Home Monitoring for Fever: An Inexpensive Screening Method to Prevent Household Spread of COVID-19.

The COVID-19 pandemic surge has exceeded testing capacities in many parts of the world. We investigated the effectiveness of home temperature monitoring for early identification of COVID-19 patients. Study Design ­: We compared home temperature measurements from a convenience sample of 1180 individuals who reported being test positive for SARS-CoV-2 to an age, sex, and location matched control group of 1249 individuals who had not tested positive. Methods ­: All individuals monitored their temperature at home using an electronic smartphone thermometer that relayed temperature measurements and symptoms to a centralized cloud based, de-identified data bank. Results -: Individuals varied in the number of times they monitored their temperature. When temperature was monitored for over 72 hours fever (≥ 37.6°C or 99.7°F or a change in temperature of ≥ 1°C or 1.8°F) was detected in 73% of test positive individuals, a sensitivity comparable to rapid SARS-CoV-2 antigen tests. When compared to our control group the specificity of fever for COVID-19 was 0.70. However, when fever was combined with complaints of loss of taste and smell, difficulty breathing, fatigue, chills, diarrhea, or stuffy nose the odds ratio of having COVID-19 was sufficiently high as to obviate the need to employ RTPCR or antigen testing to screen for and isolate coronavirus infected cases. Conclusions -: Our findings suggest that home temperature monitoring could serve as an inexpensive convenient screen for the onset of COVID-19, encourage earlier isolation of potentially infected individuals, and more effectively reduce the spread of infection in closed spaces.

Effect of Galcanezumab on Total Pain Burden in Patients Who Had Previously Not Benefited from Migraine Preventive Medication (CONQUER Trial): A Post Hoc Analysis.

INTRODUCTION: In evaluating therapies for migraine prevention, emphasis is placed on frequency and less attention is paid to duration or severity. Total pain burden (TPB) combines frequency, duration, and severity of migraine headache, and has the potential to further characterize the benefit of preventive treatment using a single composite measure. TPB was previously used to characterize response to galcanezumab (GMB) in patients with migraine. In this post hoc analysis we assessed the impact of GMB in lowering TPB in patients who had previously not benefited from two to four categories of migraine preventive medication. METHODS: CONQUER trial patients (N = 462), 18-75 years old who had previously not benefited from two to four categories of migraine preventive medication, were randomized (1:1) to monthly placebo or GMB 120 mg with 240 mg loading dose. For each patient, monthly TPB in severity-weighted hours was calculated by multiplying migraine headache duration (hours) by maximum severity for each migraine headache day, then summing these daily scores over the month for the monthly score. Changes from baseline in monthly TPB across months 1-3 were analyzed. Spearman correlations between TPB and scores on the Migraine-Specific Quality-of-Life Questionnaire (MSQ) total and Migraine Disability Assessment Scale (MIDAS) were assessed at baseline. RESULTS: Mean (SD) baseline monthly TPB was 192.1 (158.3) and 188.2 (197.4) severity-weighted hours for GMB-treated and placebo-treated patients, respectively. Across the 3-month double-blind period, GMB-treated patients experienced significantly greater mean reductions from baseline in monthly TPB compared with placebo-treated patients, both for mean change (GMB - 82.7, placebo - 15.8, p < 0.001) and percentage change (GMB - 38.6%, placebo 9.4%, p < 0.001). Furthermore, baseline TPB correlated with MSQ score (r = - 0.39) and MIDAS score (r = 0.40), suggesting good association of TPB with functional and disability outcomes. CONCLUSION: GMB reduced mean TPB in patients who had previously not benefited from two to four categories of migraine preventive medication. TRIAL REGISTRATION: NCT03559257.

Health care resource utilization and costs associated with treatment among patients initiating calcitonin gene-related peptide inhibitors vs other preventive migraine treatments in the United States.

