System-related Adverse Events Research Articles

Endocrine system-related adverse events associated with PD-1/PD-L1 inhibitors: data mining from the FDA adverse event reporting system.

Various immune checkpoint inhibitors, such as programmed cell death protein-1 (PD-1) and its ligand (PD-L1), have been approved for use, but they have side effects on the endocrine glands. Adverse event reports related to PD-1/PD-L1 inhibitors from the FDA Adverse Event Reporting System (FAERS) from the first quarter of 2019 to the first quarter of 2023 were extracted, and the reported Odds ratio methods (ROR method) and comprehensive standard methods (MHRA methods) were used for data mining and analysis. A total of 5,322 reports (accounts for 6.68% of the total reports)of AEs in endocrine system were collected, including 1852 of pabolizumab (34.80%), 2,326 of navuliumab (43.71%), 54 of cimipriliumab (1.01%), 800 of atilizumab (15.03%), 222 of duvariumab (4.17%) and 68 of averumab (1.28%). Endocrine system-related AEs were mainly present in men (excluding those treated with pembrolizumab) aged ≥65 years. The ratio of AEs components in the endocrine system for the six drugs was approximately 3-8%. The main endocrine glands involved in AEs were the thyroid (pembrolizumab), pituitary and adrenal (nivolumab), adrenal (cemiplimab, atezolizumab, and avelumab), and thyroid (durvalumab). Most patients experienced AEs between 30 and 365 (mean, 117) days,the median time was 61d. AEs resulted in prolonged hospitalization in >40% and death in >10% of cases after administration of pembrolizumab, nivolumab, or durvalumab. Men aged ≥65 years should be concerned about endocrine-related AEs. There was a lengthy interval between the use of PD-1/PD-L1 inhibitors and endocrine system-related AEs, but the outcome was serious. Special attention should be given to endocrine system-related AEs when using pembrolizumab, nivolumab, or durvalumab.

Adaptive versus conventional cardiac resynchronisation therapy in patients with heart failure (AdaptResponse): a global, prospective, randomised controlled trial

Continuous automatic optimisation of cardiac resynchronisation therapy (CRT), stimulating only the left ventricle to fuse with intrinsic right bundle conduction (synchronised left ventricular stimulation), might offer better outcomes than conventional CRT in patients with heart failure, left bundle branch block, and normal atrioventricular conduction. This study aimed to compare clinical outcomes of adaptive CRT versus conventional CRT in patients with heart failure with intact atrioventricular conduction and left bundle branch block. This global, prospective, randomised controlled trial was done in 227 hospitals in 27 countries across Asia, Australia, Europe, and North America. Eligible patients were aged 18 years or older with class 2-4 heart failure, an ejection fraction of 35% or less, left bundle branch block with QRS duration of 140 ms or more (male patients) or 130 ms or more (female patients), and a baseline PR interval 200 ms or less. Patients were randomly assigned (1:1) via block permutation to adaptive CRT (an algorithm providing synchronised left ventricular stimulation) or conventional biventricular CRT using a device programmer. All patients received device programming but were masked until procedures were completed. Site staff were not masked to group assignment. The primary outcome was a composite of all-cause death or intervention for heart failure decompensation and was assessed in the intention-to-treat population. Safety events were collected and reported in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT02205359, and is closed to accrual. Between Aug 5, 2014, and Jan 31, 2019, of 3797 patients enrolled, 3617 (95·3%) were randomly assigned (1810 to adaptive CRT and 1807 to conventional CRT). The futility boundary was crossed at the third interim analysis on June 23, 2022, when the decision was made to stop the trial early. 1568 (43·4%) of 3617 patients were female and 2049 (56·6%) were male. Median follow-up was 59·0 months (IQR 45-72). A primary outcome event occurred in 430 of 1810 patients (Kaplan-Meier occurrence rate 23·5% [95% CI 21·3-25·5] at 60 months) in the adaptive CRT group and in 470 of 1807 patients (25·7% [23·5-27·8] at 60 months) in the conventional CRT group (hazard ratio 0·89, 95% CI 0·78-1·01; p=0·077). System-related adverse events were reported in 452 (25·0%) of 1810 patients in the adaptive CRT group and 440 (24·3%) of 1807 patients in the conventional CRT group. Compared with conventional CRT, adaptive CRT did not significantly reduce the incidence of all-cause death or intervention for heart failure decompensation in the included population of patients with heart failure, left bundle branch block, and intact AV conduction. Death and heart failure decompensation rates were low with both CRT therapies, suggesting a greater response to CRT occurred in this population than in patients in previous trials. Medtronic.

