New data associate psychological resilience with better physical function and quality of life (QOL) in a cohort of older adults with a history of 

Greater resilience was linked to lower body mass index (BMI), lower self-reported disability, fewer hospitalizations, lower likelihood of frailty, and greater mental QOL (all 

Meanwhile, the association of resilience with metrics including grip strength and self-reported disability varied based on recent hospitalization history, with exploratory post hoc analyses suggesting that the associations could differ based on race and ethnicity.

“Among individuals with zero or one hospitalization, greater resilience was associated with less disability and greater grip strength,” wrote study author KayLoni L. Olson, PhD, Weight Control and Diabetes Research Center, Department of Psychiatry and Human Behavior, Warren Alpert Medical School of Brown University, The Miriam Hospital. “This association was attenuated following 2+ hospitalizations suggesting a threshold effect with resilience having a protective effect only in the context of fewer hospitalizations.”

As the population in the United States continues to age, there is increased urgency to identify contributors to healthy aging. Determining psychological resilience may have relevance for healthy aging, particularly in older adults with T2D.

The current cross-sectional study evaluated resilience, assessed its relationship to demographic factors and T2D management, evaluated the association of resilience with variables implicated in aging-related health, and evaluated resilience as a moderator of the association between hospitalization and aging-related health.

The study participants were men and women with T2D and overweight or obesity, who were 45 –76 years old, with a body mass index (BMI) of ≥25 kg/m

. They were randomly assigned to intensive lifestyle intervention (ILI), compared to diabetes support and education (DSE).

The measures included demographic information, weight/height, diabetes status, number of hospitalizations, resilience, quality of life, depressive symptoms, disability, objective physical function, and frailty. Resilience was measured using the Brief Resilience Scale (BRS), a 6-item self-report scale of perceived ability to adapt and to avoid negative outcomes associated with stress.

From the 5145 participants who were randomized in the Look AHEAD trial, 3199 participants participated in the follow-up assessment and were eligible for inclusion in the analysis.

Investigators observed the BRS was not associated with treatment (DSE: 3.8 ± 0.8; ILI: 3.8 ± 0.7; 

 = .69), but it did vary based on gender (Male: 3.9 ± 0.7; Female: 3.7 ± 0.8; 

 <.01) and race/ethnicity (White: 3.8 ± 0.8; Black: 3.9 ± 0.7; Hispanic: 3.7 ± 0.8).

The findings suggest more frequent hospitalization in the previous year was associated with lower physical (

 = .005), and increased odds of frailty status (

 <.01). Investigators added that only the associations of hospitalizations in the past year with disability (

Increasingly, resilience is believed to be dynamic and to vary over time,” Olson wrote. “The current study does not include all sociocultural factors (e.g., socioeconomic status) that may be relevant for resilience and some important  aspects  of  aging  were  not  assessed (e.g., cognitive function).”

Psychological resilience in older adults with type 2 diabetes from the Look AHEAD Trial

Journal of the American Geriatrics Society

Articles

Greater psychological resilience was associated with lower BMI, fewer hospitalizations, and greater mental QOL in the T2D population. 

Psychological Resilience Linked to Better Physical Function in Older Adults with T2D

Newly approved treatments and a general increase in awareness could help explain why incidence rates of 

 (ADHD) is increasing among adults in Japan.

A team, led by Daimei Sasayama, MD, PhD, Department of Psychiatry, Shinshu University School of Medicine, examined trends in the nationwide incidence of newly diagnosed ADHD between April 2010 and March 2020.

While ADHD is extremely common in childhood, about 50% of pediatric cases will persist into adulthood.

“However, adult ADHD is often underdiagnosed owing to inadequate recognition of the disorder,” the authors wrote.

In the study, the investigators used the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB) and collected demographic and diagnostic information, including all electronic health insurance claims between April 2009 and March 2020.

