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Jonathan Alicea

Letters informing clinicians of patient death from 

 from a scheduled drug may be an effective, lost-cost way to reduce overprescription of benzodiazepines.

A randomized clinical trial led by Jason Doctor, PhD, of the University of Southern California, and colleagues found that such injunctions were associated with reductions in overall, high-dose, and new opioid prescriptions. A new secondary analysis conducted by the same team further examined associations between distribution of these letters and benzodiazepine prescribing.

“For the present analysis,” they wrote, “we assessed the change in benzodiazepines dispensed 3 months before (pre-period) and 1 to 4 months after (post-period) the injunctions were sent.” They then compared these changes in the intervention group (n = 353) with the control group (n = 390).

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The team used a mixed-effect generalized linear model of 2-mg diazepam pill count to evaluate the differences in the change in prescribing between physicians who received the letter and those who did not.

“The model accounted for whether any prescriptions were dispensed on a given day and, if so, the quantity of 2-mg pills,” they wrote.

Secondary outcomes sought by the team included new patients and those patients’ average day’s supply.

Of the 743 patients who filled a benzodiazepine prescription during the study period, alprazolam and lorazepam were the most frequently dispensed drugs.

The investigators found that use of daily 2-mg pills decreased by 3.7% more in the intervention group when compared with the control group (95% CI, −6.9% to −0.5%; 

Furthermore, on average, there were 2.9 fewer 2-mg diazepam pills dispensed per prescriber per month in the intervention group versus the control group.

Notably, there was no significant difference between groups from the pre-period to post-period in the change in probability, number, or average day’s supply of new treatment initiations. The secondary analysis also showed that, after controlling for new users and opioid coprescriptions, prescribers in the intervention group were not any more likely to reduce daily diazepam milligram equivalents by more than 20%.

“The observed moderate reductions that were associated with the letter seemed to concentrate among continuing prescriptions, which is what was associated with the increase in benzodiazepine prescribing from 2005 to 2012,” the team wrote.

“While the mechanism of the effect is not known, death notification may increase the salience of harmsfor opioid and benzodiazepine prescribing among physicians, thus potentially affecting risk posture,” they continued.

While they acknowledged their limitation in not assessing the clinical well-being of the patients or physicians in the intervention group, the investigators nonetheless recommended that medical examiners send letters or warnings to prescribing physicians following patient death from overdose from a scheduled drug.

Association of Fatal Overdose Notification Letters With Prescription of Benzodiazepines: Secondary Analysis of a Randomized Clinical Trial

Articles

Reductions in prescribed benzodiazepines were especially noted in continuing prescriptions.

Injunction Letters May Reduce Clinician Overprescription of Benzodiazepines

A new study found a bidirectional association between 

 and depression in childhood and early adolescence. The study also observed potential developmental cascades among this young patient population.

Several studies have looked at bidirectional associations between disturbed sleep and depression in children and adolescents, and fewer have examined 3 or more time points. Furthermore, none of these studies have focused on both developmental stages.

“Understanding the longitudinal, bidirectional associations and possible developmental cascades between disturbed sleep and depression has the potential to inform risk identification and prevention programs,” wrote the present study investigators, led by Cecilia Marino, MD, PhD, Hospital for Sick Children.

To better elucidate these associations, the team looked at the Québec Longitudinal Study of Child Development, a representative birth cohort of infants born between 1997 - 1998 to mothers living in Québec, Canada, and utilized cross-lagged models covering both childhood and adolescence. The data were collected across 8 waves between ages 5 - 17 and analyzed from February to October 2021.

The team evaluated 1689 children (50.4% female) and 1113 adolescence (53.5% female). For the childhood analyses – defined as ages 5 - 9 years old – data collected at ages 5, 7, and 8 years were considered. For the adolescence analyses – defined as ages 10 - 17 years old – data collected at 10, 12,13, 15 and 17 were evaluated.

Marino and colleagues sought primary outcomes of disturbed sleep depressive symptoms, which were parent-reported. The team also noted sleep duration, time awake in bed, daytime sleepiness, sleep talking, sleepwalking, night terrors, and nightmares.