Comparative real-world (RW) evidence on darolutamide (Daro), enzalutamide (Enza), and apalutamide (Apa) for patients (Pts) with nonmetastatic castration-resistant prostate cancer (nmCRPC) in the United States: DEAR.

5097 Background: Novel androgen receptor inhibitors (ARIs) are recommended for pts with nmCRPC. Daro has a distinct structure with low blood-brain barrier penetration which may lead to a lower risk of central nervous system-related adverse events (AEs) and minimal risk of AEs commonly associated with ARIs. DEAR is the first study comparing RW utilization, outcomes, and AEs between daro and enza/apa in nmCRPC pts. Methods: This retrospective chart review cohort study uses electronic medical records from the PPS network of US urology practices. Eligible pts had nmCRPC, no prior novel hormonal therapy, and initiated first ARI treatment (index date) between 8/2019-3/2022. We describe the % of pts who discontinued initial ARI treatment (DISC), % who progressed to metastasis (PROG), and % with AEs. A comparative analysis was performed between daro and enza/apa using Cox proportional hazards models for time to DISC/time to PROG, adjusting for observed baseline (BL) factors. Results: 870 pts were included (daro/enza/apa, n=362/382/126). Median age (80/79/80 y), median BL prostate-specific antigen (PSA) doubling time (6.8/6.4/7.4 mo), other BL characteristics, and median follow-up (22.2/22.7/23.3 mo) were similar for daro/enza/apa. A lower % of pts had a DISC event on daro vs enza/apa (30.4 vs 40.8/46.0) or a PROG event (17.7 vs 28.3/27.8) during the study period. Multivariate analyses adjusting for BL factors showed that pts on daro had a lower risk of DISC and PROG over time vs enza/apa. A lower % of pts on daro had AEs vs enza/apa (24.9 vs 29.3/30.2). Conclusions: Overall, a lower % of pts discontinued initial ARI treatment, progressed to metastasis, or had AEs on daro vs enza/apa. In analyses adjusting for observed BL factors, pts on daro had considerably lower risk of DISC and PROG vs enza/apa. This study confirms daro’s strong efficacy and favorable tolerability profile in a RW setting. The longer treatment duration seen with daro may be associated with a lower risk of progression to mCRPC vs enza/apa. [Table: see text]

Evaluation of insertable cardiac monitor placement and safety in the LUX-Dx PERFORM study

Abstract Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): Boston Scientific Corporation Background The LUX-Dx PERFORM Study is designed to evaluate safety and performance of the LUX-Dx insertable cardiac monitor (ICM) in a general patient population. Enrollment and device insertions are complete, and all patients have completed 30 days of follow-up. This abstract describes the study population, characterizes device insertion, and reports on preliminary data for ICM system-related complications. Methods The LUX-Dx PERFORM study is a prospective, multi-center, single arm, post-market, observational study. The ICM system-related complication-free rate (CFR) at 30 days post-insertion was calculated using Kaplan-Meier methodology and the 97.5% one-side lower confidence limit (LCL) was compared to the prespecified performance target of 94%. All ICM system-related adverse events were adjudicated by independent physician reviewers. Results 727 patients were enrolled at 24 centers in the United States from March 2021 to May 2022. The study population was 49% male, 91% white and 66+/-14 years old. 717 patients had device insertions and were successfully registered in the LATITUDE Clarity data management system. There were 9 withdrawals prior to insertion and 1 aborted procedure due to deployment difficulty. ICM insertion was performed in-hospital 76% of the time (N=547) and in-clinic 24% of the time (N=171). 96% were de novo device insertions. A variety of closure techniques were used including surgical glue (62%), adhesive strips (45%), sutures (42%), and staples (9%). Median procedure time was 4 minutes (range 1 - 37). There were 4 ICM system-related complications in the first 30 days (CFR 99%, LCL 99%) which meets the acute safety performance goal. The system-related complications include 1 case of ICM deployment difficulty, 1 case of device expulsion three days post insertion, and 2 infections that were treated with oral antibiotics and resolved without further mitigation. Conclusion The LUX-Dx ICM can be inserted quickly, in both hospital and clinic settings, with a very low complication rate.

