 were found to be associated with increased COVID-19 severity among pediatric patients in the United States, according to new findings.

The magnitude of these associations in the study varied across the 26 cardiovascular conditions studied, but suggested a high overall cardiovascular burden associated with severe COVID-19, noted the study investigators.

“The data presented in this study highlight the need for pediatric health care professionals to provide careful monitoring and timely care to pediatric patients with preexisting cardiovascular disease and SARS-CoV-2 infection,” wrote corresponding author Louis Ehwerhemuepha, PhD, Children’s Health of Orange County.

Despite limits on early data relating to pediatric COVID-19 cases, systematic reviews found that underlying cardiovascular defects were prevalent, with congenital heart disease (CHD) associated with poor clinical outcomes. The current study evaluated cardiovascular factors associated with severe COVID-19 in pediatrics and to estimate corresponding odds ratios (ORs).

Investigators hypothesized substantial differences in the magnitude of the ORs among cardiovascular factors associated with severe COVID-19 that may translate to clinically useful information for the treatment of these patients. Their study used data on COVID-19-related encounters from 85 health systems between March 2020 - January 2021 from a large, electronic health records database in the US.

Its cohort consisted of patients between 2 months and 17 years of age who had a laboratory-confirmed diagnosis of COVID-19 or a diagnosis code indicating infection or exposure to SARS-CoV-2. Investigators identified 26 cardiovascular conditions for a comprehensive list of congenital and acquired conditions affecting the cardiovascular system.

A binary outcome variable of mild versus severe COVID-19 outcome was defined by investigators. Those who received oxygen therapy and discharged to home alive were defined as having mild COVID-19, while those who received oxygen therapy or died in the hospital were defined as having severe COVID-19.

They noted mixed-effects, random intercept logistic regression modeling assessed the significance and magnitude of associations between 26 cardiovascular conditions and COVID-19 severity.

A total of 171,416 pediatric patients from 85 health systems were found to meet inclusion criteria, with a mean age of 8 years and 50.28% male patients. From these patients, 17,065 (9.96%) had severe COVID-19.

The random intercept model reported that the following cardiovascular conditions were associated with severe COVID-19:

cardiac arrest (OR, 9.92; 95% CI, 6.93 - 14.20)

cardiogenic shock (OR, 3.07; 95% CI, 1.90 - 4.96)

heart surgery (OR, 3.04; 95% CI, 2.26 - 4.08)

cardiopulmonary disease (OR, 1.91; 95% CI, 1.56 - 2.34)

heart failure (OR, 1.82; 95% CI, 1.46 - 2.26)

hypotension (OR, 1.57; 95% CI, 1.38 - 1.79)

nontraumatic cerebral hemorrhage (OR, 1.54; 95% CI, 1.24 - 1.91)

pericarditis (OR, 1.50; 95% CI, 1.17 - 1.94)

simple biventricular defects (OR, 1.45; 95% CI, 1.29 - 1.62)

From the 258 patients with previous cardiac arrest, a total of 205 (79.46%) had severe COVID-19, with a mortality rate of 27.91% (n = 72 deaths). Investigators noted 194 of these patients (75.19%) with previous cardiac arrest were younger than 12 years.

Furthermore, the diagnosis of a cardiovascular condition during a COVID-19-related encounter was associated with a 204% increase in the odds of severe COVID-19 (OR, 4.04; 95% CI, 3.22 - 5.07; 

Association of Congenital and Acquired Cardiovascular Conditions with COVID-19 Severity Among Pediatric Patients in the US

Articles

New data suggest pediatric patients with a history of cardiac arrest are highly susceptible to hospitalization if infected with SARS-CoV-2. 

Preexisting CV Conditions May Increase COVID-19 Severity Among Pediatric Patients 

A new retrospective cohort study evaluated opioid-naive patients who were prescribed at least one opioid during an inpatient hospital visit to determine baseline factors associated with a new diagnosis of opioid use disorder (OUD). The ultimate goal was to better understand factors associated with the disorder in order to inform pain management strategies in this setting.

The team of investigators, led by Elizabeth C.S. Swart, BS, UPMC Centers for High-Value Health Care and Value-Based Pharmacy Initiatives, UPMC Health Plan, alluded not only to the 2.5 million individuals living with OUD in the US, but also the economic impact of this epidemic.

