Guideline-recommended Treatment Research Articles

A randomized, open-label, clinical trial examined the effects of canagliflozin on albuminuria and eGFR decline using an individual pre-intervention eGFR slope.

Demonstrating drug efficacy in slowing kidney disease progression requires large clinical trials when targeting participants with an early stage of chronic kidney disease (CKD). In this randomized, parallel-group, open-labeled trial (CANPIONE study), we assessed the effect of the sodium-glucose cotransporter 2 (SGLT2) inhibitor canagliflozin using the individual’s change in estimated glomerular filtration rate (eGFR) slope before (pre-intervention slope) and during treatment (chronic slope).We randomly assigned (1:1) participants with type 2 diabetes, urinary albumin-to-creatinine ratio (UACR) of 50 to under 300 mg/g, and an eGFR of at least 45 ml/min/1.73m2 to receive canagliflozin or guideline-recommended treatment except for SGLT2inhibitors (control). The first and second primary outcomes were the geometric mean percentage change from baseline in UACR and the change in eGFR slope, respectively. Of 98 randomized participants, 96 received at least one study treatment. The least-squares mean change from baseline in log-transformed geometric mean UACR was significantly greater in the canagliflozin group than the control group (between group-difference, −30.8% (95% confidence interval −42.6 to −16.8). The between-group difference (canagliflozin group – control group) of change in eGFR slope (chronic – pre-intervention) was 4.4 (1.6 to 7.3) ml/min/1.73 m2 per year, which was more pronounced in participants with faster eGFR decline. In summary, canagliflozin reduced albuminuria and the participant-specific natural course of eGFR decline in participants with type 2 diabetes and microalbuminuria. Thus, the CANPIONE study suggest that the within-individual change in eGFR slope may be a novel approach to determine the kidney protective potential of new therapies in early stages of CKD.

The Impact of Eliminating Out-of-Pocket Payments on Asthma Medication Use.

High costs of controller therapies may be a barrier to guideline-recommended asthma treatment. We determined whether eliminating out-of-pocket (OOP) payments among low-income patients with asthma impacted controller medication use. We applied a controlled interrupted time series design to administrative claims data in British Columbia, Canada from 2017-2020. Cases were individuals with an annual household income <$13,750 in whom copays were eliminated on January 2019; there was no change in public coverage for the control group with annual income >$45,000. We evaluated trends in asthma medication costs, use, the ratio of inhaled corticosteroid (ICS)-containing medications to all asthma medications, excessive use of short-acting β-agonists (SABA) (>1 canister/month), and the proportion of days (PDC) covered by controller therapies. There were 12,940 cases (62% female, mean age 30.3 years, SD 14.9), and 71,331 controls (55% female, mean age of 31.3 years, SD 16.3). Removal of OOP payments increased monthly mean medication costs by $3.32 (95% CI $0.08 - $6.56, 2020 Canadian dollars), days supply of controller medications by 1.50 days (95% CI 0.61 - 2.40), and the ratio of ICS-containing medications to total medications by 4.20% (95% CI 0.73% - 7.66%) compared to the control group. The policy had no effect on PDC by controller therapies (0.01, 95% CI -0.01 - 0.04), but non-significantly decreased the percentage of patients with excessive SABA use (-6.37%; 95% CI -12.90% - 0.16%). Removal of OOP payments increased the dispensation of controller therapies, suggesting cost-related non-adherence could impair optimal asthma management.

Hypertension evaluation and management in new young patients: are we doing our female patients a disservice?

Purpose Cardiovascular disease (CVD) is one of the leading causes of death in women, largely underpinned by hypertension. Current guidelines recommend first-line therapy with a RAAS-blocking agent especially in young people. There are well documented sex disparities in CVD outcomes and management. We evaluate the management of patients with newly diagnosed hypertension in a tertiary care clinic to assess male–female differences in investigation and treatment. Methods Clinic letters of all new patients under the age of 51 attending the Glasgow Blood Pressure Clinic between January and December 2023 were reviewed. The primary outcomes measured were first-line treatment choices, deviations from guideline-recommended treatment, investigations for secondary hypertension, and documentation of female-specific risk factors and family planning advice. Secondary outcomes included clinical characteristics such as systolic and diastolic blood pressure at referral and at the new patient appointment, age at diagnosis, age at first appointment, and the number of antihypertensive drugs prescribed at referral. Results One hundred and five (59:46, M:F) new patient encounters were reviewed after sixteen exclusions for non-attendance and inappropriate clinic coding. Choice of first line antihypertensive agent did not vary between sexes with no deviation from guideline-recommended medical therapy. Men, however, had more biochemical investigations conducted for secondary causes across all ages. This was greatest in those under 40 years old. There was suboptimal documentation of female-specific risk factors (obstetric and gynaecological history), contraceptive drug history and family planning with 35%, 20%, and 15.6%, respectively. Conclusion In 2023, women under 51 years of age seen in a tertiary care hypertension clinic received similar first-line treatment to their male peers. However, relevant female-specific histories were suboptimally documented for these patients. Whilst therapeutic approaches in men and women appear to be similar in this clinic, there are opportunities to improve CVD prevention in women, even in a specialised clinic setting.

