Symptomatic Events Research Articles

Post-traumatic stress disorder in a Canadian population of medical students, residents, and physicians.

Physicians encounter stressors with potential long-term psychological consequences. However, a comprehensive picture of post-traumatic stress disorder (PTSD) prevalence and symptomatic work-related event occurrence across practice stages is lacking. To evaluate PTSD prevalence and the occurrence of work-related symptomatic events among physicians and medical learners. In 2017, we surveyed 3,036 physicians, residents, and students within the province of Saskatchewan, Canada. Participants completed the Life Events Checklist (LEC) for DSM 4 and the PTSD Checklist for DSM 4-Civilian version (PCL-C). They also reported work-related events that triggered PTSD-like symptoms. The prevalence of a positive PTSD screen (PCL-C ≥ 36) and the proportion identifying a symptomatic work event were determined. The t-test, Chi-square test, and multiple regression were used to evaluate associations between respondent characteristics and these outcomes. Among 565 respondents, 21.2% screened positively, with similarity across career stages. Thirty-nine percent reported a symptom-inducing work event, with many training-related. Although independent PTSD predictors were not identified, partnered residents and surgical residents were more likely to identify a work-related event. Internationally trained practicing physicians were less likely to identify an event. Both symptom-inducing work events and PTSD are frequent, broadly based concerns requiring better preventive strategies across career stages.

A phase 1, randomized, double-blind, placebo-controlled trial investigating the pharmacokinetics, pharmacodynamics, safety and tolerability of oral semaglutide in healthy Chinese subjects.

The trial (NCT04016974) investigated the pharmacokinetics, pharmacodynamics, safety and tolerability of oral semaglutide, the first orally administered glucagon-like peptide-1 analogue for type 2 diabetes, in healthy Chinese subjects. This single-centre, multiple-dose, placebo-controlled trial randomized 32 healthy Chinese adults to once-daily oral semaglutide (3 mg escalating to 14 mg) or placebo for 12 weeks. Blood samples were collected regularly during treatment and follow-up. The primary endpoint was the area under the semaglutide concentration-time curve over a dosing interval (0-24 h) at steady state (AUC0-24h,sema,SS). Secondary pharmacokinetic endpoints included the maximum observed semaglutide plasma concentration at steady state (Cmax,sema,SS). Supportive secondary pharmacodynamics endpoints included changes in body weight and fasting plasma glucose. Treatment with all oral semaglutide doses showed dose-dependent increases in semaglutide exposure in healthy Chinese subjects at steady state, determined by AUC0-24h,sema,SS (233, 552 and 1288 h·nmol/L for 3, 7 and 14 mg of oral semaglutide, respectively) and Cmax,sema,SS. Oral semaglutide treatment was associated with significant reductions in body weight (p = .0001) and fasting plasma glucose (p = .0011) versus placebo at the end of treatment. The safety and tolerability of oral semaglutide were consistent with the known profile of glucagon-like peptide-1 receptor agonists, with no severe or blood-glucose-confirmed symptomatic hypoglycaemic events, serious adverse events or deaths. The most frequent adverse events were gastrointestinal disorders. At steady state, oral semaglutide exposure was dose dependent and close to dose proportionality in healthy Chinese subjects. This is consistent with previous clinical pharmacology results for oral semaglutide.

Patient-reported symptomatic events do not adequately reflect atrial arrhythmia

BackgroundManagement of atrial fibrillation is frequently geared toward improving symptoms. Yet, the magnitude of symptom-rhythm discordance is not well known in the setting of monitoring by ambulatory electrocardiography (AECG). ObjectiveWe aimed to quantify the symptom-rhythm correlation (SRC) for atrial arrhythmia (atrial tachycardia/atrial fibrillation [AT/AF]) events. MethodsThis was a retrospective cohort analysis of AECG data at a tertiary care center. All AECGs of ≥7 days with at least 1 AT/AF were included. Patient-triggered symptoms included shortness of breath, tiredness, palpitations, dizziness, or passing out with or without concurrent AT/AF. SRC was calculated for each patient. In addition, AT/AF-symptom association was evaluated at the event level by multivariable mixed effects logistic regression. ResultsWe identified 742 patients with qualifying AECG data; mean age was 64 years, 50% were female, and 22% had heart failure. The mean CHA2DS2-VASc score was 2.5. There were 6289 symptomatic events and 6900 AT/AF episodes. Of symptomatic events, 1013 (16%) had shortness of breath, 839 (13%) tiredness, 2640 (42%) palpitations, 783 (12%) dizziness, and 93 (1%) passing out. Overall SRC was 0.39 (range, 0–1.0), but presence of AT/AF increased odds of symptoms by ∼8.3 times in adjusted analyses (P < .01). In multivariable analysis, prior AF rhythm control treatment and lower heart rate were associated with worse SRC (P < .01). ConclusionWhereas AT/AF events increase the chances of symptoms, there is poor overall correlation between symptomatic events and documented AT/AF. Patient factors and prior treatments influence SRC. An improved understanding of this relationship correlation is needed to optimize clinical outcomes and to improve the rigor of AF research.

