The Day-to-Day Acute Effect of Wake Therapy in Patients with Major Depression Using the HAM-D6 as Primary Outcome Measure: Results from a Randomised Controlled Trial

Background

This paper reports day-to-day data for from a one-week intervention phase, part of a 9-weeks randomised parallel study with patient having major depression (data from weekly visits have been reported). Wake therapy (sleep deprivation) has an established antidepressant effect with onset of action within hours. Deterioration on the following night’s sleep is, however, common, and we used daily light therapy and sleep time stabilisation as a preventive measure. In particular, we evaluated the day-to-day acute effect of and tolerance to sleep deprivation and examined predictors of response.

Methods

Patients were assessed at psychiatric inpatient wards. In the wake group (n = 36), patients did three wake therapies in combination with light therapy each morning together with sleep time stabilisation. In the exercise group (n = 38), patients did daily exercise. Hamilton subscale scores were primary outcome (not blinded), secondary outcome was self-assessment data from the Preskorn scale and sleep.

Results

Patients in the wake therapy group had an immediate, large, stable, and statistically significant better antidepressant effect than patients in the exercise group with response rates at day5 of 75.0%/25.1% and remission rates of 58.6%/6.0%, respectively. The response and remission rates were diminished at day8 with response rates of 41.9%/10.1% and remission rates of 19.4%/4.7%, respectively. Patients and ward personnel found the method applicable with few side effects. Positive diurnal variation (mood better in the evening) predicted a larger response to wake therapy. In the wake group napping on days after intervention predicted greater deterioration on day8.

Conclusions

The intervention induced an acute antidepressant response without relapse between wake nights but with a diminishing effect after intervention. Development is still needed to secure maintenance of response. Avoiding napping in the days after wake therapy is important.

Trial Registration

Clinical trials.gov {"type":"clinical-trial","attrs":{"text":"NCT00149110","term_id":"NCT00149110"}}NCT00149110     

Posttraumatic Stress Reactions in Parents of Children Esophageal Atresia

Objective

The aim of this study was to investigate psychological stress in parents of children with esophageal atresia and to explore factors associated with the development of Posttraumatic Stress disorder (PTSD).

Design

Self-report questionnaires were administered to parents of children with EA. Domains included: (1) sociodemographic data, current personal difficulties, assessment scales for the quality of life and for the global health status of the child (2) French-validated versions of the Perinatal Posttraumatic Stress disorder Questionnaire and of the State-Trait Anxiety Inventory. Associations between PTSD and severity of the neonatal course, presence of severe sequelae at 2 years of age, and quality of life and global health status of children according to their parents’ perception were studied.

Setting

A Tertiary care University Hospital

Results

Among 64 eligible families, 54 parents of 38 children (59%) participated to the study. PTSD was present in 32 (59%) parents; mothers were more frequently affected than fathers (69 vs 46%, p = 0.03). Four mothers (8%) had severe anxiety. PTSD was neither associated with neonatal severity nor with severe sequelae at 2 years. Parents with PTSD rated their child’s quality of life and global health status significantly lower (7.5 vs 8.6; p = 0.01 and 7.4 vs 8.3; p = 0.02 respectively).

Conclusions

PTSD is frequent in parents of children with esophageal atresia, independently of neonatal severity and presence of severe sequelae at 2 years of age. Our results highlight the need for a long-term psychological support of families.     

The Influence of Arm Swelling Duration on Shoulder Pathology in Breast Cancer Patients with Lymphedema

Purpose

To evaluate the pathological effect of the duration of arm swelling on the shoulder pathology in patients with breast cancer-related lymphedema.

Methods

Forty seven breast cancer patients with unilateral arm lymphedema were assessed. The duration of the arm swelling and shoulder pain were recorded. Ultrasound examination of the shoulder joint was performed in all patients to detect any lesions.

Results

Abnormalities were detected by ultrasound in 41/47 (87.2%) study participants. Subacromial subdeltoid bursal thickening was found in 26/47 (55.3%) participants, distension of the biceps brachii tendon sheath was found in 14/47 (29.8%) and a supraspinatus tendon tear was found in 13/47 (27.7%). Patients with a supraspinatus tendon tear were found to have a significantly longer duration of lymphedema (1310 days vs. 398 days, p = 0.032).

Conclusions

The duration of arm lymphedema has a progressive pathological effect on rotator cuff. Clinicians should adopt an early management approach of shoulder pain in patients with breast cancer-related lymphedema.     