In the US, the cumulative societal cost of opioid use disorder is nearly $80 billion and has been associated with the rise of illicit drug use. Investigators acknowledged the numerous methods of response to this crisis, including policy and treatment approaches aimed at harm-reduction, medication-assisted treatment (MAT), Good Samaritan laws and increased availability of naloxone.

“Other efforts to curtail the epidemic have mainly focused on reducing inappropriate prescribing,” they wrote, “which have led to decreased opioid prescriptions; however, rates of OUD, nonmedical opioid use, and opioid-related overdose deaths remain prevalent.”

While many studies have evaluated inpatient opioid administration, this study explored baseline characteristics including medication use pre-admission, during hospitalization, and at discharge to identify associations with a new diagnosis of opioid use disorder in the year following hospitalization.

"To our knowledge, this is one of the first studies to evaluate patient- and medication-related risk factors in the development of OUD in opioid-naïve inpatients exposed to opioids during hospitalization," investigators wrote. "The inpatient setting is a critical setting for opioid exposure and can serve as a conduit to long-term opioid use."

Investigators developed a dataset of electronic health records (EHR), pharmacy claims, and medical claims that reflected data of patients aged 14 or older who were discharged between 2014-2017 from UPMC Health Plan, a vertically integrated healthcare delivery and finance system. Patients who were diagnosed with OUD, or prescribed an opioid prior to the study onset were excluded.

Out of the final sample of 23,033 opioid-naive patients, 2.1% were diagnosed with the disorder within a year of receiving their first opioid in the hospital. Within that population, investigators discovered that a substantial number of those individuals were young and white, residing in high opioid geo-rank regions and had a history of nonopioid related drug disorder, tobacco use, and gabapentin use.

When examining the 6 months prior to hospital admission among those with a new OUD diagnosis, investigators observed that the average number of prescriptions filled were higher, the number of days’ supply was higher, and prescriptions filled for gabapentin and skeletal muscle relaxants were higher, compared with those without a new diagnosis. 

"Notably, although a baseline history of skeletal muscle relaxant use was more common in those who were diagnosed with OUD, in our multivariable model it was not associated with subsequent OUD" they wrote. "This is contrary to similar studies which looked at factors influencing long-term opioid use among opioid-naïve patients."

Adjusted multilevel mixed-effects logistic regression models were used to indicate the factors associated with a new opioid use disorder diagnosis within 12 months of discharge.

“Overall, presence of chronic liver disease and being discharged to a long-term hospital, rehabilitation center, or special needs facility were significant factors for patients in the surgery cohort who developed OUD (

< .0001). For patients who did not receive surgery, opioid geo-rank was significant at 

< .0001 for those diagnosed with OUD compared to those who were not.”

General characteristics that were associated with higher odds of a diagnosis included being between the ages of 25–34, compared to those 65 years of age and older. When looking at race, White patients were associated with higher odds of a diagnosis.

Medical history and comorbidites played a significant role. Previous history of chronic liver disease was associated with higher odds of an OUD diagnosis in the surgery cohort. Those with nonopioid-related drug disorder (excluding cannabis and cocaine), tobacco use disorder, and mental health conditions also demonstrated higher odds of diagnosis.

Investigators noted that the use of benzodiazepines or skeletal muscle relaxants in the 12 months prior to index hospitalization event was not associated with an OUD diagnosis; however, use of gabapentin 12 months prior to index date was. 

Additionally, patients discharged to long-term hospitals, rehabilitation centers, or special needs facilities instead of going home were more likely to receive a diagnosis. 

"Future research is needed to evaluate if identification of high-risk patients can mitigate risk of subsequent OUD through proactive effective pain management strategies that include reducing opioid exposure when feasible," investigators concluded.

Patient and medication-related factors associated with opioid use disorder after inpatient opioid administration

Presence of chronic liver disease, prior use of gabapentin and being discharged to a long-term hospital or rehabilitation center are among some of the factors associated with a new opioid use disorder diagnosis.

Study Provides Novel Insight on OUD Diagnosis Factors in Opioid-Naive Patients

Half of patients with rosacea have ocular involvement, but a significant number of cases go undiagnosed due to a lack of symptom specificity, according to a new analysis.

