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The Canada Health Act requires reasonable access to all medically necessary therapies. No information is available to assess the current access to neuromodulation across Canada. This study quantifies the current rate of deep brain stimulation (DBS) for the entire country of Canada. Analyses were performed to determine whether there were differences in access based on provincial or territorial location, rural or non-rural region, or socioeconomic status.
All implanted DBS devices in Canada over a 2-year epoch (January 2015 to December 2016) were supplied by either Boston Scientific or Medtronic. Investigators received anonymized data from these companies, including patient age and home residence region. The 2016 Statistics Canada census data were used to determine the rate of DBS surgery and whether access was related to provincial location, rural versus non-rural region or socioeconomic status.
A total of 722 patients were studied. The rate of DBS surgery for the entire country was ten per million population per year. Saskatchewan was significantly above (374%) the national average, whereas Quebec (40%) and Newfoundland & Labrador (32%) were significantly below the national average. No patients from the three territories received DBS. There were no significant differences in access from rural versus non-rural areas or in regions within provinces with different socioeconomic status.
This is the first study to quantify all patients receiving DBS within an entire country. The current rate of DBS surgery within Canada is ten cases per million per year. Statistically significant regional differences were discovered and discussed.
Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88) presented a critique of our recently published paper in Cell Reports entitled ‘Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets’ (Lam et al., Cell Reports, Vol. 21, 2017, 2597–2613). Specifically, Hill offered several interrelated comments suggesting potential problems with our use of a new analytic method called Multi-Trait Analysis of GWAS (MTAG) (Turley et al., Nature Genetics, Vol. 50, 2018, 229–237). In this brief article, we respond to each of these concerns. Using empirical data, we conclude that our MTAG results do not suffer from ‘inflation in the FDR [false discovery rate]’, as suggested by Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88), and are not ‘more relevant to the genetic contributions to education than they are to the genetic contributions to intelligence’.
Our previous work revealed substantial heterogeneity in the cognitive profile of bipolar disorder (BD) due to the presence of three underlying cognitive subgroups characterized as: globally impaired, selectively impaired, or cognitively intact. In an effort to determine whether these subgroups are differentially related to genetic risk for the illness, we investigated whether cognitive deficits were more pronounced in unaffected siblings (UAS) of BD probands within identified clusters.
Cluster analysis was used to identify cognitive clusters in BD (N = 60). UAS (N = 49) were classified into groups according to their proband sibling's cluster assignment; comparisons were made across all clusters and healthy controls (HCs; N = 71).
Three cognitive clusters in BD emerged: a globally impaired (36.7%), a selectively impaired (30%), and a cognitively intact cluster (33.3%). UAS showed a qualitatively similar pattern to their BD siblings; UAS of the globally impaired BD cluster showed verbal memory and general cognitive impairments relative to HCs. In contrast, UAS of the other two clusters did not differ from HCs.
This study corroborates findings from prior work regarding the presence of cognitive heterogeneity in BD. UAS of subjects in the globally impaired BD cluster presented with a qualitatively similar cognitive profile to their siblings and performed worse than all other BD clusters and UAS groups. This suggests that inherited risk factors may be contributing to cognitive deficits more notably in one subgroup of patients with BD, pointing toward differential causes of cognitive deficits in discrete subgroups of patients with the disorder.
Current group-average analysis suggests quantitative but not qualitative cognitive differences between schizophrenia (SZ) and bipolar disorder (BD). There is increasing recognition that cognitive within-group heterogeneity exists in both disorders, but it remains unclear as to whether between-group comparisons of performance in cognitive subgroups emerging from within each of these nosological categories uphold group-average findings. We addressed this by identifying cognitive subgroups in large samples of SZ and BD patients independently, and comparing their cognitive profiles. The utility of a cross-diagnostic clustering approach to understanding cognitive heterogeneity in these patients was also explored.
Hierarchical clustering analyses were conducted using cognitive data from 1541 participants (SZ n = 564, BD n = 402, healthy control n = 575).
Three qualitatively and quantitatively similar clusters emerged within each clinical group: a severely impaired cluster, a mild-moderately impaired cluster and a relatively intact cognitive cluster. A cross-diagnostic clustering solution also resulted in three subgroups and was superior in reducing cognitive heterogeneity compared with disorder clustering independently.
Quantitative SZ–BD cognitive differences commonly seen using group averages did not hold when cognitive heterogeneity was factored into our sample. Members of each corresponding subgroup, irrespective of diagnosis, might be manifesting the outcome of differences in shared cognitive risk factors.
Hippocampal dysfunction is considered central to many neurobiological models of schizophrenia, yet there are few longitudinal in vivo neuroimaging studies that have investigated the relationship between antipsychotic treatment and morphologic changes within specific hippocampal subregions among patients with psychosis.
A total of 29 patients experiencing a first episode of psychosis with little or no prior antipsychotic exposure received structural neuroimaging examinations at illness onset and then following 12 weeks of treatment with either risperidone or aripiprazole in a double-blind randomized clinical trial. In addition, 29 healthy volunteers received structural neuroimaging examinations at baseline and 12-week time points. We manually delineated six hippocampal subregions [i.e. anterior cornu ammonis (CA) 1–3, posterior CA1–3, subiculum, dentate gyrus/CA4, entorhinal cortex, and fimbria] from 3T magnetic resonance images using an established method with high inter- and intra-rater reliability.
