Advances in euglenoid genomics: unravelling the fascinating biology of a complex clade.

Euglenids have long been studied due to their unique physiology and versatile metabolism, providing underpinnings for much of our understanding of photosynthesis and biochemistry, and a growing opportunity in biotechnology. Until recently there has been a lack of genetic studies due to their large and complex genomes, but recently new technologies have begun to unveil their genetic capabilities. Whilst much research has focused on the model organism Euglena gracilis, other members of the euglenids have now started to receive due attention. Currently only poor nuclear genome assemblies of E. gracilis and Rhabdomonas costata are available, but there are many more plastid genome sequences and an increasing number of transcriptomes. As more assemblies become available, there are great opportunities to understand the fundamental biology of these organisms and to exploit them for biotechnology.

"It's Incapacitated Me in so Many Ways": Older Adults' Lived Experience With Postoperative Symptoms at Home After Major Elective Surgery.

OBJECTIVE: This qualitative study aimed to explore the challenges faced by older adults regarding the postoperative symptom experience after major elective surgery. BACKGROUND: Although extensively studied in oncology settings, the impact of postoperative symptom burden remains largely underexplored in elective major surgery among older adults. METHODS: We employed convenience sampling to recruit adults aged 65 years or above undergoing major elective surgery at the University of California, San Francisco. Semistructured interviews regarding the surgical experience were conducted at 1 and 3 months postoperatively. An inductive qualitative approach was used to identify emerging themes. Symptoms revealed by participants during interviews were also captured. RESULTS: Nineteen participants completed a 1-month postoperative interview, and 17 additionally completed a 3-month interview. Three themes emerged: (1) postoperative symptoms significantly impacted valued life activities and psychosocial well-being, (2) participants felt "caught off guard" by the intensity and duration of postoperative symptoms, and (3) participants expressed the need for additional support, resources, and education on symptom management. The most frequently mentioned symptoms were postoperative pain (n=12, 63.1%), gastrointestinal discomfort (n=8, 42.1%), and anxiety/stress (n=8, 42.1%) at 1-month postsurgery compared with pain and depression (both n=6, 35.3%) at 3 months. CONCLUSIONS: Study participants were surprised by the negative impact of postoperative symptoms on their psychosocial well-being and ability to engage in valued life activities. Symptom burden is an important patient-reported outcome that should be assessed postoperatively. Interventions to minimize postoperative symptom burden in older adults could optimize quality of life and participation in meaningful activities during surgical recovery.

"There's So Much That They're Enduring": Experiences of Older Adults Undergoing Major Elective Surgery.

OBJECTIVE: This qualitative study aimed to explore the psychosocial experience of older adults undergoing major elective surgery from the perspective of both the patient and family caregiver. SUMMARY BACKGROUND DATA: Older adults face unique psychological and social vulnerabilities that can increase susceptibility to poor health outcomes. How these vulnerabilities influence surgical treatment and recovery is understudied in the geriatric surgical population. METHODS: Adults aged 65 and older undergoing a high-risk major elective surgery at the University of California, San Francisco and their caregivers were recruited. Semi-structured interviews were conducted at three time points: 1-2 weeks before surgery, and at 1- and 3-months following surgery. An inductive qualitative approach was used to identify underlying themes. RESULTS: Twenty-five older adult patients (age range 65-82 years, 60% male) and 11 caregivers (age range 53-78 years, 82% female) participated. Three themes were identified. First, older surgical patients experienced significant challenges to emotional well-being both before and after surgery, which had a negative impact on recovery. Second, older adults relied on a combination of personal and social resources to navigate these challenges. Lastly, both patients and caregivers desired more resources from the healthcare system to address "the emotional piece" of surgical treatment and recovery. CONCLUSIONS: Older adults and their caregivers described multiple overlapping challenges to emotional well-being that spanned the course of the perioperative period. Our findings highlight a critical component of perioperative care with significant implications for the recovery of older surgical patients.

Heavy-metal associated breast cancer and colorectal cancer hot spots and their demographic and socioeconomic characteristics.