Open-label study of androgen receptor inhibition with darolutamide plus androgen-deprivation therapy (ADT) versus ADT in men with metastatic hormone-sensitive prostate cancer using an external control arm (ARASEC).

TPS5111 Background: Darolutamide is a structurally distinct and highly potent androgen receptor inhibitor (ARI) that significantly improved metastasis-free survival by ̃2 years and reduced the risk of death by 31% vs placebo in patients with nonmetastatic castration-resistant prostate cancer (CRPC). Darolutamide has a favorable safety and tolerability profile, with only ≤2% difference vs placebo for most adverse events (AEs) of interest (falls, fractures, hypertension, mental impairment). Fatigue was the only AE with > 10% incidence in the darolutamide arm (13.2%; placebo, 8.3%). Darolutamide has shown lower blood–brain barrier penetration than other ARIs in preclinical models (supported by human neuroimaging studies), which may lead to a lower risk of central nervous system-related AEs and has a low potential for drug–drug interactions. For patients with metastatic hormone-sensitive prostate cancer (mHSPC), the combination of darolutamide and ADT is expected to offer a favorable benefit–risk profile. ARASEC will evaluate the efficacy and safety of darolutamide plus ADT in mHSPC in the US (NCT05059236) and complement the data in the ongoing ARANOTE study (NCT04736199). Methods: ARASEC is a US-based, phase 2, open-label, single-arm study with an external control arm. Eligible patients will have confirmed adenocarcinoma of the prostate, radiologic evidence of metastatic disease by conventional imaging, and Eastern Cooperative Oncology Group performance status (ECOG PS) ≤2. Patients with mHSPC will receive darolutamide 600 mg twice daily plus ADT (luteinizing hormone-releasing hormone agonist/antagonist or orchiectomy). The control arm for ARASEC will be derived from the 393 patients with mHSPC treated with ADT alone in the CHAARTED trial. Patients in the active arm will be matched 1:1 to patients in the control arm using important baseline characteristics such as age, ECOG PS, extent of disease defined as low or high volume according to CHAARTED, and presence of bone and visceral metastases. Study duration was defined as the time from the first patient’s first visit until either the event count threshold triggering the primary endpoint analysis has been met or all patients have been followed for ≥2 years after enrollment, whichever occurs later. The primary endpoint is progression-free survival (PFS), defined in CHAARTED as the time from enrollment to prostate-specific antigen (PSA) progression, clinical progression (including radiological or symptomatic progression or clinical deterioration), or death, whichever occurs first. Secondary endpoints are overall survival, radiographic PFS, time to CRPC, complete PSA response rate at 6 months, and safety. Patient recruitment is in progress. Clinical trial information: NCT05059236.

Bariatric surgery and total knee/hip arthroplasty: an analysis of the impact of sequence and timing on outcomes

BackgroundPatients with morbid obesity may require both bariatric surgery and total knee/hip arthroplasty (TKA/THA). How to sequence these two procedures with better outcomes remains largely unstudied.MethodsThis cohort study extracted claims...

Identification of the risk factors in perioperative respiratory adverse events in children under general anesthesia and the development of a predictive model.

BackgroundThis study explored the risk factors of perioperative respiratory adverse events in children under 12 years old undergoing general anesthesia surgery. A prediction model was constructed according to the related risk factors to provide a basis for timely clinical intervention and decision-making.MethodsChildren under 12 years old who underwent general anesthesia in our hospital between January 2016 and December 2020 were included in this study. The clinical data, including age, gender, weight, American Society of Anesthesiologists (ASA) grade classification, operation season, preoperative hospital stay, anesthesia time, and postoperative pain score, were collated. Continuous variables were converted to categorical variables. Logistic regression analysis was used to screen independent risk factors and a nomogram was constructed to predict the probability of adverse events. Fitting curves and receiver operating characteristic (ROC) curves were utilized to verify the model.ResultsLogistic regression analyses demonstrated that age [odds ratio (OR) =1.32, 95% confidence interval (CI): 1.08 to 1.49], body weight (OR =1.49, 95% CI: 1.21 to 1.84), anesthesia time (OR =1.61, 95% CI: 1.32 to 1.78), and surgery season (OR =1.12, 95% CI: 1.07 to 1.39) were independent risk factors for respiratory adverse events in children undergoing general anesthesia (P<0.05). The risk of respiratory-related adverse events increased in children with grade II ASA classification compared to children with grade I ASA classification (P<0.05). Similarly, the risk of respiratory adverse events increased in children with level III pain scores compared to children with level I pain scores (P<0.05). The calibration curve showed that the predicted curve was consistent with the actual curve. The area under the ROC curve (AUC) was 0.707, indicating that model showed great predictive ability.ConclusionsAge, weight, anesthesia time, operation season, ASA grade, and pain score were identified as independent risk factors for respiratory adverse events in children undergoing general anesthesia. Using the above risk factors, a nomogram was established to predict the risk of respiratory system-related adverse events. The predicted results were highly consistent with the actual risk, and the false positive rate was within a reasonable range.

