Risk Of Serious Adverse Events Research Articles

Conventional versus minimally invasive extra-corporeal circulation in patients undergoing cardiac surgery: A randomized controlled trial (COMICS).

The trial hypothesized that minimally invasive extra-corporeal circulation (MiECC) reduces the risk of serious adverse events (SAEs) after cardiac surgery operations requiring extra-corporeal circulation without circulatory arrest. This is a multicentre, international randomized controlled trial across fourteen cardiac surgery centres including patients aged ≥18 and <85 years undergoing elective or urgent isolated coronary artery bypass grafting (CABG), isolated aortic valve replacement (AVR) surgery, or CABG + AVR surgery. Participants were randomized to MiECC or conventional extra-corporeal circulation (CECC), stratified by centre and operation. The primary outcome was a composite of 12 post-operative SAEs up to 30 days after surgery, the risk of which MiECC was hypothesized to reduce. Secondary outcomes comprised: other SAEs; all-cause mortality; transfusion of blood products; time to discharge from intensive care and hospital; health-related quality-of-life. Analyses were performed on a modified intention-to-treat basis. The trial terminated early due to the COVID-19 pandemic; 1071 participants (896 isolated CABG, 97 isolated AVR, 69 CABG + AVR) with median age 66 years and median EuroSCORE II 1.24 were randomized (535 to MiECC, 536 to CECC). Twenty-six participants withdrew after randomization, 22 before and four after intervention. Fifty of 517 (9.7%) randomized to MiECC and 69/522 (13.2%) randomized to CECC group experienced the primary outcome (risk ratio = 0.732, 95% confidence interval (95% CI) = 0.556 to 0.962, p = 0.025). The risk of any SAE not contributing to the primary outcome was similarly reduced (risk ratio = 0.791, 95% CI 0.530 to 1.179, p = 0.250). MiECC reduces the relative risk of primary outcome events by about 25%. The risk of other SAEs was similarly reduced. Because the trial terminated early without achieving the target sample size, these potential benefits of MiECC are uncertain.

Should rTMS be considered a first-line treatment for major depressive episodes in adults?

Treatment-resistant depression (TRD) is an epidemic with rising social, economic, and political costs. In a patient whose major depressive episode (MDE) persists through an adequate antidepressant trial, insurance companies often cover alternative treatments which may include repetitive transcranial magnetic stimulation (rTMS). RTMS is an FDA-cleared neuromodulation technique for TRD which is safe, efficacious, noninvasive, and well-tolerated. Recent developments in the optimization of rTMS algorithms and targeting have increased the efficacy of rTMS in treating depression, improved the clinical convenience of these treatments, and decreased the cost of a course of rTMS. In this opinion paper, we make a case for why conventional FDA-cleared rTMS should be considered as a first-line treatment for all adult MDEs. RTMS is compared to other first-line treatments including psychotherapy and SSRIs. These observations suggest that rTMS has similar efficacy, fewer side-effects, lower risk of serious adverse events, comparable compliance, the potential for more rapid relief, and cost-effectiveness. This suggestion, however, would be strengthened by further research with an emphasis on treatment-naive subjects in their first depressive episode, and trials directly contrasting rTMS with SSRIs or psychotherapy.

Efficacy and safety of immune checkpoint inhibitors in recurrent or metastatic nasopharyngeal carcinoma: A systematic review and meta-analysis.

e14612 Background: Treatment options for recurrent or metastatic nasopharyngeal carcinoma (NPC) are limited. Recently, the introduction of Immune Checkpoint Inhibitors (ICIs), either as single agents or combined with other treatment options, has emerged as a potential treatment for NPC. Hence, we performed a systematic review and meta-analysis to evaluate the efficacy and safety of ICIs compared to standard chemotherapy. Methods: We systematically searched PubMed, EMBASE, and Cochrane databases for randomized controlled trials (RCTs) comparing ICIs versus standard chemotherapy in patients with NPC. The main outcomes were progression-free survival (PFS), overall survival (OS) and adverse events rate. All analyses used a random-effects model, with 95% confidence intervals (CIs) and were conducted on Review Manager 5.4. Results: A total of 1,188 patients from 5 RCTs were included, of which 634 (53.3%) received PD-1 inhibitors. In a pooled analysis of all studies, treatment with ICIs demonstrated a statistically significant benefit in OS (HR 0.73; 95% CI 0.61-0.87; p&lt;0.01). In trials evaluating ICI monotherapy versus chemotherapy (617 patients), PFS was not significantly different between groups (p=0.91). However, pooling two studies evaluating ICI combined with chemotherapy vs. chemotherapy (541 patients) demonstrated higher PFS for the ICI group (HR 0.53; 95% CI 0.42-0.67; p&lt;0.01). Overall pooled PFS was non-significant (HR 0.75; 95% CI 0.49-1.16; p=0.20). In all subgroup analyses, patients treated with ICI achieved greater PFS than chemotherapy: low EBV DNA level (HR 0.61; 95% CI 0.42-0.87; p=0.007) or high EBV DNA level (HR 0.44; 95% CI 0.35-0.56; p&lt;0.01), without liver metastasis (HR 0.68; 95% CI 0.47-0.98; p=0.04), and with liver metastasis (HR 0.56; 95% CI 0.38-0.83; p=0.04). Moreover, ICIs were well tolerated and not associated with an increased risk of serious adverse events (HR 0.96; 95% CI 0.82-1.11; p=0.56). The frequency of hypothyroidism increased in the ICI group (HR 2.07; 95% CI 1.63-2.63; p&lt;0.01). Other adverse events had similar rates in both groups, such as AST and ALT levels, diarrhea, pruritus, rash, stomatitis, and vomiting. Conclusions: This meta-analysis demonstrated that immune checkpoint inhibitors significantly enhanced overall survival without substantially increasing serious adverse events in patients with M/R NPC. Further studies are needed to identify the patients who benefit the most from ICI monotherapy or combination therapies. [Table: see text]

