RELAX (REducing Levels of AnXiety): a study protocol for a parallel two-arm randomised controlled trial evaluating a web-based early intervention for pregnant women with high levels of repetitive negative thinking to prevent escalating anxiety during pregnancy and after birth.

BACKGROUND: Perinatal anxiety is common: up to 40% of pregnant women and new mothers experience high levels of anxiety. Given its prevalence, interventions that are low-intensity, highly accessible and cost-efficient, and target modifiable risk factors for anxiety are needed. Repetitive negative thinking (RNT)-such as worrying about ways things will go wrong in the future or ruminating about past negative events-is a risk factor for the development of anxiety. RNT is maintained by the tendency to generate negative interpretations of ambiguous situations. METHODS: A parallel two-arm randomised controlled trial will assess the efficacy of adding interpretation training (RELAX) to usual maternity care. Participants (N = 268) will be randomised to (i) 12 sessions of online interpretation training (RELAX) plus usual care, or (ii) usual care alone. We will assess anxiety, depression, RNT, and work and social adjustment at baseline, plus 4, 8 and 36 weeks later. DISCUSSION: Should the intervention result in lower levels of anxiety than usual care, it could be an accessible, cost-effective way to help women who are vulnerable to experiencing anxiety in the perinatal period. TRIAL REGISTRATION: ISRCTN 12754931. Registered 25th May 2023, prior to recruitment.

Anaplastic thyroid cancer: A review of recent evidence and summary of an Australian institutional protocol.

Anaplastic thyroid cancer (ATC), a rare and highly aggressive malignancy, is characterized by an exceptionally poor prognosis, where the majority of patients present with extensive local invasion and/or distant metastases. 20-30% of ATCs harbor the BRAF-V600E mutation. Neoadjuvant BRAF-targeted therapy may have the potential to downstage and facilitate surgical resection for patients with locally advanced and unresectable primary tumors with BRAF mutation and may convey a survival advantage in those with metastatic disease. There is emerging evidence to support the use of other targeted agents, including multikinase inhibitors, as well as the incorporation of immunotherapy into the treatment regimen. Rapid molecular and pathological diagnosis and expert multidisciplinary discussion at specialized treatment centers are critical to expedite investigations and initiate treatment for this complex and rapidly progressive disease.

Implementation of Diabetic Retinopathy Screening in Adult Patients With Type 2 Diabetes in a Primary Care Setting.

Diabetic retinopathy (DR) is a microvascular complication of type 2 diabetes and the leading cause of blindness globally. Although diabetes-related eye exams are widely recognized as an effective method for early detection of DR, which can help to prevent eventual vision loss, adherence to screening exams in the United States is suboptimal. This article describes a quality improvement project to increase DR screening rates and increase knowledge and awareness of DR in adults with type 2 diabetes in a primary care setting using mobile DR screening units. This project addressed gaps of care and demonstrated that primary care settings can increase access to DR screening through a patient-centered process and thereby help to prevent irreversible outcomes of DR and improve quality of life.

Repeat Placental Growth Factor-Based Testing in Women With Suspected Preterm Preeclampsia: A Stratified Analysis of the PARROT-2 Trial.

BACKGROUND: PlGF (placental growth factor)-based testing reduces severe maternal adverse outcomes. Repeat PlGF-based testing is not associated with improved perinatal or maternal outcomes. This planned secondary analysis aimed to determine whether there is a subgroup of women who benefit from repeat testing. METHODS: Pregnant individuals with suspected preterm preeclampsia were randomized to repeat revealed PlGF-based testing, compared with usual care where testing was concealed. Perinatal and maternal outcomes were stratified by trial group, by initial PlGF-based test result, and by PlGF-based test type (PlGF or sFlt-1 [soluble fms-like tyrosine kinase-1]/PlGF ratio). RESULTS: A total of 1252 pregnant individuals were included. Abnormal initial PlGF-based test identified a more severe phenotype of preeclampsia, at increased risk of adverse maternal and perinatal outcomes. Repeat testing was not significantly associated with clinical benefit in women with abnormal initial results. Of women with a normal initial result, 20% developed preeclampsia, with the majority at least 3 to 4 weeks after initial presentation. Repeat test results were more likely to change from normal to abnormal in symptomatic women (112/415; 27%) compared with asymptomatic women (163/890; 18%). A higher proportion of symptomatic women who changed from normal to abnormal were diagnosed with preeclampsia, compared with asymptomatic women. CONCLUSIONS: Our results do not demonstrate evidence of the clinical benefit of repeating PlGF-based testing if the initial result is abnormal. Judicious use of repeat PlGF-based testing to stratify risk may be considered at least 2 weeks after a normal initial test result, particularly in women who have symptoms or signs of preeclampsia. REGISTRATION: URL: https://www.isrctn.com/ISRCTN85912420; Unique identifier: ISRCTN85912420.

