Abstract
BACKGROUND
Many transgender individuals choose to undergo gender-affirming hormone treatment (GAHT) and/or sex reassignment surgery (SRS) to alleviate the distress that is associated with ...gender dysphoria. Although these treatment options often succeed in alleviating such symptoms, they can also negatively impact future reproductive potential.
OBJECTIVE AND RATIONALE
The purpose of this systematic review was to synthesize the available psychosocial and medical literature on fertility preservation (FP) for transgender adolescents and young adults (TAYAs), to identify gaps in the current research and provide suggestions for future research directions.
SEARCH METHODS
A systematic review of English peer-reviewed papers published from 2001 onwards, using the preferred reporting items for systematic reviews and meta-analyses protocols (PRISMA-P) guidelines, was conducted. Four journal databases (Ovid MEDLINE, PubMed Medline, Ovid Embase and Ovid PsychINFO) were used to identify all relevant studies exploring psychosocial or medical aspects of FP in TAYAs. The search strategy used a combination of subject headings and generic terms related to the study topic and population. Bibliographies of the selected articles were also hand searched and cross-checked to ensure comprehensive coverage. All selected papers were independently reviewed by the co-authors. Characteristics of the studies, objectives and key findings were extracted, and a systematic review was conducted.
OUTCOMES
Included in the study were 19 psychosocial-based research papers and 21 medical-based research papers that explore fertility-related aspects specific for this population. Key psychosocial themes included the desire to have children for TAYAs; FP discussions, counselling and referrals provided by healthcare providers (HCPs); FP utilization; the attitudes, knowledge and beliefs of TAYAs, HCPs and the parents/guardians of TAYAs; and barriers to accessing FP. Key medical themes included fertility-related effects of GAHT, FP options and outcomes. From a synthesis of the literature, we conclude that there are many barriers preventing TAYAs from pursuing FP, including a lack of awareness of FP options, high costs, invasiveness of the available procedures and the potential psychological impact of the FP process. The available medical data on the reproductive effects of GAHT are diverse, and while detrimental effects are anticipated, the extent to which these effects are reversible is unknown.
WIDER IMPLICATIONS
FP counselling should begin as early as possible as a standard of care before GAHT to allow time for informed decisions. The current lack of high-quality medical data specific to FP counselling practice for this population means there is a reliance on expert opinion and extrapolation from studies in the cisgender population. Future research should include large-scale cohort studies (preferably multi-centered), longitudinal studies of TAYAs across the FP process, qualitative studies of the parents/guardians of TAYAs and studies evaluating the effectiveness of different strategies to improve the attitudes, knowledge and beliefs of HCPs.
Significance It is established that glucose tolerance decreases from the morning to the evening, and that shift work is a risk factor for diabetes. However, the relative importance of the endogenous ...circadian system, the behavioral cycle (including the sleep/wake and fasting/feeding cycles), and circadian misalignment on glucose tolerance is unclear. We show that the magnitude of the effect of the endogenous circadian system on glucose tolerance and on pancreatic β-cell function was much larger than that of the behavioral cycle in causing the decrease in glucose tolerance from morning to evening. Also, independent from circadian phase and the behavioral cycle, circadian misalignment resulting from simulated night work lowered glucose tolerance—without diminishing effects upon repeated exposure—with direct relevance for shift workers.
Glucose tolerance is lower in the evening and at night than in the morning. However, the relative contribution of the circadian system vs. the behavioral cycle (including the sleep/wake and fasting/feeding cycles) is unclear. Furthermore, although shift work is a diabetes risk factor, the separate impact on glucose tolerance of the behavioral cycle, circadian phase, and circadian disruption (i.e., misalignment between the central circadian pacemaker and the behavioral cycle) has not been systematically studied. Here we show—by using two 8-d laboratory protocols—in healthy adults that the circadian system and circadian misalignment have distinct influences on glucose tolerance, both separate from the behavioral cycle. First, postprandial glucose was 17% higher (i.e., lower glucose tolerance) in the biological evening (8:00 PM) than morning (8:00 AM; i.e., a circadian phase effect), independent of the behavioral cycle effect. Second, circadian misalignment itself (12-h behavioral cycle inversion) increased postprandial glucose by 6%. Third, these variations in glucose tolerance appeared to be explained, at least in part, by different mechanisms: during the biological evening by decreased pancreatic β-cell function (27% lower early-phase insulin) and during circadian misalignment presumably by decreased insulin sensitivity (elevated postprandial glucose despite 14% higher late-phase insulin) without change in early-phase insulin. We explored possible contributing factors, including changes in polysomnographic sleep and 24-h hormonal profiles. We demonstrate that the circadian system importantly contributes to the reduced glucose tolerance observed in the evening compared with the morning. Separately, circadian misalignment reduces glucose tolerance, providing a mechanism to help explain the increased diabetes risk in shift workers.
