A conceptual model of barriers and facilitators to primary clinical teams requesting pediatric palliative care consultation based upon a narrative review.

BACKGROUND: Despite evidence that referral to pediatric palliative care reduces suffering and improves quality of life for patients and families, many clinicians delay referral until the end of life. The purpose of this article is to provide a conceptual model for why clinical teams delay discussing palliative care with parents. DISCUSSION: Building on a prior model of parent regoaling and relevant research literature, we argue for a conceptual model of the challenges and facilitators a clinical team might face in shifting from a restorative-focused treatment plan to a plan that includes palliative aspects, resulting in a subspecialty palliative care referral. Like patients and families, clinicians and clinical teams may recognize that a seriously ill patient would benefit from palliative care and shift from a restorative mindset to a palliative approach. We call this transition "clinician regoaling". Clinicians may experience inhibitors and facilitators to this transition at both the individual and team level which influence the clinicians' willingness to consult subspecialty palliative care. The 8 inhibitors to team level regoaling include: 1) team challenges due to hierarchy, 2) avoidance of criticizing colleagues, 3) structural communication challenges, 4) group norms in favor of restorative goals, 5) diffusion of responsibility, 6) inhibited expression of sorrow, 7) lack of social support, 8) reinforcement of labeling and conflict. The 6 facilitators of team regoaling include: 1) processes to build a shared mental model, 2) mutual trust to encourage dissent, 3) anticipating conflict and team problem solving, 4) processes for reevaluation of goals, 5) sharing serious news as a team, 6) team flexibility. CONCLUSIONS: Recognizing potential team level inhibitors to transitioning to palliative care can help clinicians develop strategies for making the transition more effectively when appropriate.

Ribosomal and hematopoietic defects in induced pluripotent stem cells derived from Diamond Blackfan anemia patients.

Diamond Blackfan anemia (DBA) is a congenital disorder with erythroid (Ery) hypoplasia and tissue morphogenic abnormalities. Most DBA cases are caused by heterozygous null mutations in genes encoding ribosomal proteins. Understanding how haploinsufficiency of these ubiquitous proteins causes DBA is hampered by limited availability of tissues from affected patients. We generated induced pluripotent stem cells (iPSCs) from fibroblasts of DBA patients carrying mutations in RPS19 and RPL5. Compared with controls, DBA fibroblasts formed iPSCs inefficiently, although we obtained 1 stable clone from each fibroblast line. RPS19-mutated iPSCs exhibited defects in 40S (small) ribosomal subunit assembly and production of 18S ribosomal RNA (rRNA). Upon induced differentiation, the mutant clone exhibited globally impaired hematopoiesis, with the Ery lineage affected most profoundly. RPL5-mutated iPSCs exhibited defective 60S (large) ribosomal subunit assembly, accumulation of 12S pre-rRNA, and impaired erythropoiesis. In both mutant iPSC lines, genetic correction of ribosomal protein deficiency via complementary DNA transfer into the "safe harbor" AAVS1 locus alleviated abnormalities in ribosome biogenesis and hematopoiesis. Our studies show that pathological features of DBA are recapitulated by iPSCs, provide a renewable source of cells to model various tissue defects, and demonstrate proof of principle for genetic correction strategies in patient stem cells.

Recent insights into inherited bone marrow failure syndromes.

PURPOSE OF REVIEW: Inherited bone marrow failure syndromes (IBMFS) are a diverse set of genetic disorders characterized by the inability of the bone marrow to produce sufficient circulating blood cells. The purpose of this review is to highlight novel findings in recent years and their impact on the understanding of IBMFS. RECENT FINDINGS: Mutations in over 80 different genes have been associated with the development of bone marrow failure (BMF). The products of the genes mutated in IBMFS frequently participate in housekeeping pathways, which are important for cell growth and division rather than being specific for hematopoiesis. The common theme of these pathways, when disturbed, is the activation of p53, leading to cell cycle arrest, senescence, and cell death. With continued improvement in therapy for IBMFS, late complications, such as development of malignancies, are seen more frequently. This highlights the importance of understanding the affected pathways and their roles in cancer development. SUMMARY: The recent advancement of our understanding of IBMFS has come largely through the identification of the genetic lesions responsible for disease and the investigations of their pathways. Applied in clinical practice, these findings make it possible to unambiguously identify mutation carriers even before the development of BMF and exclude or confirm a suspected clinical diagnosis for many of the more common IBMFS. The further characterization of the pathways leading to IBMFS is likely to reveal novel targets for screening tests, prognostic biomarkers, and improved and specific therapeutics.

Severe hyponatraemia in two patients with breast cancer caused by low-dose cyclophosphamide and precipitated by aprepitant.

