A 3-part series on the manifestations of physician burnout, how COVID-19 changed its scope and revealed systemic fractures, and finally, the path towards resolution and reformation. 

Crisis Point: The Physician Burnout Crisis

. Prior to joining MJH Life Sciences in 2019, he worked as a digital reporter covering nanotechnology, life sciences, material science and more with 

. He graduated with a degree in journalism from Temple University in 2008 and began his career as a local reporter for a chain of weekly newspapers based on the Jersey shore. When not working, he enjoys going to the beach and enjoying the shore in the summer and watching North Carolina Tar Heel basketball in the winter.

Investigators continue to hold promise that developers could make a pharmacologically optimized form of Lysergic acid diethylamide (LSD) for psychiatric diseases like 

Earlier this year, MindMed’s had their Investigational New Drug (IND) application cleared by the US Food and Drug Administration (FDA) for MM-120, paving the way for the company to move forward with a phase 2b dose-optimization trial.

, Rishi Kakar, MD, Chief Scientific Officer and Associate Medical Director for Segal Trials, explained the promise of the LSD compounds in potentially treating GAD and other psychiatric disorders.

The upcoming trial will specifically focus on anxiety and multiple doses of MM-120.

“it’s really sort of revolutionary,” he said. “Here we are studying the dose response.”

Kakar said the study will also focus on other endpoints involving quality of life.

He also said testing treatments like MM-120 can potentially fill an unmet need for chronic psychiatric disorders.

Another reason for the need is anxiety rates are expected to dramatically increase, largely because of the COVID-19 pandemic.

Kakar said the trial could also open up the potential of other trials and drug development of compounds similar to MM-120 that could be a boost for patients with different psychiatric disorders.

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MM-120 is a pharmacologically optimized form of Lysergic acid diethylamide (LSD).

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Rishi Kakar, MD: The Promise of LSD as a Psych Treatment

New research explains regionally whether or not the mortality rate related to 

 (HBV) infections are rising or decreasing in the last decade.

A team, led by Kathleen N. Ly, MPH, Division of Viral Hepatitis, National Center for HIV, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, identified the characteristics of decedents with hepatitis B listed deaths between 2010-2019 and compared the age-adjusted hepatitis B-listed death rates between 2010-2019 and 2000-2009.

The majority of HBV data in the US has focused on national trends, with very little attention paid to regionally statistics to identify differences in mortality rates and decedent characteristics, including birthplace.

In the cross-sectional study, the investigators used Multiple Cause of Death data from all 50 states and Washington D.C. to assess characteristics of US residents with HBV listed as the underlying cause of death or contributing cause of death on death certificates. They identified 35,280 decedents with HBV listed as the cause of death. This included 17,483 deaths between 2010-2019.

The decedents used in the study were mostly US-born (63.3%), while 25.8% of decedents were Asian or Pacific Islander and 46.5% of decedents were White; 28.4% of decedents were listed as having hepatitis C virus (HCV) or HIV coinfection.

The investigators sought main outcomes of hepatitis B-listed death counts, age-adjusted rates, and characteristics of decedents between 2000-2019. They also examinedthe distribution of HBV deaths based on sociodemographic cTrendsharacteristics and underlying causes of death among both US and non-US born decedents.

The results show state-level rates surpassed the overall US rate of 0.47 deaths per 100,000 individuals in several areas, including Washington DC (1.78 deaths per 100 000 population), Hawaii, Oklahoma, California, Tennessee, West Virginia, Mississippi, Oregon, Washington, Louisiana, Kentucky, and New York (0.61 deaths per 100 000 population).

The team also found certain states had trends regarding age of HBV-listed deaths. For example, the deaths skewed younger in Kentucky (54.0; 95% CI, 46.0-64.0 years), West Virginia (56.0; 95% CI, 47.0-65.0 years), Tennessee (57.0; 95% CI, 50.0-65.0 years), Mississippi (58.0; 95% CI, 50.0-65.0 years), and Ohio (59.0; 95% CI, 50.0-66.0 years) than the national median (60.0; 95% CI, 53.0-69.0 years).

In addition, the national death rate already is significantly younger than non-hepatitis B-listed deaths (77; 95% CI, 63.0-87.0 years; 

Hepatitis B as the underlying cause of death represented approximately 30% of the US and non-US born decedents with hepatitis B causes of death, with liver cancer being the most predominant underlying cause of death among non-US born decadents (37.9%).

