How do we define high and low dose intensity of heart failure medications: a scoping review.

BACKGROUND: Older adults with heart failure often experience adverse drug events with high doses of heart failure medications. Recognizing whether a patient is on a high or low dose intensity heart failure medication can be helpful for daily practice, since it could potentially guide the physician on which symptoms to look for, whether from overdosing or underdosing. However, the current guideline does not provide sufficient information about the dose intensity below the target dose. Furthermore, the definition of high or low-intensity heart failure medication is unclear, and there is no consensus. METHODS: To close the knowledge gap, we conducted a scoping review of the current literature to identify the most frequently used definition of high versus low doses of heart failure medications. We searched Pubmed, Embase, CINAHL, and Cochrane Library using comprehensive search terms that can capture the intensity of heart failure medications. RESULTS: We reviewed 464 articles, including 144 articles that had information about beta-blockers (BB), 179 articles about angiotensin-converting enzyme inhibitors (ACEi), 75 articles about angiotensin receptor blockers (ARB), 80 articles about diuretics, 37 articles about mineralocorticoid receptor antagonists (MRA), and 33 articles about angiotensin receptor-neprilysin inhibitor (ARNI). For hydralazine with isosorbide dinitrate or ivabradine, we could not identify any eligible articles. We identified 40 medications with most frequently used definitions of dose intensity. Four medications (nadolol, pindolol, cilazapril, and torsemide) did not reach consensus in definitions. Most of the BBs, ACEis, or ARBs used the definition of low being < 50% of the target dose and high being ≥ 50% of the target dose from the guideline. However, for lisinopril and losartan, the most commonly used definitions of high or low were from pivotal clinical trials with a pre-defined definition of high or low. CONCLUSION: Our comprehensive scoping review studies identified the most frequently used definition of dose intensity for 40 medications but could not identify the definitions for 4 medications. The results of the current scoping review will be helpful for clinicians to have awareness whether the currently prescribed dose is considered high - requiring close monitoring of side effects, or low - requiring more aggressive up-titration.

Definition of Polypharmacy in Heart Failure: A Scoping Review of the Literature.

Patients with heart failure (HF) have a high prevalence of polypharmacy, which can lead to drug interactions, cognitive impairment, and medication non-compliance. However, the definition of polypharmacy in these patients is still inconsistent. The aim of this scoping review was to find the most common definition of polypharmacy in HF patients. We conducted a scoping review searching Medline, Embase, CINAHL, and Cochrane using terms including polypharmacy, HF and deprescribing, which resulted in 7,949 articles. Articles without a definition of polypharmacy in HF patients and articles which included patients < 18 years of age were excluded; only 59 articles were included. Of the 59 articles, 49% (n = 29) were retrospective, 20% (n = 12) were prospective, 10% (n = 6) were cross-sectional, and 27% (n = 16) were review articles. Twenty percent (n = 12) of the articles focused on HF with reduced ejection fraction, 10% (n = 6) focused on HF with preserved ejection fraction and 69% (n = 41) articles either focused on both diagnoses or did not clarify the specific type of HF. The most common cutoff for polypharmacy in HF was five medications (59%, n = 35). There was no consensus regarding the inclusion or exclusion of over-the-counter medications, supplements, or vitamins. Some newer studies used a cutoff of 10 medications (14%, n = 8), and this may be a more practical and meaningful definition for HF patients.

Maternal and Neonatal Outcomes of Gunshot Wounds in Pregnancy: A Systematic Review of Case Reports.

A systematic review was performed to compare adverse maternal and neonatal outcomes among pregnant patients with gunshot wounds (GSW) to the abdominopelvic vs other region(s) at > 20 weeks gestation. A search of Medline Ovid, Elsevier Embase, EBSCO CINAHL, and Cochrane Library in July 2022 and reference searches resulted in 1742 studies, which were screened. The 41 included studies reported outcomes for 59 pregnant patients with GSW, of which 31 (52.5%) had an isolated abdominopelvic GSW and 28 (47.5%) had an extremity, thorax, head/neck, back/spine, poly-site, or other/unknown GSW. Stillbirth occurred in 26.7% of abdominopelvic GSW and 26% of non-abdominopelvic GSW. Maternal death occurred in 3.7% of abdominopelvic GSW and 10.7% of non-abdominopelvic GSW. Neonatal death occurred in 9.1% of abdominopelvic GSW and 5.3% of non-abdominopelvic GSW. Further research is needed to standardize the approach for the evaluation and management of patients with GSW in pregnancy.

