Current ketamine-based therapies for treatment-resistant depression (TRD) often induce dissociative effects. A novel oral PR ketamine formulation (KET01) results in a low and delayed peak concentration of ketamine, high hydroxynorketamine concentration, and is associated with limited dissociative properties.

To investigate efficacy, safety, and pharmacokinetics of KET01 in TRD.

KET01-02 was a randomized, double-blind phase 2 trial in outpatients with TRD comparing adjunct 120 mg (n=42) or 240 mg (n=40) oral KET01 once-daily for 3 weeks to placebo (PBO, n=40). The primary endpoint was change from baseline in the MADRS mean score on Day 21. KET01-03 was a randomized, double-blind, cross-over phase I trial in 26 healthy volunteers comparing single doses of 240 mg oral KET01 and 84 mg an approved intranasal formulation of eketamine. The primary endpoint was maximum change of Clinician-Administered Dissociative States Scale (CADSS) score from baseline.

KET01-03 trial; the mean (±SD) maximum change of CADSS score within 24 hours after dosing was 29.6±12.5 for intranasal eketamine and 0.7±1.7 for KET01 (p<0.00000000001). KET01-02 trial; no differences in CADSS score (range: 0.2 to 1.3), and heart rate and blood pressure were observed between the groups on Day 1 and beyond. 10%, 12%, and 15% of patients in the PBO, 120 mg/day, and 240 mg/day KET01 groups, respectively had CADSS score >4 and increase from baseline. At 7 hours post first KET01 dose (240 mg), plasma concentration of ketamine (38.7±27.0 ng/ml) was lower than its metabolites norketamine (267.5±81.6 ng/ml) and hydroxynorketamine (190.2±85.5 ng/ml). 240 mg/day KET01 induced clinically relevant reduction from baseline in MADRS score already within the first 7 hours of treatment (-7.65; Δ vs PBO: -2.22, n.s.), with a statistically significant separation on Day 4 (-10.02; Δ vs PBO: -3.66, p=0.020) and Day 7 (-12.21; Δ vs PBO: -3.95, p=0.042). MADRS score decrease was sustained throughout Day 21 (-13.15; Δ vs PBO: -1.82, n.s.), and during 4-week follow-up (-12.51; Δ vs PBO: -3.35, n.s.). Treatment-emergent adverse events occurred in 47.5%, 50.0%, and 62.5% of patients in the PBO, 120 mg/day, and 240 mg/day KET01 group, respectively.

Oral 240 mg/day KET01 induces a rapid, and clinically relevant reduction of depressive symptoms with only minimal signs of dissociation, potentially due to lower ketamine levels and increased norketamine and hydroxynorketamine levels compared to intravenous administration. Our results suggest that KET01 may be an efficacious and safe take-at-home adjunct treatment for TRD.

C. zu Eulenburg Employee of: HMNC Brain Health, E. Papanastasiou Employee of: HMNC Brain Health, K. Schmid Employee of: Develco Pharma, A. Damyanova Employee of: HMNC Brain Health, A. Glas Employee of: HMNC Brain Health, C. Strote Employee of: HMNC Brain Health, L. Arvastson Employee of: HMNC Brain Health, H. Eriksson Employee of: HMNC Brain Health

To do the complexity of being a caregiver of a psychiatric inpatient justice, it is imperative to broaden the lopsided perspective of the burden of caregivers in research studies to the also existing rewards of caregiving.

Semi-structured interviews with ever 15 caregivers of patients with schizophrenia, depression, bipolar disorders and personality disorders were analysed by using a summarizing content analysis. The interviews focus on negative and positive aspects of providing care for a family member. Furthermore, the coping strategies of the caregivers were analysed by using the Freiburg Questionnaire on Coping with Illness (FQCI).

The burden of the relatives (n=60) are many-sided (787 individual statements are named), but the rewards are surprisingly numerous, too. 413 individual statements of rewards could be summarized in 23 global statements, which were assigned to six categories: “Appreciation for providing care from the patient and others and satisfaction about providing care” (30.3%), “Gain in personality and experience of life” (22.8%), “Gain in successful coping strategies” (13.6%), “Increase of cohesion and relationship within the family” (13.1%), “Changes of attitudes and opinions” (12.1%) and “Experiences of support by others” (8.2%). The most frequent coping strategies of the relatives are “Active problem-oriented coping” (mean value 3.5), “Distraction and building self-esteem” (2.7) and “Religiousness and search for meaning” (2.7).

Results demonstrate the relevance and variety of both positive and negative aspects of caregiving and targets for intervention in psychoeducation programmes as well as in self-help groups to encourage relatives in their skills and resources.

The study aimed at exploring prevalence and risk factors of attempted suicide and suicidal thoughts before hospital admission.

40.451 episodes of inpatient care from 1995 to 2004 were included. Last admission of each patient (n=20.543) was extracted to investigate attempted suicide and suicidal thoughts before admission, which were recorded by the German Basic Documentation System (BADO). Univariate analyses and multivariate logistic regression analyses were performed to explore predictors of suicidality before hospital admission.

