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In the early stage of schizophrenia (first 5 years), the most important clinical target besides symptom control is relapse prevention as each relapse significantly decreases the possibility of preferable long-term outcomes. Early discontinuation of antipsychotic medication due to intolerable side-effects is one of the most common causes of relapse.
This poster aims to present cariprazine’s tolerability in the early stage of schizophrenia.
Data from 4 randomized, double-blind, placebo-controlled trials (NCT00404573, NCT01104766, NCT01104779, NCT00694707) with similar design (1 week of wash out period, 6 weeks of treatment and 2-4 weeks of follow-up) were pooled. For the post-hoc analysis, patients with early stage of schizophrenia (defined as having a disease duration of less than 5 years) were extracted from the whole safety population, and approved doses of cariprazine (1.5-6.0 mg/day) were combined. Treatment-emergent adverse events (TEAEs) and discontinuation rates were analysed versus placebo.
Overall, 169 placebo- (PBO) and 322 cariprazine-treated (CAR) patients were identified as having schizophrenia for less than 5 years. 67.7% cariprazine- and 56.2% placebo-treated patients reported at least one TEAE; most frequently insomnia (10.9 % CAR; 12.4% PBO), akathisia (9.6% CAR; 2.4% PBO) and extrapyramidal symptoms (9.3% CAR; 1.8% PBO). Discontinuation due to adverse events was reported in only 8.4% of cariprazine- and 14.8% of placebo-treated patients. Relapse occurred in 3.1% of cariprazine- and 5.3% of placebo-treated patients.
Cariprazine was generally well-tolerated in the early stage of schizophrenia; given the limitations of this analysis, additional research is warranted.
Conflict of interest
Studies were funded by Gedeon Richter Plc. and Allergan Plc (prior to its acquisition by AbbVie). Dombi, Acsai, Dr. Barabássy, Dr. Sebe, Dr. Laszlovszky, Dr Vass, Dr. Szatmári and Dr. Németh are employees of Gedeon Richter Plc., Dr. Earley and Dr. Patel a
Motivation deficit is a significant aspect of lack of improvement in patients with schizophrenia especially with predominant negative symptoms (PNS). Therefore, improvement depends not only on symptoms reduction and better social functioning but also on patient engagement which is a key but less investigated aspect of successful treatment.
To investigate and compare patient engagement in PNS patients after cariprazine and risperidone treatment characterized by the 11 items of the Positive and Negative Syndrome Scale (PANSS-11).
In this phase 3 study patients suffering from PNS of schizophrenia (PANSS-FSNS≥24) were randomized to 26 weeks of treatment with either cariprazine or risperidone (target dose 4.5 and 4 mg/day, respectively). To compare the effects of the two drugs on patient engagement the PANSS-11 scale was used. Change from baseline (CfB) on the selected items and PANSS-11 total score were analyzed using mixed model of repeated measures approach without correction for multiplicity.
PANSS-11 total score mean CfB were -11.20 (SD=0.43) for cariprazine-, and -9.44 (SD=0.45) for risperidone-treated patients with a -1.79 (95% CI=-3.01, -0.56) mean difference (p=0.004) in favor of cariprazine. Most item differences were statistically significant (N1, N2, N3, N4, N5, G16) or numerically higher (N6, G7, G13) for cariprazine versus risperidone.
Cariprazine significantly improved patient engagement in patients with PNS of schizophrenia compared to risperidone based on the PANSS-11 post-hoc analysis. These results suggest that cariprazine treatment may improve not only the symptoms and everyday functioning of PNS patients but their engagement with life.
Conflict of interest
Studies were funded by Gedeon Richter Plc. and Allergan Plc (prior to its acquisition by AbbVie). Dr. Laszlovszky, Dombi, Balogh, Dr Barabassy, Dr Vass, Dr. Szatmári and Dr. Németh are employees of Gedeon Richter Plc.
Although monotherapy is preferable, in every day clinical practice polypharmacy is often unavoidable due to the need of treatment enhancement or cross-titration phases with shorter or longer overlaps of two or more drugs. However, administration of more than one drug treatment is often associated with more side effects.
The aim of the present post-hoc analysis was to examine treatment emergent adverse events (TEAEs) during co-administration of cariprazine with other antipsychotics.
