A reliable and valid measure of COVID-19 patient-reported symptoms in outpatients: the Symptoms Evolution of COVID-19 (SE-C19) instrument

Background: There is no valid and reliable patient self-reported measure assessing symptomology among outpatients with COVID-19. The Symptoms Evolution of COVID-19 (SE-C19) is a self-administered new instrument that includes 23 symptoms, each rated for severity at their worst moment within the last 24 hours. We studied the psychometric properties of SE-C19. Methods: Reliability, validity, and sensitivity to change of the SE-C19 were assessed in 657 outpatients with confirmed COVID-19 enrolled in NCT04425629. SE-C19 and Patient Global Impression of Severity (PGIS) were administered daily from baseline (predose at Day 1) to end of study (Day 29). Findings: Most patients (70.0%) were aged ≤50 years and white (85.5%). At baseline, patients reported an average (SD) of 6.6 (3.9) symptoms (ie, rated as at least Mild) with 3.8 (3.3) of these symptoms being rated as Moderate or Severe. By Day 29, most symptoms had resolved; 74.4% of patients reported no symptoms and on average, only 0.6 (SD 1.5) were reported as at least Mild. Stable patients according to the PGIS showed scores with intraclass correlation values indicating moderate-to-good test-retest reliability (ie, 0.50-0.90). At baseline, 20 item scores (87%) varied significantly across PGIS defined groups supporting the validity of SE-C19. A symptom resolution endpoint was defined after excluding the item 'Sneezing', due to its low ability to discriminate severity levels, and 'Confusion', 'Rash', and 'Vomiting', due to their low prevalence in this population. Symptoms resolution required complete absence of all remaining items, except 'Cough', 'Fatigue', and 'Headache', which could be Mild or Moderate in severity. Interpretation: We identified 19 items that are valid and reliable to measure disease-related symptoms in COVID-19 outpatients and propose a definition of symptom resolution that could be used in future clinical trials and potentially, also in clinical practice.

Clinically Important Change in SF-12v2 Physical (PCS) and Mental (MCS) Component Summary Scores for Patients with Cold Agglutinin Disease: An Analysis Using the Phase 3 CARDINAL and CADENZA Studies

