Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 76
Filter
Add more filters

Publication year range
1.
Crit Care Med ; 2024 Apr 25.
Article in English | MEDLINE | ID: mdl-38661459

ABSTRACT

OBJECTIVES: To date, age, frailty, and multimorbidity have been used primarily to inform prognosis in older adults. It remains uncertain, however, whether these patient factors may also predict response to critical care interventions or treatment outcomes. DATA SOURCES: We conducted a systematic search of top general medicine and critical care journals for randomized controlled trials (RCTs) examining critical care interventions published between January 1, 2011, and December 31, 2021. STUDY SELECTION: We included RCTs of critical care interventions that examined any one of three subgroups-age, frailty, or multimorbidity. We excluded cluster RCTs, studies that did not report interventions in an ICU, and studies that did not report data examining subgroups of age, frailty, or multimorbidity. DATA EXTRACTION: We collected study characteristics (single vs. multicountry enrollment, single vs. multicenter enrollment, funding, sample size, intervention, comparator, primary outcome and secondary outcomes, length of follow-up), study population (inclusion and exclusion criteria, average age in intervention and comparator groups), and subgroup data. We used the Instrument for assessing the Credibility of Effect Modification Analyses instrument to evaluate the credibility of subgroup findings. DATA SYNTHESIS: Of 2037 unique citations, we included 48 RCTs comprising 50,779 total participants. Seven (14.6%) RCTs found evidence of statistically significant effect modification based on age, whereas none of the multimorbidity or frailty subgroups found evidence of statistically significant subgroup effect. Subgroup credibility ranged from very low to moderate. CONCLUSIONS: Most critical care RCTs do not examine for subgroup effects by frailty or multimorbidity. Although age is more commonly considered, the cut-point is variable, and relative effect modification is rare. Although interventional effects are likely similar across age groups, shared decision-making based on individual patient preferences must remain a priority. RCTs focused specifically on critically ill older adults or those living with frailty and/or multimorbidity are crucial to further address this research question.

2.
Lancet ; 400 Suppl 1: S17, 2022 11.
Article in English | MEDLINE | ID: mdl-36929959

ABSTRACT

BACKGROUND: Food insecurity is an increasingly important public health concern in high-income countries following the 2008 global financial crash, and recently with the COVID-19 pandemic. Food insecurity has been understood as a highly gendered issue, affecting more women than men. As women have more complex nutritional needs because of their menstrual cycle, pregnancy, and breastfeeding, the nutritional impact of food insecurity is also greater for women than for men. This systematic review aims to explore pregnant women's experiences of food insecurity in high-income countries and to understand how food insecurity affects their health, wellbeing, diet, and nutrition. METHODS: We did a systematic review following PRISMA reporting guidelines. A comprehensive search strategy was developed using search terms such as "food insecurity" and "pregnancy outcomes". We searched seven databases (MEDLINE, Embase, Scopus, Web of Science, PsychInfo, ASSIA, and CINAHL), grey literature, reference lists, and citations, as well as contacted authors. No language restrictions were used, and only studies primarily containing data collected from Jan 1, 2008, onwards were included. Database searches were completed in April 2022; supplementary searches are ongoing. Inclusion criteria is based on PECOS. Screening, data extraction, and quality assessment were done by two authors independently. This systematic review is registered on PROSPERO, number CRD42022311669. FINDINGS: 27 studies met the inclusion criteria, with all studies published between 2015 and 2022. 24 (89%) of 27 studies were done in the USA, two (7%) in Canada, and one (4%) in the UK. Outcomes reported include dietary intake or dietary quality during pregnancy (seven [26%] of 27), gestational weight gain (seven [26%]), mental health (five [19%]), pregnancy outcomes including pregnancy complications, preterm birth, or birthweight (five [19%]), and other health outcomes or combination of nutrition, health, and wellbeing (three [11%]). Evidence synthesis is ongoing and will be complete by August, 2022. INTERPRETATION: This systematic review suggests that food insecurity experienced during pregnancy was associated with negative health and nutrition outcomes. The rigorous searches are strengths of this study. A limitation is the restricted focus on studies done from 2008 onward. More research to guide efficient interventions that address food insecurity among pregnant women is needed. FUNDING: None.


Subject(s)
COVID-19 , Premature Birth , Male , Pregnancy , Female , Infant, Newborn , Humans , Pregnant Women , Developed Countries , Pandemics , COVID-19/epidemiology , Pregnancy Outcome
3.
Lancet ; 400 Suppl 1: S78, 2022 11.
Article in English | MEDLINE | ID: mdl-36930026

