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

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.

Development of 2nd generation aminomethyl spectinomycins that overcome native efflux in Mycobacterium abscessus.

Mycobacterium abscessus (Mab), a nontuberculous mycobacterial (NTM) species, is an emerging pathogen with high intrinsic drug resistance. Current standard-of-care therapy results in poor outcomes, demonstrating the urgent need to develop effective antimycobacterial regimens. Through synthetic modification of spectinomycin (SPC), we have identified a distinct structural subclass of N-ethylene linked aminomethyl SPCs (eAmSPCs) that are up to 64-fold more potent against Mab over the parent SPC. Mechanism of action and crystallography studies demonstrate that the eAmSPCs display a mode of ribosomal inhibition consistent with SPC. However, they exert their increased antimicrobial activity through enhanced accumulation, largely by circumventing efflux mechanisms. The N-ethylene linkage within this series plays a critical role in avoiding TetV-mediated efflux, as lead eAmSPC 2593 displays a mere fourfold susceptibility improvement against Mab ΔtetV, in contrast to the 64-fold increase for SPC. Even a minor shortening of the linkage by a single carbon, akin to 1st generation AmSPC 1950, results in a substantial increase in MICs and a 16-fold rise in susceptibility against Mab ΔtetV. These shifts suggest that longer linkages might modify the kinetics of drug expulsion by TetV, ultimately shifting the equilibrium towards heightened intracellular concentrations and enhanced antimicrobial efficacy. Furthermore, lead eAmSPCs were also shown to synergize with various classes of anti-Mab antibiotics and retain activity against clinical isolates and other mycobacterial strains. Encouraging pharmacokinetic profiles coupled with robust efficacy in Mab murine infection models suggest that eAmSPCs hold the potential to be developed into treatments for Mab and other NTM infections.

Subsequent Renal Cancer Among Childhood Cancer Survivors: Analysis of Surveillance, Epidemiology, and End Results.

Renal cancer, although still rare among individuals under 45 years of age, is on the rise in the general population. The risk and timing of subsequent renal cancer in survivors of childhood cancer is not well established. Using the SEER registry, we reported the incidence of subsequent malignant renal neoplasms after treatment for primary malignancy diagnosed under 20 years of age. We evaluated clinical characteristics, standardized incidence ratio (SIR), and Kaplan-Meier survival estimates. Fifty-three survivors developed subsequent renal cancer (54 total cases). Of these, 54.7% were female, 88.7% were white, and 13.2% were Hispanic. Mean ages at primary malignancy and subsequent renal cancer were 10.1 and 31.1 years, respectively. Forty-seven cases were second cancers, 6 were third, and 1 was fourth. For survivors of childhood cancer, the overall SIR for renal cancer was 4.52 (95% CI: 3.39-5.89). The 5-year overall survival rate after development of subsequent renal cancer was 73% (95% CI: 58%-83%). Renal cancer occurs 4.5 times more frequently in childhood cancer survivors than in the general population, necessitating long-term care considerations.

Intraoperative hemodialysis with supra- and infradiaphragmatic catheters for liver transplantation.

PURPOSE: The benefits of intraoperative dialysis during orthotopic liver transplantation remain controversial. In patients with anuric renal failure and portopulmonary hypertension, maintaining venous return during caval clamping and unclamping along with minimizing fluid overload is critical to avoiding right ventricular strain and failure. CLINICAL FEATURES: We present the case of a 54-yr-old female who underwent orthotopic liver transplantation for alcohol-related liver disease with acute decompensation including severe hepatorenal syndrome (anuric requiring dialysis), probable hepatopulmonary syndrome, moderate pulmonary hypertension (right ventricular systolic pressure, 44 mm Hg), hepatic encephalopathy (grade 2), and esophageal varices. Prior to incision, pulmonary arterial pressures were 48/28 (mean, 35) mm Hg with a central venous pressure of 30 mm Hg, cardiac output of 7.4 L·min-1, and pulmonary vascular resistance of 98 dynes·sec·cm-5. In the context of right ventricular strain and volume overload observed on transthoracic echocardiography, we inserted an additional dialysis catheter into the right femoral vein. We initiated dialysis using the two catheters as a circuit (femoral line to the dialysis machine; blood was reinjected via the subclavian line) acting as a limited venovenous bypass, allowing right ventricular offloading and hemodialysis throughout the case. We removed 4.5 L via hemodialysis during the surgery, while avoiding acidosis, hyperkalemia, and sodium shifts. The patient tolerated reperfusion adequately despite pre-existing right ventricular dilation and dysfunction. CONCLUSION: We report on the use two hemodialysis catheters in a patient undergoing orthotopic liver transplantation as a circuit for simultaneous anuric hepatorenal syndrome and moderate pulmonary hypertension with right ventricular dilation and dysfunction. We believe this technique was instrumental in the patient's successful transplant.