Acupuncture for low back pain and migraine

Acupuncture has been increasingly used as an integrative or complementary therapy for pain. It is well-tolerated with little risk of serious adverse effects. Traditional acupuncture and nontraditional techniques, such as electroacupuncture and dry needling, often result in reported pain improvement. Acupuncture is an ancient Chinese medical practice that involves inserting thin needles into specific points on the body. Acupuncture can be used to treat a wide range of health conditions, including migraines and low back pain. Acupuncture works by stimulating the nervous system, releasing endorphins and increasing blood flow to the affected area. Acupuncture may also help to reduce inflammation and improve circulation in the body. Controlled trials have been published on pain syndromes, such as acupuncture for acute and chronic low back pain, knee osteoarthritis, headache, myofascial pain, neck pain, and fibromyalgia. For some conditions, enough data are available for systematic evaluations or meta-analyses. Acupuncture may provide modest benefits in the treatment of chronic low back pain, tension headache and chronic headache, migraine headache prophylaxis, and myofascial pain.The benefits of acupuncture for people with back pain has been well researched compared to many other conditions, with more higher quality clinical trials. This systematic review will focus on the use of acupuncture and its role in the treatment of low back pain to help better guide physicians in their practice. To determine the effects of a policy of ‘use acupuncture’ on headache, health status and chronic pain. The results of this study will determine if acupuncture, alone or as an adjunct to pharmacotherapy provides effective, safe and acceptable pain relief for patients.

Inhaled treprostinil in pulmonary hypertension associated with COPD: PERFECT study results.

Pulmonary hypertension (PH) accompanying COPD (PH-COPD) is associated with worse outcomes than COPD alone. There are currently no approved therapies to treat PH-COPD. The PERFECT study (ClinicalTrials.gov: NCT03496623) evaluated the safety and efficacy of inhaled treprostinil (iTRE) in this patient population. Patients with PH-COPD (mean pulmonary arterial pressure ≥30 mmHg and pulmonary vascular resistance ≥4 WU) were enrolled in a multicentre, randomised (1:1), double-blind, placebo-controlled, 12-week, crossover study. A contingent parallel design was also prespecified and implemented, based on a blinded interim analysis of missing data. Patients received treatment with iTRE up to 12 breaths (72 µg) 4 times daily or placebo. The primary efficacy end-point was change in peak 6-min walk distance (6MWD) at week 12. In total, 76 patients were randomised, 64 in the original crossover design and 12 in the contingent parallel design; 66 patients received iTRE and 58 received placebo. The study was terminated early at the recommendation of the data and safety monitoring committee based on the totality of evidence that iTRE increased the risk of serious adverse events and suggestive evidence of an increased risk of mortality. The change in 6MWD was numerically worse with iTRE exposure than with placebo exposure. The risk-benefit observations associated with iTRE in patients with PH-COPD did not support continuation of the PERFECT study. The results of this study do not support iTRE as a viable treatment option in patients with PH-COPD.