ABSTRACT

BACKGROUND: The Voluntary Community and Social Enterprise sector has a crucial role in supporting the health and wellbeing of people who are marginalised or who have multiple complex needs. We aimed to understand perceptions of those working in the sector and examine the short-term, medium-term, and long-term effects of COVID-19 on Voluntary Community and Social Enterprise organisations in northern England as they respond to the needs of marginalised communities. This research formed one component of a regional multiagency Health Inequalities Impact Assessment. METHODS: We conducted qualitative focus groups with staff and volunteers from five organisations between March and July, 2021, via a video conferencing platform. Eight of nine focus groups were audio-recorded and transcribed verbatim. One focus group was not recorded due to concerns raised over anonymity and safeguarding, but non-ascribed fieldnotes were taken. Focus group transcripts were analysed using framework analysis. FINDINGS: One organisation supported children and young people; two organisations supported vulnerable women, young people, and families; one organisation supported refugees and asylum seekers, and one organisation supported disadvantaged individuals to improve their mental and physical health and wellbeing. Three central themes were identified: the exacerbation of pre-existing inequalities, adversity, and challenges for vulnerable and marginalised populations; the cost of being flexible, innovative, and agile for Voluntary Community and Social Enterprise staff and volunteers; and the voluntary sector as a lifeline (organisational pride and resilience). INTERPRETATION: The considerable expertise, capacity, and resilience of Voluntary Community and Social Enterprise organisations and the crucial role they have in supporting marginalised communities has been clearly shown in their response to the COVID-19 pandemic. The Voluntary Community and Social Enterprise sector therefore has an essential role in the post-COVID levelling-up agenda. The implications of these findings for service provision are that the Voluntary Community and Social Enterprise sector must be recognised as an integral partner within any effectively functioning local health system and, as such, adequately resourced to safeguard sustainability and to ensure that attempts to involve the sector in addressing the social determinants of health are not jeopardised. FUNDING: National Institute for Health and Care Research (Applied Research Collaboration North East and North Cumbria (grant reference NIHR200173) and Public Health England. SSo is supported by a Health Education England and National Institute for Health and Care Research Integrated Clinical Academic Lecturer award (reference CA-CL-2018-04-ST2-010) and Research Capability Funding, National Health Service North of England Care System Support. VJM is funded by the National Institute for Health and Care Research School for Public Health Research (grant reference PD-SPH-2015).


Subject(s)
COVID-19 , State Medicine , Child , Humans , Female , Adolescent , Pandemics , COVID-19/epidemiology , England/epidemiology , Qualitative Research
4.
Mod Pathol ; 36(4): 100085, 2023 04.
Article in English | MEDLINE | ID: mdl-36788084

ABSTRACT

Endometrial carcinoma (EC) can be divided into 4 prognostic molecular subtypes, and no specific molecular profile (NSMP) type is the most commonly occurring type (∼50%). Although described as having an intermediate to favorable prognosis, this subtype encompasses pathologically and molecularly diverse tumors. We aimed to identify factors associated with outcomes within the NSMP ECs that might be used to stratify prognosis and direct treatment. Clinicopathologic, immunohistochemical, and genetic features of a large series of NSMP EC were used to identify parameters that could identify the subset associated with a very favorable outcome (disease-specific death rate <5% at 5 years, termed low-risk NSMP). A total of 1110 NSMP ECs were profiled. In a univariate analysis, stage, grade, lymphovascular invasion, estrogen receptor (ER) and progesterone receptor (PR) expression, L1CAM overexpression, and mutations in PIK3CA were associated with disease-specific survival. Two critical features, grade and ER expression, identified a low-risk NSMP subset (grade 1-2, ER-positive [>1%], 84% of cases), which showed a 5-year disease-specific death rate of 1.6% across all stages and 1.4% within stage I. The remaining cases (high-risk NSMPs, grade 3, and/or ER-negative status) were responsible for most of the disease-specific deaths (disease-specific death rate at 5 years, 22.9%; hazard ratio compared with that of low-risk NSMPs: 16.3; 95% CI, 8.4-31.7). Within NSMP EC, the low-risk and high-risk categories were of prognostic significance independent of the stage on a multivariate analysis. Low-grade and ER-positive NSMP ECs are a homogeneous low-risk group associated with an exceptionally favorable prognosis in which de-escalation and/or endocrine therapy strategies can be applied. Grade 3 and/or ER-negative status identifies a high-risk NSMP subset, including rare high-grade histotypes (eg, clear cell, dedifferentiated, and mesonephric-like), responsible for most NSMP-related deaths. Subclassification of NSMPs allows for the category of low-risk EC molecular subtypes to be dramatically expanded because it now includes both POLEmut and the much more common low-risk NSMP EC.


Subject(s)
Carcinoma, Endometrioid , Endometrial Neoplasms , Female , Humans , Receptors, Estrogen/metabolism , Endometrial Neoplasms/pathology , Prognosis , Risk Factors , Biomarkers, Tumor/genetics , Carcinoma, Endometrioid/pathology
5.
Cerebellum ; 22(2): 282-294, 2023 Apr.
Article in English | MEDLINE | ID: mdl-35305246

ABSTRACT

Cerebellar cognitive affective syndrome (CCAS) is characterized by deficits in executive functions, language processing, spatial orientation, and affect regulation in patients with cerebellar disease. The symptoms can occur isolated or along with motor and coordination symptoms. The aim of our study was to translate and culturally adapt the CCAS scale to Brazilian Portuguese and validate the scale in our population. We performed a cross-sectional study with patients with primary and secondary ataxia. The study included 111 individuals, aged between 20 and 80 years, of both genders, 20 without cognitive and/or affective complaints who participated in the pre-test phase, 40 with cerebellar disease (hereditary/neurodegenerative ataxia or acquired/secondary cerebellar ataxia), and 51 healthy controls with no evidence of cognitive impairment and no affective symptoms matched for sex, age, and educational level. The scale was translated, culturally adapted, and validated. Statistical analysis of the data was performed, with association tests, mean comparison, and ROC curve analysis. Based on the analysis of the ROC curve, optimal cutoff values ​were found for each subitem of the scale. The translated and adapted scale has good internal consistency, is reproducible, has good reliability, and has the potential to be a reliable tool for screening cognitive symptoms in patients with cerebellar disease.


