Measuring the potency labelling of onabotulinumtoxinA (Botox<Superscript>®</Superscript>) and incobotulinumtoxinA (Xeomin<Superscript>®</Superscript>) in an LD50 assay

The biological potency of botulinum toxin (BT) drugs is determined by a standardised LD50 assay. However, the potency labelling varies vary amongst different BT drugs. One reason for this may be differences in the LD50 assays applied. When five unexpired batches of onabotulinumtoxinA (Botox^®) and incobotulinumtoxinA (Xeomin^®) are compared in the Xeomin^® batch release assay, the potency variability of both BT drugs fell within the range allowed by the European Pharmacopoiea. Statistical analyses failed to detect differences in the potency labelling of both products. Although the existence of a conversion ratio has been questioned recently, our experimental data are in line with previous clinical experience showing that Botox^® and Xeomin^® can be compared using a 1:1 conversion ratio. Identical potency labelling allows easy exchange of both BT drugs in a therapeutic setting, and direct comparison of efficacy, adverse effects and costs.     

Sapphire<Superscript>®</Superscript> platinum detachable coil experience in a tertiary-care facility

Background

The Guglielmi Detachable Coil introduced by the Boston Scientific Corporation has been widely used for endovascular coiling of aneurysm. Recently, Sapphire® platinum detachable coils (eV3, Irvine, CA) have been introduced for aneurysm coiling. Herein, we report our clinical experience with the Sapphire® coil to evaluate the incidence of coil related complications and the rate of aneurysm occlusion.

Methods

Consecutive patients who underwent embolization with Sapphire® detachable coils were prospectively enrolled from January 2004 to September 2004 and the data were retrospectively analyzed. Patient demographics, including age, gender, presenting symptoms, Hunt and Hess grade, Fisher grade and locations of the vascular anomalies were collected. Additionally, complications associated with the coils and rates of aneurysm occlusion were observed and the data compiled.

Results

29 patients underwent Sapphire® coil embolization for intracranial aneurysms. Mean age was 50 ± 18 (mean ± SD) years with 81% being females. Aneurysm neck reconstruction was required in 7 cases, 6 with Neuroform stent (5 unruptured aneurysms) and 1 with balloon assistance (ruptured aneurysm). In 7 cases, Sapphire® coils were used along with other coils. There were no events of thromboembolism or ruptures of aneurysms during coil embolization. However, multi-diameter coils demonstrated stretching in 4 stent-assisted cases without any adverse consequences. Complete occlusion of the aneurysm was achieved in 79.31% of the patients, neck remnant in 6.89, and partial coiling was achieved in 13.79%.

Conclusion

The Sapphire® coil could safely be used in the treatment of both ruptured and unruptured aneurysms. However, multi-diameter non-stretch resistant coils may be associated with coil stretching when used in conjunction with a stent. Further study is still required for definitive results.

     

Understanding ethnic differences in mental health service use for adolescents’ internalizing problems: the role of emotional problem identification

Although immigrant adolescents are at least at equal risk of developing internalizing problems as their non-immigrant peers, immigrant adolescents are less likely to use mental health care. The present study is the first to examine ethnic differences in problem identification to find explanations for this disparity in mental health service use. Specifically, the extent to which emotional problem identification mediates the relationship between immigrant status and mental health service use for internalizing problems in three immigrant populations in the Netherlands (i.e., Surinamese, Turkish, and Moroccan) was investigated. A two-phase design was used to include adolescents at risk for internalizing problems. Data were used from the second phase, in which 349 parents and adolescents participated (95 native Dutch, 85 Surinamese, 87 Turkish, and 82 Moroccan). Results indicated that mental health service use for internalizing problems is far lower among immigrant adolescents than among native Dutch adolescents, although differences between immigrant groups were also substantive. A lack of emotional problem identification was identified as an essential mediator in the relationship between immigrant status and mental health service use. Since the results suggest the low levels of problem identification in our immigrant samples may serve an explanatory role in the relationship between immigrant status and mental health service use, future research should aim at understanding these ethnic differences in problem identification.     