Following antipsychotic treatment patients demonstrated significant reductions in dentate gyrus/CA4 volume and increases in subiculum volume. Healthy volunteers demonstrated non-significant volumetric changes in these subregions across the two time points. We observed a significant quadratic (i.e. inverted U) association between changes in dentate gyrus/CA4 volume and cumulative antipsychotic dosage between the scans.
This study provides the first evidence to our knowledge regarding longitudinal in vivo volumetric changes within specific hippocampal subregions in patients with psychosis following antipsychotic treatment. The finding of a non-linear relationship between changes in dentate gyrus/CA4 subregion volume and antipsychotic exposure may provide new avenues into understanding dosing strategies for therapeutic interventions relevant to neurobiological models of hippocampal dysfunction in psychosis.
Recent data suggest trait-like neurocognitive impairments in bipolar disorder (BPD), with deficits about 1 s.d. below average, less severe than deficits noted in schizophrenia. The frequency of significant impairment in BPD is approximately 60%, with 40% of patients characterized as cognitively spared. This contrasts with a more homogeneous presentation in schizophrenia. It is not understood why some BPD patients develop deficits while others do not.
A total of 136 patients with BPD completed the MATRICS Consensus Cognitive Battery and data were entered into hierarchical cluster analyses to: (1) determine the optimal number of clusters (subgroups) that fit the sample; and (2) assign subjects to a specific cluster based on individual profiles. We then compared subgroups on several clinical factors and real-world community functioning.
Three distinct neurocognitive subgroups were found: (1) an intact group with performance comparable with healthy controls on all domains but with superior social cognition; (2) a selective impairment group with moderate deficits on processing speed, attention, verbal learning and social cognition and normal functioning in other domains; and (3) a global impairment group with severe deficits across all cognitive domains comparable with deficits in schizophrenia.
These results suggest the presence of multiple cognitive subgroups in BPD with unique profiles and begin to address the relationships between these subgroups, several clinical factors and functional outcome. Next steps will include using these data to help guide future efforts to target these disabling symptoms with treatment.
There is a considerable scarcity of reliable population-based data on the prevalence of preventable ear disorders in developing countries. This study was conducted to determine the prevalence of preventable ear disorders in primary school children (aged 5 to 12 years) in northern India.
A pro forma questionnaire was used to screen 15 718 primary school children in New Delhi for ear disorders. Ear examinations were conducted using otoscopy and impedance audiometry.
Impacted cerumen was prevalent in 7.93 per cent of schoolchildren, 4.79 per cent suffered from chronic otitis media and 3.06 per cent suffered from otitis media with effusion. Acute otitis media was detected in 0.65 per cent and foreign bodies were found in 0.34 per cent of the children.
Preventable ear diseases posed a significant health problem among children at primary school level. Regular screening of children during this stage would ensure that their school lives were not affected by hearing impairments or preventable ear disorders. Information gathered in this study will help in effective treatment prioritisation of ear disorders, planning and resource allocation.
Because early treatment choice is critical in first-episode schizophrenia-spectrum disorders (FES), this meta-analysis compared efficacy and tolerability of individual second-generation antipsychotics (SGAs) with first-generation antipsychotics (FGAs) in FES. We conducted systematic literature search (until 12 December 2010) and meta-analysis of acute, randomized trials with ⩾1 FGA vs. SGA comparison; patients in their first episode of psychosis and diagnosed with schizophrenia-spectrum disorders; available data for psychopathology change, treatment response, treatment discontinuation, adverse effects, or cognition. Across 13 trials (n = 2509), olanzapine (seven trials) and amisulpride (one trial) outperformed FGAs (haloperidol: 9/13 trials) in 9/13 and 8/13 efficacy outcomes, respectively, risperidone (eight trials) in 4/13, quetiapine (one trial) in 3/13 and clozapine (two trials) and ziprasidone (one trial) in 1/13, each. Compared to FGAs, extrapyramidal symptom (EPS)-related outcomes were less frequent with olanzapine, risperidone and clozapine, but weight gain was greater with clozapine, olanzapine and risperidone. Pooled SGAs were similar to FGAs regarding total psychopathology change, depression, treatment response and metabolic changes. SGAs significantly outperformed FGAs regarding lower treatment discontinuation, irrespective of cause, negative symptoms, global cognition and less EPS and akathisia, while SGAs increased weight more (p < 0.05–0.01). Results were not affected by FGA dose or publication bias, but industry-sponsored studies favoured SGAs more than federally funded studies. To summarize, in FES, olanzapine, amisulpride and, less so, risperidone and quetiapine showed superior efficacy, greater treatment persistence and less EPS than FGAs. However, weight increase with olanzapine, risperidone and clozapine and metabolic changes with olanzapine were greater. Additional FES studies including broader-based SGAs and FGAs are needed.