Overall there were 838,265 patients diagnosed with ADHD between the fiscal year 2010 and 2019, including 121,278 patients diagnosed aged 0-6 years and 381,753 patients diagnosed with ADHD aged 7-19 years.

Overall, during the study period, the incidence of newly diagnosed ADHD increased 2.7 fold in the 0-6 age group, 2.5 fold in the 7-19 age group, and 21.1 fold among adults older than 19 years.

The authors offered reasons for the increase in ADHD diagnoses.

“One reason may be the release of the 

Diagnostic and Statistical Manual of Mental Disorders

) in 2013, which allows combined diagnosis of ADHD and autism spectrum disorder (ASD),” the authors wrote. “Although the 

 precludes a dual diagnosis of ADHD and ASD, the release of the 

 may have prompted physicians to give an additional diagnosis of ADHD to individuals with ASD to prescribe ADHD medications.”

The results also show a bigger increase among adults between 2012-2017, which could be due to increased sensitivity of diagnosis, particularly of adults with ADHD.

In 2012, the Japanese regulatory body approved the first medication for adults with ADHD, which could explain the increased ADHD awareness among this patient population.

The annual incidence of adult ADHD seems to have leveled after reaching a peak of 6 per 10,000 person-years in 2018, which is comparable to the adult ADHD incidence of Asian individuals in the US in 2016.

“Thus, the sensitivity to detect ADHD in the adult population seems to have reached a standard in Japan,” the authors wrote.

Limitations and the Need for Future Research

There were some limitations of the study, including that the available demographic data was restricted to just sex and age groups.

However, the nonetiological factors could help explain partially the apparent increase in ADHD incidence and further research is suggested to show how etiological and nonetiological factors impact the changing incidence of ADHD in Japan.

Trends in Diagnosed Attention-Deficit/Hyperactivity Disorder Among Children, Adolescents, and Adults in Japan From April 2010 to March 2020

The results also show a bigger increase among adults between 2012-2017, which could be due to increased sensitivity of diagnosis.

Incidence Rate of Adult ADHD Growing in Japan

In a new pooled analysis of patients with 

 from the DAPA-HF and DELIVER trials, dapagliflozin was found to significantly reduce the risk of cardiovascular death.

The treatment effects appeared consistent across ejection fraction (EF) levels, although higher rates of overall CV, sudden, and HF-associated deaths were observed among those with lower EF. 

The reductions in CV death from dapagliflozin were principally driven by lower rates of sudden death and death from progressive HF.

“These data provide further evidence of CV death reductions with dapagliflozin across the spectrum of EF and offer additional mechanistic insights into the clinical benefits of SGLT2 inhibition in chronic HF,” said Akshay S. Desai, MD, MPH, Cardiovascular Division, Brigham and Women’s Hospital in a presentation at the Heart Failure Society of America (HFSA) 2022 annual scientific meeting.

Treatment with sodium-glucose cotransporter 2 (SGLT2) inhibitors reduced the risk of the composite of worsening HF events or death from CV causes in previous trial findings, but specific causes of death were not measured.

In a prespecified analysis, Investigators pooled data from the DAPA-HF (n = 4,744 patients) and DELIVER (n = 6,263 patients) trials to uncover the effects of dapagliflozin on cause-specific mortality across the spectrum of EF.

Each trial randomly assigned patients with symptomatic HF to treatment with dapagliflozin (10 mg daily) or placebo, but enrolled adjacent populations with HF and reduced EF (EF ≤40%) and HF with mildly reduced or preserved ejection fraction (EF >40%), respectively.

The prespecified secondary analysis examined the adjudicated mode of death (CV, non-CV, undetermined) and the specific causes of CV death (HF, sudden death, myocardial infarction, stroke, or other CV) in the pooled populations of the 2 trials and its subgroups. Effects of randomized treatment on cause-specific mortality were estimated in Cox proportional hazards models.

Among a total of 11,007 patients in the pooled analysis, there were 1628 deaths during follow-up (mean age, 71.7 years; 1139 male [70.0%]). Of these deaths, 872 (53.5%) were attributed to CV deaths, 487 (29.9%) to non-CV deaths, and 269 (16.5%) to undetermined causes.

