Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 71
Filter
1.
Gynecol Oncol ; 187: 221-226, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38821039

ABSTRACT

OBJECTIVE: Due to limited data on homologous recombination deficiency (HRD) in older patients (≥ 70 years) with advanced stage high grade serous ovarian cancer (HGSC), we aimed to determine the rates of HRD at diagnosis in this age group. METHODS: From the Phase 3 trial VELIA the frequency of HRD and BRCA1/2 pathogenic variants (PVs) was compared between younger (< 70 years) and older participants. HRD and somatic(s) BRCA1/2 pathogenic variants (PVs) were determined at diagnosis using Myriad myChoice® CDx and germline(g) BRCA1/2 PVs using Myriad BRACAnalysis CDx®. HRD was defined if a BRCA PV was present, or the genomic instability score (GIS) met threshold (GIS ≥ 33 & ≥ 42 analyzed). RESULTS: Of 1140 participants, 21% were ≥ 70 years. In total, 26% (n = 298) had a BRCA1/2 PV and HRD, 29% (n = 329) were HRD/BRCA wild-type, 33% (n = 372) non-HRD, and 12% HR-status unknown (n = 141). HRD rates were higher in younger participants, 59% (n = 476/802), compared to 40% (n = 78/197) of older participants (GIS ≥ 42) [p < 0.001]; similar rates demonstrated with GIS ≥ 33, 66% vs 48% [p < 0.001]. gBRCA PVs observed in 24% younger vs 8% of older participants (p < 0.001); sBRCA in 8% vs 10% (p = 0.2559), and HRD (GIS ≥ 42) not due to gBRCA was 35% vs 31% (p = 0.36). CONCLUSIONS: HRD frequency was similar in participants aged < 70 and ≥ 70 years (35% vs 31%) when the contribution of gBRCA was excluded; rates of sBRCA PVs were also similar (8% v 10%), thus underscoring the importance of HRD and BRCA testing at diagnosis in older patients with advanced HGSC given the therapeutic implications.

2.
Gynecol Oncol Rep ; 53: 101390, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38623268

ABSTRACT

Endometrial cancer is the most common gynecologic malignancy in the United States, with a prevalence of 25.7 per 100,000 women per year (Mahdy et al., 2023). Recurrences of endometrial carcinoma have a mean interval of occurring 2-3 years after primary treatment, with 64 % of cases occurring within 2 years and 87 % by the third year (Kurra et al., 2013). The most common sites of recurrence include the pelvis, pelvic and para-aortic lymph nodes, peritoneum, and the lungs (Kurra et al., 2013). Here, we describe a 72-year-old female with recurrent Stage IIIA endometrial adenocarcinoma in the gastric mucosa, an unusual location for recurrence of this type of cancer.

3.
Int J Gynecol Cancer ; 33(9): 1458-1463, 2023 09 04.
Article in English | MEDLINE | ID: mdl-37666539

ABSTRACT

BACKGROUND: Treatment options for patients with platinum-resistant/refractory ovarian cancers are limited and only marginally effective. The development of novel, more effective therapies addresses a critical unmet medical need. Olvimulogene nanivacirepvec (Olvi-Vec), with its strong immune modulating effect on the tumor microenvironment, may provide re-sensitization to platinum and clinically reverse platinum resistance or refractoriness in platinum-resistant/refractory ovarian cancer. PRIMARY OBJECTIVE: The primary objective is to evaluate the efficacy of intra-peritoneal Olvi-Vec followed by platinum-based chemotherapy and bevacizumab in patients with platinum-resistant/refractory ovarian cancer. STUDY HYPOTHESIS: This phase III study investigates Olvi-Vec oncolytic immunotherapy followed by platinum-based chemotherapy and bevacizumab as an immunochemotherapy evaluating the hypothesis that such sequential combination therapy will prolong progression-free survival (PFS) and bring other clinical benefits compared with treatment with platinum-based chemotherapy and bevacizumab. TRIAL DESIGN: This is a multicenter, prospective, randomized, and active-controlled phase III trial. Patients will be randomized 2:1 into the experimental arm treated with Olvi-Vec followed by platinum-doublet chemotherapy and bevacizumab or the control arm treated with platinum-doublet chemotherapy and bevacizumab. MAJOR INCLUSION/EXCLUSION CRITERIA: Eligible patients must have recurrent, platinum-resistant/refractory, non-resectable high-grade serous, endometrioid, or clear-cell ovarian, fallopian tube, or primary peritoneal cancer. Patients must have had ≥3 lines of prior chemotherapy. PRIMARY ENDPOINT: The primary endpoint is PFS in the intention-to-treat population. SAMPLE SIZE: Approximately 186 patients (approximately 124 patients randomized to the experimental arm and 62 to the control arm) will be enrolled to capture 127 PFS events. ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: Expected complete accrual in 2024 with presentation of primary endpoint results in 2025. TRIAL REGISTRATION: NCT05281471.


