Exposure to persistent hemodynamically significant patent ductus arteriosus is associated with retinopathy of prematurity.

BACKGROUND: Hemodynamically significant patent ductus arteriosus (hsPDA) shunt may predispose infants to retinopathy of prematurity (ROP) because of its higher preductal cardiac output and blood oxygen content, which may augment ocular oxygen delivery. METHODS: A retrospective cohort study of preterm infants, born at <27 weeks' gestation and admitted at <24h postnatal age to a large quaternary referral was conducted. The primary composite outcome was death at <32 weeks or moderate-to-severe ROP (≥stage 2 or requiring treatment) in either eye. Secondary outcomes included ROP requiring treatment, and any ROP. Univariate analysis of patient characteristics and outcomes was performed as well as logistic regression. A receiver operating characteristics curve was generated for the outcome of ROP ≥stage 2 or requiring treatment. RESULTS: A total of 91 patients were screened, of whom 86 (54 hsPDA, 32 controls) were eligible for inclusion. hsPDA patients were younger and lighter at birth and had a higher burden of hyperglycemia and respiratory illness. The rates of the composite outcome (death <32 weeks or moderate-to-severe ROP) and of any ROP were more frequent in the hsPDA group. hsPDA shunt exposure was independently associated with development of any ROP among survivors to assessment (P = 0.006). PDA cumulative exposure score of 78 (clinical equivalent = 7 days high-volume shunt exposure) predicts moderate-to-severe ROP with 80% sensitivity and 78% specificity. CONCLUSIONS: Among infants <27 weeks, hsPDA shunt is associated with increased risks of a composite outcome of death or moderate-to-severe ROP, as well as ROP of any stage. Shunt modulation as a strategy to reduce ROP represents a biologically plausible avenue for investigation.

Analysis of Candy Tobacco Imitation Products Available Online in the United States.

INTRODUCTION: Youth tobacco use remains a critical public health concern, and childhood use of candy tobacco imitation products (CTIP) is associated with cigarette use among youth. However, no research has examined the full extent of CTIP available for purchase in the United States. AIMS AND METHODS: We conducted a content analysis of CTIP available on English-language, US-based websites. We identified sites that marketed CTIP utilizing Google and candy retail websites, examining each product for product names, the tobacco product being replicated (eg, cigar and cigarette), manufacturer, candy flavor, images, product rating, pack color, and if the product had packaging that may appeal to youth. RESULTS: We found 66 CTIP available. The most popular CTIP were cigars, with 39 separate products (59%), followed by candy cigarettes-14 products (21%), candy pipes-8 products (12%), and chewing tobacco-5 products (8%). In the 52 products where packaging design was available, 39 (75%) had packaging that may appeal to youth. CONCLUSIONS: CTIP, many of which contain packaging appealing to youth, are widely available for purchase online across the United States. These findings could stimulate policy actions, such as removal of CTIP from popular retail websites, labeling of CTIP as potentially dangerous to youth, or age verification requirements for purchasing CTIP. IMPLICATIONS: CTIP continues to be sold on the internet despite research indicating candy cigarette product use by youth increases their likelihood of smoking. We conducted research to understand the extent to which CTIP are sold on the internet and whether these products are being marketed to youth. The results provide evidence that some of the largest retail companies in the world continue to sell CTIP, and the majority are sold in packaging that likely appeals to youth. The results suggest that further research into the market for these products is needed, and regulatory measures should be considered to prevent CTIP from leading to youth tobacco use.

Financial Toxicity in Radiation Oncology: Impact for Our Patients and for Practicing Radiation Oncologists.

