 (HBV) infections and cirrhosis who discontinue nucleostide analogs (NA) are at an increased risk of relapse, even after achieving virologic suppression.

A team, led by Yuhao Yao, Department of Gastroenterology, Dongzhimen Hospital, Beijing University of Chinese Medicine, evaluated existing data on clinical outcomes of nucleostide analog withdrawal in patients with chronic HBV and cirrhosis.

The discontinuation of nucleostide analogs are controversial in the management of hepatitis B-related liver cirrhosis.

“The need for long-term NAs therapy raises safety issues for some patients (elderly patients with comorbidities like diabetes and renal insufficiency) and family planning issues in patients of reproductive age along with increases in treatment costs,” the authors wrote. “For these reasons, many physicians treating CHB patients with NAs for years have become interested in investigating the need for continuation as well as the safety of therapy withdrawal.”

However, investigators have not yet studies clinical outcomes following the discontinuation of nucleostide analogs.

“All NAs have an excellent tolerance and a good safety profile, but they cannot achieve HBV clearance or at least HBsAg loss in the vast majority of cases,” the authors wrote. “Therefore they should be given for very long periods, perhaps indefinitely, especially in cirrhotic patients.”

In the systematic review, the investigators searched for completed studies up until May 2022. The studies involved patients with hepatitis B-related cirrhosis who discontinued nucleostide analogs in virological remission with off-therapy follow-up for more than 12 months.

The team identified 19 studies involving 1287 patients with hepatitis B-related cirrhosis.

The majority of patients were compensated and achieved virological suppression when they concluded antiviral therapy.

The pooled proportions of virological relapse and clinical relapse after discontinuing treatment in cirrhotic patients was 55.23 (95% CI, 40.33–69.67) and 43.56% (95% CI, 26.13–61.85), respectively.

The investigators also observed HBsAg loss in 56 participants (pooled proportion = 13.68%; 95% CI, 5.82–24.18).

Finally, the pooled proportions of HCC development, hepatic decompensation, and overall mortality were 8.76 (95% CI, 2.25–18.95), 3.63 (95% CI, 1.31–7.03), and 0.85% (95% CI, 0.35–1.57), respectively.

“In hepatitis B-related compensated cirrhosis, who have achieved complete virological suppression, discontinuation of oral antivirals still carries a high relapse rate, but the incidence of adverse events is generally low and controlled during follow-up of at least 12 months,” the authors wrote. “Of attention is that discontinuation of NAs can achieve a high rate of HBsAg seroclearance. This study may be helpful in the management of NAs in cirrhotic patients.”

Systematic review: Clinical outcomes of discontinuation of oral antivirals in hepatitis B-related liver cirrhosis

Articles

The pooled proportions of virological relapse and clinical relapse after discontinuing treatment in cirrhotic patients was 55.23 and 43.56%, respectively. 

High Relapse Rate After Discontinuing Antiviral Therapy for HBV Patients With Cirrhosis

Up to 32% of patients who have been infected with COVID-19 are affected by long-onset COVID syndrome. Patients with the syndrome experience symptoms that persist for more than 4 weeks post infection, or the development of sequelae.

Some symptoms that have been associated with long COVID include fatigue, dyspnea, chest pain, cognitive disorders, 

, and psychiatric disorders. This study honed in on the symptoms related to sleep that these patients encounter. 

Alissa Elen Formiga Moura, Hospital Universitário Walter Cantídio, Neurology Service, Universidade Federal do Ceará, Fortaleza, Brazil, and a team of investigators aimed to characterize and evaluate the prevalence of sleep symptoms through clinical evaluation with a neurologist. 

The prospective cohort study initially included 207 patients with post-COVID symptoms, and 189 of them completed the study. In addition to a neurological evaluation to assess the presence of sleep disorders, a more extensive analysis was performed on the subgroup that reported excessive sleepiness. 

Evaluations took place at a neurology outpatient clinic in Hospital Universitário Walter Cantídio – Universidade Federal do Ceará in the state of Ceará, northeast Brazil, and occurred between August 2020-September 2021. 

In order to factor in the prevalence of insomnia in the general population, which was estimated at 10%, investigators calculated the sample size to discern differences that were statistically significant. According to the team, this resulted in a total of 

 = 139 patients; after which, a dropout of 25% was stipulated to compose the final sample, totaling a minimum sample size of 186 patients.