Introduction Cold Agglutinin Disease (CAD) is an autoimmune condition resulting in hemolytic anemia; the subsequent fatigue causes a reduction in patient's physical and mental health-related quality of life (HRQoL). Sutimlimab (formerly BIVV009) is a humanized monoclonal anti-C1s antibody with a clinical trial program to support its development as a treatment for CAD. CARDINAL (NCT03347396) and CADENZA (NCT03347422) are Phase 3 clinical trials that assessed the treatment-related change in HRQoL using the 12-item Short-Form Health Survey (version 2) (SF-12v2) in patients with CAD treated with sutimlimab. This analysis aimed to estimate the clinically important change (CIC) in SF-12v2 physical (PCS) and mental (MCS) component summary scores, using pooled data from CARDINAL and CADENZA. Methods CARDINAL was an open-label, single-arm, multicenter study for patients with CAD with a recent blood transfusion. CADENZA was a randomized, double-blind, placebo-controlled, multicenter study; patients with CAD (without a recent blood transfusion) were randomized 1:1 to receive sutimlimab or placebo. In both studies, patients underwent efficacy and safety assessments for 6 months (Part A). Data from the Part A 26-week component of both studies were combined for these analyses. CIC, defined as mean score change divided by SD at baseline, gave treatment effect sizes of 0.2 (small), 0.5 (moderate) or 0.8 (large), allowing for interpretation of patient-reported outcomes by pre-determining clinically meaningful improvements in physical and mental well-being. Anchor- and distribution-based analyses were performed to estimate the CIC for the following patient-reported outcome measures: Patient Global Impression of (fatigue) Severity (PGIS) and Patient Global Impression of Change (PGIC). Anchor-based approaches (mean change and model-based) examined the relationship between change in SF-12v2 PCS and MCS scores and change in related anchor variables: change in PGIS, PGIC (from baseline to Week 26) and hemoglobin levels (g/dl) (from baseline to the mean value of Weeks 23, 25 and 26). The independent variable was change in PCS and MCS scores and dependent variables were binary (improvement vs. no improvement) in model-based analyses. Results Fifty-five patients with SF-12v2 data available were included from CARDINAL (n=17) and CADENZA (n=38). The median (range) age was 70 (46-88) years and 76% of patients were female (n=42). Mean (SD) PCS and MCS scores at baseline were 40.9 (7.8) and 47.3 (9.1), respectively. From baseline to Week 26, mean (SD) changes in PCS and MCS scores were 4.1 (7.1) and 3.1 (11.6), respectively. Correlations between changes in PCS and MCS scores and PGIS, hemoglobin, and self-report of change in PGIC at Week 26 ranged from 0.36 to 0.55, indicating moderate associations (Table 1). When using an anchor-based approach that evaluated mean change in PCS and MCS scores, CIC estimates ranged from 2.9 to 7.4 for PCS and 2.2 to 7.0 for MCS (Table 2). Results from the 2 model-based anchor approaches, which estimated CIC using receiver operating characteristic curves and an adjusted logistic regression-based approach ranged from 2.0 to 7.3 for PCS and 1.1 to 4.1 for MCS (Table 2). Distribution-based analyses determined the CIC to be 3.9 and 4.6 for PCS and MCS, respectively, when based on one-half of the standard deviation of baseline scores, and 3.5 (PCS) and 4.1 (MCS) when based on the standard error of measurement. The median estimate produced by all anchor-based methods were closely aligned with results of distribution-based analyses. Therefore, taking into consideration all approaches, the median CICs for CAD patients for PCS and MCS were 3.9 and 2.8, respectively. Conclusion In this analysis, patients with CAD had median CIC values of 3.9 and 2.8 for PCS and MCS, respectively. In a previous study, anchor-based analyses for the general population gave CIC scores of 3.0 for both PCS and MCS (Maruish ME et al. 3 rd edition; Lincoln, RI; 2012). The results of this study converge well with those estimates observed for the general population involving thousands of observations. This analysis also demonstrated that meaningful physical and mental health benefits (including a reduction in fatigue) were associated with improvements in hemoglobin levels, a main clinical outcome measure of CAD. Figure 1 Figure 1. Disclosures Joly: Sanofi: Current Employment. Kosinski: QualityMetric Incorporated, LLC: Current Employment. Shafer: Sanofi: Current Employment, Current equity holder in publicly-traded company; Pfizer: Current equity holder in publicly-traded company, Divested equity in a private or publicly-traded company in the past 24 months, Ended employment in the past 24 months. Wardecki: Sanofi: Current Employment, Current equity holder in publicly-traded company, Divested equity in a private or publicly-traded company in the past 24 months, Other: May hold shares and/or stock options with Sanofi. Karaouni: BMAPS SARL(Geneva, Switzerland): Current Employment; Sanofi: Consultancy. Hill: Amgen: Honoraria; Alexion: Honoraria; ReAlta: Consultancy; Sanofi: Consultancy; Grifols: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Argenx: Consultancy; Apellis: Consultancy, Honoraria.

Lasmiditan efficacy in the acute treatment of migraine was independent of prior response to triptans: Findings from the CENTURION study

Background A significant proportion of triptan users exhibit an insufficient response or inadequate tolerability to a triptan, and some may develop a contraindication. Lasmiditan, a selective 5-HT1F receptor agonist, may be an option for these individuals. We assessed lasmiditan efficacy in a subgroup of patients in CENTURION (Phase 3 migraine consistency study) who exhibited an insufficient response to triptans, including a subgroup with insufficient response due to efficacy only. Methods Patients were randomized to lasmiditan 200 mg for four attacks, lasmiditan 100 mg for four attacks, or placebo for three and lasmiditan 50 mg for one attack. Triptan insufficient responders were pre-defined as patients with insufficient efficacy or tolerability, or who developed a contraindication. Results In triptan insufficient responders, lasmiditan was superior to placebo ( p < 0.05) for pain freedom beginning at 1 h (both doses); pain relief beginning at 0.5 (200 mg) or 1 h (100 mg); migraine-related disability freedom, much/very much better on the Patient Global Impression of Change, and most bothersome symptom freedom at 2 h; sustained pain freedom; and need for rescue medication. Lasmiditan showed benefit for consistency of effect across attacks for 2-h pain freedom and pain relief. Findings were similar in triptan responders and triptan naïve patients and when the triptan insufficient response definition was based on efficacy only. Conclusions Lasmiditan was efficacious across multiple clinically relevant endpoints in the acute treatment of migraine independent of prior response to triptans. Trial Registration: CENTURION (NCT03670810); SAMURAI (NCT02439320); SPARTAN (NCT02605174)