Risk factors for posttraumatic stress disorder following an industrial disaster in a residential area: A note on the origin of observed gender differences

Background: Studies indicate that differences in trait anxiety and trauma-related distress may mediate the gender differences observed in posttraumatic stress disorder (PTSD).Objective: We examined the contributions of gender, trait anxiety, and trauma-related distress to the development of PTSD after an industrial disaster.Methods: Three months after a massive explosion in a fireworks factory in Kolding, Denmark, in November 2004, residents in the surrounding area were asked to complete the Harvard Trauma Questionnaire, the General Health Questionnaire, and a questionaire designed for the present study. Using multivariable logistic regression with PTSD as the dependent variable, we examined 4 explanatory models: (1) gender; (2) gender and trait anxiety; (3) gender, trait anxiety, and perceived danger; and (4) gender, trait anxiety, perceived danger, perceived hostility, feeling isolated, depersonalization, and behavioral self-blame.Results: Fifty-one percent (N = 516; 265 women and 251 men) of the area residents participated in the study. The female-to-male ratio of PTSD was 2.4:1. Women experienced significantly more trait anxiety (P < 0.001), feelings of isolation (P < 0.005), and behavioral self-blame (P = 0.018), and less perceived danger (P = 0.034) than did men. In multivariable logistic regression analysis, gender alone predicted 3.7% of the variance in PTSD status (odds ratio [OR] = 2.40; 95% CI, 1.35-4.27; P < 0.005); however, in all other models, gender was not significant. The final model comprised trait anxiety (OR = 1.20; 95% CI, 1.11-1.30; P < 0.001), perceived danger (OR = 4.62; 95% Cl, 2.24-9.50; P < 0.001), perceived hostility (OR = 5.21; 95% CI, 1.93-14.09; P < 0.001), feeling isolated (OR = 3.34; 95% CI, 1.55-7.16; P < 0.002), depersonalization (OR = 2.49; 95% CI, 1.42-4.37; P < 0.001), and behavioral self-blame (OR = 0.46; 95% CI, 0.24-0.86; P = 0.015), explaining 48.9% of the variance in PTSD severity.Conclusion: This cross-sectional study found that gender was no longer associated with PTSD status when trait anxiety, perceived danger and hostility, feeling isolated, depersonalization, and behavioral selfblame were taken into account.     

The Role of Intelligence in Posttraumatic Stress Disorder: Does it Vary by Trauma Severity?

Background

Only a small minority of trauma victims develops post-traumatic stress disorder (PTSD), suggesting that victims vary in their predispositions to the PTSD response to stressors. It is assumed that the role of predispositions in PTSD varies by trauma severity: when stressors are less severe, predispositions play a bigger role. In this study, we test whether the role of intelligence in PTSD varies by trauma severity. Specifically, does low intelligence plays a bigger part among victims of lower magnitude stressors than among victims of extreme stressors?

Methods

Data come from a longitudinal study of randomly selected sample in Southeast Michigan (n = 713). IQ was measured at age 6. PTSD was measured at age 17, using the NIMH-DIS for DSM-IV. Stressors were classified as extreme if they involved assaultive violence (e.g. rape, sexual assault, threatened with a weapon); other stressors in the list (e.g. disaster, accidents) were classified as lower magnitude. Assaultive violence victims had experienced assaultive violence plus other event types or only assaultive violence. Victims of other stressors were participants who had never experienced assaultive violence. We compared the influence of age 6 IQ on PTSD among persons exposed to assaultive violence vs. other stressors, using multinomial logistic regression.

Results

Relative risk ratio (RRR) for PTSD associated with a one point drop in age 6 IQ among victims of assaultive violence was 1.04 (95% CI 1.01, 1.06); among victims of other stressors, it was 1.03 (95% CI 0.99, 1.06). A comparison of the two RRRs indicates no significant difference between the two estimates (p = 0.652). IQ does not play a bigger role in PTSD among victims of other stressors than it does among victims of assaultive violence.

Conclusions

Lower IQ exerts an adverse PTSD effect on trauma victims, with no evidence of variability by the severity of trauma they have experienced.     