3.643 (17.7%) of 20.543 inpatients attempted suicide or had suicidal thoughts before admission. 1.478 (7.2%) attempted suicide before admission. Most had diagnoses F43 (36.5%), F32/33 (19.2%) or F60/61 (8.8%). According to regression analysis risk of attempted suicide increases with life time suicide attempt, diagnosis F43, admission due to doctor´s recommendation, diagnosis F32/33, diagnosis F60/61 and period of onset of present episode less than one week. 2.165 (10.5%) had suicidal thoughts before admission without concomitant suicide attempt. Most frequent diagnoses were F43 (23.5%), F32/33 (22.7%) and F10 (11.7%). Risk of suicidal thoughts increases with diagnosis F43, diagnosis F32/33, life time suicide attempt, diagnosis F60/61, supportive psychotherapy before admission, period of onset of present episode less than one week, being younger and being not rehospitalized.

Basic rate of suicidality before admission of psychiatric inpatients is high. Therefore, risk of suicide should be carefully examined at admission but also during inpatient care. Especially, inpatients with adjustment disorder and depression seem to be a high risk groups regarding suicidality before admission and require special attention.

The study aimed to evaluate if and how online self-help forums are used by patients with bipolar affective disorders, their relatives and by professionals.

2400 postings in two German language forums for patients with bipolar affective disorders, their relatives and professionals were qualitatively and quantitatively analysed. Interrater-reliability was 0,84 (Cohen's Kappa). Chi-squared tests with Bonferroni correction were performed and exploratory factor analyses were conducted.

94% of all postings were written by patients, 4% were written by relatives, and 2% by professionals. “Disclosure” (44% of all postings), “friendship” (23%), “online-group cohesion” (22%), “empathy and support” (18%), and “provision of information” (15%) were the main self-help mechanisms. The topics most discussed were the “social network” of the patients (27%), the “symptoms of the illness” (22%), “medication” (14%), “professionals” (12%), and “diagnoses” (11%). The item “provision of information” was significantly more often named by professionals (chi(2)=32,30; p<0,001), whereas the item “gratitude” was significantly more often named by relatives (chi(2)=34,91; p<0,001). Factor analysis revealed three factors according to self-help mechanisms: “group cohesion”, “emotional support”, and “exchange of information”. Also according to fields of interest factor analysis yielded three factors: “illness related aspects”, “social aspects”, and “financial and legal issues”.

We infer that the main interest in participating in online forums for patients with bipolar affective disorders and their relatives is to share emotions. Our study also reveals that the social network is very important for patients coping with bipolar affective disorders. Psychoeducative programmes should focus on those aspects.

This study aimed to link expression patterns of AQP1, AQP5, Bcl-2 and p16 to clinicopathological characteristics of oro-hypopharyngeal squamous cell carcinomas.

Immunohistochemical expression of AQP1, AQP5, Bcl-2 and p16 was investigated in 107 consecutive oro-hypopharyngeal squamous cell carcinoma cases. Molecular interrelationship and correlations with clinicopathological parameters and survival were computed.

AQP1 was expressed exclusively by a subgroup of basaloid-like squamous cell carcinomas. AQP5 was detected in 25.2 per cent of the samples, showing significant association with the absence of p16 and Bcl-2 (p = 0.018; p = 0.010). In multivariate analysis, overexpression of p16 was significantly correlated with favourable overall survival (p = 0.014).

AQP5 defined a subset of patients with Bcl-2-negative and p16-negative tumours with a poor clinical outcome. AQP1 was found to be a marker of a subgroup of aggressive basaloid-like squamous cell carcinomas. These findings suggest that AQP1 and AQP5 are interesting candidates for further studies on risk group classification and personalised treatment of oro-hypopharyngeal squamous cell carcinomas.

To determine whether total and antianaerobic antibiotic exposure increases the risk of room contamination among vancomycin-resistant enterococci (VRE)–colonized patients.

A 14-month study in 2 intensive care units at an academic tertiary care hospital in Boston, Massachusetts.

All patients who acquired VRE or were VRE-colonized on admission and who had environmental cultures performed.

We performed weekly environmental cultures (2 sites per room) and considered a room to be contaminated if there was a VRE-positive environmental culture during the patient's stay. We determined risk factors for room contamination by use of the Cox proportional hazards model.

Of 142 VRE-colonized patients, 35 (25%) had an associated VRE-positive environmental culture. Patients who contaminated their rooms were more likely to have diarrhea than those who did not contaminate their rooms (23 [66%] of 35 vs 41 [38%] of 107; P = .005) and more likely to have received antibiotics while VRE colonized (33 [94%] of 35 vs 86 [80%] of 107; P = .02). There was no significant difference in room contamination rates between patients exposed to antianaerobic regimens and patients exposed to nonantianaerobic regimens or between patients with and patients without diarrhea, but patients without any antibiotic exposure were unlikely to contaminate their rooms. Diarrhea and antibiotic use were strongly confounded; although two-thirds of room contamination occurred in rooms of patients with diarrhea, nearly all of these patients received antibiotics. In multivariable analysis, higher mean colonization pressure in the ICU increased the risk of room contamination (adjusted hazard ratio per 10% increase, 1.44 [95% confidence interval, 1.04–2.04]), whereas no antibiotic use during VRE colonization was protective (adjusted hazard ratio, 0.21 [95% confidence interval, 0.05–0.89]).

Room contamination with VRE was associated with increased mean colonization pressure in the ICU and diarrhea in the VRE-colonized patient, whereas no use of any antibiotics during VRE colonization was protective.