Treatment emergent adverse event data (TEAE) from a randomized, double-blind, parallel-group, active-controlled study (EudraCT Number: 2012-005485-36) in adult patients with schizophrenia having predominant negative symptoms was examined in the first two weeks of the double-blind treatment period, where gradual cross-titration occurred between cariprazine (3-6 mg/day) and other antipsychotics (including amisulpride, aripiprazole, fluphenazine, haloperidol, olanzapine, paliperidone, quetiapine, and sertindole). Thereafter, 24 weeks of cariprazine monotherapy followed.
During the cross-titration period, 17.83% of patients experienced at least one TEAE. The TEAEs were in line with the well-established safety data: nausea (2.61%), insomnia (2.17%), headache (2.17%), akathisia (1.74%) and restlessness (1.3%) were the most common. Most events were mild in severity (66.1% mild, 32.2% moderate, 1.7% severe (insomnia)).
While not definitive, and limited by small sample size, the co-administration of cariprazine with other antipsychotics did not show an unexpected safety profile or overlapping toxicities. This is an important finding, if intermittent or longer co-administration of other antipsychotics are unavoidable with cariprazine treatment.
Conflict of interest
Studies were funded by Gedeon Richter Plc. and Allergan Plc (prior to its acquisition by AbbVie). Dr Vass, Dr Barabássy, Dr Laszlovszky, Dr Sebe, Dombi, Dr Szatmári and Dr Németh are employees of Gedeon Richter Plc.
Pediatric mania is difficult to distinguish from childhood hyperactivity. Both share 3 common symptoms: distractibility, motoric hyperactivity, and talkativeness. Oftentimes, children are referred from their pediatrician due to a lack of appropriate response to stimulant medication. Pediatricians have learned that merely raising the dose or changing the stimulant does not work. A thorough neuropsychological evaluation often reveals bipolar mania. They may have comorbid bipolar disorder and ADHD. This poster paper will examine measures that can assist in this important differential diagnosis as well as offer treatment options, including medication management.
This case study includes three pediatric patients diagnosed with childhood bipolar disorder and ADHD. A comprehensive psychoeducational assessment was conducted for each of the patients, which resulted in this comorbid diagnosis.
One of the most helpful measures was the TOVA (i.e., Test of Variables of Attention). When a child’s attention and impulsivity scores are normal, and response time and variability scores are abnormal, both on and off medication, that is an indication of a mood disorder, These children also performed poorly on measures of processing speed, and verbal learning and interference tasks. Measures of affect and personality were important diagnostically. A combination of amantadine and either clonidine HCL ER or propranolol, as prescribed by a medical psychologist, were found to be effective in controlling the symptoms of this comorbid diagnosis.
An evaluation of children’s intellectual, attentional, behavioral, mood, and personality functioning is crucial for a differential diagnosis. In cases of comorbidity, ADHD and childhood bipolar disorder, the sooner the child is on appropriate medications, the better. When just the surface diagnosis of ADHD is medicated, the outcome is often problematic. There may be a poor response to treatment and a higher rate of suicide.
Impaired facial emotion recognition, especially fear were widely described in adolescents with conduct disorder, and some literature data indicate similar changes in adolescents with ADHD. However, to our best knowledge the relationship between emotion recognition, conduct symptoms and hyperactivity measures in a mixed clinical population were not investigated.
A mixed clinical population of 56 adolescents (19 girls) between age 11-16 (13.4 on average) admitted to the acute department of Vadaskert Child Psychiatry Hospital was taken part in our study. The parental and self-report version of the Strength and Difficulties Questionnaire (SDQ), facial emotion recognition test including six basic emotions (FEEST) and Raven IQ measures were performed.
In the overall population, in 21 cases externalization symptoms, while in 35 cases internalizing symptoms dominated the condition. Fear recognition irrespective to age and IQ were significantly worse in externalizing teens compared to internalizing ones (p< 0.05), while the recognition of other investigated emotions (anger, disgust, happiness, sadness, surprise) did not show significant differences. In the overall population, only fear recognition was significantly related to self reported conduct (R=-0.35, p< 0.01) and hyperactivity problems (R=-0.27, p< 0.05), while overall emotion recognition was related to both self reported hyperactivity (R=-0.33, p< 0.02) and parent reported hyperactivity problems (R=-0.29, p< 0.03).
Our results indicate that hyperactivity symptoms measured by SDQ were specifically related to impairments in fear recognition, and this effect is irrespective from attention problems as no relationship between symptom severity and other emotions were observed.
