Repeated oral esketamine in patients with treatment resistant depression and comorbid posttraumatic stress disorder.

Introduction: Ketamine and its S-enantiomer esketamine are novel pharmacotherapeutic options for treatment resistant depression (TRD). There is growing evidence on the efficacy for other psychiatric disorders, including posttraumatic stress disorder (PTSD). It is hypothesized that psychotherapy may further potentiate the effects of (es)ketamine in psychiatric disorders. Methods: Repeated oral esketamine was prescribed once or twice weekly in five patients suffering from TRD and comorbid PTSD. We describe the clinical effects of esketamine and report data from psychometric instruments and patients' perspectives. Results: Esketamine treatment duration ranged from six weeks to a year. In four patients, we observed improvement in depressive symptoms, increased resilience and more receptiveness to psychotherapy. One patient experienced symptom worsening in response to a threatening situation during esketamine treatment, highlighting the need for a safe setting. Discussion: (Es)ketamine treatment within a psychotherapeutic framework appears promising in patients with treatment resistant symptoms of depression and PTSD. Controlled trials are warranted to validate these results and to elucidate the optimal treatment methods.

[The effectiveness of monoamine oxidase inhibitors in treatment-resistant depressive disorders in clinical practice; a retrospective open-label study]. / De effectiviteit van monoamineoxidase-remmers bij therapieresistente depressie in de klinische praktijk; een retrospectieve openlabelstudie.

BACKGROUND: Monoamine oxidase (mao)-inhibitors are often prescribed in patients suffering from treatment-resistant depression, but the evidence of its effectiveness in this type of depression is limited: a restricted amount of similar studies describes response-rates of 12-75%.
AIM: To get more insight in the effectiveness of mao-inhibitors in treatment-resistant depression in clinical practice.
METHOD: We investigated medical files of patients with a uni- or bipolar, treatment-resistant depression and looked at the difference in score on the Inventory of Depressive Symptomatology - Self Report (ids-sr) before and after 3 months of treatment with a mao-inhibitor. After that, we investigated how often patients achieved remission, response, partial response, no response or drop-out due to of side-effects.
RESULTS: The included 17 patients achieved a mean decrease of 8.6 (sd:15.1) points, which corresponded with a decrease of 16.8% (p = 0.032). One patient (6%) achieved remission, 2 patients (12%) achieved response, 5 patients (29%) had partial response and 7 patients (41%) did not respond at all. Three patients (18%) quitted because of side-effects.
CONCLUSION: The results of this and similar studies are modest and ask for critical thinking and critical prescribing of mao-inhibitors, because of the possibly limited effectiveness in treatment-resistant depressions.

[Lithium augmentation to monoamine oxidase-inhibitors in treatment-resistant depressive disorders: case report and overview of literature]. / Lithiumadditie bij monoamine-oxidaseremmers bij therapieresistente depressie: casusbeschrijvingen en literatuuroverzicht.

Three patients suffering from a treatment-resistant depression were being treated with a monoamine oxidase (mao-)inhibitor and received lithium augmentation to achieve better recovery. One patient showed significant improvement of depressive symptoms within 24 hours, one patient showed very little respons and one patient did not respond at all. Literature research led to other casereports, where adding lithium to mao-inhibitors had also been effective. The growing amount of arguments of a positive effect of lithium augmentation to mao-inhibitors asks for more research to collect more evidence and a better understanding of this new, potentially effective treatment.

Meta-analysis of the BDNF Val66Met polymorphism in major depressive disorder: effects of gender and ethnicity.

Brain-derived neurotrophic factor (BDNF) is a nerve growth factor that has antidepressant-like effects in animals and may be implicated in the etiology of mood-related phenotypes. However, genetic association studies of the BDNF Val66Met polymorphism (single nucleotide polymorphism rs6265) in major depressive disorder (MDD) have produced inconsistent results. We conducted a meta-analysis of studies comparing the frequency of the BDNF Val66Met-coding variant in depressed cases (MDD) and nondepressed controls. A total of 14 studies involving 2812 cases with DSM-III or -IV defined MDD and 10 843 nondepressed controls met the inclusion criteria. Analyses were stratified either by gender or ethnicity (Asian and Caucasian) because MDD is more prevalent in women and in Caucasians and because BDNF allele frequencies differ by ethnicity. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were provided for allelic analyses (Met versus Val), as well as for genotypic analyses (Met/Met and Val/Met versus Val/Val). In the total sample, the BDNF Val66Met polymorphism was not significantly associated with depression. However, the gender stratified analyses revealed significant effects in both the allelic and genotypic analyses in men (OR(MET), 95% CI; 1.27 (1.10-1.47); OR(MET/MET), 95% CI; 1.67 (1.19-2.36)). Stratification according to ethnicity did not show significant effects of the Val66Met polymorphism on MDD. Our results suggest that the BDNF Val66Met polymorphism is of greater importance in the development of MDD in men than in women. Future research into gender issues will be of interest.

Familiality of major depressive disorder and gender differences in comorbidity.