RéSUMé: OBJECTIF: Les avantages de la dialyse peropératoire pendant une transplantation hépatique orthotopique demeurent controversés. Chez la patientèle atteinte d'insuffisance rénale anurique et d'hypertension portopulmonaire, il est essentiel de maintenir le retour veineux pendant le clampage et le déclampage de la veine cave ainsi que de minimiser la surcharge hydrique, afin d'éviter la déformation et l'insuffisance ventriculaires droites. CARACTéRISTIQUES CLINIQUES : Nous présentons le cas d'une femme de 54 ans qui a bénéficié d'une transplantation hépatique orthotopique pour une maladie hépatique liée à l'alcool avec une décompensation aiguë comprenant un syndrome hépatorénal sévère (anurie nécessitant une dialyse), un syndrome hépatopulmonaire probable, une hypertension pulmonaire modérée (pression systolique ventriculaire droite, 44 mm Hg), une encéphalopathie hépatique (grade 2) et des varices œsophagiennes. Avant l'incision, les pressions artérielles pulmonaires étaient de 48/28 (moyenne, 35) mm Hg avec une pression veineuse centrale de 30 mm Hg, un débit cardiaque de 7,4 L·min−1 et une résistance vasculaire pulmonaire de 98 dynes·sec·cm−5. Dans le contexte de la déformation ventriculaire et de la surcharge volémique droites observées à l'échocardiographie transthoracique, nous avons inséré un cathéter de dialyse supplémentaire dans la veine fémorale droite. Nous avons amorcé la dialyse en créant un circuit avec les deux cathéters (ligne fémorale en direction de l'appareil de dialyse; sang réinjecté via la ligne sous-clavière) agissant comme un pontage veino-veineux limité, permettant la décharge du ventricule droit et l'hémodialyse tout au long du cas. Nous avons retiré 4,5 L par hémodialyse pendant la chirurgie, tout en évitant l'acidose, l'hyperkaliémie et les changements en sodium plasmatique. La patiente a toléré la reperfusion de manière adéquate malgré la dilatation et le dysfonctionnement préexistants du ventricule droit. CONCLUSION: Nous rapportons l'utilisation de deux cathéters d'hémodialyse pour créer un circuit chez une patiente bénéficiant d'une transplantation hépatique orthotopique pour le traitement d'un syndrome hépatorénal anurique simultané à une hypertension pulmonaire modérée avec dilatation et dysfonctionnement du ventricule droit. Nous pensons que cette technique a joué un rôle déterminant dans la réussite de la greffe chez la patiente.

Robo2 Drives Target-Selective Peripheral Nerve Regeneration in Response to Glia-Derived Signals.

