Ready, Willing and Able? An Investigation of the Theory of Planned Behaviour in Help-Seeking for a Community Sample with Current Untreated Depressive Symptoms.

Applying health behaviour change models, such as the theory of planned behaviour (TPB), to help-seeking for mental health problems can address the deficit in health care utilisation. However, previous studies largely focused on help-seeking intentions and not behaviour, which might be problematic due to the intention-behaviour gap. Hence, TPB and help-seeking were examined in a German community sample with current untreated depressive symptoms: 188 adults (Mage = 50.34; SD = 16.19; 70.7% female) participated in a baseline interview and survey measuring components of the TPB (attitudes, subjective norms and perceived behavioural control) and help-seeking intentions. They reported actual help-seeking from mental health professionals via telephone surveys 3 and 6 months later. To better understand the potential gap between help-seeking intentions and behaviour and to investigate the contributions of readiness, willingness and ability to seek help, two path models were constructed in accordance with the TPB controlling for covariates. Attitudes (ß = .24), subjective norms (ß = .25) and self-efficacy (ß = .15) were significantly associated with intentions (R2 = 26%), which predicted help-seeking (Cox and Snell's pseudo-R2 = 23%); controllability did not predict help-seeking. In sum, the TPB provides a reliable framework to explore help-seeking behaviour for mental health problems. Based on these findings, prevention efforts should focus on readiness and willingness to seek help (e.g. foster positive attitudes and social support of treatment). However, the role of ability, operationalised as perceived behavioural control and (perceived) barriers to help-seeking, warrants further research, as self-efficacy but not controllability was associated with help-seeking.

Shame, self-identification with having a mental illness, and willingness to seek help in northeast Germany.

We examined a general population sample (n = 1330) from an epidemiological study (SHIP), investigating whether shame, social distance and reluctance to self-identify as having a mental illness interfere with willingness to seek help for mental health problems. Analyses were stratified for life-time diagnosis of any mental illness. Shame was the strongest negative predictor for willingness to seek help (beta = -0.183, p < .001). Structured Estimation Modelling showed shame being a full mediator of a negative association between social distance and willingness. Our results corroborate the important role of shame as an impediment to help-seeking for mental health problems in the general population.

A Prospective Study on Structural and Attitudinal Barriers to Professional Help-Seeking for Currently Untreated Mental Health Problems in the Community.

To date, little is known about the concurrent impact of structural and attitudinal factors on help-seeking behaviour for mental health problems. Therefore, this study investigated a longitudinal German community sample of adults with currently untreated mental health problems (N = 188, mean age = 50.34, 70.7% female) regarding perceived structural (e.g. accessibility) as well as attitudinal barriers (e.g. anticipated self-stigma) to help-seeking intentions and behaviour. Overall, perceived accessibility, spatial and temporal distance from mental health services predicted help-seeking. Among attitudinal factors, treatment efficacy beliefs were strongly connected to help-seeking. In addition, among people who knew where to find a psychologist or psychotherapist, anticipated self-stigma emerged as a significant barrier to help-seeking. Therefore, creating positive treatment expectancies and dismantling erroneous perceptions of structural aspects of mental health services hold promise to further close the gap in mental health care utilisation. However, the role of anticipated self-stigma within the help-seeking process requires further research.

Individuals with currently untreated mental illness: causal beliefs and readiness to seek help.

AIMS: Many people with mental illness do not seek professional help. Beliefs about the causes of their current health problem seem relevant for initiating treatment. Our aim was to find out to what extent the perceived causes of current untreated mental health problems determine whether a person considers herself/himself as having a mental illness, perceives need for professional help and plans to seek help in the near future. METHODS: In a cross-sectional study, we examined 207 untreated persons with a depressive syndrome, all fulfilling criteria for a current mental illness as confirmed with a structured diagnostic interview (Mini International Neuropsychiatric Interview). The sample was recruited in the community using adverts, flyers and social media. We elicited causal explanations for the present problem, depression literacy, self-identification as having a mental illness, perceived need for professional help, help-seeking intentions, severity of depressive symptoms (Patient Health Questionnaire - Depression), and whether respondents had previously sought mental healthcare. RESULTS: Most participants fulfilled diagnostic criteria for a mood disorder (n = 181, 87.4%) and/or neurotic, stress-related and somatoform disorders (n = 120, 58.0%) according to the ICD-10. N = 94 (45.4%) participants had never received mental health treatment previously. Exploratory factor analysis of a list of 25 different causal explanations resulted in five factors: biomedical causes, person-related causes, childhood trauma, current stress and unhealthy behaviour. Attributing the present problem to biomedical causes, person-related causes, childhood trauma and stress were all associated with stronger self-identification as having a mental illness. In persons who had never received mental health treatment previously, attribution to biomedical causes was related to greater perceived need and stronger help-seeking intentions. In those with treatment experience, lower attribution to person-related causes and stress were related to greater perceived need for professional help. CONCLUSIONS: While several causal explanations are associated with self-identification as having a mental illness, only biomedical attributions seem to be related to increase perceived need and help-seeking intentions, especially in individuals with no treatment experiences. Longitudinal studies investigating causal beliefs and help-seeking are needed to find out how causal attributions guide help-seeking behaviour. From this study it seems possible that portraying professional mental health treatment as not being restricted to biomedical problems would contribute to closing the treatment gap for mental disorders.