Efficacy of St. John’s wort extract WS<Superscript>®</Superscript> 5570 in acute treatment of mild depression

Based on the original data from two double-blind, randomized, placebo-controlled clinical trials and the acute phase of a long-term study that investigated the antidepressant efficacy of St. John’s wort extract WS^® 5570, we present a re-analysis of a subset of patients suffering from an acute episode of mild depression according to DSM criteria. Out of a total of more than 1,200 patients included into these trials 217 had a pre-treatment total score ≤20 points on the 17-item Hamilton Rating Scale for Depression (HAMD) and were eligible for our re-analysis. They received 600, 900, or 1,200 mg/day WS^® 5570 or placebo for 6 weeks. In patients treated with WS^® 5570 the HAMD total score decreased by averages of 10.8 (600 mg/day), 9.6 (900 mg/day), and 10.7 (1,200 mg/day) points between the pre-treatment baseline value and the end of acute treatment, compared to 6.8 points in the placebo group (p < 0.01 for all pairwise comparisons of WS^® 5570 against placebo). This corresponded to average relative decreases by 49–57% for WS^® 5570 and by 36% for placebo. The rates of responders (i.e., patients with a HAMD total score decrease ≥50%) were 73%, 64%, 71%, and 37% for WS^® 5570 600 mg/day, 900 mg/day and 1,200 mg/day, and placebo, respectively. At the end of acute treatment 57% of the patients treated with WS^® 5570 600 mg/day, 33% in the 900 mg/day group and 62% in the 1,200 mg/day group, as well as 25% in the placebo group were in remission (HAMD total score ≤7 points). The analysis shows that St. John’s wort extract WS^® 5570 has a meaningful beneficial effect during acute treatment of patients suffering from mild depression and leads to a substantial increase in the probability of remission.     

Growing up in the shadow of Chornobyl: adolescents’ risk perceptions and mental health

Purpose  

Despite long-term research on risk perceptions of adults after ecological disasters, little is known about the legacy for the generation exposed to toxic elements as infants. This study examined Chornobyl-related risk perceptions and their relationship to mental health in adolescents raised in Kyiv in the aftermath of the accident.     

The use of onabotulinum toxin A (Botox<Superscript>®</Superscript>) in the treatment of chronic migraine at the Parma Headache Centre: a prospective observational study

Chronic migraine is a debilitating headache, whose treatment is often complicated by the concomitant overuse of symptomatic medication and by the poor efficacy of standard prophylactic treatments. The PREEMPT studies have demonstrated the efficacy and tolerability of onabotulinum toxin A (Botox^®) in the treatment of this headache type. Data about its use in clinical practice are still scarce. Our study evaluated all subjects with chronic migraine who were treated with onabotulinum toxin A between February 2014 and November 2015 at the Parma Headache Centre. Botox was injected according to the PREEMPT paradigm every 3 months. The data about variations in the number of headache days and in symptomatic medication intake before and after the Botox injections were collected from the patients’ headache diaries. The study also evaluated tolerability to treatment, disability, and depressive symptoms. Of the 52 treated subjects, 14 received Botox treatment for at least 9 months and showed a significant decrease in the median number of headache days (from 19 to 14.5, p = 0.011) and in the median number of days of symptomatic medications intake and symptomatic drugs. Overall, the treatment was well tolerated. The average MIDAS and BDI-II scores after 9 months were reduced, though not significantly. The treatment with Botox proved effective and well tolerated in our clinical practice. Further studies on larger patient samples will help shed light on the persistence of the drug’s effect at long term and identify the predictive factors of response to treatment.     

Efficacy and safety of nabiximols (Sativex<Superscript>®</Superscript>) on multiple sclerosis spasticity in a real-life Italian monocentric study

