Unprecedented phase 3 data were announced from the IKEMA trial that evaluated the impact of isatuximab (Sarclisa) in combination with carfilzomib and dexamethasone (Kd) on patients with multiple myeloma (MM).

, the results demonstrated the longest median progression free survival (mPFS) on a proteasome inhibitor backbone in patients with multiple myeloma who relapsed after a prior therapy, including lenalidomide.

With more than 130,000 new diagnoses of multiple myeloma worldwide, it’s the second most common hematologic malignancy. However, in the US it’s classified as a 

 Treatments are available for the disease though, it remains incurable, and as a result most patients will experience a relapse, or relapsed multiple myeloma.

Among studies examining a proteasome inhibitor backbone in the second-line setting for this patient population, this study achieved the longest mPFS. These data were presented at the Controversies in Multiple Myeloma World Congress and will also be presented at the European Society for Medical Oncology on May 19.

“The increase in progression free survival, observed consistently across all subgroups, when adding Sarclisa to carfilzomib and dexamethasone is remarkable in patients with relapsed multiple myeloma in a proteasome inhibitor combination," Philippe Moreau, MD, Head, Department of Hematology, University Hospital of Nantes said in a statement. 

"Relapse is common in multiple myeloma," he continued, "creating the need for differentiated second-line treatments that provide patients a longer period of time without disease progression. This updated analysis reinforces the potential for Sarclisa to become a new standard of care for patients with relapsed multiple myeloma.”

The results of the trial indicated that when isatuximab was combined with carfilzomib and Kd the median progression free survival of patients increased from 19.2 months to 35.7 months. When following recommendations on censoring rules of the US Food and Drug Administration (FDA), a further analysis revealed that the mean progression free survival increased from 20.8 - 41.7 months.

Investigators found the time to next treatment was 44.9 months for patients who received the isatuximab combination therapy compared with 25 months for those who were solely treated with Kd. Time to next treatment was measured by the interval from the date of randomization to the date of commencement of the next line of therapy in order to allow for measurement of the period of therapeutic benefit.

The safety profile of isatuximab was shown to be consistent with its profile in other clinical trials, with no new safety signals observed in this study. For the isatuximab combination therapy arm, treatment was 30 weeks longer than in the control arm. 83.6% of patients treated with the combination therapy reported treatment emergent adverse events (TEAEs) of ≥ Grade 3 and 73% of those treated with Kd alone.

Adverse events that occurred in the isatuximab combination therapy and Kd groups were as follows: infusion related reaction (45.8%, 3.3%), diarrhea (39.5%, 32%), hypertension (37.9%, 35.2%), upper respiratory tract infection (37.3%, 27%), fatigue (31.6%, 20.5%), dyspnoea (30.5%, 22.1%), pneumonia (27.1%, 21.3%), back pain (25.4%, 21.3%), insomnia (25.4%, 24.6%), and bronchitis (24.3%, 12.3%).

The randomized, multi-center, open label phase 3 clinical trial took place in 69 centers across 16 countries, enrolling a total of 302 patients with relapsed multiple myeloma who had received 1-3 other anti-myeloma therapies prior to the study.

Patients participating in the trial received an intravenous infusion of isatuximab (10 mg/kg) once weekly for 4 weeks followed by every other week for 28-day cycles in combination with carfilzomib (20/56mg/m2) twice weekly and Kd at the standard dose for the duration of treatment.

Progression free survival was the primary endpoint of the study. The secondary endpoints were overall response rate, the rate of complete response or better, the rate of very good partial response or better, rate of minimal residual disease-negativity, and overall survival and safety.

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Isatuximab in combination with carfilzomib and dexamethasone (Kd) demonstrate the longest median progression free survival (mPFS) on a proteasome inhibitor backbone in multiple myeloma patients who relapsed after a prior therapy, including lenalidomide.

Phase 3 Data Show Isatuximab Offers Progression Free Survival for Multiple Myeloma

A new assessment observed an association between rheumatic disease and 

Systematic review and meta analysis data from a team of investigators in China showed a correlation of potentially nonspecific, shared alterations of gut microbes in patients with either dysbiosis or rheumatic diseases including arthritis and systemic lupus erythematosus (SLE).

The findings contribute further evidence to a proposed link between the 2 disease group pathologies, and provide clearer paths for follow-up research.

