Publications by authors named "Patricia Murphy"

234 Publications

The use of personal health information outside the circle of care: consent preferences of patients from an academic health care institution.

BMC Med Ethics 2021 Mar 24;22(1):29. Epub 2021 Mar 24.

Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, ON, Canada.

Background: Immense volumes of personal health information (PHI) are required to realize the anticipated benefits of artificial intelligence in clinical medicine. To maintain public trust in medical research, consent policies must evolve to reflect contemporary patient preferences.

Methods: Patients were invited to complete a 27-item survey focusing on: (a) broad versus specific consent; (b) opt-in versus opt-out approaches; (c) comfort level sharing with different recipients; (d) attitudes towards commercialization; and (e) options to track PHI use and study results.

Results: 222 participants were included in the analysis; 83% were comfortable sharing PHI with researchers at their own hospital, although younger patients (≤ 49 years) were more uncomfortable than older patients (50 + years; 13% versus 2% uncomfortable, p < 0.05). While 56% of patients preferred broad consent, 38% preferred specific consent; 6% preferred not sharing at all. The majority of patients (63%) preferred to be asked for permission before entry into a contact pool. Again, this trend was more pronounced for younger patients (≤ 49 years: 76%). Approximately half of patients were uncomfortable sharing PHI with commercial enterprises (51% uncomfortable, 27% comfortable, 22% neutral). Most patients preferred to track PHI usage (61%), with the highest proportion once again reported by the youngest patients (≤ 49 years: 71%). A majority of patients also wished to be notified regarding study results (70%).

Conclusions: While most patients were willing to share their PHI with researchers within their own institution, many preferred a transparent and reciprocal consent process. These data also suggest a generational shift, wherein younger patients preferred more specific consent options. Modernizing consent policies to reflect increased autonomy is crucial in fostering sustained public engagement with medical research.
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http://dx.doi.org/10.1186/s12910-021-00598-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7992944PMC
March 2021

Honoring Authorship Responsibilities in Manuscript Preparation.

J Midwifery Womens Health 2021 03 7;66(2):143-144. Epub 2021 Mar 7.

Deputy Editor.

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http://dx.doi.org/10.1111/jmwh.13222DOI Listing
March 2021

Examining the Association Between Chaplain Care and Patient Experience.

J Patient Exp 2020 Dec 19;7(6):1174-1180. Epub 2020 Apr 19.

Department of Religion, Health, and Human Values, Rush University Medical Center, Chicago, IL, USA.

A developing body of evidence indicates that chaplain care is associated with higher levels of patient/family satisfaction with their hospital care. We examined the association between chaplain care and patient experience among patients at Rush University Medical Center in Chicago who responded to Hospital Consumer Assessment of Healthcare Providers and Systems and Press Ganey survey items between 2011 and 2017. Information about chaplain care was taken from the inpatients' electronic medical record. Our analyses included 11 741 patients, 26.5% of whom had received any chaplain care. Patients with lower self-rated health were more likely to have received chaplain care ( < .001). In bivariate analyses, chaplain care was associated with lower likelihood of reporting the highest score for 4 patient experience items ( < .001). In multi-variable models that adjusted for patient self-rated health and other factors, the association between chaplain care and the 4 patient experience items was nonsignificant. There was no effect modification for patient religious affiliation, self-rated health, or other demographic factors. The chaplain care-patient experience association may be more complex than has initially appeared, and further research is needed to help us better understand it.
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http://dx.doi.org/10.1177/2374373520918723DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7786773PMC
December 2020

Differences in cancer prevalence among CHEK2 carriers identified via multi-gene panel testing.

Cancer Genet 2020 08 1;246-247:12-17. Epub 2020 Aug 1.

GeneDx, 207 Perry Parkway, Gaithersburg, MD 20877, USA.

Purpose: Although CHEK2 is a well-established cancer gene, questions remain including whether risks vary substantially between different variants and whether biallelic carriers have higher risks than heterozygotes. We report on a cohort of individuals with CHEK2 pathogenic and likely pathogenic variants (collectively, PV) in order to better characterize this gene.

Methods: We retrospectively queried samples submitted for multi-gene hereditary cancer testing to identify individuals with CHEK2 PVs and assessed differences in phenotypes among various genotypes.

Results: CHEK2 PVs were identified in 2508 individuals, including 32 individuals with biallelic CHEK2 PVs. Breast (female, 59.9% and male, 11.8%), prostate (20.1%), and colorectal (3.5%), were among the most frequently reported cancers. Select missense PVs showed similar cancer prevalence to truncating PVs while some others showed lower prevalence. No significant differences were observed between biallelic carriers and heterozygotes.

Conclusions: Our data support that some, but not all, CHEK2 missense PVs demonstrate lower cancer prevalence; further studies are needed to continue characterizing possible variant specific risks. In addition, biallelic CHEK2 PVs do not appear to be associated with a more severe phenotype than single CHEK2 PVs. Furthermore, co-occurrences with PVs in other cancer risk genes are common among CHEK2 heterozygotes and often warrant additional management.
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http://dx.doi.org/10.1016/j.cancergen.2020.07.001DOI Listing
August 2020

Midwifery in the Time of COVID-19.