Summary
Allopolyploid speciation and chemical defense diversification are two of the most characteristic features of plant evolution; although the former has likely shaped the latter, this has rarely ...been documented. Here we document allopolyploidy‐mediated chemical defense evolution in the origin of cyanogenesis (HCN release upon tissue damage) in white clover (Trifolium repens).
We combined linkage mapping of the loci that control cyanogenesis (Ac, controlling production of cyanogenic glucosides; and Li, controlling production of their hydrolyzing enzyme linamarase) with genome sequence comparisons between white clover, a recently evolved allotetraploid, and its diploid progenitors (Trifolium pallescens, Trifolium occidentale).
The Ac locus (a three‐gene cluster comprising the cyanogenic glucoside pathway) is derived from T. occidentale; it maps to linkage group 2O (occidentale subgenome) and is orthologous to a highly similar cluster in the T. occidentale reference genome. By contrast, Li maps to linkage group 4P (pallescens subgenome), indicating an origin in the other progenitor species.
These results indicate that cyanogenesis evolved in white clover as a product of the interspecific hybridization that created the species. This allopolyploidization‐derived chemical defense, together with subsequent selection on intraspecific cyanogenesis variation, appears to have contributed to white clover’s ecological success as a globally distributed weed species.
The design of a randomized pilot trial evaluating the feasibility of two doses of a digital health intervention promoting changes in nutrition and physical activity in breast cancer (BC) survivors is ...described.
Eligible women were adults with history of early-stage breast cancer and > 60 days post-treatment, consumed <5 servings/day of fruits/vegetables and/or engaged in <150 min/week of aerobic moderate-to-vigorous physical activity, and had internet access. Participants were randomized to 6 months of either a “low” (1 session) or “high” (12 sessions) dose digital health intervention. Zoom-delivered sessions focused on improving diet and physical activity through didactic and experiential classes delivered by a registered dietitian, chef, exercise physiologist, and culinary educator. All study participants received weekly motivational texts, a Fitbit, and study website access. Diet, accelerometry, anthropometric, psychosocial, and biospecimen data were collected remotely at baseline and six months. Primary outcome was feasibility measured via accrual rate, adherence, retention, and acceptability.
Recruitment began in December 2019, was suspended in March 2020 due to the COVID-19 pandemic, resumed September 2020, and concluded in January 2021. Women were identified from the local BC registry and flyers posted in the oncology clinic. Of 929 women recruited, 321 completed the screening assessment, and of these, 138 were eligible. A total of 74 women were enrolled and randomized to the study.
BC survivors were successfully enrolled in a digital health nutrition and physical activity intervention. If feasible, this intervention will be tested in larger and more diverse populations of cancer survivors.