The Spectrum of Sleep Disorders in Long COVID

Results revealed the presence of sleep-related symptoms in 25.3% of patients in the long COVID sample. The marjority of the subgroup (22.2%) reported insomnia, while the remaining 6 (3.17%) reported excessive sleepiness. 

Of those who were experiencing excessive sleepiness, 4 patients underwent a polysomnography evaluation, multiple sleep latencies test, and actigraphic data. According to the results, 1 patient had narcolepsy, and 2 patients had central hypersomnia. 

Additionally, investigators found that patients with a history of steroid use demonstrated an association with insomnia and excessive sleepiness. The latter was also related to depression. The team acknowledged a high prevalence of cognitive complaints from patients. 

"Complaints related to sleep, such as insomnia and excessive sleepiness, seem to be part of the clinical post-acute syndrome (long COVID syndrome), composing part of its clinical spectrum, relating to some clinical data," investigators wrote. 

Central hypersomnia and chronic insomnia: expanding the spectrum of sleep disorders in long COVID syndrome - a prospective cohort study

Investigators aimed to characterize and evaluate the prevalence of sleep symptoms in patients with long COVID syndrome.

Insomnia, Hypersomnia Identified as Symptoms of Long COVID Syndrome

Some of the negatibe impacts from the COVID-19  pandemic included the prevalence of 

 and suicidal thoughts. A team of investigators led by Yi-Hsuan Lin, Department of Nursing, College of Medicine, National Cheng Kung University, decided to evaluate further by assessing what factors contributed to the psychological problems that intensified during this period. 

The study aimed to examine the impact of these factors among 3 study groups including healthcare workers, outpatients, and individuals in the general population of Taiwan. With further understanding, strategies to aid in these areas of mental health can be developed. 

The main findings of the study revealed that fear, trust of information, and resilience were key influences on an individual's ability to suppress suicidal thoughts and insomnia symptoms. 

How did the Pandemic Impact Mental Health?

In the analysis, investigators gathered information from online questionnaires between September 2020-May 2021. Psychometrically validated scales were given to a convenience sample of 205 outpatients, 500 healthcare workers, and 1200 individuals from the general population.

The collected data assessed insomnia severity, suicidal thoughts, fear of COVID-19, trust of information, and resilience, in each study population. Investigators then employed multivariate logistic regression methods to identify variables associated with suicidal thoughts and insomnia. 

The general population showed a statistically significant association with insomnia diagnosis and higher rates of suicidal thoughts compared with the other groups. Those with a greater fear of COVID-19 across all populations demonstrated a significant relationship with suicidal thoughts.

Higher resilience among each study group revealed a meaningful association with lower insomnia. Investigators also acknolwedged the relationship between insomnia diagnosis and greater fear of of the virus that was identified in the general population as well as the healthcare workers. 

Data indicated suicidal thoughts and lower trust of information in the outpatient population were congruent. In the general population, the relationship between suicidal thoughts and more severe insomnia was significant, while the association between insomnia diagnosis and higher suicidal thoughts showed significance in the general population. 

"Trust of information, fear, and resilience were important factors for suppressing suicidal thoughts and insomnia among the three study populations," investigators concluded. "Health policies that monitor psychological status and build resiliency of the public are recommended to help develop tailored strategies for different populations affected by the COVID-19 pandemic."

Factors associated with insomnia and suicidal thoughts among outpatients, healthcare workers, and the general population in Taiwan during COVID-19 pandemic: a cross-sectional study

Factors including trust of information, fear, and resilience were related to insomnia and suicidal thoughts in healthcare workers, general population and outpatients. 

Study Evaluates Insomnia and Suicidality Among Healthcare Workers During COVID-19 Pandemic

 conference, Brett King, MD, PhD, gives a presentation generally along the topic of “the future of the field.” He notices often that his peers are less than enthusiastic for the conversation—“nobody wants to talk about the future when the future never comes,” he explained.

Well, the future came, and it’s all any of his peers want to talk about.

In the second segment of an interview with 

King, associate professor of dermatology at the Yale School of Medicine, discussed the outburst of JAK inhibitor agents in dermatology this year—easily making the emerged drug class the headline story of 2022.