Subject(s)
Ovarian Neoplasms , Viral Vaccines , Humans , Female , Bevacizumab , Prospective Studies , Carcinoma, Ovarian Epithelial , Platinum , Ovarian Neoplasms/drug therapy , Tumor Microenvironment
4.
Gynecol Oncol ; 171: 141-150, 2023 04.
Article in English | MEDLINE | ID: mdl-36898292

ABSTRACT

OBJECTIVE: To determine whether a non­platinum chemotherapy doublet improves overall survival (OS) among patients with recurrent/metastatic cervical carcinoma. METHODS: Gynecologic Oncology Group protocol 240 is a phase 3, randomized, open-label, clinical trial that studied the efficacy of paclitaxel 175 mg/m2 plus topotecan 0.75 mg/m2 days 1-3 (n = 223) vs cisplatin 50 mg/m2 plus paclitaxel 135 or 175 mg/m2 (n = 229), in 452 patients with recurrent/metastatic cervical cancer. Each chemotherapy doublet was also studied with and without bevacizumab (15 mg/kg). Cycles were repeated every 21 days until progression, unacceptable toxicity, or complete response. The primary endpoints were OS and the frequency and severity of adverse effects. We report the final analysis of OS. RESULTS: At the protocol-specified final analysis, median OS was 16.3 (cisplatin-paclitaxel backbone) and 13.8 months (topotecan-paclitaxel backbone) (HR 1.12; 95% CI, 0.91-1.38; p = 0.28). Median OS for cisplatin-paclitaxel and topotecan-paclitaxel was 15 vs 12 months, respectively (HR 1.10; 95% CI,0.82-1.48; p = 0.52), and for cisplatin-paclitaxel-bevacizumab and topotecan-paclitaxel-bevacizumab was 17.5 vs 16.2 months, respectively (HR 1.16; 95% CI, 0.86-1.56; p = 0.34). Among the 75% of patients in the study population previously exposed to platinum, median OS was 14.6 (cisplatin-paclitaxel backbone) vs 12.9 months (topotecan-paclitaxel backbone), respectively (HR 1.09; 95% CI, 0.86-1.38;p = 0.48). Post-progression survival was 7.9 (cisplatin-paclitaxel backbone) vs 8.1 months (topotecan-paclitaxel backbone) (HR 0.95; 95% CI, 0.75-1.19). Grade 4 hematologic toxicity was similar between chemotherapy backbones. CONCLUSIONS: Topotecan plus paclitaxel does not confer a survival benefit to women with recurrent/metastatic cervical cancer, even among platinum-exposed patients. Topotecan-paclitaxel should not be routinely recommended in this population. NCT00803062.


Subject(s)
Paclitaxel , Topotecan , Uterine Cervical Neoplasms , Survival Analysis , Topotecan/therapeutic use , Paclitaxel/therapeutic use , Uterine Cervical Neoplasms/drug therapy , Uterine Cervical Neoplasms/mortality , Humans , Female , Cisplatin/therapeutic use , Bevacizumab/therapeutic use , Young Adult , Adult , Middle Aged , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/therapeutic use
5.
Clin Cancer Res ; 29(9): 1698-1707, 2023 05 01.
Article in English | MEDLINE | ID: mdl-36595569