Led by Yilun Wang, of the department of orthopedics at Xiangya Hospital in Changsha, the investigators noted prior research suggests dysbiosis may playing a contributing role to the occurrence, or even development, of various rheumatic diseases. The gut microbiota has an established association with various disease conditions including obesity, growth disorders, metabolic diseases, and mental illness.

“The emerging evidence in the past decades suggests that dysbiosis in gut microbiota and its impact on the balance between pro- and anti-inflammatory immune responses may contribute to the occurrence or development of several rheumatic diseases,” investigators wrote. “Since gut microbiota dysbiosis is potentially modifiable, it has been postulated to be a promising preventive or therapeutic target for rheumatic diseases.”

Wang and colleagues analyzed observational studies evaluating associations between dysbiosis and rheumatic disease via PubMed, Embase and Cochrane Library. They estimated a standardized mean difference (SMD) of α-diversity indices between prevalence of rheumatic disease versus control, while also qualitatively summarizing β-diversity indices and relative abundance of gut microbes.

Their assessment included 92 trials with 11,998 participants; eventually 68 provided data for α-diversity.

The team found consistent α-diversity index decreases for rheumatic diseases overall (SMD, -0.36; 95% CI, -0.63 to -0.09). However, when observing specific diseases, investigators only observed decreases in the following 4 conditions:

Rheumatoid arthritis (SMD, -0.51; 95% CI, -0.78 to -0.24)

Gout (SMD, -0.64; 95% CI, -1.07 to -0.22)

Fibromyalgia (SMD, -0.28; 95% CI, -0.44 to -0.11)

Interestingly, investigators observed an associated increase in α-diversity indices with systemic sclerosis (SMD, 1.25; 95% CI, 0.09 - 2.41).

Ankylosing spondylitis and immunoglobulin G4 (IgG4) related diseases were associated with statistically-significant differences in β-diversity.

—an anti-inflammatory butyrate-producing microbe—and enrichment of 

—a pro-inflammatory microbe—were observed in instances of rheumatoid arthritis, Sjorgen’s syndrome, and SLE. However, whenever the gut microbes merited specificity, investigators observed weaker reproductions, meaning that disease-specific alterations of gut microbes are still uncertain without further research.

Though they caution interpreting the findings—as the observed microbial associations may indicate a shared alteration to multiple rheumatic disease instead a disease-specific biologic difference—the team concluded the observed altered microbes and their metabolites could be used as “general targets for innovative preventive or therapeutic tools for different rheumatic diseases.”

“Finally, little evidence of distinct disease-specific alterations in gut microbes was evident,” they concluded. “This suggests that gut microbes serving as diagnostics for specific rheumatic diseases warrants further investigations.”

Gut dysbiosis in rheumatic diseases: A systematic review and meta-analysis of 92 observational studies

Developing research into the specific alterations of dysbiosis and diseases like arthritis suggest possibly novel pathways to therapy development.

Gut Microbiota Dybiosis May Be Linked to Rheumatic Disease

New demographic data from a large, decade-long cohort of patients diagnosed with sarcoidosis in rural and suburban areas contributed to the limited information on how the disease affects minority groups in the United States.

the American Thoracic Society 2020 International Conference

 in San Francisco during the “Emerging EPI in Obstructive and Restrictive Lung Disease” session.

, study author Edward Chen, MD, Pulmonary and Critical Care Medicine at Johns Hopkins University School of Medicine, spoke of the limited data suggesting a higher prevalence of sarcoidosis in African Americans.

“There's been numerous observations through the last 70 years- including observations from the military which keep a lot of good statistics- that sarcoidosis is much more commonly found amongst African Americans and particularly African Americans in the in the southeastern coastal areas of United States,” Chen said. “More recently, there have been some other some additional studies that refined this observation a little bit more than within African Americans that in particular, female African Americans seem to have a slightly higher prevalence of sarcoidosis compared to male African Americans.”

With these observations in mind, Chen and colleagues assembled a retrospective cohort of patients using the Penn State PaTH to Health data set to determine baseline demographic and clinical characteristics.

A total of 1594 patients who were diagnosed with sarcoidosis between 2011 and 2021 were included in the study, with 340 patients in the year 1 cohort, with the age of the first recorded diagnosis being less than 40 years old for 14.7% of the population.