Who is seeking whom? A person-centred approach to help-seeking in adults with currently untreated mental health problems via latent class analysis.

PURPOSE: Global surveys point to a gap in mental health service utilisation. However, contacting more than one source of professional help may influence the estimates of utilisation. Currently, few studies statistically differentiate between different sources of help based on patient characteristics. METHODS: We assessed sociodemographic and psychosocial data in a convenience sample of 188 adults with mental health problems (Mage = 50.34 years; SD = 16.19; 71% female), who reported their help-seeking behaviour during the next 6 months. We analysed their behaviour via latent class analysis and compared baseline characteristics between classes. RESULTS: We found four latent classes: "mental health professionals" (MHP; 9.0%), "multiple sources" (4.3%), "primary care" (35.6%), and "non-seekers" (51.1%). All classes had moderate to high probabilities of seeking help from friends or family. Primary care utilisers were more often in a cohabiting partnership; MHP utilisers were more experienced in mental health treatment and reported lower well-being and more depressive symptoms than non-seekers. By trend, non-seekers were younger, and both non-seekers and primary care utilisers reported fewer depressive and somatic symptoms than utilisers of multiple sources and MHP. CONCLUSIONS: In our analysis, MHP utilisation was even lower (9.0%) than in previous studies. However, MHP utilisers appeared to suffer from more serious conditions than other latent classes. As informal sources such as family and friends were present in all latent classes, help-seeking behaviour seems to transcend traditional MHP-focused approaches. Further research is necessary to investigate tenability and trajectories of different latent classes of help-seeking in larger and representative samples with longer follow-ups.

Is knowledge "half the battle"? The role of depression literacy in help-seeking among a non-clinical sample of adults with currently untreated mental health problems.

BACKGROUNDS: The concept of mental health literacy suggests that higher literacy increases the likelihood of seeking treatment. However, previous studies mostly use vignettes, and do not investigate actual help-seeking behaviour. METHODS: We assessed depression literacy and type of mental illness in a convenience sample of 207 adults with currently untreated mental health problems from the general population. Our analysis sample comprised 152 adults (Mage = 52.12; 73.0% female) with a depressive disorder. Help-seeking behaviour was measured 3 and 6 months after the initial assessment. We conducted multiple logistic regression models to test whether depression literacy predicted help-seeking from mental health professionals, general practitioner, family and friends, or counselling, controlling for sociodemographic data, and depression severity. RESULTS: Depression literacy was lower in men and older participants, and higher in participants with prior treatment experience. Depression literacy was negatively linked to informal help-seeking (aOR = 0.33 [0.13; 0.84]) when included as a dichotomous predictor (i.e., 'high' versus 'low' literacy). LIMITATIONS: Our sample was small, thus we did not differentiate between types of depressive disorders in our analysis. CONCLUSION: We could not corroborate most postulated associations between depression literacy and help-seeking, except for the negative association with informal help. Our findings underline differences between previous vignette-based and community-based investigations of the help-seeking process for mental health problems. To explore underlying mechanisms, future research should investigate the role of intermediary variables and processes in the association between depression literacy and help-seeking, such as self-efficacy and symptom attribution, which might be more clinically relevant in help-seeking for depressive symptoms.

An online intervention using information on the mental health-mental illness continuum to reduce stigma.