Changes in brain metabolites measured with magnetic resonance spectroscopy in antidepressant responders with comorbid major depression and posttraumatic stress disorder

In a present pilot study, performed on 11 subjects, we studied proton magnetic resonance spectroscopy (1H-MRS) changes in early to intermediate (3-6 weeks) responders to antidepressant treatment with selective serotonin reuptake inhibitors (SSRIs). All subjects had diagnosis of major recurrent depression comorbid to posttraumatic stress disorder (PTSD). Magnetic spectroscopy was done in the region of dorsolateral prefrontal cortex on a 3T MRI-unit. Participants were selected out of the larger sample due to an early response to antidepressant treatment within 3-6 weeks, measured with Beck Depression Inventory (BDI). We measured levels of neuronal marker N-acetyl-aspartate (NAA), choline (CHO) and creatine (Cr). There was no difference in NAA/Cr ratios between the first and the second spectroscopic scans (p= 0.751). However, CHO/Cr ratios showed increasing trend with mean value at the first scan of 1.09 (SD =0.22) while mean value at second scan was 1.25 (SD=0.24), displaying statistically significant difference (p=0.015). In conclusion, significant increase in choline to creatine ratio from the first to the second spectroscopic scan during the antidepressant treatment, compared to almost identical values of NAA to creatine ratio, suggests increased turnover of cell membranes as a mechanism of the early response to the antidepressant drug therapy.     

Updating versus Exposure to Prevent Consolidation of Conditioned Fear

Targeting the consolidation of fear memories following trauma may offer a promising method for preventing the development of flashbacks and other unwanted re-experiencing symptoms that characterise Posttraumatic Stress Disorder (PTSD). Research has demonstrated that performing visuo-spatial tasks after analogue trauma can block the consolidation of fear memory and reduce the frequency of flashbacks. However, no research has yet used verbal techniques to alter memories during the consolidation window. This is surprising given that the most effective treatments for PTSD are verbally-based with exposure therapy and trauma-focused cognitive behavioural therapy gaining the most evidence of efficacy. Psychological therapies aim to reduce the conditioned fear response, which is in keeping with the preliminary finding that an increased propensity for fear conditioning may be a vulnerability factor for PTSD. Our research had two aims. We investigated the degree to which individual differences in fear conditioning predict the development of PTSD symptoms. We also compared the preventative effects of two clinically informed psychological techniques administered during the consolidation window: exposure to the trauma memory and updating the meaning of the trauma. 115 healthy participants underwent a fear conditioning paradigm in which traumatic film stimuli (unconditioned stimuli) were paired with neutral stimuli (conditioned stimuli). Participants were randomly allocated to an updating, exposure or control group to compare the effects on the conditioned fear response and on PTSD symptomatology. The results showed that stronger conditioned responses at acquisition significantly predicted the development of PTSD symptoms. The updating group, who verbally devalued the unconditioned stimulus within the consolidation window, experienced significantly lower levels of PTSD symptoms during follow-up than the exposure and control groups. These findings are consistent with clinical interventions for chronic PTSD and have important implications for identifying those at risk as well as for designing novel early interventions to prevent the development of PTSD.     

Efficacy of Eye-Movement Desensitization and Reprocessing for Patients with Posttraumatic-Stress Disorder: A Meta-Analysis of Randomized Controlled Trials

Background

We performed the first meta-analysis of clinical studies by investigating the effects of eye-movement desensitization and reprocessing (EMDR) therapy on the symptoms of posttraumatic stress disorder (PTSD), depression, anxiety, and subjective distress in PTSD patients treated during the past 2 decades.

Methods

We performed a quantitative meta-analysis on the findings of 26 randomized controlled trials of EMDR therapy for PTSD published between 1991 and 2013, which were identified through the ISI Web of Science, Embase, Cochrane Library, MEDLINE, PubMed, Scopus, PsycINFO, and the Cumulative Index to Nursing and Allied Health Literature electronic databases, among which 22, 20, 16, and 11 of the studies assessed the effects of EMDR on the symptoms of PTSD, depression, anxiety, and subjective distress, respectively, as the primary clinical outcome.

Results

The meta-analysis revealed that the EMDR treatments significantly reduced the symptoms of PTSD (g = −0.662; 95% confidence interval (CI): −0.887 to −0.436), depression (g = −0.643; 95% CI: −0.864 to −0.422), anxiety (g = −0.640; 95% CI: −0.890 to −0.390), and subjective distress (g = −0.956; 95% CI: −1.388 to −0.525) in PTSD patients.

Conclusion

This study confirmed that EMDR therapy significantly reduces the symptoms of PTSD, depression, anxiety, and subjective distress in PTSD patients. The subgroup analysis indicated that a treatment duration of more than 60 min per session was a major contributing factor in the amelioration of anxiety and depression, and that a therapist with experience in conducting PTSD group therapy was a major contributing factor in the reduction of PTSD symptoms.     