Efficacy and Safety of Phentermine/Topiramate in Adults with Overweight or Obesity: A Systematic Review and Meta-Analysis.

The study objective was to examine the association between phentermine/topiramate therapy and weight loss and adverse events in adults with overweight or obesity by meta-analysis and systematic review. Medical Subject Headings and free-text terms were selected to search for eligible trials in PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), and Embase up to April 18, 2020. The quality of randomized controlled trials was evaluated by the Cochrane risk-of-bias tool. Meta-analysis was performed using random-effect models. Phentermine/topiramate therapy resulted in an average weight loss of 7.73 kg (95% CI: 6.60-8.85) in general compared with placebo. The weight loss was related to the dose of phentermine/topiramate. Compared with placebo, the average weight loss was 3.55 kg (95% CI: 2.22-4.88) for 3.75/23 mg, 7.27 kg (95% CI: 6.40-8.13) for 7.5/46 mg, and 8.25 kg (95% CI: 6.92-9.79) for 15/92 mg. For phentermine/topiramate participants in different weight-loss subgroups, the weight loss of participants with ≥5%, ≥10%, and ≥15% baseline weight loss was 3.18 (95% CI: 2.75-3.67), 5.32 (95% CI: 4.53-6.25), and 5.65 (95% CI: 3.55-9.01), respectively. Compared with placebo, the adverse events associated with the treatment mainly included dysgeusia (odds ratio [OR] = 8.86, 95% CI: 5.65-13.89), paresthesia (OR = 8.51, 95% CI: 6.20-11.67), dry mouth (OR = 6.71, 95% CI: 5.03-8.94), disturbance in attention (OR = 4.48, 95% CI: 2.39-8.41), irritability (OR = 4.10, 95% CI: 2.29-7.33), hypoesthesia (OR = 3.81, 95% CI: 1.32-11.00), constipation (OR = 2.43, 95% CI: 2.02-2.93), and dizziness (OR = 2.26, 95% CI: 1.72-2.98). Phentermine/topiramate also reduced waist circumference, blood pressure, blood sugar levels, and lipid levels. Phentermine/topiramate has considerable benefit in reducing body weight, and the efficacy was closely related to the dosage. However, it increased the risk of nervous system-related adverse events.

Risk of Cognitive Effects in Comorbid Patients With Prostate Cancer Treated With Androgen Receptor Inhibitors.

Prostate cancer (PC) is primarily a disease of older men. As the risk of neurocognitive decline increases as people age, cognitive dysfunction is a potential complication in men with PC, imposing detrimental effects on functional independence and quality of life. Importantly, risk of cognitive decline may increase with exposure to androgen deprivation therapy and other hormonal therapies. Particular consideration should be given to patients with castration-resistant PC (CRPC), many of whom require continuous, long-term androgen deprivation therapy combined with a second-generation androgen receptor inhibitor. Non-comparative evidence from interventional trials of androgen receptor inhibitors in men with non-metastatic CRPC suggests differential effects on cognitive function and central nervous system-related adverse events within this drug class. Drug-drug interactions with concomitant medications for chronic, non-malignant comorbidities differ among ARIs and thus may contribute further to cognitive impairment. Hence, establishing baseline cognitive function is a prerequisite to identifying subsequent clinical decline associated with androgen receptor-targeted therapies. Although brief, sensitive screening tools for cancer-related cognitive dysfunction are lacking, mental status can be ascertained from the initial medical history and neurocognitive examination, progressing to more in-depth evaluation when impairment is suspected. On-treatment neurocognitive monitoring should be integrated into regular clinical follow-up to preserve cognitive function and quality of life throughout disease management. This review summarizes the multiple factors that may contribute to cognitive decline in men with CRPC, awareness of which will assist clinicians to optimize individual treatment. Practical, clinic-based strategies for managing the risks for and symptoms of cognitive dysfunction are also discussed.