BACKGROUND: Limited data are available on health care resource utilization (HCRU) and health care costs of calcitonin gene-related peptide monoclonal antibodies (CGRP mAbs) for preventive treatment of migraine. OBJECTIVE: To compare all-cause and migraine-related HCRU and direct health care costs in patients with migraine initiating CGRP mAbs, galcanezumab (GMB), vs standard-of-care (SOC) preventive treatments in the United States. METHODS: This retrospective observational study used insurance claims data collected from IBM MarketScan Research Databases. Adults (aged ≥ 18 years) with 1 or more claims for CGRP mAb (GMB, erenumab, or fremanezumab) or SOC preventive treatment between May 1, 2018, and June 30, 2019, were included. The date of earliest migraine treatment claim during this period was the index date. Annual all-cause and migraine-related HCRU included inpatient visits, emergency department visits, and acute and preventive migraine medication fills. After matching, HCRU and costs at 6- and 12-month follow-up in CGRP mAb, specifically GMB, vs SOC cohorts were analyzed using paired t-test and chi-square test. RESULTS: In the 12-month follow-up study, 4,528 patients using CGRP mAb (GMB, n = 426) and 10,897 patients using SOC were included. After matching, 3,082 pairs were identified in the CGRP mAb and SOC cohorts and 421 pairs in the GMB and SOC cohorts. After matching, all variables were well balanced across cohorts. At 12-month follow-up, the percentage decrease in acute and preventive migraine medication fills was significantly greater in the CGRP mAb (acute: -1.5% vs -0.2%, P < 0.001; preventive: -1.1% vs 3.8, P < 0.001) and GMB cohorts (acute: -1.5% vs -0.2%, P = 0.002; preventive: -1.8 vs 3.0, P < 0.001) compared with the SOC cohort. At follow-up, compared with the SOC cohort, the mean change of annual all-cause total costs was significantly higher in both the CGRP mAb ($6,043 vs $1,323, P < 0.001) and GMB cohorts ($8,398 vs $68, P < 0.001), and the mean change of annual migraine-related total costs was significantly higher in both the CGRP mAb ($3,416 vs $976, P < 0.001) and GMB cohorts ($4,334 vs $1,245, P < 0.001). Significant cost savings in mean acute and preventive migraine prescription costs occurred in both the CGRP mAb (acute: -$358 vs -$80, P < 0.001; preventive: -$298 vs $1,376, P < 0.001) and GMB cohorts (acute: -$280 vs -$36, P = 0.034; preventive: -$374 vs $1,537, P < 0.001) compared with the SOC cohort. CONCLUSIONS: Although treatment with CGRP mAbs and GMB increase total costs, they may lead to significantly greater cost savings in outpatient acute and preventive migraine medication costs vs SOC. Further studies assessing indirect health care costs are important to understand additional cost savings with CGRP mAbs. DISCLOSURES: Drs Varnado, Ye, and Schuh are employees and stockholders of Eli Lilly and Company. Dr Wenzel is a former employee of Eli Lilly and Company. Dr Manjelievskaia is an employee of IBM Watson Health. Ms Perry is a former employee of IBM Watson Health. This study was sponsored by Eli Lilly and Company. IBM Watson Health received funding for this study from Eli Lilly and Company. Independent analyses were conducted by IBM Watson Health. Eli Lilly and Company and IBM Watson Health collaborated on designing the study and interpreting results.

Long-term open-label safety study of galcanezumab in patients with episodic or chronic cluster headache.

BACKGROUND: CGAR, a Phase 3b open-label study, evaluated the long-term safety of galcanezumab in patients with cluster headache who completed one of two Phase 3 double-blind studies in chronic or episodic cluster headache. METHODS: Patients (N = 164) received galcanezumab 300 mg subcutaneously up to once a month. Primary endpoint was safety, as assessed by treatment-emergent adverse events, serious adverse events, and suicidality. Other endpoints included discontinuation rates, immunogenicity, efficacy as assessed by the Patient Global Impression of Improvement, and health values. RESULTS: At baseline, mean (standard deviation) age was 48.3 (9.8) years, 75.0% were men, and 85.4% were white. Treatment-emergent adverse events (n = 119 [72.6%]) were mostly mild-to-moderate, with nasopharyngitis the most commonly reported (22.0%). One of 18 serious adverse events was judged as treatment related (constipation). Two patients (1.2%) reported suicidal ideation. Five patients (3.1%) discontinued due to an adverse event. Eight patients were treatment-emergent anti-drug antibody positive, two of whom were not treatment-emergent anti-drug antibody positive in the parent studies. On the Patient Global Impression of Improvement, ≥81% reported their cluster headache status as very much, much, or a little better at Months 1, 6, and 12. Health value scores generally improved from baseline. CONCLUSIONS: In this open-label study, galcanezumab was generally well tolerated and improved patient-reported cluster headache status.Trial registration number: NCT02797951; https://clinicaltrials.gov/ct2/show/NCT02797951.