“2022 has brought 2 new therapies for moderate to severe atopic dermatitis: abrocitinib and upadacitinib,” King said. “It brought the first ever treatment for alopecia treat: baricitinib. It brought the first ever treatment for vitiligo: ruxolitinib 1.5% cream. It brought an effective oral therapy for psoriasis: deucravacitinib. All JAK inhibitors. Holy cow, 2022 was the year of the JAK inhibitor. It’s just incredible—we’re able to do things with this class of medicine that we’ve never been able to do before.”

King also discussed his hopes for 2023 successes on the basis of this year’s developments. With a boom of agents reaching the market, he stressed the value of patience going forward.

“Honestly, I want to spend time in this moment,” King said. “But my answer is not that I want to see a pipeline with 4 new things. What I want to see a year from now is that all of us and patients have learned this important thing: it takes time.”

Speaking specifically to the ruxolitinib cream approval for vitiligo, he said clinicians need to advance “our knowledge and our sophistication in the care of these patients.”

“I want for this approval to advance the way we take care of, talk to and counsel our patients,” he said.

Videos

Brett King, MD, PhD, reviews how the drug class has altered the state of chronic skin disease management in this year alone.

2022: The Year of JAK Inhibitors

Earlier this year, the US Food and Drug Administration (FDA) 

 as the first agent designated to treat patients with 

Supported by a phase 3 clinical program portfolio that included data showing capability to repigment skin with the twice-daily JAK inhibitor, ruxolitinib cream was quickly regarded as a landmark breakthrough in dermatologic care—and representative of a promising drug class in investigation still, to boot.

Now, experts would like to take a minute more to learn about this breakthrough.

In the first segment of an interview with 

, Brett King, MD, PhD, associate professor of dermatology at Yale School of Medicine, discussed a recent 

 State of Science Summit he chaired on the subject of vitiligo management. Ruxolitinib cream was a headline discussion for King and his supporting panel—which included primary phase 3 investigator David Rosmarin, MD—though conversation deviated from standard excitement.

 that it’s critical to take time to interpret ruxolitinib cream, its benefit to patients, and its contribution toward better understanding vitiligo as a chronic disease.

“I think we all need to take a step back at timers like this, when we have a huge breakthrough, to measure what we know and what we don’t know,” King said. “One of the really great things about these sorts of advancements is that we learn a lot about the disease.”

King described the ruxolitinib approval as an opportunity for day-to-day clinicians and prescribers to reconsider their level of knowledge into vitiligo management, and to consider what the latest data on the JAK inhibitor should tell them about the disease course itself—warts and all.

“One of the really key things that have come from the ruxolitinib clinical trials is that it takes time to treat this disease,” King said. “You have to tell people, “This is going to take months.” We can erase red skin. We can erase plaques of psoriasis, literally in weeks. We cannot repigment the skin in weeks. It takes months.”

Nonetheless, King echoed the overwhelmingly positive sentiments shared by his peers on ruxolitinib cream’s status as a breakthrough in vitiligo care.

“There’s tremendous reward at the end,” he said. “We need to bring all this together to optimize benefits and treatment success for our patients.”

Why patience is key following the major FDA decision earlier this year.

Brett King, MD, PhD: Following Up the Ruxolitinib Cream Approval for Vitiligo

SDPA 20th Annual Fall Dermatology Conference

, Heather Woolery-Lloyd, MD, FAAD, spoke on dermatoses that commonly affect patients of color.

 and an internationally-known expert in skin of color. She holds lectures around the country as well as internationally regarding cosmetic concerns for those with skin of color.

Woolery-Lloyd’s presentation highlighted common dermatoses such as hair and scalp disorders, pigmentary disorders, and scarring. During the presentation, she reviewed established as well as newer treatment strategies.

“So when it comes to skin, I am primarily treating hyperpigmentation,” she said. “I talked a lot about melasma. Because melasma is probably one of the most challenging things that I treat when it comes to hyperpigmentation… So I talked about how first of all, we need to spend some time with the melasma patients, explaining to them that this is a chronic disease and that we'll work together but there's no one cream or one peel or one procedure that we can do that gets rid of melasma forever. So that's really important.”