Diagnostic yield of cardiac monitors in patients with suspected arrhythmias: systematic literature review and network meta-analysis

Abstract Objective To demonstrate the diagnostic yield (DY) across cardiac rhythm monitors stratified by monitoring duration for symptomatic patients with suspected cardiac arrhythmias (palpitations, dizziness, syncope, presyncope, lightheadedness). Methods PubMed, Embase, and Scopus were searched to identify published randomized and observational studies between January 1, 2000, and November 28th, 2021. DY data were extracted for comparative studies. The DY of cardiac monitors in these patients was reviewed for Any Arrhythmia, Clinically Relevant Arrhythmia, Explained Episodes (symptomatic and clinically relevant), New Onset Atrial Fibrillation, and Symptomatic Events. Clinically Relevant Arrhythmia was defined by the study and included atrial fibrillation, atrial flutter, atrial tachycardia, other SVT, VT, pause, and bradycardia. Patients who had a history of prior stroke or transient ischemic attack were excluded. Network meta-analysis (NMA) was used to pool estimates. Cardiac monitoring duration was categorized into the following 3 timeframes: 3 days or less (≤3 d), greater than 3 days to less than 30 days (&amp;gt;3 d), and 30 days or greater (≥ 30 d). Results Inclusion and exclusion criteria identified a pooled population of 1696 patients in 6 comparative studies, 2 Randomized Controlled Trials (RCTs) and 4 non-RCTs (Figure 1). NMA results for comparative studies show that monitoring durations of &amp;gt;3 d and ≥30 d provided significant better DY than ≤3 d (Table 1). The odds ratio for DY of &amp;gt;3 d as compared to ≤3 d was 5.75 (95% CI 2.05-19.38) in patients with Any Arrhythmias, 5.99 (95% CI 2.10 - 7.79) in patients with Clinically Relevant Arrhythmias, 10.22 (95% CI 0.61 - 4343.00) in patients with Explained Episodes, and 2.74 (95% CI 1.12 - 7.53) in patients with New Onset Atrial Fibrillation. As only a single study provided results on Symptomatic Events, NMA was not possible for this measure. The odds ratio for DY of &amp;gt;3 d as compared to ≥30 d was 0.02 (95% CI 0.00 - 0.15) in patients with Any Arrhythmias, 0.03 (95% CI 0.00 - 0.10) in patients with Clinically Relevant Arrhythmias, 0.04 (95% CI 0.01 - 0.13) in patients with Explained Episodes, and 0.17 (95% CI 0.03 - 0.66) in patients with diagnosis of New Onset Atrial Fibrillation. Conclusion NMA indicates that &amp;gt;3 d and ≥30 d provide significantly better DY than ≤3 d for identifying Any Arrhythmia, Clinically Relevant Arrhythmia, and New Onset AF. Despite favorable odds ratios for ≥30 d over &amp;gt;3 d, these values were associated with uncertainty due to the limited studies available for monitoring durations of ≥30 d. Overall, in patients experiencing symptoms of palpitations, dizziness, syncope, and without prior stroke or transient ischemic arrest, &amp;gt;3 d of monitoring improved DY compared with shorter monitoring durations.Figure 1.Prisma Flow DiagramTable 1.Diagnostic Yield Comparison.

Utilization of implantable cardiac monitors in detecting type 1 patterns in brugada syndrome