J Midwifery Womens Health 2020 05 11;65(3):299-300. Epub 2020 May 11.

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http://dx.doi.org/10.1111/jmwh.13121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7272876PMC
May 2020

A portable survivorship care plan: a tool that helps educate and improve knowledge in childhood cancer survivors.

Support Care Cancer 2021 Jan 23;29(1):169-177. Epub 2020 Apr 23.

Pediatric Oncology, UCSF Benioff Children's Hospital, 550 16th Street, 4th Floor, San Francisco/Oakland, CA, 94158, USA.

Purpose: There is a growing population of survivors of childhood cancer at risk for late effects that can affect their overall quality of life. There is evidence that they have inadequate knowledge about their diagnosis, treatment, and subsequent late effects. A randomized study was conducted to determine if a portable credit card-sized plastic card, the "Survivor Healthcare Passport," improved the survivor's knowledge of diagnosis, treatment, risks, and follow-up care. The study included 126 patients 2 years post-end of cancer treatment and took place at the UCSF Benioff Children's Hospital Survivorship Clinic.

Methods: Patients attending the UCSF Survivorship clinic were randomized to receive or not receive a passport at their first survivorship clinic visit. Each groups' knowledge of diagnosis, treatment history, and follow-up needs was assessed at three time points with a questionnaire.

Results: Patients who received the passport distributed immediately after their visit demonstrated improved and sustained knowledge compared with survivors who did not receive the passport until more than 4 months later.

Conclusion: Enhancing a survivor's knowledge is an important endeavor and a continual challenge for practitioners in survivorship clinics. This portable educational tool helps improve patient knowledge of their cancer, therapy, and follow-up needs. By providing a tangible card that is quick and easy to access, survivors have access to their treatment late effects and follow-up needs that can also be shared with other healthcare providers.
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http://dx.doi.org/10.1007/s00520-020-05422-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7686177PMC
January 2021

Examining the impact of cancer on survivors' religious faith: A report from the American Cancer Society study of cancer survivors-I.

Psychooncology 2020 06 22;29(6):1036-1043. Epub 2020 Mar 22.

Religion, Health, and Human Values, Rush University Medical Center, Chicago, Illinois, USA.

Objectives: The impact of religion/spirituality (R/S) on cancer outcomes, including health-related quality of life (HRQoL), has been the topic of much investigation. Reports of the opposite, that is, the impact of cancer on R/S and associations with HRQoL, are few. The current study sought to explore the positive and negative impacts of cancer on the religious faith of survivors as well as the associations of such impacts with HRQoL.

Methods: Participants included 2309 9-year survivors of cancer from the American Cancer Society's Studies of Cancer Survivors-I. The impact of cancer on R/S was measured using items from the Patient-Reported Outcomes Measurement Information System (PROMIS) psychosocial impact of illness-faith, and HRQoL was measured with the 12-item short form (SF-12). Hierarchical regressions were used to examine the impact of cancer on R/S controlling for medical and demographic covariates.

Results: Consistent with hypotheses, the majority of survivors (70%) reported that cancer had a positive impact on religious faith, while the negative impact of cancer on religious faith was relatively rare (17%). In multivariable models, the negative impact of cancer on faith was associated with poorer HRQoL, both mental and physical, while the positive impact of cancer on faith was associated with greater mental well-being.

Conclusions: Cancer has a negative impact on religious faith for a minority of survivors. However, when it is reported, such negative impact is indicative of poorer mental and physical well-being. As such, it is important to identify those survivors at risk early in survivorship and provide support and intervention as needed.
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http://dx.doi.org/10.1002/pon.5374DOI Listing
June 2020

Safety of lemborexant versus placebo and zolpidem: effects on auditory awakening threshold, postural stability, and cognitive performance in healthy older participants in the middle of the night and upon morning awakening.

J Clin Sleep Med 2020 05 6;16(5):765-773. Epub 2020 Feb 6.

Eisai Inc., Woodcliff Lake, New Jersey.

Study Objectives: Our aim was to evaluate the effect of lemborexant versus zolpidem tartrate extended release 6.25 mg (ZOL) or placebo (PBO) on postural stability, auditory awakening threshold (AAT), and cognitive performance (cognitive performance assessment battery [CPAB]).

Methods: Healthy women (≥ 55 years) and men (≥ 65 years) were randomized, double-blind, to 1 of 4-period, single-dose crossover sequences, starting with lemborexant 5 mg (LEM5), 10 mg (LEM10), ZOL, or PBO. A ≥ 14-day washout followed all 4 treatments. Assessments were middle-of-the-night (MOTN) change from baseline in postural stability (primary prespecified comparison: LEM vs ZOL), AAT, absolute AAT, and CPAB for LEM5 and LEM10 versus ZOL and PBO; and morning change from baseline in postural stability and CPAB for LEM5 and LEM10 versus ZOL and PBO. Change from baseline measures were time-matched to a baseline night/morning when no study drug was administered.