BACKGROUND: A core component of stigma is being set apart as a distinct, dichotomously different kind of person. We examine whether information on a continuum from mental health to mental illness reduces stigma. METHOD: Online survey experiment in a quota sample matching the German population for age, gender and region (n=1679). Participants randomly received information on either (1) a continuum, (2) a strict dichotomy of mental health and mental illness, or (3) no information. We elicited continuity beliefs and stigma toward a person with schizophrenia or depression. RESULTS: The continuum intervention decreased perceived difference by 0.19 standard deviations (SD, P<0.001) and increased social acceptance by 0.18 SD (P=0.003) compared to the no-text condition. These effects were partially mediated by continuity beliefs (proportion mediated, 25% and 26%), which increased by 0.19 SD (P<0.001). The dichotomy intervention, in turn, decreased continuity beliefs and increased notions of difference, but did not affect social acceptance. CONCLUSION: Attitudes towards a person with mental illness can be improved by providing information on a mental health-mental illness continuum.

Stable oncogenic silencing in vivo by programmable and targeted de novo DNA methylation in breast cancer.

With the recent comprehensive mapping of cancer genomes, there is now a need for functional approaches to edit the aberrant epigenetic state of key cancer drivers to reprogram the epi-pathology of the disease. In this study we utilized a programmable DNA-binding methyltransferase to induce targeted incorporation of DNA methylation (DNAme) in the SOX2 oncogene in breast cancer through a six zinc finger (ZF) protein linked to DNA methyltransferase 3A (ZF-DNMT3A). We demonstrated long-lasting oncogenic repression, which was maintained even after suppression of ZF-DNMT3A expression in tumor cells. The de novo DNAme was faithfully propagated and maintained through cell generations even after the suppression of the expression of the chimeric methyltransferase in the tumor cells. Xenograft studies in NUDE mice demonstrated stable SOX2 repression and long-term breast tumor growth inhibition, which lasted for >100 days post implantation of the tumor cells in mice. This was accompanied with a faithful maintenance of DNAme in the breast cancer implants. In contrast, downregulation of SOX2 by ZF domains engineered with the Krueppel-associated box repressor domain resulted in a transient and reversible suppression of oncogenic gene expression. Our results indicated that targeted de novo DNAme of the SOX2 oncogenic promoter was sufficient to induce long-lasting epigenetic silencing, which was not only maintained during cell division but also significantly delayed the tumorigenic phenotype of cancer cells in vivo, even in the absence of treatment. Here, we outline a genome-based targeting approach to long-lasting tumor growth inhibition with potential applicability to many other oncogenic drivers that are currently refractory to drug design.

Bidirectional modulation of endogenous EpCAM expression to unravel its function in ovarian cancer.

BACKGROUND: The epithelial cell adhesion molecule (EpCAM) is overexpressed on most carcinomas. Dependent on the tumour type, its overexpression is either associated with improved or worse patient survival. For ovarian cancer, however, the role of EpCAM remains unclear. METHODS: Cell survival of ovarian cancer cell lines was studied after induction or repression of endogenous EpCAM expression using siRNA/cDNA or artificial transcription factors (ATF) consisting of engineered zinc-fingers fused to either a transcriptional activator or repressor domain. RESULTS: Two ATFs were selected as the most potent down- and upregulator, showing at least a two-fold alteration of EpCAM protein expression compared with control. Downregulation of EpCAM expression resulted in growth inhibition in breast cancer, but showed no effect on cell growth in ovarian cancer. Induction or further upregulation of EpCAM expression decreased ovarian cancer cell survival. CONCLUSION: The bidirectional ATF-based approach is uniquely suited to study cell-type-specific biological effects of EpCAM expression. Using this approach, the oncogenic function of EpCAM in breast cancer was confirmed. Despite its value as a diagnostic marker and for immunotherapy, EpCAM does not seem to represent a therapeutic target for gene expression silencing in ovarian cancer.

Diclofenac combined with cyclosporine in treatment refractory rheumatoid arthritis: longitudinal safety assessment and evidence of a pharmacokinetic/dynamic interaction.