\u201cSide effects--part of the package\u201d: a mixed methods approach to study adverse events among patients being programmatically treated for DR-TB in Gujarat, India

BackgroundHigh rates of Adverse Events (AEs) during treatment is one of the leading causes of unsuccessful treatment outcomes among patients with drug resistant tuberculosis (DR-TB). However, information related to AEs is not systematically collected and managed under programmatic setting. The present study assessed the a) incidence and pattern of adverse events in first three months of DR-TB treatment initiation; b) treatment seeking behaviour for AE management; and c) explore the challenges in seeking treatment and reporting AEs.MethodsThis mixed methods study included all patients diagnosed and initiated on treatment under RNTCP during July–September 2018 at Ahmedabad DR-TB centre. The patients were interviewed telephonically and assessed for all AEs experienced by them. In-depth interviews and key-informant interviews were conducted among patients, DOTS supervisors and programme staff (treatment supervisors, medical officer and district program managers).ResultsTotal 207 AEs were reported by the 74 DR-TB patients. All patients experienced at least one AE during initial treatment period. Incidence rate of AEs (experienced) was 3.11 (1st month-4.6, 2nd month-2.7, 3rd month-2.02) per 100 person days. Of the 207 AEs, gastro-intestinal (59, 28.3%), ophthalmic (32, 15.4%) and otolaryngology (25, 11.9%) system related AEs were commonly experienced. Treatment was not sought in two-fifths of the AEs. Themes and sub-themes related to challenges in treatment seeking or reporting of AEs were 1) Patient related-Misconceptions, accessibility and affordability of management, lack of counselling support, stigma and discrimination, and past treatment experience; 2) Health system related- lack of guidelines and training for AE management, 3) Poor coordination between hospital and tuberculosis centre.ConclusionThe incidence of AEs was high among patients with DR-TB in the first three months of treatment and treatment seeking/reporting was low. Adequate health education and counselling of the patient and orientation of the health systems is the need of the hour. An efficient real-time reporting and management of AE should be developed and tested for effective DR-TB control.

Current concepts in the management of diabetic polyneuropathy.

Diabetic sensorimotor polyneuropathy (DSPN) is encountered in approximately one‐third of people with diabetes. This, in turn, might markedly impoverish their quality of life, mainly owing to neuropathic pain and foot ulcerations. Painful DSPN might be as frequent as 25% in diabetes patients. Symptoms as a result of DSPN typically comprise pain, paresthesia and numbness in the distal lower limbs. Asymptomatic DSPN might reach 50% among patients with this condition. Unfortunately, DSPN is still not adequately diagnosed and treated. Its management has three priorities: (i) lifestyle improvement, near‐normoglycemia and multifactorial cardiovascular risk intervention; (ii) pathogenesis‐oriented pharmacotherapy; and (iii) symptomatic alleviation of pain. Intensive diabetes therapy showed evidence for favorable effects on the incidence and deterioration of DSPN in type 1 diabetes, but not type 2 diabetes. Among pathogenesis‐oriented treatments, α‐lipoic acid, actovegin, benfotiamine and epalrestat are currently authorized to treat DSPN in several countries. Symptomatic therapy uses analgesics, notably antidepressants, opioids and anticonvulsants, reducing pain by ≥50% in approximately 50% of individuals, but might be limited, particularly by central nervous system‐related adverse events. Local treatment with the capsaicin 8% patch might offer an alternative. In addition to pain relief, therapy should improve sleep, mobility and quality of life. In conclusion, multimodal treatment of DSPN should consider the individual risk profile, pathogenetic treatment and pain management using pharmacotherapy (combinations, if required), as well as non‐pharmacological options.

Darolutamide: An Evidenced-Based Review of Its Efficacy and Safety in the Treatment of Prostate Cancer.