PURPOSE: Cancer registries offer an avenue to identify cancer clusters across large populations and efficiently examine potential environmental harms affecting cancer. The role of known metal carcinogens (i.e., cadmium, arsenic, nickel, chromium(VI)) in breast and colorectal carcinogenesis is largely unknown. Historically marginalized communities are disproportionately exposed to metals, which could explain cancer disparities. We examined area-based metal exposures and odds of residing in breast and colorectal cancer hotspots utilizing state tumor registry data and described the characteristics of those living in heavy metal-associated cancer hotspots. METHODS: Breast and colorectal cancer hotspots were mapped across Kentucky, and area-based ambient metal exposure to cadmium, arsenic, nickel, and chromium(VI) were extracted from the 2014 National Air Toxics Assessment for Kentucky census tracts. Among colorectal cancer (n = 56,598) and female breast cancer (n = 77,637) diagnoses in Kentucky, we used logistic regression models to estimate Odds Ratios (ORs) and 95% Confidence Intervals to examine the association between ambient metal concentrations and odds of residing in cancer hotspots, independent of individual-level and neighborhood risk factors. RESULTS: Higher ambient metal exposures were associated with higher odds of residing in breast and colorectal cancer hotspots. Populations in breast and colorectal cancer hotspots were disproportionately Black and had markers of lower socioeconomic status. Furthermore, adjusting for age, race, tobacco and neighborhood factors did not significantly change cancer hotspot ORs for ambient metal exposures analyzed. CONCLUSION: Ambient metal exposures contribute to higher cancer rates in certain geographic areas that are largely composed of marginalized populations. Individual-level assessments of metal exposures and cancer disparities are needed.

Fetal fraction of cell-free DNA in noninvasive prenatal testing and adverse pregnancy outcomes: a nationwide retrospective cohort study of 56,110 pregnant women.

BACKGROUND: Noninvasive prenatal testing by cell-free DNA analysis is offered to pregnant women worldwide to screen for fetal aneuploidies. In noninvasive prenatal testing, the fetal fraction of cell-free DNA in the maternal circulation is measured as a quality control parameter. Given that fetal cell-free DNA originates from the placenta, the fetal fraction might also reflect placental health and maternal pregnancy adaptation. OBJECTIVE: This study aimed to assess the association between the fetal fraction and adverse pregnancy outcomes. STUDY DESIGN: We performed a retrospective cohort study of women with singleton pregnancies opting for noninvasive prenatal testing between June 2018 and June 2019 within the Dutch nationwide implementation study (Trial by Dutch Laboratories for Evaluation of Non-Invasive Prenatal Testing [TRIDENT]-2). Multivariable logistic regression analysis was used to assess associations between fetal fraction and adverse pregnancy outcomes. Fetal fraction was assessed as a continuous variable and as <10th percentile, corresponding to a fetal fraction <2.5%. RESULTS: The cohort comprised 56,110 pregnancies. In the analysis of fetal fraction as a continuous variable, a decrease in fetal fraction was associated with increased risk of hypertensive disorders of pregnancy (adjusted odds ratio, 2.27 [95% confidence interval, 1.89-2.78]), small for gestational age neonates <10th percentile (adjusted odds ratio, 1.37 [1.28-1.45]) and <2.3rd percentile (adjusted odds ratio, 2.63 [1.96-3.57]), and spontaneous preterm birth from 24 to 37 weeks of gestation (adjusted odds ratio, 1.02 [1.01-1.03]). No association was found for fetal congenital anomalies (adjusted odds ratio, 1.02 [1.00-1.04]), stillbirth (adjusted odds ratio, 1.02 [0.96-1.08]), or neonatal death (adjusted odds ratio, 1.02 [0.96-1.08]). Similar associations were found for adverse pregnancy outcomes when fetal fraction was <10th percentile. CONCLUSION: In early pregnancy, a low fetal fraction is associated with increased risk of adverse pregnancy outcomes. These findings can be used to expand the potential of noninvasive prenatal testing in the future, enabling the prediction of pregnancy complications and facilitating tailored pregnancy management through intensified monitoring or preventive measures.