The number of patients would steadily increase by approximately 114-177 patients per year.

The cohort was predominantly White (75.7%), with 16.8% of the total population identifying as African American and 7.5% are other. Meanwhile, ethnicity was predominantly non-Hispanic (96%), with 4% identifying as Hispanic.

“In some ways this is sort of a first step,” Chen said. “It's a subset of all the data that we may have access to. So, if we can get our search or approach refined for our smaller data set that could be applied to much larger one, and we get one step closer to a more accurate view of what sarcoidosis may be like in the United States.”

To learn more about sarcoidosis research and funding, please visit 

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With this new decade-long cohort, Dr. Chen notes that researchers are "one step closer to a more accurate view of what sarcoidosis may be like in the United States", with has been suggested to be more prominent in African American communities.

Edward Chen, MD: Amassing Data on Sarcoidosis Prevalence in Rural and Suburban Areas in the US

New data from a post-hoc analysis of the VOYAGE study indicates that dupilumab reduced severe exacerbation rates and improve the percent predicted pre-bronchodilator FEV1 in pediatric patients 6-11 years old with uncontrolled moderate to severe asthma with or without atopic comorbidities .

Asthma - one of the most common chronic childhood diseases- has often been associated with comorbid atopic disorders and type 2 inflammation.

Previous phase 3 data from VOYAGE found that add-on dupilumab 100/200 mg every 2 weeks reduced severe asthma exacerbations and improved percent predicted pre-bronchodilator forced expiratory volume in 1 second (FEV1pp) at Week 12 compared to placebo.

In this post-hoc analysis, investigators led by Theresa W. Guilbert, MD, MS, of the Cincinnatti Children’s Hospital, evaluated dupilumab efficacy in pediatric patients with and without one or more ongoing atopic comorbidities.

Guilbert and colleagues analyzed the annualized rate of severe asthma exacerbations (AER) and change from baseline in bronchodilator FEV1pp (%) over the course of the 52-week treatment period in patients treated with the bioligic compared to placebo. Patients with 1 or no ongoing comorbid disease were included in the analyses.

Meanwhile, comorbid diseases including atopic dermatitis, allergic conjunctivitis, allergic rhinitis, chronic rhinosinusitis, nasal polyposis, eosinophilic esophagitis, food allergy, and hives were recorded at baseline.

A total of 408 patients were included in the study.

Investigators determined thart, compared to placebo, dupilumab reduced AER by 72% (no comorbid disease, 

= 0.07), 2% in patients with 1 ongoing comorbid disease (

= 0.96), and 69% in patients with >1 ongoing comorbid diseases (

By Week 12, patients with no atopic comorbidities showed no differences in changes from baseline in pre-bronchodilator FEV1pp.Despite this, dupilumab improved pre-bronchodilator FEV1pp in patients with atopic comorbidities compared to placebo.

The biologic also improved the change from baseline in pre-bronchodilator FEV1pp in all patients

Dupilumab reduced severe exacerbation rates and by the end of treatment, had improved the percent predicted pre-bronchodilator FEV1 in children aged 6to 11 years with uncontrolled, moderate-to-severe asthma, in patients with or without atopic comorbidities,” the team wrote.

A post-hoc analysis of the VOYAGE study also found that the biologic improved the percent predicted pre-bronchodilator FEV1 in this patient population.

Dupilumab Reduces Severe Exacerbation Rates in Pediatric Asthma Regardless of Atopic Comorbidities

A new investigation from the Division of Pulmonary, Allergy and Critical Care Medicine at Stanford School of Medicine suggested that lowering airway iron could be a potential treatment for allergic bronchopulmonary aspergillosis (ABPA) in children with cystic fibrosis.

The data were presented during a late-breaker session at 

Allergic bronchopulmonary aspergillosis can be found in approximately 10-25% of children with cystic fibrosis, and is caused by aspergillus fumigatus (

This particularspecies of fungus secretes proteases that incite a Th-2 mediated allergic response that can result in progressive lung function decline. However, no current therapies are available to modify disease progression, and some therapies such as corticosteroids have long-term negative sequelae.

Investigators cited an urgent need for new treatment strategies and hypothesized that reducing airway iron would result in a decrease in the production of 

proteases and lessen Th-2 mediated immune inflammation associated with ABPA.

