Predictors for the use of systemic therapy in stage IB Mycosis fungoides.

BACKGROUND: The PROspective Cutaneous Lymphoma International Prognostic Index (PROCLIPI) study is aprospective analysis of an international database. Here we examine front-line treatments and quality of life (QoL) inpatients with newly diagnosed mycosis fungoides (MF). OBJECTIVES: To identify (i) differences in first-line approaches according to tumour-nodes-metastasis-blood (TNMB)staging; (ii) parameters related to a first-line systemic approach and (iii) response rates and QoL measures. METHODS: In total, 395 newly diagnosed patients with early-stage MF (stage IA-IIA) were recruited from 41 centresin 17 countries between 1 January 2015 and 31 December 2018 following central clinicopathological review. RESULTS: The most common first-line therapy was skin-directed therapy (SDT) (322 cases, 81·5%), while a smallerpercentage (44 cases, 11·1%) received systemic therapy. Expectant observation was used in 7·3%. In univariateanalysis, the use of systemic therapy was significantly associated with higher clinical stage (IA, 6%; IB, 14%; IIA,20%; IA-IB vs. IIA, P < 0·001), presence of plaques (T1a/T2a, 5%; T1b/T2b, 17%; P < 0·001), higher modified Severity Weighted Assessment Tool (> 10, 15%; ≤ 10, 7%; P = 0·01) and folliculotropic MF (FMF) (24% vs. 12%, P = 0·001). Multivariate analysis demonstrated significant associations with the presence of plaques (T1b/T2b vs.T1a/T2a, odds ratio 3·07) and FMF (odds ratio 2·83). The overall response rate (ORR) to first-line SDT was 73%,while the ORR to first-line systemic treatments was lower (57%) (P = 0·027). Health-related QoL improvedsignificantly both in patients with responsive disease and in those with stable disease. CONCLUSIONS: Disease characteristics such as presence of plaques and FMF influence physician treatment choices,and SDT was superior to systemic therapy even in patients with such disease characteristics. Consequently, futuretreatment guidelines for early-stage MF need to address these issues.

Should neonatal-perinatal medicine move to two-year fellowships?

The duration of the majority of fellowships in pediatrics has been three-years. With increasing shortages of some outpatient-based pediatric subspecialists, shorter two-year fellowships are being considered for clinically oriented trainees not interested in a career based on research. Shortening the duration of fellowship may have some financial merits such as achieving a higher salary earlier after shorter training. However, we feel that continuing with a three-year duration for neonatology is more pragmatic at this time due to reductions in intensive care rotations during residency, time required to  achieve procedural excellence, the need for exposure to quality assurance methodology, proficiency in novel techniques such as bedside ultrasound, and to maintain the physician-scientist pipeline. The demand for neonatal fellowship continues to be high. Ongoing evaluation of the job market, training needs and fellowship curriculum is needed to determine if the duration of fellowship should be altered in the future.

Measuring practice preference variation for quality improvement in neonatal respiratory care.

OBJECTIVES: The authors sought to measure and compare practice preference variation in neonatal respiratory care within and between neonatal intensive care units (NICUs) using the Neonatology Survey of Interdisciplinary Groups in Healthcare Tool (NSIGHT). STUDY DESIGN: Eleven NICUs completed the NSIGHT between 2019 and 2021. Net preference was measured by mean response; agreement was ranked by standard distribution of response values. Heat maps showed comparisons between NICUs and disciplines. RESULTS: NICUs and individuals agreed most often on use of pressure support with mandatory ventilation and on use of non-invasive positive pressure ventilation for apnea. High preference variation surrounded decisions for invasive ventilation versus continuous positive airway pressure for extremely low birth weight infants. Preference difference was most frequent between neonatologists and nurses. CONCLUSIONS: Patterns of practice preference variation in neonatal respiratory care are specific to clinical scenario. Measuring preference variation may inform psychology of change and strengthen quality improvement efforts.

Laryngeal mask use during neonatal resuscitation at birth: A United States-based survey of neonatal resuscitation program providers and instructors.