Disparity in Guideline-Based Antidiabetic Drugs Prescribing for Type 2 Diabetes Patients in Primary Healthcare Facilities Across China, 2017-2019.

The purpose of this study is to evaluate the pattern, appropriateness, and cost of antidiabetic drugs prescribed for patients with Type 2 diabetes at primary healthcare facilities (PHFs) in China. We collected outpatient-visit prescriptions from 363 PHFs in 31 cities covering eastern, central, and western regions of China. The visits of adult patients with Type 2 diabetes diagnosis were collected and classified the antidiabetic medication pattern of each patient use as recommended or non-recommended according to Chinese guidelines. We then calculated the proportion of guideline-recommended patterns and the average monthly cost for each pattern, overall and by region. Of 33 519 prescriptions for Type 2 diabetes, most (73.9%) were for guideline-recommended antidiabetic treatments. The proportion of guideline-recommended prescriptions varied by region (eastern [75.9%], central [87.5%], and western [59.7%]). Metformin monotherapy was the most common guideline-recommended treatment in all three regions (eastern [20.1%], central [28.0%], and western [24.6%]). The most common non-guideline-recommended treatments were monotherapy of insulin (eastern [16.5%], central [5.1%], and western [25.7%]) and traditional Chinese antidiabetic medicines (eastern [5.6%], central [5.7%], and western [11.1%]). The average monthly costs were lower for guideline-recommended treatments compared to non-recommended treatments in all regions (eastern [13.6 ± 15.4 USD vs. 28.1 ± 22.0 USD], central [9.8 ± 10.9 USD vs. 28.7 ± 19.4 USD], and western [17.9 ± 21.4 USD vs. 30.3 ± 23.6 USD]). The majority of patients with Type 2 diabetes received guideline-recommended antidiabetic medications at PHFs in China, with only half of the prescriptions containing guideline-recommended metformin. Utilization of guideline-recommended therapies differed across regions. Tailored interventions to promote evidence-based antidiabetic prescribing are urgently needed, especially in the undeveloped western region.

Real-world clinical and economic outcomes for patients with advanced non-small cell lung cancer enrolled in a clinical trial following comprehensive genomic profiling via liquid biopsy.

Oncology clinical trial enrollment is strongly recommended for patients with cancer who are not eligible for established and approved therapies. Many trials are specific to biomarker-targeted therapies, which are typically managed as specialty pharmacy services. Comprehensive genomic profiling (CGP) of advanced cancers has been shown to detect biomarkers, guide targeted treatment, improve outcomes, and result in the clinical trial enrollment of patients, which is modeled to offset pharmacy costs experienced by US payers, yet payer policy coverage remains inconsistent. A common concern limiting coverage of CGP by payers is the potential of identifying biomarkers beyond guideline-recommended treatments, which creates a perception that insurance companies are being positioned to "pay for research." However, these biomarkers can increase clinical trial eligibility, and specialty pharmacy management may have an interest in maximizing the clinical trial enrollment of members. To investigate if clinical trial enrollment following liquid biopsy CGP for non-small cell lung cancer (NSCLC) is clinically and/or economically impactful from a payer claims perspective. Clinical and economic outcomes were studied using a real-world clinical genomic database (including payer claims data) from patients with NSCLC who enrolled in clinical trials immediately following liquid biopsy CGP (using Guardant360) and matched NSCLC patient controls also tested with liquid biopsy CGP. Real-world overall survival was significantly (log-rank P < 0.0001) better for patients enrolled in clinical trials with similar costs of care, albeit with more outpatient encounters among those enrolled compared with matched controls. The results, together with previous analyses, suggest that, in addition to the clinical benefits associated with targeted therapies directed by CGP and other testing approaches, payers and specialty pharmacy managers may consider clinical trial direction and enrollment as a clinical and economic benefit of liquid biopsy CGP and adopt this into coverage decision frameworks and formularies.