“The cystic fibrosis airway is unique; there are higher level of iron found in the cystic fibrosis airway than healthy controls, and previous studies have reported that the iron metabolism mechanism in cystic fibrosis airway is really altered in this patient population than healthy controls,” said study author Paulami Chatterjee, PhD, of Stanford University said in an interview with HCPLive.

The investigative team cultured both Wild type 

) with iron, xenosiderophore (DFO), and iron chelator (DFX) before measuring 

Meanwhile, the effect of an iron-avid pseudomonas filamentous bacteriophage (Pf4) on 

protease expression was assessed through co-culturing 

 and Pf4 in increasing iron concentrations.

Regarding in-vivo iron, Chatterjee and colleagues modulated graft iron with a nanoparticle solution containing iron or DFX. Meanwhile, protease activity was measured in sputum samples of CF pediatric patients and association of 

“Our study found that both DFX and Pf4, they can reduce iron levels and reduce protease production in the in-vitro model, ” Chatterjee said.

Currently the team are evaluating the effect of iron chelation strategies using DFX and Pf4 on an established CF-ABPA mice model.

However, the investigative team also conducted a pilot study that applied incorporated this data when evaluated sputum samples from pediatric patients.

The study evaluated the association between of aspergillus and bacteriophage infection status and correlated that association with the clinical outcomes of cystic fibrosis.

Chatterjee noted that despite the small sample size, the primary outlook was “very encouraging”, and she and her colleagues found that patients who had both aspergillus and bacteriophage in their sputum showed less exacerbation and less protease concentration in their sputum.

Meanwhile, patients with only aspergillus showed the highest level of exacerbation as well as the highest concentration of sputum protease concentration.

“We are very hopeful with this data, this is very promising and this actually supports our hypothesis,” Chatterjee said. “This shows the possible clinical translatability of our work. We are planning on doing a bigger study which can replicate the findings we have and give us more information on host-pathogen interaction and polymicrobial interaction which is happening in the ABPA and cystic fibrosis scenario.”

Watch the full interview above to hear more from Dr. Chatterjee, and click 

Dr. Chatterjee cites an urgent need for new treatment strategies, adding that reducing airway iron could result in a decrease in the production of aspergillus fumigatus proteases.

Paulami Chatterjee, PhD: Lowering Airway Iron to Treat ABPA in Pediatric Cystic Fibrosis

A 29-host-mRNA response classifier showed ability to detect bacterial co-infections, as well as superinfections, among patients with confirmed COVID-19.

In new abstract presented at the Society of Advanced Emergency Medicine (SAEM) 2022 Meeting in New Orleans this week, a team of academic and industry investigators reported that the dynamic host response platform may help emergency and acute care setting clinicians address various infection risks at once, particularly 

Led by Nikhil Ram Mohan, PhD, of the Stanford University School of Medicine’s emergency medicine department, investigators sought to assess the accuracy of the IMX-BVN-3 and IMX-SEV-3 host response classifiers in detecting SARS-CoV-2 infection, bacterial co-infections and superinfections, and predicting severity of COVID-19 disease in confirmed patients.

The team, supported by diagnostic company Inflammatix Inc., emphasized the potential significance of platforms being capable of providing such accuracy for coinciding risks during the ongoing pandemic. The 2 classifiers included in the study have been reported, they wrote, to help accurately determine both the likelihood of bacterial and viral infection—from very unlikely to very likely—and severity of illness—from low to high—in patients without COVID-19.

“The major clinical challenges currently faced by emergency department (ED) clinicians assessing patients with suspected infection include accurate identification of COVID-19, detection of bacterial co- or superinfection, and determination of severity of illness,” Mohan and colleagues wrote. “Currently no single biomarker or clinical algorithm can perform all 3 critical roles.”

Their assessment included 161 patients with PCR-confirmed COVID-19 infection who were enrolled through the Stanford University Medical Center. Median patient age was 50.0 years old; 52.2% were female. Approximately half (51.0%) were hospitalized during the assessment, and 9 had died.

Investigators extracted RNA via 2.5 mL whole blood samples assayed through PAXgene Blood RNA, and 29 host mRNAs were quantified via Nanostring nCounter. COVID-19 and bacterial co-infection or superinfection risks were defined as very unlikely, unlikely, likely, or very likely. Disease severity risks were defined as low, moderate, or high.