Multiple sclerosis (MS) patients frequently suffer from limb spasticity and pain despite antispastic treatments. To investigate nabiximols efficacy and safety in a real-world monocentric Italian cohort, the following data were collected at baseline, week 4, 14 and 48: Ambulation Index (AI), 10-min walking test (10MWT), combined Modified Ashworth scale (cMAS), scores at numerical rating scale for spasticity (sNRS) and pain (pNRS). Responder status was defined as a ≥20 % reduction in sNRS after 4 weeks of treatment. 144 MS patients (123 progressive and 21 relapsing-remitting) complaining of moderate-to-severe spasticity (mean sNRS: 7.5) were included: 138 (95.8 %) completed the first month of therapy and were classified as follows—23.2 % were non-responders, 5.1 % were responders but discontinued treatment due to side effects, 71.7 % were responders with a mean 32 % reduction in sNRS (p < 0.001). In responders sNRS further decreased between 4 and 14 weeks (p = 0.03). Similarly, pNRS improvement was seen during the first month and between 4 and 14 weeks (p < 0.001 and p = 0.004, respectively). Moreover, at 4 weeks responders showed a significant (p < 0.05) improvement in cMAS, AI and 10MWT, which was maintained at 14 weeks. At 1-year follow-up, a benefit was still evident on spasticity and painful symptoms with a low drop-out rate. Confusion/ideomotor slowing, fatigue and dizziness were the most frequent side effects; no major adverse events were reported. Shorter disease duration at treatment start was associated with better response. This real-world study confirms nabiximols efficacy and safety in the treatment of MS-related spasticity and pain, which is maintained up to 48 weeks.     

New perspectives on neurochemical effects of amantadine in the brain of parkinsonian patients: a PET – [<Superscript>11</Superscript>C]raclopride study

Summary. Amantadine, is a non competitive NMDA receptors antagonist that has been proved beneficial in Parkinson's disease. However its mechanism of action at therapeutic doses is still under discussion. Aim of this study was to evaluate the effect of repeated administration of amantadine on striatal dopaminergic system by measuring [¹¹C]raclopride binding to striatal D₂ dopamine receptors, in patients with moderate idiopathic Parkinson's disease. Eight patients completed the study undergoing a PET scan, before and after 10–14 days treatment with Amantadine (200 mg/day). Patients were on treatment with L-DOPA, which was suspended 1 night before each PET scans, and free from dopaminergic agonists, anticholinergic and antidepressants. Amantadine treatment significantly increased [¹¹C-]Raclopride binding (caudate: 10% p = 0.04; putamen 11% p = 0.01). A slight reduction (−7.3%, p = 0.062) of UPDRS total scores was also observed. The increased availability of striatal D₂ receptors, is likely to be caused by drug induced modification of receptors expression. This hypothesis is consistent with previous experiments, indicating an increase in striatal D₂ receptors in rats treated with amantadine or other non competitive NMDA antagonists and suggests that the neo-synthesis of D₂ receptors may represent a reinforcing mechanism of drug efficacy. Received October 17, 2001; accepted January 3, 2002 Published online June 28, 2002     

Reduced hippocampal neurogenesis in the GR<Superscript>+/−</Superscript> genetic mouse model of depression

Glucocorticoid receptor (GR) heterozygous mice (GR^+/− ) represent a valuable animal model for major depression. GR^+/− mice show a depression-related phenotype characterized by increased learned helplessness on the behavioral level and neuroendocrine alterations with hypothalamo-pituitary-adrenal (HPA) axis overdrive characteristic of depression. Hippocampal brain-derived neurotrophic factor (BDNF) levels have also been shown to be reduced in GR^+/− animals. Because adult hippocampal neurogenesis has been implicated in the pathophysiology of affective disorders, we studied here the effects of the GR^+/− genotype on neurogenesis in vivo. In a 2 × 2 design, GR^+/− mice and GR^+/+ littermate controls were either subjected to 1 h of restraint stress or left undisturbed in their home cages after intraperitoneal injection of BrdU. Stress exposure and BrdU injections were performed once daily for 7 days and neurogenesis analyzed 4 weeks later. BrdU cell counts were significantly reduced as an effect of GR^+/− genotype and as an effect of stress. Majority of the BrdU+ cells showed co-labeling with mature neuronal marker NeuN or astrocytic marker S100β with no further significant effect of either experimental condition or of genotype. In sum, this results in reduced neurogenesis in GR^+/− mice which is further repressed by restraint stress. Our results, thus, reinforce the link between reduced neurogenesis, stress, neurotrophins, and behavioral symptoms of and susceptibility to depression.     