Fetal Fraction of Cell-Free DNA in the Prediction of Adverse Pregnancy Outcomes: A Nationwide Retrospective Cohort Study.

OBJECTIVE: To assess the added value of fetal fraction of cell-free DNA in the maternal circulation in the prediction of adverse pregnancy outcomes. DESIGN: Retrospective cohort study. SETTING: Nationwide implementation study on non-invasive prenatal testing (NIPT; TRIDENT-2 study). POPULATION: Pregnant women in the Netherlands opting for NIPT between June 2018 and June 2019. METHODS: Two logistic regression prediction models were constructed for each adverse pregnancy outcome. The first model (base model) included prognostic clinical parameters that were selected from existing first-trimester prediction models for adverse pregnancy outcomes. The second model (fetal fraction model) included fetal fraction as a predictor on top of the prognostic clinical parameters included in the base model. The added prognostic value of fetal fraction was assessed by comparing the base and fetal fraction models in terms of goodness of fit and predictive performance. MAIN OUTCOME MEASURES: Likelihood ratio test (LRT), area under the curve (AUC) and Integrated Discrimination Improvement (IDI) index. RESULTS: The study cohort consisted of 56 110 pregnancies. The incidence of adverse pregnancy outcomes was 5.7% for hypertensive disorders of pregnancy (HDP; n = 3207), 10.2% for birthweight < p10 (n = 5726), 3.2% for birthweight < p2.3 (n = 1796), 3.4% for spontaneous preterm birth (sPTB; n = 1891), 3.4% for diabetes (n = 1902) and 1.3% for congenital anomalies (n = 741). Adding fetal fraction to the base model improved model fit for HDP, birthweight < p10, birthweight < p2.3, all sPTB, and diabetes, but not for congenital anomalies (LRT p < 0.05). For HDP, the AUC improved from 0.67 to 0.68 by adding fetal fraction to the base model (p = 0.14) with an IDI of 0.0018 (p < 0.0001). For birthweight < p10, the AUC improved from 0.65 to 0.66 (p < 0.0001) with an IDI of 0.0023 (p < 0.0001). For birthweight < p2.3, the AUC improved from 0.67 to 0.69 (p < 0.0001) with an IDI of 0.0011 (p < 0.0001). For all sPTB, the AUC was similar for both models (AUC 0.63, p = 0.021) with an IDI of 0.00028 (p = 0.0023). For diabetes, the AUC was similar (AUC 0.72, p = 0.35) with an IDI of 0.00055 (p = 0.00015). CONCLUSIONS: Fetal fraction has statistically significant but limited prognostic value in the prediction of adverse pregnancy outcomes in addition to known prognostic clinical parameters.

First-Trimester Prediction Models Based on Maternal Characteristics for Adverse Pregnancy Outcomes: A Systematic Review and Meta-Analysis.

BACKGROUND: Early risk stratification can facilitate timely interventions for adverse pregnancy outcomes, including preeclampsia (PE), small-for-gestational-age neonates (SGA), spontaneous preterm birth (sPTB) and gestational diabetes mellitus (GDM). OBJECTIVES: To perform a systematic review and meta-analysis of first-trimester prediction models for adverse pregnancy outcomes. SEARCH STRATEGY: The PubMed database was searched until 6 June 2024. SELECTION CRITERIA: First-trimester prediction models based on maternal characteristics were included. Articles reporting on prediction models that comprised biochemical or ultrasound markers were excluded. DATA COLLECTION AND ANALYSIS: Two authors identified articles, extracted data and assessed risk of bias and applicability using PROBAST. MAIN RESULTS: A total of 77 articles were included, comprising 30 developed models for PE, 15 for SGA, 11 for sPTB and 35 for GDM. Discriminatory performance in terms of median area under the curve (AUC) of these models was 0.75 [IQR 0.69-0.78] for PE models, 0.62 [0.60-0.71] for SGA models of nulliparous women, 0.74 [0.72-0.74] for SGA models of multiparous women, 0.65 [0.61-0.67] for sPTB models of nulliparous women, 0.71 [0.68-0.74] for sPTB models of multiparous women and 0.71 [0.67-0.76] for GDM models. Internal validation was performed in 40/91 (43.9%) of the models. Model calibration was reported in 21/91 (23.1%) models. External validation was performed a total of 96 times in 45/91 (49.5%) of the models. High risk of bias was observed in 94.5% of the developed models and in 58.3% of the external validations. CONCLUSIONS: Multiple first-trimester prediction models are available, but almost all suffer from high risk of bias, and internal and external validations were often not performed. Hence, methodological quality improvement and assessment of the clinical utility are needed.

