Specific Adverse Events Research Articles

Analyze the Influencing Factors and Predictability of Metabolic Syndrome in Schizophrenic Patients Treated with Olanzapine through Decision Tree Model

Abstract: Olanzapine is a typical antipsychotic that has demonstrated efficacy for the treatment of schizophrenia, but the patients treated with olanzapine usually appear it’s specific adverse events such as metabolism. It shows some factors that may affect metabolism such as age, BMI, high-dose antipsychotics, etc. Up to now the main predictors for metabolism in a patient with schizophrenia have not been comprehensively evaluated. Subjects and research methods: In this prospective cohort study, a total of 202 inpatients with schizophrenia at Vietnamese National Psychiatric Hospital No1 were included. The univariate regression and decision tree model were applied to find out the statistically significant factors. Results: The factors influencing metabolism were: baseline waist, baseline triglyceride, baseline HDL, age, baseline BMI, baseline metabolism, cholesterol ≥6.2 history, and schizophrenia duration. The final decision tree model included 3 important nodes: baseline waist < 89 cm, baseline triglyceride <3.1 mmol/l, age <36. The predictive accuracy and other parameters were good to be able to apply for predictive purposes: accuracy 0.88, precision 0.90, recall 0.69, f1-score 0.78. Conclusion: The final model was good to predict no metabolism (0 code). In contrast, it is necessary to verify the metabolism status and have appropriate routine monitoring.
 Keywords: Metabolism, schizophrenia, olanzapine, predictive model, decision tree model.

Compact Development Policy and Urban Resilience: A Critical Review

Sustainable development and urban resilience are dominant urban planning paradigms that have become buzzwords in urban planning and policy domains over the past 2–3 decades. While these two paradigms have been analyzed and scrutinized in different studies, the interconnection between them in policy realms is understudied. Compact development policy is expected to contribute to a variety of sustainability goals. However, these goals’ alignment with the principles and goals of urban resilience is under question. This research tries to shed some light on this issue. A critical review method is employed to understand how compactness as a sustainable urban development policy relates to different principles and dimensions of urban resilience. First, the conceptual and theoretical relationship between urban resilience and compact city is established. Next, the resulting framework is used to critically analyze 124 articles to understand how the compact city policy relates to urban resilience from different dimensions and principles. Densification and intensification, mixed land use and diversity, and spatial connectivity and public transportation are identified as principles of the compact city. Finally, the interconnection between compact city policy and urban resilience dimensions and principles is explored and assessed through examining the selected literature. The results of the review show some alignments between compact city policy outcomes and urban resilience. However, the level of alignment may vary depending on the context, scale, or dimension. In other words, while compact city in one scale/dimension can increase urban resilience to a specific adverse event or stressor, it might increase vulnerability to others in another scale/dimension. From the policy perspective, compact development policy and urban resilience principles should clearly be defined a priori to reach favorable outcomes.

Effect of dapagliflozin on the prognosis of patients with acute myocardial infarction undergoing percutaneous coronary intervention

Background and aimsThe effect of dapagliflozin (DAPA) on the prognosis of patients with acute myocardial infarction (AMI) is unclear. The present study was conducted to evaluate the association between DAPA administration and adverse events in patients with AMI undergoing percutaneous coronary intervention (PCI).MethodsThis single-center retrospective analysis study included a total of 786 patients with AMI from January 2019 to August 2021 who were or were not administered DAPA at discharge. The primary endpoint was the composite of major adverse cardiovascular events (MACE), including overall deaths, heart failure, nonfatal MI, nonfatal stroke, and unplanned repeat revascularization (URR). Differences in the triglyceride glucose (TyG) index and the atherogenic index of plasma (AIP) both during hospitalization and 12 months after discharge (if achievable) were also compared.ResultsDuring a median follow-up of 23 months, 130 patients had MACE (118 in the DAPA-free group and 12 in the DAPA group). Kaplan–Meier survival analyses revealed that the cumulative incidence of MACE (log-rank test, p = 0.009), heart failure (p = 0.003), nonfatal MI (p = 0.005), and URR (p = 0.031) was higher in the DAPA-free group. In addition, the multivariate Cox analysis showed that DAPA was significantly associated with the reduced risk of MACE (hazard ratio = 0.170, 95% confidence interval = 0.078–0.373, p < 0.001). Considering each specific adverse event, the DAPA-free group was associated with heart failure, nonfatal MI, and URR in multivariate Cox regression analyses. Stratification analyses suggested that DAPA has a strong protective effect in patients with AMI of advanced age with concomitant diabetes or those who are not on angiotensin receptor enkephalinase inhibitors. Furthermore, the TyG index and AIP of the patients 12 months after DAPA administration at discharge were significantly lower than those during hospitalization.ConclusionsDAPA is an independent protective factor against MACE and may provide incremental prognostic information in patients with AMI undergoing PCI.