Aim: Neonatal resuscitation guidelines promote the laryngeal mask (LM) interface for positive pressure ventilation (PPV), but little is known about how the LM is used among Neonatal Resuscitation Program (NRP) Providers and Instructors. The study aim was to characterize the training, experience, confidence, and perspectives of NRP Providers and Instructors regarding LM use during neonatal resuscitation at birth. Methods: A voluntary anonymous survey was emailed to all NRP Providers and Instructors. Survey items addressed training, experience, confidence, and barriers for LM use during resuscitation. Associations between respondent characteristics and outcomes of both LM experience and confidence were assessed using logistic regression. Results: Between 11/7/22-12/12/22, there were 5,809 survey respondents: 68% were NRP Providers, 55% were nurses, and 87% worked in a hospital setting. Of these, 12% had ever placed a LM during newborn resuscitation, and 25% felt very or completely confident using a LM. In logistic regression, clinical or simulated hands-on training, NRP Instructor role, professional role, and practice setting were all associated with both LM experience and confidence.The three most frequently identified barriers to LM use were insufficient experience (46%), preference for other interfaces (25%), and failure to consider the LM during resuscitation (21%). One-third (33%) reported that LMs are not available where they resuscitate newborns. Conclusion: Few NRP providers and instructors use the LM during neonatal resuscitation. Strategies to increase LM use include hands-on clinical training, outreach promoting the advantages of the LM compared to other interfaces, and improving availability of the LM in delivery settings.

A review of the therapeutic potential of histone deacetylase inhibitors in rhabdomyosarcoma.

This review aims to summarize the putative role of histone deacetylases (HDACs) in rhabdomyosarcoma (RMS) and the effects of HDAC inhibitors (HDACi) on RMS by elucidating and highlighting known oncogenic pathways, mechanisms of resistance, and the synergistic potential of histone deacetylase inhibitors. We searched two databases (PubMed and Google Scholar) for the keywords "Rhabdomyosarcoma, histone deacetylase, histone deacetylase inhibitors." We excluded three publications that did not permit access to the full text to review and those that focus exclusively on pleiomorphic RMS in adults. Forty-seven papers met the inclusion criteria. This review highlights that HDACi induce cytotoxicity, cell-cycle arrest, and oxidative stress in RMS cells. Ultimately, HDACi have been shown to increase apoptosis and the cessation of embryonal and alveolar RMS proliferation in vivo and in vitro, both synergistically and on its own. HDACi contain potent therapeutic potential against RMS. This review discusses the significant findings and the biological mechanisms behind the anti-cancer effects of HDACi. Additionally, this review highlights important clinical trials assessing the efficacy of HDACi in sarcomas.

Controversies in CPT® coding in the neonatal intensive care unit: - critical vs. intensive care.

Professional reimbursement to neonatal providers is based on the level of Current Procedural Terminology (CPT®) coding in the NICU, newborn nursery and other areas where neonatal care is provided. Four levels of evaluation and management (E&M) care-critical, intensive, routine-hospital care or normal newborn care can be provided to neonates. The work relative value units (wRVUs) associated with these four levels of care vary widely. This manuscript provides a brief review of basic features associated with each of these four levels with a specific perspective on differences between critical and intensive care codes. Coding and billing are constantly evolving fields with significant variation in interpretation and readers are encouraged to review the current publications on CPT® coding and make an informed decision on the best codes to be used for their patients.

National Cross-Sectional Study of Mental Health Screening Practices for Primary Caregivers of NICU Infants.

Universal screening for postpartum mood and anxiety disorders (PMADs) has been recommended for all new parents at outpatient postpartum and well-child visits. However, parents of newborns admitted to the NICU are rarely able to access these services during their infant's prolonged hospitalization. The objective of this study was to determine the prevalence of mental health screening and treatment programs for parents or other primary caregivers in NICUs across the country. In this cross-sectional study, US NICU medical directors were invited to complete an online survey about current practices in mental health education, screening, and treatment for primary caregivers of preterm and ill infants in the NICU. Comparative analyses using Fisher's exact test were performed to evaluate differences in practices among various NICU practice settings. Survey responses were obtained from 75 out of 700 potential sites (10.7%). Of participating NICUs, less than half routinely provided caregivers with psychoeducation about mental health self-care (n = 35, 47%) or routinely screened caregivers for PPD or other mental health disorders (n = 33, 44%). Nearly one-quarter of the NICUs did not provide any PMAD screening (n = 17, 23%). Despite consensus that postpartum psychosocial care is essential, routine mental health care of primary caregivers in the NICU remains inadequate.

Self-directed video versus instructor-based neonatal resuscitation training: a randomized controlled blinded non-inferiority multicenter international study.