The investigators also found that the hepatitis B-listed mortality rate significantly decreased national from 2000-2009 and 2010-2019 (-18.97%), as well as in 14 states.

However, West Virginia (change, 83.78%) and Kentucky (change, 69.44%) did see significant increase in HBV-listed mortalities.

“These findings suggest that US-born decedents constituted two-thirds of all hepatitis B–listed deaths and median age at death was youngest in Appalachian states,” the authors wrote. “Irrespective of birthplace, most decedents had liver-related UCOD; however, US-born decedents more frequently had nonliver UCOD than non-US–born decedents. In addition to addressing liver-related complications, US-born persons with chronic infection may also require diagnosis and management of multiple comorbidities.”

Regional Differences in Mortality Rates and Characteristics of Decedents With Hepatitis B Listed as a Cause of Death, United States, 2000-2019

Articles

Washington DC, Hawaii, Oklahoma, California, Tennessee, West Virginia, Mississippi, Oregon, Washington, Louisiana, Kentucky, and New York all had HBV-related mortality rates higher than the national average.

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Hepatitis B Mortality Rate Trends Explained

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 and joined the MJH Life Sciences team in April 2021. He graduated from The College of New Jersey with a degree in Journalism and Professional Writing. He enjoys listening to records, going to concerts, and playing with his cat Squish. You can reach him at 

 suggest the assessment of ganglion cell complex thinning may prove to be important in the prediction of 

From the current retrospective analysis of a longitudinal cohort, baseline faster ganglion cell complex thickness changes had an association with lower vision-related quality of life.

“After adjusting for confounding factors, faster GCC thinning and lower visual acuity were associated with a lower VRQOL,” wrote study author Robert N. Weinreb, MD, Shiley Eye Institute, University of California, San Diego. “Specifically, a lower VRQOL was associated weakly with GCC thinning in the 5.6° and 6.8° central macular areas.”

Weinreb and colleagues set out to investigate the potential of a correlation between vision-related quality of life and measurements taken using optical coherence tomography (OCT) imaging, with a specific focus on macular thickness. They evaluated the association between the rate of macular ganglion cell complex (GCC) thinning and VRQOL in a cohort of patients with glaucoma.

In the retrospective analysis, investigators selected all glaucoma-suspect patients and those with primary open angle glaucoma (POAG) enrolled in the Diagnostic Innovations in Glaucoma Study (DIGS) and African Descent and Glaucoma Evaluation study (ADAGES).

The VRQOL was thus evaluated using the 25-item National Eye Institute Visual Function questionnaire, including the 11 subscales: general vision, ocular pain, difficulty with near vision and distance activities, limitations with peripheral vision and color vision, social functioning, driving difficulties, mental health symptoms related to vision, role limitations, and dependence.

The analysis derived ganglion cell complex thickness from macular OCT scans and averaged within 3 circular areas (3.4°, 5.6°, and 6.8° from the fovea) and superior and inferior

hemi regions. Investigators used linear mixed-effects models to investigate the association between their role and Rasch-calibrated vision function questionnaire scores.

A total of 236 eyes of 118 participants, including 72 participants with bilateral POAG and 46 participants with suspected POAG/glaucoma, were included in this analysis. They had a mean age of 73.2 years, while 65 participants (55.1%) were female and 53 participants (44.9%) self-reported as African-American.

Investigators noted the mean composite Rasch-calibrated National Eye Institute Visual Function Questionnaire score was 50.3 (95% CI, 45.9 - 54.6). In the multivariable model, data show a faster annual rate of GCC thinning in the better eye had an association with a higher disability of a composite NEI VFQ score (-15.0; 95% CI, -28.4 to -1.7 per 1 µm faster; 

Moreover, a faster annual rate of inferior GCC thinning in the better eye was associated with a higher disability of composite NEI VFQ score (-28.4 [95% CI, -49.5 to -7.4] per 1 µm faster; 

= .009), although superior was not (-7.1 [95% CI, -16.1 to 1.9] per 1 µm faster; 

If stratified by degrees from the fovea, investigators found the 5.6” and 6.8” areas were associated with the composite NEI VFQ score (-14.5; [95% CI, -27.0 to -2.0] per 1 µm faster; R2 = 0.201; 

 = .03 and -23.7 [95% CI, -45.5 to -1.9] per 1 µm faster; R2 = 0.196; P = .02, respectively). Meanwhile, the 3.4” area was -8.0 (95% CI, -16.8 to 0.8) per 1 μm faster (R2 = 0.184; P = .07) after adjusting for confounding factors.