Subject(s)
Cerebellar Ataxia , Cerebellar Diseases , Spinocerebellar Degenerations , Humans , Male , Female , Young Adult , Adult , Middle Aged , Aged , Aged, 80 and over , Cross-Cultural Comparison , Brazil , Reproducibility of Results , Cross-Sectional Studies , Cerebellar Diseases/complications , Cerebellar Ataxia/complications , Language , Spinocerebellar Degenerations/complications , Ataxia/complications , Cognition/physiology , Surveys and Questionnaires
6.
Gynecol Oncol ; 170: 282-289, 2023 03.
Article in English | MEDLINE | ID: mdl-36753816

ABSTRACT

OBJECTIVES: Recent data support the predictive implications of molecular subtype assignment in endometrial cancer (EC). Our objective was to retrospectively assess clinical outcomes according to adjuvant treatment received within EC molecular subtypes. METHODS: Clinical outcomes (disease-specific and progression-free survival DSS/PFS) of EC patients from a single institution and population-based cohorts that had undergone molecular classification were assessed with respect to adjuvant therapy received and 2016 ESMO risk group. RESULTS: 2472 ECs were assessed; 184 (7.4%) POLEmut, 638 (25.8%) MMRd, 1223 (49.5%) NSMP and 427 (17.3%) p53abn. N = 774 (34.6%) of the cohort were ESMO 2016 high risk and 109 (4.8%) were advanced or metastatic. In patients with MMRd EC, assessed across and within stage, there was no observed benefit in DSS or PFS with the addition of chemotherapy +/- radiation compared to radiation alone in ESMO high risk (p = 0.694) or ESMO high, advanced, metastatic risk groups combined (p = 0.852). In patients with p53abn EC, adjuvant chemotherapy given with radiation was associated with significantly longer DSS compared to radiation alone in ESMO high risk (p = 0.007) and ESMO high, advanced and metastatic risk groups combined (p = 0.015), even when restricted to stage I disease (p < 0.001) and when compared in serous vs. non-serous histotypes (p = 0.009). CONCLUSIONS: Adjuvant chemotherapy is associated with more favorable outcomes for patients with p53abn EC, including stage I disease and non-serous histotypes, but does not appear to add benefit within MMRd ECs for any stage of disease, consistent with PORTEC-3 molecular subanalysis. Prospective trials, assessing treatment efficacy within molecular subtype are needed, however these 'real-world' data should be considered when discussing adjuvant treatment with patients.


Subject(s)
Endometrial Neoplasms , Female , Humans , Retrospective Studies , Prospective Studies , Neoplasm Staging , Endometrial Neoplasms/pathology , Combined Modality Therapy , Chemotherapy, Adjuvant/methods , Radiotherapy, Adjuvant
7.
Nutr Neurosci ; 26(8): 743-748, 2023 Aug.
Article in English | MEDLINE | ID: mdl-35857702

ABSTRACT

INTRODUCTION: Hereditary Ataxias (HAs) comprise a wide spectrum of genetically determined neurodegenerative diseases with progressive ataxia as the main symptom. Few studies have evaluated nutritional profile in HA patients and most of these focused on specific ataxia subtypes. The objectives of this study were: (1) to investigate whether hereditary ataxias were associated with changes in energy expenditure, body composition and dietary intake; (2) to verify differences in these variables according to ataxia subtype, sex, age, and disease severity. METHODS: Thirty-eight hereditary ataxia patients from two neurology centers in Northeastern Brazil and 38 controls were evaluated. Body composition was assessed with bio-impedance analysis and dietary intake was estimated with a validated questionnaire (24-hour dietary recall). RESULTS: Mean body mass index (BMI) was lower in HA compared to controls (p = 0.032). Hereditary ataxia patients showed lower protein intake, higher frequency of dysphagia and higher incidence of nausea and diarrhea. The difference in average estimated caloric intake did not reach statistical significance (2359kcal ± 622 in patients × 2713kcal ± 804 in controls, p = 0.08). Disease severity measured by the SARA scale was not associated with BMI, nor was ataxia subtype (autosomal dominant × non-autosomal dominant ataxias). CONCLUSION: Hereditary ataxia patients have lower BMI compared to healthy controls. There was no difference in this cohort between dominant or non-dominant ataxia regarding BMI. Weight loss may be a common finding among hereditary ataxias and may affect the quality of life in these patients.