With rising costs of diagnosis, treatment, and survivorship, financial burdens on patients with cancer and negative effects from high costs, called financial toxicity (FT), are growing. Research suggests that FT may be experienced by more than half of working-age cancer survivors and a similar proportion may incur debt or avoid recommended prescription medications due to treatment costs. As FT can lead to worse physical, psychological, financial, and survival outcomes, there is a discrete need to identify research gaps around this issue that constrain the development and implementation of effective screening and innovative care delivery interventions. Prior research, including within a radiation oncology-specific context, has sought to identify the scope of FT among patients with cancer, develop assessment tools to evaluate patient risk, quantify financial sacrifices, and qualify care compromises that occur when cancer care is unaffordable. FT is a multifactorial problem and potential solutions should be pursued at all levels of the health care system (patient-provider, institutional, and systemic) with specific regard for patients' individual/local contexts. Solutions may include selecting alternative treatment schedules, discussing financial concerns with patients, providing financial navigation services, low-cost transportation options, and system-wide health policy shifts. This review summarizes existing FT research, describes tools developed to measure FT, and suggests areas for intervention and study to help improve FT and outcomes for radiation oncology patients.

Care from Birth to Discharge of Infants Born at 22 to 23 Weeks' Gestation.

The clinical care of infants born at 22 weeks' gestation must be well-designed and standardized if optimal results are to be expected. Although several approaches to care in this vulnerable population are possible, protocols should be neither random nor inconsistent. We describe the approach taken at the University of Iowa Stead Family Children's Hospital neonatal intensive care unit with respect to preterm infants born at 22 weeks' gestation. We have chosen to present our standardize care plan with respect to prenatal, neurologic, nutritional, gastrointestinal, and skin management. Respiratory and cardiopulmonary care will be briefly reviewed, as these strategies have been published previously.

Acute kidney injury surveillance in the high-risk neonatal population following implementation of creatinine screening protocol.

AIM: Acute kidney injury (AKI) in neonates is associated with longer hospital stays and higher mortality rates. However, there is significant variability in prevalence rates of AKI and the true burden is incompletely understood. In November 2020, the University of Iowa Stead Family Children's Hospital Neonatal Intensive Care Unit implemented a creatinine screening protocol to enhance kidney function monitoring. We sought to evaluate adherence to the protocol to determine if increased surveillance led to increased detection of AKI events. METHODS: A retrospective chart review was conducted for neonates born at <30 weeks' gestation admitted between 2015 and 2020. We reviewed 100 charts in both the pre (2015-2016) and post (2020-2021) implementation era of the AKI surveillance protocol. AKI was defined according to neonatal modified KDIGO criteria. RESULTS: Following implementation of the protocol, neonates were significantly more likely to have creatinine checked (p < 0.001). Serum creatinine was drawn according to protocol guidelines 68% of the time, and 42% of patients (34/82) had an 80% or higher adherence to the protocol. There was a significant increase in detection of AKI in the post-protocol cohort (13/82, incidence of 16%) compared to the pre-protocol cohort (5/83, incidence of 6%), (p = 0.047). CONCLUSION: The implementation of a serum creatinine screening protocol increased the frequency of creatinine draws and detection of AKI.

Multiple Perspectives on Motivating Parents in Pediatric Primary Care to Initiate Participation in Parenting Programs.

OBJECTIVE: To use multiple perspectives to identify the key components of pediatric primary care conversations for motivating parents to utilize parenting programs. We aim to develop an actionable framework that primary care clinicians (PCCs) can follow for effective conversations with parents. METHODS: We conducted focus groups and interviews with researchers (n = 6) who have experience delivering parenting interventions through primary care, clinical personnel in federally qualified health centers (FQHCs) (n = 9), parents of 3-5-year olds who receive services at a FQHC pediatric clinic (n = 6), and parent educators (n = 5). Groups and interviews were informed by nominal group technique, and researchers triangulated consolidated strategies across the groups. RESULTS: Key strategies for PCCs to motivate parents to utilize parenting programs followed three steps: 1) learning about a parent's questions and concerns, 2) sharing resources, and 3) following up. PCCs can learn about parents' needs by empathizing, listening and responding, and asking questions that acknowledge parents' expertise. When sharing resources, PCCs can motivate participation in parenting programs by explaining each resource and its benefits, providing options that support parents' autonomy, and framing resources as strengthening rather than correcting parents' existing strategies or skills. Finally, PCCs can continue to engage parents by scheduling follow-up conversations or designating a staff member to check-in with parents. We provide examples for each strategy. CONCLUSIONS: Findings provide guidance from multiple perspectives on strategies to motivate parents in pediatric primary care setting for utilizing parenting programs.

