lung ratio (H/CL) at 1 hour and the semi-quantitative visual system at 3 hours. This study's aim was to compare both approaches and to apply the semi-quantitative method at 1 hour. METHODS: Tc-99m-PYP scans of 122 consecutive subjects were reviewed using both approaches. On 1 hour planar images, regions of interest were drawn over the heart and contralateral chest to determine H/CL. Myocardial uptake was graded on 1 and 3 hour SPECT images according to the semi-quantitative method. Concordance was examined using kappa statistics. RESULTS: 31, 10, and 81 studies were positive, negative, and equivocal, respectively, for ATTR-CA using the H/CL approach. Using the grading system, 35, 77, and 10 scans were positive, negative, and equivocal, respectively. The quantitative approach led to a significantly higher proportion of equivocal studies compared to the semi-quantitative approach (P < .0001). These approaches yielded discordant results in 2 subjects; biopsy results were concordant with SPECT grade. 1 and 3 hour SPECT grades provided concordant result in 99% of cases. CONCLUSIONS: The H/CL approach resulted in a high proportion of equivocal studies. Using SPECT imaging, the semi-quantitative approach minimized this proportion and showed high concordance at 1 and 3 hours.

Simple vaginal trachelectomy in women with early-stage low-risk cervical cancer who wish to preserve fertility: the new standard of care?

OBJECTIVE: There is a trend toward less radical surgery in women with small-volume disease who wish to preserve fertility. The objective of our study was to evaluate the oncologic and obstetrical outcome of simple vaginal trachelectomy and lymph node assessment in patients with low-risk early-stage cervical cancer (<2 cm). METHODS: From May 2007 to January 2020, 50 patients underwent a simple vaginal trachelectomy/conization with laparoscopic sentinel lymph node mapping±complete pelvic node dissection. Patients underwent loop electrocautery excision (LEEP), cone/cervical biopsies, or simple trachelectomy. A preoperative pelvic MRI with gadolinium contrast was systematically performed in all cases. The size of the lesion was established by review of the LEEP, cone or trachelectomy specimen, MRI, and clinical examination. Data was collected prospectively in a computerized database. Descriptive statistics and the Kaplan-Meier estimate were used for analysis. RESULTS: The median age was 29 years (range: 21-44) and 35 (70%) patients were nulliparous. As per FIGO 2009 classification, 11 patients had stage IA1 with lymphovascular space invasion (LVSI), 13 patients had stage IA2, and 26 patients had stage IB1. Twenty-six patients had squamous histology, 20 patients adenocarcinoma, and four patients other histologies. On final pathology, lymph nodes were negative in 46 patients (92%), three patients had isolated tumor cells, and one patient had micrometastasis. Thirty patients (60%) had either no residual disease in the trachelectomy specimen (22) or residual dysplasia only (eight). With a median follow-up of 76 months (range: 1-140), only one local recurrence occurred which was treated initially with chemoradiation. She recurred again locally and underwent a pelvic exenteration: the patient progressed again and died of disease. The 5-year progression-free survival and overall survival was 97.9% and 97.6%, respectively. There were 40 pregnancies: five (12.5%) ended in the first trimester, one (2.5%) in the second trimester, and three (7.5%) were late preterm: all the others (30 or 75%) delivered >36 weeks and one pregnancy is ongoing. CONCLUSION: Simple trachelectomy/conization and lymph node assessment is an oncologically safe fertility-preserving surgery in well-selected patients with low-risk early-stage cervical cancer (<2 cm). Obstetrical outcomes are comparable to the general population.

Reprint of: Psychosocial factors associated with pharmacists' antidepressant drug treatment monitoring.