Perspectives of pregnant women on broadening the scope of noninvasive prenatal testing from screening for foetal aneuploidies to prediction of adverse pregnancy outcomes: A qualitative study.

OBJECTIVE: To explore the perspectives of pregnant women on broadening the scope of noninvasive prenatal testing (NIPT) from screening for foetal aneuploidies to prediction of adverse pregnancy outcomes. METHODS: Four online focus groups (n = 23 participants) and 14 individual semi-structured interviews were conducted. Participants included pregnant women with and without a history of adverse pregnancy outcomes. RESULTS: Both women at low and high risk of adverse pregnancy outcomes had a positive attitude towards using NIPT to predict adverse pregnancy outcomes. Perceived benefits included the possibility to potentially improve maternal and foetal outcomes by taking risk-reducing measures and/or intensified monitoring during pregnancy and the ability to mentally prepare for the potential adverse outcome. Perceived concerns included anxiety and stress caused by a high-risk test result, a false sense of control over pregnancy, and potential false reassurance. Additionally, women reasoned that broadening the scope of NIPT could increase the complexity of prenatal screening and raised concerns on the combined screening aims in one test (prediction of adverse pregnancy outcomes to improve foetal and maternal health vs. screening for foetal aneuploidies to increase reproductive autonomy). On a societal level, considerations on the risk of medicalising pregnancy and overall pressure to opt for NIPT were mentioned. CONCLUSION: In general, pregnant women have a positive attitude towards broadening the scope of NIPT to the prediction of pregnancy outcomes, although some concerns are acknowledged.

Public Opinions About Surgery in Older Adults: A Thematic Analysis.

OBJECTIVE: To examine public opinions of surgery in older adults. BACKGROUND: Increasing numbers of older adults are undergoing surgery. National healthcare organizations recognize the increased risks of postoperative complications and mortality in the older surgical population and have made efforts to improve the care of older adults undergoing surgery through hospital-level programs. However, limited research has explored the opinions and responses of the wider U.S. public regarding surgery in older adults. METHODS: We performed a qualitative, thematic analysis of reader comments posted in response to online newspaper articles relating to surgery in older adults. Articles were published in 2019-2020 and targeted for a popular press audience. RESULTS: Nine hundred eight reader comments posted in response to 6 articles relating to surgery in older adults were identified. Articles were published in online editions of print newspapers with a digital circulation between 1.3 and 5.7 million subscribers. Three themes were identified: (1) wariness/distrust towards healthcare: including general distrust of medicine and distrust of surgery, (2) problems experienced: ineffective communication and unrealistic expectations, and (3) recommended solutions: the need for multidisciplinary teams and patient-centered communication. CONCLUSIONS: Overall, the public viewed surgery in older adults with wariness/distrust due to ineffective communication and unrealistic expectations. Specialized surgical care tailored to the unique needs of older adults is needed. The public perspective suggests that U.S. health systems should strongly consider adopting programs that provide care to meet the unique needs of older adults undergoing surgery and ultimately improve both patient outcomes and their surgical experience.

Variability in Fetal Fraction Estimation: Comparing Fetal Fractions Reported by Noninvasive Prenatal Testing Providers Globally.