Subject(s)
Nutritional Status , Spinocerebellar Degenerations , Humans , Case-Control Studies , Quality of Life , Spinocerebellar Degenerations/complications , Spinocerebellar Degenerations/diagnosis , Spinocerebellar Degenerations/epidemiology , Ataxia/complications , Feeding Behavior
8.
BMC Health Serv Res ; 23(1): 1448, 2023 Dec 20.
Article in English | MEDLINE | ID: mdl-38124113

ABSTRACT

BACKGROUND: Integrated care has become a central feature of health system reform worldwide. In England, Integrated Care Systems (ICS) are intended to improve integration across public health, the National Health Service (NHS), education and social care. By April 2021, England had been divided into 42 geographical areas, each tasked with developing local ICS provision. However, it was not clear how ICSs would address the specific needs of children and young people (CYP). This study elicited the views of senior professional stakeholders in the first year of the ICS national roll out, to learn how integrated care for CYP was being implemented within the ICSs and future plans for service provision. METHODS: A qualitative analysis of in-depth interviews with stakeholders, including healthcare professionals, NHS managers and local authority leaders (n = 25) selected from a diverse sample of ICSs (n = 7) across England, conducted during winter 2021/22. Reflexive thematic analysis involving a collaborative coding approach was used to analyse interview transcripts. RESULTS: Four themes were identified, indicating challenges and opportunities for ICSs in relation to the health of CYP: 1) Best start in life (a more holistic approach to health afforded by integrated care); 2) Local and national contexts (tensions between local and national settings and priorities); 3) Funding and planning (instituting innovative, long-term plans using limited existing CYP funding streams); 4) Organisational complexities (integrating the work of diverse organisations). CONCLUSIONS: The views of stakeholders, provided at the beginning of the journey towards developing local ICS CYP provision, revealed a common aspiration to change focus from provision of acute, largely adult-orientated services towards one with a broader, population health remit, including prevention and early intervention. This would be delivered by integration of a range of local services, including health, education, housing and social care, to set CYP on a life-long path towards improved health and wellbeing. Yet there was an awareness that change would take place over time within existing national policy and funding frameworks, and would require overcoming organisational barriers through further developing local collaborations and partnerships. As ICSs mature, the experiences of stakeholders should continue to be canvassed to identify practical lessons for successful CYP integrated care.


Subject(s)
Delivery of Health Care, Integrated , State Medicine , Child , Adult , Humans , Adolescent , Qualitative Research , Health Personnel , England/epidemiology
9.
Mod Pathol ; 35(12): 1974-1982, 2022 12.
Article in English | MEDLINE | ID: mdl-36241860

ABSTRACT

We assessed the landscape of diagnostic pathology practice and how molecular classification could potentially impact management of patients with endometrial cancer by collecting patient samples, clinicopathologic data, and patient outcomes from EC patients diagnosed in 2016 at 10 Canadian tertiary cancer centers and 19 community hospitals. ProMisE molecular subtype (POLEmut, MMRd, p53abn, No Specific Molecular Profile (NSMP)) was assigned retrospectively. 1357 patients were fully evaluable including 85 POLEmut (6.3%), 380 MMRd (28.0%), 643 NSMP (47.4%), and 249 p53abn ECs (18.3%). Immunohistochemistry (IHC) for MMR proteins was undertaken at the time of primary diagnosis in 2016 in only 42% of the cohort (570/1357; range 3.5-95.4%/center). p53 IHC had only been performed in 21.1% of the cohort (286/1357; range 10.1-41.9%/center). Thus, based on the retrospective molecular subtype assignment, 54.7% (208/380) of MMRd EC had not been tested with MMR IHC (or MSI) and 48.2% (120/249) of p53abn ECs were not tested with p53 IHC in 2016. Molecular subtype diversity within histotypes was profound; most serous carcinomas were p53abn (91.4%), but only 129/249 (51.8%) p53abn EC were serous. Low-grade (Gr1-2) endometrioid carcinomas were mostly NSMP (589/954, 61.7%) but included all molecular subtypes, including p53abn (19/954, 2.0%). Molecular subtype was significantly associated with clinical outcomes (p < 0.001) even in patients with stage I disease (OS p = 0.006, DSS p < 0.001, PFS p < 0.001). Assessment of national pathologic practice in 2016 shows highly variable use of MMR and p53 IHC and demonstrates significant opportunities to improve and standardize biomarker reporting. Inconsistent, non-reflexive IHC resulted in missed opportunities for Hereditary Cancer Program referral and Lynch Syndrome diagnosis, and missed potential therapeutic implications (e.g., chemotherapy in p53abn EC, immune blockade for MMRd EC). Routine integration of molecular subtyping into practice can improve the consistency of EC pathology assessment and classification.


Subject(s)
Carcinoma, Endometrioid , Endometrial Neoplasms , Female , Humans , Retrospective Studies , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/metabolism , Canada , Endometrial Neoplasms/pathology , Carcinoma, Endometrioid/pathology , DNA Mismatch Repair
10.
Gynecol Oncol ; 165(2): 201-214, 2022 05.
Article in English | MEDLINE | ID: mdl-35246332