Peripheral nerves are divided into multiple branches leading to divergent synaptic targets. This poses a remarkable challenge for regenerating axons as they select their original trajectory at nerve branch-points. Despite implications for functional regeneration, the molecular mechanisms underlying target selectivity are not well characterized. Danio Rerio (zebrafish) motor nerves are composed of a ventral and a dorsal branch that diverge at a choice-point, and we have previously shown that regenerating axons faithfully select their original branch and targets. Here we identify robo2 as a key regulator of target-selective regeneration (sex of experimental subjects unknown). We demonstrate that robo2 function in regenerating axons is required and sufficient to drive target-selective regeneration, and that robo2 acts in response to glia located precisely where regenerating axons select the branch-specific trajectory to prevent and correct axonal errors. Combined, our results reveal a glia-derived mechanism that acts locally via axonal robo2 to promote target-selective regeneration.SIGNIFICANCE STATEMENT Despite its relevance for functional recovery, the molecular mechanisms that direct regenerating peripheral nerve axons toward their original targets are not well defined. Zebrafish spinal motor nerves are composed of a dorsal and a ventral branch that diverge at a stereotyped nerve branch-point, providing a unique opportunity to decipher the molecular mechanisms critical for target-selective regeneration. Using a combination of live cell imaging and molecular-genetic manipulations, we demonstrate that the robo2 guidance receptor is necessary and sufficient to promote target-selective regeneration. Moreover, we demonstrate that robo2 is part of a genetic pathway that generates transient, spatially restricted, and tightly coordinated signaling events that direct axons of the dorsal nerve branch toward their original, pre-injury targets.

Regurgitation under anesthesia in a fasted patient prescribed semaglutide for weight loss: a case report.

PURPOSE: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) such as semaglutide are a class of medications prescribed to treat type 2 diabetes mellitus, and more recently, as an adjunct for weight loss because of its effects of delaying gastric emptying and suppressing appetite. Semaglutide is a long-acting agent with a half-life of approximately one week, and there are currently no guidelines that address the perioperative management of such agents. CLINICAL FEATURES: We describe an unexpected case of regurgitation of a large volume of gastric contents upon induction of general anesthesia in a nondiabetic, nonobese patient despite a long preoperative fasting period (20 hr for solids and eight hours for clear fluids). This patient had no traditional risk factors for regurgitation or aspiration but was taking the GLP-1 RA semaglutide for weight loss and had last taken the medication two days before their scheduled procedure. CONCLUSIONS: Patients taking long-acting GLP-1 RAs such as semaglutide may be at risk of pulmonary aspiration under anesthesia. We propose strategies to mitigate this risk including holding the medication four weeks prior to a scheduled procedure when feasible and considering full stomach precautions.

RéSUMé: OBJECTIF: Les agonistes des récepteurs du glucagon-like peptide-1 (AR GLP-1) tels que le sémaglutide sont une classe de médicaments prescrits pour traiter le diabète sucré de type 2 et, plus récemment, comme complément à la perte de poids en raison de ses effets de retardement de la vidange gastrique et de suppression de l'appétit. Le sémaglutide est un agent à action prolongée dont la demi-vie est d'environ une semaine, et il n'existe actuellement aucune ligne directrice traitant de la prise en charge périopératoire de ces agents. CARACTéRISTIQUES CLINIQUES: Nous décrivons un cas inattendu de régurgitation d'un important volume de contenu gastrique lors de l'induction de l'anesthésie générale chez une personne non diabétique et non obèse malgré une longue période de jeûne préopératoire (20 heures pour les solides et huit heures pour les liquides clairs). Cette personne ne présentait aucun facteur de risque traditionnel de régurgitation ou d'aspiration, mais prenait du sémaglutide (AR GLP-1) à des fins de perte de poids et avait pris le médicament pour la dernière fois deux jours avant l'intervention prévue. CONCLUSION: Les patient·es prenant des AR GLP-1 à action prolongée tels que le sémaglutide peuvent être à risque d'aspiration pulmonaire sous anesthésie. Nous proposons des stratégies pour atténuer ce risque, y compris d'interrompre la prise du médicament quatre semaines avant une intervention prévue lorsque cela est possible et d'envisager de prendre les précautions requises pour un estomac plein.

Developing a health promoting university in Trinity College Dublin-overview and outline process evaluation.