ABSTRACT

PURPOSE: To explore whether patients with BRCA1/2-mutated or homologous recombination deficient (HRD) ovarian cancers benefitted from atezolizumab in the phase III IMagyn050 (NCT03038100) trial. PATIENTS AND METHODS: Patients with newly diagnosed ovarian cancer were randomized to either atezolizumab or placebo with standard chemotherapy and bevacizumab. Programmed death-ligand 1 (PD-L1) status of tumor-infiltrating immune cells (IC) was determined centrally (VENTANA SP142 assay). Genomic alterations, including deleterious BRCA1/2 alterations, genomic loss of heterozygosity (gLOH), tumor mutation burden (TMB), and microsatellite instability (MSI), were evaluated using the FoundationOne assay. HRD was defined as gLOH ≥ 16%, regardless of BRCA1/2 mutation status. Potential associations between progression-free survival (PFS) and genomic biomarkers were evaluated using standard correlation analyses and log-rank of Kaplan-Meier estimates. RESULTS: Among biomarker-evaluable samples, 22% (234/1,050) harbored BRCA1/2 mutations and 46% (446/980) were HRD. Median TMB was low irrespective of BRCA1/2 or HRD. Only 3% (29/1,024) had TMB ≥10 mut/Mb, and 0.3% (3/1,022) were MSI-high. PFS was better in BRCA2-mutated versus BRCA2-non-mutated tumors and in HRD versus proficient tumors. PD-L1 positivity (≥1% expression on ICs) was associated with HRD but not BRCA1/2 mutations. PFS was not improved by adding atezolizumab in BRCA2-mutated or HRD tumors; there was a trend toward enhanced PFS with atezolizumab in BRCA1-mutated tumors. CONCLUSIONS: Most ovarian tumors have low TMB despite BRCA1/2 mutations or HRD. Neither BRCA1/2 mutation nor HRD predicted enhanced benefit from atezolizumab. This is the first randomized double-blind trial in ovarian cancer demonstrating that genomic instability triggered by BRCA1/2 mutation or HRD is not associated with improved sensitivity to immune checkpoint inhibitors. See related commentary by Al-Rawi et al., p. 1645.


Subject(s)
B7-H1 Antigen , Ovarian Neoplasms , Humans , Female , B7-H1 Antigen/genetics , Mutation , Double-Blind Method , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/genetics , Biomarkers, Tumor/genetics , Biomarkers, Tumor/therapeutic use , Genomics , Immunotherapy
6.
Palliat Med Rep ; 3(1): 80-86, 2022.
Article in English | MEDLINE | ID: mdl-35733444

ABSTRACT

Background: Equipping all interprofessional clinicians with foundational palliative care competencies is essential to address the complex needs of the growing number of adults living with chronic, progressive, or life-threatening serious illness. There is a paucity of high-quality, open-access primary palliative care curricula and to the best of our knowledge, none designed interprofessionally. Objective: As an interprofessional team, we aimed at designing and evaluating an interactive primary palliative care education curriculum for interprofessional clinicians and trainees. Design: We developed a curriculum that includes nine 55-minute interactive modules facilitated by two interprofessional clinicians in small groups of 8-12 interprofessional learners. Setting/Subjects: Thirty-two practicing interprofessional clinicians from the San Francisco Bay Area enrolled in the pilot. Measurements: Pilot curriculum evaluation included electronic surveys pre- and post-module and at completion of the full curriculum. Results: The final evaluation response rate was 44%. Ninety-three percent of survey respondents rated the curriculum's quality as "very good" or "excellent"; 86% of respondents felt the curriculum was "extremely" or "very useful" to their clinical practice. Comparing pre- and post-module survey data, statistically significant (p < 0.01) improvements in learner confidence were seen for each of the 25 curriculum learning objectives with an average improvement of 2.8 points. Conclusions: The curriculum was well received and was associated with an increase in learner confidence. This novel, flexible, and tuition-free curriculum fills an important educational gap and can be used to equip frontline, interprofessional clinicians with the core palliative care knowledge, skills, and attitudes to take the best possible care of seriously ill patients and families.