ABSTRACT

OBJECTIVES: We measured the variation in practice across all aspects of endometrial cancer (EC) management and assessed the potential impact of implementation of molecular classification. METHODS: Centers from across Canada provided representative tumor samples and clinical data, including preoperative workup, operative management, hereditary cancer program (HCP) referrals, adjuvant therapy, surveillance and outcomes, for all EC patients diagnosed in 2016. Tumors were classified into the four ProMisE molecular subtypes. RESULTS: A total of 1336 fully evaluable EC patients were identified from 10 tertiary cancer centers (TC; n = 1022) and 19 community centers (CC; n = 314). Variation of surgical practice across TCs was profound (14-100%) for lymphadenectomy (LND) (mean 57% Gr1/2, 82% Gr3) and omental sampling (20% Gr1/2, 79% Gr3). Preoperative CT scans were inconsistently obtained (mean 32% Gr1/2, 51% Gr3) and use of adjuvant chemo or chemoRT in high risk EC ranged from 0-55% and 64-100%, respectively. Molecular subtyping was performed retrospectively and identified 6% POLEmut, 28% MMRd, 48% NSMP and 18% p53abn ECs, and was significantly associated with survival. Within patients retrospectively diagnosed with MMRd EC only 22% had been referred to HCP. Of patients with p53abn EC, LND and omental sampling was not performed in 21% and 23% respectively, and 41% received no chemotherapy. Comparison of management in 2016 with current 2020 ESGO/ESTRO/ESP guidelines identified at least 26 and 95 patients that would have been directed to less or more adjuvant therapy, respectively (10% of cohort). CONCLUSION: Molecular classification has the potential to mitigate the profound variation in practice demonstrated in current EC care, enabling reproducible risk assessment, guiding treatment and reducing health care disparities.


Subject(s)
Endometrial Neoplasms , Chemotherapy, Adjuvant , Combined Modality Therapy , Endometrial Neoplasms/genetics , Endometrial Neoplasms/therapy , Female , Humans , Lymph Node Excision , Retrospective Studies
11.
Physiol Plant ; 174(2): e13675, 2022 Mar.
Article in English | MEDLINE | ID: mdl-35316539

ABSTRACT

In agriculture, plant growth promoting bacteria (PGPB) are increasingly used for reducing environmental stress-related crop losses through mutualistic actions of these microorganisms, activating physiological and biochemical responses, building tolerances within their hosts. Here we report the use of radioactive carbon-11 (t½ 20.4 min) to examine the metabolic and physiological responses of Zea mays to Azospirillum brasilense (HM053) inoculation while plants were subjected to salinity and low nitrogen stresses. Host metabolism of "new" carbon resources (as 11 C) and physiology including [11 C]-photosynthate translocation were measured in response to imposed growth conditions. Salinity stress caused shortened, dense root growth with a 6-fold increase in foliar [11 C]-raffinose, a potent osmolyte. ICP-MS analyses revealed increased foliar Na+ levels at the expense of K+ . HM053 inoculation relieved these effects, reinstating normal root growth, lowering [11 C]-raffinose levels while increasing [11 C]-sucrose and its translocation to the roots. Na+ levels remained elevated with inoculation, but K+ levels were boosted slightly. Low nitrogen stress yielded longer roots possessing high levels of anthocyanins. Metabolic analysis revealed significant shifts in "new" carbon partitioning into the amino acid pool under low nitrogen stress, with significant increases in foliar [11 C]-glutamate, [11 C]-aspartate, and [11 C]-asparagine, a noted osmoprotectant. 11 CO2 fixation and [11 C]-photosynthate translocation also decreased, limiting carbon supply to roots. However, starch levels in roots were reduced under nitrogen limitation, suggesting that carbon repartitioning could be a compensatory action to support root growth. Finally, inoculation with HM053 re-instated normal root growth, reduced anthocyanin, boosted root starch, and returned 11 C-allocation levels back to those of unstressed plants.


Subject(s)
Azospirillum brasilense , Plant Roots , Anthocyanins/metabolism , Azospirillum brasilense/metabolism , Carbon/metabolism , Carbon Radioisotopes , Nitrogen/metabolism , Plant Roots/metabolism , Raffinose/metabolism , Starch/metabolism
12.
Gynecol Oncol ; 157(1): 12-20, 2020 04.
Article in English | MEDLINE | ID: mdl-31954537

ABSTRACT

OBJECTIVE: Low-grade serous ovarian carcinomas (LGSC) are frequently ER/PR positive, though the mechanisms by which ER/PR regulate prognosis or anti-estrogen treatment efficacy are poorly understood. We studied ER/PR expression in LGSC tumors and cell lines to evaluate patient outcomes and cellular treatment responses. METHODS: LGSC tumors and patient-derived cell lines were studied from patients with advanced-stage (III/IV) disease. Tumor samples and clinical data were obtained from the Canadian Ovarian Experimental Unified Resource (COEUR-tissue microarray) and the Ovarian Cancer Research (OvCaRe) tissue bank. ER/PR expression was assessed by both Western blot and immunohistochemistry (IHC). Two different IHC scoring systems (simple and Allred) were used. Cox regression was used to identify factors (age, disease residuum, ER/PR status, etc.) associated with progression-free (PFS) and overall survival (OS). Estradiol and tamoxifen proliferation and viability experiments were performed in LGSC cell lines. RESULTS: In 55 LGSC cases studied, median follow-up was 56 months (range 1-227). Fifty-three (96%) cases strongly expressed ER whereas 37 (67%) expressed PR. Cox-regression analysis showed that residuum (p < 0.001) was significantly associated with PFS, whereas both ER Allred score (p = 0.005) and residuum (p = 0.004) were significant for OS. None of the LGSC cell lines expressed PR. Loss of PR and ER expression over time was detected in LGSC tumors and cell lines respectively. Estrogen and tamoxifen treatment did not alter LGSC cell proliferation or viability in-vitro. CONCLUSIONS: In patients with advanced LGSC, higher ER Allred scores were significantly associated with better overall survival. ER/PR expression changed over time in both LGSC tumors and cell lines. Better translational research models are needed to elucidate the molecular mechanisms of ER/PR signalling in LGSC.