Cariprazine is a potent D3/D2 partial agonist with preferential binding to D3 receptors.
To evaluate the efficacy and safety of cariprazine versus placebo in acute exacerbation of schizophrenia.
A multinational, multicenter, double-blind, randomized, placebo- and active-controlled, fixed-dose trial in patients aged 18–60 years with DSM-IV-TR-defined schizophrenia, current psychotic episode < 2 weeks, and PANSS total score between 80 and 120. After 1-week washout, patients received 6-weeks treatment (cariprazine 1.5, 3.0, or 4.5 mg/d, risperidone 4.0 mg/d, or placebo) and 2-week safety follow-up. Risperidone was used to assess assay sensitivity. Primary and secondary efficacy: baseline to Week 6 change (LOCF) in PANSS total and CGI-S scores, respectively. Safety: adverse events (AEs), vital signs, laboratory measures, extrapyramidal symptom (EPS) scales.
Of 732 randomized patients, 64% completed the study. Mean baseline PANSS (98) and CGI-S scores (4.8) were similar across groups. PANSS total score improvement at Week 6 was statistically significant versus placebo for cariprazine 1.5 mg/d, 3.0 mg/d, and 4.5 mg/d (placebo-adjusted improvements: −7.5, −8.9, −10.4, respectively; P < .001; LOCF) and risperidone (−15.0, P < .001, LOCF); significant improvement on CGI-S was demonstrated for all active treatments (P < .05). The most common cariprazine AEs were insomnia, EPS, akathisia, sedation, nausea, dizziness, and constipation. AE discontinuation rates were 15% for placebo, 10%, 5% and 8% for cariprazine 1.5, 3.0, and 4.5 mg/d, respectively, and 9% for risperidone 4.0 mg/d.
Cariprazine significantly improved PANSS and CGI-S scores versus placebo in acute exacerbation of schizophrenia and was generally well tolerated.
RGH-188 is an orally active, potent dopamine D3/D2 receptor antagonist/partial agonist atypical antipsychotic for the treatment of schizophrenia and bipolar mania.
RGH-188 displayed high affinity to human D3 receptors (Ki: 0.085 nM) and approximately six- and thirty-times less affinity to human D2, and 5-HT1A receptors. In various in vitro and in vivo assays RGH-188 behaved either as an antagonist or as a partial agonist on dopamine D3 and D2 receptors.
RGH-188 displayed potent antipsychotic activity (0.1-0.8 mg/kg) in rodent models such as apomorphine-induced climbing, amphetamine- and phencyclidine-induced hypermotility, conditioned avoidance response. It significantly improved the learning performance of rats (0.02-0.2 mg/kg) impaired by scopolamine in a water-labyrinth learning paradigm. RGH-188 showed no EPS liability as it produced no catalepsy up to 100-fold therapeutic range.
In a nonhuman primate positron emission tomography (PET) study using 11C-raclopride RGH-188 occupied striatal D2/D3 receptors in a dose dependent and saturable manner with an ED50 of 7 μg/kg iv. In healthy male subjects multiple administration of 1 mg RGH-188 resulted in over 70% D2/D3 receptor occupancy and the displacement showed correlation with RGH-188 and metabolites plasma levels.
After single administration to healthy volunteers, Tmax for RGH-188 was 3-4 hours and the terminal disposition half-life was 5-6 days. Over the dose range of 0.5-2.5 mg AUC of the parent drug was approximately dose-proportional. Systemic exposure to the pharmacologically active metabolites, desmethyl- and didesmethyl-RGH-188 was 20-30% and 50-200% of that to the parent, respectively.
The Baby-Mother-(Father) program started in 2007, after a preparatory phase in a collaboration with the Zentrum Für Soziale Psychiatrie - Mutter & Kind Behandlung, Heppenheim, Germany. In Hungary, this is the first dedicated program for a babymother unit, were initiated by National Institute of Child Health (OGYEI), and Saint John Hospital Psychiatric and Psychiatric Rehabilitation Department in Budapest.
Baby-mother unit introduction into the local and the Hungarian health service.
The aim of the program is to apply a collaborative therapeutic and rehabilitation model utilizing the multidisciplinary team work in the treatment of the pre-, peri- and post-natal period of mothers suffering mental disorders as well as to facilitate the early interactions and attachment with the baby.