Treatment Patterns for Calcitonin Gene-Related Peptide Monoclonal Antibodies Including Galcanezumab versus Conventional Preventive Treatments for Migraine: A Retrospective US Claims Study.

Background: Most conventional, oral, preventive treatments for migraine are non-specific and ~50% of patients discontinue them within six months. In 2018, the Food and Drug Administration approved three preventive migraine treatments: monoclonal antibodies (mAb) targeting the calcitonin gene-related peptide (CGRP) pathway implicated in migraine; galcanezumab and fremanezumab which target CGRP ligand; and erenumab which targets CGRP receptor. Real-world treatment patterns for CGRP mAb are limited. Purpose: To compare real-world treatment patterns for CGRP mAb, specifically galcanezumab versus standard-of-care (SOC) migraine preventive treatments. Patients and methods: This retrospective, observational study included 12-month baseline and 6- and 12-month follow-up analyses using IBM® MarketScan® databases. Patients identified were aged ≥18 years with ≥1 claim (first claim=index) for CGRP mAb (erenumab, fremanezumab, or galcanezumab) or SOC preventives (eg, antiepileptics, beta-blockers, antidepressants, or onabotulinumtoxinA) as index drugs between May/01/2018 and June/30/2019. Propensity score matching was used to address confounding by observed covariates. Outcomes analyzed included proportion of days covered (PDC), persistence (≤60-day gap), and first non-index drug switch. Descriptive, chi-square (categorical), and t-test (continuous) analyses were conducted. Results: The study included 3082 (CGRP mAb versus SOC) and 421 (galcanezumab versus SOC) matched patient pairs with 12-month follow-up. Mean age across cohorts ranged 43.2-44.4 years (females: 85.7-88.6%). Compared with SOC, the CGRP mAb cohort had higher mean persistence (212.5 vs 131.9 days), adherence (PDC: 55.1% vs 35.2%), and more patients were adherent with PDC ≥80% (32.7% vs 18.7%) (all p <0.001). During 12-month follow-up, fewer patients discontinued CGRP mAb versus SOC (58.8% vs 77.6%, p <0.001). Galcanezumab versus SOC comparisons yielded similar results. In the CGRP mAb cohort, most switchers (28.3%) used galcanezumab as subsequent treatment. Largely similar results were observed for 6-month follow-up cohorts. Conclusion: Patients on CGRP mAb and specifically galcanezumab showed higher adherence and persistence than patients on SOC migraine preventive treatments.

Cluster Headache: Opportunities for Pharmacists to Improve Care.

Cluster headache (CH) is a primary headache (PH) disorder characterized by recurrent attacks of severe/extremely severe unilateral pain and associated symptoms. While less prevalent than other PHs such as migraine, CH impact is substantial given the agonizing pain, negative effect on daily productivity, impaired mental health, and increased costs. Cluster headache is not optimally treated and few clinical trials are available to model therapy, especially dosing and administration. Pharmacists are well positioned to help prescribers and CH individuals with several key opportunities. Subcutaneous sumatriptan (SC SM) lower than the FDA-approved 6 mg per attack, specifically 2 mg and 3 mg, can be considered; literature describes these doses' benefits. Moreover, lower doses may improve patient access to this treatment-of-choice. Despite the SC SM's FDA-approved dose limit of 12 mg per 24 hours, the maximum CH dose has not been examined; this limit merits reevaluation since literature and clinical experience illustrate treatment exceeding this limit. Oxygen therapy for CH remains unfamiliar to, and under-utilized by, clinicians and CH individuals. Pharmacists can facilitate prescribing, distribution, and administration of oxygen via education. Patient education for the various CH medication devices, including oxygen, is paramount. Narcotics remain widely prescribed for CH, without supporting evidence, but with considerable abuse and diversion risks. Pharmacists are positioned to help guard against narcotic usage and to direct care toward medications endorsed by CH guidelines. Since the optimal method to initiate and discontinue drugs which may decrease CH attacks' remains unknown, pharmacists can educate clinicians and individuals with CH to make fully informed decisions.