Results: MOTN: Mean MOTN change from baseline in body sway was significantly higher for ZOL versus both lemborexant doses. There were no differences among the treatments regarding decibels required to awaken a participant. LEM5 was not statistically different from PBO on any CPAB domain; LEM10 and ZOL showed poorer performance on some tests of attention and/or memory. Morning: Body sway and cognitive performance following LEM5 or LEM10 did not differ from PBO; body sway was significantly higher for ZOL than PBO. Rates of treatment-emergent adverse events were low; there were no serious adverse events.

Conclusions: Lemborexant causes less postural instability than a commonly used sedative-hypnotic and does not impair the ability to awaken to auditory signals.

Clinical Trials Registration: Registry: ClinicalTrials.gov; Name: Crossover Study to Evaluate the Effect of Lemborexant Versus Placebo and Zolpidem on Postural Stability, Auditory Awakening Threshold, and Cognitive Performance in Healthy Subjects 55 Years and Older; URL: https://clinicaltrials.gov/ct2/show/NCT03008447; Identifier: NCT03008447.
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http://dx.doi.org/10.5664/jcsm.8294DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7849806PMC
May 2020

Apparently Heterozygous TP53 Pathogenic Variants May Be Blood Limited in Patients Undergoing Hereditary Cancer Panel Testing.

J Mol Diagn 2020 03 24;22(3):396-404. Epub 2019 Dec 24.

Inherited Cancer Program, GeneDx, Inc., Gaithersburg, Maryland.

Heterozygous (HET) TP53 pathogenic variants (PVs) are associated with Li-Fraumeni syndrome (LFS), a dominantly inherited condition causing high risk for sarcoma, breast, and other cancers. Recent reports describe patients without features of LFS and apparently HET TP53 PVs in blood cells but not fibroblasts (FBs), suggesting the variant occurred sporadically during hematopoiesis and rose to high allele fraction through clonal expansion. To explore possible clonal hematopoiesis in patients undergoing hereditary cancer testing, FB testing was performed for patients with apparently HET or mosaic TP53 PVs identified in blood, oral rinse, or buccal specimens via next-generation sequencing panels. Among 291 individuals with TP53 PVs, 146 (50.2%) appeared HET and 145 (49.8%) were mosaic. Twenty-eight HET cases were proven constitutional through familial testing. FB testing was completed for 17 apparently HET and 36 mosaic patients. FB testing was positive in 11 of 17 (64.7%) apparently HET patients, only one of whom met Chompret criteria. Of 36 mosaic patients, 5 (13.9%) were also mosaic in FBs, indicating constitutional mosaicism. Breast cancers in patients with constitutional TP53 PVs were diagnosed at younger ages (P < 0.0001) and more likely to demonstrate human epidermal growth factor receptor 2 overexpression (P = 0.0003). These results demonstrate the utility of cultured FB testing to clarify constitutional status for TP53 PVs identified on next-generation sequencing panels, particularly for patients not meeting LFS or Chompret criteria.
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http://dx.doi.org/10.1016/j.jmoldx.2019.12.003DOI Listing
March 2020

Comparison of Lemborexant With Placebo and Zolpidem Tartrate Extended Release for the Treatment of Older Adults With Insomnia Disorder: A Phase 3 Randomized Clinical Trial.

JAMA Netw Open 2019 12 2;2(12):e1918254. Epub 2019 Dec 2.

Eisai Inc, Woodcliff Lake, New Jersey.

Importance: Insomnia disorder is prevalent and associated with health risks in older adults; however, efficacy and safety issues with existing treatments create significant unmet needs in this patient population.

Objective: To compare treatment with the orexin receptor antagonist lemborexant with placebo and zolpidem tartrate extended release in participants with insomnia disorder.

Design, Setting, And Participants: The Study of the Efficacy and Safety of Lemborexant in Subjects 55 Years and Older With Insomnia Disorder (SUNRISE 1) clinical trial was a global randomized double-blind parallel-group placebo-controlled active-comparator phase 3 study conducted at 67 sites in North America and Europe from May 31, 2016, to January 30, 2018. Data analyses were conducted from January 31, 2018, to September 10, 2018. Participants were 55 years and older with insomnia disorder characterized by reported sleep maintenance difficulties and confirmed by sleep history, sleep diary, and polysomnography. Participants could have also had sleep onset difficulties.

Interventions: Participants received placebo, zolpidem tartrate extended release (6.25 mg), or lemborexant (5 mg or 10 mg) for 1 month at bedtime.

Main Outcomes And Measures: Paired polysomnograms were collected at baseline, the first 2 nights, and the last 2 nights of treatment. The primary end point was the change from baseline in latency to persistent sleep for lemborexant therapy vs placebo. Key secondary end points were changes from baseline in sleep efficiency and wake-after-sleep onset compared with placebo, and wake-after-sleep onset in the second half of the night compared with zolpidem therapy.

