Depression remission after six months of collaborative care management: role of initial severity of depression in outcome

Aim The impact of initial severity of depression on the rate of remission has not been well studied. The hypothesis for this study was that increased depression severity would have an inverse relationship on clinical remission at six months while in collaborative care management.Participants The study cohort was 1128 primary care patients from a south-eastern Minnesota practice and was a longitudinal retrospective chart review analysis.Results Clinical remission at six months was less likely in the severe depression group at 29.6% compared with 36.9% in the moderately severe group and 45.6% in the moderate depression group (P < 0.001). Multivariate analysis of a sub-group demonstrated that increased initial anxiety symptoms (odds ratio [OR] 0.9645, 95% confidence interval [CI] 0.9345–0.9954, P = 0.0248) and an abnormal screening for bipolar disorder (OR 0.4856, 95% CI 0.2659–0.8868, P = 0.0187) predicted not achieving remission at six months. A patient with severe depression was significantly less likely to achieve remission at six months (OR 0.6040, 95% CI 0.3803–0.9592, P = 0.0327) compared with moderate depression, but not moderately severe depression (P = 0.2324). There was no statistical difference in the adjusted means of the PHQ-9 score for those patients who were in remission at six months. However, in the unremitted patients, the six-month PHQ-9 score was significantly increased by initial depression severity when controlling for all other variables.Conclusion Multivariate analysis in our study demonstrated that patients with severe depression have a decreased OR for remission at six months compared with moderate depression. Also, there was a significant increase in the six-month PHQ-9 score for those unremitted patients in the severe vs. moderate depression groups.     

The Prevalence of Anxiety and Depression in Chinese Asthma Patients

It is well documented that the psychiatric disorders are common in Asthma patients in China while the studies on the relationship between asthma control and psychological disorder are comparatively rare. We therefore performed a cross-sectional study on asthmatic outpatients in one Chinese tertiary center to investigate the correlation among asthma, anxiety and depression. Demographic data, anxiety and depression scores, the level of asthma control were collected in 261 patients. All patients were evaluated with Asthma Control Test (ACT), Self-Rating Anxiety Scale (SAS) and Self-rating depression scale (SDS) questionnaires. A multivariate analysis was performed to investigate the relationship between asthma control and psychological disorder. The result showed that 31 asthma patients had anxiety symptom while thirty-five asthma patients had depression. One hundred and ninety-two asthma patients were well controlled and 69 patients were not. The study found a negative correlation between ACT and SAS(r = −0.231, p<0.001) as well as ACT and SDS(r = −0.23, p<0.001) and depression (OR: 12.295, 95%CI: [5.374–28.128], p<0.001) were both independently associated with poor asthma control. We concluded that Asthma control is greatly affected by psychological disorder in Chinese patients.     

The Association of Depression and Anxiety with Pain: A Study from NESDA

Chronic pain is commonly co-morbid with a depressive or anxiety disorder. Objective of this study is to examine the influence of depression, along with anxiety, on pain-related disability, pain intensity, and pain location in a large sample of adults with and without a depressive and/or anxiety disorder. The study population consisted of 2981 participants with a depressive, anxiety, co-morbid depressive and anxiety disorder, remitted disorder or no current disorder (controls). Severity of depressive and anxiety symptoms was also assessed. In separate multinomial regression analyses, the association of presence of depressive or anxiety disorders and symptom severity with the Chronic Pain Grade and location of pain was explored. Presence of a depressive (OR = 6.67; P<.001), anxiety (OR = 4.84; P<.001), or co-morbid depressive and anxiety disorder (OR = 30.26; P<.001) was associated with the Chronic Pain Grade. Moreover, symptom severity was associated with more disabling and severely limiting pain. Also, a remitted depressive or anxiety disorder showed more disabling and severely limiting pain (OR = 3.53; P<.001) as compared to controls. A current anxiety disorder (OR = 2.96; p<.001) and a co-morbid depressive and anxiety disorder (OR = 5.15; P<.001) were more strongly associated with cardio-respiratory pain, than gastro-intestinal or musculoskeletal pain. These findings remain after adjustment for chronic cardio respiratory illness. Patients with a current and remitted depressive and/or anxiety disorder and those with more severe symptoms have more disabling pain and pain of cardio-respiratory nature, than persons without a depressive or anxiety disorder. This warrants further research.     

