Is Self-Compassion a Worthwhile Therapeutic Target for ICD-11 Complex PTSD (CPTSD)?

BACKGROUND: Two 'sibling' disorders have been proposed for the fourthcoming 11th version of the International Classification of Diseases (ICD-11): post-traumatic stress disorder (PTSD) and complex PTSD (CPTSD). Examining psychological factors that may be associated with CPTSD, such as self-compassion, is an important first step in its treatment that can inform consideration of which problems are most salient and what interventions are most relevant. AIMS: We set out to investigate the association between self-compassion and the two factors of CPTSD: the PTSD factor (re-experiencing, avoidance, sense of threat) and the Disturbances in Self-Organization (DSO) factor (affect dysregulation, negative self-concept and disturbances in relationships). We hypothesized that self-compassion subscales would be negatively associated with both PTSD and DSO symptom clusters. METHOD: A predominantly female, clinical sample (n = 106) completed self-report scales to measure traumatic life events, ICD-11 CPTSD and self-compassion. RESULTS: Significant negative associations were found between the CPTSD DSO clusters of symptoms and self-compassion subscales, but not for the PTSD ones. Specifically it was also found that self-judgement and common humanity significantly predicted hypoactive affect dysregulation whereas self-judgement and isolation significantly predicted negative self-concept. CONCLUSIONS: Our results indicate that self-compassion may be a useful treatment target for ICD-11 CPTSD, particularly for symptoms of negative self-concept and affect dysregulation. Future research is required to investigate the efficacy and acceptability of interventions that have implicit foundations on compassion.

Endometrial cancer surveillance adherence reduces utilization and subsequent costs.

OBJECTIVES: In June 2011, the SGO recommended that physical exam and symptoms be the primary surveillance methods in patients with endometrial cancer. We sought to evaluate adherence to these guidelines by comparing the use of CT scans, paps and serum CA125 ordered for endometrial cancer surveillance before and after publication of these guidelines. METHODS: A retrospective review was performed for all patients undergoing surveillance for endometrial cancer at a single institution between June 2009 and June 2013. We assessed the number of patients without symptoms or abnormal physical exam findings who underwent surveillance CT scans, paps and/or CA125 during the 2years pre- and 2years post-SGO guidelines. RESULTS: 92 patients (n=48 pre-6/2011, n=44 post-6/2011) were identified. Mean patient age was 58years. No significant difference in age, ethnicity, body mass index, or disease grade or stage was noted. There was a significant decline in surveillance CT scans (n=13, 27% vs. n=4, 9%, p=0.03), CA125 (n=14, 29% vs. 5, 11%, p=0.035) and paps (n=34, 71% vs. n=8 vs. 18%, p<0.001). There was no significant difference in disease status at the last follow-up. Institutional cost of surveillance also declined ($14,102.46 2years pre-guidelines, $3,054.99 2years post-guidelines). CONCLUSIONS: In a single urban academic public hospital, after only 2years, clinical adherence to the 2011 SGO endometrial cancer surveillance guidelines resulted in a significant decline in the use of CT scans, CA125 and paps. This reduction does not appear to affect patient outcomes and led to an appreciable decrease in surveillance costs.

A qualitative study of ovarian cancer survivors' perceptions of endpoints and goals of care.

OBJECTIVES: A survey of the Ovarian Cancer National Alliance revealed a communication gap between physicians and survivors. This qualitative study explored the space between perceptions in hopes of better defining treatment endpoints meaningful to treating physicians and their patients. METHODS: A focus group of ovarian cancer survivors (n=22) was assembled via the survivor support network SHARE. A physician-guided session explored expectations of treatment, perceived outcomes, toxicity thresholds and decision making. The session was recorded, transcribed and coded. Common themes were identified and used to perform intra-case analysis by two independent reviewers. RESULTS: The main themes identified were barriers to communication, importance of frequent communication between patient and physician regarding goals, and expectations of treatment changing with position along the treatment continuum. One hundred percent of participants identified communication with their physician as an essential element in determining treatment course. However, only 14% reported having a discussion about goals, values and perceptions with their physician preceding treatment decisions. Participants reported that the terms progression free and overall survival held minimal significance for them and instead they preferred an individualized approach to care focusing on quality of life. Many women underreported side effects with reasons ranging from fear of dose reductions and additional tests to forgetting about symptoms due to anxiety. CONCLUSIONS: An objective measure of treatment success meaningful to survivors, physicians and regulators is, at present, elusive and may not exist. Ideally, future trial design would place equal weight on quantitative and qualitative measures and include information about goals of treatment.

Multi-scale in vivo systems analysis reveals the influence of immune cells on TNF-α-induced apoptosis in the intestinal epithelium.

