Impact of the absence of dental support on cancer patients during the COVID-19 pandemic

Purpose With the suspension of routine services due to the coronavirus disease-2019 (COVID-19) pandemic, a significant number of the population has been presenting acute oral alterations without proper treatment. Through telecontact, this study aimed to identify individuals in treatment and had been treated for cancer who had their clinical dental care interrupted by the COVID-19 pandemic. Methods Individuals with oncologic diseases were selected from a telephone list of a clinical research center specializing in the care of cancer patients. We included those who answered an online questionnaire about their general health status and oral problems when they were unable to access dental care during the pandemic. Statistical analysis was performed using Fisher and Chi-square tests. The significance level was set at 5% (p<0.05). Results Of the 280 patients recruited, 104 answered the questionnaire. There were 75 (72.1%) were women, of which 22 (36.7%) were under antineoplastic treatment, and 30 (68.2%) had already been treated; 29 (27.9%) were men, of which 15 (25.0%) were under antineoplastic treatment and 14 (31.8%) had already been treated. Of the universal sample, 64 (61.5%) had no complaints regarding their general health, and 74 (71.1%) had no difficulties in their daily activities due to teeth/mouth problems. However, the rates of oral problems were not statistically significant (p=NS). Conclusion In dentistry, telephone support and digital tools are useful and necessary instruments for the follow-up of cancer patients during the pandemic.

982. Effect of Hepatic Impairment on the Safety and Pharmacokinetics of Rezafungin

Background Rezafungin (RZF) is a novel echinocandin antifungal being developed for treatment of candidemia and invasive candidiasis, and for prevention of invasive fungal diseases among immunosuppressed patients. In the Phase 2 and Phase 3 treatment trials of rezafungin compared with caspofungin (STRIVE [NCT02734862] and ReSTORE [NCT03667690], respectively), patients with severe hepatic impairment (HI) were not included due to lack of caspofungin data in this population. Rezafungin was previously evaluated in patients with moderate hepatic impairment. Here we report an open-label, single-dose study on rezafungin in patients with HI (Child-Pugh class C). Methods To investigate the safety, tolerability, and pharmacokinetics (PK) of RZF in subjects with HI and healthy subjects (HS), 8 subjects with HI and 8 HS matched for age, sex, and body mass index (BMI) were enrolled and received a single 400-mg intravenous 1-hour infusion of RZF. Plasma PK sampling was performed at various time points through 336 hours postdose. RZF PK parameters were derived using non-compartmental analysis. Safety was assessed throughout the study. Results The majority of the HI subjects were White (87.5%) and male (75%) while equal distribution between White and Black or African American was observed among HS (50%) and 75% were male. The mean age of HI subjects was 58 years (range, 41–68 years) and 56.6 years (range, 50–61 years) for the HS. Mean BMI was 29.7 kg/m2 (range, 24.5–34.3 kg/m2) for HI subjects and 29.7 kg/m2 (range, 25.4–34.2 kg/m2) for the HS. RZF exposure (Cmax and AUC) in subjects with HI was ~30% lower than that in HS (Table 1), while half-life was generally similar (HI: 121 h, HS:124 h; Figure 1). Three HI subjects had one adverse event (AE) each (bronchitis, worsening hepatic encephalopathy, hyponatremia), all moderate in severity; one HS had 1 AE of infusion site infiltration mild in severity. No AEs were considered related to RZF, and all were resolved or resolving by the end of the study. Table 1. Plasma Rezafungin PK Parameter Estimates in Subjects with Severe Hepatic Impairment or Normal Hepatic Function After a Single 400 mg IV Infusion of Rezafungin Figure 1. Mean (+SD) Plasma Rezafungin Concentration-Time Profiles in Subjects with Severe Hepatic Impairment or Normal Hepatic Function After a Single 400-mg IV Infusion of Rezafungin (Semi-Logarithmic Scale) Conclusion RZF was well tolerated in HI subjects and showed modestly reduced exposure that was within the range observed in matched HS. These findings support no RZF dose adjustment in subjects with severe hepatic impairment. Disclosures Voon Ong, PhD, Cidara Therapeutics (Employee, Shareholder) Taylor Sandison, MD, MPH, Cidara Therapeutics (Employee, Shareholder) Rebeca M. Melara, M.S., Altasciences (contract research organization) (Employee) Thomas C. Marbury, MD, Orlando Clinical Research Center (Employee, Other Financial or Material Support, Equity owner of Orlando Clinical Research Center) Alena Jandourek, MD, Cidara therapeutics (Consultant) Shawn Flanagan, PhD, Cidara Therapeutics (Employee, Shareholder)