White Matter Microstructural Changes as Vulnerability Factors and Acquired Signs of Post-Earthquake Distress

Many survivors of severe disasters need psychological support, even those not suffering post-traumatic stress disorder (PTSD). The critical issue in understanding the psychological response after experiencing severe disasters is to distinguish neurological microstructural underpinnings as vulnerability factors from signs of emotional distress acquired soon after the stressful life event. We collected diffusion-tensor magnetic resonance imaging (DTI) data from a group of healthy adolescents before the Great East Japan Earthquake and re-examined the DTIs and anxiety levels of 30 non-PTSD subjects from this group 3–4 months after the earthquake using voxel-based analyses in a longitudinal DTI study before and after the earthquake. We found that the state anxiety level after the earthquake was negatively associated with fractional anisotropy (FA) in the right anterior cingulum (Cg) before the earthquake (r = −0.61, voxel level p<0.0025, cluster level p<0.05 corrected), and positively associated with increased FA changes from before to after the earthquake in the left anterior Cg (r = 0.70, voxel level p<0.0025, cluster level p<0.05 corrected) and uncinate fasciculus (Uf) (r = 0.65, voxel level p<0.0025, cluster level p<0.05 corrected). The results demonstrated that lower FA in the right anterior Cg was a vulnerability factor and increased FA in the left anterior Cg and Uf was an acquired sign of state anxiety after the earthquake. We postulate that subjects with dysfunctions in processing fear and anxiety before the disaster were likely to have higher anxiety levels requiring frequent emotional regulation after the disaster. These findings provide new evidence of psychophysiological responses at the neural network level soon after a stressful life event and might contribute to the development of effective methods to prevent PTSD.     

Who is the Treatment-Seeking Young Adult with Severe Obesity: A Comprehensive Characterization with Emphasis on Mental Health

Objective

To characterize treatment-seeking young adults (16–25 years) with severe obesity, particularly mental health problems.

Study Design and Participants

Cross-sectional study of 165 participants (132 women, 33 men) with BMI ≥35 kg/m² or ≥30 kg/m² with comorbidities, enrolling in a multidisciplinary obesity treatment program.

Method

Data collection at admission of present and life-time health issues including symptomatology of anxiety, depression (Hospital Anxiety and Depression Scale) and attention-deficit/hyperactivity disorder (Adult ADHD Self-Report scale); self-esteem (Rosenberg Self-Esteem Scale), suicide attempts, health-related quality of life (Short Form-36 Health Survey), psychosocial functioning related to obesity (Obesity-related Problems Scale), cardiorespiratory fitness (Astrand´s bicycle ergometer test), somatic and psychiatric co-morbidities, cardiometabolic risk factors, and micronutritional status. We used multiple regression analysis to identify variables independently associated with present anxiety and depressive symptomatology.

Results

Mean body mass index was 39.2 kg/m² (SD = 5.2). We found evidence of poor mental health, including present psychiatric diagnoses (29%), symptomatology of anxiety (47%), depression (27%) and attention-deficit/hyperactivity disorder (37%); low self-esteem (42%), attempted suicide (12%), and low quality of life (physical component score = 46, SD = 11.2; mental component score = 36, SD = 13.9, P<0.001 for difference). Variables independently associated with present anxiety symptomatology (R ² = 0.33, P<0.001) included low self-esteem (P<0.001) and pain (P = 0.003), whereas present depressive symptomatology (R ² = 0.38, P<0.001) was independently associated with low self-esteem (P<0.001), low cardiorespiratory fitness (P = 0.009) and obesity-related problems (P = 0.018). The prevalence of type 2 diabetes was 3%, and hypertension 2%. Insulin resistance was present in 82%, lipid abnormality in 62%, and poor cardiorespiratory fitness in 92%. Forty-eight percent had at least one micronutritional deficiency, vitamin D being the most common (35%).

Conclusion

A wide range of health issues, including quite severe mental health problems, was prevalent in treatment-seeking young adults with severe obesity. These are likely to constitute a major treatment challenge, including options relating to bariatric surgery.     

Sleep Disturbances and Health-Related Quality of Life in Adults with Steady-State Bronchiectasis

Background

Sleep disturbances are common in patients with chronic lung diseases, but little is known about the prevalence in patients with bronchiectasis. A cross sectional study was conducted to investigate the prevalence and determinants associated with sleep disturbances, and the correlation between sleep disturbances and quality of life (QoL) in adults with steady-state bronchiectasis.

Methods

One hundred and forty-four bronchiectasis patients and eighty healthy subjects were enrolled. Sleep disturbances, daytime sleepiness, and QoL were measured by utilizing the Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS) and St. George Respiratory Questionnaire (SGRQ), respectively. Demographic, clinical indices, radiology, spirometry, bacteriology, anxiety and depression were also assessed.

Results

Adults with steady-state bronchiectasis had a higher prevalence of sleep disturbances (PSQI>5) (57% vs. 29%, P<0.001), but not daytime sleepiness (ESS≥10) (32% vs. 30%, P = 0.76), compared with healthy subjects. In the multivariate model, determinants associated with sleep disturbances in bronchiectasis patients included depression (OR, 10.09; 95% CI, 3.46–29.37; P<0.001), nocturnal cough (OR, 1.89; 95% CI, 1.13–3.18; P = 0.016), aging (OR, 1.04; 95% CI, 1.01–1.07; P = 0.009) and increased 24-hour sputum volume (OR, 2.01; 95% CI, 1.22–3.33; P = 0.006). Patients with sleep disturbances had more significantly impaired QoL affecting all domains than those without. Only 6.2% of patients reported using a sleep medication at least weekly.

