User-Centered Development of a Mobile App to Assess the Quality of Life of Patients With Cancer: Iterative Investigation and Usability Testing.

BACKGROUND: The treatment for cancer can have a negative impact not only on physical well-being but also on mental health and the quality of life (QoL). Health apps enable the monitoring of different parameters, but to date, there are only few that support patients with cancer and none that focuses on the assessment of QoL. Furthermore, patients as stakeholders are often only integrated at the late stage of the development process, if at all. OBJECTIVE: The aim of this research was to develop and evaluate a smartphone app (Lion-App) to enable patients with cancer to autonomously measure the QoL with an iterative, user-centered approach. METHODS: Patients with cancer were involved in a 3-stage process from conceptualization to the point when the app was available on the tester's private device. First, focus groups with members (N=21) of cancer support groups were conducted to understand their expectations and needs. Thereafter, individual tests were performed. After developing a prototype that incorporated findings from the focus groups, a second test cycle was conducted, followed by a beta test lasting 2 months. In our app, the QoL can be assessed via a patient diary and an integrated questionnaire. Through all stages, usability was evaluated using the modular extended version of the User Experience Questionnaire (UEQ+), including the calculation of a key performance indicator (KPI). If possible, the impact of sex on the results was evaluated. As part of the beta test, usage rates as well as age-dependent differences were also assessed. RESULTS: A total of 21 participants took part in the initial 3 focus groups. In the subsequent usability testing (N=18), 17 (94%) participants rated their impression through the UEQ+, with a mean KPI of 2.12 (SD 0.64, range: -3 to 3). In the second usability test (N=14), the mean KPI increased to 2.28 (SD=0.49). In the beta test, the usage rate of 19 participants was evaluated, of whom 14 (74%) also answered the UEQ+ (mean KPI 1.78, SD 0.84). An influence of age on the number of questionnaire responses in Lion-App was observed, with a decrease in responses with increasing age (P=.02). Sex-dependent analyses were only possible for the first usability test and the beta test. The main adjustments based on user feedback were a restructuring of the diary as well as integration of a shorter questionnaire to assess the QoL. CONCLUSIONS: The iterative, user-centered approach for development and usability testing resulted in positive evaluations of Lion-App. Our app was rated as suitable for everyday use to monitor the QoL of patients with cancer. Initial results indicated that the sex and age of participants seem to play only a minor role.

The modulating impact of cigarette smoking on brain structure in panic disorder: a voxel-based morphometry study.

Cigarette smoking increases the likelihood of developing anxiety disorders, among them panic disorder (PD). While brain structures altered by smoking partly overlap with morphological changes identified in PD, the modulating impact of smoking as a potential confounder on structural alterations in PD has not yet been addressed. In total, 143 PD patients (71 smokers) and 178 healthy controls (62 smokers) participated in a multicenter magnetic resonance imaging (MRI) study. T1-weighted images were used to examine brain structural alterations using voxel-based morphometry in a priori defined regions of the defensive system network. PD was associated with gray matter volume reductions in the amygdala and hippocampus. This difference was driven by non-smokers and absent in smoking subjects. Bilateral amygdala volumes were reduced with increasing health burden (neither PD nor smoking > either PD or smoking > both PD and smoking). As smoking can narrow or diminish commonly observed structural abnormalities in PD, the effect of smoking should be considered in MRI studies focusing on patients with pathological forms of fear and anxiety. Future studies are needed to determine if smoking may increase the risk for subsequent psychopathology via brain functional or structural alterations.

Subtle changes of gray matter volume in fibromyalgia reflect chronic musculoskeletal pain rather than disease-specific effects.