From the CV deaths, 289 (33.1%; 17.8% of total deaths) were due to HF, 441 (50.6%; 27.1% of total deaths) were sudden, 69 (7.9%; 4.2% of total deaths) were due to stroke, 47 (5.4%; 2.9% of total deaths) to myocardial infarction, and 26 (3.0%; 1.6% of total deaths) were due to other CV causes.

Investigators noted the proportion of deaths attributed to CV causes (overall and specific cause) was inversely correlated with EF, due to higher proportions of sudden and HF death in the lower EF categories.

In the pooled population, dapagliflozin was associated with lower rates of all-cause death, CV death (HR, 0.86; 95% CI, 0.75 - 0.98; 

 = .02), and the composite of CV or unknown death.

Reductions in CV death were driven principally by lower rates of sudden death (HR, 0.84; 95% CI, 0.70 - 1.01; 

 = .07) and HF death (HR, 0.88; 95% CI, 0.70 - 1.11; 

 = .30). There were little differences observed in the rates of death from stroke or myocardial infarction.

Effect of Dapagliflozin on Cause-Specific Mortality in Patients With Heart Failure Across the Spectrum of Ejection Fraction

The observed reductions in CV mortality in patients treated with dapagliflozin were primarily due to lower rates of HF and sudden death. 

Dapagliflozin Associated with Lower Risk of CV Death Across Ejection Fraction Spectrum

Research suggests that depressive symptoms in older adults were associated with poor visual acuity, and that visual health was associated with altered brain neurobiology.

One of the primary contributors to diminished health and well-being of older populations is known to be visual health decline. Visual impairment is known to play a major role in depression for 

, potentially due to its effects on vision, mobility, and even risk of poverty.

This study sought out to analyze the associations between depressive symptoms and visual health in middle-aged and older adults within the United Kingdom. The research was led by Xiayin Zhang, PhD, and Honghua Yu, PhD, of the Guangdong Eye Institute in Guangdong Provincial People’s Hospital’s Department of Ophthalmology.

“From a health policy perspective, finding ways to prevent depression and improve daily functioning has substantial public health impacts,” Zhang and colleagues wrote. “Our findings highlight the value of visual health in association with mental health. Screening of vision at an early stage should be embedded in the middle-aged and older population to stratify the vulnerable population at risk for depression.”

The investigators used a cohort study, with a sample of 114,583 older adult participants from the UK Biobank database. The volunteers were included at baseline from March through June 2006 up until July 2010. They found that about 55% (62,401) of participants were female and about 46% (52,182) were male. The participants’ mean age was about 56.8 years.

The research team also analyzed participants’ demographic information and covariates such as obesity, alcohol use, physical activity, and genetic history of depression. Depression scores for participants were assessed through either an interview-based diagnosis from a psychiatrist or through the Patient Health Questionnaire (PHQ).

The investigators also analyzed multimodal magnetic resonance imaging (MRI) brain scans of a subgroup of 7844 eligible participants. Participants with brain-damaging diseases such as Parkinson’s or strokes were excluded from the study. They analyzed the research data from May 5 to August 9, 2022.

The investigators found that a 1-line worse visual acuity was associated with 5% higher chance of depressive symptoms (odds ratio, 1.05 [95% CI, 1.04 - 1.07]). This statistic was found after adjusting for demographic characteristics, Townsend index, education, alcohol and tobacco consumption, obesity, physical exercise, hyperlipidemia, hypertension history, diabetes, and familial history of depression.

In the subgroup recruited to receive MRI scans, the investigators found that there were linear associations between PHQ scores and extracellular water diffusion in the fornix of the brain and/or the stria terminalis. They also found linear associations between the participants’ PHQ scores and the left volume of gray matter in supracalcarine cortex

Participants’ levels of visual acuity could moderate these associations, as higher PHQ scores were associated with higher isotropic volume fraction (ISOVF) levels only with participants with diminished visual acuity.