“Understanding how structural changes influence VRQOL is vital for understanding which patients may need more frequent observation and additional treatment to prevent visual disability and reduced quality of life,” Weinreb concluded.

The study, “Association Between Ganglion Cell Complex Thinning and Vision-Related Quality of Life in Glaucoma,” was published in 

A faster rate and central location of GCC thinning was associated with lower vision-related quality of life.

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Assessing Ganglion Cell Complex Thinning Aids in Predicting QOL in Glaucoma 

New findings suggest that the risk variant at the age-related maculopathy susceptibility 2/ high-temperature requirement A serine peptidase 1 (ARMS2/HTRA-1) locus was associated with intermediate and late 

Carriers of the homozygote were linked to a particularly high risk of late AMD at early age, according to investigators.

“Compared with other genetic variants, the ARMS2/HTRA1 risk variant showed a similar phenotypic pattern of AMD but also showed strikingly greater risks of the end stages at earlier ages,” wrote study author Caroline C.W. Klaver, MD, PhD, Department of Ophthalmology, Erasmus Medical Centre.

The locus carrying the highest risk is age-related maculopathy susceptibility 2 (ARMS2), but its biological function is still under investigation for AMD. There are still uncertainties on the phenotypic differences between carriers of the ARMS2/HTRA-1 risk variant and those with risk in complement genes.

In a large dataset of the European Eye Epidemiology and EYE-RISK Consortia, the investigators set out to determine the full range of AMD characteristics associated with the risk haplotype at ARMS2/HTRA1 and with variants at the complement pathway. The design was a pooled analysis of 4 case-control and 6 cohort studies.

A total of 17,204 participants had gradable fundus photographs, genotype information for the ARMS2/HTRA1 risk variants, and a baseline age of 55 years or older. They determined AMD features and macular thickness on multimodal images, while data on genetics and phenotype were harmonized.

Additionally, the risks of AMD features for genotypes at the ARMS2/HTRA1 locus were determined by logistic regression and were compared with a genetic risk score of 19 variants at the complement pathway. Investigators estimated lifetime risks with Kaplan-Meier analyses in population-based cohorts.

Out of 2068 individuals identified with late AMD, 64.7% carried the ARMS2/HTRA1 risk allele. Meanwhile, for homozygous carriers, the odds ratio (OR) of geographic atrophy was 8.6 (95% confidence interval [CI], 6.5 - 11.4) and of choroidal neovascularization was 11.2 (95% CI, 9.4 - 13.3), as well as 12.2 for mixed late AMD (95% CI, 7.3 - 20.6).

The cumulative lifetime risk of late AMD had a range of 4.4% for carriers of the non risk genotype to 9.4% and 26.8% for heterozygous and homozygous carriers. Investigators noted the latter patients received the diagnosis of late AMD 9.6 years (95% CI, 8.0 - 11.2) earlier than carriers of the non risk genotype.

Data show the risk haplotype was not associated with hard or soft drusen <125 μm, (OR, 1.2; 95% CI, 0.9 - 1.7), but the risks increased significantly for soft drusen ≥125 μm (OR, 2.1; 95% CI, 1.5 - 3.0), up to an OR of 7.2 (95% CI, 3.8 - 13.8) for reticular pseudodrusen.

In comparison to individuals with a high genetic risk score, homozygous carriers of ARMS2/HTRA1 had a higher risk of choroidal neovascularization (OR, 4.1; 95% CI, 3.2 - 5.4). However, the risks of other characteristics were not different, investigators found.

“More in-depth investigation into the biological properties of ARMS2/HTRA1 will be a significant step toward unraveling AMD pathogenesis,” Klaver concluded.

The Phenotypic Course of Age-Related Macular Degeneration for ARMS2/HTRA1: The Eye-Risk Consortium

Data show the lifetime risk of late AMD ranged from 4.4% for carriers of the nonrisk genotype to 9.4% and 26.8% for heterozygous and homozygous carriers. 

Age-Related Macular Degeneration

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Carriers of ARMS2/HTRA1 Locus Linked to High Risk of Late AMD at Early Age

Armand Butera is the assistant editor for 

. He attended Fairleigh Dickinson University and graduated with a degree in communications with a concentration in journalism. Prior to graduating, Armand worked as the editor-in-chief of his college newspaper and a radio host for WFDU. He went on to work as a copywriter, freelancer, and human resources assistant before joining 

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Swiss pharmaceutical company Galderma announced new data from a pivotal phase 3 trial indicating that 38% of patients with prurigo nodularis reached clearance or almost-clearance of skin lesion following treatment with nemolizumab.