Men treated with androgen deprivation therapy for rising PSA after failed local therapy will often develop castrate resistance, and the appearance of metastases predicts a poor prognosis. Thus, researchers have long sought to prolong the onset of metastasis in patients with nonmetastatic castration-resistant prostate cancer (CRPC). Until 2018, patients in this group had no FDA-approved treatment options. They were typically managed with androgen-deprivation therapy (ADT) to maintain castrate systemic testosterone levels and given approved therapies for metastatic CRPC once metastases appeared. However, third-generation androgen receptor inhibitors (ARIs) have dramatically changed the treatment paradigm, having shown the ability to extend metastasis-free survival (MFS) significantly over ADT alone in Phase 3 trials. The newest of these, darolutamide, prolonged MFS 22 months over placebo while also improving a host of secondary and exploratory endpoints such as overall survival (OS), prostate-specific antigen (PSA) progression and time to pain progression, chemotherapy initiation, and symptomatic skeletal events. Among third-generation ARIs, darolutamide is unique in that it incorporates two pharmacologically active diastereomers and has demonstrated resistance to all known androgen receptor (AR) mutations. Additionally, patients taking darolutamide appear to experience comparatively few central nervous system-related adverse events (AEs) such as fatigue and falls, and no increases in seizures have been reported in the drug’s clinical or preclinical development. Various authors attribute the low incidence of CNS-related AEs to darolutamide’s minimal penetration of the blood–brain barrier (BBB). Other side effects ranging from hot flashes to hypothyroidism also occurred at rates similar to those of the placebo arm in Phase 3. As ADT in itself raises cardiovascular risk, the cardiovascular safety of third-generation antiandrogens as a category warrants continued scrutiny. In total, however, published data suggest that darolutamide provides a reasonable option for patients with nonmetastatic CRPC. Ongoing research will determine darolutamide’s potential role in additional disease states such as localized and castration-sensitive PCa.

Exploring the Association Between Organizational Culture and Large-Scale Adverse Events: Evidence from the Veterans Health Administration

Large-scale adverse events (LSAEs) involve unsafe clinical practices stemming from system issues that may affect multiple patients. Although literature suggests a supportive organizational culture may protect against system-related adverse events, no study has explored such a relationship within the context of LSAEs. This study aimed to identify whether staff perceptions of organizational culture were associated with LSAE incidence. The team conducted an exploratory analysis using the 2008-2010 data from the US Department of Veterans Affairs (VA) All Employee Survey (AES). LSAE incidence was the outcome variable in two facilities where similar infection control practice issues occurred, leading to LSAEs. For comparison, four facilities where LSAEs had not occurred were selected, matched on VA-assigned facility complexity and geography. The AES explanatory factors included workgroup-level (civility, employee engagement, leadership, psychological safety, resources, rewards) and hospital-level Likert-type scales for four cultural factors (group, rational, entrepreneurial, bureaucratic). Bivariate analyses and logistic regressions were performed, with individual staff as the unit of analysis from the anonymous AES data. Responses from 209 AES participants across the six facilities in the sample indicated that the four comparison facilities had significantly higher mean scores compared to the two LSAE facilities for 9 of 10 explanatory factors. The adjusted analyses identified that employee engagement significantly predicted LSAE incidence (odds ratio = 0.58, 95% confidence interval = 0.37-0.90). Staff at the two exposure facilities in this study described their organizational culture to be less supportive. Lower scores in employee engagement may be a contributing factor for LSAEs.

Evaluation of Flibanserin Safety: Comparison with Other Serotonergic Medications.