OBJECTIVE: Gender differences exist in the prevalence and psychiatric comorbidity of major depressive disorder (MDD). This study investigates whether familiality of MDD contributes to observed gender differences in comorbidity. METHOD: Familial (f-MDD) and non-familial (nf-MDD) MDD cases from a population sample were assessed for comorbid dysthymia, anxiety disorders and alcohol-related disorders using the Composite International Diagnostic Interview (CIDI). Logistic regression analyses were performed to examine the effect of f-MDD on gender differences in comorbidity, adjusted for confounders. RESULTS: Women with f-MDD reported significantly more comorbid dysthymia and generalized anxiety disorder (GAD) than their male counterparts; women with nf-MDD reported significantly more comorbid simple phobias and agoraphobia than their male counterparts. Gender differences in comorbid panic disorder and alcohol-related disorders occurred independently of the familial load. Adjustment for age of onset, severity and recurrence of MDD did not change these results. CONCLUSION: Models to explain comorbidity patterns of MDD differ by gender. Familiality of MDD should be taken into account.

Outcome of bone grafting in relation to cleft width in unilateral cleft lip and palate patients.

OBJECTIVE: The purpose of this study was to determine the relationship between cleft width and the residual amount of bone after bone grafting in 53 unilateral cleft lip and palate patients. STUDY DESIGN: The fate of the bone graft was determined by the residual amount of bone calculated from computed tomography scans taken immediately after surgery and 1 year postoperatively. Initial cleft width was measured on the computed tomography scans taken immediately after bone grafting. RESULTS: An average cleft width of 6.4 mm (range 3.0-12.2 mm) was found. The average amount of residual bone in the cleft area after 1 year was 64% of the initial bone graft. Linear regression analysis showed that a significant correlation (r = -0.29, P =.04) was found for cleft width in relation to the percentage of residual bone after 1 year. CONCLUSION: The regression analysis indicates that a relation between cleft width and the fate of the bone graft exists. Bone grafts in wider clefts are more prone to resorption than those in more narrow ones.

Bone volume after secondary bone grafting in unilateral and bilateral clefts determined by computed tomography scans.

OBJECTIVE: The purpose of this study was to evaluate the outcome of bone grafts in cleft palate patients, thus assessing the amount of bone necessary to facilitate eruption-especially in the buccopalatal direction-of the permanent canine into the bone graft. STUDY DESIGN: Computed tomography scans taken immediately postoperatively and 1 year postoperatively of 42 unilateral and of 8 bilateral cleft lip and palate patients who underwent surgery at the age of 9 years (early secondary bone graft) or 12 years (late secondary bone graft) were compared. Three slices from the computed tomography scans taken immediately after the surgery were selected from the center of the bone graft and were then compared with corresponding slices from the 1-year postoperative computed tomography scans. Statistical analysis was performed by using the Wilcoxon 2-sample rank sum test. RESULTS: In the unilateral cleft group, 70% of the transplanted bone remained in the cleft area after 1 year, whereas in the bilateral cleft group, only 45% of the initial bone graft remained after 1 year. CONCLUSION: No statistically significant difference was found between early secondary bone grafting and late secondary bone grafting. In most cases, a sufficient amount of bone was present in the target area to facilitate eruption of the permanent canine.

Random errors in localization of landmarks in postero-anterior cephalograms.

The aim of the present study was to evaluate the random error in localization of the most common landmarks in postero-anterior cephalograms (PAC). The study took place at the Department of Orthodontics of Aarhus University during the period 1993-1995. The material consisted of 30 standardized PAC taken in natural head position. Five examiners had to identify 34 landmarks on each cephalogram. Subsequently, all examiners had to identify again the same 34 landmarks on one randomly selected cephalogram five times with a time interval of at least 24 hours. All landmarks were digitized, related to an X-Y co-ordinate system, and an arithmetical mean was calculated. The accuracy of digitizing was evaluated by digitizing one randomly selected cephalogram 10 times. The main findings of this study are: (1) The digitizing error is negligible compared to the errors introduced by landmark identification. (2) Each landmark has its own characteristic pattern of variance, which is very similar on both sides. (3) Significant differences in accuracy exist between the various postero-anterior landmarks. The six most accurate landmarks are mastoid left (l) and right (r), latero-orbitale (l) and (r), and antegonion (l) and (r). The six least accurate landmarks are coronoid (l) and (r), condylar (l) and (r), and mandibular foramen (l) and (r). (4) A significant difference in the accuracy of landmark identification between the five examiners was only seen for seven of the 34 landmarks. (5) No evidence was found that one examiner was consistently better/worse than the others. (6) No improvement in the accuracy was found after repeated identification, thus there seems to be no short-term 'learning process'. Refereed Paper

A nationwide study of the epidemiology, treatment and survival of oropharyngeal carcinoma in The Netherlands.