In the childhood cohort, parents reported depressive symptoms using the Child Behavior Checklist and Revised Ontario Child Health Study Scales. Adolescents self-reported using the Mental Health and Social Inadaptation Assessment for Adolescents.

Significant bidirectional associations between depressive symptoms and disturbed sleep at all time points were found in childhood, thus indicating cascade processes (range β, 0.07; 95% CI, 0.02-012 to β = 0.15; 95% CI, 0.10-0.19).

Among adolescence, the team observed significant bidirectional associations from depressive symptoms to disturbed sleep (β = 0.09; 95% CI, 0.04-0.14) and vice versa (β, 0.10; 95% CI, 0.04-0.16) between 10 and 12 years.

Furthermore, depressive symptoms were modestly associated with disturbed sleep (β, 0.05; 95% CI, 0.001-0.10) in patients 12 and 13 years old. However, the reverse association was not significant.

Marino and team found that cross-lagged estimates were not significant after 13 years of age; further, the associations did not vary by either sex or puberty-by-sex.

“Taken together, our findings suggest that there might be a sensitive window between 5 and 12 years for sleep interventions to mitigate the emergence and/or growth of later depressive symptoms,” they wrote. “Starting prevention efforts in childhood may have a similar, or even greater impact on depression compared with treatment initiated in adolescence,because it would reduce the risk before depression consolidated.”

Nevertheless, the team highlighted the study’s reliance on self-report data as limitation for their study. They urged further need for objective measurements and/or validated questionnaires.

The study, “Pediatrics Testing Bidirectional, Longitudinal Associations Between Disturbed Sleep and Depressive Symptoms in Children and Adolescents Using Cross-Lagged Models,” was published online in 

The cohort study is the first to report developmental cascades between disturbed sleep and depressive symptoms throughout childhood and early adolescence.

Disturbed Sleep, Depression May Have Bidirectional Relationship Through Early Years

A new study suggests a difference in clinical characteristics between late onset and early onset 

The observational study was performed by investigators at Seoul National University College of Medicine, who recruited 89 female patients with clinical diagnosis of acne vulgaris with a duration not exceeding 5 years from onset.

“Although there have been some studies documenting the clinical characteristics of postadolescent acne, little is known about the clinical characteristics of acne based on the age of onset,” the investigators wrote.

“Accordingly, this is the first study that investigates the clinical characteristics of acne based on the age of onset by using objective and quantitative evaluation methods and elucidates the relationship with topographical andaetiological factors, such as the density of 

The mean age among all enrolled patients was 23 years old, with ages ranging from 10 - 43 years. Patients were divided and observed in 4 groups: <16, 16-20, 21-25, and over 25 years.

The clinical characteristics of the youngest age group (<16) were then compared with that of the other groups.

Facial sebum secretion was measured using a Sebumeter, and sebum was collected at the forehead, nose, cheeks, and chin.Clinical photographs included an anterior view of the entire face as well as lateral views on each side.

“For the regional comparison of the clinical characteristics, the face was divided into the T-zone (forehead, nose and upper chin area) and U-zone (both cheeks, perioral and lower chin area),” the investigators noted. “The lesion counts for the inflammatory papules or non-inflammatory papules (comedones) for each zone were assessed by one dermatologist who was unaware of specific patient information.”

They used a stereotactic fluorescent photography unit to quantitatively evaluate the degree of 

The team performed the Student’s t-test for comparison between the groups, as well as Pearson’s correlation test for the correlation of clinical characteristics, age of onset, sebum level and density of 

The investigators found that patients with acne that developed after the age of 21 presented with different clinical characteristics compared with those with acne onset at younger ages.

The mean lesion counts for the comedones and total acne lesions in the T-zone were found to be significantly less in this late onset group when compared with the early onset group (

.001, respectively).Similarly, for the entire face, the mean comedone count and total lesion counts were significantly less in the late onset group compared with the early onset group (

The late onset group presented with a significantly lower proportion of comedones in the T-zone and entire face than the early onset group (

.013 respectively). Nevertheless, the investigators observed no significant differences in mean lesion counts for the inflammatory lesions between both groups.