Vasodilators for Acute Heart Failure — A Systematic Review with Meta-Analysis

Background Acute heart failure is a public health concern. This study systematically reviewed randomized clinical trials (RCTs) to evaluate vasodilators in acute heart failure. Methods The search was conducted across the databases of Medline, Embase, Latin American and the Caribbean Literature on Health Sciences, Web of Science, and the Cochrane Central Register of Controlled Trials. Inclusion criteria consisted of RCTs that compared vasodilators versus standard care, placebo, or cointerventions. The primary outcome was all-cause mortality; secondary outcomes were serious adverse events (SAEs), tracheal intubation, and length of hospital stay. Risk of bias was assessed in all trials. Results The study included 46 RCTs that enrolled 28,374 patients with acute heart failure. Vasodilators did not reduce the risk of all-cause mortality (risk ratio, 0.95; 95% confidence interval [CI], 0.87 to 1.04; I2=9.51%; P=0.26). No evidence of a difference was seen in the risk of SAEs (risk ratio, 1.01; 95% CI, 0.97 to 1.05; I2=0.94%) or length of hospital stay (mean difference, –0.10; 95% CI, –0.28 to 0.08; I2=69.84%). Vasodilator use was associated with a lower risk of tracheal intubation (risk ratio, 0.54; 95% CI, 0.30 to 0.99; I2=51.96%) compared with no receipt of vasodilators. Conclusions In this systematic review with meta-analysis of patients with acute heart failure, vasodilators did not reduce all-cause mortality.

Effectiveness and Safety of Ustekinumab in Pediatric Ulcerative Colitis: A Multi-center Retrospective Study from the Pediatric IBD Porto Group of ESPGHAN.

Current data on ustekinumab therapy in children with ulcerative colitis (UC) or unclassified inflammatory bowel disease (IBDU) are limited. We aimed to evaluate the effectiveness and safety of ustekinumab in pediatric UC and IBDU. This multicenter retrospective study included 16 centers affiliated with the IBD Interest and Porto groups of ESPGHAN. Children with UC or IBDU treated with ustekinumab were enrolled. Demographic, clinical, laboratory, endoscopic, and imaging data as well as adverse events were recorded. Analyses were all based on the intention-to-treat principle. Fifty-eight children (39 UC and 19 IBDU, median age 14.5 [IQR 11.5-16.5] years) were included. All had failed biologic therapies, and 38 (66%) had failed two or more biologics. Corticosteroid-free clinical remission (CFR) was observed in 27 (47%), 33 (57%), and 37 (64%) children at 16, 26, and 52 weeks, respectively. Normalization of C-reactive protein and calprotectin <150μg/g were achieved in 60% and 52%, respectively, by 52 weeks. Endoscopic and radiologic remissions were reached in 8% and 23%, respectively. The main predictors of CFR were diagnosis of UC compared with IBDU (hazard ratio [HR] 2.2, 95% CI 1.03-4.85; p=0.041) and no prior vedolizumab therapy (HR 2.1, 95% CI 1.11-4.27; p=0.023). Ustekinumab serum levels were not associated with disease activity. Adverse events were recorded in six (10%) children, leading to discontinuation of the drug in three. Based on these findings, ustekinumab appears as an effective therapy for pediatric refractory UC and IBDU. The potential efficacy should be weighed against the risks of serious adverse events.

ADVERSE EVENTS ASSOCIATED WITH GLP1–RECEPTOR AGONISTS TREATMENT IN DIABETIC PATIENTS WITH HIGH CARDIOVASCULAR RISK: A META–ANALYSIS

Abstract Background GLP1–receptor agonists (GLP1–RA) have been associated with a reduction of cardiovascular (CV) outcomes in diabetic patients with high cardiovascular risk. However, these drugs have some adverse effects. The aim of this study was to assess the relative risk (RR) of adverse effects in patients with a high risk of developing CV disease treated with GLP1–agonists. Methods we considered randomized controlled trials (RCTs) aimed to assess the cardiovascular effects of GLP1–RA in diabetic patients with high CV risk. The following outcomes were explored: pancreatitis, severe hypoglycemia, renal and urinary serious adverse events (SAE), gastrointestinal SAE and AE, pancreatic cancer, and neoplasms. Results 8 RCTs, enrolling 60008 patients, were included in the analysis. There was no difference between GLP1–RA and placebo in the risk of pancreatitis (RR 0.99; 95% CI 0.73–1.35; p=0.972), severe hypoglycemia (0.93; 95% CI 0.76–1.15; p=0.501), renal and urinary SAE (0.94; 95% CI 0.82–1.07; p=0.339), pancreatic cancer (RR 0.98; 95% CI 0.56–1.70; p=0.936) and neoplasms (RR 1.02; 95% CI 0.95–1.09; p=0.547) (Fig 1 A e B). Conversely, GLP1–agonist treatment was associated with an increased risk of gastrointestinal AE (RR 1.95; 95% CI 1.23–3.06; p=0.004) (Fig 2). However, when gastrointestinal SAE were considered, GLP1–agonists demonstrated similar risk compared to placebo (RR 1.09; 95% CI 0.92–1.28; p= 0.318) (Fig 2). Conclusion in diabetic patients with high cardiovascular risk, the treatment with GLP1–RA has been associated with an increased risk of gastrointestinal AE. No difference in severe gastrointestinal AE has been associated with GLP1–RA.

