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The efficacy of electroconvulsive therapy (ECT) is widely recognized and indications are well defined for acute treatments. Surprisingly, the use of continuation and maintenance ECT (M-ECT) is uncommon after acute remission. This is partly because of the scarcity of scientific evidence. Indications are poorly defined and the practice is based on case reports and small open studies. Recent data suggest that M-ECT is a viable treatment option in severe affective and psychotic illnesses, especially in recurring, drug-resistant or medically compromised patients who suffer toxic effects with psychotropics.
Studies regarding the duration and frequency of treatment sessions are laking. The time interval between sessions and duration of treatment vary according to clinical requirements, and should be individualized. The length of treatment and deciding when to stop it are still uncertain. Controversial data about the relation between the frequency of sessions and diagnostic is found. An inverse relation between good prognostic factors for each patient and the frequency of M-ECT was described. During continuation and maintenance ECT, seizure threshold increases until a plateau not being clear when the plateau is reached and if it depends on other treatment variables.
The risk of cognitive dysfunction following M-ECT is one major concern. A transient memory and attention dysfunction are described after acute ECT. Recent studies seem to suggest that M-ECT is cognitively safe.
There is robust evidence recommending electroconvulsive therapy (ECT) in treating severe acute affective disorders. The clinical use of bitemporal electrode placement is still favoured to unilateral placement with just a relative disadvantage in cognitive side effects. Recently, bifrontal placement has gained popularity but there is still limited evidence on its relative benefits.
Compare bitemporal and bifrontal ECT efficacy in patients with pharmacologically resistant affective disorders, based on the number of acute phase treatments required to reach symptomatic remission.
Review of all patients' charts submitted to acute phase ECT, between June 2006 and June 2011. A total of 70 ECT treatment courses performed in a group of 67 patients met inclusion criteria. Thirty-eight of the total 70 courses received bitemporal ECT, and 32 received bifrontal ECT. A statistical analysis was performed. An attempt to use t-test was foiled due to breach of population variance homogeneity (p = 0,021). The non-parametric Mann-Whitney test was the alternative choice (M-W = 534;p = 0,377).
Bitemporal and bifrontal groups matched for age and sex. Bitemporal patients received on average five ECT treatments, while the average of bifrontal treatments to remission was six, but this difference was not statistically significant (p > 0.05).
Our results showed that bitemporal and bifrontal placements are equally effective. According to the largest randomised controlled trial conducted on ECT in depressive illness (Kellner et al,2010), bitemporal placement led to a faster rate of improvement. Additional studies and larger samples are required to understand if bifrontal placement's efficacy and cognitive advantages justify its popularity.
Bipolar mixed states were systematically described for the first time by Emil Kraepelin. Since then, their high prevalence has been repeatedly recognized, but they still remain poorly understood. These patients appear to be extremely difficult to treat, many being refractory to pharmacological approaches. Clinical experience supports the use of electroconvulsive therapy (ECT) in mixed states, but there is little information on its effectiveness in scientific literature.
Report our experience in using acute phase ECT (aECT) in mixed states.
The authors reviewed the clinical records of all patients submitted to aECT between June 2006 and June 2011. The inclusion criteria were: a) presence of a mixed state according to Akiskal's criteria (Akiskal et al,2005); b) completed treatment course with aECT. The following variables were collected: demographic characteristics, previous response to pharmacotherapy, presence of psychotic symptoms, number of aECT sessions, referral to continuation or maintenance ECT (c/mECT), number of readmissions. Relation between the diagnostics and the number of ECT sessions was validated with Eta-coefficient. Comparison between these two groups was carried out with One-Way-ANOVA.
Eighteen patients met inclusion criteria and were resistant to pharmacotherapy. Eight patients had psychotic features. All patients but one showed a positive clinical response, as documented on CGI. The average number of ECT sessions was five, while the mean of ECT treatments in manic and depressive patients was seven and six respectively. Thirteen patients were scheduled for c/mECT.
Our results confirm the effectiveness of ECT in medication nonresponsive patients experiencing a mixed state.
The Gender Identity Disorder (GID) is characterized by a strong sense of identity with the opposite gender, by a persistent discomfort with the one's gender and with a feeling of inadequacy to the social role of the biological gender.
The possibility of a higher presence of Borderline Personality Disorder (BPD) in patients with GID has been a subject of research in several studies.
The diagnosis criteria of the BPD includes a global disorder in the individual identity.
Both BPD and GID are associated with a high risk of self-mutilation and suicide.
To analyze and discuss a case report, addressing subjects related to the psychopatology, differential diagnosis and prognosis and therapeutic implications.
Our discussion is focused on a case report, that led us to a non systematic review of the literature.
Our case report is related to a 20 year old man with GID and BPD. This situation is lived in a great social isolation and frequent self-mutilation episodes and suicide attempts.