Concordance With Screening and Treatment Guidelines for Chronic Kidney Disease in Type 2 Diabetes

Chronic kidney disease (CKD) is an often-asymptomatic complication of type 2 diabetes (T2D) that requires annual screening to diagnose. Patient-level factors linked to inadequate screening and treatment can inform implementation strategies to facilitate guideline-recommended CKD care. To identify risk factors for nonconcordance with guideline-recommended CKD screening and treatment in patients with T2D. This retrospective cohort study was performed at 20 health care systems contributing data to the US National Patient-Centered Clinical Research Network. To evaluate concordance with CKD screening guidelines, adults with an outpatient clinician visit linked to T2D diagnosis between January 1, 2015, and December 31, 2020, and without known CKD were included. A separate analysis reviewed prescription of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) and sodium-glucose cotransporter 2 (SGLT2) inhibitors in adults with CKD (estimated glomerular filtration rate [eGFR] of 30-90 mL/min/1.73 m2 and urinary albumin-to-creatinine ratio [UACR] of 200-5000 mg/g) and an outpatient clinician visit for T2D between October 1, 2019, and December 31, 2020. Data were analyzed from July 8, 2022, through June 22, 2023. Demographics, lifestyle factors, comorbidities, medications, and laboratory results. Screening required measurement of creatinine levels and UACR within 15 months of the index visit. Treatment reflected prescription of ACEIs or ARBs and SGLT2 inhibitors within 12 months before or 6 months following the index visit. Concordance with CKD screening guidelines was assessed in 316 234 adults (median age, 59 [IQR, 50-67] years), of whom 51.5% were women; 21.7%, Black; 10.3%, Hispanic; and 67.6%, White. Only 24.9% received creatinine and UACR screening, 56.5% received 1 screening measurement, and 18.6% received neither. Hispanic ethnicity was associated with lack of screening (relative risk [RR], 1.16 [95% CI, 1.14-1.18]). In contrast, heart failure, peripheral arterial disease, and hypertension were associated with a lower risk of nonconcordance. In 4215 patients with CKD and albuminuria, 3288 (78.0%) received an ACEI or ARB; 194 (4.6%), an SGLT2 inhibitor; and 885 (21.0%), neither therapy. Peripheral arterial disease and lower eGFR were associated with lack of CKD treatment, while diuretic or statin prescription and hypertension were associated with treatment. In this cohort study of patients with T2D, fewer than one-quarter received recommended CKD screening. In patients with CKD and albuminuria, 21.0% did not receive an SGLT2 inhibitor or an ACEI or an ARB, despite compelling indications. Patient-level factors may inform implementation strategies to improve CKD screening and treatment in people with T2D.

Patient out-of-pocket costs for guideline-recommended treatments for erectile dysfunction: a medicare cost modeling analysis.

Patient out-of-pocket (OOP) cost represents an access barrier to erectile dysfunction (ED) treatment. We determined OOP cost for men with ED covered by Fee-for-Service Medicare. Coverage policies were obtained from the Medicare Coverage Database for treatments recommended by the 2018 American Urological Association (AUA) guidelines. OOP cost was retrieved from the 2023 Centers for Medicare & Medicaid Services Final Rule. OOP cost for treatments without Medicare coverage were extracted from GoodRx® or literature and inflated to 2022 dollars. Annual prescription costs were calculated using the published estimate of 52.2 yearly instances of sexual intercourse. Medicare has coverage for inflatable penile prostheses (IPP; strong recommendation), non-coverage for vacuum erection devices (VED; moderate recommendation) and phosphodiesterase type-5 inhibitors (PDE5i; strong recommendation), and no policies for intracavernosal injections (ICI; moderate recommendation), intraurethral alprostadil (IA; conditional recommendation), or low-intensity extracorporeal shock wave therapy (ESWT; conditional recommendation). Annual IA prescription is most costly ($4022), followed by ICI prescription ($3947), one ESWT course ($3445), IPP ($1600), PDE5i prescription ($696), and one VED ($213). PDE5i and IPP, both strongly recommended by AUA guidelines, are associated with lower OOP cost. Better understanding of patient financial burden may inform healthcare decision-making.

Comment on: Patient out-of-pocket costs for guideline-recommended treatments for erectile dysfunction: a medicare cost modeling analysis.

Comment on: Patient out-of-pocket costs for guideline-recommended treatments for erectile dysfunction: a medicare cost modeling analysis.