Conclusions

In adults with steady-state bronchiectasis, sleep disturbances are more common than in healthy subjects and are related to poorer QoL. Determinants associated with sleep disturbances include depression, aging, nighttime cough and increased sputum volume. Assessment and intervention of sleep disturbances are warranted and may improve QoL.     

Associations of parental depression during adolescence with cognitive development in later life in China: A population-based cohort study

BackgroundPrior research has underscored negative impacts of perinatal parental depression on offspring cognitive performance in early childhood. However, little is known about the effects of parental depression during adolescence on offspring cognitive development.Methods and findingsThis study used longitudinal data from the nationally representative China Family Panel Studies (CFPS). The sample included 2,281 adolescents aged 10–15 years (the median age was 13 years with an interquartile range between 11 and 14 years) in 2012 when their parents were surveyed for depression symptoms with the 20-item Center for Epidemiologic Studies Depression Scale (CES-D). The sample was approximately balanced by sex, with 1,088 females (47.7%). We examined the associations of parental depression in 2012 with offspring cognitive performance (measured by mathematics, vocabulary, immediate word recall, delayed word recall, and number series tests) in subsequent years (i.e., 2014, 2016, and 2018) using linear regression models, adjusting for various offspring (i.e., age, sex, and birth order), parent (i.e., parents’ education level, age, whether living with the offspring, and employment status), and household characteristics (i.e., place of residence, household income, and the number of offspring). We found parental depression during adolescence to be significantly associated with worse cognitive performance in subsequent years, in both crude and adjusted models. For example, in the crude models, adolescents whose mothers had depression symptoms in 2012 scored 1.0 point lower (95% confidence interval [CI]: −1.2 to −0.8, p < 0.001) in mathematics in 2014 compared to those whose mothers did not have depression symptoms; after covariate adjustment, this difference marginally reduced to 0.8 points (95% CI: −1.0 to −0.5, p < 0.001); the associations remained robust after further adjusting for offspring earlier cognitive ability in toddlerhood (−1.2, 95% CI: −1.6, −0.9, p < 0.001), offspring cognitive ability in 2012 (−0.6, 95% CI: −0.8, −0.3, p < 0.001), offspring depression status (−0.7, 95% CI: −1.0, −0.5, p < 0.001), and parents’ cognitive ability (−0.8, 95% CI: −1.2, −0.3, p < 0.001). In line with the neuroplasticity theory, we observed stronger associations between maternal depression and mathematical/vocabulary scores among the younger adolescents (i.e., 10–11 years) than the older ones (i.e., 12–15 years). For example, the association between maternal depression and 2014 vocabulary scores was estimated to be −2.1 (95% CI: −2.6, −1.6, p < 0.001) in those aged 10–11 years, compared to −1.2 (95% CI: −1.6, −0.8, p < 0.001) in those aged 12–15 years with a difference of 0.9 (95% CI: 0.2, 1.6, p = 0.010). We also observed a stronger association of greater depression severity with worse mathematical scores. The primary limitations of this study were the relatively high attrition rate and residual confounding.ConclusionsIn this study, we observed that parental depression during adolescence was associated with adverse offspring cognitive development assessed up to 6 years later. These findings highlight the intergenerational association between depression in parents and cognitive development across the early life course into adolescence.

In this cohort study, Zhihui Li and colleagues explore associations between parental depression and offspring cognitive development up to six years later.     

Elevated Hair Cortisol Levels among Heroin Addicts on Current Methadone Maintenance Compared to Controls

Whether methadone maintenance treatment (MMT) can improve the basal function of the hypothalamic–pituitary–adrenal (HPA) axis, which is suppressed by long-term heroin consumption, is a matter of debate. The stress state and depression and anxiety symptoms may affect the basal activity of the HPA axis in MMT patients. However, the effect of psychological factors on HPA activity was not simultaneously controlled in previous studies. This study investigated differences in HPA basal activity between MMT patients and controls using psychological variables as covariates. The participants included 52 MMT patients and 41 age-matched, non-heroin-dependent controls. Psychological states were self-reported with the Perceived Stress Scale, Self-Rating Depression Scale and Self-Rating Anxiety Scale. The hair cortisol level was adopted as a biomarker of HPA basal activity and was determined with liquid chromatography tandem mass spectrometry. The results revealed that MMT patients had significantly higher hair cortisol levels than the controls (p<0.05), but the difference was not significant (p>0.05) when the perceived stress, depression and anxiety scores were used as covariates. We concluded that patients with long-term MMT showed higher basal activity of the HPA axis. The high chronic stress state and increase in depression and anxiety symptoms may mask the suppression effect of methadone on the HPA activity.     