Since 2007, 82 mothers, 1 father entered into the program. 54 mothers were participated as inpatient, 29 were treated only as outpatient. 24.9% of the cases were diagnosed (ICD 10 – F20–F29) schizophrenia or spectrum disorders, 27,6% were in the major affective disorders, including bipolar, (F 31, 14.5%). 38,6% were diagnosed in the anxiety disorders spectrum. 23% entered in the prenatal period (pregnancy), while 76,3% entered post-natal.
Therapeutic methods used
Case-management, individual, group and family interventions (psychotherapy), pharmacotherapy, case conferences, individual and staff supervision, video-feedback, mother-child consultation.
New treatment model introduction in Hungary, which may reduce the risk of the separation of the baby, enhances the mother recovery, as well as the utilization of the family's and the supportive network resources. Further research is needed to prove the higher efficacy.
Mapping cognitive functions in schizophrenia is important for approaching the etiological background of the disease.
To examine the explicit and the implicit learning processes with experimental psychological methods in neurocognitive subgroups identified by us earlier (Szendi et al, 2010).
To find substantial cognitive differences between the neurocognitive subgroups
Patients with schizophrenia (n=19) and matched healthy control persons (n=11) participated in the study. The patients were recruited randomly from the patient pool which constitued the subject base for the original clustering process, we enrolled n=9 patients from the cluster S, and n=10 from the cluster Z. Besides the comprehensive neuropsychiatric assessment, the explicit learning performances were tested by a verbal learning task, while the implicit learning by the Alternating Serial Reaction Time Task.
While the whole group of patients did not differ from the healthy persons regarding either the explicit or the implicit memory tasks, the performances of the two subgroups of patients showed a double dissociation in these tasks. Whereas patients belonging to cluster S could recall significantly less words in the explicit cued recall test after the word-list learning than patients in cluster Z (and the healthy persons), the performance of patients in cluster Z in the implicit sequence-specific learning fell behind the cluster S (and the healthy group).
The double dissociation of explicit and implicit memory's impairments suggests that the neurocognitive background of the two subgroups of schizophrenia (S vs Z) might substantially differ from each other.
Pragmatic language skills were examined in schizophrenia patients compared to IQ-matched control subjects measured by the decoding of the flouting of the four Gricean maxims.
19 schizophrenic patients and 19 matched controls were evaluated. Five experimental conditions (all included four stories) were used, such as „quantity maxim” (QNM) condition, „quality maxim” (QLM) condition, „relevance maxim” (RM) condition, „manner maxim” (MM) condition and "control” (C) condition. An investigator presented the stories and asked for the hidden communicative intentions. PANSS scores and general intelligence were also measured.
Patients with schizophrenia performed significantly worse than controls in each of the conditions containig the flouting of the Gricean maxims. The response accuracy in the C condition was not differed significantly between the two groups (QNM:p< 0.001; QLM:p< 0.001; RM:p< 0.001; MM:p< 0.001; C:p=0.487). Significant positive correlations were found between QLM and IQ (p< 0.001) and between RM and IQ (p=0.025), and there was no significant correlatios between PANSS scores and response accuracy. Full scale IQ was not differed significantly between the two groups (p=0.095).
We found that a complex pragmatic language deficit exists in schizophrenia. The impairment do not seem to have a relationship with symptom severity. Besides, it seems, that good intellectual function supports pragmatic language skills in schizophrenia.
Cariprazine, a dopamine D3/D2 receptor partial agonist with preferential binding to D3 receptors, is being developed for the treatment of schizophrenia
To explore the effect of cariprazine on negative symptoms of schizophrenia.
Subjects aged 18-60 years with acute schizophrenia, current acute episode >2 weeks, and a PANSS total score ≥80 and ≤120 were randomly allocated in a 6-Week study NCT01104766 to cariprazine 3 mg/d, cariprazine 6 mg/d, aripiprazole 10 mg/d (active control), or placebo . Post–hoc analyses were performed on subjects with severe negative symptoms and low-to-moderate positive symptoms, defined according to Marder.
Results of the Post-Hoc Analyses
Data of 26 subjects were included in the cariprazine 3 mg/d (17.2% of the total sample), 34 in the cariprazine 6 mg/d (22.1%), 35 in the aripiprazole (23.3%) and 35 in the placebo (23.5%) groups, respectively. Change from baseline to Week 6 in the PANSS Factor Score for Negative Symptoms (PFSNS) was statistically significant for cariprazine 6 mg/d versus placebo (least squares mean difference: cariprazine 3 mg/d=-2.15, p= 0.20; cariprazine 6 mg/d = −3.68, p=.019). Cariprazine 6 mg/d was superior to placebo at each weekly assessment from Week 3. The changes in PFSNS for aripiprazole were not statistically significant at any weekly assessment.