Abstract Introduction In individuals with Brugada syndrome, the presence of the type 1 pattern (BP1) is linked to an elevated risk of severe arrhythmias. However, the identification and measurement of BP1 can be challenging due to its intermittent nature. Implantable cardiac monitors (ICMs) provide extended continuous monitoring, potentially overcoming the limitations of intermittent ambulatory ECG monitoring in detecting spontaneous BP1. Nevertheless, their specific application for this purpose remains unevaluated. Methods From November 2022 to September 2023, all patients presenting with pharmacologically induced BP1 were enrolled at our centre. An ICM was surgically placed in the left second intercostal space at a 45° angle, enabling readings with a morphology similar to the right precordial ECG leads during ajmaline testing (AT). Patients were remotely monitored, and in addition to routine automatic transmissions, each patient was provided with a remote control to transmit in case of fever or symptomatic events. Transmissions were scrutinized to detect: 1) ST-segment elevation; 2) ventricular arrhythmias; 3) burden of ventricular extrasystoles (PVC). A reading was classified as positive for BP1 if it bore a similar morphology to that recorded during AT. The frequency of BP1-positive transmissions was evaluated across four hourly intervals. Results The ICM was successfully implanted in 21 patients (male-to-female ratio 1.62:1, mean age 43.9±13.1 years). Over an average follow-up of 168±70.6 days, a total of 7818 transmissions were received, evenly spread across hourly intervals (minimum of 1296 transmissions per interval). Among these, 173 transmissions were identified as BP1 positive (2.2%), originating from 6 patients (28.6% of the total, all newly diagnosed with spontaneous BP1). The median duration between implantation and the diagnosis of spontaneous BP1 was 16.5 days (range 2-23). The median number of days with at least one positive transmission was 30.2 (range 13.4-73.9). The evening period (6 pm to midnight) displayed a significantly higher rate of positive transmissions compared to the morning (p=0.04) and afternoon (p=0.01); however, not in contrast to the nighttime (p=0.8). No sustained ventricular arrhythmias were observed, and there were no significant differences in PVC burden among patients. Conclusions The utilization of ICM for continuous monitoring in patients with pharmacologically induced BP1 led to the identification of spontaneous BP1 patterns in almost 30% of cases during an approximately 6-month follow-up. Evening and nighttime periods exhibited the highest incidence of BP1. This methodology shows promise in quantifying BP1 incidence and could serve as a tool for stratifying arrhythmic risk in individuals with Brugada syndrome.

Economic burden of generalized myasthenia gravis (MG) in the United States and the impact of common comorbidities and acute MG-events

Background This study assessed the incremental healthcare costs and resource utilization (HRU) associated with generalized myasthenia gravis (gMG), as well as variability in these outcomes among patients with gMG and common comorbidities and acute MG-related events. Methods Adults with gMG and without MG were identified from a large US database (2017–2021). The index date was the first MG diagnosis (gMG cohort) or random date (non-MG cohort). Cohorts were propensity score matched 1:1. The gMG cohort included subgroups of patients with a 12-month pre-index (baseline) cardiometabolic or psychiatric comorbidity, or a post-index MG exacerbation/crisis. Monthly healthcare costs (2021 USD) and HRU were compared post-index between gMG and non-MG cohorts. Results The gMG and matched non-MG cohorts each contained 2,739 patients. Mean incremental healthcare costs associated with MG were $4,155 (gMG: $5,567; non-MG: $1,411), with differences driven by incremental inpatient costs of $2,166 (gMG: $2,617; non-MG: $452); all p < 0.001. The gMG versus non-MG cohort had 4.36 times more inpatient admissions and 2.26 times more outpatient visits; all p < 0.001. Among patients with gMG in cardiometabolic (n = 1,859), psychiatric (n = 1,308), and exacerbation/crisis (n = 419) subgroups, mean monthly healthcare costs were $6,660, $7,443, and $17,330, respectively. Conclusions gMG is associated with substantial incremental costs and HRU, with inpatient costs driving the total incremental costs. Costs increased by 20% and 34% among patients with cardiometabolic and psychiatric conditions, respectively, and over three times among those with acute MG-related events. gMG is a complex disease requiring management of comorbidities and treatment options that can prevent acute symptomatic events.

Final Results of RIGHT Choice: Ribociclib Plus Endocrine Therapy Versus Combination Chemotherapy in Premenopausal Women With Clinically Aggressive Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer.

A head-to-head comparison of efficacy between a cyclin-dependent kinase 4/6 inhibitor plus endocrine therapy (ET) versus combination chemotherapy (CT) has never been reported in patients with clinically aggressive hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer (ABC). In this open-label, multicenter, randomized phase II trial, pre/perimenopausal women with clinically aggressive HR+/HER2- ABC were randomly assigned 1:1 to first-line ribociclib (600 mg once daily; 3 weeks on, 1 week off) plus letrozole/anastrozole and goserelin or investigator's choice of combination CT (docetaxel plus capecitabine, paclitaxel plus gemcitabine, or capecitabine plus vinorelbine). The primary end point was progression-free survival (PFS). Among 222 patients randomly assigned to ribociclib plus ET (n = 112) or combination CT (n = 110), 150 (67.6%) had symptomatic visceral metastases, 41 (18.5%) had rapid disease progression per investigator's judgment, and 31 (14.0%) had symptomatic nonvisceral disease. Overall, 106 (47.7%) patients had investigator-assessed visceral crisis. The median follow-up time was 37.0 months. At data cutoff, 31.3% (ribociclib arm) and 15.5% (CT arm) of patients had completed study treatment and transitioned to post-trial access. The median PFS was 21.8 months (ribociclib plus ET; [95% CI, 17.4 to 26.7]) and 12.8 months (combination CT; [95% CI, 10.1 to 18.4); hazard ratio, 0.61 [95% CI, 0.43 to 0.87]; P = .003. The overall response rates and the median time to response in the ribociclib versus CT arms, respectively, were 66.1% and 61.8% and 4.9 months and 3.2 months (hazard ratio, 0.76 [95% CI, 0.55 to 1.06]). Lower rates of symptomatic adverse events were observed in the ribociclib versus CT arm. First-line ribociclib plus ET showed a significant PFS benefit, similar response rates, and better tolerability over combination CT in patients with clinically aggressive HR+/HER2- ABC.