Effectiveness of Group Problem Management Plus,a brief psychological intervention for adults affected by humanitarian disasters in Nepal: A cluster randomized controlled trial

BackgroundGlobally, 235 million people are impacted by humanitarian emergencies worldwide, presenting increased risk of experiencing a mental disorder. Our objective was to test the effectiveness of a brief group psychological treatment delivered by trained facilitators without prior professional mental health training in a disaster-prone setting.Methods and findingsWe conducted a cluster randomized controlled trial (cRCT) from November 25, 2018 through September 30, 2019. Participants in both arms were assessed at baseline, midline (7 weeks post-baseline, which was approximately 1 week after treatment in the experimental arm), and endline (20 weeks post-baseline, which was approximately 3 months posttreatment). The intervention was Group Problem Management Plus (PM+), a psychological treatment of 5 weekly sessions, which was compared with enhanced usual care (EUC) consisting of a family psychoeducation meeting with a referral option to primary care providers trained in mental healthcare. The setting was 72 wards (geographic unit of clustering) in eastern Nepal, with 1 PM+ group per ward in the treatment arm. Wards were eligible if they were in disaster-prone regions and residents spoke Nepali. Wards were assigned to study arms based on covariate constrained randomization. Eligible participants were adult women and men 18 years of age and older who met screening criteria for psychological distress and functional impairment. Outcomes were measured at the participant level, with assessors blinded to group assignment. The primary outcome was psychological distress assessed with the General Health Questionnaire (GHQ-12). Secondary outcomes included depression symptoms, posttraumatic stress disorder (PTSD) symptoms, “heart–mind” problems, social support, somatic symptoms, and functional impairment. The hypothesized mediator was skill use aligned with the treatment’s mechanisms of action. A total of 324 participants were enrolled in the control arm (36 wards) and 319 in the Group PM+ arm (36 wards). The overall sample (N = 611) had a median age of 45 years (range 18–91 years), 82% of participants were female, 50% had recently experienced a natural disaster, and 31% had a chronic physical illness. Endline assessments were completed by 302 participants in the control arm (36 wards) and 303 participants in the Group PM+ arm (36 wards). At the midline assessment (immediately after Group PM+ in the experimental arm), mean GHQ-12 total score was 2.7 units lower in Group PM+ compared to control (95% CI: 1.7, 3.7, p < 0.001), with standardized mean difference (SMD) of −0.4 (95% CI: −0.5, −0.2). At 3 months posttreatment (primary endpoint), mean GHQ-12 total score was 1.4 units lower in Group PM+ compared to control (95% CI: 0.3, 2.5, p = 0.014), with SMD of −0.2 (95% CI: −0.4, 0.0). Among the secondary outcomes, Group PM+ was associated with endline with a larger proportion attaining more than 50% reduction in depression symptoms (29.9% of Group PM+ arm versus 17.3% of control arm, risk ratio = 1.7, 95% CI: 1.2, 2.4, p = 0.002). Fewer participants in the Group PM+ arm continued to have “heart–mind” problems at endline (58.8%) compared to the control arm (69.4%), risk ratio = 0.8 (95% CI, 0.7, 1.0, p = 0.042). Group PM+ was not associated with lower PTSD symptoms or functional impairment. Use of psychosocial skills at midline was estimated to explain 31% of the PM+ effect on endline GHQ-12 scores. Adverse events in the control arm included 1 suicide death and 1 reportable incidence of domestic violence; in the Group PM+ arm, there was 1 death due to physical illness. Study limitations include lack of power to evaluate gender-specific effects, lack of long-term outcomes (e.g., 12 months posttreatment), and lack of cost-effectiveness information.ConclusionsIn this study, we found that a 5-session group psychological treatment delivered by nonspecialists modestly reduced psychological distress and depression symptoms in a setting prone to humanitarian emergencies. Benefits were partly explained by the degree of psychosocial skill use in daily life. To improve the treatment benefit, future implementation should focus on approaches to enhance skill use by PM+ participants.Trial registrationClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT03747055","term_id":"NCT03747055"}}NCT03747055.

Mark Jordans and co-workers evaluate a group therapy intervention in adults affected by psychological distress in Nepal.     

Early PTSD Symptom Trajectories: Persistence,Recovery, and Response to Treatment: Results from the Jerusalem Trauma Outreach and Prevention Study (J-TOPS)

Context

Uncovering heterogeneities in the progression of early PTSD symptoms can improve our understanding of the disorder''s pathogenesis and prophylaxis.