Prostate Cancer Therapy Cardiotoxicity Map (PROXMAP) for Advanced Disease States: A Systematic Review and Network Meta-analysis with Bayesian Modeling of Treatment Histories.

BACKGROUND AND OBJECTIVE: Recommendations of first-line therapies for metastatic hormone-sensitive (mHSPC), nonmetastatic castrate-resistant (M0CRPC), and metastatic castrate-resistant (mCRPC) prostate cancer do not account for cardiotoxicity due to a lack of clear prior evidence. This manuscript assesses cardiotoxicity of these therapies. METHODS: We searched Ovid Medline, Elsevier Embase, and the Cochrane Library for randomized clinical trials (RCTs) from database inception to January 14, 2024. Network meta-analyses of first-line mHSPC, M0CRPC, and mCRPC therapies were constructed for the five cardiotoxicity metrics defined by the International Cardio-Oncology Society: heart failure, myocarditis, vascular toxicity, hypertension, and arrhythmias. Additional Bayesian network meta-analyses also accounted for prior treatment history. KEY FINDINGS AND LIMITATIONS: Thirteen RCTs (16 292 patients) were included. For mHSPC, androgen deprivation therapy (ADT) plus docetaxel (DTX) plus abiraterone acetate (AA) with prednisone (P) demonstrated a significant increase in hypertension and arrhythmias versus ADT + DTX (risk ratio [RR] 2.85, 95% confidence interval [CI] 1.67-4.89, and RR 2.01, 95% CI 1.17-3.44, respectively); however, no corresponding differences were observed between ADT + DTX plus darolutamide (DAR) and ADT + DTX (RR 1.55, 95% CI 0.73-3.30, and RR 0.94, 95% CI 0.63-1.40, respectively). For mCRPC assuming a history of mHSPC treatment, ADT + AA + P plus olaparib (OLA) demonstrated a statistically significant decrease in hypertension versus ADT + AA + P (RR 0.20, 95% CI 0.16-0.26). M0CRPC results were unremarkable. CONCLUSIONS AND CLINICAL IMPLICATIONS: For mHSPC, ADT + DTX + DAR demonstrates less cardiotoxicity than ADT + DTX + AA + P due to a lower risk of hypertension and arrhythmias from decreased mineralocorticoid excess. In addition, OLA counterintuitively offers decreased hypertension when superimposed on ADT + AA + P for mCRPC treatment after prior androgen deprivation from mHSPC therapy.

A scoping review of randomized trials assessing the impact of n-of-1 trials on clinical outcomes.

BACKGROUND: The single patient (n-of-1) trial can be used to resolve therapeutic uncertainty for the individual patient. Treatment alternatives are systematically tested against each other, generating patient-specific data used to inform an individualized treatment plan. We hypothesize that clinical decisions informed by n-of-1 trials improve patient outcomes compared to usual care. Our objective was to provide an overview of the clinical trial evidence on the effect of n-of-1 trials on clinical outcomes. METHODS: A systematic search of medical databases, trial registries, and gray literature was performed to identify trials assessing clinical outcomes in a group of patients undergoing an n-of-1 trial compared to those receiving usual care for any clinical condition. We abstracted elements related to study design and results and assessed risk of bias for both the overall randomized trials and the n-of-1 trials. The review was registered on PROSPERO. (CRD: 42020166490). FINDINGS: Twelve randomized trials of the n-of-1 approach were identified in conditions spanning chronic pain, osteoarthritis, chronic irreversible airflow limitation, attention-deficit hyperactivity disorder, hyperlipidemia, atrial fibrillation, statin intolerance, and hypertension. One trial showed a statistically significant benefit in the primary outcome. Only one reached the pre-specified sample size target. Secondary outcomes showed modest benefits, including decreasing medication use, fewer atrial fibrillation episodes, and improved patient satisfaction. INTERPRETATION: Very few trials have been undertaken to assess the effectiveness of n-of-1 trials in improving clinical outcomes, and most trials were underpowered for the primary outcome. Barriers to enrollment and retention in these trials should be explored, as well-powered randomized trials are needed to clarify the clinical impact of n-of-1 trials and assess their utility in clinical practice.

A meta-analysis of the global impact of the COVID-19 pandemic on stroke care & the Houston Experience.