“Studies on mental health supported our hypothesis that the fornix and stria terminalis are involved in the pathophysiology of schizophrenia, bipolar disorder, and autism spectrum disorder,” they wrote.”Thus, our findings suggest that poorer visual acuity was associated with greater depressive symptoms and may have contributed to the related deterioration of the fornix and stria terminalis.”

Association of Visual Health With Depressive Symptoms and Brain Imaging Phenotypes Among Middle-Aged and Older Adults

A recent study found that worsened visual acuity and depression were associated with neurobiological changes visible through MRI scans.

Poor Visual Acuity in Older Adults Associated With Depression, Altered Neurobiology

 (HCV) infections with direct-acting antivirals (DAA), there remains a risk of liver-related complications for patients with inherited bleeding disorders after the HCV is cured.

A team, led by Cas J. Isfordink, Van Creveldkliniek, Department of Benign Hematology, University Medical Center Utrecht, Utrecht University, identified liver-related complications during long-term chronic HCV infections and following sustained virological response (SVR) in patients with inherited bleeding disorders.

DAA treatments have gone a long way in curing HCV infections for patients with inherited bleeding disorders. However, there is not much data on the risk of liver-related complications after patients with inherited bleeding disorders are cured of HCV.

“Although successful HCV treatment is considered to substantially reduce the risk of liver-related complications, this risk is not entirely eradicated,” the authors wrote. “In the general HCV population, liver-related complications following SVR are more frequent after DAA-induced SVR than following interferon-induced SVR because in contrast to interferon, also patients with more advanced liver disease are eligible for DAA therapy.”

In the retrospective follow-up, the investigators examined patients with positive HCV antibodies with inherited bleeding disorders at a single center that provides care for approximately 50% of the Dutch population with hemophilia.

Data was collected on age, body mass index (BMI), hemophilia-related variables, alcohol use, hepatitis B virus and HIV co-infections, and date and cause of death for each patient.

The investigators sought primary endpoints of liver-related complications, including hepatocellular carcinoma (HCC), decompensated cirrhosis, bleeding gastroesophageal varices. Each liver-related complication was reported separately during chronic HCV and following SVR. The complications were stratified for interferon-based and DAA-based SVR.

Of the 381 patients included in the study, 81% (n = 309) of HCV antibody-positive patients developed a chronic HCV infection with a median follow-up of 44 years. Of this group, 12% (n = 36) developed a liver-related complication after a median of 31 years of chronic infection.

There were 199 patients with SVR, 97 of which were cured with interferon-based regimens and 102 of which were cured with DAA after a median infection duration of 29 years and 45 years, respectively.

After the follow-up period, 21% had advanced fibrosis and 42% had cirrhosis. After SVR, 4% (n = 7) of patients had a liver-related complication, the majority of which were HCC (n = 4).

The incidence of liver-related complications per 100 patient-years post-SVR follow-up was 0.2 for interferon-cured and 1.0 for DAA-cured patients (

“Successful HCV treatment does not eliminate the risk of liver-related complications in persons with inherited bleeding disorders,” the authors wrote. “Due to higher baseline risk, incidence was higher after DAA than interferon-based SVR. We advise continuing HCC surveillance post-SVR in all with advanced fibrosis or cirrhosis.”

Liver-related complications before and after successful treatment of chronic hepatitis C virus infection in people with inherited bleeding disorders

Liver Disease Risk Remains for HCV Patients With Bleeding Disorders

New research examined opioid consumption in patients that underwent knee or shoulder arthroscopy. Patients were randomized and either received standard opioid treatment, or a multimodal opioid-sparing pain management protocol for postoperative recovery. 

The findings showed a significant reduction of opioid consumption over a period of 6 weeks among those participating in the opioid-sparing approach compared with those who received standard opioid prescribing practices.