OBJECTIVE: Patients undergoing antidepressant drug treatment (ADT) may face challenges regarding its adverse effects, adherence, and efficacy. Community pharmacists are well positioned to manage ADT-related problems. Little is known about the factors influencing pharmacists' ADT monitoring. This study aimed to identify the psychosocial factors associated with pharmacists' intention to perform systematic ADT monitoring and report on this monitoring. DESIGN: Cross-sectional study based on the Theory of Planned Behavior (TPB). SETTING AND PARTICIPANTS: Community pharmacists in the province of Quebec, Canada. OUTCOME MEASURES: Pharmacists completed a questionnaire on their performance of ADT monitoring, TPB constructs (intention; attitude; subjective norm; perceived behavioral control; and attitudinal, normative, and control beliefs), and professional identity. Systematic ADT monitoring was defined as pharmacists' reporting 4 or more consultations with each patient during the first year of ADT to address adverse effects, adherence, and efficacy. Hierarchical linear regression models were used to identify the factors associated with the intention and reporting of systematic ADT monitoring and Poisson working models to identify the beliefs associated with intention. RESULTS: A total of 1609 pharmacists completed the questionnaire (participation = 29.6%). Systematic ADT monitoring was not widely reported (mean score = 2.0 out of 5.0), and intention was moderate (mean = 3.2). Pharmacists' intention was the sole psychosocial factor associated with reporting systematic ADT monitoring (P < 0.0001; R2 = 0.370). All TPB constructs and professional identity were associated with intention (P < 0.0001; R2 = 0.611). Perceived behavioral control had the strongest association. CONCLUSION: Interventions to promote systematic ADT monitoring should focus on developing a strong intention among pharmacists, which could, in turn, influence their practice. To influence intention, priority should be given to ensuring that pharmacists feel capable of performing this monitoring. The main barriers to overcome were the presence of only 1 pharmacist at work and limited time. Other factors identified offer complementary intervention targets.

Psychosocial factors associated with pharmacists' antidepressant drug treatment monitoring.

OBJECTIVE: Patients undergoing antidepressant drug treatment (ADT) may face challenges regarding its adverse effects, adherence, and efficacy. Community pharmacists are well positioned to manage ADT-related problems. Little is known about the factors influencing pharmacists' ADT monitoring. This study aimed to identify the psychosocial factors associated with pharmacists' intention to perform systematic ADT monitoring and report on this monitoring. DESIGN: Cross-sectional study based on the Theory of Planned Behavior (TPB). SETTING AND PARTICIPANTS: Community pharmacists in the province of Quebec, Canada. OUTCOME MEASURES: Pharmacists completed a questionnaire on their performance of ADT monitoring, TPB constructs (intention; attitude; subjective norm; perceived behavioral control; and attitudinal, normative, and control beliefs), and professional identity. Systematic ADT monitoring was defined as pharmacists' reporting 4 or more consultations with each patient during the first year of ADT to address adverse effects, adherence, and efficacy. Hierarchical linear regression models were used to identify the factors associated with the intention and reporting of systematic ADT monitoring and Poisson working models to identify the beliefs associated with intention. RESULTS: A total of 1609 pharmacists completed the questionnaire (participation = 29.6%). Systematic ADT monitoring was not widely reported (mean score = 2.0 out of 5.0), and intention was moderate (mean = 3.2). Pharmacists' intention was the sole psychosocial factor associated with reporting systematic ADT monitoring (P < 0.0001; R2 = 0.370). All TPB constructs and professional identity were associated with intention (P < 0.0001; R2 = 0.611). Perceived behavioral control had the strongest association. CONCLUSION: Interventions to promote systematic ADT monitoring should focus on developing a strong intention among pharmacists, which could, in turn, influence their practice. To influence intention, priority should be given to ensuring that pharmacists feel capable of performing this monitoring. The main barriers to overcome were the presence of only 1 pharmacist at work and limited time. Other factors identified offer complementary intervention targets.

Assessment of left ventricular ejection fraction with cardiofocal collimators: Comparison between IQ-SPECT, planar equilibrium radionuclide angiography, and cardiac magnetic resonance.