Fibromyalgia syndrome (FMS) is a chronic pain syndrome. Neuroimaging studies provided evidence of altered gray matter volume (GMV) in FMS but, similarly, in chronic pain of other origin as well. Therefore, the purpose of this study was to evaluate the disease specificity of GMV alterations in FMS by direct comparison. Structural MRI data of the brain were acquired in 25 females with FMS and two different control groups: 21 healthy subjects and 23 patients with osteoarthritis. Regional GMVs were compared by voxel-based morphometry and additional ROI-analyses. In conclusion, we did not identify significant GMV alterations in either FMS or OA patients compared to healthy controls when adopting a conservative statistical approach with multiple comparison correction. However, even under a more liberal approach no FMS-specific GMV changes were found because both pain groups presented increased gray matter volumes in the precentral gyrus and decreased GMV in the angular gyrus/middle occipital gyrus and middle temporal gyrus in comparison with healthy controls. Since no differences between both pain groups could be detected cortical GMV changes in FMS should not be interpreted as FMS-specific but might rather reflect changes in chronic pain in general. This previously held notion is confirmed in this study by direct comparison with a control group consisting of another pain disorder.

Coordinate-based (ALE) meta-analysis of brain activation in patients with fibromyalgia.

There are an increasing number of neuroimaging studies that allow a better understanding of symptoms, neural correlates and associated conditions of fibromyalgia. However, the results of these studies are difficult to compare, as they include a heterogeneous group of patients, use different stimulation paradigms, tasks, and the statistical evaluation of neuroimaging data shows high variability. Therefore, this meta-analytic approach aimed at evaluating potential alterations in neuronal brain activity or structure related to pain processing in fibromyalgia syndrome (FMS) patients, using quantitative coordinate-based "activation likelihood estimation" (ALE) meta-analysis. 37 FMS papers met the inclusion criteria for an ALE analysis (1,264 subjects, 274 activation foci). A pooled ALE analysis of different modalities of neuroimaging and additional analyses according functional and structural changes indicated differences between FMS patients and controls in the insula, amygdala, anterior/mid cingulate cortex, superior temporal gyrus, the primary and secondary somatosensory cortex, and lingual gyrus. Our analysis showed consistent results across FMS studies with potential abnormalities especially in pain-related brain areas. Given that similar alterations have already been demonstrated in patients with other chronic pain conditions and the lack of adequate control groups of chronic pain subjects in most FMS studies, it is not clear however, whether these findings are associated with chronic pain in general or are unique features of patients with FMS. Hum Brain Mapp 37:1749-1758, 2016. © 2016 Wiley Periodicals, Inc.

Diagnostic classification based on functional connectivity in chronic pain: model optimization in fibromyalgia and rheumatoid arthritis.

RATIONALE AND OBJECTIVES: The combination of functional magnetic resonance imaging (fMRI) of the brain with multivariate pattern analysis (MVPA) has been proposed as a possible diagnostic tool. Goal of this investigation was to identify potential functional connectivity (FC) differences in the salience network (SN) and default mode network (DMN) between fibromyalgia syndrome (FMS), rheumatoid arthritis (RA), and controls (HC) and to evaluate the diagnostic applicability of derived pattern classification approaches. MATERIALS AND METHODS: The resting period during an fMRI examination was retrospectively analyzed in women with FMS (n = 17), RA (n = 16), and HC (n = 17). FC was calculated for SN and DMN subregions. Classification accuracies of discriminative MVPA models were evaluated with cross-validation: (1) inferential test of a single method, (2) explorative model optimization. RESULTS: No inferentially tested model was able to classify subjects with statistically significant accuracy. However, the diagnostic ability for the differential diagnostic problem exhibited a trend to significance (accuracy: 69.7%, P = .086). Optimized models in the explorative analysis reached accuracies up to 73.5% (FMS vs. HC), 78.8% (RA vs. HC), and 78.8% (FMS vs. RA) whereas other models performed at or below chance level. Comparable support vector machine approaches performed above average for all three problems. CONCLUSIONS: Observed accuracies are not sufficient to reliably differentiate between FMS and RA for diagnostic purposes. However, some indirect evidence in support of the feasibility of this approach is provided. This exploratory analysis constitutes a fundamental model optimization effort to be based on in further investigations.

Early affective processing in patients with acute posttraumatic stress disorder: magnetoencephalographic correlates.