Results: Among 1006 participants randomized (placebo, n = 208; zolpidem, n = 263; lemborexant 5 mg, n = 266; and lemborexant 10 mg, n = 269), 869 (86.4%) were women and the median age was 63 years (range, 55-88 years). Both doses of lemborexant therapy demonstrated statistically significant greater changes from baseline on objective sleep onset as assessed by latency to persistent sleep (log transformed) that was measured using polysomnography at the end of 1 month of treatment (nights 29 and 30) compared with placebo (primary end point for least squares geometric means treatment ratio vs placebo: for lemborexant 5 mg, 0.77; 95% CI, 0.67-0.89; P < .001; for lemborexant 10 mg, 0.72; 95% CI, 0.63-0.83; P < .001). For nights 29 and 30, as measured using polysomnography, the mean change from baseline in sleep efficiency (LSM treatment difference vs placebo for lemborexant 5 mg, 7.1%; 95% CI, 5.6%-8.5%; P < .001 and for lemborexant 10 mg, 8.0%; 95% CI, 6.6%-9.5%; P < .001) and wake-after-sleep onset (least squares mean treatment ratio vs placebo for lemborexant 5 mg, -24.0 min; 95% CI, -30.0 to -18.0 min; P < .001 and for lemborexant 10 mg, -25.4 min; 95% CI, -31.4 to -19.3 min; P < .001) were significantly greater for both doses of lemborexant therapy compared with placebo. Also, for nights 29 and 30, wake-after-sleep onset in the second half of the night (least squares mean treatment difference vs zolpidem for lemborexant 5 mg, -6.7 min; 95% CI, -11.2 to -2.2 min; P = .004 and for lemborexant 10 mg, -8.0 min; 95% CI, -12.5 to -3.5 min; P < .001) was significantly greater for both doses of lemborexant therapy compared with zolpidem therapy measured using polysomnography. Six participants (4 in the zolpidem group and 2 in the lemborexant 5 mg group) reported serious adverse events; none were treatment-related. Other adverse events were mostly mild or moderate in severity.

Conclusions And Relevance: In this randomized clinical trial, lemborexant therapy significantly improved both sleep onset and sleep maintenance, including in the second half of the night, compared with both placebo and zolpidem measured objectively using polysomnography. Lemborexant therapy was well tolerated.

Trial Registrations: ClinicalTrials.gov identifier: NCT02783729; EudraCT identifier: 2015-001463-39.
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http://dx.doi.org/10.1001/jamanetworkopen.2019.18254DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6991236PMC
December 2019

Insurance impacts survival for children, adolescents, and young adults with bone and soft tissue sarcomas.

Cancer Med 2020 02 15;9(3):951-958. Epub 2019 Dec 15.

Helen Diller Family Comprehensive Cancer Center, UCSF, San Francisco, CA, USA.

Background: While racial/ethnic survival disparities have been described in pediatric oncology, the impact of income has not been extensively explored. We analyzed how public insurance influences 5-year overall survival (OS) in young patients with sarcomas.

Methods: The University of California San Francisco Cancer Registry was used to identify patients aged 0-39 diagnosed with bone or soft tissue sarcomas between 2000 and 2015. Low-income patients were defined as those with no insurance or Medicaid, a means-tested form of public insurance. Survival curves were computed using the Kaplan-Meier method and compared using log-rank tests and Cox models. Causal mediation was used to assess whether the association between public insurance and mortality is mediated by metastatic disease.

Results: Of 1106 patients, 39% patients were classified as low-income. Low-income patients were more likely to be racial/ethnic minorities and to present with metastatic disease (OR 1.96, 95% CI 1.35-2.86). Low-income patients had significantly worse OS (61% vs 71%). Age at diagnosis and extent of disease at diagnosis were also independent predictors of OS. When stratified by extent of disease, low-income patients consistently had significantly worse OS (localized: 78% vs 84%, regional: 64% vs 73%, metastatic: 23% vs 30%, respectively). Mediation analysis indicated that metastatic disease at diagnosis mediated 15% of the effect of public insurance on OS.

Conclusions: Low-income patients with bone and soft tissue sarcomas had decreased OS regardless of disease stage at presentation. The mechanism by which insurance status impacts survival requires additional investigation, but may be through reduced access to care.
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http://dx.doi.org/10.1002/cam4.2739DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6997066PMC
February 2020

Measuring Quality of Life Loss in Litigation.

Phys Med Rehabil Clin N Am 2019 08 30;30(3):589-598. Epub 2019 Apr 30.

Department of Women & Gender Studies, University of Toledo, 2801 W. Bancroft Street, MS 965, Toledo, OH 43606-3390, USA. Electronic address:

This article discusses measuring quality of life (QOL) loss in litigation. Case examples are provided. The complexity challenge in QOL assessment is more easily addressed since the advent of computer adaptive testing, which is used by physicians and rehabilitationists in the administration of psychometric instruments to determine QOL loss. It is now possible to write algorithms to capture QOL data through text-mining. If QOL domains and their factors could be accessed through text-mining, it would make for an extraordinary opportunity for much needed doctoral level research in QOL issues for injured workers in workers' compensation programs.
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http://dx.doi.org/10.1016/j.pmr.2019.03.007DOI Listing
August 2019

Distress and self-care among chaplains working in palliative care.

Palliat Support Care 2019 10;17(5):542-549

Rush University Medical Center, Chicago, IL.