The Use of Computed Tomography to Quantify Renal Calculi Strain to Estimate Potential Symptomatic Incidents

This study investigates into the historical evolution and contemporary applications of Computed Tomography (CT) in renal stone estimation, with a focus on the innovative use of CT to quantify renallcalculiistrain for estimating potentiallsymptomatic incidents. Historically, CT has played a pivotal role in diagnosing renal calculi, offering unparalleled sensitivity and specificity in detecting stones of varying composition and size. However, the clinical significance of renal calculi extends beyond mere detection, prompting researchers to explore novel approaches to predict symptomatic events associated with stone disease. This research aimed to determine the right way to classify asymptomatic radiographic calculi strain on computed tomography (CT) scans in Al-Hussein Teaching Hospital, Al-Muthanna, Iraq. A survey was made available to calculi formers who had a CT scan during asymptomatic after a calculi clinical assessment. A survey and a study of medical records revealed symptomatic calculi route incidents after a CT scan. The amount of calculus, the biggest calculi thickness, electronic total calculi size (TSV), and two-pronged calculus were measured radiographically and linked as predictors of calculi events. There were 55 calculi formers in the study, and 61% had a calculi event one year after the CT scan. The calculus number was (0–1, 2–3, 4–6, 7), the highest calculi diameter was (0–2, 3–4, 5–7, 8 mm), and 48% had bilateral calculus. The number of calculus per quartile had a danger ratio of 1.30 (p = 0.001), the largest calculi diameter had a hazard ratio of 1.26 (p 0.001), TSV had a hazard ratio of 1.38 (p = 0.001), and bilateral calculus had a hazard ratio of 1.80 (p = 0.001). Only TSV wass an unbiased measure offsymptomaticceventssin multivariable regression (HR = 1.35 per quartile, p = 0.01). TSV-related incidents were also unaffected by demographics, urinary chemistry, or calculi composition. A drastic rise in TSV between CT scans (&gt; 31 mm3/year) expected additional eventssin the 49 patients with interim events (HR = 2.8, p = 0.05). For calculating calculi pressure on CT scan, automated TSV is more accurate for asymptomatic events than physical approaches.

Long-term Monitoring to Detect Risk of Sudden Cardiac Death in Inherited Arrhythmia Patients

BackgroundRisk stratification in inherited arrhythmia syndromes is challenging. Implantable cardioverter defibrillators (ICDs) are effective in the prevention of sudden cardiac death but are associated with significant complications. We aimed to determine the value of long-term implantable loop recorder (ILR) monitoring to determine risk factors for arrhythmias in inherited arrhythmia patients. MethodsWe conducted a prospective multicentre study between 2015 and 2020 recruiting inherited arrhythmia probands and family members at intermediate arrhythmic risk, with no class 1 indication for ICD implantation. The primary endpoint was the detection by ILR of nonsustained ventricular tachycardia over ≥ 10 consecutive beats. Secondary endpoints included ICD insertion during follow-up, all-cause mortality, and ILR complication rates. ResultsA total of 45 individuals (30 female participants) were enrolled in the study. The most common diagnoses were long-QT syndrome (28%), Brugada syndrome (26%), and arrhythmogenic cardiomyopathy (11%). Following ILR insertion (mean follow-up 633 days; range, 387-969), cardiac symptoms occurred in 19 of 45 patients (42%), 5 of whom had nonsustained ventricular tachycardias (11%), which were symptomatic in 3 individuals. This situation led to ICD implantation based on ILR in 5 of 45 patients (11%). Fifty percent of symptomatic events occurred in ARVC patients. The median time from ILR insertion to ICD implantation was 152 days (interquartile range (25th, 75th percentiles) 55 of 209). No patient experienced sudden cardiac death. ConclusionsILRs enable the detection of high-risk arrhythmic features and facilitate selection of ICD candidates in inherited arrhythmia patients with borderline indications.