Pituitary Imaging Abnormalities and Related Endocrine Disorders in Erdheim–Chester Disease

Purpose: We examined abnormal pituitary imaging (API) and associated endocrine dysfunction in subjects with ECD. Methods: A cross-sectional descriptive examination of a natural history cohort study diagnosed with ECD was conducted at a clinical research center. Subjects underwent baseline endocrine tests of anterior and posterior pituitary function and dedicated pituitary gland MRI scans. We determined the frequency of various pituitary imaging abnormalities in ECD and assessed its relationships with age, sex, body mass index (BMI), BRAF V600E status, high sensitivity C-reactive protein (hsCRP), erythrocyte sedimentation rate (ESR), pituitary hormone deficits and number, diabetes insipidus (DI), and panhypopituitarism. Results: Our cohort included 61 subjects with ECD [age (SD): 54.3 (10.9) y, 46 males/15 females]. API was present in 47.5% (29/61) of ECD subjects. Loss of the posterior pituitary bright spot (36.1%) followed by thickened pituitary stalk (24.6%), abnormal enhancement (18.0%), and pituitary atrophy (14.8%) were the most common abnormalities. DI and panhypopituitarism were more frequent in subjects with API without differences in age, sex distribution, hsCRP, ESR, and BRAF V600E status compared to normal pituitary imaging. Conclusions: We noted a high burden of API and endocrinopathies in ECD. API was highly associated with the presence of panhypopituitarism and DI. Therefore, a thorough assessment of hypothalamic–pituitary integrity should be considered in subjects with ECD.

Research Ethics Consultation in Nursing Studies

Despite the importance and acceptance of research ethics consultation as an entity in many medical research areas, little is known about its status in nursing research. Focusing on inquiries from nurse researchers, we retrospectively analyzed records of integrated clinical research consultation, provided by members of the Clinical Research Center independently of the research ethics committee, at a Japanese university hospital during 2018–2019. Among various consultations in nursing studies ( n = 101), 43 were related to research ethics. The main issues in research ethics consultation were compatibility with guidelines ( n = 28; 65%) and application of ethics review ( n = 12; 28%). Future studies should investigate international settings and address the relevance of research ethics consultation to promote proper nursing studies.

The Value of NLR Combined SOFA in Assessing the Prognosis of Sepsis Patients

Background: In order to evaluate the risk factors and its assessment values in patients with sepsis, and to explore a method to improve the prognosis prediction efficiency of patients with sepsis.Methods: Patients with sepsis admitted to Emergency Medicine Clinical Research Center, Beijing Chao-Yang Hospital, Capital Medical University from January 2020 to December 2020 were enrolled, and they were divided into survival group and death group according to the prognosis at 28 days. Demographic data of patients and laboratory values at admission were collected. In terms of the first time data within 24h of patients admitted to hospital, the sequential organ failure assessment (SOFA) score and acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score were calculated, and compared the difference between the two groups, the logistic regression was used to analysis the risk factors for death within 28 days, as well as the calculated combined predictor of SOFA and neutrophil to lymphocyte ratio (NLR). Predicted values of various indicators for 28 days’ mortality in sepsis patients were analyzed by receiver operating characteristic (ROC) curve.Results: 302 patients in total were included in this study, including 238 patients in survival group and 64 patients in death group. The age (78.36±9.8 years old vs. 71.6±14.1 years old), procalcitonin (PCT) (1.00 ng/ml vs. 0.05 ng/ml), C-reactive protein (CRP) (93 mg/l vs 14 mg/l), lactic acid (Lac) (1.20 mmol/l vs. 2.20 mmol/l), NLR (11.7 vs. 6.20), SOFA score (8 vs. 4) and APACHE Ⅱ score(20.5 vs. 11.0) of death group were significantly higher than those of survival group (all P<0.001). Age (OR=1.046, 95%CI 1.020-1.074, P=0.001), PCT (OR=1.115, 95%CI 1.055-1.177, P<0.001), CRP (OR=1.016, 95%CI 1.011-1.021, P<0.001), Lac (OR=1.887, 95%CI 1.518-2.346, P<0.001), NLR (OR=1.038, 95%CI 1.016-1.060, P=0.001), APACHE Ⅱ score (OR=1.231, 95%CI 1.166-1.300, P<0.001), SOFA score (OR=1.499, 95%CI1.344-1.671, P<0.001), NLR combined SOFA (SOFA+NLR×0.085) (OR=1.492, 95%CI1.341-1.660, P<0.001) were risk factors of 28 days’ mortality in sepsis patients, and the area under the curve (AUC) of APACHE Ⅱ, NLR combined SOFA were 0.853 and 0.855, higher than Lac (0.767, P<0.05), CRP (0.746, P<0.05) and PCT (0.761, P<0.05), the AUC of APACHE Ⅱ was similar with NLR combine SOFA (P>0.05). The sensitivity and specificity of APACHE Ⅱ and NLR combined SOFA to predict the 28 days’ prognosis of sepsis patients were better than the other indicators. Conclusion: NLR combined SOFA was a risk factor for the death of sepsis patients, and its predictive efficacy was similar with that of APACHE Ⅱ score, which is superior to other predictive indexes.