The Value of Medical Registries and Observational Studies Early in Pandemics: The Coronavirus Disease 2019 (COVID-19) Experience.

Whereas randomized clinical trials remain the gold standard for evaluating new therapies for infections, we argue that registries and observational studies early in the coronavirus disease 2019 (COVID-19) pandemic provided invaluable understanding of the natural history and preliminary data on risk factors and possible treatments. We review the data from the current pandemic, the history of registries in general, and their value in public health emergencies. Lessons from these experiences should be incorporated into rigorous planning for the next pandemic.

Tolerability and safety of galcanezumab in patients with chronic cluster headache with up to 15 months of galcanezumab treatment.

OBJECTIVE: The objective of the study was to assess the tolerability and safety of galcanezumab in patients with chronic cluster headache (CH) with up to 15 months of treatment. BACKGROUND: Chronic CH is a highly debilitating disease with a substantial and unmet medical need. METHODS: Patients were randomized to receive placebo or galcanezumab (300 mg) monthly for 12 weeks, followed by an optional 52-week open-label extension and 16-week posttreatment follow-up (washout). This is a secondary analysis and long-term follow-up of a previously conducted clinical trial. The safety analysis included patients who received galcanezumab at any time during the study. Outcomes included adverse events (AEs), discontinuations, laboratory values, vital signs, electrocardiograms (ECGs), and suicidality ratings. RESULTS: A total of 233 patients received at least one galcanezumab dose. The mean exposure was 341 days. Galcanezumab-treated patients were mostly male (n = 169/233; 72.5%) with a mean age of 44.9 (±10.9) years. Treatment-emergent adverse events (TEAEs) were reported by 185 patients (n = 185/233; 79.4%), 23 patients (n = 23/233; 9.9%) reported serious adverse events (SAEs), and 18 patients (n = 18/233; 7.7%) discontinued due to AEs. The SAE CH was reported by three patients. The most common TEAEs (>10%) were nasopharyngitis (n = 41/233; 17.6%) and injection site pain (n = 33/233; 14.2%). 27.5% of patients (n = 64/233) had TEAEs related to injection sites. Likely hypersensitivity events, including injection site rash, injection site urticaria, and injection site hypersensitivity were reported (n = 14/233; 6.0%). There were past histories of suicidal ideation (n = 55/237; 23.2%) and suicidal behavior (n = 9/236; 3.8%). During the study, 15 patients (n = 15/230; 6.5%), seven with previous history, reported suicidal ideation. One patient had a nonfatal suicide attempt during the open-label extension and an aborted attempt during the washout. There were no new safety findings compared with the placebo-controlled treatment period in laboratory values, vital signs, or ECGs. CONCLUSIONS: Galcanezumab 300 mg monthly had a favorable tolerability and safety profile in patients with chronic CH with up to 15 months of treatment.

Severe Sepsis: The Fragile Anatomy of Crude Mortality.

Clinical trials of severe sepsis that target crude mortality are underpowered to detect mortality differences due to intervention. We discuss the importance of including subcomponents of crude mortality in study design; how the proportion of attributable mortality affects sample size requirements; and how minor changes from predicted outcomes affect interpretation.

Impact of Galcanezumab on Total Pain Burden: A Post Hoc Analysis of a Phase 3, Randomized, Double-Blind, Placebo-Controlled Study in Patients with Episodic Cluster Headache.