Subject(s)
Cystadenocarcinoma, Serous/metabolism , Ovarian Neoplasms/metabolism , Receptors, Estrogen/biosynthesis , Receptors, Progesterone/biosynthesis , Biomarkers, Tumor/biosynthesis , Cell Line, Tumor , Cystadenocarcinoma, Serous/drug therapy , Cystadenocarcinoma, Serous/pathology , Disease Progression , Estradiol/pharmacology , Estrogen Antagonists/pharmacology , Female , Hep G2 Cells , Humans , Immunohistochemistry , MCF-7 Cells , Middle Aged , Neoplasm Grading , Neoplasm Staging , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/pathology , Prognosis , Receptors, Estrogen/antagonists & inhibitors , Tamoxifen/pharmacology , Tissue Array Analysis
13.
Gynecol Oncol ; 157(1): 36-45, 2020 04.
Article in English | MEDLINE | ID: mdl-32001076

ABSTRACT

OBJECTIVE: Patients with advanced low-grade serous carcinoma (LGSC) have poor long-term survival rates. As a rare histotype, there are uncertainties regarding the use of current therapies. Thus, we studied practice patterns and treatment outcomes as part of a national initiative to better understand and improve the care of women with advanced LGSC. METHODS: This retrospective cohort study was conducted in 5 Canadian referral institutions from 2000 to 2016. Data collection and pathology reporting were standardized. Outcome measures included overall survival (OS), progression-free survival (PFS), progression-free intervals (PFI), and time to next treatment (TTNT). Cox regression analysis was used to evaluate the effects of clinical and pathologic factors on outcomes and prognosis. RESULTS: There were 134 patients (stage II-IV) with a median follow-up of 32.4 months (range 1.6-228). Four primary treatments were compared across institutions: 1) surgery followed by chemotherapy (56%), 2) neoadjuvant chemotherapy (NACT) followed by surgery (27%), 3) surgery alone (9%), and 4) surgery followed by anti-hormone therapy (4%). Primary platinum/paclitaxel chemotherapy was used in 81%. Patients treated with NACT had worse PFS. Multivariable Cox regression analysis identified lesser residual disease, younger age, and primary peritoneal origin as variables significantly associated with better OS/PFS (p < 0.03). One institution had significantly better PFS than the others (p = 0.025), but this finding could be related to a higher frequency of primary peritoneal LGSC. PFI and TTNT intervals in patients with relapsed disease were not significantly different after the first relapse irrespective of treatment type. CONCLUSIONS: There are notable differences in practice patterns across Canada. This underscores the need for ongoing strategies to measure, evaluate and achieve optimal patient outcomes for women with advanced LGSC.


Subject(s)
Cystadenocarcinoma, Serous/drug therapy , Cystadenocarcinoma, Serous/surgery , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/surgery , Practice Patterns, Physicians' , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carboplatin/administration & dosage , Cisplatin/administration & dosage , Cohort Studies , Cystadenocarcinoma, Serous/pathology , Female , Humans , Middle Aged , Neoplasm Grading , Neoplasm Staging , Ovarian Neoplasms/pathology , Paclitaxel/administration & dosage , Progression-Free Survival , Retrospective Studies , Survival Rate , Treatment Outcome
14.
Appetite ; 144: 104449, 2020 01 01.
Article in English | MEDLINE | ID: mdl-31520670

ABSTRACT

Alcohol use peaks in early adulthood and can contribute both directly and indirectly to unhealthy weight gain. This is the first qualitative study to explore the links between unhealthy eating behaviour and heavy alcohol use in the social, emotional and cultural lives of young adults. We conducted 45 in-depth interviews with 18-25-year-olds in North-East England to inform development of a dual-focused intervention to reduce health risk due to excess weight gain and alcohol use. Data were analysed thematically, following the principles of constant comparison, resulting in three intersecting themes: (1) how food and alcohol consumption currently link together for this population group; (2) influences upon linked eating and drinking behaviours and (3) young adults' feelings and concerns about linked eating and drinking behaviours. Socio-cultural, physical and emotional links between food and alcohol consumption were an unquestioned norm among young adults. Eating patterns linked to alcohol use were not tied only to hunger, but also to sociability, traditions and identity. Young adults conceptualised and calculated risks to weight, appearance and social status, rather than to long-term health. This study is the first to evidence the deeply interconnected nature of food and alcohol consumption for many young adults. Findings have important implications for intervention development, UK public health policy and practice, and point to a need for similar research in other countries.