Background: The prevalence of burnout and distress among palliative care professionals has received much attention since research suggests it negatively impacts the quality of care. Although limited, research suggests low levels of burnout or distress among healthcare chaplains; however, there has been no research among chaplains working in specific clinical contexts, including palliative care.

Objective: This study explored the distress, self-care, and debriefing practices of chaplains working in palliative care.

Method: Exploratory, cross-sectional survey of professional chaplains. Electronic surveys were sent to members of four professional chaplaincy organizations between February and April 2015. Primary measures of interest included Professional Distress, Distress from Theodicy, Informal Self-care, Formal Self-care, and debriefing practices.

Result: More than 60% of chaplains working in palliative care reported feeling worn out in the past 3 months because of their work as a helper; at least 33% practice Informal Self-care weekly. Bivariate analysis suggested significant associations between Informal Self-care and both Professional Distress and Distress from Theodicy. Multivariate analysis also identified that distress decreased as Informal and Formal Self-care increased.

Significance Of Results: Chaplains working in palliative care appear moderately distressed, possibly more so than chaplains working in other clinical areas. These chaplains also use debriefing, with non-chaplain palliative colleagues, to process clinical experiences. Further research is needed about the role of religious or spiritual beliefs and practices in protecting against stress associated with care for people at the end of life.
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http://dx.doi.org/10.1017/S1478951518001062DOI Listing
October 2019

Trajectories of spiritual well-being in long-term survivors of cancer: A report from the American Cancer Society's Studies of Cancer Survivors-I.

Cancer 2019 05 11;125(10):1726-1736. Epub 2019 Jan 11.

Religion, Health, and Human Values, Rush University Medical Center, Chicago, Illinois.

Background: Existing research indicates that religion, spirituality, or both are important to the quality of life of patients with cancer. The current study is the first to characterize trajectories of spiritual well-being (SWB) over time and to identify their predictors in a large, diverse sample of long-term cancer survivors.

Methods: The participants were 2365 cancer survivors representing 10 cancer diagnoses from the American Cancer Society's Studies of Cancer Survivors-I, and they were assessed at 3 time points: 1, 2, and 9 years after their diagnosis. SWB was assessed with the 3 subscales of the Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being (FACIT-Sp; ie, Meaning, Peace, and Faith). Predictors included demographic, medical, and psychosocial variables. Latent growth mixture modeling was used to identify trajectories and test their predictors.

Results: Four distinct trajectories of SWB were identified for each of the FACIT-Sp subscales: stable-high (45%-61% of the sample, depending on the subscale), stable-moderate (23%-33%), stable-low (7%-16%), and declining (6%-10%). Significant predictors of these trajectories included age, sex, race, education, comorbidities, symptom burden, social support, and optimism, but not always in the hypothesized direction. For some of the subscale trajectories, a recurrence of cancer, multiple cancers, or metastatic cancer was associated with lower SWB.

Conclusions: This is the first study to establish the existence and predictors of heterogeneous trajectories of SWB in long-term survivors of cancer. Because SWB is an important component of quality of life, the current results indicate characteristics of persons who could be at greater risk for a decline or consistently low scores in SWB and may warrant clinical attention.
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http://dx.doi.org/10.1002/cncr.31967DOI Listing
May 2019

On-the-road driving performance the morning after bedtime administration of lemborexant in healthy adult and elderly volunteers.

Sleep 2019 04;42(4)

Department of Neuropsychology and Psychopharmacology, Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, The Netherlands.

Study Objectives: To assess potential effects of lemborexant on next-morning driving performance in adult and elderly healthy volunteers.

Methods: Randomized, double-blind, double-dummy, placebo and active-controlled, four period incomplete crossover study in 48 healthy volunteers (22 females), 23-78 years old. Participants were treated at bedtime for eight consecutive nights with two of three dose levels of lemborexant (2.5, 5, or 10 mg), zopiclone 7.5 mg (on the first and last night with placebo on intervening nights), or placebo. Driving performance was assessed in the morning on days 2 and 9 using a standardized highway driving test in normal traffic, measuring standard deviation of lateral position (SDLP). Drug-placebo differences in SDLP >2.4 cm were considered to reflect clinically meaningful driving impairment.

Results: Mean drug-placebo differences in SDLP following lemborexant 2.5, 5, and 10 mg on days 2 and 9 were 0.74 cm or less. The upper bound of the 95% confidence intervals (CIs) for lemborexant treatment groups were all below 2.4 cm and the 95% CIs included zero, indicating that the effects were neither clinically meaningful nor statistically significant. Symmetry analysis further supported the lack of clinically meaningful impairment with lemborexant.

Conclusions: When assessed starting ~9 h after lemborexant administration at bedtime the previous night, there was no statistically significant or clinically meaningful effect on driving performance in healthy adults and elderly, as assessed by either mean differences in SDLP relative to placebo or symmetry analysis. In this study, lemborexant at doses up to 10 mg was well-tolerated.

Clinical Trial Registration: clinicaltrials.gov, NCT02583451. https://clinicaltrials.gov/ct2/show/NCT02583451.
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http://dx.doi.org/10.1093/sleep/zsy260DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6448281PMC
April 2019

Germline pathogenic variants identified in women with ovarian tumors.