The report was a rare large-scale study of ocular rosacea that offered insights into how physicians could better identify and treat patients with rosacea who may have eye involvement.

Corresponding author Markus Reinholz, MD, PhD, of the University Hospital of Munich, and colleagues, noted that rosacea is most identifiable as an inflammatory disease affecting the facial skin, but it can also extend to the eyes.

However, the author said the ocular manifestations of the disease have received relatively little attention until recently. Yet it remains a multidisciplinary challenge.

“Ophthalmic rosacea can affect the eyelids (blepharitis, chalazion, and meibomianitis), the conjunctiva (conjunctivitis and keratoconjunctivitis sicca), the iris (iritis and iridocyclitis), and the cornea (corneal thinning, ulceration, and superficial keratitis),” they wrote.

Patients with the condition often report symptoms such as burning, tearing up, and photophobia. The condition is generally classified into one of 3 categories, based on severity.

Though much is known about the disease, at least 2 major questions remain: first, how exactly does the disease come about and second, how common are ocular manifestations among patients with rosacea.

In an effort to answer the latter question, the investigators developed a detailed online questionnaire, which was given to 777 patients with rosacea.

The survey asked patients questions about ocular and skin symptoms, type 1 hypersensitivities, Demodex testing results, and their previous experiences with healthcare professionals.

The surveys showed that a slight majority (399 of 777) experienced ocular symptoms. The most common were styes and chalazia (309 of 399), itching (187 of 399), and red eyes (179 of 399).

About half of the patients (393) in the study had type 1 hypersensitivity, and more than half of those (225) said they suffered from ocular symptoms.

The investigators said it is important for physicians to question patients with rosacea about ocular symptoms. If symptoms are present, it is beneficial to refer patients to an ophthalmologist for a full examination, since eye symptoms are often unspecific and may or may not be related to rosacea.

In the study cohort, 309 patients had previously consulted an opthalmologist, and about half (149) were confirmed to have ocular rosacea.

If patients do have ocular rosacea, Reinholz and colleagues said, dryness of eyes can be helped by intense pulsed light (IPL) therapy and the use of artificial tears with omega-3 fatty acids, according to previous studies.

The investigators also discussed the topic of Demodex infection, since it has been discussed as a probable trigger of ocular rosacea. In the current study, no statistically significant association was identified between Demodex prevalence and ocular rosacea manifestation.

That may be because Demodex-induced symptoms could be dose-dependent or dependent on individual immunologic mechanisms, they said. In the study, 45 patients were Demodex-positive, and just half (21) had ocular symptoms. 

The authors said their study’s strength is its large size and broad scope of symptoms, but they said more work will be needed to better understand the mechanisms that cause ocular rosacea to develop, as well as the role of potential risk factors.

“Here, immunological studies will be key to elucidate the exact triggers of this chronic inflammatory disease,” they said.

"Clinical clues to identify patients with ocular rosacea – a Germany-wide epidemiologic analysis,"

About half of a cohort of nearly 800 patients said they experience ocular symptoms.

Ocular Symptoms Common in Rosacea, But Often Undiagnosed

Investigative therapy dextromethorphan-bupropion (AXS-05) provided significantly improved 

 versus lone sustained-release bupropion while remaining tolerable in adult patients over 6 weeks, according to new phase 2 trial findings.

In a randomized, double-blind, multi center, parallel-group study of the NMDA/sigma-1 receptor antagonist combination therapy, investigators observed significant improvements in the Montgomery-Asberg Depression Rating Scale (MADRS) of adults with major depression treated with dextromethorphan-bupropion versus those treated with lone antidepressant bupropion.

The new findings from the ASCEND trial contribute to the clinical profile of the Axsome Therapeutics agent, which previously received breakthrough therapy designation by the US Food and Drug Administration (FDA). They also offer differentiated outcomes for clinical assessment of depression—a field which due to increasing rates of placebo-controlled assessments has reported an approximate 50% clinical trial signal response rate in the last 25 years, according to the investigators.

Led by chief executive officer Herriot Tabuteau, MD, the Axsome research team sought to compare mean MADS score change in patients randomized to either dextromethorphan-bupropion or bupropion from baseline to each week of treatment through 6 weeks.