Overcoming the cardiac toxicities of cancer therapy immune checkpoint inhibitors.

Immune checkpoint inhibitors (ICIs) have led recent advances in the field of cancer immunotherapy improving overall survival in multiple malignancies with abysmal prognoses prior to their introduction. The remarkable efficacy of ICIs is however limited by their potential for systemic and organ specific immune-related adverse events (irAEs), most of which present with mild to moderate symptoms that can resolve spontaneously, with discontinuation of therapy or glucocorticoid therapy. Cardiac irAEs however are potentially fatal. The understanding of autoimmune cardiotoxicity remains limited due to its rareness. In this paper, we provide an updated review of the literature on the pathologic mechanisms, diagnosis, and management of autoimmune cardiotoxicity resulting from ICIs and their combinations and provide perspective on potential strategies and ongoing research developments to prevent and mitigate their occurrence.

Matching-adjusted indirect comparison of axi-cel and liso-cel in relapsed or refractory large B-cell lymphoma

In the absence of a randomized head-to-head trial, an unanchored matching-adjusted indirect comparison was performed to estimate the relative treatment effects of axicabtagene ciloleucel (axi-cel; ZUMA-1) versus lisocabtagene maraleucel (liso-cel; TRANSCEND-NHL-001) for treatment of relapsed/refractory (R/R) large B-cell lymphoma (LBCL) after at least two lines of therapy. After matching, axi-cel and liso-cel had comparable objective response rates and duration. Compared to liso-cel, axi-cel was associated with improvements in overall survival (hazard ratio [HR]: 0.53 [95% CI: 0.34–0.82]) and progression-free survival (HR: 0.61 [95% CI: 0.40–0.92]). Axi-cel was associated with a higher rate of grade ≥3 cytokine release syndrome (odds ratio [OR]: 3.64 [95% CI: 1.04–12.76]) and neurological events (OR: 3.45 [95% CI: 1.65–7.19]), with smaller differences estimated in scenario analyses including ZUMA-1 safety management cohorts. Results suggest axi-cel improved survival compared to liso-cel but with increased odds of specific adverse events.

COVID-19 Vaccination in Autoimmune Diseases (COVAD) study: Vaccine safety in idiopathic inflammatory myopathies.

Introduction/AimsIn this study we investigated COVID‐19 vaccination–related adverse events (ADEs) 7 days postvaccination in patients with idiopathic inflammatory myopathies (IIMs) and other systemic autoimmune and inflammatory disorders (SAIDs).MethodsSeven‐day vaccine ADEs were collected in an international patient self‐reported e‐survey. Descriptive statistics were obtained and multivariable regression was performed.ResultsTen thousand nine hundred respondents were analyzed (1227 IIM cases, 4640 SAID cases, and 5033 healthy controls [HCs]; median age, 42 [interquartile range, 30‐455] years; 74% female; 45% Caucasian; 69% completely vaccinated). Major ADEs were reported by 76.3% of the IIM patients and 4.6% reported major ADEs. Patients with active IIMs reported more frequent major (odds ratio [OR], 2.7; interquartile range [IQR], 1.04‐7.3) and minor (OR, 1.5; IQR, 1.1‐2.2) ADEs than patients with inactive IIMs. Rashes were more frequent in IIMs (OR, 2.3; IQR, 1.2‐4.2) than HCs. ADEs were not impacted by steroid dose, although hydroxychloroquine and intravenous/subcutaneous immunoglobulins were associated with a higher risk of minor ADEs (OR, 1.9; IQR, 1.1‐3.3; and OR, 2.2; IQR, 1.1‐4.3, respectively). Overall, ADEs were less frequent in inclusion‐body myositis (IBM) and BNT162b2 (Pfizer) vaccine recipients.DiscussionSeven‐day postvaccination ADEs were comparable in patients with IIMs, SAIDs, and HCs, except for a higher risk of rash in IIMs. Patients with dermatomyositis with active disease may be at higher risk, and IBM patients may be at lower risk of specific ADEs. Overall, the benefit of preventing severe COVID‐19 through vaccination likely outweighs the risk of vaccine‐related ADEs. Our results may inform future guidelines regarding COVID‐19 vaccination in patients with SAIDs, specifically in those with IIMs. Studies to evaluate long‐term outcomes and disease flares are needed to shed more light on developing future COVID‐19 vaccination guidelines.