Has the practice and outcome of ECT in adolescents changed? findings from a whole-population study

OBJECTIVE: To investigate whether there were changes in the practice and outcome of electroconvulsive therapy (ECT) in adolescents in a whole population over a decade. METHOD: All persons younger than 19 years who received ECT in the state of New South Wales, Australia, in the period from 1990 to 1999 were identified. Detailed information about diagnosis, treatment and outcome were then obtained. RESULTS: Seventy-two patients aged 14-18 years underwent a total of 84 courses of ECT (1.53/100,000 adolescents were treated with ECT per year). In 1996 to 1999 compared with 1990 to 1995, there was an increase in ECT among females hospitalized involuntarily, EEG monitoring, stimulus dosing, bilateral ECT, and use of thiopentone. Overall, mood disorders derived most benefit from ECT while comorbid personality disorder predicted poorer short term outcome. Side effects were minor and transient. CONCLUSIONS: The changes in ECT practice are consistent with changes in ECT practice generally over the survey period. The overall data on effectiveness and safety further support the treatment's use in young people.     

Distribution of Peripherally Injected Peptide YY ([<Superscript>125</Superscript>I] PYY (3–36)) and Pancreatic Polypeptide ([<Superscript>125</Superscript>I] hPP) in the CNS: Enrichment in the Area Postrema

The mechanism by which blood-borne peptide YY (3-36) (PYY(3-36)) and pancreatic polypeptide (PP) inhibit food intake is not clear and could implicate peripheral (vagal afferent pathways) and/or central (direct action on specific brain nuclei) mechanisms. To identify the primary brain structure(s) that could be activated after a peripheral injection of neuropeptide Y-related peptides, we investigated the distribution of radioactive materials using whole body autoradiography and coronal brain sections. Rats were injected with [125I] porcine (p) PYY(3-36) (i.p., 10 microCi) and killed after 30 min, 1, 2, or 4 h. After i.p. administration, significant amounts of radioactive materials were rapidly (<30 min) detected in the blood circulation and various tissues including the kidneys, liver, lung, heart, bone marrow, gastrointestinal tract, and thyroid gland, whereas in the brain, low but significant amounts of radioactive materials were detected at the level of the area postrema. Next, we investigated the distribution of radioactive labeling in the brain after i.v. injections of [125I]pPYY(3-36) (Y2 and Y5 subtypes), [125I] human (h) PP (Y4 and Y5 receptors), and [125I][Leu(31), Pro(34)] pPYY (Y1, Y4 and Y5 classes) in the rat brain. Fifteen minutes post injection, autoradiograms revealed positive signals only in the area postrema after the injection of [125I]-hPP and [125I][Leu(31), Pro(34)]pPYY. Whereas the presence of [125I]pPYY(3-36)-related labeling was detected in the area postrema, subfornical organ, and median eminence. In all other brain structures, including all hypothalamic nuclei and other circumventricular organs, near background level signals were detected. These data suggest that the inhibition of food intake observed after peripheral injections of pPYY(3-36) and hPP could involve receptor activation preferentially located at the level of the area postrema, a structure well-known to be involved in the modulation of food intake.     

Lost in transition? Perceptions of health care among young people with mental health problems in Germany: a qualitative study

Background

The transitioning of young patients from child and adolescent to adult mental health services when indicated often results in the interruption or termination of service. The personal views of young service users on current clinical practice are a valuable contribution that can help to identify service gaps. The purpose of this qualitative study was to explore the perceptions of health care of young people with mental health problems in the transition age range (16–25 years), and to better understand health behaviour, care needs and the reasons for disengaging from care at this point in time.

Methods

Seven group discussions and three interviews were conducted with 29 young people in this age range. Discussions were audio-taped, transcribed verbatim and analysed following the reconstructive approach of R. Bohnsack’s documentary method.

Results

An overarching theme and nine subthemes emerged. Participants displayed a pessimistic and disillusioned general attitude towards professional mental health services. The discussions highlighted an overall concern of a lack of compassion and warmth in care. When they come into contact with the system they often experience a high degree of dependency which contradicts their pursuit of autonomy and self-determination in their current life stage. In the discussions, participants referred to a number of unmet needs regarding care provision and strongly emphasised relationship issues. As a response to their care needs not being met, they described their own health behaviour as predominantly passive, with both an internal and external withdrawal from the system.