Long-term outcomes of transvaginal mesh surgery for pelvic organ prolapse: a retrospective cohort study

Background The objective of this study was to evaluate the overall outcomes and complications of transvaginal mesh (TVM) placement for the management of pelvic organ prolapse (POP) with different meshes with a greater than 10-years of follow-up. Methods We performed a retrospective review of patients with POP who underwent prolapse repair surgery with placement of transvaginal mesh (Prolift kit or self-cut Gynemesh) between January 2005 and December 2010. Baseline of patient characteristics were collected from the patients’ medical records. During follow-up, the anatomical outcomes were evaluated using the POP Quantification system, and the Patient Global Impression of Improvement (PGI-I) was used to assess the response of a condition to therapy. Overall postoperative satisfaction was assessed by the following question: “What is your overall postoperative satisfaction, on a scale from 0 to 10?”. Relapse-free survival was analyzed using Kaplan–Meier curves. Results In total, 134 patients were included. With a median 12-year (range 10–15) follow-up, 52 patients (38.8%) underwent TVM surgery with Prolift, and Gynemesh was used 82 (61.2%). 91% patients felt that POP symptom improved based on the PGI-I scores, and most satisfied after operation. The recurrence rates of anterior, apical and posterior compartment prolapse were 5.2%, 5.2%, and 2.2%, respectively. No significant differences in POP recurrence, mesh-associated complications and urinary incontinence were noted between TVM surgery with Prolift versus Gynemesh. Conclusions Treatment of POP by TVM surgery exhibited long-term effectiveness with acceptable morbidity. The outcomes of the mesh kit were the same as those for self-cutmesh.

P096 Subjective ratings of medication strength of lemborexant over 6 months in subjects with moderate or severe insomnia

Introduction In Study 303 (SUNRISE-2), significantly more subjects reported a positive effect of lemborexant (LEM), a dual orexin receptor antagonist, versus placebo (PBO) on their sleep at 1mo, 3mo and 6mo, as assessed by items 1–3 of the Patient Global Impression–Insomnia (PGI-I). LEM-treated subjects also reported larger and statistically significant decreases in the Insomnia Severity Index (ISI) versus PBO. This analysis examined potential LEM tolerance via patient-reported ratings of medication strength on PGI-I item 4 in subjects with moderate/severe insomnia. Methods In this 12mo double-blind, PBO-controlled (first 6mo), phase 3 study, subjects ≥18y with insomnia disorder and ISI scores ≥15 were randomized to PBO (n=318) or LEM (5mg, [LEM5], n=316; 10mg, [LEM10], n=315). The ISI and PGI-I were administered at 1mo, 3mo and 6mo. Results The percentage of subjects with moderate (ISI=15–21; n=692) or severe (ISI=22–28; n=223) insomnia at baseline who rated LEM as “just right” increased from 1mo (moderate: LEM5=46.4%; LEM10=43.3%; PBO=31.3%; severe: LEM5=35.8%; LEM10=40.6%; PBO=15.0%) to 6mo (moderate: LEM5=56.5%; LEM10=53.9%; PBO=39.7%; severe: LEM5= 54.8%; LEM10=55.4%; PBO=21.6%). Ratings of “too weak” decreased over 6 months in both ISI severity groups. PBO group ratings of “too weak” always exceeded the LEM groups by &gt;15%. Ratings of “too strong” were low and stable over time. Conclusions Findings suggest that LEM tolerance does not occur over 6mo with either LEM dose since patient perceptions of LEM treatment being “too weak” did not increase over the study period. These data support the persistent efficacy of long-term LEM treatment for chronic insomnia.