Evidence has been compiling on the benefits of these multimodal protocols to decrease postoperative opioid use following knee or shoulder arthroscopy while still addressing patients' pain. This team of investigators, led by Olufemi R. Ayeni, MD, PhD, Division of Orthopaedic Surgery, Department of Surgery, McMaster University, aimed to add to the existing evidence, which lacks prospective, comparitive trials by evaluating the effect of the opioid-sparing approach. 

The Multimodal Opioid-Sparing Pain Management Protocol

Measurement of the outcomes included postoperative oral morphine equivalent (OME) consumption at 6 weeks after surgery for the primary endpoint, and pain, patient satisfaction, opioid refills, quantity of OMEs prescribed at the time of hospital discharge, and adverse events, which was all reported at week 6 post-surgery.

The randomized clinical trial enrolled 200 patients from March 2021-March 2022 from 3 clinical sites in Ontario, Canada. The 6 week postoperative follow-up concluded in April 2022. 

Patients in the intervention group were prescribed naproxen, acetaminophen (paracetamol), and pantoprazole, along with a limited rescue perscription of hydromorphone and an educational infographic. For the control group, the treating surgeon decided how to prescribe opioid analgesics—the current standard of care. 

Standard Opioid Consumption ≠ Less Pain

When compared with the control group (median, 40 mg), data demonstrated that patients in the opioid-sparing protocol (median, 0 mg) had significantly lower opioid consumption 6 weeks after surgery. And although 4 of the 5 secondary endpoints revealed no significance, this indicated no meaningful difference in patient-reported pain between the groups.

The secondary outcome that yielded a significant difference was the amount of prescribed OMEs, with the average amount of 341.2 mg in the standard care group and 40.4 mg in the intervention group. Investigators reported a mean difference of 300.8 mg. 

While the number of adverse events were not significantly different between the groups, with 2 events in standard care and 3 in the opioid-sparing protocol, investigators noted that significantly more patients in the standard care group (32%) reported medication-related adverse events than the intervention group (19%) at 6 weeks (

Of the 200 patients randomized into 2 groups of 100, the mean age was 43 years with a male majority (62%). At the end of the trial, 98 patients in standard care, and 95 in opioid-sparing protocol completed the trial. 

"The underlying premise is that concurrent administration of multiple analgesics results in an additive effect and has the potential to reduce opioid consumption while maximizing pain control," investigators wrote. "NSAIDS are potent analgesics that form a cornerstone of multimodal analgesic protocols. Although NSAIDs carry risks, they were well tolerated in the current study and may be considered a first-line analgesic for patients without contraindications."

Effect of a Postoperative Multimodal Opioid-Sparing Protocol vs Standard Opioid Prescribing on Postoperative Opioid Consumption After Knee or Shoulder Arthroscopy: A Randomized Clinical Trial

After undergoing arthroscopic knee or shoulder surgery, patients treated with an opioid-sparing postoperative pain management protocol had reduced opioid use compared with standard treatment.

Opioid-Sparing Postoperative Pain Management Reduces Opioid Use While Controlling Pain

Levels of cerebrospinal fluid (CSF) metal ions indicate a physiological association between cigarette smoking and risk of depression and 

In research from a team of China investigators, the CSF levels of multiple metal ions in a population of male participants showed raised counts of elements like magnesium and zinc—common among current smokers—are linked to measures of depression like the Beck Depression Inventory (BDI) and insomnia like the Pittsburgh Sleep Quality Index (PSQI).

Led by Yuying Li, of the Wenzhou Medical College Affiliated Third Hospital in China, investigators sought to determine links between cigarette smoking and neuropsychiatric burdens including anxiety, depression and insomnia via CSF metal ion levels. As they noted, previous laboratory-level analyses have associated ions including aluminum, manganese, and zinc with these conditions, and cigarette smoke is known to cause accumulation of such metals quickly in users.

“However, no study has been published yet that uses CSF metal ions to investigate the relationship between active smoking and emotional dysfunction and sleep disorder,” they wrote.