BACKGROUND: Fetal fraction (FF) measurement is considered important for reliable noninvasive prenatal testing (NIPT). Using minimal FF threshold as a quality parameter is under debate. We evaluated the variability in reported FFs of individual samples between providers and laboratories and within a single laboratory. METHODS: Genomic quality assessment and European Molecular Genetics Quality Network provide joint proficiency testing for NIPT. We compared reported FFs across all laboratories and stratified according to test methodologies. A single sample was sequenced repeatedly and FF estimated by 2 bioinformatics methods: Veriseq2 and SeqFF. Finally, we compared FFs by Veriseq and SeqFF in 87 351 NIPT samples. RESULTS: For each proficiency test sample we observed a large variability in reported FF, SDs and CVs ranging from 1.7 to 3.6 and 17.0 to 35.8, respectively. FF measurements reported by single nucleotide polymorphism-based methods had smaller SDs (0.5 to 2.4) compared to whole genome sequencing-based methods (1.8 to 2.9). In the internal quality assessment, SDs were similar between SeqFF (SD 1.0) and Veriseq v2 (SD 0.9), but mean FF by Veriseq v2 was higher compared to SeqFF (9.0 vs 6.4, P 0.001). In patient samples, reported FFs were on average 1.12-points higher in Veriseq than in SeqFF (P 0.001). CONCLUSIONS: Current methods do not allow for a reliable and consistent FF estimation. Our data show estimated FF should be regarded as a laboratory-specific range, rather than a precise number. Applying strict universal minimum thresholds might result in unnecessary test failures and should be used with caution.

Association between low fetal fraction in cell-free DNA screening and fetal chromosomal aberrations: A systematic review and meta-analysis.

OBJECTIVE: To perform a systematic review and meta-analysis of the available literature on low fetal fraction (LFF) in cell-free DNA (cfDNA) screening and the risk of fetal chromosomal aberrations. METHOD: We searched articles published between January 2010 and May 2021 in PubMed and EMBASE databases. Risk of bias was assessed using QUADAS-2. RESULTS: Twenty-seven studies met the inclusion criteria, comprising data of 243,700 singleton pregnancies. Compared to normal fetal fraction, LFF was associated with a higher risk of trisomy 13 (OR 5.99 [3.61-9.95], I 2 of heterogeneity = 0%, n = 22 studies), trisomy 18 (OR 4.46 [3.07-6.47], I 2  = 0%, n = 22 studies), monosomy X (OR 5.88 [2.34-14.78], I 2  = 18%, n = 10 studies), and triploidy (OR 36.39 [9.83-134.68], I 2  = 61%, n = 6 studies), but not trisomy 21 (OR 1.25 [0.76-2.03], I 2  = 36%, n = 23 studies). LFF was also associated with a higher risk of various other types of fetal chromosomal aberrations (OR 4.00 [1.78-9.00], I 2  = 2%, n = 11 studies). Meta-analysis of proportions showed that absolute rates of fetal chromosomal aberrations ranged between 1% and 2% in women with LFF. A limitation of this review is the potential risk of ascertainment bias because of differences in outcome assessment between pregnancies with LFF and those with normal fetal fraction. Heterogeneity in population characteristics or applied technologies across included studies may not have been fully addressed. CONCLUSION: An LFF test result in cfDNA screening is associated with an increased risk of fetal trisomy 13, trisomy 18, monosomy X, and triploidy, but not trisomy 21. Further research is needed to assess the association between LFF and other specific types of fetal chromosomal aberrations.

Transparency in hip fracture recovery over institutional boundaries: The transmural monitoring pathway.

OBJECTIVES: To develop a transmural pathway for healthcare professionals across institutions to monitor the recovery of hip fracture patients. The secondary objectives were to evaluate the pathway's feasibility and initial outcomes. DESIGN: Prospective cohort study. METHOD: Stakeholders of the hospital and geriatric rehabilitation institutions implemented a transmural monitoring pathway in which different geriatric health domains were monitored during three phases: The in-hospital, inpatient rehabilitation, and outpatient follow-up phase. The outcomes for the first 291 patients and the feasibility of the pathway were evaluated. If the outcomes of the clinimetrics significantly improved over time, progress in functional recovery was assumed. Feasibility was assessed according to the rate of adherence to the clinimetric tests. RESULTS: During the in-hospital phase, patients showed a decline in functional level (the Katz index of independence in Activities of Daily Living (Katz-ADL) pre-fracture vs. discharge: 0 (0-2) vs. 4 (4-5), P < 0.001). Patients, in which 78.6% (n = 140) had cognitive impairment and 41.2% had malnutrition, showed the most progress (Katz-ADL 2 (1-3)) during the inpatient rehabilitation phase. In the outpatient follow-up phase, recovery remained ongoing, but most patients had not returned to their pre-fracture functional levels (Katz-ADL 1 (1-3)). The pathway feasibility during the first phase was excellent (>85%), whereas room for improvement existed during other phases (<85%). CONCLUSION: The transmural monitoring pathway provides insight into the entire recovery process for all involved healthcare professionals. Patients showed the most progress during the rehabilitation phase. The pathway feasibility was excellent during the in-hospital phase, but improvements could be made during other phases.