“Currently approved oral antidepressants work primarily via monoamine pathways,” investigators explained. “Partial or inadequate response is common with these agents, and they typically take several weeks to produce clinically meaningful effects.”

Their assessment included patients aged 18-65 years old with a diagnosis of major depressive disorder of moderate to greater severity. Patients were randomized to either 45 mg/105 mg dextromethorphan-bupropion tablet or 105 mg bupropion, taken once-daily for the first 3 days then twice daily thereafter, for 6 weeks.

Patient diagnoses and disease severity were confirmed by an independent assessor, and all patients received ≥1 study medication dose and ≥1 post-baseline assessment.

Of the 97 patients randomized in the trial, 17 did not have a confirmed diagnosis and severity based on the independent assessment—leaving 80 patients randomized to either dextromethorphan-bupropion (n = 43) or bupropion (n = 37).

The MADRS is a 10-item clinician-led questionnaire that scores patients on a scale from 0 - 60, with greater scores representing more severe depression. Tabuteau and colleagues sought secondary endpoints including ≥50% reduction from baseline in MADRS total score, representing clinical response, and MADRS total scores of ≤10, representing remission.

At 6 weeks, investigators observed a mean reduction of 13.7 points in MADRS score from baseline among patients treated with dextromethorphan-bupropion, versus just 8.8 points in the comparator group—a mean difference of 4.9 points (95% CI, -3.1 to -6.8). In fact, patients treated with the investigative drug reported significantly greater MADRS reductions starting at week 2 and every week thereafter.

Patients treated with dextromethorphan-bupropion also reported significantly greater remission rates beginning at week 2 and continuing through the study (46.5% vs 16.2%; mean difference, 30.3; 95% CI, 11.2 - 49.3). Another 60.5% of patients treated with dextromethorphan-bupropion achieved the response rate, versus 40.5% of patients treated with bupropion (mean difference, 19.9; 95% CI, -1.6 to 41).

Commonly observed adverse events with the investigative drug included dizziness, nausea, dry mouth, decreased appetite and anxiety; investigators observed no associations with psychotomimetic effects, unlike other NMDA receptor antagonists.

Investigators described the benefit of care as “rapid, substantial, and statistically significant” in treating the primary endpoints of major depression symptoms in adults versus lone bupropion.

“Dextromethorphan-bupropion demonstrated a rapid onset of effect on depressive symptoms and global measures, with statistically significant improvements compared with bupropion observed starting at week 2 on several measures, despite the small sample size of the study,” they wrote. "The team concluded that ASCEND, the first controlled trial for dextromethorphan-bupropion in patients with depression, showed clinically meaningful improvements against the active comparator.

"ASCEND is one of the pivotal efficacy trials that forms the basis of our (New Drug Application) for AXS-05 in depression, which is currently under review by the FDA,” Tabuteau said in a 

. “Axsome is positioned to move expeditiously to make this product available to patients as quickly as possible, should it be approved."

Effect of AXS-05 (Dextromethorphan-Bupropion) in Major Depressive Disorder: A Randomized Double-Blind Controlled Trial

The first controlled trial of the combination therapy shows its benefit in 6-week depressive symptom improvement versus lone bupropion.

Dextromethorphan-Bupropion Significantly Improves Major Depression Symptoms in Phase 2 ASCEND

, President and CEO of the Sickle Cell Disease Association of America (SCDAA) said the association's 

 will soon be accessible as a mobile app. 

Currently, the trial finder can be used through the SCDAA website to help people with 

 identify which clinical trials they're eligible for participating in. Trials can be particularly difficult to find for individuals with sickle cell disease; the SCDAA platform simplifies the process with its comprehensive database and guided search feature. 

"We're very encouraged by the number of users that we have and the feedback that we're getting about the clinical trial finder," Hartfield said. "It's a one stop shop."

Hartfield also spoke about the difficulty that many individuals with sickle cell disease have when transitioning from pediatric care to adult care. Typically patients make this transition just before or during their teenage years. 

"It's a very, very difficult and challenging transition point," she explained, "and we don't want to lose those living with sickle cell disease in their young age–early teens and 12 year olds–we don't want to do that. And we want to look at the opportunities we have to kind of bridge that gap and make the transition easier."