Due to smoking prevalence being very low among women in China, Li and colleagues’ analysis included 178 male pariticpants recruited from September 2014 - January 2016. Among participants, 64 (30.3%) were active smokers. Investigators recorded sociodemographic data including age, years of education and body mass index (BMI). They also included patient-reported clinical data relevant to the analysis.

Investigators conducted patient questionnaires including PSQI, BDI, the Self-Rating Anxiety Scale (SRAS), and the Fagerstrom Test for Nicotine Dependence (FTND) to interpret insomnia status, depression, anxiety and nicotine dependence, respectively, in each patient.

At the time of recruitment, each male patient was undergoing anterior cruciate ligament (ACL) reconstructive surgery; because of this, they had underwent a lumbar puncture that allowed for a CSF sample extraction. Investigators assessed for levels of magnesium, zinc, iron, lead, lithium, copper, manganese and aluminum.

Investigators observed significantly greater higher scores for BMI (25.7 vs 24.37; 

 <.001) among active smokers than nonsmokers—indicating greater obesity, depression and insomnia rates, respectively. Smokers also had significantly greater CSF levels of magnesium, zinc, iron, lead, lithium and aluminum (

Using a Spearman’s correlations assessment, investigators interpreted a positive correlation between zinc, iron, lead and aluminum, depression per BDI (

 <.01). They additionally observed a positive correlation between metal ions including zinc and lead, and sleep quality per PSQI (

Though the trial was limited by potentially confounding health associated with ACL injury patients, as well as the exclusivity of male participants, the team concluded their findings were promising enough to warrant future assessment.

“Cigarette smoking was associated with depression and insomnia, as shown by higher BDI and PSQI scores,” they wrote. “Significantly higher magnesium, zinc, iron, lead, lithium, and aluminum CSF levels were found in active smokers than in nonsmokers. Furthermore, CSF aluminum played a mediating role in the relationship between smoking and depression, which further confirmed its neurotoxicity.”

The study, “Metal ions in cerebrospinal fluid: Associations with anxiety, depression, and insomnia among cigarette smokers,” was published online in 

A new analysis suggests raise levels of zinc, iron, lead and aluminum—linked to cigarette use—is positively correlated with insomnia.

Cigarette Smoking, Insomnia and Depression Linked by CSF Metal Ion Levels

The negative consequence of social isolation is fairly well known, but new data show patients with 

 (IBD) who are socially isolated are at an increased risk of premature mortality.

A team, led by Jie Chen, Department of Gastroenterology, The Third Xiangya Hospital of Central South University, examined the joint association of social isolation and IBD with premature deaths.

While research on the impact of social isolation continues to expand, the effect of social isolation on patients with IBD remains poorly understood. A recent analysis shows social isolation in patients with IBD is 1 of the main obstacles to leading a normal life.

However, this information thus far is largely limited to qualitative studies that could capture patients more prone to social isolation because of disease-related stress, negative perception of social support, lack of public awareness, and surrounding stigma.

“Patients with IBD are known to have distressing and severe physical symptoms such as abdominal pain, diarrhea, fecal urgency, weight loss, and rectal bleeding,” the authors wrote. “These can cause emotional and social stress that persists even during remission periods, contributing to the deterioration of the quality of life.”

In the longitudinal cohort study, the investigators identified the data of 486,014 patients from the UK Biobank, including 5791 individuals with IBD. There was a mean follow-up of 11.84 years with 32,390 incident cases of all-cause mortality documented. The mean age of the patient population was 56.5 years.

In addition, 10.4% (n = 600) of patients with IBD and 9.2% (n = 44,401) of non-IBD participants were socially isolated.

Each patient’s IBD diagnosis and subtype was confirmed using a combination of self-reporting, primary care, and hospital admission data. The investigators also measured social isolation by the frequency of meeting family and friends, leisure and social activity, and communal or solitary living.

The team also obtained mortality information through data linkage with national death registries.