She went on to discuss the various steps in how she recommends helping patients struggling with 

“So the treatment and the first phase is actually quite easy,” she said. “But the second phase, the maintenance, is where the challenge begins. The other thing I emphasize for my melasma patients is sunscreens. I recommend a broad spectrum, UVA UVB and ideally also visible light, which contains iron oxides. And the last thing I mentioned is that you can also use oral photoprotection, which doesn't replace sunscreen, but it makes sunscreens work better.”

Woolery-Lloyd also described various types of research into her presentation topics that she feels may contain some gaps in research. One example she gave was that of alopecia.

“When it comes to alopecia and hair loss, there are definitely still gaps but the research in that area is growing too,” she said. “Not as quickly as in the pigmentation area but definitely growing.”

View Woolery-Lloyd’s full interview above to learn more about her 

An interview on the SDPA 2022 presentation of Dr. Woolery-Lloyd in which she discusses dermatoses affecting patients of color.

Heather Woolery-Lloyd, MD, FAAD: Interview on Common Skin of Color Dermatoses

 segment with Orit Markowitz, MD, she described areas in need of greater research in the field of skin health relating to her 

 presentation, as well as innovations she hoped for in the future.

Markowitz works as a dermatologist and a skin cancer specialist. She is also CEO and Founder of Markowitz Medical is known for her work in developing minimally-invasive diagnostic and treatment protocols for 

The presentation Markowitz was interviewed about explored some of the ways 

 and physician associates can distinguish pigmented squamous and pigmented basal cell skin cancers and melanomas, from less dangerous skin issues.

In this interview segment, she first highlighted some gaps in research that she hoped would be expanded upon, such as the field of artificial intelligence (AI) which she describes as helpful for efficiency in the medical field.

“How can we make it better?” Markowitz asked about artificial intelligence. “How can we evolve? How can we make people more efficient? And definitely not ‘how can we replace,’ because AI hasn't really done that in pretty much any field, and certainly not in medicine. It's more what it can do to make us better at what we do, and also to make us more efficient. So that's certainly an area of interest in research.”

Markowitz also described some of the research that she is involved with, such as the ways in which various kinds of medical technology may be used in other spaces.

“But what a lot of the research now that I'm doing is let's take the modalities that we use to diagnose skin cancer, non-invasive imaging, various other technologies, and let's apply them to other aspects of skin and dermatology,” she explained. “Maybe there's things we can learn in the cosmetic space, maybe there are ways to diagnose or even to manage other skin diseases. And so a lot of the research that I'm now doing is actually in those spaces as well.”

Markowitz finished with a description of the future regarding patient knowledge of skin health and skin cancer.

“We have more cases of skin cancer each year than breast, colon, lung, and prostate combined,” she said. “So patients are now more aware of that, due to the fact that they're just more there's just so many more outlets of education for patients.”

View the full interview above regarding Markowitz’s 

A discussion with Dr. Markowitz on her presentation from SDPA 2022, during which she described various gaps in knowledge on skin health and future innovations she hoped to see.

Orit Markowitz, MD: Artificial Intelligence, Patient Knowledge on Skin Cancer

Topical JAK inhibitor ruxolitinib cream was associated with substantial improvements in patients’ skin-related quality of life, pain symptoms, and mental health and wellbeing across both adolescents and adults with 

Society of Dermatology Physician Assistants (SDPA) 2022 Annual Meeting

 in Miami, FL last week showed that patients reported improvements in not only signs and symptoms of atopic dermatitis when treated with ruxolitinib cream over 52 weeks, but additionally improvements in anxiety and depression scoring.

Led by Eric L. Simpson, MD, a group of US investigators sought to define the impact of long-term as-needed ruxolitinib cream treatment on patient-reported quality of life using pooled data from the phase 3 TRuE-AD clinical trial program assessing the JAK inhibitor in adolescent and adult patients with atopic dermatitis.

The assessment included patients aged 12 years and older with atopic dermatitis for at least 2 years who had a baseline Investigator's Global Assessment (IGA) score of 2 or 3 , as well as an affected body surface area (BSA) of 3% to 20%.