Nearly all patients (n = 151 [93.8%]) were allocated into the Very Likely or Likely viral bands; 5 patients each were placed into the Unlikely and Very Unlikely viral bands. Of the latter 10 patients, 6 had positive COVID-19 tests >9 days prior to admission; the remaining 4 had results oscillating between positive or negative, or were asymptomatic.

Regarding bacterial infection risk, 155 (96.3%) were classified in the Unlikely or Very Unlikely groups; 6 were classified as Likely. Of the latter 6, clinical adjudication confirmed that 4 (66.7%) had either bacterial coinfection 

colitis, fecal pathogens in urine, or clinically suspected bacterial superinfections. All 9 patients to die during hospitalization came from either the Low (n = 2 [2.8%]) or Moderate (n = 7 [11.7%]) severity disease classifications.

“In conclusion, IMX-BVN-3/SEV-3 accurately identified patients with COVID-19, bacterial co/ superinfections, and stratified clinical outcomes,” investigators wrote. “Such a multifaceted host response-based platform could improve ED patient management, accurate diagnoses, and optimized resource utilization.”

The study, “29-mRNA Host Response Classifier Detects Bacterial Co-infection and Superinfection and Predicts Outcomes in COVID-19 Patients,” was presented at SAEM 2022.

New data suggest prediction of SARS-CoV-2 and bacterial co-infection or superinfection could be provided for hospitalized patients.

Classifiers Could Identify Gastric Co-Infection Risks in Patients with COVID-19

The implementation of the US Preventive Services Task Force (USPSTF) 2021 and the American Diabetes Association (ADA) 2022 guidelines would increase screening eligibility for 

 by nearly 7 percentage points, according to new findings.

Both organizations recommended in these recent updates that lowering the starting age for diabetes screening to 35 years may help facilitate earlier detection and treatment.

Data show an approximate 4- to 6-percentage point increase in prediabetes detection and an approximate 2- to 9-percentage-point increase in undiagnosed diabetes detection with these new guidelines.

“Starting diabetes screening at age 35 years may place even greater demands on clinicians to care for younger populations,” wrote study author Elizabeth Selvin, PhD, MPH, Johns Hopkins Bloomberg School of Public Health. “Expanding health care access, developing targeted outreach for high-risk individuals, and scaling prevention programs will be critical.”

Selvin and colleagues analyzed data from the cross-sectional 2015 - 2020 National Health and Nutrition Examination Survey (NHANES) of the US population. Adults aged ≥20 years without a history of diagnosed prediabetes or diabetes who were fasting, were not pregnant, and had hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), weight, and height measured during examination were included.

The investigators defined prediabetes as an FPG level of 100 to 125 mg/dL or HbA1c of 5.7% to 6.4% and defined undiagnosed diabetes as an FPG level of ≥126 mg/dL or HbA1c of ≥6.5%. They then defined screening eligibility as

Aged 40 - 70 years with BMI of ≥25 (USPSTF, 2015)

Aged 35 - 70 years with BMI of ≥25 (USPSTF, 2021)

Aged 45 years or older with BMI of ≥25 and ≥1 risk factor (ADA, 2003)

Aged 35 years or older or a BMI of ≥25 and ≥1 risk factors (ADA, 2022)

As well, they estimated the proportion of US adults eligible for screening based on these guidelines overall and among those with prediabetes or undiagnosed diabetes. From a total of 4836 eligible adults, 4480 (92.6%) had HbA1c, FPG, and BMI data available and were included (mean age, 45.6 years; 51.2% women).

Investigators observed the weighted proportion eligible for screening increased from 36.3% (95% CI, 34.1% - 38.5%) to 43.0% (95% CI, 40.5% - 45.6%) comparing USPSTF 2015 with USPSTF 2021 guidelines. Additionally, eligibility increased from 76.7% (95% CI, 73.8% - 79.3%) to 82.9% (95% CI, 80.1% - 85.3%) when comparing ADA 2003 with ADA 2022 guidelines, according to investigators.