Accordance of Registered Drug Packages with Guideline-Recommended Treatment Durations for Community-Acquired Pneumonia-A New Antibiotic Stewardship Target?

In most countries, antibiotics for oral administration are put on the market in fixed packages. When there is no exact unit dispensing of antimicrobials, drug pack size may influence prescribers' choice of treatment duration. The aim of this study was to investigate the accordance of approved antibiotic packages with national guidelines for the treatment of community-acquired pneumonia (CAP). For the purpose of this study, criteria were developed to determine the accordance of approved antibiotic packages for treating CAP (criteria), which are based on recommendations from national guidelines for treating CAP. Subsequently, the accordance of approved antibiotic packages with the number of antibiotic doses resulting from the specified criteria was determined. Of 39 identified therapeutic option-package size combinations, 11 were found to be matched (28.2%), meaning there were no leftover medication units after completing therapy, and 28 were mismatched combinations (71.8%), indicating that there were excess doses of antibiotics remaining at the end of therapy. The results of this research showed a significant non-accordance of the approved antibiotic packages with the national guidelines for the treatment of CAP and, consequently, the creation of a large amount of residues of unit doses of antibiotics in the community.

Racialized Economic Segregation and Treatment and Outcomes of Small Cell Lung Cancer.

Little is known about the role of residential segregation in the treatment and outcomes of small cell lung cancer (SCLC), a highly recalcitrant disease, among non-Hispanic White (NHW) and non-Hispanic Black (NHB) patients. We used the Surveillance, Epidemiology, and End Results database to identify men and women diagnosed with SCLC from January 2007 to December 2015 (n = 38,393). An Index of Concentration at the Extremes was computed to measure county-level racialized economic segregation and categorized into Quartile 1 (most privileged: highest concentration of high-income NHW residents) through Quartile 4 (least privileged: highest concentration of low-income NHB residents). Multilevel logistic regression was used to estimate the ORs for extensive-stage diagnosis and nonadherence to guideline-recommended treatment. HRs for lung cancer-specific and overall mortalities were computed using multilevel Cox regression. Patients in the least privileged counties had higher risks of nonadherence to guideline-recommended treatment [OR = 1.23; 95% confidence interval (CI): 1.08-1.40; Ptrend < 0.01], lung cancer-specific mortality (HR = 1.08; 95% CI: 1.04-1.12; Ptrend < 0.01), and all-cause mortality (HR = 1.13; 95% CI: 1.09-1.17; Ptrend < 0.0001) compared with patients in the most privileged counties. Adjustment for treatment did not significantly reduce the association with mortality. These associations were comparable between NHB and NHW patients. Segregation was not significantly associated with extensive-stage diagnosis. The results suggest that living in the neighborhoods with higher proportions of low-income households and Black residents had adverse impacts on stage-appropriate treatment of and survival from SCLC. This highlights the need for improving the access to quality lung cancer care in the less privileged neighborhoods.

Primary care clinician perspectives on automated nephrology e-consults for diabetic kidney disease: a pre-implementation qualitative study

BackgroundMany patients with diabetic kidney disease (DKD) do not receive evidence-based, guideline-recommended treatment shown to reduce DKD progression and complications. Proactive electronic consultations (e-consults) are an emerging intervention strategy that could potentially allow nephrologists to provide timely and evidence-based guidance to primary care providers (PCPs) engaged in early DKD care.MethodsThe objective of this study was to explore perspectives about potential barriers and facilitators associated with a proactive e-consult program to improve DKD care delivery. We conducted semi-structured qualitative interviews with PCPs across three different health systems. Interview transcripts were reviewed in a rapid qualitative analysis approach to iteratively identify, refine, and achieve consensus on a final list of themes and subthemes.ResultsA total of 18 interviews were conducted. PCPs across all sites identified similar challenges to delivering guideline-recommended DKD care. PCPs were supportive of the proactive e-consult concept. Three major themes emerged surrounding (1) perceived potential benefits of proactive e-consults, including educational value and improved specialist access; (2) concerns about the proactive nature of e-consults, including the potential to increase PCP workload and the possibility that e-consults could be seen as documenting substandard care; and (3) leveraging of care teams to facilitate recommended DKD care, such as engaging clinic-based pharmacists to implement specialist recommendations from e-consults.ConclusionIn this pre-implementation qualitative study, PCPs noted potential benefits and identified concerns and implementation barriers for proactive e-consults for DKD care. Strategies that emerged for promoting successful implementation included involving clinic support staff to enact e-consult recommendations and framing e-consults as a system improvement effort to avoid judgmental associations.