Throughout the interview, Hartfield emphasized the importance of listening to the "warriors' voice". Individuals living with the condition sometimes refer to themselves as "sickle cell warriors" because the complications they encounter with the disease can make each day feel like they're fighting a war. 

Unfortunately, the emergency department (ED), where many warriors find themselves during a vaso-occlusive episode (VOC), or pain crisis, can often feel like a battleground. According to Hartfield, they're not always given the quality of care that they deserve, or that other patients receive. 

Understanding the voice and experience of a warrior is imperative to addressing obstructive issues like these, in sickle cell care. The goal is to become aware and help to alleviate those issues. 

SCDAA implemented the clinical trial finder to improve the ease of access to trials and also to encourage participation. Not only can a clinical trial have a positive impact on an individual, but the information provided by that individual's participation contributes to the clinical progress and therapeutic treatments, she said. 

"With clinical trials–and having the participation of those who are living with sickle cell disease–they are empowered to be part of the research and to be part of the solution," Hartfield said.

Videos

Sickle cell warriors are empowered to be part of the research and to be part of the solution, Regina Hartfield says. 

Regina Hartfield: SCDAA is Launching a SCD Clinical Trial Finder Mobile App

New findings from a recent randomized clinical trial suggest that the regulation of cues (ROC) intervention and ROC combined with behavioral weight loss [BWL] (ROC+) were successful in weight loss among adults with 

These findings support the use of these interventions as an alternative method for the treatment of overweight and obesity due to specifically targeting appetitive traits and may be used among adults with high levels of food responsiveness, investigators found.

“There were no significant differences between ROC, BWL, and ROC+ for weight loss at posttreatment or 12-month follow-up, which is notable given that the ROC group did not include any energy restriction recommendations,” wrote study author Kerri N. Boutelle, PhD, Herbert Wertheim School of Public Health and Human Longevity Science, University of California San Diego.

Both food responsiveness and eating offset driven by satiety responsiveness are key aspects of appetite explained in the behavioral susceptibility theory (BST), according to the study authors. The BST theorized that genetically determined appetitive traits interact with the individual's food environment and lead to overeating and weight gain.

The current trial evaluated where ROC or ROC+ would improve weight loss across 12 months of treatment and 12 months of follow-up, compared to an active comparator (AC) and BWL only. The Providing Adult Collaborative Interventions for Ideal Changes (PACIFIC) study was conducted at UC San Diego from December 2015 - December 2019.

It included adults of any sex and race or ethnicity if they had a body mass index (BMI) of 25 to 45, were aged 18 to 65 years, and did not meet exclusion criteria, including type 2 diabetes, recent stroke or angina, and pregnancy.

A total of 4 intervention groups were included and patients were randomized to each:

ROC targeted food responsiveness and satiety responsiveness

BWL included energy restriction, increased physical activity, and behavior therapy techniques

AC consisted of mindfulness, social support, and nutrition education

From 1488 volunteers from the community who inquired about the study, a total of 271 adults were assessed at baseline, mid treatment, posttreatment, and 6- and 12-month follow-up. They had a mean age of 47 years, 81.6% were female, 61.9% were White, and they had a mean BMI of 34.59. This population was then randomized to AC (n = 66), ROC (n = 69), ROC+ (n = 67), and BWL (n = 69), according to investigators.

Their findings showed that the ROC, ROC+, and BWL intervention led to significantly lower BMI at the end of treatment (BMI ROC, -1.18, 95% CI, -2.10 to -0.35; BMI ROC+, -1.56, 95% CI, -2.43 to -0.67; BMI BWL, -1.58; 95% CI, -2.45 to -0.71). They saw no significant difference in rate of change in BMI after treatment ended for ROC or ROC+ compared with AC.

Then, compared with BWL, they additionally observed BMI at end of treatment was not significantly different from ROC or ROC+ (BMI ROC, 0.40, 95% CI, -0.55 to 1.36; BMI ROC+, 0.03, 95% CI, -0.88 to 0.93). Meanwhile, the BMI of AC was found to be substantially higher (BMI AC, 1.58, 95% CI, 0.72 to 2.45).