Conclusions

Research and clinical practice should focus more on developing needs-oriented and autonomy-supporting care practice. This should include both a shift in staff training towards a focus on communicative skills, and the development of skills training for young patients to strengthen competences in health literacy.

     

Psychosocial risk factors associated with fathers’ mental health in the postnatal period: results from a population-based study

Purpose

Fathers’ psychological distress in the postnatal period can have adverse effects on their children’s wellbeing and development, yet little is known about the factors associated with fathers’ distress. This paper examines a broad range of socio-demographic, individual, infant and contextual factors to identify those associated with fathers’ psychological distress in the first year postpartum.

Methods

Secondary analysis of data from 3,219 fathers participating in the infant cohort of the Longitudinal Study of Australian Children at wave 1 when children were 0–12 months of age.

Results

Approximately 10 % of fathers reported elevated symptoms of psychological distress. Logistic regression analyses revealed that the risk factors were poor job quality, poor relationship quality, maternal psychological distress, having a partner in a more prestigious occupation and low parental self-efficacy.

Conclusion

These findings provide new information to guide the assessment of fathers’ risk for psychological distress in postnatal period. There are also important social policy implications related to workplace entitlements and the provision of services for fathers.     

Influence of mental health literacy on help-seeking behaviour for mental health problems in the Swiss young adult community: a cohort and longitudinal case–control study

Poor knowledge about mental health disorders and their treatment likely contributes to the large treatment gap reported for mental health problems. Therefore, we studied the association between mental health literacy (MHL) and active help-seeking in a community sample. Participants were recruited from an add-on questionnaire study to the ‘Bern Epidemiological At-Risk’ (BEAR) study on 16–40-year-old community subjects of the Swiss canton Bern. At baseline, data of N = 1504, and at 3-year follow-up, data of N = 535 were available. Based on an unlabelled case vignette (on depression or schizophrenia), MHL was assessed by the questionnaire of Angermeyer and colleagues. Cross-sectional and longitudinal baseline predictors of help-seeking were analysed using path analyses. Additionally, sensitivity analyses of the prospective model were computed for sex, vignette, and baseline mental health problems/disorders. Cross-sectionally, help-seeking was associated with non-endorsement of biogenetic causal explanations, presence of mental health problems/disorders, help-seeking before baseline, poorer functioning, and lower health satisfaction. The prospective model was similar; yet, help-seeking at follow-up was associated with endorsements of the causal explanation ‘biogenetics’ and, additionally, ‘childhood trauma’ but not the presence of baseline mental health problems/disorders. Sensitivity analyses revealed a significant impact on sex, vignette, and mental health problems/disorders. For example, actual functional problems were predictive in males, while health satisfaction was predictive in females. Our findings indicate that future studies on drivers of help-seeking should assess very large community samples with case vignettes on different mental disorders to examine appropriate subgroups and their likely interaction to address group-specific factors in awareness campaigns.

     

Impact of shared mental health care in the general population on subjects’ perceptions of mental health care and on mental health status

Objective A community survey evaluated whether the development of a shared mental health care intervention had an impact on health care perceptions and mental health status of subjects with common mental health problems (MHP). Methods Adults <70 years old with common MHP (DSM-IV/CIDI-SF major depressive disorder, generalized anxiety or MHI-SF 36 psychic distress diagnoses), were randomly drawn from the general population in the intervention area (IA, n = 349) and in a control area (CA, n = 360), and evaluated twice at an interval of 18 months (percentage of follow-up: IA = 69.3%, CA = 71.9%, P = .44). CA and IA groups did not differ for the criteria of interest at baseline. Results At 18 months, compared to CA, IA reported significantly different help-seeking attitudes or behaviours (P = .02 for all subjects and .006 for subjects with current MHP) and greater general satisfaction with care (P = .03 for both). Remission rates and daily life functioning did not differ. Conclusions After 4 years of development of a mental health network based on a consultation-liaison model, Shared Mental Health Care was associated with greater satisfaction and access with care among subjects with common MHP. The association was not found with mental health status, but the study lacked power to adequately address the issues.