Health-related quality of life with sacituzumab govitecan in HR+/HER2- metastatic breast cancer in the phase III TROPiCS-02 trial.

The TROPiCS-02 study (NCT03901339) demonstrated that sacituzumab govitecan (SG) has superior clinical outcomes over treatment of physician's choice (TPC) chemotherapy in patients with hormone receptor-positive, human epidermal growth factor 2 receptor-negative (HR+/HER2-) metastatic breast cancer (mBC). Here, we present health-related quality of life (HRQoL) patient-reported outcome (PRO) findings from this study. Eligible adults with HR+/HER2- mBC who previously received a taxane, endocrine-based therapy, a CDK4/6 inhibitor, and 2-4 lines of chemotherapy were randomized 1:1 to receive SG or TPC until progression or unacceptable toxicity. PROs were assessed at baseline and on day 1 of each cycle, using the European Organization for Research and Treatment of Cancer Quality-of-Life Core 30 (EORTC QLQ-C30), EQ-5D-5L, and PRO Common Terminology Criteria for Adverse Events (PRO-CTCAE). Compared to TPC, overall least square mean change from baseline was significantly better for SG for physical functioning and dyspnea, but worse for diarrhea. Time to first clinically meaningful worsening or death was significantly longer for SG in global health status/quality of life, physical functioning, fatigue, emotional functioning, dyspnea, insomnia, and financial difficulties of the EORTC QLQ-C30 and the EQ-VAS, but longer for TPC in diarrhea. Few patients in both arms reported experiencing any worsening to level 3 or 4 treatment-related symptomatic events during treatment, as assessed by 16 PRO-CTCAE items, except for diarrhea frequency and amount of hair loss, which favored TPC. SG was associated with an HRQoL benefit in most symptoms and functioning, compared with TPC. This supports the favorable profile of SG as a treatment option for patients with pretreated HR+/HER2- mBC.

Association of preprocedural antiplatelet use with decreased thromboembolic complications for intracranial aneurysms undergoing intrasaccular flow disruption.

This study was conducted to investigate the impact of antiplatelet administration in the periprocedural period on the occurrence of thromboembolic complications (TECs) in patients undergoing treatment using the Woven EndoBridge (WEB) device for intracranial wide-necked bifurcation aneurysms. The primary objective was to assess whether the use of antiplatelets in the pre- and postprocedural phases reduces the likelihood of developing TECs, considering various covariates. A retrospective multicenter observational study was conducted within the WorldWideWEB Consortium and comprised 38 academic centers with endovascular treatment capabilities. Univariable and multivariable logistic regression analyses were performed to determine the association between antiplatelet use and TECs, adjusting for covariates. Missing predictor data were addressed using multiple imputation. The study comprised two cohorts: one addressing general thromboembolic events and consisting of 1412 patients, among whom 103 experienced TECs, and another focusing on symptomatic thromboembolic events and comprising 1395 patients, of whom 50 experienced symptomatic TECs. Preprocedural antiplatelet use was associated with a reduced likelihood of overall TECs (OR 0.32, 95% CI 0.19-0.53, p < 0.001) and symptomatic TECs (OR 0.49, 95% CI 0.25-0.95, p = 0.036), whereas postprocedural antiplatelet use showed no significant association with TECs. The study also revealed additional predictors of TECs, including stent use (overall: OR 4.96, 95% CI 2.38-10.3, p < 0.001; symptomatic: OR 3.24, 95% CI 1.26-8.36, p = 0.015), WEB single-layer sphere (SLS) type (overall: OR 0.18, 95% CI 0.04-0.74, p = 0.017), and posterior circulation aneurysm location (symptomatic: OR 18.43, 95% CI 1.48-230, p = 0.024). The findings of this study suggest that the preprocedural administration of antiplatelets is associated with a reduced likelihood of TECs in patients undergoing treatment with the WEB device for wide-necked bifurcation aneurysms. However, postprocedural antiplatelet use did not show a significant impact on TEC occurrence.