Investigators additionally observed reduction in BMI at 24-months following randomization saw similar findings in ROC, ROC+, and BWL. Food responsiveness was a moderator of treatment effects with increased weight loss for individuals who scored higher in the marker in the ROC and ROC+ groups, according to the authors.

Effect of a Novel Intervention Targeting Appetitive Traits on Body Mass Index Among Adults With Overweight or Obesity: A Randomized Clinical Trial

Both the regulation of cues intervention and ROC with behavioral weight loss were found successful in individuals with high levels of food responsiveness. 

Appetitive Trait Weight Loss Programs May Be Successful in Adults with Obesity

A new sex-based cohort study identified several pulmonary and extra-pulmonary disorders in patients with chronic obstructive pulmonary disease (COPD) that showed marked differences between men and women regarding their association with mortality.

the American Thoracic Society 2020 International Conference

, study author Franziska Trudzinski, MD, of the University of Heidelberg in Germany, spoke of limited data regarding COPD prevalence in female patients.

Recent research has suggested that COPD prevalence is underreported in female patients, with some literature even suggesting higher prevalence in females compared to male patients.

“In most studies, females report more exacerbations than males, and we know also that females have a higher symptom burden,” Trudzinski said. “Also, with regard to comorbidities- and this was actually what inspired us to do this study now- we saw that (females) present with different symptoms. According to the same comorbidity, females with cardiac disease presented with a chest tightness and males with cardiac comorbidities reported a loss in energy. So, I do think that comorbidities have different impact in different genders.”

Trudzinski and colleagues examines sex differences in COPD comorbidities regarding prognosis by classifying comorbidities regarding the disease into a comorbidome related to extrapulmonary disorders and a pulmorbidome.

A total of 1044 women and 1531 men with a diagnosis of COPD were assessed for these comorbidities, with significant differences between gender regarding the association with pulmorbidome and comorbidome being observed.

Comorbidities such as obesity, hypertension, liver cirrhosis, and kidney disease predicted mortality in male patients, while hyperuricemia, mental disorders, kidney disease and increased heart rate predicted mortality in female patients.

Regarding the pulmorbidome, significant predictors in men were impairment in diffusion capacity and hyperinflation, in women asthma and hyperinflation.

Trudzinski suggested that physicians could use these data on different comorbidities to accurately diagnose COPD in both women and men in an unbiased way, stating that “reliable information about comorbidities” for patients was urgently needed.

“We need to question whether it would make sense also to include gender in our risk assessment, because different comorbidities have a different impact on prognosis in in males and females,” she noted. “So maybe we need to judge the impact of comorbidities in a different way.”

To hear more from Dr. Trudzinski, watch the full interview above.

Dr. Trudzinski speaks of the importance of diagnosing sex-specific pulmonary and extra-pulmonary comorbidities in women with COPD, as well as the lack of research regarding COPD prevalence in women.

Franziska Trudzinski, MD: Identifying Gender-Specific Pulmonary Disorders in COPD

Investigators observed that nearly half of all 

tests conducted at a Korean teaching hospital were done so inappropriately, according to a new study that highlights continued need for improved and communicated diagnostic stewardship for the gastric infection.

In new retrospective analysis data from Seoul National University College of Medicine, investigators reported significant differences in rates of inappropriate 

testing based on the clinical setting and prescribing clinician’s profession. The team additionally observed via questionnaire that physicians’ confidence in ordering an appropriate 

Led by Dr. Hee Bum Jo, of the division of infectious diseases in the department of internal medicine at Seoul National University Bundang Hospital, the research team conducted a retrospective review of patient medical records at a 1300-bed tertiary-care teaching hospital who were tested for 

infection from September - November 2019. They additionally conducted a physician survey to assess the knowledge and ordering patterns of testing for such infections.

As the most common healthcare-associated infection, 

prevalence in Korea alone had increased more than 3-fold from 2008 to 2011—while nations including the US have reported increasing greater management of the infection. Investigators cited the 2017 Infectious Diseases Society of America (IDSA) and the Society for Healthcare Epidemiology of America (SHEA) guideline updates recommending testing in relevant clinical settings, defined as instances of unexplained and new-onset ≥3 unformed stools within 24 hours, to improve the reliability of the various available 

“Although asymptomatic colonization is not an indication for treatment, the 

 nucleic acid amplification test (NAAT) and glutamate dehydrogenase (GDH), the currently used methods cannot discriminate between CDI and asymptomatic colonization with 

, which results in overdiagnosis and overtreatment,” they wrote. Therefore, there is a need to consider the relevant clinical situations and symptoms for effective CDI diagnosis.”