Gynecol Oncol 2018 12 12;151(3):481-488. Epub 2018 Oct 12.

GeneDx, Gaithersburg, MD, USA.

Objective: The recognition of genes implicated in ovarian cancer risk beyond BRCA1, BRCA2, and the Lynch syndrome genes has increased the variety of testing options available to providers and patients. We report the frequency of pathogenic variants identified among individuals with ovarian cancer undergoing clinical genetic testing via a multi-gene hereditary cancer panel.

Methods: Genetic testing of up to 32 genes using a hereditary cancer panel was performed on 4439 ovarian cancer cases, and results were analyzed for frequency of pathogenic variants. Statistical comparisons were made using t-tests and Fisher's exact tests.

Results: The positive yield was 13.2%. While BRCA1/2 pathogenic variants were most frequent, one third (33.7%) of positive findings were in other homologous recombination genes, and accounted for over 40.0% of findings in endometrioid and clear cell cases. Women with a personal history of breast cancer (22.1%), who reported a family history of ovarian cancer (17.7%), and/or serous histology (14.7%) were most likely to harbor a pathogenic variant. Those with very early onset (<30 years) and late onset (≥70 years) ovarian cancer had low positive yields.

Conclusions: Our study highlights the genetic heterogeneity of ovarian cancer, showing that a large proportion of cases are not due to BRCA1/2 and the Lynch syndrome genes, but still have an identifiable hereditary basis. These findings substantiate the utility of multi-gene panel testing in ovarian cancer care regardless of age at diagnosis, family history, or histologic subtype, providing evidence for testing beyond BRCA1/2 and the Lynch syndrome genes.
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http://dx.doi.org/10.1016/j.ygyno.2018.09.030DOI Listing
December 2018

Interprofessional Models for Shared Decision Making: The Role of the Health Care Chaplain.

J Health Care Chaplain 2019 Jan-Mar;25(1):20-44. Epub 2018 Oct 15.

e Rush University Medical Center , Chicago , Illinois.

Shared decision making (SDM) is a central component of patient-centered care; however, a minimal amount is known about what health care chaplains contribute to this process. Data from 463 full-time chaplains practicing in the United States collected by an online survey was analyzed using SPSS 26 for bivariate and multivariate logistical regressions to identify variables impacting chaplain integration into SDM. Coding of free text responses yielded multiple domains for chaplain contributions and barriers. Thirty-eight percent of chaplains reported being often or frequently integrated into health care team discussions regarding medical decisions, with years of professional experience, time spent supporting the emotional processing of medical decisions, and being well-prepared as the strongest predictors for high integration. Qualitative analysis yielded a multifaceted picture that includes chaplain attention to the impact religion has on decision making, a focus on the patient story, and chaplains as mediators between patients, families, and the health care team. The full integration of chaplains into SDM will require education of the interdisciplinary team regarding the scope of chaplain knowledge and skills, as well as organizational level changes in chaplain to patient ratios and coverage models. In this era of increased fragmentation of health care provision and advancing complexity of medical decision making, models of Interprofessional Shared Decision Making (IP-SDM) such as the one proposed here that appreciate the specialized knowledge and skills of each member of the health care team hold promise for enhancing patient-centered care.
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http://dx.doi.org/10.1080/08854726.2018.1501131DOI Listing
April 2020

Utility of Expedited Hereditary Cancer Testing in the Surgical Management of Patients with a New Breast Cancer Diagnosis.

Ann Surg Oncol 2018 Nov 30;25(12):3556-3562. Epub 2018 Aug 30.

GeneDx, Gaithersburg, MD, USA.

Background: Knowledge of a germline pathogenic/likely pathogenic variant (PV) may inform breast cancer management. BRCA1/2 PV often impact surgical decisions, but data for multi-gene panel testing are lacking. Expedited genetic testing reduces turn-around times based on request for treatment-related decision making. This report aims to describe the clinical utility of expedited multi-gene panel testing for patients with newly diagnosed breast cancer.

Methods: Clinical and demographic information were reviewed for patients with newly diagnosed female breast cancer undergoing expedited panel testing between 2013 and 2017. The National Comprehensive Cancer Network guidelines (NCCN, version 1.2018) were evaluated in terms of published management recommendations for the genes in which PVs were identified.

Results: The overall PV yield was 9.5% (678/7127) for women undergoing expedited panel testing, with 700 PVs identified among 678 women. PVs were identified in genes other than BRCA1/2 in 55.9% (391/700) of cases. The NCCN guidelines recommend management for the genes in which 96.6% (676/700) of PVs are identified. The NCCN guidelines also recommend risk-reducing mastectomy for 46.0% (322/700) of PVs identified. An additional 45.6% (319/700) of PVs were identified in genes for which NCCN recommends mastectomy based on family history. In addition, 49.9% (349/700) of PVs were in genes with NCCN guidelines recommending prophylactic surgery for tissues other than breast.