OBJECTIVE: To review the global impact of the COVID-19 pandemic on stroke care-metrics and report data from a health system in Houston. METHODS: We performed a meta-analysis of the published literature reporting stroke admissions, intracerebral hemorrhage (ICH) cases, number of thrombolysis (tPA) and thrombectomy (MT) cases, and time metrics (door to needle, DTN; and door to groin time, DTG) during the pandemic compared to prepandemic period. Within our hospital system, between January-June 2019 and January-June 2020, we compared the proportion of stroke admissions and door to tPA and MT times. RESULTS: A total of 32,640 stroke admissions from 29 studies were assessed. Compared to prepandemic period, the mean ratio of stroke admissions during the pandemic was 70.78% [95% CI, 65.02%, 76.54%], ICH cases was 83.10% [95% CI, 71.01%, 95.17%], tPA cases was 81.74% [95% CI, 72.33%, 91.16%], and MT cases was 88.63% [95% CI, 74.12%, 103.13%], whereas DTN time was 104.48% [95% CI, 95.52%, 113.44%] and DTG was 104.30% [95% CI, 81.99%, 126.61%]. In Houston, a total of 4808 cases were assessed. There was an initial drop of ~30% in cases at the pandemic onset. Compared to 2019, there was a significant reduction in mild strokes (NIHSS 1-5) [N (%), 891 (43) vs 635 (40), P = 0.02]. There were similar mean (SD) (mins) DTN [44 (17) vs 42 (17), P = 0.14] but significantly prolonged DTG times [94 (15) vs 85 (20), P = 0.005] in 2020. INTERPRETATION: The COVID-19 pandemic led to a global reduction in stroke admissions and treatment interventions and prolonged treatment time metrics.

Developing interagency collaboration to address the opioid epidemic: A scoping review of joint criminal justice and healthcare initiatives.

BACKGROUND: With the current opioid epidemic impacting well over half of all counties across the United States, initiatives that encourage interagency collaboration between first responder organizations appear necessary to comprehensively address this crisis. Police, fire, and emergency medical services (EMS) are in a unique position to identify substance users and provide necessary resources to initiate treatment, yet there is not sufficient evidence of joint collaborative programs between law enforcement/first responders and healthcare providers. METHODS: In this scoping review we examine the current state of joint criminal justice and healthcare interventions, specifically, opioid and substance use pre-arrest initiatives via emergency first responders and police officers. We relied on data from the last 10 years across three major databases to assess the extent of criminal justice (CJ) and healthcare collaborations as a response to individuals with opioid use disorder (OUD). We specifically focused on interventional programs between criminal justice first responders (pre-arrest) and healthcare providers where specific outcomes were documented. RESULTS: We identified only a small number (6) of studies involving interventions that met this criteria, suggesting very limited study of joint interagency collaboration between law enforcement first responders and healthcare providers. Most had small samples, none were in the southern states, and all but one were initiated within the last 5 years. CONCLUSIONS: Although studies describing joint efforts of early intercept criminal justice responses and healthcare interventions were few, existing studies suggest that such programs were effective at improving treatment referral and retention outcomes. Greater resources are needed to encourage criminal justice and healthcare collaboration and policies, making it easier to share data, refer patients, and coordinate care for individuals with OUD.

N-of-1 Trials as a Decision Support Tool in Clinical Practice: A Protocol for a Systematic Literature Review and Narrative Synthesis.

The n-of-1 trial can utilized in clinical practice as a decision support tool, which may improve patient outcomes by providing both the patient and the clinician with objective evidence to inform personalized treatment decisions. As its use broadens, it will be important to study whether the added time and effort of an n-of-1 trial results in measurable improvements in important patient outcomes compared to usual clinical practice. Parallel-group randomized clinical trials testing the n-of-1 approach versus usual care have been undertaken in a number of medical settings. A systematic review will be performed according to PRISMA guidelines, using MEDLINE, Embase, Cochrane, CINAHL, PsycINFO, Scopus, and Web of Science to search for randomized clinical trials in humans, without date or language restriction. Reports from the gray literature and ongoing studies in trial registries will be included. Articles will be screened by two independent reviewers with a third reviewer consulted to adjudicate disagreement. The quality of included studies will be assessed using the Cochrane Collaboration's tool for assessing risk of bias. A narrative synthesis will explore the differing methodological approaches of the included studies. The protocol will be registered in the PROSPERO registry, and the results of the review will be published in a peer-reviewed journal. To our knowledge, this systematic review will be the first to comprehensively assess the existing research on randomized trials testing the n-of-1 trial approach in clinical practice.