Higher Education Institutions (HEIs) have the potential to impact positively on the health and wellbeing of their staff and students. Using and expanding on the 'health promoting university' (HPU) platform within HEIs, this article provides a description of 'Healthy Trinity', which is an initiative underway in Trinity College Dublin, the University of Dublin. First, Healthy Trinity is contextualized in background literature including international and national policy and practice. Second, an overview of Healthy Trinity is provided including its vision and goals. Third, the article describes the steps taken relating to the identification of stakeholders and use of a network and a co-lead model. Within this approach, the article describes a partnership approach whereby responsibilities regarding health and wellbeing are shared by individuals and the institution. Fourth, the design and implementation of Healthy Trinity is discussed by taking a 'settings approach', in which the emphasis for change is placed on individual behaviours, environment, policy and organizational culture. Consideration is given to the interplay between intervention, implementation strategy and context for successful systemic implementation. The fifth element presented is the early-stage challenges encountered during implementation, such as the need to secure recurrent funding and the importance of having a direct input to the governance of the University to enable systemic change. The sixth and final component of the article is an outline of Healthy Trinity's intention to utilize a process evaluation of the early implementation phases of this complex intervention within a settings approach. Potential deliverables and impacts of this HPU initiative are presented and discussed.

Universities, such as Trinity College Dublin, the University of Dublin, can be looked at as a community of staff and students. The university community has needs in terms of health and wellbeing. 'Healthy Trinity' attempted to build strategies and practices to meet these needs for its community. The approach taken was from multiple angles and involved students and staff, focusing on both individual and organizational responsibility to promote and encourage healthy behaviours. Healthy Trinity achieved some successes as well as encountering some challenges. This article explores how the university might build upon the successes of Healthy Trinity in order to embed a culture which prioritizes health and wellbeing for the entire university community. The article also looks at the broader impact of achieving this goal, namely the University's contribution to a healthier community beyond the university setting.

HIV and Sexually Transmitted Infections Among Persons with Monkeypox - Eight U.S. Jurisdictions, May 17-July 22, 2022.

High prevalences of HIV and other sexually transmitted infections (STIs) have been reported in the current global monkeypox outbreak, which has affected primarily gay, bisexual, and other men who have sex with men (MSM) (1-5). In previous monkeypox outbreaks in Nigeria, concurrent HIV infection was associated with poor monkeypox clinical outcomes (6,7). Monkeypox, HIV, and STI surveillance data from eight U.S. jurisdictions* were matched and analyzed to examine HIV and STI diagnoses among persons with monkeypox and assess differences in monkeypox clinical features according to HIV infection status. Among 1,969 persons with monkeypox during May 17-July 22, 2022, HIV prevalence was 38%, and 41% had received a diagnosis of one or more other reportable STIs in the preceding year. Among persons with monkeypox and diagnosed HIV infection, 94% had received HIV care in the preceding year, and 82% had an HIV viral load of <200 copies/mL, indicating HIV viral suppression. Compared with persons without HIV infection, a higher proportion of persons with HIV infection were hospitalized (8% versus 3%). Persons with HIV infection or STIs are disproportionately represented among persons with monkeypox. It is important that public health officials leverage systems for delivering HIV and STI care and prevention to reduce monkeypox incidence in this population. Consideration should be given to prioritizing persons with HIV infection and STIs for vaccination against monkeypox. HIV and STI screening and other recommended preventive care should be routinely offered to persons evaluated for monkeypox, with linkage to HIV care or HIV preexposure prophylaxis (PrEP) as appropriate.

An International Commentary on Dysphagia and Dysphonia During the COVID-19 Pandemic.