OBJECTIVE: (1) To characterize potential changes in diclofenac pharmacokinetics and renal function in patients with rheumatoid arthritis (RA) treated with diclofenac and cyclosporine; (2) to prospectively collect longitudinal safety data during use of this drug combination. METHODS: Twenty patients with severe, treatment refractory RA were sequentially treated with stable doses of diclofenac (100-200 mg/day) for one month followed by diclofenac combined with cyclosporine (3 mg/kg/day) for one month. Pharmacokinetic profiles of diclofenac were obtained at the end of each treatment period. Combined therapy was continued for an additional 5 months, during which doses of both drugs could be individually titrated and safety data collected. RESULTS: During co-administration, diclofenac exposure doubled, as shown by an average 104% increase in the area-under-the-curve. Diclofenac half-life was not altered. Serum creatinine was significantly elevated from a baseline value of 0.8 +/- 0.1 mg/dl on diclofenac alone to 1.0 +/- 0.3 mg/dl after one month co-administration with cyclosporine. The magnitude of creatinine elevation was not correlated with that of change in diclofenac exposure, suggesting the pharmacokinetic interaction per se may not additionally contribute to the effect on renal function resulting from this drug combination. During longterm treatment with both medications, prospectively collected safety data indicated that renal function could be stabilized when drug doses were individually titrated in response to serial clinical and laboratory evaluations. The overall pattern of adverse events and laboratory abnormalities in the study population were similar to those reported in patients with RA treated with other nonsteroidal antiinflammatory agents and concomitant cyclosporine. CONCLUSION: Diclofenac can be safely combined with cyclosporine in the management of RA when appropriate clinical monitoring and dose titrations are performed. Due to the pharmacokinetic interaction that increases diclofenac systemic exposure, it would be prudent to start combination therapy with diclofenac doses at the lower end of the therapeutic dose range.

[Contact cyclophotocoagulation with the continuous wave Nd:YAG laser with quartz fiber. Optimizing coagulation parameters]. / Kontaktzyklophotokoagulation mit dem Dauerstrich-Nd:YAG-Laser über Quarzfaser. Optimierung der Koagulationsparameter.

Transscleral cyclo-photocoagulation with a cw-Nd:YAG-laser was studied in enucleated porcine eyes with application times of between 10 ms and 1.5 s. Contact coagulation via a quartz fiber (core 600 microns) required about 32% less power to create visible ciliary body coagulation compared to non-contact coagulation via a focusing handpiece. Application of focusing fiber tips led to a further reduction in the coagulation threshold by a factor of 0.6. The energy per laser application required for ciliary body coagulation increased with application time. During contact coagulation using plane fiber tips a pronounced temperature rise was sometimes observed at the fiber tip due to deposits of carbonized tissue with the subsequent risk of scleral damage. In a pilot study five eyes with secondary glaucoma were treated under coagulation conditions found to be optimal (8 W at 0.2 s).

Treatment of refractory acute lymphoblastic leukemia in adults with high dose cytosine arabinoside and mitoxantrone (HAM).

In a clinical phase II study the combination of high dose cytosine arabinoside and mitoxantrone (HAM) was applied to 24 patients with refractory acute lymphoblastic leukemia (ALL). All patients had received a standardized first line treatment and were considered refractory against conventional chemotherapy as defined by nonresponse to induction treatment (n = 8), nonresponse to an alternative salvage regimen at first relapse (n = 9), second and third relapses (n = 5) and relapse after bone marrow transplantation (n = 2). Therapy consisted of HD-araC 3 g/m2 q 12 hr days 1-4 and mitoxantrone 10 mg/m2/d days 2-5 or 2-6. Twelve of the 24 patients (50%) achieved a complete remission (CR), one patient had a partial remission, and five patients were nonresponders. Five patients died in aplasia due to infections, one additional patient succumbed to HD-araC related CNS toxicity. Nonhematologic side effects consisted predominantly in infection, nausea and vomiting, mucositis and diarrhea. Recovery of blood counts occurred at a median of 28 days from the onset of treatment; the median time to CR was 33 days. Three of the 12 responders underwent subsequent bone marrow transplantations and one is alive disease free at 40+ months. The median remission duration for the remaining nine patients is 3.5 months, with one case in ongoing CCR at 36+ months; the median survival time is 5 months. Considering the selection of a highly unfavorable group of patients, these data demonstrate a significant antileukemic activity of HAM in refractory ALL and support its application as consolidation treatment during first line ALL therapy.

Thermal side reactions during in vitro contact cyclophotocoagulation with the continuous wave Nd:YAG laser.

We compared the effects of continuous wave Nd:YAG laser irradiation on the ciliary body and sclera of enucleated porcine eyes produced by two means of transmission: contact coagulations via a quartz fiber (core 600 microns), and noncontact coagulations via a focussing handpiece. Application times ranged from 10 ms to 1.5 seconds. During contact coagulations using plane fiber tips the temperature at the fiber tip, due to deposits of carbonized tissue, sometimes increased markedly, increasing the risk of perforation. Clinical application of the contact method using plain fiber tips is not recommended.