Vasodilators for acute heart failure. A systematic review of randomized clinical trials with meta-analysis and trial sequential analysis

Abstract Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): Danish Cardiovascular Academy Novo Nordisk Foundation. Background Acute heart failure (AHF) is an increasing public health concern with limited evidence for current treatments, such as vasodilators. Recent studies have shown mixed results regarding the efficacy of vasodilation in AHF, leading to downgraded recommendations in European Society of Cardiology (ESC) 2021 guidelines. Method We conducted a systematic review of randomized clinical trials (RCTs) to assess vasodilator therapy's effectiveness in managing AHF. The search for relevant studies was conducted without restrictions across the major databases: Medline, Embase, Latin American and Caribbean Health Sciences Literature (LILACS), Web of Science, and the Cochrane Central Register of Controlled Trials. The study protocol was published and registered at PROSPERO, and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. We included RCTs that compared vasodilators to standard care, placebo, no-intervention, or co-interventions. Our primary outcome was all-cause mortality, while secondary outcomes included serious adverse events (SAEs), tracheal intubation and length of hospital stay. Systolic blood pressure difference was an exploratory outcome. We assessed the risks of bias in individual trials using the Cochrane Collaboration risk of bias tool. Results We included 46 RCTs comprising 28,374 patients with AHF. Meta-analysis and Trial Sequential Analysis showed that vasodilators did not reduce the risk of all-cause mortality (risk ratio (RR) = 0.96, 95% CI: 0.90 to 1.03; I2 = 0%; P = 0.26). However, meta-analysis showed evidence of a beneficial effect of vasodilators in reducing the need for tracheal intubation (RR = 0.82, 95% CI: 0.68 to 0.99; I2 = 55.05%; P = 0.04). No evidence of a difference was seen in the risk of SAEs (RR = 1.01, 95% CI: 0.97 to 1.06; I2 = 0%; P = 0.50) or length of hospital stay (Mean difference (MD) = -0.28, 95% CI: -0.73 to 0.16; I2 = 69.84%; P = 0.28). Finally, a significant decrease in systolic blood pressure (MD = -6.26, 95% CI: -8.06 to -4.46; I2 = 90.51%; P &amp;lt; 0.01) was demonstrated. Conclusion In patients hospitalised with AHF, vasodilator therapy did not result in a reduction of all-cause mortality, SAEs or length of hospital stay. However, the need for tracheal intubations was significantly decreased.Forest plot of all-cause mortalityForest plot of Tracheal intubation

Mineral composition and heavy metal risk assesment of selected geophagic soils from Tanzania

Geophagy or Pica is the unintentional traditional behavior of eating soil by indigenous people in different countries. practiced in many countries due to nausea among pregnant women and mineral deficiencies without knowing the associated health risks. In this study the mineral composition of geophagic soil and its associated health risk among consumers was determined. Dry soil sticks consumed by women were obtained from open markets in Morogoro, Njombe and Mwanza regions in Tanzania. The elemental concentration of geophagic soil was analyzed using Flame Atomic Absorption spectrophotometer. Health risk assessment methods were used to obtain health information after chronic exposure to geophagic soils. The tests used were Target Hazard Quotients (THQ), Total Target Hazard Quotients (TTHQ) and Cancer Risks (CR). The concentration range of metals in samples obtained from three different regions were 16,335.7–47,773.7 mg/kg for Fe, 46.2–1073.5 mg/kg for Ca, 155.3–514.9 mg/kg for K, 44.5–112.4 mg/kg for Zn, 40.7–95.1 mg/kg for Na, 2.4–66.7 mg/kg for Cu, 109.5–572.6 mg/kg for Mn, 3.8–6.85 mg/kg for Pb, 3.1–93 mg/kg for Ni, 62.7–638.6 mg/kg for Cr and 0.4 mg/kg for Cd. The Provisional Daily Intake (PDI), THQ, TTHQ and CR ranged between 3.0 × 10−3 –34.12 mg/kg/day bw, 0.043–48.75, 34.52–77.36 and 2.55×10−5- 0.23 respectively. The TTHQ>1 was evident for metals in all sampling sites which is indicative of non-carcinogenic health effects. Prolonged exposure to Pb at low concentrations in samples from all the sites can cause pathological effects. The cancer risk values for Pb, Ni, Cr and Cd were <1 in which the consumer is likely not to develop cancer in a life time. Essential minerals – Fe, Ca, Zn, Na, K and toxic metals Pb, Cr, Ni and Cu were detected in all the samples. Cd occurred only in samples from Mwanza region that was below the tolerable daily intake. According to WHO/FAO expert’s joint committee any amount of Pb consumption is not permitted. Given the presence of essential minerals in the geophagic soils which are however accompanied by toxic minerals in some cases which might have carcinogenic effects, prolonged consumption should be discouraged to avoid risks of serious adverse effects to the health of the general population.