Subject(s)
Alcohol Drinking/psychology , Diet, Healthy/psychology , Feeding Behavior/psychology , Adolescent , Adult , England , Female , Humans , Male , Qualitative Research , Social Norms , Young Adult
15.
J Obstet Gynaecol Can ; 42(8): 1021-1029.e3, 2020 08.
Article in English | MEDLINE | ID: mdl-32736853

ABSTRACT

OBJECTIVES: To aid primary care physicians, emergency medicine physicians, and gynaecologists in the initial investigation of adnexal masses, defined as lumps that appear near the uterus or in or around ovaries, fallopian tubes, or surrounding connective tissue, and to outline recommendations for identifying women who would benefit from a referral to a gynaecologic oncologist for further management. INTENDED USERS: Gynaecologists, obstetricians, family physicians, general surgeons, emergency medicine specialists, radiologists, sonographers, nurses, medical learners, residents, and fellows. TARGET POPULATION: Adult women 18 years of age and older presenting for the evaluation of an adnexal mass. OPTIONS: Women with adnexal masses should be assessed for personal risk factors, history, and physical findings. Initial evaluation should also include imaging and laboratory testing to triage women for management of their care either by a gynaecologic oncologist or as per SOGC guideline no. 404 on the initial investigation and management of benign ovarian masses. EVIDENCE: A search of PubMed, Cochrane Wiley, and the Cochrane systematic reviews was conducted in January 2018 for English-language materials involving human subjects published since 2000 using three sets of terms: (i) ovarian cancer, ovarian carcinoma, adnexal disease, ovarian neoplasm, adnexal mass, fallopian tube disease, fallopian tube neoplasm, ovarian cyst, and ovarian tumour; (ii) the above terms in combination with predict neoplasm staging, follow-up, and staging; and (iii) the above two sets of terms in combination with ultrasound, tumour marker, CA 125, CEA, CA19-9, HE4, multivariable-index-assay, risk-of-ovarian-malignancy-algorithm, risk-of-malignancy-index, diagnostic imaging, CT, MRI, and PET. Relevant evidence was selected for inclusion in descending order of quality of evidence as follows: meta-analyses, systematic reviews, guidelines, randomized controlled trials, prospective cohort studies, observational studies, non-systematic reviews, case series, and reports. Additional articles were identified through cross-referencing the identified reviews. The total number of studies identified was 2350, with 59 being included in this review. VALIDATION METHODS: The content and recommendations were drafted and agreed upon by the authors. The Executive and Board of the Society of Gynecologic Oncology of Canada reviewed the content and submitted comments for consideration. The Board of Directors of the Society of Obstetricians and Gynaecologists of Canada approved the final draft for publication. The quality of evidence was rated using the criteria described in the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology framework (Table A1 of Online Appendix A). See Table A2 of Online Appendix A for the interpretation of strong and weak recommendations. The summary of findings is available upon request. BENEFITS, HARMS, COSTS: Adnexal masses are common, and guidelines on how to triage them and manage the care of patients presenting with adnexal masses will continue to guide the practice of primary care providers and gynaecologists. Ovarian cancer outcomes are improved when initial surgery is performed by a gynaecologic oncologist, likely as a result of complete surgical staging and optimal cytoreduction. Given these superior outcomes, guidelines to assist in the triage of adnexal masses and the referral and management of the care of patients with an adnexal mass are critical. SUMMARY STATEMENTS (GRADE RATINGS IN PARENTHESES): RECOMMENDATIONS (GRADE RATINGS IN PARENTHESES).


Subject(s)
Adnexal Diseases/diagnosis , Adnexal Diseases/therapy , Fallopian Tube Neoplasms/diagnosis , Fallopian Tube Neoplasms/therapy , Gynecology/standards , Ovarian Neoplasms/diagnosis , Ovarian Neoplasms/therapy , Ovary/diagnostic imaging , Adolescent , Adult , Canada , Female , Humans , Ultrasonography
16.
Radiographics ; 39(5): 1368-1392, 2019.
Article in English | MEDLINE | ID: mdl-31498743

ABSTRACT

Gender-affirming surgeries expand the options for physical transition among transgender patients, those whose gender identity is incongruent with the sex assigned to them at birth. Growing medical insight, increasing public acceptance, and expanding insurance coverage have improved the access to and increased the demand for gender-affirming surgeries in the United States. Procedures for transgender women, those patients with feminine gender identity, include breast augmentation using implants and genital reconstruction with vaginoplasty. Some transgender women receive medically unapproved silicone injections for breast augmentation or other soft-tissue contouring procedures that can lead to disfigurement, silicone pulmonary embolism, systemic reactions, and even death. MRI is preferred over CT for postvaginoplasty evaluation given its superior tissue contrast resolution. Procedures for transgender men, patients with a masculine gender identity, include chest masculinization (mastectomy) and genital reconstruction (phalloplasty or metoidioplasty, scrotoplasty, and erectile device implantation). Urethrography is the standard imaging modality performed to evaluate neourethral patency and other complications, such as leaks and fistulas. Despite a sizeable growth in the surgical literature about gender-affirming surgeries and their outcomes, detailed descriptions of the imaging features following these surgeries remain sparse. Radiologists must be aware of the wide variety of anatomic and pathologic changes unique to patients who undergo gender-affirming surgeries to ensure accurate imaging interpretation. Online supplemental material is available for this article. ©RSNA, 2019.