Circulating microRNAs and therapy-associated cardiac events in HER2-positive breast cancer patients: an exploratory analysis from NeoALTTO

PurposeThe relevance of cardiotoxicity in the context of HER2-positive breast cancer is likely to increase with increasing patient treatment exposure, number of treatment lines, and prolonged survival. Circulating biomarkers to early identify patients at risk of cardiotoxicity could allow personalized treatment and follow-up measures. The aim of this study is to examine the relationship between circulating microRNAs and adverse cardiac events in HER2-positive breast cancer patients.MethodsWe based our work on plasma samples from NeoALTTO trial obtained at baseline, after 2 weeks of anti-HER2 therapy, and immediately before surgery. Eleven patients experienced either a symptomatic or asymptomatic cardiac event. Circulating microRNAs were profiled in all patients presenting a cardiac event (case) and in an equal number of matched patients free of reported cardiac events (controls) using microRNA-Ready-to-Use PCR (Human panel I + II). Sensitivity analyses were performed by increasing the number of controls to 1:2 and 1:3. Normalized microRNA expression levels were compared between cases and controls using the non-parametric Kruskal–Wallis test.ResultsEight circulating microRNAs resulted differentially expressed after 2 weeks of anti-HER2 therapy between patients experiencing or not a cardiac event. Specifically, the expression of miR-125b-5p, miR-409-3p, miR-15a-5p, miR-423-5p, miR-148a-3p, miR-99a-5p, and miR-320b increased in plasma of cases as compared to controls, while the expression of miR-642a-5p decreases. Functional enrichment analysis revealed that all these microRNAs were involved in cardiomyocyte adrenergic signaling pathway.ConclusionThis study provides proof of concept that circulating microRNAs tested soon after treatment start could serve as biomarkers of cardiotoxicity in a very early stage in breast cancer patients receiving anti-HER2 therapy.

Frequency of hypoglycaemia with basal insulin treatments in adults with type 1 diabetes treated with basal-bolus insulin regimens in treat-to-target trials: A narrative review.

To summarise, in a narrative review, published data on hypoglycaemia occurrence with basal insulin therapy in adults with type 1 diabetes treated with basal-bolus insulin regimens in treat-to-target randomised controlled trials. Data were included from 21 eligible trials, which mainly used self-measured blood glucose or plasma glucose to detect hypoglycaemia. All-day self-measured blood glucose or plasma glucose level 2 (glucose threshold of 3.1 or 3.0 mmol/L) and level 3 (severe, requiring assistance) hypoglycaemic events were reported, respectively, by a range of 69.0%-97.5% and 0%-13.4% adults when receiving basal-bolus insulin therapy, with rates of 10.6-68.1 and 0.0-0.4 events per patient-year of exposure, respectively. Hypoglycaemia rates measured using continuous glucose monitoring (three studies) were numerically, yet consistently, higher than with either other method, except when limiting to symptomatic events. Nocturnal hypoglycaemia rates were generally less than 30% of the equivalent all-day rates. Differences across the studies in design (e.g., titration targets) and participant characteristics hindered comparison of hypoglycaemia rates by insulin formulation. Consequently, few trends were identified by insulin formulation, study methodology or individuals' characteristics, suggesting that further research is required to identify treatment strategies that facilitate development of individualised recommendations to lower hypoglycaemia risk. These findings are useful to understand hypoglycaemia risk with available basal insulin therapies when used in a multiple daily injection regimen, as well as to provide context for the results of ongoing and future clinical trials, including those for two once-weekly basal insulins, insulin icodec and basal insulin Fc.

Current state of theranostics in metastatic castrate-resistant prostate cancer.

Prostate cancer remains one of the leading causes of cancer-related death in the world. There have been significant advances in chemotherapy, hormonal therapy and targeted therapy options for patients with castrate-resistant disease. However, these systemic treatments are often associated with unwanted toxicities. Targeted therapy with radiopharmaceuticals has become of key interest to limit systemic toxicity and provides a more precision oncology approach to treatment. Strontium-89, Samarium-153 EDTMP and Radium-223 have been trialled with mixed results. Strontium-89 and Samarium-153 EDTMP have shown benefits in palliating metastatic bone pain but with no impact on survival outcomes. Early therapeutic radiopharmaceuticals targeting PSMA that were developed were beta-emitting agents, but recently alpha-emitting agents are being investigated as potentially superior options. Radium-223 is the first alpha-particle emitter therapeutic agent approved by the FDA, with phase III trial evidence showing benefits in overall survival and delay in symptomatic skeletal events for patients. Recently, 177-Lutetium-PSMA-617 has demonstrated significant survival advantages in pre-treated metastatic castrate-resistant cancer patients in a number of phase II and III studies. Furthermore, 225-Actinium-PSMA-617 also showed promise even in patients pre-treated with 177-Lutetium-PSMA-617. Hence, there has been an explosion of radiopharmaceutical treatment options for patients with prostate cancer. This review explores past and current theranostic capacities in the radiopharmaceutical treatment of metastatic castrate-resistant prostate cancer.

Network meta-analysis of combination strategies in metastatic hormone-sensitive prostate cancer.