Opt-Out and Opt-In Testing Increases Syphilis Screening of HIV-Positive Men Who Have Sex with Men in Australia

Background

Since 2005, Australian clinicians were advised to undertake quarterly syphilis testing for all sexually active HIV-positive men who have sex with men (MSM). We describe differences in syphilis testing frequency among HIV-positive MSM by clinic testing policies since this recommendation.

Methods

Three general practices, two sexual health clinics and two hospital HIV outpatient clinics provided data on HIV viral load and syphilis testing from 2006–2010. Men having ≥1 viral load test per year were included; >95% were MSM. We used Chi-2 tests to assess changes in syphilis testing frequency over time, and differences by clinic testing policy (opt-out, opt-in and risk-based).

Results

The proportion of men having HIV viral loads with same-day syphilis tests increased from 37% in 2006 to 63% in 2007 (p<0.01) and 68–69% thereafter. In 2010, same-day syphilis testing was highest in four clinics with opt-out strategies (87%, range:84–91%) compared with one clinic with opt-in (74%, p = 0.121) and two clinics with risk-based strategies (22%, range:20–24%, p<0.01). The proportion of men having ≥3 syphilis tests per year increased from 15% in 2006 to 36% in 2007 (p<0.01) and 36–38% thereafter. In 2010, the proportion of men having ≥3 syphilis tests in a year was highest in clinics with opt-out strategies (48%, range:35–59%), compared with opt-in (39%, p = 0.121) and risk-based strategies (8.4%, range:5.4–12%, p<0.01).

Conclusion

Over five years the proportion of HIV-positive men undergoing syphilis testing at recommended frequencies more than doubled, and was 5–6 times higher in clinics with opt-out and opt-in strategies compared with risk-based policies.     

Lower Urinary Tract Symptoms,Depression, Anxiety and Systemic Inflammatory Factors in Men: A Population-Based Cohort Study

Background

The relationship between lower urinary tract symptoms (LUTS) and common mental health disorders such as depression and anxiety in men remains unclear. Inflammation has recently been identified as an independent risk factor for LUTS and depression. This study aimed to assess the association between depression, anxiety and LUTS, and the moderating influence of systemic inflammation, in the presence of other biopsychosocial confounders.

Methods

Participants were randomly-selected from urban, community-dwelling males aged 35–80 years at recruitment (n = 1195; sample response rate:67.8%). Of these, 730 men who attended baseline (2002–5) and follow-up clinic visits (2007–10), with complete outcome measures, and without prostate or bladder cancer and/or surgery, neurodegenerative conditions, or antipsychotic medications use, were selected for the present study. Unadjusted and multi-adjusted regression models of incident storage and voiding LUTS and incident depression and anxiety were combined with serum inflammatory markers (high-sensitive C-reactive protein (hsCRP), tumor necrosis factor-alpha (TNF-α), interleukin–6 (IL–6), myeloperoxidase (MPO), soluble e-selectin (e-Sel)) and socio-demographic, lifestyle, and health-related factors. Hierarchical multiple regression was used to assessed the moderating effect of inflammatory markers.

Results

The incidence of storage, voiding LUTS, depression and anxiety was 16.3% (n = 108), 12.1% (n = 88), 14.5% (n = 108), and 12.2% (n = 107). Regression models demonstrated that men with depression and anxiety at baseline were more likely to have incident storage, but not voiding LUTS (OR: 1.26, 99%CI: 1.01–4.02; and OR:1.74; 99%CI:1.05–2.21, respectively). Men with anxiety and storage LUTS at baseline were more likely to have incident depression (OR: 2.77, 99%CI: 1.65–7.89; and OR:1.45; 99%CI:1.05–2.36, respectively), while men with depression and voiding LUTS were more likely to have anxiety at follow-up (OR: 5.06, 99%CI: 2.81–9.11; and OR:2.40; 99%CI:1.16–4.98, respectively). CRP, TNF-α, and e-Sel were found to have significant moderating effects on the development of storage LUTS (1.06, 0.91–1.96, R² change: 12.7%), depression (1.17, 1.01–1.54, R² change: 9.8%), and anxiety (1.35, 1.03–1.76, R² change: 10.6%), respectively.

Conclusions

There is a bidirectional relationship between storage, but not voiding, LUTS and both depression and anxiety. We observed variable moderation effects for selected inflammatory markers on the development of depression, anxiety and storage LUTS.     