Conclusion: A majority of the patients with newly diagnosed breast cancer were candidates for surgical intervention according to the NCCN guidelines, and half of these patients would have been missed if only BRCA1/2 testing had been ordered. Expedited multi-gene hereditary cancer panel testing should be considered as a first-line approach to provide comprehensive information for breast cancer management.
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http://dx.doi.org/10.1245/s10434-018-6581-8DOI Listing
November 2018

Somatic hematopoietic TP53 mosaicism in women with breast cancer exposed to ionizing radiation.

Breast J 2018 09 21;24(5):852-854. Epub 2018 May 21.

Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, Pittsburgh, PA, USA.

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http://dx.doi.org/10.1111/tbj.13056DOI Listing
September 2018

Light-focusing human micro-lenses generated from pluripotent stem cells model lens development and drug-induced cataract .

Development 2018 01 9;145(1). Epub 2018 Jan 9.

School of Medicine, Western Sydney University, Campbelltown, NSW 2560, Australia

Cataracts cause vision loss and blindness by impairing the ability of the ocular lens to focus light onto the retina. Various cataract risk factors have been identified, including drug treatments, age, smoking and diabetes. However, the molecular events responsible for these different forms of cataract are ill-defined, and the advent of modern cataract surgery in the 1960s virtually eliminated access to human lenses for research. Here, we demonstrate large-scale production of light-focusing human micro-lenses from spheroidal masses of human lens epithelial cells purified from differentiating pluripotent stem cells. The purified lens cells and micro-lenses display similar morphology, cellular arrangement, mRNA expression and protein expression to human lens cells and lenses. Exposing the micro-lenses to the emergent cystic fibrosis drug Vx-770 reduces micro-lens transparency and focusing ability. These human micro-lenses provide a powerful and large-scale platform for defining molecular disease mechanisms caused by cataract risk factors, for anti-cataract drug screening and for clinically relevant toxicity assays.
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http://dx.doi.org/10.1242/dev.155838DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5825866PMC
January 2018

From Mental Illness to Mental Health: Improving Access to Care.

J Midwifery Womens Health 2017 11 15;62(6):655-656. Epub 2017 Nov 15.

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http://dx.doi.org/10.1111/jmwh.12700DOI Listing
November 2017

Religious/Spiritual Struggle in Young Adult Hematopoietic Cell Transplant Survivors.

J Adolesc Young Adult Oncol 2018 04 3;7(2):210-216. Epub 2017 Nov 3.

7 Division of Pediatric Oncology, Department of Pediatrics, Mary Bridge Hospital/MultiCare Health System , Tacoma, Washington.

Purpose: This study describes the prevalence of religious and/or spiritual (R/S) struggle in long-term young adult (YA) survivors following hematopoietic cell transplantation (HCT) as well as existential concerns (EC), social support, and demographic, medical, and emotional correlates of R/S struggle.

Methods: Data were collected as part of an annual survey of survivors of HCT aged 18-39 years at survey completion; age at HCT was 1-39 years. Study measures included measures of R/S struggle (defined as any non-zero response on the negative religious coping subscale from Brief RCOPE), quality of life (QOL), and depression. Factors associated with R/S struggle were identified using multivariable logistic regression models.

Results: Fifty-two of the 172 respondents (30%), who ranged from less than a year to 33 years after HCT, had some R/S struggle. In bivariate analysis, depression was associated with R/S struggle. In a multivariable logistic regression model, individuals with greater EC were nearly five times more likely to report R/S struggle. R/S struggle was not associated with age at transplant, time since transplant, gender, race, R/S self-identification, or medical variables.

Conclusion: R/S struggle is common among YA HCT survivors, even many years after HCT. There is a strong correlation between EC and R/S struggle. Given the prevalence of R/S struggle and its associations with EC, survivors should be screened and referred to professionals with expertise in EC and R/S struggle as appropriate. Further study is needed to determine longitudinal trajectory, impact of struggle intensity, causal relationships, and effects of R/S struggle on health, mood, and QOL for YA HCT survivors.
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http://dx.doi.org/10.1089/jayao.2017.0069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5899275PMC
April 2018

Lemborexant, A Dual Orexin Receptor Antagonist (DORA) for the Treatment of Insomnia Disorder: Results From a Bayesian, Adaptive, Randomized, Double-Blind, Placebo-Controlled Study.

J Clin Sleep Med 2017 Nov 15;13(11):1289-1299. Epub 2017 Nov 15.

Eisai Inc, Woodcliff Lake, New Jersey.

Study Objectives: To identify dose(s) of lemborexant that maximize insomnia treatment efficacy while minimizing next-morning residual sleepiness and evaluate lemborexant effects on polysomnography (PSG) measures (sleep efficiency [SE], latency to persistent sleep [LPS], and wake after sleep onset [WASO]) at the beginning and end of treatment.

Methods: Adults and elderly subjects with insomnia disorder per the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition were enrolled in a multicenter, randomized, double-blind, placebo-controlled, Bayesian, adaptive, parallel-group study, receiving lemborexant (1, 2.5, 5, 10, 15, 25 mg) or placebo for 15 nights. Efficacy assessments included a utility function that combined efficacy (SE) and safety (residual morning sleepiness as measured by Karolinska Sleepiness Scale [KSS]), PSG measures, and sleep diary. Safety assessments included KSS, Digit Symbol Substitution Test, computerized reaction time tests, and adverse events (AEs).