7.
Gynecol Oncol ; 164(2): 245-253, 2022 02.
Article in English | MEDLINE | ID: mdl-34906376

ABSTRACT

OBJECTIVE: In the Phase 3 VELIA trial (NCT02470585), PARP inhibitor (PARPi) veliparib was combined with first-line chemotherapy and continued as maintenance for patients with ovarian carcinoma enrolled regardless of chemotherapy response or biomarker status. Here, we report exploratory analyses of the impact of homologous recombination deficient (HRD) or proficient (HRP) status on progression-free survival (PFS) and objective response rates during chemotherapy. METHODS: Women with Stage III-IV ovarian carcinoma were randomized to veliparib-throughout, veliparib-combination-only, or placebo. Stratification factors included timing of surgery and germline BRCA mutation status. HRD status was dichotomized at genomic instability score 33. During combination therapy, CA-125 levels were measured at baseline and each cycle; radiographic responses were assessed every 9 weeks. RESULTS: Of 1140 patients randomized, 742 had BRCA wild type (BRCAwt) tumors (HRP, n = 373; HRD/BRCAwt, n = 329). PFS hazard ratios between veliparib-throughout versus control were similar in both BRCAwt populations (HRD/BRCAwt: 22.9 vs 19.8 months; hazard ratio 0.76; 95% confidence interval [CI] 0.53-1.09; HRP: 15.0 vs 11.5 months; hazard ratio 0.765; 95% CI 0.56-1.04). By Cycle 3, the proportion with ≥90% CA-125 reduction from baseline was higher in those receiving veliparib (pooled arms) versus control (34% vs 23%; P = 0.0004); particularly in BRCAwt and HRP subgroups. Complete response rates among patients with measurable disease after surgery were 24% with veliparib (pooled arms) and 18% with control. CONCLUSIONS: These results potentially broaden opportunities for PARPi utilization among patients who would not qualify for frontline PARPi maintenance based on other trials.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Benzimidazoles/therapeutic use , Carcinoma, Ovarian Epithelial/drug therapy , Hereditary Breast and Ovarian Cancer Syndrome/drug therapy , Ovarian Neoplasms/drug therapy , Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use , Recombinational DNA Repair/genetics , Adult , Aged , Aged, 80 and over , Allelic Imbalance/genetics , CA-125 Antigen/metabolism , Carboplatin/administration & dosage , Carcinoma, Ovarian Epithelial/genetics , Carcinoma, Ovarian Epithelial/metabolism , Carcinoma, Ovarian Epithelial/pathology , Cytoreduction Surgical Procedures , Female , Genes, BRCA1 , Genes, BRCA2 , Genomic Instability/genetics , Hereditary Breast and Ovarian Cancer Syndrome/genetics , Hereditary Breast and Ovarian Cancer Syndrome/metabolism , Hereditary Breast and Ovarian Cancer Syndrome/pathology , Humans , Induction Chemotherapy , Loss of Heterozygosity/genetics , Maintenance Chemotherapy , Middle Aged , Neoplasm Staging , Ovarian Neoplasms/genetics , Ovarian Neoplasms/metabolism , Ovarian Neoplasms/pathology , Paclitaxel/administration & dosage , Progression-Free Survival , Proportional Hazards Models , Young Adult
8.
Urol Case Rep ; 39: 101850, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34557384

ABSTRACT

The insertion of a foreign body into the urethra is a delicate matter that may prevent patients from presenting promptly. It can have serious long-term implications. Sexual experimentation and gratification, as well as underlying mental disorders, are considered the main causes of retained foreign bodies in the urethra and bladder. Management varies depending on the shape and size of the object, and the mechanism of insertion. Here we describe the case of a 15-year-old boy who self-inserted a USB wire into his proximal urethra. Manual and endoscopic attempts at removal were unsuccessful. A peno-scrotal urethrostomy was performed.

9.
Front Mol Biosci ; 8: 662888, 2021.
Article in English | MEDLINE | ID: mdl-34026835

ABSTRACT

Culture-independent and meta-omics sequencing methods have shed considerable light on the so-called "microbial dark matter" of Earth's environmental microbiome, improving our understanding of phylogeny, the tree of life, and the vast functional diversity of microorganisms. This influx of sequence data has led to refined and reimagined hypotheses about the role and importance of microbial biomass, that paradoxically, sequencing approaches alone are unable to effectively test. Post-genomic approaches such as metabolomics are providing more sensitive and insightful data to unravel the fundamental operations and intricacies of microbial communities within aquatic systems. We assert that the implementation of integrated post-genomic approaches, specifically metabolomics and metatranscriptomics, is the new frontier of environmental microbiology and ecology, expanding conventional assessments toward a holistic systems biology understanding. Progressing beyond siloed phylogenetic assessments and cataloging of metabolites, toward integrated analysis of expression (metatranscriptomics) and activity (metabolomics) is the most effective approach to provide true insight into microbial contributions toward local and global ecosystem functions. This data in turn creates opportunity for improved regulatory guidelines, biomarker discovery and better integration of modeling frameworks. To that end, critical aquatic environmental issues related to climate change, such as ocean warming and acidification, contamination mitigation, and macro-organism health have reasonable opportunity of being addressed through such an integrative approach. Lastly, we argue that the "post-genomics" paradigm is well served to proactively address the systemic technical issues experienced throughout the genomics revolution and focus on collaborative assessment of field-wide experimental standards of sampling, bioinformatics and statistical treatments.