Flibanserin, a multifunctional serotonin agonist and antagonist, is approved by the U.S. Food and Drug Administration (FDA) for treatment of acquired, generalized hypoactive sexual desire disorder in premenopausal women. During the FDA's review of flibanserin, concerns were raised about the risks of hypotension, syncope, and sedation-related adverse events, which increase with alcohol use. Based on the results of an alcohol challenge study, the FDA required a boxed warning and alcohol contraindication in the flibanserin prescribing information, as part of a risk evaluation and mitigation strategy program. To evaluate the adverse event profile of flibanserin in the context of that seen with other medications that affect serotonin in the brain and are commonly prescribed for women. This was a review of data provided in the product prescribing information for flibanserin, selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, other serotonergic antidepressants, and triptans. The incidence of adverse events was assessed. The incidences of hypotension, syncope, and sedation-related adverse events (eg, dizziness, somnolence, fatigue) in studies of flibanserin were within the ranges observed for serotonergic antidepressants; the rates of these adverse events were generally lower with triptan medications. Other flibanserin-associated adverse events (eg, nausea, insomnia, dry mouth) occurred more commonly in patients taking antidepressant medications. Although medications that affect the serotonin system have varying adverse event profiles (likely mediated by differences in serotonin-related mechanisms of action, specific brain structures affected, and effects on other neurotransmitter systems), the occurrence of central nervous system-related adverse events was not dissimilar between flibanserin and serotonergic antidepressants. Kingsberg SA, McElroy SL, Clayton AH. Evaluation of Flibanserin Safety: Comparison with Other Serotonergic Medications. Sex Med Rev 2019;7:380-392.

Do etoricoxib and indometacin have similar effects and safety for gouty arthritis? A meta-analysis of randomized controlled trials.

BackgroundGout, a common medical condition that causes pain, can be treated by painkillers and anti-inflammatories. Indometacin and etoricoxib are two such drugs. However, no synthesized evidence exists comparing etoricoxib with indometacin in treating patients with gout.MethodsWe searched PubMed, Embase, Ovid MEDLINE, Web of Science, ScienceDirect, and the Cochrane Library without restrictions on language or publication date for potential randomized clinical trials comparing etoricoxib with indometacin for gout. The meta-analysis was conducted using a random-effects model.ResultsSearch results yielded 313 references from six electronic databases, four of which met the eligibility criteria. These four were randomized clinical trials, and they involved a total of 609 patients with gouty arthritis. No significant differences were observed in pain score change, tenderness, or swelling between etoricoxib and indometacin; the mean differences were −0.05 (95% CI, −0.21 to 0.10), −0.06 (95% CI, −0.18 to 0.05), and −0.04 (95% CI, −0.17 to 0.09). However, the pooled data revealed that significantly fewer overall adverse events occurred in the etoricoxib group (n=105, 33.5%) than in the indometacin group (n=130, 44.1%) and the risk ratio was 0.77 (95% CI, 0.62–0.94).ConclusionOur meta-analysis revealed that etoricoxib and indometacin have similar effects on pain relief. However, etoricoxib has a significantly lower risk of adverse events than does indometacin, especially digestive system-related adverse events.

Minimizing radiographic contrast administration during coronary angiography using a novel contrast reduction system: A multicenter observational study of the DyeVert™ plus contrast reduction system.

To evaluate contrast media (CM) volume (CMV) saved using the DyeVert™ Plus Contrast Reduction System (DyeVert Plus System, Osprey Medical) in patients undergoing diagnostic coronary angiogram (CAG) and/or percutaneous coronary interventional (PCI) procedures performed with manual injections. Current guidelines advocate for monitoring and minimization of the total volume of CM in chronic kidney disease (CKD) patients undergoing invasive cardiac procedures. The DyeVert Plus System is an FDA cleared device designed to reduce CMV delivered during angiography and permit real-time CMV monitoring. We performed a multicenter, single-arm, observational study. Eligible subjects were ≥ 18 years old with baseline estimated glomerular filtration rate (eGFR) 20-60 mL/min/1.73 m2 . The primary endpoint was % CMV saved over the total procedure. A secondary objective was to evaluate adverse events (AEs) related to DyeVert Plus System or to CM use. A total of 114 subjects were enrolled at eight centers. Mean age was 72 ± 9 years, 72% were male, and mean body mass index was 29 ± 5. Baseline eGFR was 43 ± 11 mL/min/1.73 m2 . CAG-only was performed in 65% of cases. One hundred and five subjects were evaluable for the primary endpoint. Mean CMV attempted was 112 ± 85 mL (range 22-681) and mean CMV delivered was 67 ± 51 mL (range 12-403), resulting in an overall CMV savings of 40.1 ± 8.8% (95% CI 38.4, 41.8; P < 0.0001) per procedure. Image quality was maintained in all but one case where the system was turned off for one injection. No DyeVert Plus System-related AEs were reported. Acute kidney injury (AKI; defined as serum creatinine rise of >0.3 mg/dL from baseline) was reported in 11 cases with seven occurring in subjects with baseline eGFR < 30 and three AKI events were attributed to CM. AKI rates increased as CMV/eGFR ratios increased. These data suggest DyeVert Plus System use in CKD patients undergoing CAG and/or PCI results in clinically meaningful CMV savings while maintaining image quality.