Self-rated health and risk of incident cardiovascular events among individuals with hypertension.

The relationship between self-rated health (SRH) and cardiovascular events in individuals with hypertension, but without diabetes mellitus, is understudied. We performed a post hoc analysis of data from SPRINT (Systolic Blood Pressure Intervention Trial). SRH was categorized into excellent, very good, good and fair/poor. Using multivariable Cox regression, we estimated hazard ratios and 95% confidence intervals (CIs) for the association of SRH with both all-cause mortality and a composite of cardiovascular events (the primary outcome), which was defined to include myocardial infarction (MI), other acute coronary syndromes, stroke, acute decompensated heart failure, and cardiovascular death. We included 9319 SPRINT participants (aged 67.9 ± 9 years, 35.6% women) with a median follow-up of 3.8 years. Compared with SRH of excellent, the risk [hazard ratio (95% CI)] of the primary outcome associated with very good, good, and fair/poor SRH was 1.11(0.78-1.56), 1.45 (1.03-2.05), and 1.87(1.28-2.75), respectively. Similarly, compared with SRH of excellent, the risk of all-cause mortality [hazard ratio (95% CI)] associated with very good, good, and fair/poor SRH was 1.13 (0.73-1.76), 1.72 (1.12-2.64), and 2.11 (1.32-3.38), respectively. Less favorable SRH (LF-SRH) was also associated with a higher risk of each component of the primary outcome and serious adverse events (SAE). Among individuals with hypertension, SRH is independently associated with the risk of incident cardiovascular events, all-cause mortality, and SAE. Our study suggest that guidelines should consider the potential significance of including SRH in the clinical history of patients with hypertension.

Comparative efficacy and safety of different drugs in patients with systemic juvenile idiopathic arthritis: A systematic review and network meta-analysis.

The goal of this study was to estimate the relative efficacy and safety of different biological agents (infliximab, canakinumab, baricitinib, anakinra, adalimumab, tofacitinib, tocilizumab, and rilonacept) compared with placebo for systemic juvenile idiopathic arthritis (JIA) patients, through a network meta-analysis. Pubmed, Embase, and Cochrane Library were searched from database inception to July 2023 for randomized controlled trials comparing different biological agents (infliximab, canakinumab, baricitinib, anakinra, adalimumab, tofacitinib, tocilizumab, and rilonacept) or placebo directly or indirectly in JIA. Bayesian network meta-analyses were conducted. Data was extracted and analyzed by R with gemtc package. The treatment options were ranked using the surface under the cumulative ranking curve (SUCRA) value. We identified 10 randomized controlled trials and analyzed 898 participants. Canakinumab (odds ratio 55.0, 95% credible intervals 2.4-67.0) was more effective than the placebo, and the difference was statistically significant. However, there was no statistical significance between other drugs versus placebo in terms of the modified ACRpedi30 (P > .05). The SUCRA shows that canakinumab ranked first (SUCRA, 86.9%), anakinra ranked second (SUCRA, 77.7%), adalimumab ranked third (SUCRA, 61.9%), and placebo ranked the last (SUCRA, 6.3%). Nevertheless, there were no notable discrepancies in the occurrence of adverse events, hepatic-related adverse events, infectious adverse event, serious adverse events, and serious infection following treatment with canakinumab, anakinra, tocilizumab, rilonacept, or the placebo. Based on the clustergram of modified ACRpedi30 and adverse events, canakinumab is suggested for JIA according to the surface under SUCRAs considering the symptom and adverse events simultaneously. Among patients with JIA, canakinumab exhibited the highest likelihood of being the optimal treatment for achieving the modified ACRpedi30 response rate, and neither of the tested biological agents carried a significant risk of serious adverse events.