Trial registration:ClinicalTrials.govNCT04200482
Although cancer care is often contextualized in terms of survival, there are other important cancer care outcomes, such as quality of life and cost of care. The ASCO Value Framework assesses the ...value of cancer therapies not only in terms of survival but also with consideration of quality of life and financial cost. Early palliative care for patients with advanced cancer is associated with improved quality of life, mood, symptoms, and overall survival for patients, as well as cost savings. While palliative care has been shown to have numerous benefits, the impact of real-world implementation of outpatient embedded palliative care on value-based metrics is not fully understood. We sought to describe the association between outpatient embedded palliative care in a multidisciplinary thoracic oncology clinic and inpatient value-based metrics. We performed a retrospective cohort study of 215 patients being treated for advanced thoracic malignancies with non-curative intent. We evaluated the association between outpatient embedded palliative care and inpatient clinical outcomes including emergency room visits, hospitalizations, intensive care unit admissions, hospital charges, as well as hospital quality metrics including 30-day readmissions, admissions within 30 days of death, inpatient mortality, and inpatient hospital charges. Outpatient embedded palliative care was associated with lower hospital charges per day (USD 3807 vs. USD 4695,
= 0.024). Furthermore, patients who received outpatient embedded palliative care had lower hospital admissions within 30 days of death (O.R. 0.45; 95% CI 0.29, 0.68;
< 0.001) and a lower inpatient mortality rate (IRR 0.67; 95% CI 0.48, 0.95;
= 0.024). Our study further supports that outpatient palliative care is a high-value intervention and alternative models of palliative care, including one embedded into a multidisciplinary thoracic oncology clinic, is associated with improved value-based metrics.
Abstract We tested the feasibility and preliminary efficacy of an online diet and physical activity program for women with early-stage breast cancer who had completed surgery, chemotherapy, and ...radiation therapy (ongoing endocrine therapy allowed). Participants with low fruit and vegetable (F/V) consumption and/or low moderate-to-vigorous physical activity (MVPA) levels were randomized to one of two doses - low (one Zoom group session) or high (12 Zoom group sessions) - of an online lifestyle program with the goal of improving F/V intake and MVPA. All participants received eHealth communications (text messages, study website access), a Fitbit, and a WiFi-enabled scale. Primary objectives evaluated feasibility. Secondary objectives compared the 6-month change in F/V intake and MVPA between the two dose groups. Seventy-four women (mean age = 58.4 years; 87% non-Hispanic White; mean time since diagnosis = 4.6 years) were accrued. Among women in the low dose group, 94% attended the single session; among women in the high dose group, 84% attended at least 8 of the 12 sessions. Retention at 6 months was 93%. High relative to low dose participants consumed 1.5 more servings/day of F/V at 6 months ( P = 0.007) but MVPA levels did not differ between groups. We successfully implemented an online lifestyle program for early-stage breast cancer survivors. The high dose intervention demonstrated preliminary efficacy in improving F/V consumption in early-stage breast cancer survivors. Future trials can test the intervention in a larger and more diverse population of breast cancer survivors.
Unplanned hospitalization during cancer treatment is costly, can disrupt treatment, and affect patient quality of life. However, incidence and risks factors for hospitalization during lung cancer ...radiotherapy are not well characterized.
Patients treated with definitive intent radiation (≥45 Gy) for lung cancer between 2008 and 2018 at a tertiary academic institution were identified. In addition to patient, tumor, and treatment related characteristics, specific baseline frailty markers (Charlson comorbidity index, ECOG, patient reported weight loss, BMI, hemoglobin, creatinine, albumin) were recorded. All cancer-related hospitalizations during or within 30 days of completing radiation were identified. Associations between baseline variables and any hospitalization, number of hospitalizations, and overall survival were identified using multivariable linear regression and multivariable Cox proportional-hazards models, respectively.
Of 270 patients included: median age was 66.6 years (31-88), 50.4% of patients were male (n = 136), 62% were Caucasian (n = 168). Cancer-related hospitalization incidence was 17% (n = 47), of which 21% of patients hospitalized (n = 10/47) had > 1 hospitalization. On multivariable analysis, each 1 g/dL baseline drop in albumin was associated with a 2.4 times higher risk of any hospitalization (95% confidence interval (CI) 1.2-5.0, P = 0.01), and baseline hemoglobin ≤10 was associated with, on average, 2.7 more hospitalizations than having pre-treatment hemoglobin > 10 (95% CI 1.3-5.4, P = 0.01). After controlling for baseline variables, cancer-related hospitalization was associated with 1.8 times increased risk of all-cause death (95% CI: 1.02-3.1, P = 0.04).
Our data show baseline factors can predict those who may be at increased risk for hospitalization, which was independently associated with increased mortality. Taken together, these data support the need for developing further studies aimed at early and aggressive interventions to decrease hospitalizations during treatment.