BACKGROUND: In chronic PTSD, a preattentive neural alarm system responds rapidly to emotional information, leading to increased prefrontal cortex (PFC) activation at early processing stages (<100 ms). Enhanced PFC responses are followed by a reduction in occipito-temporal activity during later processing stages. However, it remains unknown if this neuronal pattern is a result of a long lasting mental disorder or if it represents changes in brain function as direct consequences of severe trauma. METHODOLOGY: The present study investigates early fear network activity in acutely traumatized patients with PTSD. It focuses on the question whether dysfunctions previously observed in chronic PTSD patients are already present shortly after trauma exposure. We recorded neuromagnetic activity towards emotional pictures in seven acutely traumatized PTSD patients between one and seven weeks after trauma exposure and compared brain responses to a balanced healthy control sample. Inverse modelling served for mapping sources of differential activation in the brain. PRINCIPAL FINDINGS: Compared to the control group, acutely traumatized PTSD patients showed an enhanced PFC response to high-arousing pictures between 60 to 80 ms. This rapid prefrontal hypervigilance towards arousing pictorial stimuli was sustained during 120-300 ms, where it was accompanied by a reduced affective modulation of occipito-temporal neural processing. CONCLUSIONS: Our findings indicate that the hypervigilance-avoidance pattern seen in chronic PTSD is not necessarily a product of an endured mental disorder, but arises as an almost immediate result of severe traumatisation. Thus, traumatic experiences can influence emotion processing strongly, leading to long-lasting changes in trauma network activation and expediting a chronic manifestation of maladaptive cognitive and behavioral symptoms.

Cerebral activation and catastrophizing during pain anticipation in patients with fibromyalgia.

OBJECTIVE: Anticipation of pain influences its cerebral processing and dysfunctional cognitive style like catastrophizing correlates with the severity of pain. Patients with fibromyalgia syndrome (FMS) exhibit higher levels of catastrophizing, increased attention to pain, and augmented cerebral pain processing. Therefore, alteration in cerebral processing during anticipation of experimental pain and its relation to catastrophizing are the main focus of the study. METHODS: Functional magnetic resonance imaging of the brain was acquired during the time of pain anticipation with announcement of its intensity or not in 12 patients with FMS and 14 healthy controls. Within a two-factorial model (factors "group" and "session"), the main effect of group and the interaction effect were tested in a whole-brain analysis. In addition, activation of the periaqueductal gray (PAG) was analyzed in a region-of-interest analysis. RESULTS: Patients with FMS generally displayed greater catastrophizing behavior (p = .003) but not during the anticipation of the experimental pain (p > .16). Furthermore, patients showed greater activation of the dorsolateral prefrontal cortex (p = .05), the PAG (p = .04), and the posterior parietal cortex (p = .03) during the anticipation of pain, independent of the pain coping behavior during anticipation. CONCLUSIONS: The lack of difference in catastrophizing during the experimental pain suggests independent coping mechanisms during experimental and clinical pain. Regarding the importance of the frontal cortex and the PAG in the descending pain modulation system, it seems reasonable to assume that these functional changes related to the context of stimulus presentation may contribute to central sensitization in FMS.

Fibromyalgia unique temporal brain activation during experimental pain: a controlled fMRI Study.

Studies with functional neuroimaging support the hypothesis of central pain augmentation in fibromyalgia syndrome (FMS) with functional differences in areas of the medial pain system. To clarify whether these findings are unique to patients with FMS, BOLD-signal patterns during and before tonic experimental pain were compared to healthy controls and patients with rheumatoid arthritis (RA) as a chronic pain disorder of somatic origin. We expected different BOLD-signal patterns in areas of the medial pain system that were most pronounced in patients with FMS. An fMRI-block design before, during and after an incision was performed in patients with FMS (n = 17), RA (n = 16) and in healthy controls (n = 17). A 2-factorial model of BOLD-signal changes was designed to explore significant differences of brain activation between the groups during the pain stimulus. Additionally, the correlation of brain activity during the anticipation of pain with the amount of the impending pain was determined. We observed a FMS-unique temporal brain activation of the frontal cortex in patients with FMS. Moreover, areas of the motor cortex and the cingulate cortex presented a FMS-specific relation between brain activity during pain anticipation and the magnitude of the subsequent pain experience. Our results support the hypothesis that central mechanisms of pain processing in the frontal cortex and cingulate cortex may play an important role in patients with FMS.