Development of a rapid HPLC-fluorescence method for monitoring warfarin metabolites formation: In vitro studies for evaluating the effect of piperine on warfarin metabolism and plasma coagulation

Warfarin, a widely prescribed anticoagulant, is highly effective for various coagulation disorders. However, its efficacy is limited by a narrow therapeutic index and frequent drug interactions, especially those involving metabolism by Cytochrome P450 (CYP450) enzymes. Piperine, found in black and long pepper, possesses blood-thinning properties and has been observed to inhibit CYP3A and CYP2C enzymes linked to warfarin metabolism. This study investigated the effect of piperine on warfarin metabolism in liver microsomes using a rapid and sensitive HPLC-Fluorescence method. The use of PFP (pentafluorophenyl) column with core shell particles provided the selectivity and resolution to resolve warfarin and its 4-, 6-, 7-, and 10-hydroxy metabolites in addition to the internal standard naproxen in less than 3 min. This is the fastest analytical assay for warfarin and its major metabolites reported to date, making it ideal for metabolic studies. The applicability of the method was demonstrated by monitoring the metabolism of S-warfarin in human and rat liver microsomes, and evaluating the inhibitory effect of piperine on metabolite formation. The results showed that piperine inhibited the formation of the major metabolite, 7-hydroxywarfarin, with half-maximal inhibitory concentration (IC50) 14.2 μM and 3.2 μM in human and rat liver microsomes, respectively. Furthermore, coagulation studies in vitro using rat plasma showed that piperine does not affect prothrombin time (PT) and activated partial thromboplastin time (aPTT). This study suggested that piperine may present a potential drug interaction with warfarin at the metabolism level, but has no direct effect on the activation of the extrinsic or intrinsic coagulation cascades. Further clinical investigation is therefore required, as piperine may increase the bioavailability of warfarin, thus increasing risk of serious adverse events in patients.

Development and validation of a clinical decision support system to prevent anticoagulant duplications

Background and ObjectiveUnintended duplicate prescriptions of anticoagulants increase the risk of serious adverse events. Clinical Decision Support Systems (CDSSs) can help prevent such medication errors; however, sophisticated algorithms are needed to avoid alert fatigue. This article describes the steps taken in our hospital to develop a CDSS to prevent anticoagulant duplication (AD). MethodsThe project was composed of three phases. In phase I, the status quo was established. In phase II, a clinical pharmacist developed an algorithm to detect ADs using daily data exports. In phase III, the algorithm was integrated into the hospital's electronic health record system. Alerts were reviewed by clinical pharmacists before being sent to the prescribing physician. We conducted a retrospective analysis of all three phases to assess the impact of the interventions on the occurrence and duration of ADs. Phase III was analyzed in more detail regarding the acceptance rate, sensitivity, and specificity of the alerts. ResultsWe identified 91 ADs in 1581 patients receiving two or more anticoagulants during phase I, 70 ADs in 1692 patients in phase II, and 57 ADs in 1575 patients in phase III. Mean durations of ADs were 1.8, 1.4, and 1.1 calendar days during phases I, II, and III, respectively. In comparison to the baseline in phase I, the relative risk reduction of AD in patients treated with at least two different anticoagulants during phase III was 42% (RR: 0.58, CI: 0.42–0.81). A total of 429 alerts were generated during phase III, many of which were self-limiting, and 186 alerts were sent to the respective prescribing physician. The acceptance rate was high at 97%. We calculated a sensitivity of 87.4% and a specificity of 87.9%. ConclusionThe stepwise development of a CDSS for the detection of AD markedly reduced the frequency and duration of medication errors in our hospital, thereby improving patient safety.

Bone marrow transplantation and bone marrow-derived mesenchymal stem cell therapy in epidermolysis bullosa: A systematic review.

Epidermolysis bullosa (EB) is a genodermatosis that lacks effective treatments and requires supportive care for its severe, life-threatening manifestations. Bone marrow transplantation (BMT) and its derived cells have been suggested to improve clinical symptoms and quality of life. A comprehensive search was conducted for publications evaluating BMT and bone marrow-derived mesenchymal stem cell (BM-MSC) therapy for EB in PubMed/MEDLINE, Google Scholar, and Cochrane databases from inception until June 2023. A total of 55 participants with severe forms of EB had BMT and/or BM-MSCs, with recessive dystrophic EB as the most common EB type; 53 (96.4%) patients had better wound healing, and 3 (5.5%) patients died of sepsis. The most common adverse events reported were graft failure, sepsis, graft-versus-host disease, and renal insufficiency. Allogeneic BMT is a high-risk procedure with possible benefits and adverse events. BM-MSCs revealed favorable outcomes to improve the safety of EB cell-based therapy by minimizing the risk of serious adverse events, reducing blisters, and accelerating wound healing. Further studies are needed to assess the treatment's long-term effects and clarify the risk/benefit ratio of procedure versus conventional therapy.