Selective Personalized RadioImmunotherapy for Locally Advanced Non-Small-Cell Lung Cancer Trial (SPRINT).

PURPOSE: Standard therapy for locally advanced non-small-cell lung cancer (LA-NSCLC) is concurrent chemoradiotherapy followed by adjuvant durvalumab. For biomarker-selected patients with LA-NSCLC, we hypothesized that sequential pembrolizumab and risk-adapted radiotherapy, without chemotherapy, would be well-tolerated and effective. METHODS: Patients with stage III NSCLC or unresectable stage II NSCLC and an Eastern Cooperative Oncology Group performance status of 0-1 were eligible for this trial. Patients with a PD-L1 tumor proportion score (TPS) of ≥50% received three cycles of induction pembrolizumab (200 mg, once every 21 days), followed by a 20-fraction course of risk-adapted thoracic radiotherapy (55 Gy delivered to tumors or lymph nodes with metabolic volume exceeding 20 cc, 48 Gy delivered to smaller lesions), followed by consolidation pembrolizumab to complete a 1-year treatment course. The primary study end point was 1-year progression-free survival (PFS). Secondary end points included response rates after induction pembrolizumab, overall survival (OS), and adverse events. RESULTS: Twenty-five patients with a PD-L1 TPS of ≥50% were enrolled. The median age was 71, most patients (88%) had stage IIIA or IIIB disease, and the median PD-L1 TPS was 75%. Two patients developed disease progression during induction pembrolizumab, and two patients discontinued pembrolizumab after one infusion because of immune-related adverse events. Using RECIST criteria, 12 patients (48%) exhibited a partial or complete response after induction pembrolizumab. Twenty-four patients (96%) received definitive thoracic radiotherapy. The 1-year PFS rate is 76%, satisfying our efficacy objective. One- and 2-year OS rates are 92% and 76%, respectively. The most common grade 3 adverse events were colitis (n = 2, 8%) and esophagitis (n = 2, 8%), and no higher-grade treatment-related adverse events have occurred. CONCLUSION: Pembrolizumab and risk-adapted radiotherapy, without chemotherapy, are a promising treatment approach for patients with LA-NSCLC with a PD-L1 TPS of ≥50%.

Predicting Patterns of Distant Metastasis in Breast Cancer Patients following Local Regional Therapy Using Machine Learning.

Up to 30% of breast cancer (BC) patients will develop distant metastases (DM), for which there is no cure. Here, statistical and machine learning (ML) models were developed to estimate the risk of site-specific DM following local-regional therapy. This retrospective study cohort included 175 patients diagnosed with invasive BC who later developed DM. Clinicopathological information was collected for analysis. Outcome variables were the first site of metastasis (brain, bone or visceral) and the time interval (months) to developing DM. Multivariate statistical analysis and ML-based multivariable gradient boosting machines identified factors associated with these outcomes. Machine learning models predicted the site of DM, demonstrating an area under the curve of 0.74, 0.75, and 0.73 for brain, bone and visceral sites, respectively. Overall, most patients (57%) developed bone metastases, with increased odds associated with estrogen receptor (ER) positivity. Human epidermal growth factor receptor-2 (HER2) positivity and non-anthracycline chemotherapy regimens were associated with a decreased risk of bone DM, while brain metastasis was associated with ER-negativity. Furthermore, non-anthracycline chemotherapy alone was a significant predictor of visceral metastasis. Here, clinicopathologic and treatment variables used in ML prediction models predict the first site of metastasis in BC. Further validation may guide focused patient-specific surveillance practices.

Palliative radiotherapy for hepatic tumors: a narrative review of indications and recommendations.