Implementation of a medication delivery service for ambulatory oncology infusion patients.

OBJECTIVE: Patients receiving infusions for the treatment of cancer are commonly prescribed supportive care medications which are filled through retail pharmacies. The initial phase of the COVID-19 pandemic created hurdles for patients to receive supportive care medications due to concerns related to exposure risk. Meds-to-Chemo Chairs (M2CC) was created allowing an onsite retail pharmacy to dispense and hand-deliver supportive care prescriptions to patients in the infusion suite. The purpose of this study was to assess the value of this program. DATA SOURCES: The volume of prescriptions dispensed through the M2CC service, as well as the financial impact, was tracked through the prescription software system used by the onsite retail pharmacy dispensing and delivering the medications. DATA SUMMARY: Through the first 2.5 years of the program, M2CC has delivered over 13,000 prescriptions with an estimated gross revenue of $3.5 million. CONCLUSIONS: The M2CC medication delivery program has proved to be highly successful and feasible.

Relationships and resilience at work and at home: Impact of relational coordination on clinician work-life balance and well-being in times of crisis.

BACKGROUND: The COVID-19 pandemic has been an unusually comprehensive crisis that has taken a toll on people in their roles both at work and at home, giving rise to a new normal. PURPOSE: Relational coordination theory shows how communicating and relating for the purpose of task integration drives positive outcomes for workers, their clients, and their employers. The ecological theory of work-family spillover shows how relational dynamics from work spillover into family life, and vice versa. We build upon these two theories to understand how relationships at work impact work-life balance and worker well-being, especially in times of crisis. METHODOLOGY: This study was based on surveys of clinicians affiliated with a large California health system during the COVID-19 pandemic. Mediation and multilevel logistic regression models were used to assess how relational coordination among colleagues impacts well-being (job satisfaction and lack of burnout) through its effects on work-life balance (schedule control and personal time). RESULTS: A 1-point increase in relational coordination tripled clinician odds of having schedule control ( OR = 3.33, p < .001) and nearly doubled the odds of having adequate personal time ( OR = 1.83, p < .001). A 1-point increase in relational coordination nearly quadrupled odds of being satisfied with their job ( OR = 3.92, p < .001) and decreased odds of burnout by 64% ( OR = 0.36, p < .001). The impact of relational coordination on worker well-being was mediated by greater schedule control and personal time. CONCLUSION: Relational coordination among colleagues impacts worker well-being by enabling greater control over one's schedule and more personal time, thus creating a positive spillover from work to home in times of crisis. PRACTICE IMPLICATIONS: In times of crisis, leaders should prioritize relational coordination among colleagues in order to support their resilience both at work and at home.

AIR SAC TREMATODES (CYCLOCOELIDAE STOSSICH, 1902) INFECTING BIRDS IN ZOOLOGICAL INSTITUTIONS IN THE UNITED STATES.

Air sac trematodes (Digenea: Cyclocoelidae) were detected in 23 avian species from eight aviaries in the United States. Most of the infected host species were passeriform birds, but a few species in other orders also were infected. Four species of adult flukes were encountered: Circumvitellatrema momota, Morishitium sp., Psophiatrema greineri, and Szidatitrema yamagutii. Findings from retrospective review of medical records, necropsy records, and author observations are presented. Potential terrestrial snail intermediate hosts were collected from three indoor aviaries. A high prevalence (47%) of larval trematode infections was demonstrated in one species of nonnative snail (Prosopeas achatinacea); one larva was isolated and matched to the adult species (C. momota) from birds using PCR. Problems with introducing potentially infected wild-caught birds into aviaries, and exchanging captive individuals between aviaries where they potentially may carry infections, are discussed.