OBJECTIVE: To compare the efficacy of video-assisted self-directed neonatal resuscitation skills course with video-assisted facilitator-led course. METHODS: This multicenter, randomized, blinded, non-inferiority-controlled trial compared two methods of teaching basic neonatal resuscitation skills using mask ventilation. Groups of novice providers watched an instructional video. One group received instructor facilitation (Ins-Video). The other group did not (Self-Video). An Objective Structured Clinical Exam (OSCE) measured skills performance, and a written test gauged knowledge. RESULTS: One hundred and thirty-four students completed the study. Sixty-three of 68 in the Self-Video Group (92.6%) and 59 of 66 in the Ins-Video Group (89.4%) achieved post-training competency in positive pressure ventilation (primary outcome). OSCE passing rates were low in both groups. Knowledge survey scores were comparable between groups and non-inferior. CONCLUSIONS: Video self-instruction taught novice providers positive pressure ventilation skills and theoretical knowledge, but it was insufficient for mastery of basic neonatal resuscitation in simulation environment.

Recent Recommendations and Emerging Science in Neonatal Resuscitation.

The Neonatal Resuscitation Program, initially an expertise- and consensus-based approach, has evolved into an evidence-based algorithm. Ventilation remains the key component of successful resuscitation of neonates. Recent changes in recommendations include management of cord clamping, multiple methods to prevent hypothermia, rescinding of mandatory intubation and suction of the nonvigorous meconium-stained infant, electrocardiographic monitoring, and establishing an airway for ventilation before initiation of chest compressions. Emerging science, including issues such as cord milking, oxygen targeting, and laryngeal mask use, may lead to future program modifications. Technology such as video laryngoscopy and telemedicine will affect the way training and care is delivered.

Fatigue during Chest Compression Using a Neonatal Patient Simulator.

OBJECTIVE: The objective of this study was to evaluate chest compression (CC) quality and operator fatigue during CC, with coordinated ventilation, on a neonatal simulator and to explore its association with provider aerobic activity and body mass index. METHODS: This was a prospective observational experimental study on pediatricians, neonatologists, and neonatal nurses who frequently deliver newborns and who have signed the informed consent. Subjects performed CC coordinated with ventilations at a ratio of 3:1 for 10 minutes on a neonatal mannequin. Proxy of fatigue was defined as four consecutive CC below target. RESULTS: Forty subjects participated; 62% were women. Twenty one (52%) evidenced weariness, as they performed. No gender-based differences were found in weariness. No subject abandoned the procedure due to fatigue. Subjects who participated in aerobic exercise had a significantly better performance than those who did not participate. Early fatigue was significantly associated with higher BMI. The reduction in effectiveness occurred at a mean time of 7.7 minutes (range 3.5-9 minutes). CONCLUSION: CC performance quality decreased and fatigue was frequent before 10 minutes had elapsed on a neonatal simulator. Provider fatigue was associated with both lack of aerobic activity and BMI ≥ 25. Our findings support the need for guidelines requiring frequent rotation of CC providers during prolonged neonatal resuscitation.

Impact of Specialized Nursery Care for Late Preterm Infants on NICU Admission Rate and Length of Stay.

OBJECTIVE: To compare neonatal intensive care unit (NICU) admission rates and length of stay (LOS) of late preterm infants (LPIs) born before and after opening a specialized care nursery (SCN) at our academic, pediatric tertiary care center with ∼4,500 total deliveries annually. STUDY DESIGN: Retrospective chart review of inborn LPIs (35(0/7)-36(6/7) weeks) who were asymptomatic or minimally symptomatic at birth and delivered 7 months before the opening of the SCN (pre-SCN) or 7 months subsequently (post-SCN). Infants were excluded for major congenital anomalies or other conditions requiring immediate NICU admission. The pre-SCN options for care were standard couplet care or NICU. The post-SCN options for care were standard couplet care, SCN, or NICU. RESULTS: Pre-SCN (n = 109), 73 (67%) infants received standard couplet care, while 36 (33%) infants were ever admitted/transferred to the NICU. Post-SCN (n = 112), 59 (53%) infants received standard couplet care, while 20 (18%) were ever admitted/transferred to the NICU. A total of 33 (29%) infants were admitted/transferred to the SCN and avoided a NICU stay. Median LOS for all infants was 3 days. CONCLUSION: The frequency of LPIs admitted/transferred to the NICU decreased by ∼50% after the opening of the SCN. LOS did not differ by birth cohort, but did differ significantly by location of care (standard couplet care < SCN < NICU).