Objectives

To describe discrete symptom trajectories and examine their relevance for preventive interventions.

Design

Latent Growth Mixture Modeling (LGMM) of data from a randomized controlled study of early treatment. LGMM identifies latent longitudinal trajectories by exploring discrete mixture distributions underlying observable data.

Setting

Hadassah Hospital unselectively receives trauma survivors from Jerusalem and vicinity.

Participants

Adult survivors of potentially traumatic events consecutively admitted to the hospital''s emergency department (ED) were assessed ten days and one-, five-, nine- and fifteen months after ED admission. Participants with data at ten days and at least two additional assessments (n = 957) were included; 125 received cognitive behavioral therapy (CBT) between one and nine months.

Approach

We used LGMM to identify latent parameters of symptom progression and tested the effect of CBT on these parameters. CBT consisted of 12 weekly sessions of either cognitive therapy (n = 41) or prolonged exposure (PE, n = 49), starting 29.8±5.7 days after ED admission, or delayed PE (n = 35) starting at 151.8±42.4 days. CBT effectively reduced PTSD symptoms in the entire sample.

Main Outcome Measure

Latent trajectories of PTSD symptoms; effects of CBT on these trajectories.

Results

Three trajectories were identified: Rapid Remitting (rapid decrease in symptoms from 1- to 5-months; 56% of the sample), Slow Remitting (progressive decrease in symptoms over 15 months; 27%) and Non-Remitting (persistently elevated symptoms; 17%). CBT accelerated the recovery of the Slow Remitting class but did not affect the other classes.

Conclusions

The early course of PTSD symptoms is characterized by distinct and diverging response patterns that are centrally relevant to understanding the disorder and preventing its occurrence. Studies of the pathogenesis of PTSD may benefit from using clustered symptom trajectories as their dependent variables.     

Improved Outcome with Early Rifampicin Combination Treatment in Methicillin-Sensitive Staphylococcus aureus Bacteraemia with a Deep Infection Focus – A Retrospective Cohort Study

Introduction

Rifampicin has been used as adjunctive therapy in Staphylococcus aureus bacteraemia (SAB) with a deep infection focus. However, data for prognostic impact of rifampicin therapy is unestablished including the optimal initiation time point. We studied the impact of rifampicin therapy and the optimal initiation time for rifampicin treatment on prognosis in methicillin-sensitive S. aureus bacteraemia with a deep infection.

Methods

Retrospective, multicentre study in Finland including 357 SAB patients with a deep infection focus. Patients with alcoholism, liver disease or patients who died within 3 days were excluded. Patients were categorised according to duration of rifampicin therapy and according to whether rifampicin was initiated early (within 7 days) or late (7 days after) after the positive blood cultures. Primary end point was 90 days mortality.

Results

Twenty-seven percent of patients received no rifampicin therapy, 14% received rifampicin for 1-13 days whereas 59% received rifampicin ≥14 days. The 90 day mortality was; 26% for patients treated without rifampicin, 16% for rifampicin therapy of any length and 10% for early onset rifampicin therapy ≥14 days. Lack of rifampicin therapy increased (OR 1.89, p=0.026), rifampicin of any duration decreased (OR 0.53, p=0.026) and rifampicin therapy ≥14 days with early onset lowered the risk for a fatal outcome (OR 0.33, p<0.01) during 90 days follow-up.

Conclusion

Rifampicin adjunctive therapy for at least 14 days and initiated within 7 days of positive blood culture associated with improved outcome among SAB patients with a deep infection.     

Food biodiversity and total and cause-specific mortality in 9 European countries: An analysis of a prospective cohort study