Women, Younger Clinicians', and Caregivers' Experiences of Burnout and Well-being During COVID-19 in a US Healthcare System.

BACKGROUND: The COVID-19 pandemic brought rapid changes to the work and personal lives of clinicians. OBJECTIVE: To assess clinician burnout and well-being during the COVID-19 pandemic and guide healthcare system improvement efforts. DESIGN: A survey asking about clinician burnout, well-being, and work experiences. PARTICIPANTS: Surveys distributed to 8141 clinicians from June to August 2020 in 9 medical groups and 17 hospitals at Sutter Health, a large healthcare system in Northern California. MAIN MEASURES: Burnout was the primary outcome, and other indicators of well-being and work experience were also measured. Descriptive statistics and multivariate logistic regression analyses were performed. All statistical inferences were based on weighted estimates adjusting for response bias. KEY RESULTS: A total of 3176 clinicians (39.0%) responded to the survey. Weighted results showed 29.2% reported burnout, and burnout was more common among women than among men (39.0% vs. 22.7%, p<0.01). In multivariate models, being a woman was associated with increased odds of reporting burnout (OR=2.19, 95% CI: 1.51-3.17) and being 55+ years old with lower odds (OR=0.54, 95% CI: 0.34-0.87). More women than men reported that childcare/caregiving was impacting work (32.9% vs. 19.0%, p<0.01). Even after controlling for age and gender, clinicians who reported childcare/caregiving responsibilities impacted their work had substantially higher odds of reporting burnout (OR=2.19, 95% CI: 1.54-3.11). Other factors associated with higher burnout included worrying about safety at work, being given additional work tasks, concern about losing one's job, and working in emergency medicine or radiology. Protective factors included believing one's concerns will be acted upon and feeling highly valued. CONCLUSIONS: This large survey found the pandemic disproportionally impacted women, younger clinicians, and those whose caregiving responsibilities impacted their work. These results highlight the need for a holistic and targeted strategy for improving clinician well-being that addresses the needs of women, younger clinicians, and those with caregiving responsibilities.

Moral distress amongst palliative care doctors working during the COVID-19 pandemic: A narrative-focussed interview study.

BACKGROUND: Palliative care professionals have had to adapt to rapidly changing COVID-19 restrictions with personal protective equipment and physical distancing measures impacting face-to-face communication with patients and relatives. AIM: To explore the narratives of palliative care doctors working during the pandemic to understand their experiences at a personal and professional level. DESIGN: In-depth narrative interviews were carried out via video call. Interviews were transcribed verbatim and analysed using a joint paradigmatic and narrative approach to elucidate common themes and closely explore individual narratives. SETTING/PARTICIPANTS: Eight palliative care doctors who had worked on a hospice inpatient unit in the UK before and during the pandemic were recruited from two hospices in Scotland. RESULTS: Three intersecting themes are described, the most significant being moral distress. Participants articulated a struggle to reconcile their moral convictions with the restrictions enforced, for example, wanting to provide support to patients through physical proximity but being unable to. To differing degrees, this resulted in internal conflict and emotional distress. Two further themes arose: the first concerned a loss of humanity in interaction and a striving to re-humanise communication through alternative means; the second being a change in staff morale as the pandemic progressed. CONCLUSIONS: Restrictions had a considerable impact on palliative care doctors' ability to communicate with and comfort patients which led to moral distress and contributed to decreasing morale. Future research could explore moral distress in palliative care settings internationally during the pandemic with a view to compare the factors affecting how moral distress was experienced.

How, when, and why individuals with stage IV cancer seen in an outpatient setting are referred to palliative care: a mixed methods study.