The clinical outcome is aggravated by a severe instability in the personal relationships, self-image, ambitions and the future projects.
We have discussed the differential diagnosis, psychopatology, prognosis and the identity disorder that the subject presents.
The biologic gender, age and the treatment phase are factors that influence the risk of suicide and self-mutilation in these patients. We did not found a higher probability of BPD in a patient with GID.
Tuberous sclerosis complex is a rare genetic disorder leading to the growth of hamartomas in multiple organs, including cardiac rhabdomyomas. Children with symptomatic cardiac rhabdomyoma require frequent admissions to intensive care units, have major complications, namely, arrhythmias, cardiac outflow tract obstruction and heart failure, affecting the quality of life and taking on high healthcare cost. Currently, there is no standard pharmacological treatment for this condition, and the management includes a conservative approach and supportive care. Everolimus has shown positive effects on subependymal giant cell astrocytomas, renal angiomyolipoma and refractory seizures associated with tuberous sclerosis complex. However, evidence supporting efficacy in symptomatic cardiac rhabdomyoma is limited to case reports. The ORACLE trial is the first randomised clinical trial assessing the efficacy of everolimus as a specific therapy for symptomatic cardiac rhabdomyoma.
ORACLE is a phase II, prospective, randomised, placebo-controlled, double-blind, multicentre protocol trial. A total of 40 children with symptomatic cardiac rhabdomyoma secondary to tuberous sclerosis complex will be randomised to receive oral everolimus or placebo for 3 months. The primary outcome is 50% or more reduction in the tumour size related to baseline. As secondary outcomes we include the presence of arrhythmias, pericardial effusion, intracardiac obstruction, adverse events, progression of tumour reduction and effect on heart failure.
ORACLE protocol addresses a relevant unmet need in children with tuberous sclerosis complex and cardiac rhabdomyoma. The results of the trial will potentially support the first evidence-based therapy for this condition.
The SCN5A gene is implicated in many arrhythmogenic and cardiomyopathic processes. We identified a novel SCN5A variant in a family with significant segregation in individuals affected with progressive sinus and atrioventricular nodal disease, atrial arrhythmia, dilated cardiomyopathy, and early sudden cardiac arrest.
A patient pedigree was created following the clinical evaluation of three affected individuals, two monozygotic twins and a paternal half-brother, which lead to the evaluation of a paternal half-sister (four siblings with the same father and three mothers) all of whom experienced varying degrees of atrial arrhythmias, conduction disease, and dilated cardiomyopathy in addition to a paternal history of unexplained death in his 50s with similar autopsy findings. The index male underwent sequencing of 58 genes associated with cardiomyopathies. Sanger sequencing was used to provide data for bases with insufficient coverage and for bases in some known regions of genomic segmental duplications. All clinically significant and novel variants were confirmed by independent Sanger sequencing.
All relatives tested were shown to have the same SCN5A variant of unknown significance (p. Asp197His) and the monozygotic twins shared a co-occurring NEXN (p. Glu575*). Segregation analysis demonstrates likely pathogenic trait for the SCN5A variant with an additional possible role for the NEXN variant in combination.
There is compelling clinical evidence suggesting that the SCN5A variant p. Asp197His may be re-classified as likely pathogenic based on the segregation analysis of our family of interest. Molecular mechanism studies are pending.
Facial transplantation is emerging as a therapeutic option for self-inflicted gunshot wounds. The self-inflicted nature of this injury raises questions about the appropriate role of self-harm in determining patient eligibility. Potential candidates for facial transplantation undergo extensive psychosocial screening. The presence of a self-inflicted gunshot wound warrants special attention to ensure that a patient is prepared to undergo a demanding procedure that poses significant risk, as well as stringent lifelong management. Herein, we explore the ethics of considering mechanism of injury in the patient selection process, referring to the precedent set forth in solid organ transplantation. We also consider the available evidence regarding outcomes of individuals transplanted for self-inflicted mechanisms of injury in both solid organ and facial transplantation. We conclude that while the presence of a self-inflicted gunshot wound is significant in the overall evaluation of the candidate, it does not on its own warrant exclusion from consideration for a facial transplantation.