COVID-19 has had an impact globally with millions infected, high mortality, significant economic ramifications, travel restrictions, national lockdowns, overloaded healthcare systems, effects on healthcare workers' health and well-being, and large amounts of funding diverted into rapid vaccine development and implementation. Patients with COVID-19, especially those who become severely ill, have frequently developed dysphagia and dysphonia. Health professionals working in the field have needed to learn about this new disease while managing these patients with enhanced personal protective equipment. Emerging research suggests differences in the clinical symptoms and journey to recovery for patients with COVID-19 in comparison to other intensive care populations. New insights from outpatient clinics also suggest distinct presentations of dysphagia and dysphonia in people after COVID-19 who were not hospitalized or severely ill. This international expert panel provides commentary on the impact of the pandemic on speech pathologists and our current understanding of dysphagia and dysphonia in patients with COVID-19, from acute illness to long-term recovery. This narrative review provides a unique, comprehensive critical appraisal of published peer-reviewed primary data as well as emerging previously unpublished, original primary data from across the globe, including clinical symptoms, trajectory, and prognosis. We conclude with our international expert opinion on what we have learnt and where we need to go next as this pandemic continues across the globe.

Physician Champions of Quality and Safety: Perspectives of MD Quality and Safety Leads to Drive Quality Innovation at an Academic Hospital.

While the importance of physician involvement in organizational quality and safety (Q&S) activities has been well established, a paucity of information exists on tangible supports needed to effectively execute this role. Interviews with 13 MD Q&S leads uncovered common enablers, including valuing Q&S work academically, hiring skilled collaborators, ensuring appropriate power and authority to advance Q&S initiatives, facilitating connections, emphasizing culture change and strong action by leadership. To operationalize these enablers and drive quality innovation, organizations should prioritize the identification and appointment of MD Q&S leads for each department/division and facilitate their assembly as a formal physician Q&S committee.

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

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.

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

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.

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

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.

Post-extubation dysphagia and dysphonia amongst adults with COVID-19 in the Republic of Ireland: A prospective multi-site observational cohort study.

OBJECTIVES: This study aims to (i) investigate post-extubation dysphagia and dysphonia amongst adults intubated with SARS-COV-2 (COVID-19) and referred to speech and language therapy (SLT) in acute hospitals across the Republic of Ireland (ROI) between March and June 2020; (ii) identify variables predictive of post-extubation oral intake status and dysphonia and (iii) establish SLT rehabilitation needs and services provided to this cohort. DESIGN: A multi-site prospective observational cohort study. PARTICIPANTS: One hundred adults with confirmed COVID-19 who were intubated across eleven acute hospital sites in ROI and who were referred to SLT services between March and June 2020 inclusive. MAIN OUTCOME MEASURES: Oral intake status, level of diet modification and perceptual voice quality. RESULTS: Based on initial SLT assessment, 90% required altered oral intake and 59% required tube feeding with 36% not allowed oral intake. Age (OR 1.064; 95% CI 1.018-1.112), proning (OR 3.671; 95% CI 1.128-11.943) and pre-existing respiratory disease (OR 5.863; 95% CI 1.521-11.599) were predictors of oral intake status post-extubation. Two-thirds (66%) presented with dysphonia post-extubation. Intubation injury (OR 10.471; 95% CI 1.060-103.466) and pre-existing respiratory disease (OR 24.196; 95% CI 1.609-363.78) were predictors of post-extubation voice quality. Thirty-seven per cent required dysphagia intervention post-extubation, whereas 20% needed intervention for voice. Dysphagia and dysphonia persisted in 27% and 37% cases, respectively, at hospital discharge. DISCUSSION: Post-extubation dysphagia and dysphonia were prevalent amongst adults with COVID-19 across the ROI. Predictors included iatrogenic factors and underlying respiratory disease. Prompt evaluation and intervention is needed to minimise complications and inform rehabilitation planning.

Rising to the challenge: a COVID-19 vaccination service for the housebound population.

The COVID-19 pandemic has necessitated innovations in practice in almost all areas of healthcare, not least community nursing services. This article details how one organisation planned and executed a home vaccination programme for housebound members of the population in its remit. It discusses the challenges faced by the team, as well as the key learnings achieved from this programme, which will guide future home immunisation programmes. Implementation of this programme required excellent coordination between clinicians and administrative staff. Importantly, support from the procurement and IT teams and the medicines management committee went a long way in the ironing out of early hiccups and in ensuring smooth running of the programme.

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

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.

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

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.

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

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.

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

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.

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

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.