To analyze this data, the team conducted multivariable Cox regression models to estimate hazard ratios and 95% confidence intervals.

The hazard ratios of mortality for patients with IBD who were socially isolated was 2.06 (95% CI, 1.69-2.51) compared to a non-isolated non-IBD population. The hazard ratio for patients with IBD who were not socially isolated was 1.33 (95% CI, 1.21-1.45).

The excess risk of death was found in socially isolated patients with IBD (HR, 1.69; 95% CI, 1.36-2.11). This was particularly strong among patients with Crohn’s disease (HR, 2.06; 95% CI, 1.48-2.87) than patients with Crohn’s disease who were not socially isolated.

Subgroup and sensitivity data analyses were consistent from the data from the primary analysis.

“Patients with IBD, especially CD, are more likely to be affected when socially isolated, associating with a higher risk of early death in patients with CD,” the authors wrote. “Therefore, social isolation merits attention, and targeted social support strategies and interventions ought to be devised.”

The investigators suggest future studies look at the differing consequences of social isolation between different IBD subtypes.

Associations between inflammatory bowel disease, social isolation, and mortality: evidence from a longitudinal cohort study,

Recent qualitative studies found social isolation in patients with IBD is 1 of the main obstacles to leading a normal life. 

Social Isolation Increases Risk of Premature Death for IBD Patients

Folic acid prescriptions result in a significant drop in 

 and overall suicidal events, according to new research.

A team, led by Robert D. Gibbons, PhD, University of Chicago, confirmed a previous signal for a decreased risk of suicide attempts after prescription fills for folic acid.

Overall, suicides have increased by more than 30% in the US between 2000-2018.

“An inexpensive, safe, widely available treatment for preventing suicidal behavior could reverse this trend,” the authors wrote.

In the national pharmacoepidemiologic study, the investigators examined data from 866,586 patients treated with folic acid with a within-person exposure only cohort design to identify the dynamic association between folic acid prescription fills over a 24-month time period and suicide attempts and intentional self-harm.

Of the more than 850,000 patients with data included in the analysis, 81.30% (n = 704,514) were female and 10.42% (n = 90,296) were aged 60 years or older.

The team used a pharmacoepidemiologic database of US medical claims to identify patients with private health insurance who filled a folic acid prescription between 2012-2017. They then repeated the analysis with a control supplement of cyanocobalamin.

The investigators sought main outcomes of suicide attempts or intentional self-harm resulting in an outpatient visit or inpatient admission as identified by codes from the 

International Statistical Classification of Diseases, Ninth and Tenth Revisions, Clinical Modification

The analysis shows 261 suicidal events during months covered by a folic acid prescription (5,512,597 person-months. The rate of suicidal events was 4.73 events per 100,000 person-months. This was lower than the 895 suicidal events during months without folic acid (8,432,340 person-months) for a rate of 10.61 suicidal events per 100,000 person-months.

After adjusting for age and sex, the investigators found diagnoses related to suicidal behavior, folic acid deficiency, folate-reducing medications, history of folate-reducing medications, and history of suicidal events yielded a hazard ratio for folic acid for suicide events of 0.56 (95% CI, 0.48-0.65).

There were similar results for modal dosage of 1 mg of folic acid per day (HR, 0.57; 95% CI, 0.48-0.69) and women of childbearing age (HR, 0.60; 95% CI, 0.50-0.73).

However, a further duration-response analysis of 1-mg dosage produced a 5% decrease in suicidal events per month of additional treatment (HR, 0.95; 95% CI, 0.93-0.97) and the same analysis for cyanocobalamin showed no association with suicide attempts (HR, 1.01; 95% CI, 0.80-1.27).

“This large-scale pharmacoepidemiologic study of folic acid found a beneficial association in terms of lower rates of suicide attempts,” the authors wrote. “The results warrant the conduct of a randomized clinical trial with suicidal ideation and behavior as outcomes of interest. If confirmed, folic acid may be a safe, inexpensive, and widely available treatment for suicidal ideation and behavior.”