The Study of Clinical Pharmacist Participating in the Pain Management of Outpatients with Cancer in A Prescription Period

Purpose. The management of outpatients with cancer painis very important for medication safety. Medical interviews by CP is conducive to pain management. Our objective was to describe the contribution of the clinical pharmacist (CP) to outpatients in pain-relief clinic.Methods. This was a prospective, case-by-case self-control study. One clinical pharmacist conducted three questionnaire surveys. The first happened in the clinic face to face, the second by telephone one week later after the visit and the third by telephone two weeks later. The interventions by CP and comprehensive pain assessment (scored by NRS, sleep, mood and general activities) were both recorded. Analgesic-related knowledge were delivered by CP and were measured both before and after therapy. 1.Department of Pharmacy ,National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China E-mail: [email protected] of Comprehensive Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China E-mail: [email protected]. 51 patients were enrolled. The top 5 interventions in the first telephone interview(second survey) was suggestions for treating adverse drug reactions(47%), correcting the wrong usage(35%), medication education(26%), recommendations for dosage adjustment(18%) and suggestions for further treatment(15%). While in the second telephone interview (third survey), the rankings were totally inverted. Comprehensive pain assessment showed better in the first interview and then worse in the second. Analgesic-related knowledge increased significantly after the education by CP.Conclusions. CP made a totally different interventions at the different stages of medication in the outpatients with cancer pain,which may be related to the pain control. Patients’ knowledge regarding analgesics significantly increased after education by CP.

Prestroke Glucose Control and Functional Outcome in Patients With Acute Large Vessel Occlusive Stroke and Diabetes After Thrombectomy

OBJECTIVE <p>To evaluate whether prestroke glucose control is associated with functional outcomes in patients with acute large vessel occlusive stroke and diabetes who underwent intraarterial thrombectomy (IAT). </p> <p>RESEARCH DESIGN AND METHODS</p> <p>From the Clinical Research Center for Stroke-Korea registry, we included patients with emergent large vessel occlusive stroke with diabetes who underwent IAT between January 2009 and March 2020. The association between the HbA1c level at admission and functional outcomes (modified Rankin Scale at 3 months after the index stroke) was assessed. </p> <p>RESULTS</p> <p>A total of 1351 patients were analyzed. Early neurological deterioration was more common in patients with higher levels of HbA1c at admission (<i>p</i> = 0.02 according to HbA1c quintiles, <i>p</i> = 0.003 according to an HbA1c cut-off value of 7.0) than in those with lower HbA1c levels. Higher HbA1c levels at admission were significantly associated with decreased odds of favorable functional outcomes at a threshold of 7.0%–7.1%. The association was consistently observed in subgroups divided according to age, sex, stroke subtype, occlusion site, degree of recanalization, thrombolysis modalities, time from symptom onset to groin puncture, and treatment period. </p> <p>CONCLUSIONS</p> <p>Prestroke glucose control with a target HbA1c of ≤ 7.0 may be beneficial for neurological recovery in patients with diabetes undergoing IAT for large vessel occlusive stroke, regardless of stroke subtype, bridging intravenous thrombolysis, occlusion site, degree of recanalization, and treatment period. </p>

Prestroke Glucose Control and Functional Outcome in Patients With Acute Large Vessel Occlusive Stroke and Diabetes After Thrombectomy