BackgroundFood biodiversity, encompassing the variety of plants, animals, and other organisms consumed as food and drink, has intrinsic potential to underpin diverse, nutritious diets and improve Earth system resilience. Dietary species richness (DSR), which is recommended as a crosscutting measure of food biodiversity, has been positively associated with the micronutrient adequacy of diets in women and young children in low- and middle-income countries (LMICs). However, the relationships between DSR and major health outcomes have yet to be assessed in any population.Methods and findingsWe examined the associations between DSR and subsequent total and cause-specific mortality among 451,390 adults enrolled in the European Prospective Investigation into Cancer and Nutrition (EPIC) study (1992 to 2014, median follow-up: 17 years), free of cancer, diabetes, heart attack, or stroke at baseline. Usual dietary intakes were assessed at recruitment with country-specific dietary questionnaires (DQs). DSR of an individual’s yearly diet was calculated based on the absolute number of unique biological species in each (composite) food and drink. Associations were assessed by fitting multivariable-adjusted Cox proportional hazards regression models. In the EPIC cohort, 2 crops (common wheat and potato) and 2 animal species (cow and pig) accounted for approximately 45% of self-reported total dietary energy intake [median (P₁₀–P₉₀): 68 (40 to 83) species consumed per year]. Overall, higher DSR was inversely associated with all-cause mortality rate. Hazard ratios (HRs) and 95% confidence intervals (CIs) comparing total mortality in the second, third, fourth, and fifth (highest) quintiles (Qs) of DSR to the first (lowest) Q indicate significant inverse associations, after stratification by sex, age, and study center and adjustment for smoking status, educational level, marital status, physical activity, alcohol intake, and total energy intake, Mediterranean diet score, red and processed meat intake, and fiber intake [HR (95% CI): 0.91 (0.88 to 0.94), 0.80 (0.76 to 0.83), 0.69 (0.66 to 0.72), and 0.63 (0.59 to 0.66), respectively; P_Wald < 0.001 for trend]. Absolute death rates among participants in the highest and lowest fifth of DSR were 65.4 and 69.3 cases/10,000 person-years, respectively. Significant inverse associations were also observed between DSR and deaths due to cancer, heart disease, digestive disease, and respiratory disease. An important study limitation is that our findings were based on an observational cohort using self-reported dietary data obtained through single baseline food frequency questionnaires (FFQs); thus, exposure misclassification and residual confounding cannot be ruled out.ConclusionsIn this large Pan-European cohort, higher DSR was inversely associated with total and cause-specific mortality, independent of sociodemographic, lifestyle, and other known dietary risk factors. Our findings support the potential of food (species) biodiversity as a guiding principle of sustainable dietary recommendations and food-based dietary guidelines.

Dr. Giles T. Hanley-Cook and colleagues, analyzed data from a prospective cohort study to investigate the association between food biodiversity, and total and cause-specific mortality in nine European countries.     

Focus: The Science of Stress: PTSD Among Shidu Parents in China: The Roles of Personality Types and Social Support

Background: The psychological problems of Shidu Parents (SDP) under the China’s One-Child Policy have been documented. The purpose of this study was to investigate the relationships among personality types, social support, and post-traumatic stress disorder (PTSD) in SDP. Methods: The PTSD Checklist-Civilian Version (PCL-C), The Big Five Personality Traits (NEO), and Social Support Revalued Scale (SSRS) were administered to the sample of 149 SDP who were over 50 years old and had lost their only child more than one year ago. Results: Among SDP, mothers were more likely to develop PTSD than fathers (χ² = 11.16, p < 0.01). Parents who were extraverted had a lower risk of developing PTSD-related symptoms (χ² = 8.58, p < 0.01), and the effect of neuroticism was significant (χ² = 23.73, p < 0.01). The more social support parents utilized, the lower the incidence of PTSD (t = 4.56, p < 0.01). The result of multilevel linear regression showed that sex, neuroticism, and objective social support remained significantly different after combining all personality types and social support systems in the same model. Social support partially mediated the relationship between neuroticism and PTSD. Meanwhile, it was a complete mediator between extraversion and PTSD. Conclusions: Female sex/gender, neuroticism, and introversion were risk factors of developing PTSD, while receiving social support protected SDP from developing PTSD symptoms. Losing an only child is undoubtedly an enormous disaster for the family, which has become a huge, unavoidable social problem that must be addressed in China.     

A Comparison of Twice-Daily Biphasic Insulin Aspart 70/30 and Once-Daily Insulin Glargine in Persons With Type 2 Diabetes Mellitus Inadequately Controlled on Basal Insulin and Oral Therapy: A Randomized,Open-Label Study