This study compared different doublet and triplet therapies for efficacy and safety in metastatic hormone-sensitive prostate cancer (mHSPC). PubMed, EMBASE, and the Cochrane Library were comprehensively searched for eligible randomized controlled trials (RCTs) published from inception to October 2023. Interventions included abiraterone, apalutamide, enzalutamide, docetaxel, darolutamide, and androgen deprivation therapy (ADT), either as doublet or triplet therapies. The outcomes examined were overall survival (OS), progression-free survival (PFS), castration-resistant prostate cancer (CRPC)-free survival, time to symptomatic skeletal event (SSE), and toxicity. The surface under the cumulative ranking curve (SUCRA) was determined to identify the preferred treatments. Ten RCTs were included. The combination of darolutamide, docetaxel, and ADT had the highest SUCRA of 84.3 for OS, followed by combined abiraterone, docetaxel, and ADT (SUCRA = 71.6). The highest SUCRAs for PFS were observed for triplet therapies (abiraterone, docetaxel, and ADT [SUCRA = 74.9], followed by enzalutamide, docetaxel, and ADT [SUCRA = 74.3]) and other androgen receptor axis-targeted therapy-based doublet therapies (SUCRAs: 26.5-59.3). Darolutamide, docetaxel, and ADT had the highest SUCRAs, i.e ., 80.8 and 84.0 regarding CRPC-free survival and time to SSE, respectively. Regarding Grade >3 adverse events (AEs), the SUCRAs of triplet therapies (SUCRAs: 14.8-31.5) were similar to that of docetaxel and ADT (SUCRA = 39.5). Three studies had a low risk of bias in all categories; the remaining studies had at least an unclear risk of bias in at least one category. Triplet therapy demonstrated potentially enhanced effectiveness than doublet therapy in mHSPC, with acceptable safety concerns. Darolutamide might be the optimal option for triplet therapy in combination with docetaxel and ADT.

Transition from asymptomatic to symptomatic systolic chronic heart failure: rationale and design of TransitionCHF.

Chronic systolic heart failure (CHF) is a major health burden. A relevant number of patients shows asymptomatic left ventricular dysfunction (ALVSD) before symptomatic CHF or becomes asymptomatic after initiating heart failure therapy. Clinical course, prognosis, and response to pharmacological and device-based treatment are largely unknown in these two distinct groups of patients. Current pharmacological and interventional therapies do neither properly address the underlying pathophysiology nor prevent malignant loss of function. New therapeutic paradigms are needed to stop the progression from asymptomatic to symptomatic heart failure. Key questions are what causes progression of clinically asymptomatic New York Heart Association (NYHA) I heart failure to overt heart failure (>NYHA I) in some but not all patients and the underlying reasons for this transition. This requires the identification of disease mechanisms and biomarkers that predict outcome in well-defined cohorts for innovative preclinical and clinical trials. TransitionCHF is a prospective, multicentre, longitudinal pathophysiological evaluation cohort study in patients with asymptomatic systolic dysfunction NYHA I and left ventricular ejection fraction ≤40%. The cohort comprises both incidental findings and patients who had become asymptomatic after a previous symptomatic event. TransitionCHF has recruited 1000 patients with ALVSD caused by various aetiologies in 20 university heart failure clinics across Germany. Both patients with and without comorbidities at study entry will be recruited. Patients will be systematically investigated and followed up annually over the course of the study. The primary composite endpoint is time to hospitalization for heart failure and cardiovascular death. The secondary endpoints assess time to all-cause mortality, to cardiovascular mortality, to heart failure mortality, to all-cause hospitalization, to heart failure hospitalization, and to recurrent heart failure hospitalizations, as well as time to assist device implantation/transplantation. Additional investigations focusing on biomarkers, comorbidities, gender aspects, nutrition, and functional parameters including quality of life will be performed. TransitionCHF will provide a more thorough pathophysiological understanding of the progression of asymptomatic systolic dysfunction into symptomatic heart failure that will help develop therapies tailored to prevent progressive heart failure.

5-EPIFAT trial protocol: a multi-center, randomized, placebo-controlled trial of the efficacy of pharmacotherapy for fatigue using methylphenidate, bupropion, ginseng, and amantadine in advanced cancer patients on active treatment