Two postmenopausal women with breast cancer developed acute confusion and seizures, less than 24 hours after the first cycle of neoadjuvant chemotherapy with fluorouracil, epirubicin and low-dose cyclophosphamide. They were found to have severe, life-threatening hyponatraemia with sodium levels of 113 and 115 mEq/L, respectively. Both women made a full recovery within 24 hours of admission with slow correction of sodium levels. Following investigational workup, the most likely diagnosis was cyclophosphamide-associated syndrome of inappropriate antidiuretic hormone secretion (SIADH). Aprepitant - a commonly used antiemetic and moderate cytochromeP450 3A4 inhibitor was identified as the precipitating factor. Aprepitant was discontinued and both women were successfully re-challenged with full dose cyclophosphamide in an outpatient setting with no subsequent adverse events. This is a typical case of a rare cause of a common medical problem. A systematic approach to diagnosis and treatment of hyponatraemia in an oncology patient requires awareness of toxicities of systemic anticancer agents.

Clinical implication of recent randomized control trial in primary angle-closure disease management.

Blindness due to primary angle-closure glaucoma (PACG) can be reduced significantly if the ongoing angle-closure process is arrested at an early stage. Various treatments such as laser peripheral iridotomy (LPI), iridoplasty, and clear lens extraction (CLE) have been advocated as first-line therapy for primary angle-closure (PAC), PACG, and high-risk cases of primary angle-closure suspect (PACS). EAGLE study, propagated the effectiveness of CLE over LPI for the management of primary angle closure and have sparked controversy regarding the role of LPI as a first line procedure. Randomized controlled trials (RCT), systematic reviews, and meta-analyses of RCTs done on the same question provide us with a solid base for creating guidelines/modules for our day-to-day clinical practice. A systematic review was conducted, searching several databases, including PubMed, Cochrane Library, EMBASE, and ClinicalTrials.gov, for the last 16 years (January 2005-December 2021) for RCTs with data published related to primary angle-closure disease (PACD). The search strategy included the following terms: "Primary Angle Closure disease," "Primary Angle Closure Glaucoma," "Primary Angle Closure," "Primary Angle Closure Suspect," "clear lens extraction," "laser iridotomy," "laser peripheral iridotomy," "argon laser peripheral iridoplasty," "selective laser trabeculoplasty," "trabeculectomy," "randomized control trial," and "meta-analysis of randomized control trial." In this review, we will discuss recently published RCTs (within the last 16 years) for the management of PACD and their clinical implications in day-to-day practice.

Retinal nerve fiber layer thickness in amblyopia.

Purpose: To report retinal nerve fiber layer thickness (RNFLT) in eyes with amblyopia compared with contralateral healthy eyes. Methods: In this cross-sectional study, we included patients with anisometropic amblyopia, strabismic amblyopia, and mixed amblyopia. All subjects underwent complete ophthalmic examination, including RNFLT measurement with time-domain OCT (Stratus OCT) and scanning laser polarimeter (GDX VCC). A paired "t" test was used to compare average and quadrant-wise RNFL thickness between the amblyopic and contralateral normal eyes. In addition, an analysis of variance test was used to compare various RNFL thickness parameters between the three groups. Results: A total of 33 eyes of 33 subjects with anisometropic amblyopia, 20 eyes of 20 subjects with strabismic amblyopia, and 38 eyes of 38 subjects with mixed amblyopia were included. In the anisometropic amblyopia group, the average RNFLT in the amblyopic eye was 98.2 µm and 99.8 µm in the fellow normal eye (P = 0.5), the total foveal thickness was 152.82 µm (26.78) in the anisometropic eye and 150.42 µm (23.84) in the fellow eye (P = 0.38). The difference between amblyopic and contralateral normal eye for RNFL and macular parameters was statistically insignificant in all three groups. The RNFL thickness in four quadrants was similar in the amblyopic and non-amblyopic eye between all three groups and statistically non-significant. Conclusion: Our study showed that RNFL thickness was similar in amblyopic and non-amblyopic eyes between all three amblyopia groups.

Chemical disinfectants in ophthalmic practice.

The instrumentation used in ophthalmic clinics can be a source of epidemics in health care set up. Contact tonometry with Schiotz or Applanation tonometer is associated with nosocomial epidemic keratoconjunctivitis outbreaks. Recently identified SARS-CoV-2 (COVID -19) spreads mainly via the respiratory route and fomites and can transmit through other body fluids, including tear film. Various ophthalmic instruments can become a common source of spreading cross infections. Chemical disinfection is one of the most common methods employed to decontaminate instruments and environmental surfaces and prevent transmission of infectious pathogens to patients through medical and surgical instruments. Various chemical disinfectants are available with a varied spectrum to work on a different group of organisms. In this article, we briefly cover commonly used chemical disinfectants in ophthalmic practice like Alcohol (Ethyl Alcohol, Isopropyl Alcohol), Chlorine-based solution (mainly Sodium Hypochlorite), Glutaraldehyde, Hydrogen Peroxide, Formaldehyde, Iodophors, and Quaternary Ammonium Compounds.