10.
J Pediatr Surg ; 56(10): 1811-1815, 2021 Oct.
Article in English | MEDLINE | ID: mdl-33789801

ABSTRACT

OBJECTIVE: Children with anorectal malformations (ARM) have a high rate of renal anomalies and increased risk of urinary tract infection (UTI). We aimed to determine whether using routine Micturating Cystourethrogram (MCUG) to detect VUR is effective in reducing the incidence of UTI or renal scarring in children with ARM. METHODS: A retrospective study of consecutive children diagnosed with ARM in two centres with a minimum of 3 years follow-up was performed, excluding those with cloaca or an MCUG prior to ARM repair. Univariate and multivariate logistic regression analysis was used to determine variables which were associated with VUR, UTI and renal scarring. Associations are described as Odd's Ratio (OR), 95% Confidence Interval. Significance was taken as p<0.05. RESULTS: 344 children were included with a median age of 8 years (IQR 5-11 years). 150 (44%) were female. 89 (26%) had renal anomalies and 101 (29%) had spine anomalies. 148 patients had routine MCUG and VUR was found in 62 (42%) of these children. Univariate analysis did not correlate any of the assessed variables with VUR or renal scarring. However, abnormal renal ultrasound - OR 6.18 (95% CI 2.99-13.07, p 0.0001) was associated with UTI whilst abnormal spine - OR 0.27 (95% CI 0.10-0.62, p 0.009), low ARM - OR 0.30 (CI 0.14-0.63, p 0.006) and intermediate ARM - OR 0.35 (CI 0.17-0.70, p 0.01) were associated with a reduced risk of UTI. On multivariate analysis, only abnormal renal USS retained a significant association with UTI (p<0.0001). CONCLUSIONS: VUR is common in patients with ARM. Children with an abnormal R-USS are at increased risk of UTI. Performing routine MCUG does not reduce the risk of UTI in children with ARM.


Subject(s)
Anorectal Malformations , Urinary Tract Infections , Vesico-Ureteral Reflux , Child , Child, Preschool , Female , Humans , Infant , Kidney/diagnostic imaging , Retrospective Studies , Urinary Tract Infections/epidemiology , Urinary Tract Infections/etiology , Urinary Tract Infections/prevention & control , Vesico-Ureteral Reflux/complications
11.
Chemosphere ; 272: 129873, 2021 Jun.
Article in English | MEDLINE | ID: mdl-33592515

ABSTRACT

Cyanobacterial blooms and the associated hepatotoxins produced (e.g., microcystins, MCs) create a significant human health risk in freshwater lakes around the world, including Lake Erie. Though various physical and chemical treatment options are utilized, these are costly and their effectiveness decreases when other organics are present. Laboratory studies have identified a remediation option based on a mlr gene operon that can systematically degrade this toxin; however, studies on Lake Erie have been unable to amplify mlr genes from MC-degrading bacteria. These results suggest that either existing primers may be inefficient for broad identification of the mlr genes or that MC degradation genes and/or pathways may vary among bacterial taxa. To investigate the dynamics of the Lake Erie microbial community involved in the degradation of microcystin-LR (MC-LR), a flow-through column experiment using collected beach sand was conducted over a period of six weeks. Increasing concentrations of lake water spiked with MC-LR were continuously delivered to both biotic and abiotic (sterilized) sand columns, with influent and effluent MC-LR concentrations measured by LC-MS/MS. Despite the toxin concentrations far exceeding natural conditions during a bloom event (maximum dosage = 15.4 µg/L), MC-LR was completely removed within 21 h of contact time in the biotic columns. Stimulation of community taxa during the degradation process included Burkholderiaceae, Illumatobacteraceae, Pseudomonadaceae, Rhodocyclaceae and Nitrosomonadaceae. The overall results suggest several critical species may be required for the most complete and effective degradation of MC-LR.


Subject(s)
Lakes , Microcystins , Chromatography, Liquid , Humans , Marine Toxins , Sand , Tandem Mass Spectrometry
12.
J Palliat Med ; 23(1): 40-47, 2020 01.
Article in English | MEDLINE | ID: mdl-31381469