Post–hoc analyses performed on subjects with acute schizophrenia, high level of negative symptoms and low-to-moderate positive symptoms, showed that the patients in the cariprazine 6 mg/d group had a significantly greater improvement relative to placebo on the PFSNS.
According to Nemeth et al. (2011), pediatric mania is difficult to distinguish from childhood hyperactivity. Both share 3 common symptoms: distractibility, motoric hyperactivity, and talkativeness (Biederman, 2000). Oftentimes, children are referred from their pediatrician due to a lack of appropriate response to stimulant medication. Pediatricians have learned that merely raising the dose or changing the stimulant does not work. A thorough neuropsychological evaluation often reveals Bipolar Mania. They may have comorbid Bipolar Disorder and ADHD. This poster paper will examine measures that can assist in this important differential diagnosis as well as offer treatment options, including medication management.
This case study includes three pediatric patients diagnosed with Childhood Bipolar Disorder and ADHD. A comprehensive psychoeducational assessment was conducted for each of the patients, which resulted in this comorbid diagnosis.
One of the most helpful measures was the TOVA. When a child’s attention and impulsivity scores are normal, and response time and variability scores are abnormal, both on and off medication, that is an indication of a mood disorder (Nemeth et al., 2007). These children also performed poorly on measures of processing speed, and verbal learning and interference tasks (Henin et al., 2007). Measures of affect and personality were important diagnostically. A combination of Amantadine and either Clonidine HCL ER or Propranolol, as prescribed by a medical psychologist, were found to be effective in controlling the symptoms of this comorbid diagnosis.
An evaluation of children’s intellectual, attentional, behavioral, mood, and personality functioning is crucial for a differential diagnosis. In cases of comorbidity, ADHD and Childhood Bipolar Disorder, the sooner the child is on appropriate medications, the better. When just the surface diagnosis of ADHD is medicated, the outcome is often problematic. There may be a poor response to treatment and a higher rate of suicide.
To examine the effect of cariprazine, a dopamine D3/D2 receptor partial agonist with preferential binding to D3 receptors, on predominant negative symptoms of schizophrenia.
Subjects with schizophrenia and PANSS factor score for negative symptoms (PANSS-FSNS) ≥ 24 and no pseudospecific factors (e.g. extrapyramidal symptoms, depression) were randomized to cariprazine 4.5 mg/d (dose range: 3-6 mg/d) or risperidone 4 mg/d (dose range: 3-6 mg/d) for 6 months.
Four hundred and sixty-one patients were randomized 1:1 to double-blind risperidone (n = 231) or cariprazine (n = 230) treatment. Change from Baseline (CfB) at week 26 in the primary parameter, PANSS-FSNS, was larger in the cariprazine group than in the risperidone group (LSMD = −1.47; 95% CI: [−2.39, −0.53]; P = 0.002) significant from week 14 onwards. CfB at week 26 in the functional parameter, Personal and Social Performance (PSP) total score, showed similarly greater improvement with cariprazine than risperidone (LSMD = 4.63; 95% CI: [2.71, 6.56]; P < 0.001) significant from week 10 onward. Statistically significant differences in favor of cariprazine at week 26 were shown in the PSP areas of self-care, socially useful activities and personal and social relationships. Most patients tolerated the study treatment well, as reflected by low discontinuation rates due to adverse events (AEs). Adverse event profiles of cariprazine and risperidone were similar. The most common AEs during study treatment were insomnia (10.0%), and headache (10.4%), both in the risperidone group.
26-week cariprazine treatment, given as antipsychotic monotherapy, was significantly more effective on negative symptoms and on functioning than risperidone in patients with predominant negative symptoms of schizophrenia.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Negative symptoms have substantial impact on day-to-day functioning of patients with schizophrenia affecting their ability to perform activities of daily living and to maintain personal relationships.
To present post hoc data on day-to-day and social functioning of patients with predominant negative symptom (PNS) of schizophrenia, treated with cariprazine versus risperidone.