Direct-acting antivirals (DAAs) have become the standard treatment for patients with chronic hepatitis C infections because of their high cure rates and favourable side effect profiles; however, ...access to this new class of agents has been limited because of its high cost. Public payers across Canada have implemented strict criteria for drug coverage in order to contain expenditures. Efforts have been made to improve access to medication for this high-burden condition. Recent coverage criteria across national and international jurisdictions have been compared.
Coverage criteria for several DAAs were reviewed by accessing Canadian provincial drug formularies. International coverage (e.g., Europe, Australia, United States, Egypt, India) was reviewed by searching available literature.
Coverage criteria vary across Canada. By April 2018, most Canadian jurisdictions had removed the stage 2 liver fibrosis requirement for patients to be eligible for coverage. Internationally, patients' access to DAAs differs significantly. Many jurisdictions restrict DAA prescribing authority to specialists and request documentation of chronic hepatitis C. In the US, considerable gaps of coverage are identifiable and patients might face significant financial burden to receive treatment.
DAAs appear to be generally accessible through public drug plans in Canada compared to other countries.
Summary Background Blunted diurnal cortisol variation has been associated with overt cardiovascular disease in adults. The relationship between the diurnal cortisol variation and subclinical ...atherosclerosis in youth has yet to be investigated. The objectives of this study were to (1) determine the relationship between overnight cortisol measures and CIMT in overweight and obese, African-American and Latino children; (2) assess ethnic differences in these relationships; and (3) explore whether overnight cortisol and CIMT relationships were independent of inflammatory markers, C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor-∝ (TNF-∝). Methods One hundred fifty-six overweight and obese African-American and Latino children (ages 8–17, 86 M/70 F, 55 African-American/101 Latino) underwent measures of CIMT by B-mode ultrasound, nocturnal cortisol rise (NCR = salivary cortisol rise from 2200 h to awakening at 0530 h), cortisol awakening response (CAR = salivary cortisol from time of awakening to 30 min later), fasting serum cortisol and overnight urinary free cortisol. Results Using linear regression, salivary cortisol 0530 h and NCR were negatively associated with CIMT ( βstandardized = −0.215 and −0.220, p < 0.01) independent of age, height, percent body fat, ethnicity and systolic blood pressure. Nocturnal salivary cortisol 2200 h , morning serum cortisol, and overnight urinary free cortisol were not associated with CIMT. Using ANCOVA, participants with LOW NCR (NCR < 0.44 μg/dL, n = 52) had significantly greater CIMT than those with HIGH NCR (NCR ≥ 0.91 μg/dL, n = 52; 0.632 ± 0.008 vs. 0.603 ± 0.008 mm, p = 0.01) after controlling for covariates. Ethnicity was independently associated with CIMT, whereby African-American children had greater CIMT than Latino children (−0.028 ± 0.009, p = 0.006). The relationships between cortisol measures and CIMT did not differ between the two ethnic groups (all pinteraction = 0.28–0.97). CRP, IL-6 and TNF-∝ were not associated with CIMT ( p > 0.05). IL-6 was inversely related to NCR ( r = −0.186, p = 0.03), but it did not explain the relationship between NCR and CIMT. Conclusions Salivary cortisol 0530 h and NCR, but not CAR, nocturnal salivary cortisol 2200 h , morning serum cortisol or overnight urinary free cortisol were associated with CIMT, independent of relevant covariates, including inflammatory factors. A low awakening salivary cortisol or a blunted NCR may be related to increased atherosclerosis risk in overweight and obese minority youth. These findings support adult studies suggesting flattened daytime diurnal cortisol variation impacts cardiovascular disease risk.
Pulmonary embolism is associated with significant mortality and impaired long-term functional outcomes. Timely identification and treatment is crucial for successful management. Unfortunately, prompt ...diagnosis can be challenging in patients without overt signs of cardiovascular compromise. Point-of-care cardiac ultrasound (POCCUS) can be used to identify signs of acute pulmonary embolism, risk stratify patients for adverse outcomes and assess response to therapy. This report describes a patient with submassive pulmonary embolism and evidence of acute right ventricular strain on POCCUS successfully treated with thrombolytic therapy. The dynamic changes observed on point-of-care ultrasound are presented.
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