Medicare Coverage and Patient Out-of-Pocket Costs for Cardiovascular-Kidney-Metabolic Medications.

This cross-sectional study evaluates the association between Medicare coverage and patient out-of-pocket costs for cardiovascular-kidney-metabolic medications.

Repeat placental growth factor-based testing in women with suspected preterm pre-eclampsia (PARROT-2): a multicentre, parallel-group, superiority, randomised controlled trial.

BACKGROUND: Placental growth factor (PlGF)-based testing has high diagnostic accuracy for predicting pre-eclampsia needing delivery, significantly reducing time to diagnosis and severe maternal adverse outcomes. The clinical benefit of repeat PlGF-based testing is unclear. We aimed to determine whether repeat PlGF-based testing (using a clinical management algorithm and nationally recommended thresholds) reduces adverse perinatal outcomes in pregnant individuals with suspected preterm pre-eclampsia. METHODS: In this multicentre, parallel-group, superiority, randomised controlled trial, done in 22 maternity units across England, Scotland, and Wales, we recruited women aged 18 years or older with suspected pre-eclampsia between 22 weeks and 0 days of gestation and 35 weeks and 6 days of gestation. Women were randomly assigned (1:1) to revealed repeat PlGF-based testing or concealed repeat testing with usual care. The intervention was not masked to women or partners, or clinicians or data collectors, due to the nature of the trial. The trial statistician was masked to intervention allocation. The primary outcome was a perinatal composite of stillbirth, early neonatal death, or neonatal unit admission. The primary analysis was by the intention-to-treat principle, with a per-protocol analysis restricted to women managed according to their allocation group. The trial was prospectively registered with the ISRCTN registry, ISRCTN 85912420. FINDINGS: Between Dec 17, 2019, and Sept 30, 2022, 1253 pregnant women were recruited and randomly assigned treatment; one patient was excluded due to randomisation error. 625 women were allocated to revealed repeat PlGF-based testing and 627 women were allocated to usual care with concealed repeat PlGF-based testing (mean age 32·3 [SD 5·7] years; 879 [70%] white). One woman in the concealed repeat PlGF-based testing group was lost to follow-up. There was no significant difference in the primary perinatal composite outcome between the revealed repeat PlGF-based testing group (195 [31·2%]) of 625 women) compared with the concealed repeat PlGF-based testing group (174 [27·8%] of 626 women; relative risk 1·21 [95% CI 0·95-1·33]; p=0·18). The results from the per-protocol analysis were similar. There were four serious adverse events in the revealed repeat PlGF-based testing group and six in the concealed repeat PlGF-based testing group; all serious adverse events were deemed unrelated to the intervention by the site principal investigators and chief investigator. INTERPRETATION: Repeat PlGF-based testing in pregnant women with suspected pre-eclampsia was not associated with improved perinatal outcomes. In a high-income setting with a low prevalence of adverse outcomes, universal, routine repeat PlGF-based testing of all individuals with suspected pre-eclampsia is not recommended. FUNDING: Tommy's Charity, Jon Moulton Charitable Trust, and National Institute for Health and Care Research Guy's and St Thomas' Biomedical Research Centre.

Participant Safety in Multisite, Randomized, Double-Blind, Placebo-Controlled Clinical Trials in Hospice/Palliative Care: Data from the Contracted Studies of the Australian National Palliative Care Clinical Studies Collaborative.

Objective: To describe the harms in all arms of six consecutive multi-site, double-blind, placebo-controlled randomised clinical trials. Background: Controversies surround conduct of phase III clinical trials in palliative care. Concerns include risks to participants' safety, use of placebo arms, participants' burden, and justification when therapies are already widely used. Methods: This study collates safety data of the first six studies of the Australian national Palliative Care Clinical Studies Collaborative. On an intention-to-treat basis, all harms are described using standard international definitions, their severity, outcomes, and level of attribution. Results: Studies recruited 1,232 participants: 65/1,232 (5.3%) participants had serious adverse events of which none had a definite (blinded) attribution, all of which settled with ceasing the intervention; 49/1,232 (4.0%) participants had adverse events. No participants on placebo arms had adverse or serious adverse events with definite (blinded) attribution. Discussion: These studies are safe for participants and generate knowledge to support informed patient decision making.

Rationale, Design, and Patient Characteristics of a Cluster-Randomized Pragmatic Trial to Improve Mineralocorticoid Antagonist Use.