ABSTRACT

Background: Communication training is a hallmark of palliative care education. The purpose of this article is to report on the development, exploratory outcomes, and lessons learned from a pilot project, "TeamTalk," which adapted VitalTalk methodology for interprofessional learners. Materials and Methods: TeamTalk included a series of interactive workshops led by an interprofessional faculty team at a health sciences university. Teaching methods were small group discussion, reflection, and high-fidelity simulated patient/family encounters, using a "Skills and Capacities" handout. The course was offered between January and May of 2015 and 2016 to medical fellows, advanced practice nursing students, and chaplain interns. Pre- and post-test design and qualitative data analysis were used to assess the learners' response to the TeamTalk curriculum. Validated instruments assessed attitudes toward interprofessional collaboration and self-confidence for interprofessional communication. Results: Sixty-one learners participated in TeamTalk over two academic years. Attitudes toward interprofessional collaboration improved from pre- to post-test (126.1 ± 6.9-130.0 ± 7.1; p < 0.01) with no difference among the professional groups. Self-confidence for interprofessional communication improved in "eliciting the contributions of colleagues, including those from other disciplines" (p < 0.001) for all learners during year two; chaplains improved in the greatest number of areas (15/19), followed by nurses (7/19) and physicians (4/19). Learners expressed appreciation for the opportunity to explore their professional roles together with other professions. Conclusion: Preliminary findings indicate that TeamTalk improved attitudes toward interprofessional collaboration and self-confidence for participating on an interprofessional team. The lessons derived from creating and implementing this course may be applicable to interprofessional education in serious illness management.


Subject(s)
Education, Nursing , Interprofessional Relations , Communication , Cooperative Behavior , Curriculum , Humans , Patient Care Team , Pilot Projects
13.
Article in English | MEDLINE | ID: mdl-31480371

ABSTRACT

Physical activity levels decline, and screen-viewing behaviours increase during childhood and adolescence. The transition to secondary school appears to coincide with a sharp decline in physical activity. Parents have the potential to influence their child's behaviours, yet little is known about their expectations for their child's physical activity and screen-viewing during this transition. This paper explores parents' expectations for their children's physical activity and screen-viewing as they transition from primary to secondary school, and their proposed strategies for managing these behaviours during this time. Forty-two parents of children aged 10-11 years participated in a semi-structured telephone interviews in July 2017 or March 2018. The interview data were analysed via inductive and deductive content analysis to explore parents' perceptions of physical activity and screen-viewing during the transition, the reasons for their perceptions, and the strategies they intended to implement to help their child balance their behaviours. Most parents expected both physical activity and screen-viewing to increase during this transition. There were several individuals, social and school-level factors influencing these expectations. Overall, parents felt that helping their child balance their activity levels, screen-viewing and homework would be challenging.


Subject(s)
Child Behavior/psychology , Exercise , Motivation , Parents/psychology , Sedentary Behavior , Child , Female , Humans , Male , Schools/classification
14.
Br J Cancer ; 121(3): 211-217, 2019 07.
Article in English | MEDLINE | ID: mdl-31231122

ABSTRACT

BACKGROUND: This exploratory single-arm phase II study evaluated the efficacy and safety of RRx-001 followed by reintroduction of platinum plus etoposide in patients with previously treated small-cell lung cancer (SCLC). METHODS: Patients were treated with RRx-001 4 mg IV on day 1 of each week of a 21-day cycle followed at progression by re-challenge with etoposide 80-100 IV mg/m2 on days 1, 2 and 3 and cisplatin 60-80 mg/m2 IV on day 1 or carboplatin AUC 5-6 IV on day 1, every 21 days. The primary end points were overall survival (OS) and overall response rate to platinum regimen. RESULTS: Twenty-six patients were enroled and received at least one dose of RRx-001. The median number of prior lines of therapy was 2 (range 1-9) and 19 (73.1%) patients had platinum-resistant disease. In the intention-to-treat population, one patient (3.8%) had complete response and six (23.1%) had partial response on platinum plus etoposide. The estimated median and 12-month OS from enrolment were 8.6 months and 44.1%, respectively. The most common treatment-emergent adverse event from RRx-001 was mild discomfort at the infusion site (23%). CONCLUSIONS: RRx-001 followed by re-challenge with platinum plus etoposide chemotherapy is feasible and associated with promising results. CLINICAL TRIAL REGISTRATION: NCT02489903.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Lung Neoplasms/drug therapy , Small Cell Lung Carcinoma/drug therapy , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Azetidines/administration & dosage , Carboplatin/administration & dosage , Cisplatin/administration & dosage , Etoposide/administration & dosage , Female , Humans , Lung Neoplasms/mortality , Male , Middle Aged , Nitro Compounds/administration & dosage , Small Cell Lung Carcinoma/mortality
15.
Article in English | MEDLINE | ID: mdl-31091825

ABSTRACT

Children's physical activity decreases during school holidays. Less structured days and reduced participation in organised activities may account for some of the decrease. Little is known about the factors that influence parents' decision to enrol their child in organised activity such as holiday clubs. This paper sought to explore parents' perceptions of their child's physical activity during school holidays and the factors that influence holiday activity-based decision making. Semi-structured telephone interviews were conducted with 42 parents of children aged 10-11 years in July 2017 or March 2018. Data were analysed using a combination of inductive and deductive content analysis to explore parents' perceptions of holiday-based physical activity and the factors associated with how they provide physical activity opportunities for their children. The data revealed that most parents consider their child's physical activity levels when planning for the school holidays. However, work commitments in the holidays meant many parents had to rely on both informal and formal childcare. Grandparents were the primary source of informal childcare, despite a perception that children were not as physically active when with them. Holiday clubs were also a viable option, but the cost, location and age-appropriateness of provision inhibit parents signing older children up to these regularly.