Relation of Sociodemographic Factors With Primary Cause of Hospitalization Among Patients With Left Ventricular Assist Devices (from the National Inpatient Sample 2012 to 2017)

Left ventricular assist devices (LVADs) are an established intervention for end-stage heart failure (HF). Rehospitalization for serious complications remains common during the continuous-flow LVAD era. Whether sociodemographic factors are associated with differences in the frequency of severe complications leading to hospitalization remains unclear. Using data from the National Inpatient Sample, we identified all hospitalizations from 2012 to 2017 of adults aged ≥18 years with previous LVAD placement. We categorized the primary cause of hospitalizations into key adverse diagnoses, including bleeding, HF, arrhythmias, LVAD complications, stroke, and a composite of device-related infection or sepsis. We assessed the association of sociodemographic markers with primary diagnoses using modified Poisson regression. We identified 62,630 hospitalizations during the study period (41% aged ≥65, 77% men, 26% Black, 5% Hispanic). Bleeding (18%), infections (15%), and HF (15%) were the most common primary diagnoses. In the multivariable analyses, gastrointestinal bleeding was more likely among older adults (relative risk [RR] 95% confidence interval [CI] 4.69 [3.57 to 6.16]; age ≥65 vs 18 to 44 years), among Black than White patients (RR 95% CI 1.17 [1.04 to 1.32]), and less likely for the highest income quartile than the lowest (RR 95% CI 0.79 [0.69 to 0.91]). Device-related infection/sepsis was also less likely for patients with higher income (RR 95% CI 0.80 [0.67 to 0.96]). Ventricular arrhythmias were less frequent diagnoses for women than men (RR 95% CI 0.59 [0.46 to 0.75]). LVADs complications were less likely in older adults than younger adults (RR 95% CI 0.70 [0.50 to 0.98]). In conclusion, after LVAD implantation, the frequency in which specific adverse events are the primary cause of rehospitalization varies significantly by sociodemographic factors. Further study is needed to determine if there are opportunities for targeted preventive measures based on sociodemographic markers.

Local Estrogen Therapy for Pelvic Organ Prolapse in Postmenopausal Women: A Systematic Review and Meta-Analysis.

Background:The prevalence of pelvic organ prolapse (POP) is expected to increase in the next few decades, imposing a substantial medical burden. The effect of local estrogen therapy (LET) on POP in postmenopausal women is still controversial; therefore, we aimed to provide reliable evidence to address this issue from the perspective of vaginal health and quality of life (QoL).Methods:We searched in the PubMed, the Web of Science, Embase and the Cochrane Library databases for eligible RCTs from beginning to Apr 2021. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed in our study.Results:Seven RCTs(n=570) were included. No significant improvement of the epithelial thickness (SMD=1.38, 95%CI −0.54 to 3.31, P=0.16) or vaginal pH (SMD=−0.98, 95%CI −2.65 to 0.69, P=0.25) after LET compared with the control. A slight increase was observed in the VMI (MD=16.58, 95%CI 1.14 to 32.02, P=0.04). Regarding QoL, no significant differences between the estrogen group and the control group in PFIQ-7 (6m: MD=3.60, 95%CI −3.13 to 10.33, P=0.29; 12m: MD=3.53, 95%CI −3.35 to 10.41, P=0.31), PISQ-12(6m: MD=0.62, 95%CI −0.73 to 1.98, P=0.37; 12m: MD=0.36, 95%CI −1.06 to 1.77, P=0.62), or PGI-I (6m: RR=0.99, 95%CI 0.92 to 1.07, P=0.88; 12m: RR=1.01, 95%CI 0.95 to 1.07, P=0.72) score. Moreover, no more specific adverse events (AEs) (RR=1.11, 95%CI 0.84 to 1.48, P=0.46) were observed in the interventional group.Conclusion:Not find LET caused either a significant improvement in vaginal health and QoL or more AEs.

Left atrial appendage occlusion should be offered only to select atrial fibrillation patients.