Optic disc morphology in primary open-angle glaucoma versus primary angle-closure glaucoma in South India.

Purpose: The aim of this study was to investigate the optic disc morphology in primary angle-closure glaucoma (PACG) versus primary open-angle glaucoma (POAG) in South Indians. Methods: A total of 60 patients (60 eyes) with PACG and 52 patients (52 eyes) with POAG were included in a cross-sectional observational study. The glaucoma diagnosis was based on a glaucomatous appearance of the optic disc correlating with visual field defects. The glaucoma was graded as early, moderate, or severe, depending upon perimetric loss. All patients underwent an ophthalmic evaluation, including visual field examination and planimetric analysis of 30° stereoscopic color optic disc photographs. Results: The POAG and PACG groups did not differ significantly in a disc or rim area, rim width, and frequencies of disc hemorrhages or rim notches. However, early POAG group (n = 15) had a significantly deeper cup depth (P = 0.01), larger beta zone (P = 0.01), and a higher frequency of localized retinal nerve fiber layer (RNFL) defects (P = 0.02) than early PACG (n = 20). Conclusion: In the early stage of the disease, POAG compared to PACG may be characterized by deeper disc cupping, a larger beta zone of peripapillary atrophy, and a higher frequency of localized RNFL defects. Such differences in early glaucoma may suggest differences in pathophysiology in POAG and PACG.

Live streaming ward rounds using wearable technology to teach medical students: a pilot study.

Background: The COVID-19 pandemic resulted in a loss of clinical clerkship opportunities for medical students. To address this problem while maintaining patient safety, this pilot study explored the feasibility of using a wearable headset to live stream teaching ward rounds to remotely based medical students. Methods: Three live streamed teaching ward rounds were delivered to three groups of medical students (n=53) using the Microsoft HoloLens 2 device and Microsoft Teams software, and results pooled for analysis. Feedback was gathered from students and instructors using the evaluation of technology-enhanced learning materials (ETELM). Patient feedback was gathered using the Communication Assessment Tool to explore any impact on interpersonal communication. Results: The response rate for the ETELM-learner perceptions was 58% (31/53), 100% for the ETELM-instructor perceptions. Students strongly agreed that the overall quality of the teaching session and instructors was excellent. However, 32% experienced issues with audio or video quality and one remote student reported cyber sickness. The statement 'educational activities encouraged engagement with session materials/content' returned the most varied response. Instructors reported technological problems with delivery while using the HoloLens 2 device and environmental noise in the ward was a disruptive factor. Preparation and skilled facilitation were key to delivering a high-quality teaching session. Patients reacted generally favourably to the technology and no negative effects on interpersonal communication were identified. Conclusion: The experience of live streamed ward rounds was well received by patients, medical students and teaching faculty. However, there remain limitations to the routine use of HoloLens 2 technology in our setting including steep learning curves, hardware costs and environmental factors such as noise and WiFi connectivity. Live streamed ward rounds have potential postpandemic implications for the judicious use of resources, and the possibility for few educationally minded clinicians to teach at scale in a patient-friendly manner.

An Interprofessional Team-Based Intervention to Address Barriers to Initiating Palliative Care in Pediatric Oncology: A Multiple-Method Evaluation of Feasibility, Acceptability, and Impact.

CONTEXT: Many children with advanced cancer are not referred to palliative care despite both professional recommendations to do so and bereaved parental preference for earlier support from sub-specialty palliative care. OBJECTIVES: To assess the feasibility, acceptability, and impact of an adaptive intervention to address individual and team-level barriers to specialty palliative care referrals. METHODS: A multiple-method approach assessed feasibility and acceptability among clinicians from pediatric oncology teams at a single institution. Quantitative measures of comfort with palliative care consultations, team cohesion, and team collaboration were conducted before and after the intervention. Number of palliative care consults were examined before, during, and after sessions. Intervention satisfaction surveys and qualitative interviews were conducted after the intervention. RESULTS: Twenty-six team members (90% of consented) attended at least one intervention session with 20 (69%) participants completing 75% or more sessions. The intervention was modified in response to participant feedback. After the intervention, participants reported greater team cohesion, comfort discussing palliative care consultation, team collaboration, process satisfaction, and decision satisfaction. Participants agreed that the training was useful, effective, helpful, and worthwhile, that they would use the skills, and that they would recommend the training to other providers. The numbers of palliative care consults increased before intervention sessions were conducted, but did not significantly change during or after the sessions. In the interviews, participants reported overall favorably regarding the intervention with some participants reporting changes in practice. CONCLUSION: An adaptive intervention to reduce barriers to initiating palliative care for pediatric oncology teams is feasible and acceptable.