BackgroundCancer-related fatigue (CRF) is still undertreated in most patients, as evidence for pharmacological treatments is limited and conflicting. Also, the efficacy of the pharmacological agents relative to each other is still unclear. Therefore, medications that may potentially contribute to improving CRF will be investigated in this head-to-head trial. Our main objective is to compare the efficacy of methylphenidate vs. bupropion vs. ginseng vs. amantadine vs. placebo in patients with advanced cancer.MethodsThe 5-EPIFAT study is a 5-arm, randomized, multi-blind, placebo-controlled, multicenter trial that will use a parallel-group design with an equal allocation ratio comparing the efficacy and safety of four medications (Methylphenidate vs. Bupropion vs. Ginseng vs. Amantadine) versus placebo for management of CRF. We will recruit 255 adult patients with advanced cancer who experience fatigue intensity ≥ 4 based on a 0–10 scale. The study period includes a 4-week intervention and a 4-week follow-up with repeated measurements over time. The primary outcome is the cancer-related fatigue level over time, which will be measured by the functional assessment of chronic illness therapy-fatigue (FACIT-F) scale. To evaluate safety, the secondary outcome is the symptomatic adverse events, which will be assessed using the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events in cancer clinical trials (PRO-CTCAE). Also, a subgroup analysis based on a decision tree-based machine learning algorithm will be employed for the clinical prediction of different agents in homogeneous subgroups.DiscussionThe findings of the 5-EPIFAT trial could be helpful to guide clinical decision-making, personalization treatment approach, design of future trials, as well as the development of CRF management guidelines.Trial registrationIRCT.ir IRCT20150302021307N6. Registered on 13 May 2023.

Risk factors for venous thromboembolism after primary total joint arthroplasty: An analysis of 7511 Taiwanese patients.

The need for thromboprophylaxis in Asian patients after primary total joint arthroplasty (TJA) remains inconclusive. We aimed to identify the risk factors for venous thromboembolism (VTE) events following primary TJA in a Taiwanese population. From January 2010 to December 2019, we studied 7511 patients receiving primary TJA from a single surgeon. We validated the incidence and risk factors for 30- and 90-day symptomatic VTE events, including age, sex, body mass index (BMI), smoking, medical comorbidities, VTE history, presence of varicose veins, total knee arthroplasty (TKA) vs total hip arthroplasty (THA), unilateral vs bilateral procedure and receipt of VTE prophylaxis, transfusion, and length of stay. The incidence of 30- and 90-day symptomatic VTE events was 0.33% and 0.44%, respectively. Multivariate regression analysis showed that BMI ≥30 (adjusted odds ratio (aOR): 4.862, 95% CI, 1.776-13.313), bilateral TJA procedure (aOR: 2.665, 95% CI, 1.000-7.104), and presence of varicose veins (aOR: 9.946, 95% CI, 1.099-90.024) were associated with increased odds of 30-day symptomatic VTE events. Age ≥77 years (aOR, 2.358, 95% CI, 1.034-5.381) and BMI ≥30 (aOR: 2.832, 95% CI, 1.039-7.721) were associated with increased odds of 90-day symptomatic VTE events. Age ≥77 years, BMI ≥30, bilateral TJA procedure, or presence of varicose veins may require pharmacological thromboprophylaxis because such patients have a higher risk of VTE after primary TJA.

Ocular Effects of MEK Inhibitor Therapy: Literature Review, Clinical Presentation, and Best Practices for Mitigation.

MEK signaling pathway targeting has emerged as a valuable addition to the options available for the treatment of advanced cancers including melanoma and non-small cell lung cancer. Ophthalmologic monitoring of patients taking part in clinical trials of MEK inhibitors has shown that while ocular effects are common, generally emerging during the first days to weeks of treatment, the majority are either asymptomatic or have minimal visual impact and are benign, resolving without intervention or the need to reduce or stop MEK inhibitor therapy. However rare cases of serious, potentially vision-threatening ocular toxicities have been reported during MEK inhibitor therapy. There is currently no recommendation for routine ophthalmologic screening or monitoring of patients with advanced cancer who are initiating MEK inhibitor therapy. However, baseline ophthalmologic examination may be useful for all patients initiating MEK inhibitor therapy to allow the differentiation of preexisting pathology versus the development of MEK inhibitor-associated retinopathy in the event of the emergence of symptomatic ocular events. Regular ophthalmologic examination may be appropriate for patients at increased risk for ocular events, such as patients with a history of ocular inflammation, infection, or underlying macular/retinal disease. All patients reporting visual disturbance should be referred for prompt ophthalmologic review to determine the potential seriousness of any underlying abnormalities and whether there is a need for treatment modification or specific intervention. Understanding the potential consequences of ocular toxicities is of particular importance in the context of decision-making for the continuation of potentially life-prolonging medications such as MEK inhibitors.

Transradial versus transfemoral access for diagnostic cerebral angiography: frequency of acute MRI findings in 500 consecutive patients at a single center

BackgroundThe frequency of clinically symptomatic and asymptomatic diffusion-weighted imaging (DWI) hyperintense lesions and their correlation with the transradial artery (TRA) approach is unclear.ObjectiveTo assess the frequency of abnormal diffusion restriction...