The TRuE-AD 1 and 2 clinical trial program included patients who were randomized to 2:1 to either of two ruxolitinib cream strength regimens of 0.75% or 1.5% twice-daily, or vehicle cream twice-daily for 8 weeks. Both trials were double-blinded continuous treatment assessments in which patients were encouraged to continue treating their lesions even after improvement through treatment.

Afterward, patients continued in a double-blind, long-term safety assessment through up to 52 weeks. Investigators collected pooled data from the trial program to interpret quality-of-life, pain symptoms and mental wellbeing outcomes among adolescents and adults treated with ruxolitinib cream.

Simpson and colleagues assessed skin-related quality of life scores via the Dermatology life Quality Index (DLQI) for patients aged 16 years and older, and Children's Dermatology Quality of Life (CDLQI).  Investigators additionally assessed patient skin pain and discomfort, as well as anxiety and depression via the EuroQoL 5-Dimension 5-Levels (EQ-5D-5L) questionnaire.

Their final assessment included 1031 total patients receiving either ruxolitinib cream 0.75% (n = 409), 1.5% (n = 428), vehicle then 0.75% (n = 98), or vehicle then 1.5% (n = 96). Mean patient age was 33.0 years old; 61.7% of patients were female. Mean BSA was 9.7% at baseline, and median duration of atopic dermatitis was 15.1 years.

Mean DLQI score was 9.6; CDLQI score was 8.2, and Itch NRS score was 5.1.

Each of the 4 treatment arms achieved a significant improvement in DLQI from baseline to week 52:

Approximately two-thirds of treated patients achieved a DLQI score of 0 or 1 by week 52 with ruxolitinib cream:

Investigators similarly observed improvements per CDLQI from baseline, as well as proportion of patients to achieve scores of 0 or 1 at week 52.

Regarding measures of skin pain per EQ-5D-5L, investigators observed that more patients who were initiated in either ruxolitinib group reported no skin pain or discomfort compared to patients receiving vehicle or control at week 8. By week 52, ≥63% of each treatment arm had achieved such an outcome.

In measures of anxiety or depression per EQ-5D-5L, investigators observed that ≥72.% of each treatment arm achieved measures of no anxiety nor depression by week 52.

The team noted that 677 (63.2%) patients who applied ruxolitinib cream experienced a treatment-emergent adverse event (TEAE). The most common TEAEs were upper respiratory tract infections (10.1%) and nasopharyngitis (9.7%).

Simpson and colleagues concluded that ruxolitinib cream provided both adolescents and adults with atopic dermatitis significant improvements to their skin-related quality of life, measures of pain and mental health through 52 weeks of therapy.

“Patients who switched from vehicle cream to ruxolitinib cream…had similar improvements in quality of life at week 52 compared to patients initially randomized to ruxolitinib cream,” they wrote.

The study, “Effects of Ruxolitinib Cream on Patient-Reported Quality of Life in Atopic Dermatitis: 52-Week Pooled Results From Phase 3 Studies,” was presented at SDPA 2022.

New long-term phase 3 data show adults and adolescents both improved measures of quality of life when treated with either of 2 doses of ruxolitinib cream.

Ruxolitinib Cream Improves Atopic Dermatitis Pain, Anxiety and Depression Over 52 Weeks

New findings from a post-hoc analysis suggest that baseline optical coherence tomography (OCT) features may help determine the odds of a functional response to risuteganib in individuals with dry 

Nearly 50% of eyes in the treatment arm demonstrated treatment response, compared to approximately 7% in the sham group.

“The characterization of higher-order OCT features may provide important information regarding biomarkers for treatment response and could facilitate optimized clinical trial enrollment and enrichment,” wrote study author Justis P. Ehlers, MD, Department of Ophthalmology, Cleveland Clinic.

The study set out to perform a post-hoc analysis to explore the effect of baseline anatomic characteristics identified on OCT on best-corrected visual acuity (BCVA) responses to risuteganib from a completed phase II study in patients with dry AMD. The phase II study was randomized, double-masked, and placebo controlled.

The subjects included in the study were eyes with intermediate dry AMD with BCVA between 20/40 and 20/200. It excluded patients with concurrent vision-influencing or macula-obscuring ocular pathologies.

The study participants were randomized to receive a 1-mg intravitreal risuteganib injection or a sham injection at baseline. At week 16, a second 1-mg intravitreal injection of risuteganib was given to those in the treatment arm. Two independent, masked reading centers evaluated the baseline anatomic characteristics on OCT in order to explore features associated with positive responses to risuteganib.

