Residual Symptoms of Posttraumatic Stress Disorder and Alcohol Use Disorder Following Integrated Exposure Treatment Versus Coping Skills Treatment

Although some studies have demonstrated residual symptoms in patients who have participated in posttraumatic stress disorder (PTSD) treatment, no studies to date have assessed residual PTSD symptoms following treatment for comorbid alcohol use disorder (AUD) and PTSD (PTSD/AUD). We examined residual symptoms of PTSD and AUD in 73 veterans with PTSD/AUD who completed a posttreatment assessment after being randomized to receive either Concurrent Treatment of PTSD and Substance Use Disorders Using Prolonged Exposure (COPE) or Seeking Safety (SS). We used logistic regression to identify differences (a) in residual PTSD and AUD symptoms among participants randomized to COPE versus SS and (b) among those with versus without a posttreatment PTSD/AUD diagnosis within both treatment conditions. Participants randomized to SS were more likely to report persistent avoidance, inability to experience positive emotions, hypervigilance, difficulty concentrating, and difficulty sleeping, ORs = 3.74–6.21. There were no differences between COPE and SS regarding the likelihood of persistent AUD symptoms. Participants without a posttreatment PTSD diagnosis had lower conditional probabilities of most symptoms, although exaggerated startle, OR = 0.71, and irritability/aggression, OR = 0.58, were most likely to persist. Participants without a posttreatment AUD diagnosis had lower conditional probabilities of most symptoms, although withdrawal, OR = 0.21; unsuccessful quit attempts, OR = 0.04; and higher intake, OR = 0.01, were most likely to persist. Findings indicate hyperarousal may warrant additional intervention following PTSD treatment. Residual AUD symptoms may relate to the enduring nature of some AUD symptoms rather than a lack of treatment efficacy.     

Radiographic Outcomes in Treatment of Thumb Basal Joint Arthritis: Does Interposition of Acellular Dermal Allograft Prevent Metacarpal Settling?

Background  Osteoarthritis at the thumb carpometacarpal joint can have a profound impact on quality of life. Here, we evaluate radiographic outcomes in patients who have had open complete trapeziectomy, ligament reconstruction with tendon interposition, and acellular dermal matrix (GraftJacket) interposition—Group A, and compare them with those without GraftJacket interposition—Group B. Materials and Methods  Thirty patients who had undergone operative treatment for thumb basal joint arthritis by a single surgeon from 2009 to 2016 were identified, and charts were retrospectively reviewed for demographic data, surgical and radiographic outcomes, and complications. Results  There was no significant difference in pre- and postoperative radial abduction or pre- and postoperative palmar abduction. The difference in intraoperative joint space was significant ( p = 0.006), but the difference in postoperative joint space was not ( p = 0.310). The average amount of metacarpal settling was 6.9 versus 3.7 mm ( p = 0.035) (Groups A and B, respectively). Three patients in Group A developed an inflammatory reaction to the GraftJacket, and one required reoperation for allograft removal. Conclusion  This study suggests that thumb basal joint arthroplasty with GraftJacket interposition does not lead to more favorable radiographic outcomes at long-term follow-up. The increased costs associated with GraftJacket use may not be justified in light of these outcomes.     

The selective poly(ADP-ribose) polymerase-1(2) inhibitor, CEP-8983, increases the sensitivity of chemoresistant tumor cells to temozolomide and irinotecan but does not potentiate myelotoxicity

The effect of the potent and selective poly(ADP-ribose) (PAR) polymerase-1 [and PAR polymerase-2] inhibitor CEP-8983 on the ability to sensitize chemoresistant glioblastoma (RG2), rhabdomyosarcoma (RH18), neuroblastoma (NB1691), and colon carcinoma (HT29) tumor cells to temozolomide- and camptothecin-induced cytotoxicity, DNA damage, and G(2)-M arrest and on the potentiation of chemotherapy-induced myelotoxicity was evaluated using in vitro assays. In addition, the effect of the prodrug CEP-9722 in combination with temozolomide and/or irinotecan on PAR accumulation and tumor growth was also determined using glioblastoma and/or colon carcinoma xenografts relative to chemotherapy alone. CEP-8983 sensitized carcinoma cells to the growth-inhibitory effects of temozolomide and/or SN38 increased the fraction of and/or lengthened duration of time tumor cells accumulated in chemotherapy-induced G(2)-M arrest and sensitized tumor cells to chemotherapy-induced DNA damage and apoptosis. A granulocyte-macrophage colony-forming unit colony formation assay showed that coincubation of CEP-8983 with temozolomide or topotecan did not potentiate chemotherapy-associated myelotoxicity. CEP-9722 (136 mg/kg) administered with temozolomide (68 mg/kg for 5 days) or irinotecan (10 mg/kg for 5 days) inhibited significantly the growth of RG2 tumors (60%) or HT29 tumors (80%) compared with temozolomide or irinotecan monotherapy, respectively. In addition, CEP-9722 showed "stand alone" antitumor efficacy in these preclinical xenografts. In vivo biochemical efficacy studies showed that CEP-9722 attenuated PAR accumulation in glioma xenografts in a dose- and time-related manner. These data indicate that CEP-8983 and its prodrug are effective chemosensitizing agents when administered in combination with select chemotherapeutic agents against chemoresistant tumors.     