OBJECTIVE <p>To evaluate whether prestroke glucose control is associated with functional outcomes in patients with acute large vessel occlusive stroke and diabetes who underwent intraarterial thrombectomy (IAT). </p> <p>RESEARCH DESIGN AND METHODS</p> <p>From the Clinical Research Center for Stroke-Korea registry, we included patients with emergent large vessel occlusive stroke with diabetes who underwent IAT between January 2009 and March 2020. The association between the HbA1c level at admission and functional outcomes (modified Rankin Scale at 3 months after the index stroke) was assessed. </p> <p>RESULTS</p> <p>A total of 1351 patients were analyzed. Early neurological deterioration was more common in patients with higher levels of HbA1c at admission (<i>p</i> = 0.02 according to HbA1c quintiles, <i>p</i> = 0.003 according to an HbA1c cut-off value of 7.0) than in those with lower HbA1c levels. Higher HbA1c levels at admission were significantly associated with decreased odds of favorable functional outcomes at a threshold of 7.0%–7.1%. The association was consistently observed in subgroups divided according to age, sex, stroke subtype, occlusion site, degree of recanalization, thrombolysis modalities, time from symptom onset to groin puncture, and treatment period. </p> <p>CONCLUSIONS</p> <p>Prestroke glucose control with a target HbA1c of ≤ 7.0 may be beneficial for neurological recovery in patients with diabetes undergoing IAT for large vessel occlusive stroke, regardless of stroke subtype, bridging intravenous thrombolysis, occlusion site, degree of recanalization, and treatment period. </p>

Systemic inflammatory markers and psychophysical olfactory scores in coronavirus disease 2019 patients: is there any correlation?

Objective To analyse the correlations between olfactory psychophysical scores and the serum levels of D-dimer, C-reactive protein, ferritin, lactate dehydrogenase, procalcitonin and neutrophil-to-lymphocyte ratio in coronavirus disease 2019 patients. Methods Patients underwent psychophysical olfactory assessment with the Connecticut Chemosensory Clinical Research Center test, and determination of blood serum levels of the inflammatory markers D-dimer, C-reactive protein, ferritin, lactate dehydrogenase, procalcitonin and neutrophil-to-lymphocyte ratio within 10 days of the clinical onset of coronavirus disease 2019 and 60 days after. Results Seventy-seven patients were included in this study. D-dimer, procalcitonin, ferritin and neutrophil-to-lymphocyte ratio correlated significantly with severe coronavirus disease 2019. No significant correlations were found between baseline and 60-day Connecticut Chemosensory Clinical Research Center test scores and the inflammatory markers assessed. Conclusion Olfactory disturbances appear to have little prognostic value in predicting the severity of coronavirus disease 2019 compared to D-dimer, ferritin, procalcitonin and neutrophil-to-lymphocyte ratio. The lack of correlation between the severity and duration of olfactory disturbances and serum levels of inflammatory markers seems to further suggest that the pathogenetic mechanisms underlying the loss of smell in coronavirus disease 2019 patients are related to local rather than systemic inflammatory factors.

The Use of Morning Urinary Gonadotropins and Sexual Hormones in the Management of Early Puberty in Chinese Girls

Context Although gonadotropin-releasing hormone stimulation test (GnRHST) is the gold standard in diagnosing central precocious puberty (CPP), it is invasive, expensive, and time-consuming, requiring multiple blood samples to measure gonadotropin levels. Objective We evaluated whether urinary hormones could be potential biomarkers for pre- or post- puberty, aiming to simplify the current diagnosis and prognosis procedure. Design, Setting, and Participants We performed a cross-sectional study of a total of 355 girls with CPP in National Clinical Research Center for Child Health in China, including 258 girls with positive and 97 girls with negative results from GnRHST. Twenty patients received GnRH analogue (GnRHa) treatment and completed a six-month follow up. Main Outcome Measures We measured luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol, prolactin, progesterone, testosterone, and human chorionic gonadotropin in the first morning voided urine samples. Results Their urinary LH levels and the ratios of LH: FSH increased significantly with the advancement in Tanner Stages. uLH levels were positively associated with basal and peak LH levels in the serum after GnRH stimulation. A cut-off value of 1.74 IU/L for uLH reached a sensitivity of 69.4% and a specificity of 75.3% in predicting a positive GnRHST result. For the combined threshold (uLH≥1.74+uLH: uFSH ratio &gt;0.4), the specificity reached 86.6%. After 3 months of GnRHa therapy, the uLH and uFSH levels decreased accordingly. Conclusions uLH could be a reliable biomarker for the initial CPP diagnosis and screening; uLH also could be an effective marker for evaluating the efficacy of clinical treatment.