Left atrial appendage occlusion should be offered only to select atrial fibrillation patients.

The Timing of Acute and Late Complications Following Mastectomy and Implant-based Reconstruction.

Implant-based breast reconstruction is a common plastic surgery procedure with well-documented clinical outcomes. Despite this, the natural history and timing of key complication endpoints are not well described. The goal of this study is to determine when patients are most likely to experience specific adverse events after implant-based reconstruction. Retrospective consecutive series of patients who received mastectomy and implant-based reconstruction over a 6-year period were included. Complications and unfavorable outcomes including hematoma, seroma, wound infection, skin flap necrosis, capsular contracture, implant rippling, and implant loss were identified. A time-to-event analysis was performed and Cox regression models identified patient and treatment characteristics associated with each outcome. Of 1473 patients and 2434 total reconstructed breasts, 785 complications/unfavorable outcomes were identified. The 12-month cumulative incidence of hematoma was 1.4%, seroma: 4.3%, infection: 3.2%, skin flap necrosis: 3.9%, capsular contracture: 5.7%, implant rippling: 7.1%, and implant loss: 3.9%. In the analysis, 332/785 (42.3%) complications occurred within 60 days of surgery; 94% of hematomas, 85% of skin necrosis events, and 75% of seromas occurred during this period. Half of all infections and implant losses also occurred within 60 days. Of the remaining complications, 94% of capsular contractures and 93% of implant rippling occurred >60 days from surgery. Complications following mastectomy and implant-based reconstruction exhibit a discrete temporal distribution. These data represent the first comprehensive study of the timing of adverse events following implant-based reconstruction. These findings are immediately useful to guide postoperative care, follow-up, and clinical trial design.

Serious adverse event rates and reoperation after arthroscopic shoulder surgery: population based cohort study

ObjectiveTo provide clinicians and patients with accurate risk estimates of serious adverse events after common elective shoulder arthroscopic procedures, including reoperation within one year.DesignPopulation based cohort study.SettingHospital Episode Statistics for...

The short term safety of COVID-19 vaccines in Australia: AusVaxSafety active surveillance, February - August 2021.

Objective:To assess the short term safety of the COVID‐19 vaccines Comirnaty (Pfizer–BioNTech BNT162b2) and Vaxzevria (AstraZeneca ChAdOx1) in Australia.Design:Prospective observational cohort study; online surveys by AusVaxSafety, a national active vaccine safety surveillance system, three and eight days after vaccination.Setting, participants:People aged 16 years or more who received COVID‐19 vaccines at sentinel vaccination hubs, general practices, or Aboriginal Community Controlled Health Organisation clinics, 22 February – 30 August 2021.Main outcome measures:Primary outcome: proportion of respondents who reported any adverse event following immunisation (AEFI) 0–3 days after vaccination. Secondary outcomes: proportions of respondents who reported specific adverse events or medical review for AEFI within seven days of vaccination; impact on usual daily activities; recovery.Results:4 851 480 people received COVID‐19 vaccines at participating sentinel sites during the study period (25% of all COVID‐19 vaccine doses administered in Australia to 30 August 2021). 3 035 983 people responded to both surveys (response rate, 62.6%); 35.9% of respondents reported one or more AEFI 0–3 days after Comirnaty dose 1, 54.7% after Comirnaty dose 2, 52.8% after Vaxzevria dose 1, and 22.0% after Vaxzevria dose 2. Local pain, fatigue, headache, and myalgia were the most frequently reported symptoms. After adjusting for demographic characteristics, vaccination site type, jurisdiction, and self‐reported medical conditions, the odds of reporting any AEFI were higher for women than men (range of adjusted odd ratios [aORs], by vaccine and dose, 1.53–1.84), for people with a history of anaphylaxis (aOR range, 1.28–1.45), and for people reporting certain underlying conditions, including obesity (aOR range, 1.15–1.75), immunodeficiency (aOR range, 1.04–2.24), or chronic inflammatory disease (aOR range, 1.05–1.75). 0.9% of respondents sought medical advice in the three days following vaccination, most frequently after Comirnaty dose 2 (1.4%) and Vaxzevria dose 1 (1.2%).Conclusion:AusVaxSafety active surveillance affirms the short term safety profile of Comirnaty and Vaxzevria vaccines in a large population sample during the first six months of the Australian COVID‐19 vaccination program.