Depression and Health Related Quality of Life in Adolescent Survivors of a Traumatic Brain Injury: A Pilot Study

Traumatic brain injury is (TBI) a leading cause of morbidity and mortality in youth. Adult survivors of a severe pediatric TBI are vulnerable to global impairments, including greater employment difficulties, poor quality of life (HRQoL) and increased risk of mental health problems. When estimating the health related quality of life in adolescents, the presence of anxiety and depression and the quality of social relationships are important considerations, because adolescents are entrenched in social development during this phase of maturation. The influence of anxiety, depression and loneliness on health related quality of life in adolescent survivors of TBI has not been documented. This pilot study aimed to identify and measure the relationship between anxiety, depression and loneliness and perceived health related quality of life in adolescent survivors of a TBI. Method: mixed method/cohort pilot study (11 adolescents, mild to severe TBI; 9 parents), using self-report and proxy-report measures of anxiety, depression, health related quality of life, loneliness and clinical psychiatric interviews (adolescent only). Results: Self-reported depression was significantly correlated with self-reported HRQoL (rs [11] = −0.88, p<0.001). Age at injury was significantly correlated with self-reported HRQoL (rs [11] = −0.68, p = 0.02). Self-reported depression predicted self-reported HRQoL (R² = 0.79, F [1, 10] = 33.48, p<0.001), but age at injury did not (R² = 0.19, F [1, 10] = 2.09, p = 0.18). Conclusions: Our results suggest that depression is a predictor of health related quality of life in youth post-TBI. The possibility of using targeted assessment and therapy for depression post-TBI to improve health related quality of life should be explored.     

Prevalence of Depression in a Large Urban South Indian Population — The Chennai Urban Rural Epidemiology Study (Cures – 70)

Background

In India there are very few population based data on prevalence of depression. The aim of the study was to determine the prevalence of depression in an urban south Indian population.

Methods and Findings

Subjects were recruited from the Chennai Urban Rural Epidemiology Study (CURES), involving 26,001 subjects randomly recruited from 46 of the 155 corporation wards of Chennai (formerly Madras) city in South India. 25,455 subjects participated in this study (response rate 97.9%). Depression was assessed using a self-reported and previously validated instrument, the Patient Health Questionnaire (PHQ) – 12. Age adjustment was made according to the 2001 census of India. The overall prevalence of depression was 15.1% (age-adjusted, 15.9%) and was higher in females (females 16.3% vs. males 13.9%, p<0.0001). The odds ratio (OR) for depression in female subjects was 1.20 [Confidence Intervals (CI): 1.12–1.28, p<0.001] compared to male subjects. Depressed mood was the most common symptom (30.8%), followed by tiredness (30.0%) while more severe symptoms such as suicidal thoughts (12.4%) and speech and motor retardation (12.4%) were less common. There was an increasing trend in the prevalence of depression with age among both female (p<0.001) and male subjects (p<0.001). The prevalence of depression was higher in the low income group (19.3%) compared to the higher income group (5.9%, p<0.001). Prevalence of depression was also higher among divorced (26.5%) and widowed (20%) compared to currently married subjects (15.4%, p<0.001).

Conclusions

This is the largest population-based study from India to report on prevalence of depression and shows that among urban south Indians, the prevalence of depression was 15.1%. Age, female gender and lower socio-economic status are some of the factors associated with depression in this population.     

Adverse childhood experiences,adult depression,and suicidal ideation in rural Uganda: A cross-sectional,population-based study

BackgroundDepression is recognized globally as a leading cause of disability. Early-life adverse childhood experiences (ACEs) have been shown to have robust associations with poor mental health during adulthood. These effects may be cumulative, whereby a greater number of ACEs are progressively associated with worse outcomes. This study aimed to estimate the associations between ACEs and adult depression and suicidal ideation in a cross-sectional, population-based study of adults in Uganda.Methods and findingsBetween 2016 and 2018, research assistants visited the homes of 1,626 adult residents of Nyakabare Parish, a rural area in southwestern Uganda. ACEs were assessed using a modified version of the Adverse Childhood Experiences-International Questionnaire, and depression symptom severity and suicidal ideation were assessed using the Hopkins Symptom Checklist for Depression (HSCL-D). We applied a validated algorithm to determine major depressive disorder diagnoses. Overall, 1,458 participants (90%) had experienced at least one ACE, 159 participants (10%) met criteria for major depressive disorder, and 28 participants (1.7%) reported suicidal ideation. We fitted regression models to estimate the associations between cumulative number of ACEs and depression symptom severity (linear regression model) and major depressive disorder and suicidal ideation (Poisson regression models). In multivariable regression models adjusted for age, sex, primary school completion, marital status, self-reported HIV status, and household asset wealth, the cumulative number of ACEs was associated with greater depression symptom severity (b = 0.050; 95% confidence interval [CI], 0.039–0.061, p < 0.001) and increased risk for major depressive disorder (adjusted relative risk [ARR] = 1.190; 95% CI, 1.109–1.276; p < 0.001) and suicidal ideation (ARR = 1.146; 95% CI, 1.001–1.311; p = 0.048). We assessed the robustness of our findings by probing for nonlinearities and conducting analyses stratified by age. The limitations of the study include the reliance on retrospective self-report as well as the focus on ACEs that occurred within the household.ConclusionsIn this whole-population, cross-sectional study of adults in rural Uganda, the cumulative number of ACEs had statistically significant associations with depression symptom severity, major depressive disorder, and suicidal ideation. These findings highlight the importance of developing and implementing policies and programs that safeguard children, promote mental health, and prevent trajectories toward psychosocial disability.