PURPOSE: Early palliative care (PC) for individuals with advanced cancer improves patient and family outcomes and experience. However, it is unknown when, why, and how in an outpatient setting individuals with stage IV cancer are referred to PC. METHODS: At a large multi-specialty group in the USA with outpatient PC implemented beginning in 2011, clinical records were used to identify adults diagnosed with stage IV cancer after January 1, 2012 and deceased by December 31, 2017 and their PC referrals and hospice use. In-depth interviews were also conducted with 25 members of medical oncology, gynecological oncology, and PC teams and thematically analyzed. RESULTS: A total of 705 individuals were diagnosed and died between 2012 and 2017: of these, 332 (47%) were referred to PC, with 48.5% referred early (within 60 days of diagnosis). Among referred patients, 79% received hospice care, versus 55% among patients not referred. Oncologists varied dramatically in their rates of referral to PC. Interviews revealed four referral pathways: early referrals, referrals without active anti-cancer treatment, problem-based referrals, and late referrals (when stopping treatment). Participants described PC's benefits as enhancing pain/symptom management, advance care planning, transitions to hospice, end-of-life experiences, a larger team, and more flexible patient care. Challenges reported included variation in oncologist practices, patient fears and misconceptions, and access to PC teams. CONCLUSION: We found high rates of use and appreciation of PC. However, interviews revealed that exclusively focusing on rates of referrals may obscure how referrals vary in timing, reason for referral, and usefulness to patients, families, and clinical teams.

Association between low fetal fraction in cell-free DNA testing and adverse pregnancy outcome: A systematic review.

OBJECTIVE: Low fetal fraction (LFF) in prenatal cell-free DNA (cfDNA) testing is an important cause of test failure and no-call results. LFF might reflect early abnormal placentation and therefore be associated with adverse pregnancy outcome. Here, we review the available literature on the relationship between LFF in cfDNA testing and adverse pregnancy outcome. METHOD: A systematic literature search was conducted in MEDLINE and EMBASE up to November 1, 2020. RESULTS: Five studies met the criteria for inclusion; all were retrospective observational cohort studies. The cohort sizes ranged from 370 to 6375 pregnancies, with all tests performed in the first trimester or early second trimester. A 4% cutoff for LFF was used in two studies, two studies used the 5th and 25th percentiles, respectively, and one study used a variety of cutoff values for LFF. LFF in prenatal cfDNA testing was observed to be associated with hypertensive disease of pregnancy, small for gestational age neonates, and preterm birth. Conflicting results were found regarding the association between LFF and gestational diabetes mellitus. CONCLUSIONS: LFF in cfDNA testing is associated with adverse pregnancy outcome,specifically pregnancy-related hypertensive disorders, preterm birth, and impaired fetal growth related to placental dysfunction. Since the available evidence is limited, a large prospective cohort study on the relationship between fetal fraction and pregnancy outcomes is needed.

Low fetal fraction in cell-free DNA testing is associated with adverse pregnancy outcome: Analysis of a subcohort of the TRIDENT-2 study.

OBJECTIVES: To assess the association between low fetal fraction (FF) in prenatal cell-free DNA (cfDNA) testing and adverse pregnancy outcomes. METHODS: We conducted a retrospective cohort study of participants of the TRIDENT-2 study (Dutch nationwide government-supported study offering cfDNA screening for fetal aneuploidies) who received a failed test result due to low FF (<4%) between April 2017 until February 2018. Outcome measures included pregnancy-induced hypertension (PIH), pre-eclampsia (PE), small for gestational age neonates (SGA), spontaneous preterm birth (sPTB), gestational diabetes mellitus (GDM), chromosomal aberrations, and congenital structural anomalies. RESULTS: Test failure due to low FF occurred in 295 women (1.12% of tests performed). Information regarding pregnancy outcomes was available for 96.3% of these women. The incidence of PIH, PE, SGA, sPTB, and GDM was 11.2%, 4.1%, 7.3%, 5.1%, and 14.8%, respectively. The prevalence of chromosomal aberrations and congenital structural anomalies was 1.4% and 4.1%, respectively. Incidences of PIH, PE ≥ 34 weeks of gestation, GDM, and prevalence of aneuploidy and congenital structural anomalies were higher in women with low FF compared to the general Dutch obstetric population. CONCLUSION: Low FF is associated with adverse pregnancy outcomes. The value of FF in the prediction of these outcomes needs to be further established.