The emerging field of checkpoint inhibitors

Immunotherapy as a new method allows effective control of the tumor growth. At the same time, the continuous treatment and the novel mechanism of action leads to the possible appearance of the specific immune-mediated adverse events, some of which can be fatal. Functional tests, analysis of the risk factors for the development of the complications, the search for the predictive markers will improve the effectiveness of immunotherapy. The perspective is the development of the prophylaxis based on in-depth understanding of the immune tolerance disorders

Efficacy of Fecal Microbiota Transplantation in the Treatment of Active Ulcerative Colitis: A Systematic Review and Meta-Analysis of Double-Blind Randomized Controlled Trials.

Fecal microbiota transplantation (FMT) has been investigated as a treatment option for patients with inflammatory bowel disease with controversial results.We sought to perform a systematic review and meta-analysis to evaluate the benefit of FMT in patients with ulcerative colitis. Double-blind randomized controlled trials (RCTs) including adult patients with active ulcerative colitis who received either FMT or placebo were eligible for inclusion. Outcomes of interest included the rate of combined clinical and endoscopic remission, endoscopic remission or response, clinical remission or response, and specific adverse events. The results were pooled together using Reviewer Manager 5.4 software. Publication bias was assessed using the Egger's test. Six RCTs involving 324 patients were included. Our findings demonstrate that compared with placebo, FMT has significant benefit in inducing combined clinical and endoscopic remission (odds ratio, 4.11; 95% confidence interval, 2.19-7.72; P < .0001). Subgroup analyses of influencing factors showed no differences between pooled or single stool donors (P = .71), fresh or frozen FMT (P = .35), and different routes or frequencies of delivery (P = .80 and .48, respectively). Pre-FMT antibiotics, bowel lavage, concomitant biologic therapy, and topical rectal therapy did not affect combined remission rates (P values of .47, .38, .28, and .40, respectively). Clinical remission or response and endoscopic remission or response were significantly higher in patients who received FMT compared with placebo (P < .05) without any differences in serious or specific adverse events. FMT demonstrated a clinical and endoscopic benefit in the short-term treatment of active ulcerative colitis, with a comparable safety profile to placebo. Future RCTs are required to standardize study protocols and examine data on maintenance therapy.

Hidradenitis Suppurativa Leads to Increased Risk of Wound-Related Complications following Total Joint Arthroplasty

BackgroundHidradenitis suppurativa (HS) is a skin disorder characterized by inflammatory skin lesions that are most commonly in the inguinal and axillary regions. These skin lesions are common sites of bacterial growth and are thus a potential risk factor for infection following procedures such as total hip arthroplasty (THA) or total knee arthroplasty (TKA). Material and methodsAdult patients undergoing THA or TKA for degenerative etiologies were identified from PearlDiver datasets. For THA and TKA, HS patients were matched 1:4 with non-HS patients based on age, sex, and Elixhauser Comorbidity Index. The incidence of 90-day any, severe, minor, and specific adverse events was compiled and compared with multivariate analyses. Five-year revision rates were plotted on Kaplan-Meier survival curves and compared with log-rank tests. ResultsFor THA, 331,627 patients were identified, of which HS was noted for 481 patients (0.15%). For TKA, 274,161 patients were identified, of which HS was noted for 290 patients (0.11%). Following THA, HS patients had increased odds of wound dehiscence (odds ratio = 2.55, P = .002). Following TKA, HS patients had increased odds of surgical site infection (odds ratio = 1.95, P = .006). All other 90-day adverse events were not significantly different. There was no significant difference in 5-year implant survival in either procedure. ConclusionsHS is a rare but identified comorbidity for those undergoing THA or TKA. Although most 90-day adverse events and 5-year implant survival were similar to those without this condition, specific wound-related issues were elevated by roughly twofold. These findings could help inform patients and surgeons.