Intestinal epithelial cells exist within a complex environment that affects how they interpret and respond to stimuli. We have applied a multi-scale in vivo systems approach to understand how intestinal immune cells communicate with epithelial cells to regulate responses to inflammatory signals. Multivariate modeling analysis of a large dataset composed of phospho-signals, cytokines, and immune cell populations within the intestine revealed an intimate relationship between immune cells and the epithelial response to TNF-α. Ablation of lymphocytes in the intestine prompted a decrease in the expression of MCP-1, which in turn increased the steady state number of intestinal plasmacytoid dendritic cells (pDCs). This change in the immune compartment affected the intestinal cytokine milieu and subsequent epithelial cell signaling network, with cells becoming hypersensitive to TNF-α-induced apoptosis in a way that could be predicted by mathematical modeling. In summary, we have uncovered a novel cellular network that regulates the response of intestinal epithelial cells to inflammatory stimuli in an in vivo setting.

In vivo systems analysis identifies spatial and temporal aspects of the modulation of TNF-α-induced apoptosis and proliferation by MAPKs.

Cellular responses to external stimuli depend on dynamic features of multipathway network signaling; thus, cell behavior is influenced in a complex manner by the environment and by intrinsic properties. Methods of multivariate systems analysis have provided an understanding of these convoluted effects, but only for relatively simplified examples in vitro. To determine whether such approaches could be successfully used in vivo, we analyzed the signaling network that determines the response of intestinal epithelial cells to tumor necrosis factor-α (TNF-α). We built data-driven, partial least-squares discriminant analysis (PLSDA) models based on signaling, apoptotic, and proliferative responses in the mouse small intestinal epithelium after systemic exposure to TNF-α. The extracellular signal-regulated kinase (ERK) signaling axis was a critical modulator of the temporal variation in apoptosis at different doses of TNF-α and of the spatial variation in proliferation in distinct intestinal regions. Inhibition of MEK, a mitogen-activated protein kinase kinase upstream of ERK, altered the signaling network and changed the temporal and spatial phenotypes consistent with model predictions. Our results demonstrate the dynamic, adaptive nature of in vivo signaling networks and identify natural, tissue-level variation in responses that can be deconvoluted only with quantitative, multivariate computational modeling. This study lays a foundation for the use of systems-based approaches to understand how dysregulation of the cellular network state underlies complex diseases.

Impact of iron salts on activated sludge and interaction with nitrite or nitrate.

Iron salts are often used in activated sludge treatment plants as coagulants or to improve reactor performance. Previous studies have indicated that iron itself has an impact on the activated sludge process. However, the interaction of iron with nitrite or nitrate present in the sludge has received little attention. In this research, the influence of addition of Fe(II) or Fe(III), alone or together with NO(2)(-) or NO(3)(-) on bench-scale activated sludge reactors was examined. Large differences were established between the distinct treatments, regarding reactor performance, sludge characteristics as well as microbial community. Ferric iron was more detrimental than ferrous iron. In some cases, nitrite was found to enhance inhibitory effects of the added iron, whereas nitrate had more a neutralizing effect. It was found that precipitation of phosphate by the iron was not responsible for the observed inhibition. Decrease in pH upon formation of iron hydroxides and the impairment of the floc structure could partially explain the toxicity of the iron dosages. The formation of toxic nitrogen oxides, such as nitric oxide, can also be of importance. The observed positive effect of nitrate on the floc activity is of interest and warrants further elucidation.

Changes in the microbiology of activated sludge upon the addition of iron salts with or without nitrite or nitrate.

Iron salts are frequently used in activated sludge treatment as coagulants or to improve reactor performance. However, the effect of the iron salts on the microbiology has received little attention. Furthermore, the interaction of iron ions with nitrite or nitrate present in the sludge has not been considered. In this research, the influence of ferrous and ferric iron additions, and their possible interactions with nitrite or nitrate at levels of a few mM, on the activated sludge microbiology of semi-continuous bench-scale reactors were examined. Conventional as well as molecular techniques have been used to investigate the microbial communities. Microscopic investigations showed that repeated addition of ferric iron at 2 mM gave rise to breaking of the sludge flocs, resulting in massive growth of sessile-protozoa and lowering of the numbers of nitrifiers. Ferrous iron at the same dosage resulted in large coherent flocs. Nitrite hereby seemed to enhance the detrimental effect of the ferric iron on the floc structure, whereas nitrate had a neutralizing character. 16S rRNA gene analysis showed a clear impact of the different iron respectively nitrogen treatments on the composition of bacterial communities. Cloning the sludge samples revealed the increased presence of denitrifying Feoxidizing bacteria in both the Fe(II) and Fe(III) reactors, suggesting a redox-state cycling between Fe(II) and Fe(III) in the mixed liquor.