Stress Hyperglycemia in Patients with Tuberculosis Disease: Epidemiology and Clinical Implications

Purpose of Review

The intersection of tuberculosis (TB) disease and type 2 diabetes mellitus is severely hindering global efforts to reduce TB burdens. Diabetes increases the risk of developing TB disease and negatively impacts TB treatment outcomes including culture conversion time, mortality risk, and TB relapse. Recent evidence also indicates plausible mechanisms by which TB disease may influence the pathogenesis and incidence of diabetes. We review the epidemiology of stress hyperglycemia in patients with TB and the pathophysiologic responses to TB disease that are related to established mechanisms of stress hyperglycemia. We also consider clinical implications of stress hyperglycemia on TB treatment, and the role of TB disease on risk of diabetes post-TB.

Recent Findings

Among patients with TB disease, the development of stress hyperglycemia may influence the clinical manifestation and treatment response of some patients and can complicate diabetes diagnosis.

Summary

Research is needed to elucidate the relationship between TB disease and stress hyperglycemia and determine the extent to which stress hyperglycemia impacts TB treatment response. Currently, there is insufficient data to support clinical recommendations for glucose control among patients with TB disease, representing a major barrier for efforts to improve treatment outcomes for patients with TB and diabetes.

     

Desferioxamine increases iron depletion and apoptosis induced by ara-C of human myeloid leukaemic cells

We investigated whether changes in iron metabolism and the transferrin receptor (TRF-R) expression were involved in the antileukaemic effects of arabinoside cytosine (ara-C). Treatment with 100 n M ara-C for 48 h reduced thymidine uptake and increased the surface expression of the TRF-R on leukaemic blasts derived from 13/16 (81%) patients and on the HL-60 and U-937 cell lines. Whereas intracellular non-haem iron was strongly depleted 24 h after ara-C addition, TRF-R up-regulation and recovery of intracellular non-haem iron concentration occurred together after a longer exposure of the cultured cells to the drug. Since iron is an essential regulator of cell proliferation we have evaluated the effects of the combination between ara-C and the iron chelator desferioxamine (DSF) on the growth of HL-60 and U-937 cells. We found that desferioxamine strongly potentiated the effects of ara-C on leukaemic cell growth inhibition and apoptosis. This is the first report of a positive interaction between ara-C and an iron chelator in terms of antileukaemic effects.     

Stress hyperglycemia in general surgery: Why should we care?

Aims

To determine the frequency of increasing levels of stress hyperglycemia and its associated complications in surgery patients without a history of diabetes.

Parent–Adolescent Relationship Quality and Nondisclosure as Mediators of the Association Between Exposure to Community Violence and Psychological Distress

Background

African American youth residing in urban poverty have been shown to be at increased risk for exposure to violence and for psychological symptoms, but there has been little investigation of mediating processes that might explain this association.

Objectives

This study tested the quality of parent–adolescent relationships and adolescent nondisclosure to adults as mediating mechanisms through which exposure to community violence may lead to psychological symptoms.

Methods

The current study surveyed a sample of 152 low-income urban African American early adolescents (aged 12–14). Participants completed self-report questionnaires assessing exposure to community violence, nondisclosure, parent–adolescent relationship, and psychological symptoms (i.e., internalizing and externalizing symptoms).

Results

Path analyses revealed that parent–adolescent relationship quality and nondisclosure both functioned as mediators of the relation between exposure to community violence and both internalizing and externalizing symptoms, though significant direct effects for violence exposure on externalizing symptoms remained. Decomposition of effects revealed that nondisclosure was a stronger mediator than parent–adolescent relationship quality. Results also indicated that exposure to violence can lead to externalizing (but not internalizing) symptoms first by way of parent–adolescent relationship quality and then nondisclosure.

Conclusions

Combined, these findings suggest that the development of preventive interventions designed to assist adults and parents improve communication and strengthen relationships with adolescents might reduce the negative effects of exposure to community violence on adolescent mental health.

     

Nonpharmacologic Treatments for Depression Related to Reproductive Events

With the rapid and ubiquitous acceptance of new technologies, algorithms will be used to estimate new measures of mental state and behavior based on digital data. The algorithms will analyze data collected from sensors in smartphones and wearable technology, and data collected from Internet and smartphone usage and activities. In the future, new medical measures that assist with the screening, diagnosis, and monitoring of psychiatric disorders will be available despite unresolved reliability, usability, and privacy issues. At the same time, similar non-medical commercial measures of mental state are being developed primarily for targeted advertising. There are societal and ethical implications related to the use of these measures of mental state and behavior for both medical and non-medical purposes.