Although the level of sebum secretion was generally higher across all regions in those with late onset acne than in those with early onset acne, these findings were not considered statistically significant. There was also no statistically significant difference in the density of 

“The clinical characteristics of early onset acne and late onset acne may indicate a need for different treatment approaches,” the investigators concluded. “Further studies are needed to investigate differences in men with regard to age of onset of acne,” they wrote.

The study, “The clinical features of late onset acne compared with early onset acne in women,” was published online in

 Journal of the European Academy of Dermatology and Venereology.

Patients over 21 years who developed acne presented with different clinical characteristics than younger patients.

Study Observes Differences Between Late Onset and Early Onset Acne in Women

 conditions generally suffer from poorer oral health and oral health‐related quality of life, a new study finds.

The study investigators, led by Yvonne Kiernan, BDS NUI, MFDS RCSEdin, prospectively evaluated the oral health and quality of life of patients with various chronic inflammatory dermatologic/rheumatologic diseases treated with systemic/biologic therapy.

“Oral health is essential to general health and QoL, and the impact of poor oral health on health and QoL is increasingly recognised,” they wrote. “Poor oral health has been associated with adverse pregnancy outcomes, cardiovascular disease pulmonary disease, and diabetes, although causal relations have not yet been clearly established.”

They further noted that those with inflammatory dermatologic and rheumatologic diseases have reported often more oral discomfort/pain, higher levels of periodontal disease, dry mouth and oral mucosal lesions (OML) than healthy controls.

In their observational cross-sectional study, they recruited a total of 100 patients (≥18 years), with 2 groups evenly divided between those with chronic inflammatory dermatologic or rheumatologic disease and patients without a history of chronic inflammation.

Patients then received an oral health assessment, which included a questionnaire of 16 items that related to self-assessed oral health, oral pain/discomfort, dry mouth, oral hygiene habits, oral health‐related quality of life, diet, smoking, alcohol, and education.

The physical exam portion of the assessment, which was performed using internationally standardized templates from the World Health Organization (WHO), was conducted by a dentist in each patient’s respective dermatology or rheumatology clinic as supplemental to their standard clinical care. The examination included dental findings and evaluated periodontal health and presence of oral mucosal lesions.

Kiernan and colleagues found a statistically significant difference in the prevalence of dry mouth, as reported in the questionnaire, between patients with dermatologic/rheumatologic inflammatory diseases and the control group (82% vs 20%, respectively; 

Furthermore, patients with inflammatory disease were 18 times more likely to have dry mouth (odds ratio [OR], 18.2; 95% CI, 6.7– 49.6); as many as 57% of these patients reported having dry mouth ‘very often.’

Furthermore, only 60% of patients with inflammatory dermatological or rheumatological disease diagnoses brushed their teeth twice daily – compared with 80% of the control group (

The oral health examination revealed that the patients with inflammatory diseases had an average of 7.7 missing teeth, while patients in the control group had an average of 4.4 missing teeth (

= .029). The former had a mean of 5.6 filled teeth, and the latter had a mean of 7.6 filled teeth (

And finally, patients with dermatological/rheumatologic disease had a significantly greater loss of clinical attachment (a marker for periodontal disease) in all sextants compared to controls.

The most common inflammatory diagnoses were psoriasis/psoriatic arthritis (48%), followed by rheumatoid arthritis (36%), and systemic lupus erythematosus (6%). Adalimumab (28%) was the most commonly prescribed treatment for these patients, as were etanercept (28%) and methotrexate (16%).

“This study shows an association between oral health and oral health‐related quality of life in patients with severe inflammatory skin and joint disease treated with systemic and biologic therapy,” wrote the investigators

“Dermatologists should receive specific oral health training to optimise the management of oral health in our patients with severe inflammatory diseases,” they concluded.

The study, “Oral health in patients with severe inflammatory dermatologic and rheumatologic disease,” was published online in 

An observational cross-sectional study finds that patients suffering from such inflammatory conditions had a higher average number of missing teeth compared to the control group.