BACKGROUND AND OBJECTIVE: Primary and metastatic liver cancer presents heterogeneously. New radiotherapy techniques have reduced toxicity concerns, leading to increased use of liver radiotherapy. This review synthesizes available evidence and offers recommendations for palliative radiotherapy for liver cancer. METHODS: PubMed, Ovid Medline, Embase, Cochrane Central, and Web of Science were searched from inception to December 28th, 2022. Articles reporting local control (LC), survival, toxicity, symptom control, and response after stereotactic body radiotherapy (SBRT), partial-liver, or whole-liver radiotherapy (WLRT) techniques were reviewed. We also identified nomograms identifying patients who may benefit from radiotherapy. KEY CONTENT AND FINDINGS: Nine randomized-controlled trials were found, in addition to many retrospective, feasibility, and phase I or II studies. Patients with favorable prognosis may receive SBRT using 30-50 Gray (Gy) in 3-5 fractions for primary cancer and up to 60 Gy for metastases, provided normal-tissue constraints are met. Select patients with multiple (>5) or large (>10 cm) lesions or macrovascular invasion (MVI) may be considered, but with potentially reduced LC and increased toxicity. Lower SBRT doses (i.e., 25 Gy in 5 fractions) can be considered on a cautionary basis for patients with poorer liver function or health. Patients with larger tumor burden, poor performance status (PS), or inability to tolerate SBRT positioning or motion-management can consider partial-liver three-dimensional conformal radiotherapy (3DCRT). For patients with extremely guarded prognosis and/or extremely poor performance, WLRT provides pain and symptom relief over several weeks. Combining radiotherapy and systemic therapy may allow radiotherapy de-escalation while maintaining good outcomes. CONCLUSIONS: Radiotherapy has a definite role for palliation of liver cancer with practical research providing guidance in the use of techniques and different regimens in various patient subgroups. Future investigation, including randomized trials, is needed to optimize patient selection, radiotherapy techniques, and integration with other therapies.

A Cluster Randomized Controlled Trial of a Primary Care Provider-Delivered Social Media Counseling Intervention.

PURPOSE: Evidence and clinical policy support that providers screen and counsel for media use for youth, but most pediatricians lack this training. The purpose of this study was to test a primary care provider (PCP)-delivered intervention to promote safe social media use among youth. METHODS: We enrolled pediatric PCP practices for this clinical trial to test a social media counseling intervention (SMCI) between 2011 and 2013. Youth were recruited during clinic visits; follow-up interviews were conducted at 6 months. Outcomes included media behaviors and caregiver communication. Multivariate regression models examined associations between social media counseling and PCP counseling score. Multivariate logistic regression evaluated four social media behavior outcomes. RESULTS: A total of 120 practices enrolled; PCPs in the SMCI were more likely to provide social media counseling (B = 1.43, 95% confidence interval [CI]: 1.1-1.7). Youth whose PCP received the SMCI were twice as likely to report a decrease in online "friending" of strangers (adjusted odds ratio = 2.23, 95% CI 1.17-4.25) and were more likely to report communication with their caregivers about their social media use (adjusted odds ratio = 1.2; 95% CI: 1.1-1.4) compared to youth whose PCPs were in the active control group. DISCUSSION: Youth whose PCP had received social media counseling training reported a higher receipt of counseling about social media and improved safety behaviors.

Individualising radiation therapy decisions in breast cancer patients based on tumour infiltrating lymphocytes and genomic biomarkers.

Radiation therapy (RT) has long been fundamental for the curative treatment of breast cancer. While substantial progress has been made in the anatomical and technological precision of RT delivery, and some approaches to de-escalate or omit RT based on clinicopathologic features have been successful, there remain substantial opportunities to refine individualised RT based on tumour biology. A major area of clinical and research interest is to ascertain the individualised risk of loco-regional recurrence to direct treatment decisions regarding escalation and de-escalation of RT. Patient-tailored treatment with RT is considerably lagging behind compared with the massive progress made in the field of personalised medicine that currently mainly applies to decisions on the use of systemic therapy or targeted agents. Herein we review select literature surrounding the use of tumour genomic biomarkers and biomarkers of the immune system, including tumour infiltrating lymphocytes (TILs), within the management of breast cancer, specifically as they relate to progress in moving toward analytically validated and clinically tested biomarkers utilized in RT.