Meanwhile, 56% of nemolizumab-treated patients achieved a 4-point reduction in itch compared to 21% of placebo patients.

The OLYMPIA 2 trial – the largest clinical program of prurigo nodularis to date- met all primary and key secondary endpoints, indicating that the monotherapy improved skin lesions and pruritus itch compared to placebo in adults with moderate to severe disease.

“Prurigo nodularis is known to have a profoundly negative impact on quality of life with currently no approved therapeutic options,” said Flemming Ørnskov, MD, MPH, Chief Executive Officer at Galderma. “These phase 3 trial results indicate that nemolizumab has the potetial to be a key therapeutic solution for patients suffering from moderate to severe prurigo nodularis.”

The OLYMPIA 2 trial featured 540 adult patients aged 18 years and older, 274 of whom struggled with prurigo nodularis. Among these patients, approximately 104 experienced improvements in itch and quality of skin lesions.

A second phase 3 trial with a similar structure to OLYMPIA 2 named OLYMPIA 1, is ongoing.

, Peter A. Lio, MD, of Medical Dermatology Associates in Chicago, Illinois, expressed interest in the potential of nemolizumab for the rare, inflammatory skin condition.

“(Nemolizumab) could be really different and presumably will not have too much of a dampening effect on the immune system,” he said. “It might be a little more of a pure anti-itch [medication], although we know it has an effect in some of the earlier trials we’ve seen on the lesions themselves.”

The treatment is currently approved in Japan for pruritus with atopic dermatitis, and was granted Breakthrough Therapy designation by the Us Food and Drug Administration (FDA) in December 2019 for the treatment of pruritus associated with prurigo nodularis.

Nearly 40% of patients with prurigo nodularis reached clearance or almost-clearance of skin lesions following treatment with nemolizumab.

Atopic Dermatitis

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Nemolizumab Reduces Itch, Improves Skin Lesions of Patients with Prurigo Nodularis

Weekly 300 mg doses of dupilumab were associated with significant, clinically meaningful improvements by week 24 in patients with eosinophilic esophagitis 

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Improvements in Histology, Gene Expression in Dupilumab-Treated Patients with EoE

Travis Vandergriff, MD, discusses the unique collaboration with ophthalmologists and urologists in the rare skin condition.

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The Adequate Evaluation Teams, Treatment Plans for Stevens-Johnson Syndrome

The interventional pulmonology specialist discusses new technology and devices available for diagnosing lung cancer.

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Carla Lamb, MD: Innovations in CT Scan Accuracy

An analysis of PSOARING 1 and 2 data show the topical therapy is efficacious across a wide spectrum of psoriatic disease and patient demographics.

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Tapinarof Cream Benefits Psoriasis Regardless of Baseline Disease Severity, Duration

With guselkumab, patients with active psoriatic arthritis achieved efficacy that was sustained through a 2 year clinical trial. Results show that the treatment offered continuous improvement across measures of health-related quality of life.

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Non-radiographic Axial Spondyloarthritis

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Philip Mease, MD: Guselkumab Addresses the Complexities of Treating Psoriatic Arthritis

Women with the highest PTSD symptoms level experienced significantly worse rates of change regarding learning and working memory.

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PTSD Significantly Associated with Cognitive Decline in Middle Age Women

Event rates were inversely proportional to kidney function in patients with chronic coronary disease.

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 Invasive Management Shows No QoL Benefit in Patients with Poorer Kidney Function 

Drs Pandya discusses vitiligo pathophysiology, the role of genetic and environmental factors, and how to communicate with patients about it.

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Tenofovir was linked to a decreased incidence rate of HCC compared to entecavir. However, this difference was not considered statistically significant.

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Latest News

Rishi Kakar, MD: The Promise of LSD as a Psych Treatment

Hepatitis B Mortality Rate Trends Explained

Assessing Ganglion Cell Complex Thinning Aids in Predicting QOL in Glaucoma

Carriers of ARMS2/HTRA1 Locus Linked to High Risk of Late AMD at Early Age

Nemolizumab Reduces Itch, Improves Skin Lesions of Patients with Prurigo Nodularis