Main outcome measures for the study includued treatment response, defined as a gain of ≥8 letters in BCVA from baseline to week 28 in the treatment arm, compared with baseline to week 12 in the sham group. Additionally, anatomic parameters, measured by retinal segmentation platforms, including measures of retinal thickness were compared between the responders and nonresponders to risuteganib.

A total of 39 patients completed the study and underwent analysis. Within the treatment arm, investigators observed 48% of eyes demonstrated treatment responses, compared with 7% in the sham group. Then, in the quantitative anatomic assessment, enhanced ellipsoid integrity, greater outer retinal thickness, and decreased geographic atrophy were associated with increased BCVA gains to risuteganib.

The abstract, “Impact of Baseline Quantitative OCT Features on Response to Risuteganib for the Treatment of Dry Age-Related Macular Degeneration: The Importance of Outer Retinal Integrity,” was published in 

Enhanced ellipsoid integrity, greater outer retinal thickness, and decreased GA were associated with increased BCVA gains with risuteganib.


Baseline OCT Features May Determine Functional Response to Risuteganib in Dry AMD 

Rates of subpar sleep increased by half, or more, among adolescents from 1991-2019, and these disruptions are associated with a number of health consequences. 

 specifically raises an individual's risk of hypertension, diabetes, obesity, depression, heart attack, and stroke.

A cohort study aimed to examine the risk of overdose when treating patients with benzodiazepines compared with alternative therapies for sleep disorders, specifically in young people. Adolescents with sleep disorders are prescribed benzodiazepines and unfortunately, when the treatment is combined with opioid use it can result in an overdose. 

Greta Bushnell, PhD, and investigators, evaluated the overdose risk associated with benzodiazepine treatment compared with other pharmacologic treatments like trazodone, hydroxyzine, xolpidem, zalplon, and eszopiclone in patients with sleep disorders. 

Studying Risks of Sleep Disorder Treatment

This cohort study collected information from a US commercial claims database on individuals aged 10-29 years between 2009-2018. Investigators sought to include those who had a sleep disorder diagnosis and were initiating benzodiazepine, or a comparative treatment. 

In the study, exposures were new use of benzodiazepine treatment or comparator pharmacologic treatments, which was defined as a year or more without a prescrition for the treatment. 

Overdose rates were gathered from inpatient and emergency department (ED) records within 6 months from the beginning of treatment. Analysis included the propensity score–adjusted cumulative incidence of overdose and hazard ratios (HRs) that were estimated with intention-to-treat and as-treated analyses. Investigators stratified results by prior prescription opioid fill.

The investigation included 23,084 individuals initiating benzodiazepine treatment and 66,706 initiating a comparator treatment. The mean age was 23 years and 62.6% of the study population was female. 

When evaluated 6 months following the start of treatment, 9.7% of those on benzodiazepine were still on treatment, which was lower than the 12.3% of those who were on comparator treatment. The crude incidence of drug overdose at the 6 month mark was similar, with 0.9% among the benzodiazepine group and 0.8% in the comparator group. 

However, the adjusted analyses demonstrated an increased risk of drug overdose associated with benzodiazepines compared with the comparator treatments. Compared with individuals who had not recently filled an opioid prescription, the association was more prominent among young people with a recent prescription opioid fill.

"The findings of this study suggest that benzodiazepines, compared with alternative pharmacologic treatments for common sleep disorders, were associated with an increased risk of drug overdose among young people during the following 6-month period,especially among those with a recent opioid prescription," investigators wrote. "Drug overdose is an important safety consideration when treating young people with benzodiazepines."

Association of Benzodiazepine Treatment for Sleep Disorders
With Drug Overdose Risk Among Young People

A cohort study aimed to examine the risk of overdose when treating patients with benzodiazepines compared with alternative therapies for sleep disorders, specifically in young people.

Compared With Other Treatments for Sleep Disorders, Benzodiazepines Increase Risk of Overdose

news page, resources on the topics of disease- and specialty-specific medical news and expert insight can be found. Content includes articles, interviews, videos, podcasts, and breaking news on health care research, treatment, and drug development.

All News

Latest News