Data from 26 weeks, phase 3, randomized, double-blind, active-controlled study in PNS patients were analyzed (EudraCT 2012-005485-36). Subjects with PNS (PANSS factor score for negative symptoms ≥24) were randomized to cariprazine 4.5 mg/d or risperidone 4 mg/d. Change from baseline to end of treatment on the personal and social performance scale (PSP) and PANSS prosocial subscale (P3, P6, N2, N4, N7, G16) was analyzed.
Significantly greater improvements were seen with cariprazine compared to risperidone in the change from baseline to end of treatment on the PSP (LSMD + 4.632 [2.71, 6.56]; P < 0.001) from week 10 onwards (effect size 0.48); in the PSP subdomains of self-care (LSMD −0.2 [−0.3; −0.1]; P = 0.004), personal and social relationships (LSMD −0.2 [−0.4;−0.1]; P < 0.001) and socially useful activities (LSMD −0.4 [−0.5; −0.2]; P < 0.001); in the number of patients who improved at least 10 points on the PSP (OR 2.1; P = 0.001) or shifted to a higher category (OR 2.2; P = 0.001); and on the PANSS prosocial subscale (LSMD −0.8 [−1.41, −0.16]; P = 0.014).
Post hoc evaluation of this study showed that cariprazine treatment is associated with a clinically relevant improvement in patient functioning and social competence compared to risperidone.
To present, post hoc analyses from a controlled, prospective study of predominant negative symptoms (PNS) of schizophrenia on baseline patient characteristics, severity of symptoms and their variability among participating countries.
Data were analyzed from a phase 3, randomized, double-blind, active-controlled, parallel-group study in adult PNS patients with schizophrenia (EudraCT Number 2012-005485-36). Subjects with a PANSS factor score for negative symptoms (PANSS-FSNS) ≥ 24 and no pseudo-specific factors (e.g. high positive symptoms, extrapyramidal symptoms, depression) were randomized to cariprazine 4.5 mg/d (dose range: 3–6 mg/d) or risperidone 4 mg/d (dose range: 3–6 mg/d) for 26 weeks. Baseline values of PANSS-FSNS, individual PANSS items, personal and social performance (PSP), and clinical global impression of severity (CGI-S) were analyzed based on the data gained from 11 European participating countries.
Average PANSS-FSNS of patients was 27.6 ± 2.48, reflecting severe negative symptoms. Patients were moderately ill (CGI-S 4.2 ± 0.75), with marked difficulties (PSP 48.4 ± 10.78) predominantly in social functioning. The investigated patient population was fairly homogeneous as shown by small variability in all three scores. Moreover, baseline values in the 11 countries presented low variability while number of enrolled patients per country showed high variance (n = 7–118). Narrative description of symptoms and individual PANSS items rated as most severe and prominent were in high correlation.
Post hoc evaluation of this predominant negative symptom study showed that, this patient population can be identified reliably by psychiatrist. Additional training on the judgment of personal and social relationships can increase the diagnostic accuracy.
We conducted a matched-cohort study to assess mortality in schizophrenia and the relationship of mortality with comorbid somatic conditions and suicide attempts.
A full-population register-based prospective matched-cohort study was performed including all eligible patients with schizophrenia in Hungary between 01/01/2005 and 31/12/2013. Control subjects were individually matched to patients with schizophrenia at a 5:1 ratio. The principal outcome measure was death due to any reason. A non-parametric approach was used for descriptive statistical purposes, the Kaplan-Meier model for survival analysis, and the Cox proportional-hazards regression model for inferential statistics.
Patients with schizophrenia (n = 65,169) had substantially higher risk of all-cause mortality than the control subjects (n = 325,435) (RR = 2.4; P < 0.0001). Comorbidities and suicide attempts were associated with significantly increased mortality in both groups. As compared to the controls, 20-year old males with schizophrenia had a shorter life expectancy by 11.5 years, and females by 13.7 years; the analogous numbers for 45-year old schizophrenics were 8.1 and 9.6 years, respectively.
A significant mortality gap – mainly associated with somatic comorbidities – was detected between patients with schizophrenia and individually matched controls. Improved medical training to address the disparity in mortality, and many other factors including lack of resources, access to and model of medical care, lifestyle, medication side effects, smoking, stigma, need for early intervention and adequate health care organization could help to better address the physical health needs of patients with schizophrenia.