Subject(s)
Exercise , Holidays , Parents/psychology , Adult , Child , Decision Making , Female , Humans , Male , Middle Aged , Perception , Schools
16.
Sci Total Environ ; 665: 113-124, 2019 May 15.
Article in English | MEDLINE | ID: mdl-30772540

ABSTRACT

The success and sustainability of aquatic ecosystems are driven by the complex, cooperative metabolism of microbes. Ecological engineering strategies often strive to harness this syntrophic synergy of microbial metabolism for the reclamation of contaminated environments worldwide. Currently, there is a significant knowledge gap in our understanding of how the natural microbial ecology overcomes thermodynamic limitations in recovering contaminated environments. Here, we used in-situ metatranscriptomics and associated metataxonomic analyses on sediments collected from naturalized freshwater man-made reservoirs within the Athabasca Oil Sands region of Alberta, Canada. These reservoirs are unique since they are untouched by industrial mining processes and serve as representative endpoints for model landscape reconstruction. Results indicate that a microbial syntrophic cooperation has been established represented by the oxygenic and anoxygenic phototrophs, sustained through the efficient use of novel cellular mechanistic adaptations tailored to these unique thermodynamic conditions. Specifically, chemotaxis transcripts (cheY & MCPs-methyl-accepting chemotaxis proteins) were highly expressed, suggesting a highly active microbial response to gradients in environmental stimuli, resulting indirectly from hydrocarbon compound alteration. A high expression of photosynthetic activity, likely sustaining nutrient delivery to the similarly highly expressed methanogenic community acting in syntrophy during the breakdown of organics. Overall the more diversified functionality within sub-oxic sample locations indicates an ability to maintain efficient metabolism under thermodynamic constraints. This is the first study to holistically identify and characterize these types of in-situ, metabolic processes and address their thermodynamic feasibility within a global context for large landscape reconstruction. These characterizations of regional, natural landscapes surrounding the oil sands mining operation are severely lacking, but truly provide invaluable insight into end-point goals and targets for reclamation procedures.


Subject(s)
Environmental Monitoring , Lakes/chemistry , Oil and Gas Fields , Water Microbiology , Water Pollutants, Chemical/analysis , Alberta , Ecosystem , Eutrophication , Lakes/microbiology , Mining
17.
BMJ Case Rep ; 20182018 Apr 17.
Article in English | MEDLINE | ID: mdl-29666083

ABSTRACT

The use of synthetic mesh in the abdominal compartment has recently become a topic of debate as high profile public cases have called into question their safety. Several case reports have demonstrated significant complications due to intra-abdominal mesh. Furthermore, some studies have suggested that the rates of these severe complications are underestimated. We present the case of a patient who developed an enteroenteric and enterocutaenous fistulae, an abdominal wall collection and an intraperitoneal inflammatory mass from intraluminal migration of a synthetic mesh inserted during laparoscopic incisional hernia repair. We discuss the considerations and complications of using synthetic mesh for ventral hernia repair and discuss the scientific evidence behind the increasingly apparent 'mesh problem'.


Subject(s)
Foreign-Body Migration/surgery , Hernia, Ventral/surgery , Herniorrhaphy , Intestinal Fistula/surgery , Postoperative Complications/surgery , Surgical Mesh/adverse effects , Abdominal Wall , Aged, 80 and over , Female , Foreign-Body Migration/diagnostic imaging , Herniorrhaphy/adverse effects , Humans , Intestinal Fistula/diagnostic imaging , Postoperative Complications/diagnostic imaging , Treatment Outcome
18.
BMC Pediatr ; 18(1): 129, 2018 04 07.
Article in English | MEDLINE | ID: mdl-29626932