Anesthesia Adverse Events Voluntarily Reported in the Veterans Health Administration and Lessons Learned.

Anesthesia providers have long been pioneers in patient safety. Despite remarkable efforts, anesthesia errors still occur, resulting in complications, injuries, and even death. The Veterans Health Administration (VHA) National Center of Patient Safety uses root cause analysis (RCA) to examine why system-related adverse events occur and how to prevent future similar events. This study describes the types of anesthesia adverse events reported in VHA hospitals and their root causes and preventative actions. RCA reports from VHA hospitals from May 30, 2012, to May 1, 2015, were reviewed for root causes, severity of patient outcomes, and actions. These elements were coded by consensus and analyzed using descriptive statistics. During the study period, 3228 RCAs were submitted, of which 292 involved an anesthesia provider. Thirty-six of these were specific to anesthesia care. We reviewed these 36 RCA reports of adverse events specific to anesthesia care. Types of event included medication errors (28%, 10), regional blocks (14%, 5), airway management (14%, 5), skin integrity or position (11%, 4), other (11%, 4), consent issues (8%, 3), equipment (8%, 3), and intravenous access and anesthesia awareness (3%, 1 each). Of the 36 anesthesia events reported, 5 (14%) were identified as being catastrophic, 10 (28%) major, 12 (34%) moderate, and 9 (26%) minor. The majority of root causes identified a need for improved standardization of processes. This analysis points to the need for systemwide implementation of human factors engineering-based approaches to work toward further eliminating anesthesia-related adverse events. Such actions include standardization of processes, forcing functions, separating storage of look-alike sound-alike medications, limiting stock of high-risk medication strengths, bar coding medications, use of cognitive aids such as checklists, and high-fidelity simulation.

October 2016 at a glance: treatment of heart failure.

October 2016 at a glance: treatment of heart failure.

High recurrence of device‐related adverse events following transvenous lead extraction procedure in patients with cardiac resynchronization devices

Little is known about the clinical outcome and recurring system-related adverse events (SAE) in cardiac resynchronization therapy (CRT) patients after transvenous lead extraction (TLE). From January 2009 to June 2014, 256 consecutive CRT patients (mean age 68.3 ± 11.6 years, 216 male, 88% in New York Heart Association class II-IV, ejection fraction 35.1 ± 10.8%) were treated at four European institutions with TLE. Indications for TLE included systemic (18%) or local (45%) infection, system malfunction (34%), or other (3%). Demographic, clinical, TLE procedural, and follow-up data were collected retrospectively. Adverse events (AE) were considered as death from any cause, cardiovascular hospitalization, and SAE (SAE included pocket and/or systemic infection, lead malfunction, or pocket haematoma requiring revision). Complete removal was achieved for 609 out of 614 leads (99.2%) by using either manual traction (28%), mechanical (52%) or laser (20%) sheaths. Over a median follow-up of 21 (interquartile range 12-29) months, cumulative incidences of any AE and SAE were 53.9% and 21.1%, respectively. Recurring system malfunction occurred in 23 patients (9.0%), infection in 16 patients (6.2%), and pocket haematoma requiring revision in 15 patients (5.9%). Oral anticoagulation therapy was an independent predictor of both any AE [hazard ratio (HR) 2.09, 95% confidence interval (CI) 1.35-3.22, P = 0.001] and SAE (HR 2.38, 95% CI 1.21-4.68, P = 0.012) after TLE. Even though TLE is safe and effective to treat CRT patients, a high burden of recurring SAE after TLE was observed at mid-term follow-up. Careful evaluation of both patient characteristics as well as implantation strategy is suggested when indicating TLE in a CRT patient, particularly in patients receiving oral anticoagulation therapy.

P-400: The Multidimensional Prognostic Index (MPI) predicts central nervous system-related adverse drug events (CNS-ADRs) in older patients admitted to hospital: a prospective 3-year observational study

P-400: The Multidimensional Prognostic Index (MPI) predicts central nervous system-related adverse drug events (CNS-ADRs) in older patients admitted to hospital: a prospective 3-year observational study