Quantification of treatment-related time toxicity in patients with advanced stage cancer.

12137 Background: Treatment-related Time Toxicity (TrTT) in cancer patients is a recently proposed metric to describe the burden of time spent in pursuing medical care, including office/hospital visits, side effect management, lab tests, imaging scans, and travel time. Time toxicity is a valuable concept in patient-centered shared-decision making, especially in the palliative management of end-stage cancer patients with limited life expectancy. Despite tremendous progress in cancer treatment, most of the guideline-recommended treatment options convey short survival benefits of around 3-6 months when compared to supportive care. While medication toxicities are meticulously reviewed with patients, the cumulative burden and impact of time are rarely included in the discussion, partly due to the lack of standardized measurement of TrTT, and the absence of data from clinical trials. Thus, there is a compelling need for the quantification of time toxicity to guide clinical practice and patient preference. Methods: This was an observational analysis of the time toxicity from palliative treatment for patients with incurable solid tumors at a regional safety-net oncology office that focuses on underserved communities. Time toxicity is calculated as the number of days a patient spent with any healthcare-related encounters during a 3-month period from our medical record system. Results: The median age of the total 94 included patients was 57. 54% of the population were Hispanic. The ratios for mild, moderate, and severe time toxicity were 38%, 44%, and 18%, respectively. Immunotherapy was associated with significantly less time toxicity (TrTT = 8.5 days, 95% CI = 6.3-9.7) compared to chemotherapy (26.3 days, 95% CI = 18.3-34.4, P &lt; 0.001), while targeted therapy (13.4, 95% CI = 7.0-19.8, P = 0.01) and hormone therapy (11.9, 95% CI = 4.1-19.7, P &lt; 0.01) also has lower TrTT than chemotherapy. Patients with a worse performance status (ECOG PS 3-4, 30.1 days, 95% CI = 18.3-41.9) experienced higher time toxicity than fitter patients (PS 0-2, 16.7 days, 95% CI = 13.2-20.2, P &lt; 0.05). Among different cancer types, gastrointestinal malignancies were associated with the highest time toxicity with average TrTT of 30.2 days/3 months (95% CI =22.5-37.2). Conclusions: This is the first comprehensive study to quantify real-world Treatment-Related Time Toxicity across multiple cancer and therapy types in an underserved population. We found 18% of patients with incurable solid malignancies experienced severe time toxicity (&gt; 1 in 3 days). Higher TrTT was associated with cytotoxic chemotherapies, GI malignancies, and poor performance status. Time toxicity should be taken into account with other quality-of-life outcomes in treatment pathways and patient-centered oncology care.

Frailty evidence-practice gaps in acute care hospitals.

Frailty is common in hospitalised older people. Clinical practice guidelines for the management of frailty provide recommendations for identification and management; however, adoption into practice in hospitals is limited. This study identified and quantified the evidence-practice gap between frailty guidelines and clinical practice in two hospitals using an audit tool. A cross-sectional audit of medical records of frail older patients admitted to two hospitals was conducted. Data were collected using an audit tool based on the Asia Pacific Clinical Practice Guidelines for frailty management. Data were analysed using descriptive statistics and inter-rater reliability of the tool was assessed. Auditing of n = 70 electronic medical records showed that assessment of frailty in the acute setting did not regularly occur (17%). Few participants received guideline-recommended interventions. Physiotherapy treatment was limited, with 23% of participants receiving progressive resistance strength training. Gaps exist in provision of nutritional supplementation (26%) with limited recordings of weight during the admission for 10% of participants. Pharmacy review of medications was consistently documented on admission (84%) and discharge (93%). Vitamin D was prescribed for 57% of participants. Inter-rater reliability showed a high level of agreement using the audit tool. An audit tool was feasible to assess frailty evidence-practice gaps in the hospital setting. Further understanding of the contextual barriers is needed to inform implementation strategies (dedicated staffing, education and training and ongoing audit of practice cycles) for the uptake of frailty guidelines in hospital settings.