Seven head and neck oncology cooperative groups in the Netherlands have reviewed the epidemiology, staging, treatment and survival of oropharyngeal carcinoma patients treated between 1986 and 1990. In all, 640 patients with squamous cell carcinoma (628, 98%) or undifferentiated carcinoma (12, 2%) referred for primary treatment were analyzed. The total group included 441 males (69%) and 199 females (31%), with a median age of 59 years (range, 30-92). Tumor distribution by subsite was the tonsillar region (372 patients, 58%), base of the tongue/vallecula (179, 28%), soft palate/uvula (62, 10%) and posterior oropharyngeal wall (27, 4%). Forty-four patients (7%) had stage I disease, 106 (17%) had stage II disease, 157 (24%) stage III, and 319 (50%) stage IV. Staging was unknown in 14 patients (2%). Radiotherapy was given to the primary tumor in 408 patients (64%), surgery and radiotherapy to 147 (23%), surgery alone to 42 (7%), other treatments to 14 (2%) and no treatment to 29 patients (4%). The 5-year overall survival was 28% and the 5-year disease-specific survival was 41%. This latter survival was 35% in males and 51% in females (P = 0.003). Five-year survival by subsite was 54% in the soft palate/uvula, 42% in the tonsillar region, 33% in the base of the tongue and 32% in the posterior oropharyngeal wall (P = 0.003). When analyzing survival by stage, 5-year survival in patients with stage I disease was 68% and decreased significantly to 27% in stage IV disease (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Computed tomography in evaluation of early secondary bone grafting.

Computed tomography (CT) was used to determine the fate of the bone graft in cleft lip and palate patients. Eight right-sided unilateral cleft lip and palate patients from the Free University Hospital in Amsterdam, treated with early, secondary bone grafting, were evaluated immediately after the operation and 1 year postoperatively. Approximately 70% of the volume of transplanted iliac crest bone was still present in the cleft area after 1 year.

[Uni- and multivariate analysis of prognostic factors in T3 laryngeal cancers]. / Uni- und Multivarianzanalyse prognostischer Faktoren bei T3-Kehlkopfkarzinomen.

In 511 patients with T3N0-3M0 laryngeal carcinoma, 24 possible prognostic factors were analysed retrospectively. The factors were age, sex, mode of treatment, duration of several clinical symptoms, the presence of sore throat, otalgia, dyspnoea, and dysphagia, previous tracheotomy, tumour extension, lymph node status (five items), histologic grading, smoking habits, and alcohol intake. For 300 patients in whom surgery was part of the primary treatment, pathologic staging of the primary tumour and of lymph nodes in neck dissection specimens, cartilage invasion, radicality of the operation, differentiation grade, and subglottic extension were also evaluated. Univariate analysis revealed prognostic significance on survival for tumour extension (limited to the glottic region), lymph node status (clinically palpable lymph nodes, cytologically confirmed positive lymph nodes), level of lymph node metastasis (high and midjugular site), histologic grading (poor differentiation grade), and treatment modality (planned combined therapy). In the group that underwent surgery, all factors derived from specimens of the larynx and neck dissections had prognostic significance. Multivariate analysis revealed that the glottic site of the tumour, the presence of cyto- and histopathologically proven metastatic lymph nodes, pretreatment tracheotomy, positive resection margins, and planned combined treatment had a significant influence on corrected actuarial survival.

Prognostic factors for survival in patients with T3 laryngeal carcinoma.

In a total of 511 patients with T3,N0-3,M0 laryngeal carcinoma, 24 possible prognostic factors were analyzed retrospectively. The factors were age, sex, mode of treatment, duration of several clinical symptoms, the presence of sore throat, otalgia, dyspnea, and dysphagia, previous tracheotomy, tumor extension, lymph node status (five items), histologic grading, smoking habits, and alcohol intake. For 300 patients in whom surgery was part of the primary treatment, pathologic staging of the primary tumor and of lymph nodes in neck dissection specimens, cartilage invasion, radicality of the operation, differentiation grade, and subglottic extension ware also evaluated. In a univariate analysis for the whole group, tumor extension (limited to the glottic region), lymph node status (clinically palpable lymph nodes, cytologically confirmed positive lymph nodes), level of lymph node metastasis (high and midjugular site), histologic grading (poor differentiation grade), and treatment modality (planned combined therapy) were considered to be prognostic factors of corrected actuarial survival. In the group that underwent surgery, all factors derived from specimens of the larynx and neck dissections had prognostic significance. Multivariate analysis revealed that the glottic site of the tumor, the presence of cyto- and histopathologically proven metastatic lymph nodes, pretreatment tracheotomy, positive resection margins, and planned combined treatment had a significant influence on corrected actuarial survival.

A helpful device in cricopharyngeal surgery.

Extramucosal myotomy of the pharyngoesophageal sphincter muscle, ie, the cricopharyngeal muscle, is a widely used therapy for dysphagia due to neurologic diseases. The cricopharyngeal muscle is dissected free via a lateral cervical incision. To cut the muscle fibers it is necessary to expose and to stretch them. A device is developed to make this possible. A light source is brought within a cuffed tube. The tube is inserted in the esophagus with the cuff in the cricopharyngeal sphincter. Inflating the cuff with air causes stretching of the muscle fibers, whereas the light source inside makes all muscle fibers visible. They can be cut carefully, leaving the mucosa intact.