Abstract 3560: Quantified kinematics and wearable sensors to predict serious adverse events in patients undergoing cancer therapy trials

Abstract Background: Serious adverse events (SAEs) are a critical determinant of drug toxicity in clinical trials. However the drivers of toxicity may be related to patient factors as much or more than drug related factors. Prior studies have shown that time in non-sedentary activity predicted toxicity in cancer patients receiving highly emetogenic chemotherapy. SAEs are a critical determinant of drug toxicity in clinical trials. However, predicting SAEs using conventional PS scales measurements, such as ECOG is challenging because measurements can vary among observers. Prior studies have used activity trackers to measure physical activity and showed that time spent in non-sedentary activity predicted toxicity in cancer patients receiving highly emetogenic chemotherapy. Here, we sought to extend these findings to early phase clinical trial participants by examining data collected in two single-arm, observational, prospective studies at USC Keck and MD Anderson centers. We explored the use of out-of-clinic wearable sensors as an objective metric of frailty so as to identify patients at risk for therapy complications. Methods: Adult patients diagnosed with cancer and enrolled in early stage clinical trials across USC Keck and MD Anderson centers were included in parallel single-arm, observational, prospective studies. Patients used a consumer grade wearable activity tracker (Fitbit) and the study examined associations between the number of severe adverse events to activity levels measured by metabolic equivalents (METs) and get-up-go times across the first 30 days. Trends were assessed using t-tests. Results: 36 eligible patients were included in METs activity analysis. There was a total of 16 recorded incidences of SAEs within the first 30 study days, with 10 patients experiencing at least one SAE. The median non-sedentary time for patients with no SAEs was 27.5 hours above 1.5 METs per week, compared to 21.5 hours for those with at least one SAE occurrence (p-value=0.0146, r2=0.1629). The median get-up-go times for those without SAEs was 10.0 seconds (n=26) and with SAEs was 9.8 seconds (n=10), (p-value=0.828, r2=0.0014). Conclusions: Non-sedentary time, as an objective measure of activity, can be used to identify those patients who are at greatest risk for SAEs in clinical trials. Widely available and inexpensive consumer grade sensors can be used as a stratification tool. Findings should be confirmed in larger patient cohorts across a wider variety of trial settings. Figure 1: Weekly non-sedentary hours vs. presence of SAE in first 30 days of trial enrollment Citation Format: Eli Tran, Luciano Nocera, Anand Kolatkar, Anthony El-Khoueiry, Jacob Thomas, Peter Kuhn, Andrew Zeng, Megumi Kai, Meghan Karuturi, Jorge Nieva. Quantified kinematics and wearable sensors to predict serious adverse events in patients undergoing cancer therapy trials [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3560.

Effectiveness and safety of biological and target synthetic drugs treatment for psoriatic arthritis: a systematic review with network meta-analysis

BackgroundPsoriatic arthritis (PA) is a chronic inflammatory systemic arthritis that can result in loss of functional capacity and joint deformation. This systematic review assessed the effectiveness and safety of biological and target synthetic drugs for treating PA.MethodsWe searched for randomized clinical trials (RCTs) that evaluated the use of Adalimumab, Etanercept, Infliximab, Golimumab, Secukinumab, Certolizumab Pegol and Tofacitinib in the main general databases and clinical trial registers databases. The primary outcomes were ACR 50, PsARC, and serious adverse events. Two independent reviewers performed study selection and data extraction. Network meta-analyses were conducted using a random effects model and frequentist approach. The CINeMA software was used to assess the certainty of evidence.ResultsWe included 33 RCTs (n = 11,034). The results from the network meta-analysis for the ACR 50 at 6-months follow-up showed that all drugs were superior to placebo, with Secukinumab (high certainty of evidence), Infliximab (very low certainty of evidence) and Adalimumab (high certainty of evidence) ranking the highest. Regarding the PsARC (at 6-months follow-up), all drugs, except for Golimumab (very low certainty of evidence), were superior to placebo, with Etanercept (low certainty of evidence), Infliximab (low certainty of evidence) and Certolizumab Pegol (low certainty of evidence) being the most effective drugs. There were no significant differences in the risk of serious adverse events between the drugs and placebo. Golimumab (very low certainty of evidence), Secukinumab (low certainty of evidence), and Adalimumab (very low certainty of evidence) ranked the highest for safety.ConclusionsIn conclusion, based on the balance between efficacy and safety, Secukinumab and Adalimumab may be the preferred options among the evaluated drugs for treating patients with PsA. However, caution is necessary when interpreting the safety findings, as they are supported by evidence of low to very low certainty. Consequently, the balance between benefits and potential risks may change as new safety evaluation studies become available.Protocol registrationPROSPERO: CRD42022315577

Patient Preferences for Treatment Attributes in Inflammatory Bowel Disease: Results From a Large Survey Across Seven European Countries Using a Discrete Choice Experiment.