Patent ductus arteriosus (PDA) and response to late surfactant treatment in premature infants.

OBJECTIVE: To determine the clinical/echocardiography (ECHO) phenotype of patients with hypoxic respiratory failure (HRF) and response to late surfactant, according to patent ductus arteriosus (PDA) status. STUDY DESIGN: This retrospective study included infants ≤26+6 weeks gestation who received ≥1 surfactant dose after 6 postnatal days and where PDA status was available by ECHO. Response to surfactant was appraised based on change in respiratory severity score over 48 h. The relationship between PDA status and response to surfactant was evaluated via univariate analysis. RESULT: We studied late surfactant (n = 71 doses) administration in 35 preterm infants born at a mean weight and GA at birth were 595 g (508, 696) and 23.3 (22.7, 25) weeks, respectively of whom 16 (46%) had a diagnosis of PDA. Positive response to late surfactant treatment was independently associated with absence of PDA [OR 26 (2, 334), p = 0.01] whereas presence of PDA was independently associated with negative response [OR 12 (1.1, 126), p = 0.04]. CONCLUSIONS: In neonates ≤26+6 weeks gestation, with HRF, response to surfactant after postnatal day 6 is influenced by PDA status. Future trials should consider PDA status which may enhance diagnostic precision and refine patient selection for late surfactant treatment.

Impact of Early Hemodynamic Screening on Extremely Preterm Outcomes in a High-Performance Center.

Rationale: Increasing survival of extremely preterm infants with a stable rate of severe intraventricular hemorrhage represents a growing health risk for neonates. Objectives: To evaluate the role of early hemodynamic screening (HS) on the risk of death or severe intraventricular hemorrhage. Methods: All eligible patients 22-26+6 weeks' gestation born and/or admitted <24 hours postnatal age were included. As compared with standard neonatal care for control subjects (January 2010-December 2017), patients admitted in the second epoch (October 2018-April 2022) were exposed to HS using targeted neonatal echocardiography at 12-18 hours. Measurements and Main Results: A primary composite outcome of death or severe intraventricular hemorrhage was decided a priori using a 10% reduction in baseline rate to calculate sample size. A total of 423 control subjects and 191 screening patients were recruited with a mean gestation and birth weight of 24.7 ± 1.5 weeks and 699 ± 191 g, respectively. Infants born at 22-23 weeks represented 41% (n = 78) of the HS epoch versus 32% (n = 137) of the control subjects (P = 0.004). An increase in perinatal optimization (e.g., antepartum steroids) but with a decline in maternal health (e.g., increased obesity) was seen in the HS versus control epoch. A reduction in the primary outcome and each of severe intraventricular hemorrhage, death, death in the first postnatal week, necrotizing enterocolitis, and severe bronchopulmonary dysplasia was seen in the screening era. After adjustment for perinatal confounders and time, screening was independently associated with survival free of severe intraventricular hemorrhage (OR 2.09, 95% CI [1.19, 3.66]). Conclusions: Early HS and physiology-guided care may be an avenue to further improve neonatal outcomes; further evaluation is warranted.

Embedding OR modelling as decision support in health capacity planning: insights from an evaluation.

Literature reviews over five decades have reported the paucity of examples of OR methods being routinely used to support decision-making in health and social care. This paper presents insights from an independent evaluation of a project intended to overcome some of the barriers to implementation by establishing a "community of practice" in Kent (England). The project itself was undertaken by practitioners, and had two main aims: providing training in system dynamics modelling to analysts, and making senior managers aware of the benefits of modelling. The findings largely confirmed previous studies, but also raised issues about style of training delivery and selection of problems to be modelled. Project leaders fully understood the barriers to embedding OR modelling skills, and made considerable efforts to avoid them, but nevertheless the main barrier, pressures on people's time, remained an obstacle. The paper concludes with general reflections and advice.