Jo and colleagues’ analysis included 715 tests from 520 patients. They classified testing as either hospital-onset or community-onset, and they used an algorithmic method to define appropriate or inappropriate testing. Patients were ≥18 years old, did not receive outpatient testing, and did not have colostomies.

A total of 576 tests were hospital-onset, having occurred >3 days after admission or transfer from another hospital; the remaining 139 were community-onset. Of the hospital-onset tests, nearly two-thirds (n = 355 [61.6%]) were conducted having met IDSA and SHEA’s ≥3 unformed stools in 24-hour criteria, and the remaining 221 (38.4%) did not.

Of the tests of patients with ≥3 unformed stools, 282 (49.0%) did not include laxative use in patients; 73 (12.7%) included laxative use <48 hours prior to the test. Just 15 tests (2.6%) were conducted when patient had shock or were positive for ileus.

The team concluded that 297 tests (51.6%) for 

were conducted appropriately based on the recommended in-hospital guidelines, while 279 (48.4%) were conducted inappropriately.

The appropriately tested group was equally conducted in the hospital’s general ward (81.8%) as the inappropriately tested group (86.7%; 

 = .1.06). But the former group were far less conducted in the emergency room (0.3%) than the latter group (5.0%; 

The appropriately tested group additionally had greater proportions of internal medicine physicians ordering the test than the inappropriately testing group (72.4% vs 63.4%; 

 = .021). Investigators observed no differences in the 2 groups’ median number of days between admission and testing.

The team observed a significantly increased risk of inappropriate testing conducted in the emergency room (odds ratio [OR], 20.06; 95% CI, 2.60 - 154.78; 

< .004), and a decreased risk in the intensive care unit (OR, 0.33; 95% CI, 0.18 - 0.61; 

In their survey of 61 physicians, investigators observed significantly higher mean scores on the 10-point score among internal medicine physicians (7.1) versus other physicians (5.7; 

“Specifically, the question regarding repeat testing had the lowest correct answer rate (36.7% in internal medicine physicians; 38.7% in non-internal medicine physicians; 37.7% in total population),” investigators noted. “There was a significant between-speciality difference in questions regarding culture testing, toxin EIA with GDH EIA testing, GDH EIA with culture testing, and requirement of test of cure.”

The team concluded that this assessment—potentially the first to assess the appropriateness and physician practice patterns in a country with a growing burden of 

—showed institution-specific lanes of improvement for diagnostic stewardship.

“Diagnostic stewardship for CDI should be implemented, particularly through educational interventions for those working in the emergency room and for non-internal medicine physicians,” they wrote. “Prospective multicentre studies on the effectiveness of diagnostic stewardship are warranted.”

Prevalence of and factors associated with inappropriate Clostridioides difficile testing in a teaching hospital in Korea

,” was published online in Antimicrocial Resistance & Infection Control.

A South Korea in-hospital assessment found that approximately half of all ordered CDI tests did not meet recommendation standards.

Appropriate C Difficile Testing May Vary by Hospital Setting, Physician

A new investigation into the novel oral asthma therapy MRx-4DP0004 found it to be safe and well tolerated in patients with asthma when paired with inhaled corticosteroids (ICS) with or without long-acting beta-agonist (LABA).

Part A of this investigation was detailed at 

Previous data has shown that the novel, gut microbiome-derived, oral, single strain Live Biotherapeutic Product (LBP) was effective in reducing lung infiltration of neutrophils and eosinophils, lung inflammatory scores, tissue damage, and more in animals models of severe asthma.

Currently, the therapeutic is being evaluated in human adults with partly controlled asthma as an add-on maintenance therapy via a 2-part phase 1 and 2 study.

For their ATS 2022 session, study author Christopher Brightling, PhD, of the University of Leicester, presented safety and efficacy data from Part A of the study.