In a cross-sectional, population based study of adults in rural Uganda, Emily Satinsky and colleagues investigate adverse childhood experiences and associations with depression and suicidal ideation.     

Hemoglobin A1c Levels and Risk of Severe Hypoglycemia in Children and Young Adults with Type 1 Diabetes from Germany and Austria: A Trend Analysis in a Cohort of 37,539 Patients between 1995 and 2012

Background

Severe hypoglycemia is a major complication of insulin treatment in patients with type 1 diabetes, limiting full realization of glycemic control. It has been shown in the past that low levels of hemoglobin A1c (HbA1c), a marker of average plasma glucose, predict a high risk of severe hypoglycemia, but it is uncertain whether this association still exists. Based on advances in diabetes technology and pharmacotherapy, we hypothesized that the inverse association between severe hypoglycemia and HbA1c has decreased in recent years.

Methods and Findings

We analyzed data of 37,539 patients with type 1 diabetes (mean age ± standard deviation 14.4±3.8 y, range 1–20 y) from the DPV (Diabetes Patienten Verlaufsdokumentation) Initiative diabetes cohort prospectively documented between January 1, 1995, and December 31, 2012. The DPV cohort covers an estimated proportion of >80% of all pediatric diabetes patients in Germany and Austria. Associations of severe hypoglycemia, hypoglycemic coma, and HbA1c levels were assessed by multivariable regression analysis. From 1995 to 2012, the relative risk (RR) for severe hypoglycemia and coma per 1% HbA1c decrease declined from 1.28 (95% CI 1.19–1.37) to 1.05 (1.00–1.09) and from 1.39 (1.23–1.56) to 1.01 (0.93–1.10), respectively, corresponding to a risk reduction of 1.2% (95% CI 0.6–1.7, p<0.001) and 1.9% (0.8–2.9, p<0.001) each year, respectively. Risk reduction of severe hypoglycemia and coma was strongest in patients with HbA1c levels of 6.0%–6.9% (RR 0.96 and 0.90 each year) and 7.0%–7.9% (RR 0.96 and 0.89 each year). From 1995 to 2012, glucose monitoring frequency and the use of insulin analogs and insulin pumps increased (p<0.001). Our study was not designed to investigate the effects of different treatment modalities on hypoglycemia risk. Limitations are that associations between diabetes education and physical activity and severe hypoglycemia were not addressed in this study.

Conclusions

The previously strong association of low HbA1c with severe hypoglycemia and coma in young individuals with type 1 diabetes has substantially decreased in the last decade, allowing achievement of near-normal glycemic control in these patients. Please see later in the article for the Editors'' Summary     

A Meta-Analysis on the Relationship between Self-Reported Presence and Anxiety in Virtual Reality Exposure Therapy for Anxiety Disorders

In virtual reality exposure therapy (VRET) for anxiety disorders, sense of presence in the virtual environment is considered the principal mechanism that enables anxiety to be felt. Existing studies on the relation between sense of presence and level of anxiety, however, have yielded mixed results on the correlation between the two. In this meta-analysis, we reviewed publications on VRET for anxiety that included self-reported presence and anxiety. The comprehensive search of the literature identified 33 publications with a total of 1196 participants. The correlation between self-reported sense of presence and anxiety was extracted and meta-analyzed. Potential moderators such as technology characteristics, sample characteristics including age, gender and clinical status, disorder characteristics and study design characteristics such as measurements were also examined. The random effects analysis showed a medium effect size for the correlation between sense of presence and anxiety (r = .28; 95% CI: 0.18–0.38). Moderation analyses revealed that the effect size of the correlation differed across different anxiety disorders, with a large effect size for fear of animals (r = .50; 95% CI: 0.30–0.66) and a no to small effect size for social anxiety disorder (r = .001; 95% CI: −0.19–0.19). Further, the correlation between anxiety and presence was stronger in studies with participants who met criteria for an anxiety disorder than in studies with a non-clinical population. Trackers with six degrees of freedom and displays with a larger field of view resulted in higher effect sizes, compared to trackers with three degrees of freedom and displays with a smaller field of view. In addition, no difference in effect size was found for the type of presence measurement and the type of anxiety measurement. This meta-analysis confirms the positive relation between sense of presence and anxiety and demonstrates that this relation can be affected by various moderating factors.     