Association Between Folic Acid Prescription Fills and Suicide Attempts and Intentional Self-harm Among Privately Insured US Adults

A duration-response analysis of 1-mg dosage produced a 5% decrease in suicidal events per month of additional treatment.

Folic Acid Decreases Rate of Suicidal Attempts

A recent study found that 8-weeks of apremilast and phototherapy as a combined treatment may be sufficient with 

, but it may require a longer regimen length.

Patients with moderate to severe psoriasis vulgaris are frequently 

 with apremilast—an oral phosphodiesterase-4 inhibitor—and phototherapy. However, their combined use’s safety and efficacy were not viewed to be properly studied prior to this research.

This study into their combined use was led by Akimichi Morita of the Nagoya City University Graduate School of Medical Sciences Department of Geriatric and Environmental Dermatology.

“Phototherapy has many advantages in the treatment of psoriasis, but continued use is inconvenient because the effects of the therapy appear only after a long time, and patients are required to frequently visit the clinic for irradiation,” Morita and colleagues wrote. “In this study, the combination of apremilast and phototherapy demonstrated sufficient therapeutic effects in psoriasis despite the reduced frequency of visits to the clinic, which may have considerable implications in clinical practice.”

The investigators’ research compared the safety and efficacy of only phototherapy (monotherapy) with that of the combination of apremilast and phototherapy (combination).

The investigators used a multicenter, randomized active-controlled study that was open-label and parallel-group, through 4 institutions in Japan between November of 2018 and February of 2020. Inclusion criteria for patients consisted of being 20 to 80 years old, having a moderate to severe psoriasis vulgaris diagnosis, and having an inadequate topical treatment response.

The researchers’ primary endpoint for the study—from baseline to 8 weeks of treatment—was a Psoriasis Area and Severity Index (PASI) score improvement rate. There were 7 secondary endpoints for their research, including:

The PASI score and improvement rate from baseline to 4 and 8 weeks after treatment;

Number and percentage of patients achieving PASI scores with ≥90%, ≥75%, and ≥50% improvements, or PASI90, PASI75, and PASI50

PASI score changes from baseline to each evaluation time point

BSA changes from baseline to each evaluation time point;

sPGA scores at baseline and at each time point;

Percentage of study participants having an sPGA score of 0 (disappeared) or 1 (almost disappeared)

Changes in EuroQol 5-dimensions 5-level (EQ-5D-5L), Dermatology Life Quality Index (DLQI), and visual analog scale (VAS) scores regarding itchiness from baseline to each evaluation time point

The investigators had the patients receive apremilast as 10, then 20, then 30, then 40, then 50 mg of apremilast on the first 5 days of the study, with 60 mg each day beginning on the sixth day. For phototherapy, NB-UVB treatment was administered 2 times per week.

In total, there were 42 participants recruited for the study, with 29 in the combination arm and 13 in the monotherapy arm. The results of the study found that the combination group reported significantly lower PASI scores by 4 and 8 weeks. The combination group also reported more patients achieving a PASI score improvement of ≥75% by 8 weeks.

By week 8, they did not observe a statistically significant difference between both groups. The investigators found that both the combination and the monotherapy group had a significant decrease in BSA. The combination group data leaned toward a greater BSA reduction. Adverse events (AEs) were also reported more often in the combination arm than the monotherapy arm of the study.

“Our findings indicate that phototherapy as monotherapy was insufficient in patients with high baseline BSA, and concomitant administration of apremilast improved the outcomes,” they wrote. “However, an 8-week treatment regimen may be insufficient for inducing subjective improvement.”

Efficacy and safety of apremilast and phototherapy versus phototherapy only in psoriasis vulgaris

A combination therapy approach may be useful for psoriasis treatment, though an 8-week regimen may not be long enough.

Study Suggests Combination of Phototherapy, Apremilast Effective for Psoriasis Vulgaris

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