Introduction: The number of CT scans prescribed in the Emergency department (ED) for suspected renal colic has increased over recent years without an associated improvement in patient-centred outcomes. We assessed whether Point-of-Care Ultrasound (PoCUS) decreases the use of formal radiologic imaging. Methods: We completed a retrospective cohort study on consecutive patients 18 years of age and older presenting to the ED with suspected uncomplicated renal colic in a tertiary care centre in Québec in 2016. Exclusion criteria included: previous urologic intervention, solitary kidney, dialysis, fever, pyuria, acute kidney injury, pregnancy, suspicion of a serious alternative diagnosis or persistent symptoms despite analgesia. We compared the proportion (95%CI) of formal radiologic imaging performed (Ultrasound or CT) in patients who had PoCUS in the ED vs. those who did not. Two-tailed Fisher exact test (α = 0.05) and odds ratios (95%CI) calculated from multivariate logistic regression models adjusted for age, gender, Charlson Index and previous renal colic were used to compare the two groups. The reliability of data collection was evaluated with a kappa score (95%CI). Results: 169 patients with uncomplicated renal colic were included. There was no difference between the groups in terms of age, gender, Charlson Index, or previous renal colic. The PoCUS level of training and the doctor's education level was significantly higher in the PoCUS group. There was a non-significant trend towards less formal imaging in patients of the PoCUS group 65/88 (73.9% [63.4-82.7%]) vs. the non-PoCUS group 69/81 (85.2% [75.6-92.1%]), p = 0.087. After adjustment for confounders, the patients not evaluated with PoCUS were more likely to have formal imaging with a significant odds ratio of 2.41 [1.05-5.56]). Among patients who underwent a CT, incidentalomas were found in 16.5% and only 2.0% demonstrated significant findings leading to changes in ED management, such as an alternative diagnosis, need for admission, or an urgent urological intervention. Inter-observer agreement was excellent between assessers with a kappa score of 0.88 [0.66-1.00]. Conclusion: ED patients with uncomplicated renal colic who are investigated with PoCUS tend to have fewer formal imaging test. When CT scans were performed, incidentalomas were found in 16.5% and ED management changed only 2.0% of the time. PoCUS appears to be a useful tool for decreasing CT utilisation in this low-risk ED population.
Takotsubo cardiomyopathy is characterised by akinesis and ballooning of the left ventricular apex during contraction of the otherwise normal base of the heart. We describe the case of a 7-month-old previously healthy female who presented with an unwitnessed cardiac arrest. Workup raised suspicion for non-accidental trauma. Despite progression to brain death, the severely decreased ventricular function and apical akinesis of the left ventricle improved within 40 hours of admission. This report will familiarise paediatricians with this rare cardiomyopathy and emphasise the importance of considering non-accidental trauma as an inciting event for patients with unwitnessed cardiac arrest found to have decreased ventricular function.
For most patients, adenoviruses cause few acute health concerns and are often self-limiting. Patients who are immunocompromised or immunosuppressed, however, are at risk for disseminated adenovirus and suffer high morbidity and mortality, without well-defined treatment options. We report the case of a 9-month-old boy who was successfully treated for disseminated adenovirus infection with intravenous immunoglobulin and cidofovir 3 months post heart transplant, tailored to serum adenoviral load and clinical response. We emphasise the importance of early identification, monitoring, and a potentially novel treatment in the paediatric cardiac transplant population with disseminated adenovirus infection.
FK506 binding protein 5 (FKBP5) alters stress response system functioning, and childhood maltreatment is associated with methylation of the FKBP5 gene. Yet it is unknown if maltreatment contributes to change in FKBP5 methylation over time. The current study draws upon a sample of 231 preschoolers, including 123 with child welfare documentation of moderate to severe maltreatment in the past 6 months, to understand if maltreatment contributes to change in FKBP5 methylation over a 6-month period. Review of child protection records and semistructured interviews in the home were used to assess maltreatment and exposure to other contextual stressors, as well as service utilization. Methylation of FKBP5 at two CpG sites in intron 7 was measured from saliva DNA at the time of initial study enrollment, and 6 months following enrollment. Child maltreatment was associated with change in FKBP5 methylation over time, but only when children were exposed to high levels of other contextual stressors. Service utilization was associated with increases in methylation over time, but only among children with the FKPB5 rs1360780 protective CC genotype. Methylation of FKBP5 is sensitive to stress exposure and may be a mechanism linking early adversity to long-term health and developmental outcomes.
Epigenetics processes may play a vital role in the biological embedding of early environmental adversity and the development of psychopathology. Accumulating evidence suggests that maltreatment is linked to methylation of the glucocorticoid receptor gene, nuclear receptor subfamily 3, group C, member 1 (NR3C1), which is a key regulator of the hypothalamus–pituitary–adrenal axis. However, prior work has been exclusively cross-sectional, greatly constraining our understanding of stress-related epigenetic processes over time. In the current study, we examined the effect of maltreatment and other adversity on change in NR3C1 methylation among at-risk preschoolers to begin to characterize within-child epigenetic changes during this sensitive developmental period. Participants were 260 preschoolers (3–5 years old, 53.8% female), including 51.5% with moderate to severe maltreatment in the past 6 months. Child protection records, semistructured interviews, and parent reports were used to assess child stress exposure. Methylation of exons 1D and 1F of NR3C1 via saliva DNA were measured at two time points approximately 6 months apart. Results indicate that maltreated children evidence higher baseline levels of NR3C1 methylation, significant decreases in methylation over time, and then at follow-up, lower levels of methylation, relative to nonmaltreated preschoolers. Findings from the current study highlight the complex nature of stress-related epigenetic processes during early development.