Further, data show screening eligibility increased among those with prediabetes comparing USPSTF 2015 with USPSTF 2021 guidelines (from 50.1% to 56.2%) and ADA 2003 with ADA 2022 guidelines (from 89.4% to 93.7%). For those with undiagnosed diabetes, screening eligibility increased when comparing USPSTF 2015 with USPSTF 2021 guidelines (from 58.7% to 67.8%), but did not increase comparing ADA 2003 with ADA 2022 guidelines (from 97.6% to 99.1%).

“Harmonizing recommendations may reduce confusion for clinicians and facilitate implementation,” investigators concluded.

Prediabetes and Diabetes Screening Eligibility and Detection in US Adults After Changes to US Preventive Services Task Force and American Diabetes Association Recommendations

Implementation of the USPSTF 2021 and ADA 2022 guidelines would increase screening eligibility by approximately 6 to 7 percentage points. 

New Guidelines Increase Screening Eligibility for Prediabetes, Diabetes Among US Adults 

A new study examined the reliability of patient-reports of vaso-occlusive crises (VOC), or pain crises, using a 

 diary. The results demonstrated that patients were able to describe their experiences of VOC-related pain crises accurately, and were able to differentiate these experiences from everyday pain.

A team of investigators led by Karin Coyne, PhD, MPH, Patient-Centered Research, Evidera, aimed to validate a daily patient-reported outcome for patients with sickle cell disease to accurately report their VOC status and experience of a pain crisis. VOC episodes have typically been assessed through medical utilization, excluding events managed at home.

Individuals with sickle cell disease experience VOCs frequently, as they can begin at any time. During a VOC, the blood vessels of the patient are obstructed which leads to ischemic tissue injury and severe pain. These episodes can increase morbidity and mortality, especially in older patients, as a result of the organ damage caused by repeated VOCs.

Investigators noted that pain crises are the most common reason that these patients visit the emergency department (ED) and are responsible for missed school, work, and decreased health-related quality of life (HRQoL). The impacts of decreased HRQoL include inhibited physical, emotional, and social functioning, and research has shown that impacts are worse among individuals with sickle cell disease compared to the general population and to some other chronic diseases.

The timing of VOC episodes are difficult to predict, investigators wrote. A reliable tracking method over long periods of time for these crises are needed. The current practice has physicians relying on patient recall and medical record documentation in order to get a history of the patient’s incidence and severity of a VOC episode. However, these records don’t include episodes that are managed at home–which is a majority of them.

Investigators believed that the medical utilization definition of a VOC likely only represents a subset of the overall patient experience with these crises. Actually, the frequency of SCD patient-reported crisis pain was higher than what was captured by their healthcare providers, and crisis pain was largely managed at home, according to results from The Pain in Sickle Cell Epidemiology Study (PiSCES).

“Requiring medical utilization for a VOC episode to be recorded underestimates patient burden of VOC and limits the ability to fully evaluate the benefit of new treatments. Thus, there is a need for a patient-reported outcome (PRO) measure to accurately capture and record VOCs,” investigators wrote.

The team performed the ELIPSIS study, which was non-interventional, longitudinal, and assessed novel biomarkers in order to identify and document the complete natural history of VOCs experienced by patients with sickle cell disease who had hemoglobin SS (HbSS) or S-β thalassemia (HbS- β) genotype. Patients were at least 12 years old and had a confirmed diagnosis of stable SCD.

Patients kept a daily SCD Diary where they responded to questions regarding their experiences with VOC, pain, tiredness, functioning, and medical utilization. The patients reported these entries on a secure, electronic, FDA compliant, handheld device.

In the SCD Diary, a description of a pain crisis was included that read: “People like yourself describe a pain crisis day as a day when your pain is more than usual, you cannot do what you would normally do, you may be more tired than usual, and often use extra pain medication to get by. Sometimes you may need to speak to or see a doctor or go to the emergency room or hospital, and other times you may treat yourself at home.”

The SCD Diary Provides Accurate, Comprehensive Insight

Of the 37 patients enrolled in the study, 35 completed it. The average age of the population was 24.7 ± 9.5 years and just over half were female (51.4%). Only 10 patients (28.6%) completed entries in their SCD Diary more than 80% of the time, making the average completion rate in this group 88.6% compared to the rest of the patients who had a 57.4% completion rate.