ObjectiveTo compare efficacy and safety of biphasic insulin aspart 70/30 (BIAsp 30) with insulin (glargine) in type 2 diabetic patients who were not maintaining glycemic control on basal insulin and oral antidiabetic drugs.MethodsIn a 24-week, open-label, parallel-group trial, type 2 diabetic patients who were not maintaining glycemic control on basal insulin (glargine or neutral protamine Hagedorn) + oral antidiabetic drugs were randomly assigned to twice-daily BIAsp 30 + metformin or oncedaily glargine + metformin + secretagogues (secretagogues were discontinued in the BIAsp 30 arm).ResultsOne hundred thirty-seven patients were randomly assigned to the BIAsp 30 group and 143 patients were randomly assigned to the glargine group. Of 280 patients randomized, 229 (81.8%) completed the study. End-of-trial hemoglobin A_1c reductions were − 1.3% (BIAsp 30) vs − 1.2% (glargine) (treatment difference: 95% confidence interval, − 0.06 [− 0.32 to 0.20]; P = .657). Of patients taking BIAsp 30, 27.3% reached a hemoglobin A_1c level < 7.0% compared with 22.0% of patients taking glargine (treatment difference: P = .388). Glucose increment averaged over 3 meals was lower in the BIAsp 30 arm (treatment difference: − 17.8 mg/dL, P = .001). Fasting plasma glucose reductions from baseline were − 13.8 mg/ dL (BIAsp 30) vs − 42.5 mg/dL (glargine) (P = .0002). Final minor hypoglycemia rate, insulin dose, and weight change were higher in the BIAsp 30 arm (6.5 vs 3.4 events/patient per year, P <.05; 1.19 vs 0.63 U/kg; and 3.1 vs 1.4 kg, P = .0004, respectively).ConclusionsDespite not receiving secretagogues, patients taking BIAsp 30 + metformin achieved similar hemoglobin A_1c levels and lower postprandial plasma glucose compared with those receiving glargine + metformin + secretagogues. The large improvement in the glargine group suggests the patients were not true basal failures at randomization. While switching to BIAsp 30 improves glycemic control in this patient population, remaining on basal insulin and optimizing the dose may be equally effective in the short term. (Endocr Pract. 2011;17:41-50)     

Overt and Subclinical Adrenal Insufficiency in Pulmonary Tuberculosis

BackgroundTuberculosis of the adrenal glands may cause overt or subclinical adrenal insufficiency. An algorithm-based approach including assessment of paired basal cortisol and plasma adrenocorticotropic hormone (ACTH), short Synacthen, and plasma renin activity assays could be useful to diagnose all forms of adrenal insufficiency.MethodsThis cross-sectional study included consecutive, treatment-naive subjects diagnosed with pulmonary tuberculosis. Tuberculosis severity was classified by radiological criteria. Baseline parameters plus morning (8 am) serum cortisol and paired plasma ACTH were measured in all patients. Synacthen stimulation tests and plasma renin activity assays were performed as required.ResultsEighty-four treatment-naive consecutive cases of pulmonary tuberculosis were evaluated for adrenal insufficiency. Twenty-seven (32.14%) subjects had normal adrenocortical function and 8 (9.5%), 7 (8.3%), 40 (47.6%), and 2 (2.4%) subjects had stage 1, stage 2, stage 3, and stage 4 adrenal insufficiency, respectively. Serum cortisol was negatively correlated with radiological severity (P = .01) and duration of illness (P = .001). Adrenal dysfunction was present in 27.3%, 82.5%, and 80% of those with radiologically minimal, moderately advanced, and far-advanced disease, respectively. Mean cortisol was 19.74 ± 5.52, 17.42 ± 8.53, and 15.71 ± 7.14 (μg/dL) in the 3 groups, respectively (P = .042). Hyponatremia was present in 83.3% of the patients. Serum sodium was negatively correlated with severity but not with the duration of disease.ConclusionThe prevalence of overt and subclinical adrenal dysfunction in pulmonary tuberculosis was high and was correlated with disease severity and duration. An algorithmic approach may be useful to detect the same and may have important clinical implications.     

Anti-PD1 checkpoint inhibitor with or without chemotherapy for patients with recurrent and metastatic nasopharyngeal carcinoma