Cost-Effectiveness of Medical Therapy for Heart Failure With Mildly Reduced and Preserved Ejection Fraction

BackgroundThree medications are now guideline-recommended treatments for heart failure with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF), however, the cost-effectiveness of these agents in combination has yet to be established. ObjectivesThe purpose of this study was to determine the cost-effectiveness of mineralocorticoid receptor antagonists (MRA), angiotensin receptor-neprilysin inhibitors (ARNIs), and sodium glucose co-transporter 2 inhibitors (SGLT2is) in individuals with HFmrEF/HFpEF. MethodsUsing a 3-state Markov model, we performed a cost-effectiveness study using simulated cohorts of 1,000 patients with HFmrEF and HFpEF. Treatment with 1-, 2-, and 3-drug combinations was modeled. Based on a United States health care sector perspective, outcome data was used to calculate incremental cost-effectiveness ratios (ICERs) in 2023 United States dollars based on a 30-year time horizon. ResultsTreatment with MRA, MRA+SGLT2i, and MRA+SGLT2i+ARNI therapy resulted in an increase in life years of 1.04, 1.58, and 1.80 in the HFmrEF subgroup, respectively, and 0.99, 1.54, and 1.77 in the HFpEF subgroup, respectively, compared with placebo. At a yearly cost of $18, MRA therapy resulted in ICERs of $10,000 per quality-adjusted life year (QALY) in both subgroups. The ICER for the addition of SGLT2i therapy ($4,962 per year) was $113,000 per QALY in the HFmrEF subgroup and $141,000 in the HFpEF subgroup. The addition of ARNI therapy ($5,504 per year) resulted in ICERs >$250,000 per QALY in both subgroups. If SGLT2i and ARNI were available at generic pricing the ICERs become <$10,000 per QALY in both EF subgroups. Outcomes were highly sensitive to assumed benefit in cardiovascular death. ConclusionsFor patients with heart failure, MRA was of high value, SGLT2i was of intermediate value, and ARNI was of low value in both HFmrEF and HFpEF subgroups. For patients with HFmrEF/HFpEF increased use of MRA and SGLT2i therapies should be encouraged and be accompanied with efforts to lower the cost of SGLT2i and ARNI therapies.

PEERLESS II: A Randomized Controlled Trial of Large-Bore Thrombectomy Versus Anticoagulation in Intermediate-Risk Pulmonary Embolism

BackgroundAnticoagulation (AC) is the guideline-recommended treatment for intermediate-risk pulmonary embolism (PE); however, it remains unclear whether mechanical thrombectomy provides benefit over AC alone. The PEERLESS II study aims to evaluate outcomes in intermediate-risk PE patients randomized to treatment with large-bore mechanical thrombectomy and AC vs AC alone. MethodsPEERLESS II is an international randomized controlled trial enrolling up to 1200 patients with intermediate-risk PE and additional clinical risk factors from up to 100 sites. Treatment is randomized 1:1 to large-bore mechanical thrombectomy with the FlowTriever System (Inari Medical) and AC or AC alone. Outcomes will be evaluated for up to 3 months, with safety events independently adjudicated. The primary end point is a hierarchical composite win ratio of (1) all-cause mortality by 30 days, (2) clinical deterioration (earlier of discharge or 30 days), (3) all-cause hospital readmission by 30 days, (4) bailout therapy (earlier of discharge or 30 days), and (5) Modified Medical Research Council (mMRC) dyspnea score of ≥1 at the 48-hour visit. Secondary end points include all-cause and PE-related mortality (30-day and 90-day), all-cause and PE-related readmission (30-day and 90-day), major bleeding (30-day and 90-day), clinical deterioration (earlier of discharge or 30 days), bailout (earlier of discharge or 30 days), right ventricle-to-left ventricle diameter ratio (48-hour visit), mMRC dyspnea score (48-hour, 1-month, and 3-month visits), quality of life using Pulmonary Embolism Quality of Life and EuroQol-5 Dimensions-5 Levels (1-month and 3-month visits), 6-minute walk distance (1-month visit), and post-PE impairment diagnosis (3-month visit). ConclusionsPEERLESS II will inform the understanding of mechanical thrombectomy treatment for intermediate-risk PE and provide evidence for consideration in future treatment guidelines.

Trends and prescribing patterns of antimigraine medicines in nine major cities in China from 2018 to 2022: a retrospective prescription analysis