PB2270: CLEARANCE OF PERSISTENT SARS-COV2 INFECTION WITH ANTIBODY CONTAINING PLASMA IN LEUKEMIA AND LYMPHOMA PATIENTS

Background: Patients with hematological malignancies or other reasons for inadequate immune response are at high risk for poor outcome of COVID-19 disease. In addition, a significant fraction of patients unable to mount an antibody response fail to clear SARS-Cov2 virus putting them at risk for clinical deterioration. Also, persistent COVID-19 infection impedes further treatment of the underlying disease. So far, no treatment has been established for persistent COVID-19 infection in immunocompromised patients. Aims: Here, we treated eight immunocompromised patients with active SARS-COV2 infection with plasma from convalescent or/and vaccinated donors in a case series of individual treatments. Methods: Patients were eligible for treatment if active SARS-Cov2 infection was confirmed at least 14 days after initial detection. In two out of eight patients sequencing results confirmed the omicron variant. Therapies before plasma treatment included antivirals and monoclonal antibodies. Underlying diseases were B-ALL (n=3; including one patient after allogeneic stem cell transplantation), multiple myeloma (n=2), lymphoma (n=2) and immunosuppression after kidney transplantation (n=1). Median age was 48 years (range 7 – 78). Antibody containing plasma was obtained from healthy donors either after confirmed SARS-COV2 infection or after mRNA vaccination. Overall, 22 treatment cycles were administered in 8 patients (median 2, range 1 to 7). For each patient the available plasma with the highest titers of neutralizing antibodies and matching blood type was administered. Results: Neutralizing antibody titers in plasma were median 1:320 (range 1:40 to 1:2560). Titers of neutralizing antibodies in convalescent plasma (n=10 treatments; median titer: 1:80) were lower than in vaccinated donor plasma (median 1:320; p=0.058, Mann-Whitney U test) (n=12 treatments). Median Ct-values of viral load before treatment were 20.5 (range 14.9 to 37.3). After treatment (median 5 days), the Ct-values changed to median 26.9 (range 19.5 to non-detectable). The median fold decrease in viral load was estimated to be 127-fold with a range from 0.8 to >2x104 (p<10-4, paired t-test). Similar reductions in viral load were achieved after administration of either plasma from convalescent (median 109) or vaccinated donors. SARS-COV2 virus was cleared in 7 of 8 (87.5%) patients with ongoing treatment in one patient. No specific adverse events were observed. Figure 1: Fold reduction in viral load after a single treatment with anti-SARS-COV2 containing plasma. Image:Summary/Conclusion: Plasma with high titers of neutralizing SARS-COV2 antibodies can clear persistent infection in patients with hematological malignancies and immunocompromised patients. Plasma obtained either from convalescent patients or vaccinated donors might constitute an effective and inexpensive treatment in this situation.

Therapy of genomic unstable solid tumours (WHO grade 3/4）in clinical stage III/IV using individualised neoantigen tumour peptides-INP trial (individualised neoantigen tumour peptides immunotherapy): study protocol for an open-label, non-randomised, prospective, single-arm trial

IntroductionNeoantigens derived from tumour somatic mutations are recognised as ideal vaccine targets. Tumour neoantigens have been studied in a wide range of tumours. Most of research on neoantigens has focused...

P-124 Patient preferences for unresectable hepatocellular carcinoma (HCC) treatments: Balancing overall survival and quality of life

Atezolizumab plus bevacizumab has become the new standard-of-care treatment option for unresectable HCC, replacing oral tyrosine kinase inhibitors (e.g., sorafenib, lenvatinib). As these treatments have varying benefit-risk profiles and routes of administration, we aimed to quantify patients’ benefit-risk preferences for attributes associated with various first-line systemic treatments for unresectable HCC and estimate the minimum acceptable additional months of overall survival (OS) patients would require in exchange for specific treatment-related adverse events. A cross-sectional, web-based discrete-choice experiment (DCE) survey was developed. The survey development was informed by qualitative interviews with patients, published literature and treatment guidelines, expert clinical opinion, and cognitive debriefing interviews. Respondents answered nine DCE questions. Each question offered a choice between two hypothetical treatment profiles created by an experimental design and defined by six attributes with varying levels: OS, number of months to maintain daily function, severity of palmar-plantar syndrome, severity of hypertension, risk of bleeding in the digestive tract, and mode and frequency of administration. Data were analyzed using a random-parameters logit model, and results were used to calculate the minimum number of additional months of OS required to offset worse levels of adverse events. Between August 30, 2021, and October 14, 2021, patients with self-reported unresectable HCC in the United States (N = 200) completed the survey. Mean age was 59 years, 25.0% were White, 41.5% had at least a 4-year college degree, 33.5% reported less than $50,000 annual income, 93.0% were diagnosed less than 5 years ago, 23.0% reported needing help taking care of themselves, 85.5% were currently receiving treatment for their HCC, 51.5% of those currently receiving medicines by intravenous infusion, and 71.3% by oral pills. On average, patients regarded an additional 10 months of maintaining daily function without decline to be as important or more important than an additional 10 months of OS, indicating a willingness to trade off months of maintaining daily function for months of OS. Among the adverse events, respondents placed the most importance on avoiding moderate-to-severe palmar-plantar syndrome and hypertension, requiring an average of more than 10 additional months of OS to offset the increased burden of these two adverse events. Respondents placed the least importance on a 5-percentage-point reduction in the risk of bleeding in the digestive tract (from 2% to 7%), requiring only 1.6 (confidence interval, 0.04-3.17) additional months of OS to offset this change. Additionally, more convenient dosing (e.g., daily oral pill vs. IV infusion every 3 weeks) was less important to respondents than OS, maintenance of daily function, and avoiding severe instances of palmar-plantar syndrome or hypertension. Patients with unresectable HCC prioritized avoiding side effects that would severely impact their quality of life during treatment much more compared with mode and frequency of treatment administration and digestive tract bleeding risk. For patients with unresectable HCC, the ability to maintain quality of life and conduct daily activities is as important or more important than a treatment’s survival benefit.