Injectable amniotic membrane/umbilical cord particulate for facet joint syndrome: A retrospective, single-center study

BACKGROUND: Facet joint syndrome (FJS) pain is a significant contributor to back pain and has a high rate of opioid prescription. Unfortunately, there are a limited number of therapeutic options for these patients. OBJECTIVE: To evaluate the safety and effectiveness of amniotic membrane/umbilical cord particulate (AM/UC) in managing FJS pain. METHODS: A single-center, investigator-initiated, retrospective study was performed on consecutive patients with FJS pain who received intra- or peri-articular injection of AM/UC between July 1, 2018 and July 26, 2019. Primary outcome was change in Patient Global Impression of Change (PGIC) at 6 weeks, 3 months, 6 months, and 12 months to assess the self-reported percent improvement relative to baseline. Safety was assessed by AM/UC- and procedure-related complications. Paired t-tests were used to determine whether there is a statistically significant improvement of pain post-injection compared to baseline. RESULTS: There were a total of 54 patients (69.7 ± 13.4 years; 31 female) presenting baseline pain score of 9.2 ± 1.0 despite prior treatments of activity modification (66.7%), NSAIDs (61.1%), opioids (37.0%), and physical therapy (35.2%). Mean GPIC improvement was 65.3%, 67.5%, 56.9%, and 56.7% among responders30, respectively. There were no complications. CONCLUSION: This study supports the safety and effectiveness of AM/UC particulate injection in managing FJS pain.

Holmium:YAG Laser for the Treatment of Genital and urethral Warts: Multicentre Prospective Evaluation of Safety and Efficacy

Introduction: Genital condylomatosis is a highly contagious disease caused by the human papilloma virus (HPV). The aim of this prospective multicentre study was to evaluate the safety and efficacy of the Holmium:YAG (yttrium-aluminium-garnet) laser in the treatment of genital and intra-urethral warts; the secondary aim was to assess the patients’ postoperative satisfaction and cosmetic results. Methods: From December 2016 to March 2019, patients with genital warts were prospectively enrolled in three hospitals. The inclusion criteria were male gender, age over 18 years-old and treatment-naïve. External and urethral genitalia warts were treated by the Holmium YAG laser. The follow-up analysis consisted of physical examination, flexible urethro-cystoscopy in case of meatal lesions, and administration of Dermatology Quality of Life Index (DLQI) and Patient Global Impression of Improvement (PGI-I) questionnaires at 1, 3, 6 and 12 months after surgery and subsequently yearly. Results: Sixty patients were enrolled. The single treatment was effective in 57/60 patients (95%). At a mean follow-up of 26 months, recurrences occurred in 8 patients (13.3%). No peri- or post-operative complication occurred. An improvement in pre-operative condition was highlighted with PGI-I and DLQI questionnaires. Conclusion: Our prospective multicentre study showed that holmium laser surgery seems to be a safe and effective treatment for external genital and urethral warts. Good dermatological outcomes aid to further improve patient satisfaction.

The role of the multi-disciplinary team and multi-disciplinary therapeutic protocol in the management of the chronic pelvic pain: There is strenght in numbers!

Introduction: The aim of the study is to evaluate the effectiveness of a Multi-disciplinary team (MDT) and multi-disciplinary approach in the treatment of Chronic Pelvic Pain (CPP). Methods: The data of all consecutive patients referred for a CPP from 11/2016 to 2/2019 has been prospectively collected. The sample was divided in two groups: Group A, made by patients managed after the institution of our MDT, and Group B, made of patients managed before this date. The MDT is composed by three urogynecologists, a psychologist and a physiotherapist. All Group A patients underwent a weekly bladder instillation with dimethyl sulfoxide (DMSO), kinesiotherapy for trigger points and Percutaneous Tibial Nerve Stimulation for 10 consecutive weeks. Patients were asked to perform a self-treatment following the Stanford Protocol and to adhere to a specific diet. All Group B patients were managed only with DMSO instillations and a strict diet. Results: The Group A was made of 41 females and 6 males while the Group B was made of 38 females and 5 males. The Group A patients showed a statistically significant improvement in the Pelvic Pain Urgency Frequency, in the frequency times reported at the 6 months voiding diary, and a better Patient Global Impression of Improvement. Conclusions: Our data support the efficacy of the MDT in the management of CPP. The multimodal approach might represent an effective and reproducible non-invasive option to manage successfully CPP.