Rheumatoid Arthritis and the Risk of Bipolar Disorder: A Nationwide Population-Based Study

Background

Studies have suggested that chronic inflammation plays an essential role in the pathophysiology of both rheumatoid arthritis (RA) and bipolar disorder. The most common clinical features associated with RA are anxiety and depression. The risk of bipolar disorder among patients with RA has not been characterized adequately.

Objective

To determine the association between RA and the subsequent development of bipolar disorder and examine the risk factors for bipolar disorder among patients with RA.

Methods

We identified patients who were diagnosed with RA in the Taiwan National Health Insurance Research Database. A comparison cohort was created by matching patients without RA with those with RA according to age, sex, and comorbidities. The occurrence of bipolar disorder was evaluated in both cohorts.

Results

The RA cohort consisted of 2,570 patients, and the comparison cohort consisted of 2,570 matched control patients without RA. The incidence of bipolar disorder (incidence rate ratio  = 2.13, 95% confidence interval [CI]  = 1.12–4.24, P =  .013) was higher among patients with RA than among control patients. Multivariate, matched regression models revealed that asthma (hazard ratio [HR]  = 2.76, 95% CI 1.27–5.96, P =  .010), liver cirrhosis (HR  = 3.81, 95% CI  = 1.04–14.02, P =  .044), and alcohol use disorders (HR  = 5.29, 95% CI  = 1.71–16.37, P =  .004) were independent risk factors for the development of bipolar disorder among patients with RA.

Conclusion

RA might increase the incidence of bipolar disorder development. Based on our data, we suggest that, following RA diagnosis, greater attention be focused on women with asthma, liver cirrhosis, and alcohol use disorder. Prospective clinical studies of the relationship between RA and bipolar disorder are warranted.     

Interferon-Inducible Transmembrane Protein 3 Genetic Variant rs12252 and Influenza Susceptibility and Severity: A Meta-Analysis

BackgroundThe pandemic influenza A (H1N1) pdm09 virus, avian influenza A (H5N1) virus, and influenza A (H7N9) virus induced severe morbidity and mortality throughout the world. Previous studies suggested a close association between the interferon-induced transmembrane protein-3 (IFITM3) genetic variant rs12252 and influenza. Here, we explored the correlation between the rs12252 and influenza susceptibility and severity using meta-analysis.MethodsRelevant studies published before May 22, 2014 were retrieved from PubMed, ISI web of knowledge, EBSCO, and Cochrane central register of controlled trials databases. Association between rs12252 and influenza susceptibility and severity were determined using statistical analysis of odds ratios (ORs).ResultsA total of four studies consisting of 445 cases and 4180 controls were included in our analysis. Generally, there is increased risk of influenza in subjects carrying rs12252 in the recessive model (CC vs. CT+TT: OR = 2.35, 95% CI: 1.49-3.70, P<0.001), the dominant model (CC+CT vs. TT: OR=1.60, 95% CI: 1.18–2.22, P=0.003), the homozygote comparison (CC vs. TT: OR=4.11, 95% CI: 2.15–7.84, P<0.001), and the allele contrast (C vs. T: OR=1.67, 95% CI: 1.32–2.13, P<0.001). Stratification analysis of ethnicity and severity revealed a significant increase in influenza susceptibility by IFITM3-SNP rs12252 among both Asian and Caucasian population. SNP rs12252 shows significant impact on severe infections (P<0.05), but not on mild influenza. Besides, our result also associated rs12252 with influenza severity (severe vs. mild: OR=2.37, 95% CI: 1.32–4.25, P=0.004), (severe vs. control: OR=2.70, 95% CI: 1.85–3.94, P<0.001).ConclusionOur meta-analysis suggests a significant association between a minor IFITM3 allele (SNP rs12252-C) with severe influenza susceptibility, but not in mild influenza subjects, in both UK Caucasians and Han Chinese population. The rs12252-C allele causes a 23.7% higher chance of infection and also constitutes a risk factor for more severe influenza.     

Effects of Baseline Problematic Alcohol and Drug Use on Internet-Based Cognitive Behavioral Therapy Outcomes for Depression,Panic Disorder and Social Anxiety Disorder

Purpose

Patients’ problematic substance use prevalence and effects were explored in relation to internet-based cognitive behavioral therapy (ICBT) outcomes for depression, panic disorder and social anxiety disorder.

Methods

At baseline and treatment conclusion, 1601 ICBT patients were assessed with self-rated measures for alcohol and drug use (AUDIT/DUDIT), depressive symptoms (MADRS-S), panic disorder symptoms (PDSS-SR) and social anxiety symptoms (LSAS-SR).