BACKGROUND: Despite robust evidence and strong guideline recommendations supporting use of mineralocorticoid receptor antagonists (MRAs) to improve outcomes in patients with heart failure with reduced ejection fraction (HFrEF), these medications remain underused in clinical practice. OBJECTIVES: The goal is to determine if providing a tailored best practice alert (BPA) to outpatient providers suggesting guideline-recommended MRAs or information about available hyperkalemia treatment, if present, for patients with HFrEF will increase short-term MRA prescriptions. METHODS: PROMPT-MRA (Pragmatic Trial of Messaging to Providers About Treatment With Mineralocorticoid Receptor Antagonists) is a pragmatic, cluster-randomized, controlled study. A total of 119 providers were randomized to receive a BPA or usual care. During an outpatient visit with participating providers, the BPA displayed recent laboratory test values and ejection fraction. The alert suggested guideline-recommended MRAs for eligible patients with a serum potassium of <5.0 mEq/L or novel potassium binders for those with a serum potassium of ≥5.0 mEq/L, each linked to an order set containing the corresponding medication and laboratory monitoring. RESULTS: PROMPT-MRA completed enrollment with 1,210 patients. The primary outcome of PROMPT-MRA is to determine if a tailored BPA for outpatients with HFrEF will lead to higher MRA prescriptions 6 months following randomization compared with usual care. Secondary outcomes included incidence of hyperkalemia, use of novel potassium binders, heart failure hospitalizations, and mortality. CONCLUSIONS: If effective, the BPA can be scaled to improve population health outcomes with increased MRA prescribing among eligible patients with HFrEF, with or without a history of hyperkalemia. (Pragmatic Trial of Alerts for Use of Mineralocorticoid Receptor Antagonists [PROMPT-MRA]; NCT04903717).

Defining a path toward improved heart failure care.

Defining a path toward improved heart failure (HF) care is essential, as there is a clear need to improve HF treatment quality, outcomes, and value. This article reviews potential strategies to help improve the quality of HF clinical care and decrease costs. To start, HF phenotyping may be useful in guiding patient treatment, as some phenotypes are associated with higher hospitalization costs and longer length of stay. Identifying and addressing social determinants of health that may be barriers to optimal health may improve management of HF and help to prevent disease progression. In addition, patient-reported outcomes can be useful for evaluating the effectiveness of treatment regimens and assessing which treatments lead to a genuine improvement in quality of life (QOL). Recent innovations in payment reform have seen the implementation of value-based payment (VBP) models over the traditional fee-for-service (FFS) models. FFS models can lead to low-quality care focused on treating illness instead of supporting wellness initiatives. By contrast, VBP models aim to decrease excessive health care costs, thereby increasing incentives to hospitals that deliver high-quality patient care. Further, novel care delivery approaches, such as hospital-at-home and other digital tools, can provide patients with lower-cost care and are associated with improved QOL, including reductions in hospital readmission.

Electronic Health Record Embedded Strategies for Improving Care of Patients With Heart Failure.

PURPOSE: A majority of clinical decisions use the electronic health record (EHR) and there is an unmet need to use its capability to help providers to make evidence-based decisions that improve care for heart failure patients. These electronic nudges are rooted in the human psychology of decision-making and often target specific cognitive biases. This review outlines the development of novel EHR nudges and specific lessons learned from each experience to inform the development of future interventions. RECENT FINDINGS: There have been several randomized clinical trials examining the impact of EHR alerts on quality of care for heart failure patients. These interventions have targeted both clinicians and patients. There are features of each trial that inform best practices and future directions for EHR nudges. Recent clinical trials have demonstrated that some EHR alerts can improve care for heart failure patients. These trials utilized default options, involved clinicians in the alert design process, provided actionable recommendations, and aimed to minimize disruptions to typical workflow. Alerts aimed at improving care should be examined in a randomized fashion in order to evaluate their impact on clinician satisfaction and patient care.

Defining research priorities and needs in cancer symptoms for adults diagnosed with cancer: an Australian/New Zealand modified Delphi study.