BACKGROUND: IQ-SPECT has been shown to significantly reduce acquisition time and administered dose while preserving image quality in myocardial perfusion imaging. Whether IQ-SPECT provides accurate left ventricular ejection fractions (LVEF) with gated blood pool SPECT (GBPS) remains unknown. METHODS: Sixty patients underwent IQ-SPECT GBPS and planar imaging. Among those patients, 11 underwent both cMRI and GBPS. GBPS LVEF, LVEDV, and LVESV were calculated using 2 validated software; QBS (Cedars-Sinai Medical Center, Los Angeles, USA) and MHI (Montreal Heart Institute, Montreal, Canada). LVEF, LVEDV, and LVESV obtained with the different modalities were compared. RESULTS: Average planar LVEF was 48 ± 11% (mean ± SD), average LVEDV was 177 ± 59 mL (range 63 to 342 mL), and average LVESV was 96 ± 46 mL (range 16 to 234 mL). GBPS LVEF and their correlation coefficient with planar LVEF were 40 ± 12% (r = 0.70) and 44 ± 12% (r = 0.83) with QBS and MHI, respectively. Correlation coefficient between cMRI and planar LVEF was 0.65 and were 0.69 and 0.52 between cMRI and GBPS using QBS and MHI, respectively. CONCLUSIONS: LVEF calculated with GBPS using IQ-SPECT correlates with planar measurements. Correlation is best using the MHI method and variation is independent of LVEDV.

Risk of pulmonary toxicity of bleomycin and filgrastim.

OBJECTIVES: To estimate the relative risk of pulmonary toxicity in patients exposed to a bleomycin-based chemotherapy including filgrastim compared to a similar chemotherapy without filgrastim. METHODS: We conducted a nested case-control study of patients treated with BEP (bleomycin, etoposide and cisplatin) for germ cell cancer or with ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine) for Hodgkin's lymphoma at the Hôtel-Dieu de Lévis Hospital between 31 October 2000 and 30 June 2016. The relative risk was estimated by an adjusted odds ratio (aOR) using a propensity score-adjusted regression analysis. RESULTS: Thirteen cases of pulmonary toxicity, representing 14.7% of the 88 patients included in the study, were matched with 65 controls. A higher proportion of women (31.8%) than men (11.3%) developed pulmonary toxicity although the difference was not statistically significant (P = 0.08). Within the cohort, two deaths related to lung toxicity were observed among cases where no filgrastim was used. The risk of pulmonary toxicity associated with the addition of filgrastim was not statistically significant (aOR = 2.48 95% CI = 0.50 to 12.19). CONCLUSION: The results add further evidence that the concomitant use of filgrastim might not increase the risk of pulmonary toxicity of bleomycin. It also suggests that female patients might be more likely to develop this adverse effect. A clinical trial would be needed to confirm this result.

Effectiveness of an Enhanced Recovery After Surgery Program in Gynaecology Oncologic Surgery: A Single-Centre Prospective Cohort Study.

OBJECTIVE: This study sought to evaluate whether the partial implementation of an Early Recovery After Surgery (ERAS) program lowers length of hospital stay (LOS) without compromising postoperative outcome. METHODS: A single-centre prospective cohort study was conducted in a tertiary gynaecologic oncology department, by comparing standard perioperative care with a partially implemented ERAS protocol. Data on postoperative evolution were gathered for patients who underwent laparotomy for suspected or confirmed endometrial, adnexal, or cervical neoplasia between July 1, 2015 and June 30, 2017 at the Hôtel-Dieu de Québec. RESULTS: A total of 390 cases were identified; 140 patients followed the ERAS protocol, and 250 patients received standard perioperative care. The median LOS in hours was significantly reduced for patients in the ERAS group (65.5 hours [interquartile range 59.8, 71.0] vs. 69.0 hours [interquartile range 64.3, 81.0], P < 0.001). There was no difference in complication rates, neither grade 1 (3% vs. 7%, P = 0.155) nor grades 2 to 4 (7% vs. 5%, P = 0.577), or in readmission rates (0.7% vs. 1.2%, P > 0.99). CONCLUSION: Even a partially implemented ERAS program can significantly affect LOS without compromising patient care.