Results

Problematic substance use (AUDIT ≥8 for men, ≥6 for women; DUDIT ≥1) occurred among 32.4% of the patients; 24.1% only alcohol, 4.6% only drugs, and 3.7% combined alcohol and drug use. Hazardous alcohol use and probable alcohol dependence negatively affected panic disorder outcomes, and hazardous drug use led to worse social anxiety outcomes. Depression outcomes were not affected by substance use. Treatment adherence was negatively affected by problematic drug use among men and 25–34 year olds; combined substance use negatively affected adherence for women and 35–64 year olds.

Conclusion

Problematic substance use does not preclude ICBT treatment but can worsen outcomes, particularly problematic alcohol use for panic disorder patients and hazardous drug use for social anxiety patients. ICBT clinicians should exercise particular caution when treating men and younger patients with problematic drug use, and women or older patients with combined substance use.     

A Naturalistic Study of the Acceptability and Effectiveness of Internet-Delivered Cognitive Behavioural Therapy for Psychiatric Disorders in Older Australians

Objectives

The current study investigates the acceptability, effectiveness and uptake of internet-delivered cognitive behavioural therapy (iCBT) amongst older individuals (>60 years) seeking psychiatric treatment in general practice.

Methods

The sample consisted of 2413 (mean age 39.5; range 18–83 years) patients prescribed iCBT through This Way Up clinic by their primary care clinician. The intervention consisted of six fully automated, unassisted online lessons specific to four disorders major depression, generalised anxiety disorder, panic disorder or social phobia. Patients were categorised into five age groups (18–29 years, 30–39 years, 40–49 years, 50–59 years, 60 years and above). 225 (9.3%) patients were aged over 60 years. Analyses were conducted across the four disorders to ensure sufficient sample sizes in the 60 years and older age group. Age differences in adherence to the six lesson courses were assessed to demonstrate acceptability. Age-based reductions in psychological distress (Kessler Psychological Distress Scale; K10) and disability (the World Health Organisation Disability Assessment Schedule; WHODAS-II) were compared to demonstrate effectiveness. To evaluate the uptake of iCBT, the age distribution of those commencing iCBT was compared with the prevalence of these disorders in the 2007 Australian National Survey of Mental Health and Well-Being.

Results

Older adults were more likely to complete all six lessons when compared with their younger counterparts. Marginal model analyses indicated that there were significant reductions in the K10 and WHODAS-II from baseline to post-intervention, regardless of age (p<0.001). The measurement occasion by age interactions were not significant, indicating that individuals showed similar reductions in the K10 and WHODAS-II regardless of age. In general, the age distribution of individuals commencing the iCBT courses matched the age distribution of the four diagnoses in the Australian general population, indicating that iCBT successfully captures older individuals who need treatment.

Conclusion

iCBT is effective and acceptable for use in older populations.     

Mycobacterium ulcerans in the Elderly: More Severe Disease and Suboptimal Outcomes

Background

The clinical presentation of M. ulcerans disease and the safety and effectiveness of treatment may differ in elderly compared with younger populations related to relative immune defficiencies, co-morbidities and drug interactions. However, elderly populations with M. ulcerans disease have not been comprehensively studied.

Methodology/Principal Findings

A retrospective analysis was performed on an observational cohort of all confirmed M. ulcerans cases managed at Barwon Health from 1/1/1998-31/12/2014. The cohort included 327 patients; 131(40.0%) ≥65 years and 196(60.0%) <65 years of age. Patients ≥65 years had a shorter median duration of symptoms prior to diagnosis (p<0.01), a higher proportion with diabetes (p<0.001) and immune suppression (p<0.001), and were more likely to have lesions that were multiple (OR 4.67, 95% CI 1.78–12.31, p<0.001) and WHO category 3 (OR 4.59, 95% CI 1.98–10.59, p<0.001). Antibiotic complications occurred in 69(24.3%) treatment episodes at an increased incidence in those aged ≥65 years (OR 5.29, 95% CI 2.81–9.98, p<0.001). There were 4(1.2%) deaths, with significantly more in the age-group ≥65 years (4 compared with 0 deaths, p = 0.01). The overall treatment success rate was 92.2%. For the age-group ≥65 years there was a reduced rate of treatment success overall (OR 0.34, 95% CI 0.14–0.80, p = <0.01) and when surgery was used alone (OR 0.21, 95% CI 0.06–0.76, p<0.01). Patients ≥65 years were more likely to have a paradoxical reaction (OR 2.06, 95% CI 1.17–3.62, p = 0.01).

Conclusions/Significance

Elderly patients comprise a significant proportion of M. ulcerans disease patients in Australian populations and present with more severe and advanced disease forms. Currently recommended treatments are associated with increased toxicity and reduced effectiveness in elderly populations. Increased efforts are required to diagnose M. ulcerans earlier in elderly populations, and research is urgently required to develop more effective and less toxic treatments for this age-group.