ABSTRACT

BACKGROUND: The ubiquity of technology in modern society has led to the American Academy of Pediatrics adapting their screen-viewing (SV) recommendations for children. The revised guidelines encourage families to identify an appropriate balance between SV and other activities. The aims of this study were to explore parents' views of their child's SV time and how important it is for families to achieve a 'digital balance'. METHODS: Semi-structured telephone interviews were conducted with 51 parents of 8-9-year-old children, between July and October 2016. Inductive and deductive content analyses were used to explore parents' perceptions of their child's level of SV (low, medium, high), how parents feel about child SV, and the importance placed on achieving a digital balance. Parent report of child SV behaviours on weekdays and weekend days were assessed via questionnaire. RESULTS: Interview data revealed that because SV is considered the 'norm', parents struggle to limit it, partly because they want their children to be equipped for the modern technological world. While most parents believe SV to have negative effects on children, parents also report advantages to SV. Many parents feel that not all SV is equal, with tablets considered worse than television because of the isolated nature of activities, and educational SV considered more beneficial than non-educational SV. Most parents feel it is important for their family to achieve a digital balance, primarily to spend more quality family time together. Large variation was observed in parents' descriptions of child SV time on weekdays and weekend days. CONCLUSIONS: Parents recognise the importance of digital balance but want their children to fit into the ever-advancing digital world. Parents do not treat all SV equally. Watching television and engaging in educational SV may be encouraged, while 'playing' on tablets is discouraged. These findings highlight the challenge faced by researchers and policy makers to help families achieve a digital balance, and strategies are needed to support parents to plan child SV time.


Subject(s)
Child Behavior , Computers/statistics & numerical data , Fathers/psychology , Mothers/psychology , Perception , Television/statistics & numerical data , Video Games/statistics & numerical data , Adult , Child , Female , Humans , Male , Sedentary Behavior , Surveys and Questionnaires , Time Factors , Video Games/psychology
19.
Water Res ; 136: 1-11, 2018 06 01.
Article in English | MEDLINE | ID: mdl-29486256

ABSTRACT

Baseline biogeochemical surveys of natural environments is an often overlooked field of environmental studies. Too often research begins once contamination has occurred, with a knowledge gap as to how the affected area behaved prior to outside (often anthropogenic) influences. These baseline characterizations can provide insight into proposed bioremediation strategies crucial in cleaning up chemical spill sites or heavily mined regions. Hence, this study was conducted to survey the in-situ microbial activity within freshwater hydrocarbon-rich environments cutting through the McMurray formation - the geologic strata constituting the oil sands. We are the first to report in-situ functional variations among these freshwater microbial ecosystems using metatranscriptomics, providing insight into the in-situ gene expression within these naturally hydrocarbon-rich sites. Key genes involved in energy metabolism (nitrogen, sulfur and methane) and hydrocarbon degradation, including transcripts relating to the observed expression of methane oxidation are reported. This information provides better linkages between hydrocarbon impacted environments, closing knowledge gaps for optimizing not only oil sands mine reclamation but also enhancing microbial reclamation strategies in various freshwater environments. These finding can also be applied to existing contaminated environments, in need of efficient reclamation efforts.


Subject(s)
Bacteria/metabolism , Fresh Water/analysis , Geologic Sediments/chemistry , Hydrocarbons/analysis , Bacteria/genetics , Bacteria/isolation & purification , Biodegradation, Environmental , Ecosystem , Fresh Water/microbiology , Geologic Sediments/microbiology , Hydrocarbons/metabolism , Metagenome , Methane/metabolism , Mining , Petroleum/metabolism
20.
Ecol Lett ; 21(2): 287-295, 2018 02.
Article in English | MEDLINE | ID: mdl-29243313

ABSTRACT

Organisms can modify their surrounding environment, but whether these changes are large enough to feed back and alter their evolutionary trajectories is not well understood, particularly in wild populations. Here we show that nutrient pulses from decomposing Atlantic salmon (Salmo salar) parents alter selection pressures on their offspring with important consequences for their phenotypic and genetic diversity. We found a strong survival advantage to larger eggs and faster juvenile metabolic rates in streams lacking carcasses but not in streams containing this parental nutrient input. Differences in selection intensities led to significant phenotypic divergence in these two traits among stream types. Stronger selection in streams with low parental nutrient input also decreased the number of surviving families compared to streams with high parental nutrient levels. Observed effects of parent-derived nutrients on selection pressures provide experimental evidence for key components of eco-evolutionary feedbacks in wild populations.


Subject(s)
Biological Evolution , Nutrients , Salmon , Animals , Phenotype , Selection, Genetic
SELECTION OF CITATIONS
SEARCH DETAIL
...