BackgroundThe objective of this study was to investigate the trends and prescribing patterns of antimigraine medicines in China.MethodsThe prescription data of outpatients diagnosed with migraine between 2018 and 2022 were extracted from the Hospital Prescription Analysis Cooperative Project of China. The demographic characteristics of migraine patients, prescription trends, and corresponding expenditures on antimigraine medicines were analyzed. We also investigated prescribing patterns of combination therapy and medicine overuse.ResultsA total of 32,246 outpatients who were diagnosed with migraine at 103 hospitals were included in this study. There were no significant trend changes in total outpatient visits, migraine prescriptions, or corresponding expenditures during the study period. Of the patients who were prescribed therapeutic medicines, 70.23% received analgesics, and 26.41% received migraine-specific agents. Nonsteroidal anti-inflammatory drugs (NSAIDs; 28.03%), caffeine-containing agents (22.15%), and opioids (16.00%) were the most commonly prescribed analgesics, with corresponding cost proportions of 11.35%, 4.08%, and 19.61%, respectively. Oral triptans (26.12%) were the most commonly prescribed migraine-specific agents and accounted for 62.21% of the total therapeutic expenditures. The proportion of patients receiving analgesic prescriptions increased from 65.25% in 2018 to 75.68% in 2022, and the proportion of patients receiving concomitant triptans decreased from 29.54% in 2018 to 21.55% in 2022 (both P < 0.001). The most frequently prescribed preventive medication classes were calcium channel blockers (CCBs; 51.59%), followed by antidepressants (20.59%) and anticonvulsants (15.82%), which accounted for 21.90%, 34.18%, and 24.15%, respectively, of the total preventive expenditures. Flunarizine (51.41%) was the most commonly prescribed preventive drug. Flupentixol/melitracen (7.53%) was the most commonly prescribed antidepressant. The most commonly prescribed anticonvulsant was topiramate (9.33%), which increased from 6.26% to 12.75% (both P < 0.001). A total of 3.88% of the patients received combined therapy for acute migraine treatment, and 18.63% received combined therapy for prevention. The prescriptions for 69.21% of opioids, 38.53% of caffeine-containing agents, 26.61% of NSAIDs, 13.97% of acetaminophen, and 6.03% of triptans were considered written medicine overuse.ConclusionsMigraine treatment gradually converges toward evidence-based and guideline-recommended treatment. Attention should be given to opioid prescribing, weak evidence-based antidepressant use, and medication overuse in migraine treatment.

Liver cancer wars: plant-derived polyphenols strike back.

Liver cancer currently represents the leading cause of cancer-related death worldwide. The majority of liver cancer arises in the context of chronic inflammation and cirrhosis. Surgery, radiation therapy, and chemotherapy have been the guideline-recommended treatment options for decades. Despite enormous advances in the field of liver cancer therapy, an effective cure is yet to be found. Plant-derived polyphenols constitute a large family of phytochemicals, with pleiotropic effects and little toxicity. They can drive cellular events and modify multiple signaling pathways which involves initiation, progression and metastasis of liver cancer and play an important role in contributing to anti-liver cancer drug development. The potential of plant-derived polyphenols for treating liver cancer has gained attention from research clinicians and pharmaceutical scientists worldwide in the last decades. This review overviews hepatic carcinogenesis and briefly discusses anti-liver cancer mechanisms associated with plant-derived polyphenols, specifically involving cell proliferation, apoptosis, autophagy, angiogenesis, oxidative stress, inflammation, and metastasis. We focus on plant-derived polyphenols with experiment-based chemopreventive and chemotherapeutic properties against liver cancer and generalize their basic molecular mechanisms of action. We also discuss potential opportunities and challenges in translating plant-derived polyphenols from preclinical success into clinical applications.

Sequential endoluminal gemcitabine and docetaxel vs. Bacillus Calmette–Guérin for the treatment of upper tract carcinoma in situ

IntroductionNephroureterectomy is commonly performed for high-grade (HG) upper tract (UT) urothelial carcinoma (UC). However, some patients may benefit from a de-escalation of surgical management, particularly for noninvasive disease and carcinoma in situ (CIS). Bacillus Calmette–Guerin (BCG) is currently the only guideline-recommended endoluminal treatment option. Gemcitabine/Docetaxel (Gem/Doce) has shown promising efficacy as a treatment for noninvasive HG UTUC, though a comparison to BCG is lacking. We report the outcomes of patients treated with endoluminal Gem/Doce vs. BCG for UT-CIS. MethodsA single-institutional retrospective review of patients treated with Gem/Doce vs. BCG for UT-CIS was performed. Treatment was instilled via nephrostomy or retrograde ureteral catheter. In both treatment groups, induction consisted of 6 weekly instillations. Maintenance was initiated if disease-free and consisted of 6 monthly instillations in the Gem/Doce group and a reduced dose (one-tenth) 3-week course at 3 months in the BCG group. Recurrence was defined as biopsy-proven disease or HG cytology. ResultsThe final cohort included 53 patients with 65 upper tract units; 31 received BCG and 34 received Gem/Doce. Median follow-up was 88 and 29 months in the BCG and Gem/Doce groups, respectively. Presenting pathology included biopsy-proven CIS and HG cytology in 9.7% and 90% of the BCG group, and 8.8% and 91% of the Gem/Doce group, respectively. The 2-year estimates for recurrence-free and nephroureterectomy-free survival were 61% and 89% for the BCG group and 54% and 100% for the Gem/Doce group, respectively. Upon multivariable analysis, instillation via percutaneous nephrostomy tube was associated with an increased risk of recurrence (HR 3.89, 95% CI 1.59–9.53). The development of any symptom was not statistically different between treatment groups (P = 0.12). There were 2 treatment-related deaths that occurred, 1 within each treatment group. ConclusionEndoluminal Gem/Doce and BCG have similar oncological outcomes and major adverse event rates in the treatment of UT-CIS. Further prospective evaluation is warranted.