The SCD Diary items on the first day of a VOC event showed a strong correlation with one another (worst pain range: r = 0.574 to 0.584; tiredness range: r = 0.574 to 0.693; all p<0.0001). Additionally, the items for VOC days were also strongly correlated (worst pain range: r = 0.648 to 0.658; tiredness: r = 0.648 to 0.758; all p<0.0001). Due to the lack of responses reported on non-VOC days, correlations on these days did not converge.

Of the total patients, 31 (88.6%) reported at least 1 VOC day during the study. The mean number of VOC days experienced per patient within the 6 month observation period in the study was 9.9 ± 18.5 days. The average number of VOC days for patients who completed the diary at least 80% of the time was 19.9 ± 30.7 days and 5.9 ± 8.5 for non-completers.

Investigators noted the large discrepancy between the 2 groups as driven in part by an outlier in the completer group who reported 91 VOC days. Without this patient-report, the average number of VOC days for diary completers changed to 12.0 ± 18.9.

Investigators found that the mean severity of worst pain was higher on VOC days compared to non-VOC days (7.6 vs 2.6, respectively). The mean severity of tiredness was similarly higher on VOC days compared to non-VOC days (6.3 vs 4.1, respectively). As for the functioning items, mean impact scores were higher on VOC days (usual physical activities = 3.6; social activities = 2.6; daily activities = 3.5 self-care = 2.9) compared to non-VOC Days (usual physical activities = 2.6; social activities = 2.1; daily activities = 2.5; self-care = 1.8).

Results displayed that the magnitude of difference between VOC Days and non-VOC days for the functioning scores was smaller than the differences observed for worst pain and tiredness scores between VOC and non-VOC days.

“Previously reported results from ELIPSIS15 showed that the majority of VOC Events (62.3%) were treated at home, 18.4% culminated in a hospitalization, 17.5% resulted in direct healthcare utilization, while the remaining (1.8%) had indirect healthcare utilization. These results, in conjunction with results from the PiSCES14 study that found VOC pain was largely managed at home, indicate that relying on the medical utilization operational VOC definitions results in a substantial number of missed VOC episodes,” investigators wrote.

In response to this study, investigators called for the use of patient-reports to be adopted into clinical and investigative practices.

“Participants in the ELIPSIS study were able to use the SCD Diary to reliably report their VOC related pain crises,” they concluded. “Moreover, results from these analyses demonstrate that the SCD Diary is valid and can be implemented into clinical trials to capture the full patient experience of VOC-related pain crises. This finding is critical as it signals the ability to shift from a medical utilization definition of a VOC to a patient-reported definition.”

Validation of Patient-reported Vaso-occlusive Crisis Day as an Endpoint in Sickle Cell Disease Studies

Investigators who say that assessing vaso-occlusive crises solely through medical utilization doesn’t provide a full picture of the SCD experience because many VOCs are managed from home, are now backed by research.

New Study Supports the Reliability SCD Patient-Reports of VOC-Related Pain Crises

The intensity level of thyroid hormone treatment may be a modifiable risk factor for 

Both exogenous hyperthyroidism and exogenous hypothyroidism were found to have associations with increased risk of cardiovascular mortality after adjustments for a comprehensive set of demographic and traditional CV risk factors, said investigators.

“The emergence of the intensity of thyroid hormone treatment as a potential associated risk factor provides a highly relevant and easily modifiable clinical parameter for patients who receive thyroid hormone treatment,” wrote study author Maria Papaleontiou, MD, Division of Metabolism, Endocrinology and Diabetes, Department of Internal Medicine, University of Michigan.

There has been a lack of data specifically regarding the association between the intensity of thyroid hormone treatment and CV mortality, said the study authors. Thus, they hypothesized that both exogenous hyperthyroidism and hypothyroidism would be associated with increased CV mortality, even after adjusting for risk factors.

A nationwide population was collected between January 2004 and December 2017 using data from 705,307 adults who received thyroid hormone treatment from the Veterans Health Administration. Investigators studied two cohorts:

701,929 adults ≥18 years who initiated thyroid hormone treatment with ≥2 thyrotropin measurements between treatment initiation and death or end of the study period

373,981 patients with ≥2 free thyroxine (FT4) measurements

Investigators then defined exogenous hyperthyroidism by thyrotropin levels lower than 0.5 mIU/L or by FT4 levels higher than 1.9 ng/dL and euthyroidism defined by thyrotropin levels from 0.5 to 5.5 mIU/L and FT4 levels from 0.7 to 1.9 ng/dL. Additionally, exogenous hypothyroidism was defined by thyrotropin levels higher than 5.5 mIU/L or by FT4 levels lower than 0.7 ng/dL.