PURPOSE: This study asked consumers (patients, carers) and healthcare professionals (HCPs) to identify the most important symptoms for adults with cancer and potential treatment interventions. METHODS: A modified Delphi study was conducted involving two rounds of electronic surveys based on prevalent cancer symptoms identified from the literature. Round 1 gathered information on participant demographics, opinions and/or experience on cancer symptom frequency and impact, and suggestions for interventions and/or service delivery models for further research to improve management of cancer symptoms. In Round 2, respondents ranked the importance of the top ten interventions identified in Round 1. In Round 3, separate expert panels of consumers and healthcare professionals (HCPs) attempted to reach consensus on the symptoms and interventions previously identified. RESULTS: Consensus was reached for six symptoms across both groups: fatigue, constipation, diarrhoea, incontinence, and difficulty with urination. Notably, fatigue was the only symptom to reach consensus across both groups in Round 1. Similarly, consensus was reached for six interventions across both groups. These were the following: medicinal cannabis, physical activity, psychological therapies, non-opioid interventions for pain, opioids for breathlessness and cough, and other pharmacological interventions. CONCLUSIONS: Consumers and HCPs prioritise differently; however, the symptoms and interventions that reached consensus provide a basis for future research. Fatigue should be considered a high priority given its prevalence and its influence on other symptoms. The lack of consumer consensus indicates the uniqueness of their experience and the need for a patient-centred approach. Understanding individual consumer experience is important when planning research into better symptom management.

Wearable-Triggered Ecological Momentary Assessments Are Feasible in People With Advanced Cancer and Their Family Caregivers: Feasibility Study from an Outpatient Palliative Care Clinic at a Cancer Center.

Background: Emerging digital health approaches could play a role in better personalized palliative care. Aim: We conducted a feasibility study testing wearable sensor (WS)-triggered ecological momentary assessments (EMAs) and electronic patient-reported outcomes in community palliative care with patient-caregiver dyads. Design: All wore consumer-grade WS for five weeks. Sensor-detected "stress" (heart rate variability algorithm) that passed individualized thresholds triggered a short smartphone survey. Daily sleep surveys, weekly symptom surveys (Integrated Palliative care Outcome Scale), and a poststudy experience survey were conducted. Setting/Participants: Fifteen dyads (n = 30) were recruited from an outpatient palliative care clinic for people with cancer. Results: Daytime sensor wear-time had 73% adherence. Participants perceived value in this support. Quantity and severity of "stress" events were higher in patients. Sleep disturbance was similar but for different reasons: patients (physical symptoms) and caregivers (worrying about the patient). Conclusions: EMAs are feasible and valued in community palliative care.

The use of sodium-glucose cotransporter 2 inhibitors in heart failure with reduced or preserved ejection fraction: new guidelines hot off the press and directly into guidelines!

It is well known that the prevalence of heart failure (HF) is high and continues to grow. Sodium-glucose cotransporter 2 (SGLT2) inhibitors, although initially developed as a therapy for type 2 diabetes, have been found to be beneficial in patients with HF, regardless of diabetic status. Given the clinical benefit demonstrated in recent large randomized clinical trials in those with HF, they have been rapidly incorporated into clinical practice and adopted by the national guidelines hot off the press. SGLT2 inhibitors are now recommended for patients with symptomatic HF, with any ejection fraction. These medications are generally very well tolerated by patients, and adverse effects include genital and soft tissue infections, euglycemic ketoacidosis, and volume depletion. SGLT2 inhibitors have now become a pillar of the pharmacologic treatment of HF, thus providers should be familiar with their use for not only those with type 2 diabetes, but also those with HF.

Exploring biopsychosocial correlates of pregnancy risk and pregnancy intention in women with chronic kidney disease.

INTRODUCTION: Women with Chronic Kidney Disease (CKD) are at increased risk of adverse pregnancy and renal outcomes. It is unknown how women with CKD understand their pregnancy risk. This nine-centre, cross-sectional study aimed to explore how women with CKD perceive their pregnancy risk and its impact on pregnancy intention, and identify associations between biopsychosocial factors and perception of pregnancy risk and intention. METHODS: Women with CKD in the UK completed an online survey measuring their pregnancy preferences; perceived CKD severity; perception of pregnancy risk; pregnancy intention; distress; social support; illness perceptions and quality of life. Clinical data were extracted from local databases. Multivariable regression analyses were performed. Trial registration: NCT04370769. RESULTS: Three hundred fifteen women participated, with a median estimated glomerular filtration rate (eGFR) of 64 ml/min/1.73m2 (IQR 56). Pregnancy was important or very important in 234 (74%) women. Only 108 (34%) had attended pre-pregnancy counselling. After adjustment, there was no association between clinical characteristics and women's perceived pregnancy risk nor pregnancy intention. Women's perceived severity of their CKD and attending pre-pregnancy counselling were independent predictors of perceived pregnancy risk. Importance of pregnancy was an independent predictor of pregnancy intention but there was no correlation between perceived pregnancy risk and pregnancy intention (r = - 0.002, 95% CI - 0.12 to 0.11). DISCUSSION: Known clinical predictors of pregnancy risk for women with CKD were not associated with women's perceived pregnancy risk nor pregnancy intention. Importance of pregnancy in women with CKD is high, and influences pregnancy intention, whereas perception of pregnancy risk does not.