Impact of disease volume on survival efficacy of triplet therapy for metastatic hormone-sensitive prostate cancer: a systematic review, meta-analysis, and network meta-analysis.

Triplet therapy, androgen receptor signaling inhibitors (ARSIs) plus docetaxel plus androgen-deprivation therapy (ADT), is a novel guideline-recommended treatment for metastatic hormone-sensitive prostate cancer (mHSPC). However, the optimal selection of the patient most likely to benefit from triplet therapy remains unclear. We performed a systematic review, meta-analysis, and network meta-analysis to assess the oncologic benefit of triplet therapy in mHSPC patients stratified by disease volume and compare them with doublet treatment regimens. Three databases and meeting abstracts were queried in March 2023 for randomized controlled trials (RCTs) evaluating patients treated with systemic therapy for mHSPC stratified by disease volume. Primary interests of measure were overall survival (OS). We followed the PRISMA guideline and AMSTAR2 checklist. Overall, eight RCTs were included for meta-analyses and network meta-analyses (NMAs). Triplet therapy outperformed docetaxel plus ADT in terms of OS in both patients with high-(pooled HR: 0.73, 95%CI 0.64-0.84) and low-volume mHSPC (pooled HR: 0.71, 95%CI 0.52-0.97). There was no statistically significant difference between patients with low- vs. high-volume in terms of OS benefit from adding ARSI to docetaxel plus ADT (p = 0.9). Analysis of treatment rankings showed that darolutamide plus docetaxel plus ADT (90%) had the highest likelihood of improved OS in patients with high-volume disease, while enzalutamide plus ADT (84%) had the highest in with low-volume disease. Triplet therapy improves OS in mHSPC patients compared to docetaxel-based doublet therapy, irrespective of disease volume. However, based on treatment ranking, triplet therapy should preferably be considered for patients with high-volume mHSPC while those with low-volume are likely to be adequately treated with ARSI + ADT.

Low-Risk Staphylococcus aureus Bacteremia Patients Do Not Require Routine Diagnostic Imaging: A Multicenter, Retrospective, Cohort Study.

Stratification to categorize patients with Staphylococcus aureus bacteremia (SAB) as low or high risk for metastatic infection may direct diagnostic evaluation and enable personalized management. We investigated the frequency of metastatic infections in low-risk SAB patients, their clinical relevance, and whether omission of routine imaging is associated with worse outcomes. We performed a retrospective cohort study at 7 Dutch hospitals among adult patients with low-risk SAB, defined as hospital-acquired infection without treatment delay, absence of prosthetic material, short duration of bacteremia, and rapid defervescence. Primary outcome was the proportion of patients whose treatment plan changed due to detected metastatic infections, as evaluated by both actual therapy administered and by linking a adjudicated diagnosis to guideline-recommended treatment. Secondary outcomes were 90-day relapse-free survival and factors associated with the performance of diagnostic imaging. Of 377 patients included, 298 (79%) underwent diagnostic imaging. In 15 of these 298 patients (5.0%), imaging findings during patient admission had been interpreted as metastatic infections that should extend treatment. Using the final adjudicated diagnosis, 4 patients (1.3%) had clinically relevant metastatic infection. In a multilevel multivariable logistic regression analysis, 90-day relapse-free survival was similar between patients without imaging and those who underwent imaging (81.0% versus 83.6%; adjusted odds ratio, 0.749; 95% confidence interval, .373-1.504). Our study advocates risk stratification for the management of SAB patients. Prerequisites are follow-up blood cultures, bedside infectious diseases consultation, and a critical review of disease evolution. Using this approach, routine imaging could be omitted in low-risk patients.