Decreased gray matter volumes in the cingulo-frontal cortex and the amygdala in patients with fibromyalgia.

OBJECTIVE: Studies in fibromyalgia syndrome with functional neuroimaging support the hypothesis of central pain augmentation. To determine whether structural changes in areas of the pain system are additional preconditions for the central sensitization in fibromyalgia we performed voxel based morphometry in patients with fibromyalgia and healthy controls. METHODS: We performed 3 Tesla magnetic resonance imaging of the brain in 14 patients with fibromyalgia and 14 healthy controls. Regional differences of the segmented and normalized gray matter volumes in brain areas of the pain system between both groups were determined. In those areas in which patients structurally differed from healthy controls, the correlation of disease-related factors with gray matter volumes was analyzed. RESULTS: Patients presented a decrease in gray matter volume in the prefrontal cortex, the amygdala, and the anterior cingulate cortex (ACC). The duration of pain or functional pain disability did not correlate with gray matter volumes. A trend of inverse correlation of gray matter volume reduction in the ACC with the duration of pain medication intake has been detected. CONCLUSIONS: Our results suggest that structural changes in the pain system are associated with fibromyalgia. As disease factors do not correlate with reduced gray matter volume in areas of the cingulo-frontal cortex and the amygdala in patients, one possible interpretation is that volume reductions might be a precondition for central sensitization in fibromyalgia.

Altered brain activity during pain processing in fibromyalgia.

Fibromyalgia syndrome (FMS) is characterized by widespread pain. Studies with functional neuroimaging support the hypothesis of central pain augmentation in FMS. We tested this in our study with a novel paradigm of tonic pain induced by a single stimulus. Tonic pain, in contrast to phasic pain, seems to be a more appropriate experimental approach to study adaptive mechanisms of pain processing in FMS. We hypothesized that brain areas related to the "medial" pain system and the amygdalae will present different activation in patients compared to healthy subjects. An fMRI-block design before, during and after an incision was made in patients with FMS and in healthy controls. Acute pain caused by the incision was measured during the course of the experiment. A 2 factorial model of BOLD-signal changes was designed to explore significant differences of brain activation between both groups during the pain stimulus. Additionally the first Eigenvariates in those areas which show an interaction between both factors were determined over the time course of pain stimulation. Differences of activation in the fronto-cingulate cortex, the supplemental motor areas, and the thalamus were found between both groups with distinct differences in BOLD-signals changes over the time course of pain stimulation, even during anticipation of pain. Our results support the hypothesis that central mechanisms of pain processing in the medial pain system, favourable cognitive/affective factors even during the anticipation of pain, may play an important role for pain processing in patients with FMS.

Comparative examination of complaints of patients with breast-cancer with and without silicone implants.

OBJECTIVE: To measure the relationship between silicone breast implants and various symptoms using a control group. STUDY DESIGN: A matched-pair-analysis of 96 women with breast-cancer (32 with silicone implants (K I); 64 without implants (K II)) was performed with help of a standardized questionnaire in respect to 50 single criteria. The condition of implants was monitored by MR-imaging. RESULTS: Athralgias and myalgias were not significantly more frequent in K I. Only six symptoms were reported significantly more often in patients with implants. Positive correlation with implant rupture was given only for the numb feeling/tingling sensation in extremities (P=0.02). There was no correlation between silicone implants and the symptoms of the "chronic-fatigue syndrome" nor any other described silicone-induced disease. CONCLUSIONS: According to our analysis many of the symptoms examined here are present in middle-aged women regardless of silicone implants and underlying disease.