Following a 2-week placebo run-in period, Brightling and colleagues randomized 34 patients to receive MRx-4DP0004 2 capsules PO BID (1x109 to 1x1010 CFU) or placebo in addition to their regular maintenance asthma medication of ICS with or without LABA for up to 12 weeks or until withdrawal.

Eligible patients were those with partly controlled asthma, and the primary endpoint of Part A of the study was safety and tolerability of the oral therapy. Meanwhile, secondary endpoints were asthma controls and exacerbations.

Overall, the therapy was well-tolerated among patients in the treatment group, and the frequency of adverse events and treatment discontinuations were similar to placebo.

Notably, all adverse events were mild and moderate, and no treatment-related serious adverse events were reported.

Investigators observed that a significantly greater proportion of patients receiving MRx-4DP0004 experienced improvements in their ACQ-6 from baseline compared to placebo, with a reduced ACQ-6 scores being present In 83.3% of patients treated with the therapy compared to 56.3% of those in the placebo group (P=0.088).

Additionally, 50.0% of patients receiving MRx-4DP0004 reduced their total weekly use of SABA rescue medication from baseline, compared to 18.8% for placebo by the end of treatment (P=0.06), and 50% of patients receiving the therapy had also experience clinically meaningful improvements in AQLQ score from baseline of ≥0.5.

Only one asthma exacerbation was recorded in the MRx-4DP0004 treatment arm, compared to 2 in the placebo arm.

“MRx-4DP0004 is a potential novel oral asthma therapy that is safe and well-tolerated in asthma patients in addition to ICS±LABA,” the team wrote. “Part A of the study generated preliminary signals of clinical activity compared to placebo. Part B of the study will assess clinical and biomarker activity.”

Safety and efficacy data for the oral asthma therapy was presented at a late-breaking session at ATS 2022.

MRx-4DP0004 Well Tolerated in Adult Patients with Asthma

A new investigation into benralizumab found that the therapy significantly improved mannitol airway hyperresponsiveness (AHR) and led to better asthma control and quality of life in affected patients.

In their written abstract, investigators led by Rory Chan, PhD, of the University of Dundee School of Medicine, UK, cited AHR as “a hallmark of persistent asthma”, noting that it could also be assessed via indirect challenge with mannitol.

With their study, Chan and colleagues sought to determine the affect of the anti-IL5ra monoclonal antibody benralizumab on AHA, which is currently unknown.

Following an initial 4 week run-in period with usual inhaled corticosteroid (ICS) and LABA treatment at baseline, the team administered 3 doses of open label benralizumab 30mg for 4 weeks in addition to usual therapy in adult patients with severe eosinophilic asthma.

The primary endpoint was the doubling dose (DD) change in mannitol sensitivity as PD10 FEV1 after 12 weeks compared to baseline. This was powered at 90% with 18 patients to detect a 1 DD difference.

Meanwhile, key secondary outcomes included mannitol reactivity as response dose ratio (RDR), spirometry, oscillometry, ACQ-6, mini-AQLQ, peripheral blood eosinophils (PBE) and FeNO.

Among the 19 patients included in the study, the mean age was 53 years and the mean ICS dose was 1884µg. Meanwhile, 11 patients were currently being treating with LAMA.

Investigators found that benralizumab significantly improved mannitol PD10 by 1.7 DD (95%CI 0.7 to 2.8) (P=0.004), as well as significantly improved mannitol RDR, PBE, ACQ and mini-AQLQ by week 12.

Notably, significant attenuation of mannitol AHR was dissociated form a lack of improvement across all lung function outcomes.

Investigators also noted that 10 patients experienced an improvement in PD10 that exceeded ≥1.0 DD. Meanwhile, 18 and 15 patients respectively experienced ACQ and AQLQ improvements which exceeded the MCID ≥0.5 units, and increased FeNO over the 12 week period suggested to investigators that ICS adherence was “unlikely”.

“Benra significantly improved mannitol AHR, in conjunction with better asthma control and quality of life,” the team wrote. “The disconnect between improvements in AHR but not airway calibre infers an anti-inflammatory action due to eosinophil depletion.”

Investigators defined AHR as “a hallmark of persistent asthma”, noting that it could also be assessed via indirect challenge with mannitol.

Benralizumab Significantly Improves Mannitol Airway Hyper-responsiveness 

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