While many studies focus on the association between early life adversity and the later risk for psychopathology, few simultaneously explore diverse forms of environmental adversity. Moreover, those studies that examined the cumulative impact of early life adversity focus uniquely on postnatal influences. The objective of this study was to focus on the fetal period of development to construct and validate a cumulative prenatal adversity score in relation to a wide range of neurodevelopmental outcomes. We also examined the interaction of this adversity score with a biologically informed genetic score based on the serotonin transporter gene. Prenatal adversities were computed in two community birth cohorts using information on health during pregnancy, birth weight, gestational age, income, domestic violence/sexual abuse, marital strain, as well as maternal smoking, anxiety, and depression. A genetic score based on genes coexpressed with the serotonin transporter in the amygdala, hippocampus, and prefrontal cortex during prenatal life was constructed with an emphasis on functionally relevant single nucleotide polymorphisms, that is, expression quantitative trait loci. Prenatal adversities predicted a wide range of developmental and behavioral alterations in children as young as 2 years of age in both cohorts. There were interactions between the genetic score and adversities for several domains of the Child Behavior Checklist (CBCL), with pervasive developmental problems remaining significant adjustment for multiple comparisons. Scores combining different prenatal adverse exposures predict childhood behavior and interact with the genetic background to influence the risk for psychopathology.
Serotonin signaling pathways play a key role in brain development, stress reactivity, and mental health. Epigenetic alterations in the serotonin system may underlie the effect of early life stress on psychopathology. The current study examined methylation of the serotonin receptor 2A (HTR2A) gene in a sample of 228 children including 119 with child welfare documentation of moderate to severe maltreatment within the last 6 months. Child protection records, semistructured interviews in the home, and parent reports were used to assess child stress exposure, psychiatric symptoms, and behavior. The HTR2A genotype and methylation of HTR2A were measured at two CpG sites (–1420 and –1224) from saliva DNA. HTR2A genotype was associated with HTR2A methylation at both CpG sites. HTR2A genotype also moderated associations of contextual stress exposure and HTR2A methylation at site –1420. Contextual stress was positively associated with –1420 methylation among A homozygotes, but negatively associated with –1420 methylation among G homozygotes. Posttraumatic stress disorder and major depressive disorder symptoms were negatively associated with methylation at –1420, but positively associated with methylation at –1224. Results support the view that the serotonin system is sensitive to stress exposure and psychopathology, and HTR2A methylation may be a mechanism by which early adversity is biologically encoded.
Pulmonary balloon valvuloplasty is a safe and effective treatment for children with pulmonary valve stenosis. A few studies evaluate the long-term outcomes of the procedure, particularly the degree of pulmonary regurgitation. We evaluated the outcomes of children >1 year following valvuloplasty for pulmonary valve stenosis.
A retrospective analysis of children with pulmonary valve stenosis following pulmonary balloon valvuloplasty at a single institution was performed. Clinic summaries, catheterisation data, and echocardiographic data were reviewed. Inclusion criteria were isolated pulmonary valve stenosis, age <19 years at the time of intervention, and at least one echocardiogram performed at least 1 year after valvuloplasty.
A total of 53 patients met inclusion criteria. The median age at valvuloplasty was 0.4 years (0.01–10.6 years). The last follow-up was 4.8±2.3 years following valvuloplasty. The pre-valvuloplasty peak instantaneous gradient by echocardiography was 60.6±14.6 mmHg. The peak gradient at the first postoperative echocardiography was reduced to 25.5±12 mmHg (p<0.001), and further decreased to 14.8±15.8 mmHg (p<0.001) at the most recent follow-up. The degree of regurgitation increased from before valvuloplasty to after valvuloplasty (p<0.001) but did not progress at the most recent follow-up (p=0.17). Only three patients (5.7%) required re-intervention for increasing pulmonary stenosis (two surgical; one repeat balloon). No significant procedural complications occurred.
Pulmonary balloon valvuloplasty remains a safe and effective treatment for children with isolated pulmonary valve stenosis, with excellent long-term outcomes and no mortality. A few patients require further intervention. Long-term follow-up demonstrates decreased, residual stenosis. Patients have a small, acute increase in pulmonary regurgitation following valvuloplasty, but no long-term progression.
Takotsubo cardiomyopathy or transient apical ballooning syndrome very rarely presents in children. In all patients with takotsubo, it is estimated that only 3.5% will have recurrence. In this study, we describe a case of recurrent takotsubo cardiomyopathy in a child, likely triggered by status epilepticus.