Dual inhibition (2i) of Ras–MEK–ERK and GSK3β pathways enables the derivation of embryo stem cells (ESCs) from refractory mouse strains and, for permissive strains, allows ESC derivation with no external protein factor stimuli involvement. In addition, blocking of ERK signalling in 8-cell-stage mouse embryos leads to ablation of GATA4/6 expression in hypoblasts, suggesting fibroblast growth factor (FGF) dependence of hypoblast formation in the mouse. In human, bovine or porcine embryos, the hypoblast remains unaffected or displays slight-to-moderate reduction in cell number. In this study, we demonstrated that segregation of the hypoblast and the epiblast in rabbit embryos is FGF independent and 2i treatment elicits only a limited reinforcement in favour of OCT4-positive epiblast populations against the GATA4-/6-positive hypoblast population. It has been previously shown that TGFβ/Activin A inhibition overcomes the pervasive differentiation and inhomogeneity of rat iPSCs, rat ESCs and human iPSCs while prompting them to acquire naïve properties. However, TGFβ/Activin A inhibition, alone or together with Rho-associated, coiled-coil containing protein kinase (ROCK) inhibition, was not compatible with the viability of rabbit embryos according to the ultrastructural analysis of preimplantation rabbit embryos by electron microscopy. In rabbit models ovulation upon mating allows the precise timing of progression of the pregnancy. It produces several embryos of the desired stage in one pregnancy and a relatively short gestation period, making the rabbit embryo a suitable model to discover the cellular functions and mechanisms of maintenance of pluripotency in embryonic cells and the embryo-derived stem cells of other mammals.
In Hungary, between February 2017 and July 2019, 70 confirmed measles cases were reported, raising questions about the adequacy of population-level immunity. Although the assumed vaccination coverage is ≥99%, in a recent study, we detected potential gaps in the anti-measles humoral immunity. In Hungary, according to a decree by the Ministry of Public Welfare, beginning from 2021, the healthcare provider should conduct a serosurvey of anti-measles protection levels of healthcare professionals. To facilitate the compliance with this requirement, we developed a quick ‘three-in-one’ or ‘triple’ MMR (measles, mumps and rubella) indirect ELISA (IgG); an assay format that is currently not available commercially. High throughput applicability of the ‘three-in-one’ ELISA was verified using 1736 sera from routine laboratory residual samples, using an automated platform (Siemens BEP 2000 Advance). Assay verification was performed by comparing the full antigen repertoire-based ‘target’ assay with in-house ‘control’ assays using recombinant viral antigen coatings, and by validated commercially available kits. Indirect immunofluorescence was used as an independent reference method. Data were analysed using OriginLab, IBM SPSS, RStudio and MedCalc. In case of measles, we combined our current results with previously published data (Ntotal measles = 3523). Evaluation of anti-mumps and anti-rubella humoral antibody levels was based on the measurement of 1736 samples. The lowest anti-measles seropositivity (79.3%) was detected in sera of individuals vaccinated between 1978 and 1987. Considering the antigen-specific seropositivity ratios of all samples measured, anti-measles, -mumps and -rubella IgG antibody titres were adequate in 89.84%, 91.82% and 92.28%, respectively. Based on the virus-specific herd immunity threshold (HIT) values (HITMeasles = 92–95%, HITMumps = 75–86%, HITRubella = 83–86), it can be stated that regarding anti-measles immunity, certain age clusters of the population may have inadequate levels of humoral immunity. Despite the potential gaps in herd immunity, the use of MMR vaccine remains an effective and low-cost approach for the prevention of measles, mumps and rubella infections.
We documented the consequences of large-scale habitat loss on a community of Galápagos native bird species on San Cristóbal island, based on point counts conducted between 2010 and 2017. Surprisingly, despite considerable habitat change and a variety of other threats, the landbirds of San Cristóbal have fared much better than on the neighbouring islands Floreana or Santa Cruz. While two species went extinct very soon after human colonisation, the majority have adapted well to subsequent vegetation change and habitat loss. The endemic San Cristóbal Mockingbird Mimus melanotis is more widespread than previously thought and its population seems to be stable since the 1980s. We thus propose a change in IUCN classification from ‘Endangered’ to ‘Near threatened’. We present evidence gained by interviewing locals which suggests that a small population of the Least Vermilion Flycatcher Pyrocephalus dubius, classified as ‘Extinct’ by BirdLife International, may have persisted until very recently. Although extensive searches in 2018 and 2019 were unsuccessful, the possibility remains that a few birds may have survived in remote parts of the island. Further searches that involve the general public and other interested parties are therefore deemed necessary.