Subject(s)
Diagnostic Imaging , Sex Reassignment Procedures , Transgender Persons , Female , Humans , Male
17.
J Obstet Gynaecol Can ; 41(1): 116-126, 2019 Jan.
Article in English | MEDLINE | ID: mdl-30580824

ABSTRACT

OBJECTIVE: This guideline provides guidance to gynaecologists regarding the use of tissue morcellation in gynaecologic surgery. OUTCOMES: Morcellation may be used in gynaecologic surgery to allow removal of large uterine specimens, thus providing women with a minimally invasive surgical option. Adverse oncologic outcomes of tissue morcellation should be mitigated through improved patient selection, preoperative investigations, and novel techniques that minimize tissue dispersion. EVIDENCE: Published literature was retrieved through searches of PubMed and Medline in the spring of 2014 using appropriate controlled vocabulary (leiomyosarcoma, uterine neoplasm, uterine myomectomy, hysterectomy) and key words (leiomyoma, endometrial cancer, uterine sarcoma, leiomyosarcoma, and morcellation). Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies. There were no date limits, but results were limited to English or French language materials. Searches were updated on a regular basis and incorporated in the guideline to July 2017. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. VALUES: The quality of evidence in this document was rated using the criteria described in the report of the Canadian Task Force on Preventive Health Care. BENEFITS, HARMS, AND COSTS: Gynaecologists offer women minimally invasive surgery, and this may involve tissue morcellation and the use of a power morcellator for specimen retrieval. Women should be counselled that in the case of unexpected uterine (sarcoma, endometrial), cervical, and/or tubo-ovarian cancer, the use of a morcellator is associated with increased risk of tumour dissemination. Tissue morcellation should be performed only after complete investigation, appropriate patient selection, and informed consent and by surgeons with appropriate training in the safe practices of tissue morcellation. SUMMARY STATEMENTS: RECOMMENDATIONS.


Subject(s)
Hysterectomy/methods , Laparoscopy/methods , Leiomyoma/surgery , Leiomyosarcoma/surgery , Morcellation/methods , Uterine Myomectomy/methods , Uterine Neoplasms/surgery , Female , Humans , Leiomyoma/epidemiology , Leiomyosarcoma/epidemiology , Minimally Invasive Surgical Procedures , Morcellation/adverse effects , Neoplasm Seeding , Risk , Uterine Neoplasms/epidemiology
18.
J Obstet Gynaecol Can ; 41(1): 127-138, 2019 Jan.
Article in English | MEDLINE | ID: mdl-30580825

ABSTRACT

OBJECTIF: La présente directive clinique conseille les gynécologues quant au recours au morcellement tissulaire pendant une chirurgie gynécologique. RéSULTATS: Le morcellement effectué au cours d'une chirurgie gynécologique peut permettre l'ablation de masses utérines volumineuses, offrant ainsi aux femmes une solution chirurgicale à effraction minimale. Les conséquences oncologiques indésirables du morcellement tissulaire devraient être atténuées par l'amélioration de la sélection des patientes, la tenue d'examens préopératoires et l'adoption de techniques novatrices réduisant au minimum la dispersion tissulaire. ÉVIDENCE: La littérature publiée a été récupérée au moyen de recherches menées dans PubMed et Medline au printemps 2014 à l'aide d'une terminologie contrôlée (« leiomyosarcoma ¼, « uterine neoplasm ¼, « uterine myomectomy ¼, « hysterectomy ¼) et de mots-clés (« leiomyoma ¼, « endometrial cancer ¼, « uterine sarcoma ¼, « leiomyosarcoma ¼, « morcellation ¼). Les résultats retenus provenaient de revues systématiques, d'essais cliniques randomisés, d'essais cliniques contrôlés et d'études observationnelles de langue anglaise ou française. Aucune restriction de date n'a été imposée. Les recherches ont été refaites régulièrement, et les résultats ont été incorporés à la directive clinique jusqu'en juillet 2017. Nous avons également tenu compte de la littérature grise (non publiée) trouvée sur les sites Web d'organismes d'évaluation des technologies de la santé et d'autres organismes liés aux technologies de la santé, dans des collections de directives cliniques et dans des registres d'essais cliniques, et obtenue auprès d'associations nationales et internationales de médecins spécialistes. VALEURS: La qualité des données probantes a été évaluée en fonction des critères décrits dans le rapport du Groupe d'étude canadien sur les soins de santé préventifs. AVANTAGES, INCONVéNIENTS ET COûTS: Les gynécologues offrent aux femmes une chirurgie à effraction minimale pouvant comprendre le recours à un morcellateur électromécanique pour faciliter le retrait des tissus. Les femmes devraient être informées que l'utilisation d'un morcellateur en présence de tumeurs utérines (sarcomes, tumeurs endométriales), cervicales ou tubo-ovariennes jusque-là insoupçonnées est associée à un risque accru de dissémination. Le morcellement tissulaire devrait être précédé d'une évaluation complète, d'une sélection appropriée des patientes et de l'obtention du consentement éclairé de ces dernières, et devrait être effectué par des chirurgiens ayant une formation adéquate en matière de pratiques de morcellement tissulaire sûres. DéCLARATIONS SOMMAIRES: RECOMMANDATIONS.

SELECTION OF CITATIONS
SEARCH DETAIL