Inflammatory bowel disease requires long-term treatment; therefore, understanding patient preferences is important in aiding informed treatment decision making. This study explored patients' preferences for treatment attributes of available inflammatory bowel disease therapies. Adult patients from 7 European countries who self-reported previous/current treatment for Crohn's disease (CD) or ulcerative colitis (UC) participated in an online survey via the Carenity platform. In a discrete choice experiment, the relative importance of treatment attributes for CD and UC was estimated using conditional logit models. Latent class analysis was conducted to estimate heterogeneous treatment preferences based on patient profiles. Patients' perspectives and preferences regarding their quality of life were assessed. Across 686 completed survey responses (CD, n = 360; UC, n = 326), the mean patient age was 48 and 50 years, respectively. Patients with CD ranked route of administration as the most important attribute (attribute importance: 32%), preferring subcutaneous over intravenous treatment (P < .001). Patients with UC ranked route of administration and frequency of serious adverse events as the most important attributes (attribute importance: 31% and 23%, respectively), preferring oral (P < .001) and subcutaneous (P < .001) over intravenous treatment and treatment that minimized the risk of serious adverse events (P < .001) or mild adverse events (P < .01). Latent class analyses confirmed the impact of patients' sociodemographic profile on their preferences. All patients prioritized general well-being, energy level, and daily activities as the most important aspects for improvement through treatment. Patient preferences for treatment attributes varied among patients with CD or UC, highlighting the importance of personalized care and shared decision making to maximize treatment benefits.

Efficacy and safety of low-dose corticosteroids combined with leflunomide for progressive IgA nephropathy: a systematic review and meta-analysis

Background and objectiveThe effectiveness of immunosuppressive and corticosteroid treatments for Immunoglobulin A (IgA) nephropathy (IgAN) remains thoroughly evaluated. We undertook a meta-analysis to investigate the efficacy and safety of low-dose corticosteroids plus leflunomide for progressive IgA nephropathy.MethodsEligible studies were obtained from PubMed, Embase, and Cochrane Library databases. We also searched the references of the included studies. Our protocol followed the preferred reporting items for systematic reviews and meta-analyses (PRISMA) checklist. Eligibility criteria were defined using a PICOS framework.ResultsOur study included three articles presenting 342 patient cases. Findings revealed that low-dose corticosteroids combined with the leflunomide group were effective in relieving urine protein excretion (UPE) [mean difference (MD) = -0.35, 95% confidence interval (CI): -0.41 to -0.30, P < 0.00001] compared with the full-dose corticosteroids group. Regarding serum creatinine (SCr), estimated glomerular filtration rate (eGFR), complete remission rate, and overall response rate, there was no difference between the groups (p > 0.05). Regarding safety, low-dose corticosteroids combined with leflunomide significantly reduced the risk of serious adverse events [odds ratio (OR): 0.11, 95% CI: 0.01 to 0.91, P = 0.04]. Besides, no significant differences were observed between the two groups in the incidence of respiratory infection, abnormal liver function, diarrhea, herpes zoster, alopecia, pruritus, insomnia, pneumonia, diabetes, and urinary tract infection (P > 0.05).ConclusionsLow-dose corticosteroids combined with leflunomide are a safe and effective treatment for progressive IgA nephropathy.Trial registrationThe PROSPERO registration number is CRD42022361883.

A retrospective analysis of serious adverse events and deaths in U.S.-based lifestyle clinical trials for cognitive health

ObjectiveThis retrospective analysis examined serious adverse events (SAEs) and deaths in U.S. lifestyle clinical trials aimed at enhancing cognitive health in older adults. MethodsData was gathered from trials completed between January 1, 2000, and July 19, 2023, via ClinicalTrials.gov's API. ResultsAmong these trials, 76% did not report results. The remaining studies fell into four intervention categories: Cognitive/Behavioral, Exercise/Movement, Diet/Supplement, and Multi-modal. When considering all trial types collectively, the findings suggest that lifestyle clinical trials are generally safe. There was no significant increase in the relative risk of experiencing an SAE in the intervention group compared to the control group. However, in terms of relative risk of death, an increase of 28% was observed in the intervention compared to the control, which was statistically significant (X2 (1, N = 36), p < 0.00688). Nevertheless, this increase did not surpass age-adjusted U.S. mortality rates. Assessing the data by intervention type, Diet/Supplement, and Multi-modal trials displayed an elevated relative risk of SAEs in the intervention. Diet/Supplement trials had a 16% increase (X2 (1, N = 2), p < 0.0263), and Multi-modal trials had a 365% increase (X2 (1, N = 5), p < 0.000213). Diet/Supplement trials also showed a 67% increased risk of death (X2 (1, N = 2), p < 0.000197). ConclusionsThese findings should be cautiously considered due to the low rate of reporting, but underscore the significance of reporting clinical trial results, enhancing transparency, and facilitating more accurate safety assessments in cognitive aging and lifestyle interventions for older adults.