PURPOSE: In a phase 3 study, galcanezumab significantly reduced the frequency of episodic cluster headache attacks across weeks 1-3 (primary endpoint) compared with placebo. However, multiple pain dimensions may contribute to the total burden of episodic cluster headache pain. This post hoc analysis assessed the impact of galcanezumab on the total pain burden of episodic cluster headache using a composite measure. PATIENTS AND METHODS: Patients with episodic cluster headache were randomized 1:1 to galcanezumab 300 mg or placebo once monthly for 8 weeks. Mean weekly total pain burden was calculated (daily cluster headache attack frequency × average duration × average pain severity summed over 7 days) using data collected in an electronic patient-reported outcomes diary. Change from baseline in weekly total pain burden across weeks 1-3 was compared between galcanezumab and placebo. To explore construct validity, mean weekly total pain burden scores were stratified by Patient Global Impression of Improvement (PGI-I) responses at the week 4 clinic visit. RESULTS: The reduction from baseline in mean weekly total pain burden was significantly greater with galcanezumab (N=49) than with placebo (N=57): the least squares mean difference was -11.18 severity-weighted hours (p=0.035). Median weekly total pain burden decreased as PGI-I ratings improved, from 33.6 to 5.0 severity-weighted hours for patients who felt "very much worse" and "very much better," respectively. CONCLUSION: Galcanezumab significantly reduced mean weekly total pain burden compared with placebo in patients with episodic cluster headache. The composite pain measure demonstrated construct validity. Total pain burden may provide a holistic measure of the pain of episodic cluster headache. CLINICAL TRIALS: ClinicalTrials.gov, NCT02397473.

No clinical benefit in mortality associated with hydroxychloroquine treatment in patients with COVID-19.

BACKGROUND: The use of hydroxychloroquine (HCQ), with or without concurrent administration of azithromycin (AZM), for treatment of COVID-19 has received considerable attention. The purpose of this study was to determine whether HCQ administration is associated with improved mortality in COVID-19 patients. METHODS: We conducted a retrospective analysis of data collected during the care process for COVID-19 positive patients discharged from facilities affiliated with a large healthcare system in the United States as of April 27, 2020. Patients were categorized by treatment with HCQ (in addition to standard supportive therapy) or receipt of supportive therapy with no HCQ. Patient outcomes were evaluated for in-hospital mortality. Patient demographics and clinical characteristics were accounted for through a multivariable regression analysis. RESULTS: A total of 1669 patients were evaluated (no HCQ, n = 696; HCQ, n = 973). When adjusting for patient characteristics, receipt of AZM, and severity of disease at admission, there was no beneficial effect of receipt of HCQ on the risk of death. In this population, there was an 81% increase in the risk of mortality among patients who received HCQ at any time during their hospital stay versus no HCQ exposure (OR: 1.81, 95% CI: 1.20-2.77, p = 0.01). CONCLUSIONS: In this retrospective analysis, we found that there was no benefit of administration of HCQ on mortality in COVID-19 patients. These results support recent changes to clinical trials that discourage the use of HCQ in COVID-19 patients.

Patient characteristics and admitting vital signs associated with coronavirus disease 2019 (COVID-19)-related mortality among patients admitted with noncritical illness.

OBJECTIVE: To determine risk factors for mortality among COVID-19 patients admitted to a system of community hospitals in the United States. DESIGN: Retrospective analysis of patient data collected from the routine care of COVID-19 patients. SETTING: System of >180 acute-care facilities in the United States. PARTICIPANTS: All admitted patients with positive identification of COVID-19 and a documented discharge as of May 12, 2020. METHODS: Determination of demographic characteristics, vital signs at admission, patient comorbidities and recorded discharge disposition in this population to construct a logistic regression estimating the odds of mortality, particular for those patients characterized as not being critically ill at admission. RESULTS: In total, 6,180 COVID-19+ patients were identified as of May 12, 2020. Most COVID-19+ patients (4,808, 77.8%) were admitted directly to a medical-surgical unit with no documented critical care or mechanical ventilation within 8 hours of admission. After adjusting for demographic characteristics, comorbidities, and vital signs at admission in this subgroup, the largest driver of the odds of mortality was patient age (OR, 1.07; 95% CI, 1.06-1.08; P < .001). Decreased oxygen saturation at admission was associated with increased odds of mortality (OR, 1.09; 95% CI, 1.06-1.12; P < .001) as was diabetes (OR, 1.57; 95% CI, 1.21-2.03; P < .001). CONCLUSIONS: The identification of factors observable at admission that are associated with mortality in COVID-19 patients who are initially admitted to non-critical care units may help care providers, hospital epidemiologists, and hospital safety experts better plan for the care of these patients.