Evaluation of aqueous humor concentrations of Istalol and Betimol following a single ocular instillation in rabbit eyes.

PURPOSE: The aim of this study was to evaluate the pharmacokinetic absorption profiles of two commercially available ophthalmic solutions following a single instillation into each eye of New Zealand white rabbit eyes. METHODS: A single dose of either timolol maleate with potassium sorbate (TLA) or timolol hemihydrate (THH) was instilled into each eye of New Zealand white rabbits (15 rabbits/drug preparation, 50-microL dose). Animals were euthanized 15, 30, 60, 120, and 180 min after instillation, with 3 animals/drug/time intervals. Aqueous humor from both eyes of each animal was pooled and analyzed for timolol concentration, using the high-performance liquid chromatography method. RESULTS: TLA reached a mean peak concentration of 3.705 +/- 0.3012 microg/mL at 15 min, tapering to 0.539 +/- 0.1431 microg/mL by 180 min. THH reached a mean peak concentration of 2.239 +/- 0.1430 microg/mL at 15 min postinstillation, tapering to 0.148 +/- 0.0282 microg/mL by 180 min. CONCLUSIONS: TLA containing potassium sorbate demonstrated an absorption profile of more rapid absorption (1.7 fold greater at 15 minutes) and longer residences time (3.6 fold greater at 180 minutes) than the THH. At every time point throughout the study, TLA demonstrated greater drug concentration than THH.

24-hour evaluation of the ocular distribution of (14)C-labeled bromfenac following topical instillation into the eyes of New Zealand White rabbits.

PURPOSE: The aim of this study was to determine the distribution and concentrations of bromfenac ophthalmic solution in ocular tissues following topical instillation in New Zealand White (NZW) rabbits. DESIGN: Two animal studies were conducted. METHODS: A single 50-muL (14)C-bromfenac ophthalmic solution (20-25 muCi or 0.09%) was administered into the right eyes of 14-18 randomly assigned NZW rabbits. At various time points, ocular tissues were collected and analyzed for (14)C-bromfenac contents. Ocular tissues were combusted and the amount of radioactivity was determined by liquid scintillation counting (LSC). Aqueous-humor samples were directly transferred to LSC vials. RESULTS: Peak concentrations of (14)C-bromfenac were observed in the aqueous humor and most ocular tissues at or before 2-hours. The highest concentrations were in the cornea, conjunctiva, and sclera. Similar amounts were detected in the aqueous humor, iris-ciliary body, choroid, and, to a slightly lesser degree, in the retina. Measurable amounts of bromfenac were detected in all samples at the 24-hours time point (> or =0.001 mug equivalent/g). CONCLUSIONS: Significant penetration and measurable amounts of (14)C-bromfenac were detected in all ocular tissues over 24 h, including the sclera, choroid, and retina. These results strongly suggest the utility of bromfenac ophthalmic solution 0.09% in treating inflammation of both the anterior and posterior ocular segments.

Lack of medication dose uniformity in commonly split tablets.

OBJECTIVE: To divide 11 commonly split tablets and evaluate the resulting half-tablets for content uniformity. DESIGN: Pre-post comparison. SETTING: Laboratory. INTERVENTIONS: A trained individual split tablets of 11 products using a single-edged razor blade and 3 products by hand alone. MAIN OUTCOME MEASURES: The Uniformity of Dosage Units test published in the United States Pharmacopeia 24 (USP), which applies to whole tablets, was adapted liberally to assess the dose uniformity of the resulting split tablets. RESULTS: Of the 11 razor-split products, 8 failed the liberal adaptation of the USP uniformity test. No visible tablet features (e.g., scoring) predisposed a product's split tablets to pass or fail the uniformity test. All three hand-split tablets failed the uniformity test and yielded worse results than did razor-split tablets. CONCLUSION: The majority of the 11 drug products we tested, when assessed for their ability to be split into half-tablets of equal dose, failed a liberally interpreted USP uniformity test. The practice of dividing tablets to save costs or to improve a dosage regimen may not cause problems for patients using drugs with low toxicity and relatively flat dose-response relationships, but it is not recommended for patients using drugs with more substantial toxicity and steep dose-response efficacy curves.