The efficacy and safety of anti–PD-1 antibody toripalimab combined with surufatinib in neoadjuvant treatment of locally advanced thyroid cancer: A phase II study.

6084 Background: Surgery is the primary treatment for locally advanced thyroid cancer. However, some locally advanced patients are not candidates for R0/1 resection. There is limited evidence of neoadjuvant treatment in locally advanced thyroid cancer. Surufatinib targets multiple kinases (VEGFR1-3, FGFR1 and CSF-1R) involved in tumor angiogenesis and tumor immune evasion. It is efficient, tolerable and safe for patients with radioiodine-refractory differentiated thyroid cancer to receive surufatinib. In addition, surufatinib plus toripalimab (an anti-PD-1 antibody) showed encouraging antitumor activity and an acceptable safety profile in advanced solid tumors. This study aimed to evaluate the efficacy and safety of surufatinib plus toripalimab in locally advanced thyroid cancer in the neoadjuvant setting. Methods: In this single-arm phase II study, patients with pathologically confirmed diagnosis of unresectable or borderline resectable differentiated thyroid cancer were eligible and received a combination of 250 mg surufatinib (oral, qd) with 240 mg toripalimab (IV, q3w). Treatment was continued until satisfied for curative surgery, disease progression, withdrawal of consent, unacceptable toxicity or investigator decision. Primary endpoint was objective response rate (ORR) by RECIST 1.1. Secondary endpoints included R0/1 resection rate, disease control rate (DCR), time to remission (TTR), adverse events (AEs), etc. Results: This study is ongoing. 10/10 patients were enrolled. 6 patients received ≥4 cycles of surufatinib plus toripalimab treatment and were also evaluated for efficacy. The ORR was 66.7% with 4 partial response (PR) and 2 stable disease (SD). 4 PR and 1 SD patients received R0 resections after neoadjuvant treatment. The safety was consistent with previously reported. No grade ≥3 AEs were observed. Specific AEs data are still being counted. Conclusions: Surufatinib in combination with toripalimab as neoadjuvant therapy for locally advanced thyroid cancer was feasible and majority of patients achieved R0 resection. AEs were mainly grade 1-2, and this combination was well-tolerated. The combination of these two agents should be further investigated for neoadjuvant treatment of locally advanced thyroid cancer based on good results. Clinical trial information: NCT04524884.

Clinical Utility of Medication-Based Risk Scores to Reduce Polypharmacy and Potentially Avoidable Healthcare Utilization.

The management of multiple chronic health conditions often requires patients to be exposed to polypharmacy to improve their health and enhance their quality of life. However, exposure to polypharmacy has been associated with an increased risk for adverse effects, drug-drug interactions, inappropriate prescribing, medication nonadherence, increased healthcare utilization such as emergency department visits and hospitalizations, and costs. Medication-based risk scores have been utilized to identify patients who may benefit from deprescribing interventions and reduce rates of inappropriate prescribing. These risk scores may also be utilized to prompt targeted discussions between patients and providers regarding medications or medication classes contributing to an individual’s risk for harm, eventually leading to the deprescribing of the offending medication(s). This opinion will describe existing medication-based risk scores in the literature, their utility in identifying patients at risk for specific adverse events, and how they may be incorporated in healthcare settings to reduce rates of potentially inappropriate polypharmacy and avoidable healthcare utilization and costs.