PurposeTo compare the efficacy and safety of anti-PD1 checkpoint inhibitor plus chemotherapy with anti-PD1 checkpoint inhibitor alone in recurrent and metastatic nasopharyngeal carcinoma (R/M NPC) progressing after first or subsequent-line therapy.Methods and materialsA total of 67 patients with recurrent and metastatic nasopharyngeal carcinoma from our hospital were included. All patients were sorted into two arms: anti-PD1 checkpoint inhibitor+ chemotherapy arm and anti-PD1 checkpoint inhibitor arm. We retrospectively estimated objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) in patients of both arms. Chi-square test and Kaplan–Meier methodology were used to analyze.ResultsFrom September 2018 to March 2020, this research included 67 patients. For anti-PD1 checkpoint inhibitor+ chemotherapy arm, partial response and stable disease were observed in fourteen and 11 patients, respectively, for an ORR of 53.8%. For anti-PD1 checkpoint inhibitor arm, complete response and partial response were observed in one and 5 patients, respectively, for an ORR of 14.6%. The incidence of hyperprogressive disease was higher in the anti-PD1 checkpoint inhibitor group compared with anti-PD1 checkpoint inhibitor+ chemotherapy group (39.0% vs 3.8%, p<0.05). Univariable analyses discovered that 6-month PFS and OS benefits were observed for anti-PD1 checkpoint inhibitor+ chemotherapy arm compared to anti-PD1 checkpoint inhibitor arm (65.4% vs. 28.6%, P = 0.001; 100.0% vs. 73.5%, P = 0.014).ConclusionIn present study, we revealed that adding chemotherapy to anti-PD1 checkpoint inhibitor significantly improved 6-month PFS and OS for patients with R/M NPC progressing after first-line therapy. It warrants further study.     

Adding Rapid-Acting Insulin or Glp-1 Receptor Agonist to Basal Insulin: Outcomes in A Community Setting

ObjectiveTo evaluate real-world outcomes in patients with type 2 diabetes mellitus (T2DM) receiving basal insulin who initiate add-on therapy with a rapid-acting insulin (RAI) or a glucagon-like peptide 1 (GLP-1) receptor agonist.MethodsData were extracted retrospectively from a U.S. health claims database. Adults with T2DM on basal insulin who added an RAI (basal + RAI) or GLP-1 receptor agonist (basal + GLP-1) were included. Propensity score matching (with a 1 up to 3 ratio) was used to control for differences in baseline demographics, clinical characteristics, and health resource utilization. Endpoints included prevalence of hypoglycemia, pancreatic events, all-cause and diabetes-related resource utilization, and costs at 1-year follow-up.ResultsOverall, 6,718 matched patients were included: 5,013 basal + RAI and 1,705 basal + GLP1. Patients in both groups experienced a similar proportion of any hypoglycemic event (P = .4079). Hypoglycemic events leading to hospitalization were higher in the basal + RAI cohort (2.7% vs. 1.8%; P = .0444). The basal + GLP-1 cohort experienced fewer all-cause (13.55% vs. 18.61%; P < .0001) and diabetes-related hospitalizations (11.79% vs. 15.68%; P < .0001). The basal + GLP-1 cohort had lower total all-cause health care costs ($18,413 vs. $20,821; P = .0002) but similar diabetes-related costs ($9,134 vs. $8,985; P < .0001) compared with the basal + RAI cohort.ConclusionsAdd-on therapy with a GLP-1 receptor agonist in T2DM patients receiving basal insulin was associated with fewer hospitalizations and lower total all-cause costs compared with add-on therapy using an RAI and could be considered as an alternative to an RAI in certain patients with T2DM who do not achieve effective glycemic control with basal insulin. (Endocr Pract. 2015; 21:68-76)     

Ultrasound Targeted Apoptosis Imaging in Monitoring Early Tumor Response of Trastuzumab in a Murine Tumor Xenograft Model of Her-2–Positive Breast Cancer1

OBJECTIVE: Our study aimed to monitor the trastuzumab therapy response of murine tumor xenograft model with human epidermal growth factor receptor 2 (Her-2)–positive breast cancer using ultrasound targeted apoptosis imaging. METHODS: We prepared targeted apoptosis ultrasound probes by nanobubble (NB) binding with Annexin V. In vitro, we investigated the binding rate of NB–Annexin V with breast cancer apoptotic cells after the trastuzumab treatment. In vivo, tumor-bearing mice underwent ultrasound targeted imaging over 7 days. After imaging was completed, the tumors were excised to determine Her-2 and caspase-3 expression by immunohistochemistry (IHC). The correlation between parameters of imaging and histologic results was then analyzed. RESULTS: For seeking the ability of targeted NB binding with apoptotic tumor cells (Her-2 positive), we found that binding rate in the treatment group was higher than that of the control group in vitro (P = .001). There were no differences of tumor sizes in all groups over the treatment process in vivo (P = .98). However, when using ultrasound imaging to visualize tumors by targeted NB in vivo, we observed that the mean and peak intensities from NBs gradually increased in the treatment group after trastuzumab therapy (P = .001). Furthermore, these two parameters were significantly associated with caspase-3 expression of tumor excised samples (P = .0001). CONCLUSION: Ultrasound targeted apoptosis imaging can be a non-invasive technique to evaluate the early breast tumor response to trastuzumab therapy.