Results: A total of 616 subjects were screened; 291 were randomized. Baseline characteristics were similar between lemborexant groups and placebo (∼63% female, median age: 49.0 years). The study was stopped for early success after the fifth interim analysis when the 15-mg dose met utility index/KSS criteria for success; 3 other doses also met the criteria. Compared with placebo, subjects showed significant improvements in SE, subjective SE, LPS, and subjective sleep onset latency at the beginning and end of treatment for lemborexant doses ≥ 5 mg ( < .05). WASO and subjective WASO showed numerically greater improvements for doses > 1 mg. AEs, mostly mild to moderate, included dose-related somnolence.

Conclusions: Lemborexant doses ranging from 2.5-10 mg provided efficacy for the treatment of insomnia while minimizing next-morning residual sleepiness.

Clinical Trial Registration: Title: A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group, Bayesian Adaptive Randomization Design, Dose Response Study of the Efficacy of E2006 in Adults and Elderly Subjects With Chronic Insomnia; URL: https://clinicaltrials.gov/ct2/show/NCT01995838; Identifier: NCT01995838.
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http://dx.doi.org/10.5664/jcsm.6800DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5656478PMC
November 2017

Use of a structured panel process to define antimicrobial prescribing appropriateness in critical care.

J Antimicrob Chemother 2018 Jan;73(1):246-249

University Health Network, 101 College St., Toronto, Ontario M5G 1L7, Canada.

Background: Antimicrobial prescribing is frequently reported as appropriate or inappropriate, particularly in the ICU. However, the definitions used are non-standardized and lack validity and reliability.

Objectives: To develop standardized definitions of appropriateness for antimicrobial prescribing in the critical care setting.

Methods: We used consensus-based modified Delphi and RAND appropriateness methodology to develop criteria to define appropriateness of antimicrobial prescribing. A multiphased approach with an online questionnaire followed by a facilitated in-person meeting was utilized and included clinicians from a variety of practice areas (e.g. surgeons, infectious diseases specialists, intensivists, transplant specialists and pharmacists).

Results: There were a total of 23 criteria agreed upon to define the following categories of antimicrobial prescribing: appropriate; effective but unnecessary; inappropriate; and under-treatment.

Conclusions: These standardized criteria for appropriateness may be generalizable to other patient populations and utilized with other tools to adjudicate prescribing practices.
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http://dx.doi.org/10.1093/jac/dkx341DOI Listing
January 2018

Mutation of the Human Circadian Clock Gene CRY1 in Familial Delayed Sleep Phase Disorder.

Cell 2017 04;169(2):203-215.e13

Laboratory of Genetics, The Rockefeller University, New York, NY 10065, USA. Electronic address:

Patterns of daily human activity are controlled by an intrinsic circadian clock that promotes ∼24 hr rhythms in many behavioral and physiological processes. This system is altered in delayed sleep phase disorder (DSPD), a common form of insomnia in which sleep episodes are shifted to later times misaligned with the societal norm. Here, we report a hereditary form of DSPD associated with a dominant coding variation in the core circadian clock gene CRY1, which creates a transcriptional inhibitor with enhanced affinity for circadian activator proteins Clock and Bmal1. This gain-of-function CRY1 variant causes reduced expression of key transcriptional targets and lengthens the period of circadian molecular rhythms, providing a mechanistic link to DSPD symptoms. The allele has a frequency of up to 0.6%, and reverse phenotyping of unrelated families corroborates late and/or fragmented sleep patterns in carriers, suggesting that it affects sleep behavior in a sizeable portion of the human population.
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http://dx.doi.org/10.1016/j.cell.2017.03.027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5479574PMC
April 2017

Examining the Validity of the Rush Protocol to Screen for Religious/Spiritual Struggle.

J Health Care Chaplain 2017 Jul-Sep;23(3):98-112. Epub 2017 Apr 3.

b Seattle Cancer Care Alliance , Seattle , Washington , USA.

Effective deployment of limited spiritual care resources requires valid and reliable methods of screening that can be used by nonchaplain health care professionals to identify and refer patients with potential religious/spiritual (R/S) need. Research regarding the validity of existing approaches to R/S screening is limited. In a sample of 1,399 hematopoietic stem cell transplant survivors, we tested the validity of the Rush Protocol and two alternative versions of it. The negative religious coping subscale of the Brief RCOPE provided the reference standard. Based on the Protocol, 21.9% of the survivors were identified as having potential R/S struggle. The sensitivity of the Protocol was low (42.1%) and the specificity was marginally acceptable (81.3%). The sensitivity and specificity of the two alternative versions were similar to those for the unmodified Protocol. Further research with the Rush Protocol, and other models, should be pursued to develop the best evidence-based approaches to R/S screening.
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http://dx.doi.org/10.1080/08854726.2017.1294861DOI Listing
September 2017

Listening to Midwives.

J Midwifery Womens Health 2017 Jan;62(1):7-8

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http://dx.doi.org/10.1111/jmwh.12599DOI Listing
January 2017