Study outcomes were identified as cardiovascular mortality (myocardial infarction, heart failure, or stroke) and survival analyses were conducted using Cox proportional hazards regression models using serum thyrotropin and FT4 levels as time-varying covariates.

Of the study population, 625,444 (88.7%) were male, 559,173 (79.3%) patients were White, and the median age was 67 years. During the study period, 75,963 patients (10.8%) died of cardiovascular causes.

Following adjustment for age, sex, and traditional cardiovascular risk factors, investigators found patients with exogenous hyperthyroidism (thyrotropin levels, <0.1 mIU/L; adjusted hazard ratio [AHR], 1.39; 95% CI, 1.32 - 1.47; FT4 >1.9 ng/dL: AHR, 1.29; 95% CI, 1.20 - 1.40) and with exogenous hypothyroidism (thyrotropin levels, >20 mIU/L: AHR, 2.67; 95% CI, 2.55 - 2.80; FT4 levels, <0.7 ng/dL: AHR, 1.56; 95% CI, 1.50 - 1.63) had an increased risk of CV mortality compared to those with euthyoridism.

The study authors noted the risk of CV mortality seems to be directly associated with the degree of thyrotropin abnormality outside the euthyroid range, while thyrotropin level may be more associated with CV risk than the FT4 level in older adults.

“Our study findings have the potential to affect how we think about the risks and benefits associated with thyroid hormone treatment, particularly for vulnerable populations, such as older adults or those with underlying cardiovascular disease,” Papaleontiou concluded.

Association of Thyroid Hormone Treatment Intensity With Cardiovascular Mortality Among US Veterans

Both exogenous hyperthyroidism and exogenous hypothyroidism were associated with increased risk of cardiovascular mortality. 

Thyroid Hormone Treatment Intensity May Be Modifiable Risk Factor for CV Mortality

Carolyn Rowley, PhD, is the executive director of the Cayenne Wellness Center, which is devoted to supporting people living with 

 in California. Recently, the center launched the California Sickle Cell Disease Mental Health and Wellness Initiative to provide mental health services at no cost to those with the disease. 

Unfortunately, in addition to the various challenges that people with sickle cell disease already face as a direct result of their condition, they often coincide with mental and emotional challenges as well. The initiative focuses on addressing these challenges, like depression and anxiety, which are prevalent in this population.

Rowley emphasized the importance of the initiative because there's been a need for mental health resources, particularly for those living with SCD. The Cayenne Center is known for hosting educational platforms, and according Rowley, the topic of mental health gets discussed in each one.

"We recommended that people seek out mental health, however, that's been challenging," she explained. 

The center's community health workers conducted a focus group last year to get more insight on what clients are looking for and what would motivate them to participate in mental health care.

"They found out that their clients would like to go to a provider that looks like them and also knows about sickle cell disease," Rowley said. "And that's actually quite rare."

People with sickle cell disease, particularly children, may struggle with frequent hospitalizations due to pain crises if their parents or caregivers are unaware of the triggers that precede a crisis. 

"I'm not speaking about the type of depression that is debilitating," Rowley clarified, "but the type of depression that leads to isolation at times, even as a child."

When a patient and their support system are aware of the patient's triggers that lead to a pain criss, that can be the difference between good and poor quality of life. 

Rowley, who also lives with sickle cell disease, said that people have a choice when they realize a pain episode is coming and it's unavoidable, in how they face it. What she does is acknowledge that the episode is coming, but she tells herself "it's not going to shadow everything, it's not going to paint my entire picture."

"I encourage others to do what you can do to manage," Rowley said, "but it's about to come and you're about to be on top of it and so it won't be as bad as it could be, because now, you already know you have tools as to how you can conquer this next pain episode."

Dr. Carolyn Rowley is leading the California Sickle Cell Disease Mental Health and Wellness Initiative to provide mental health services free to people living with sickle cell disease. 

Carolyn Rowley, PhD, Addresses Mental Health and Wellness in People with Sickle Cell Disease

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