Cognitive deficits are core to the disability associated with many psychiatric disorders. Both variation in cognition and psychiatric risk show substantial heritability, with overlapping genetic variants contributing to both. Unsurprisingly, therefore, these fields have been mutually beneficial: just as cognitive studies of psychiatric risk variants may identify genes involved in cognition, so too can genome-wide studies based on cognitive phenotypes lead to genes relevant to psychiatric aetiology. The purpose of this review is to consider the main issues involved in the phenotypic characterization of cognition, and to describe the challenges associated with the transition to genome-wide approaches. We conclude by describing the approaches currently being taken by the international consortia involving many investigators in the field internationally (e.g. Cognitive Genomics Consortium; COGENT) to overcome these challenges.
Incidence of colourblindness among 3325 males belonging to 21 endogamous Dhangar castes (shepherds) of Maharashtra, India, has been reported. Of the 21 castes studied 5 lacked the gene for colourblindness, while in other groups it varied from 1% to 55%, with a series average of 2·65%. The low incidence of observed colourblindness has been discussed in the light of the nomadic way of the life of some of the Dhangar castes. The results have been compared with other nomadic populations of Maharashtra. The results, in general, are compatible with the Post and Pickford's hypothesis of differential selection for colourblindness.
Allelic variation in the gene encoding brain-derived neurotrophic factor (BDNF) has been associated with affective disorders, but generally not schizophrenia. Brain-derived neurotrophic factor variants may help clarify the status of schizoaffective disorder.
To test the hypothesis that BDNF haplotypes are associated with psychiatric illness marked by a prominent affective component.
Frequencies of a 5-marker BDNF haplotype were examined in 600 White participants across four diagnostic categories and healthy controls.
Individuals with schizoaffective disorder and other affective disorders were significantly more likely to carry two copies of the most common BDNF haplotype (containing the valine allele of the Val66Met polymorphism) compared with healthy volunteers. Moreover, when compared with people with schizophrenia, individuals with schizoaffective disorder were significantly more likely to carry two copies of the common haplotype.
To our knowledge, this is the first candidate gene study to demonstrate association with schizoaffective disorder but not schizophrenia. Variation in the BDNF gene may be associated with the clinical phenotype of affective dysregulation across several DSM–IV diagnostic categories.
Although neurocognitive deficits have been identified in obsessive-compulsive disorder (OCD), little research has focused on whether these deficits are generalized or specific to a given cognitive domain. We assessed the relative strengths and weaknesses of 26 adult patients with OCD compared to 38 age- and sex-matched healthy volunteers in domains of motor, verbal memory, visual memory, reasoning/problem solving, processing speed processing, and language. Profile analysis revealed an overall neurocognitive deficit of ½ standard deviation in OCD patients versus healthy volunteers, with relative weaknesses in motor and processing speed domains. In contrast, relative strengths were observed in language, verbal memory, and reasoning/problem solving. Our findings demonstrate neurocognitive impairment in OCD that may relate to functional outcome in this population. Findings of specific abnormalities on tasks of motor and processing speed are consistent with a hypothesized role of thalamocortical and basal ganglia regions in the pathogenesis of OCD. (JINS, 2008, 14, 640–645.)
Pulsed laser deposited cerium oxide (CeO2) nanoporous thin film on platinum (Pt) coated glass has been used for immobilization of glucose oxidase (GOx) by electrostatic interaction. Atomic force microscopy studies reveal the formation of nanoporous surface morphology of CeO2 thin film. Differential pulse voltammetric and optical measurements show that the GOx/CeO2/Pt bioelectrode is sensitive to the detection of glucose over the concentration upto 300 mg/dl. A low value of enzyme's kinetic parameter (Michaelis-Menten constant∼1.01 mM) indicates enhanced enzyme affinity of GOx to glucose.
The morphologic variations of mixed totally anomalous pulmonary venous connection are many and varied. In this review, we give an account of all cases previously described as mixed totally anomalous pulmonary venous connection, analyzing in detail those cases where an accurate anatomical description was provided. We identified 182 suitable cases, from 54 investigations, and reviewed the clinical presentation, anatomic variations, diagnostic features, and management of the patients described.
Cross-sectional echocardiography, and cardiac catheterization, provided the necessary diagnostic information, and defined the anatomy before surgery in 139 patients. Magnetic resonance imaging and computerized tomographic angiography had been used for further clarification of the pulmonary venous anatomy. An obstructive pattern of drainage, involving one or more pulmonary veins, had been described in over half of the patients. We then grouped the lesions into categories that have a bearing on the appropriate surgical approach, discussing the appropriate repair for each group. For the overall group, the operative mortality remains high, at 22.9%. We submit that an increased appreciation of various types of mixed totally anomalous pulmonary venous connection may well contribute to improved future surgical management.
A patent vertical vein might be desirable in patients with obstructive totally anomalous pulmonary venous connection with pulmonary hypertension, in order to decrease perioperative pulmonary arterial pressure and avoid pulmonary hypertensive crises. A subset of patients with an unligated vertical vein requires interruption of the vein due to the development of significant left-to-right shunt and right heart failure. We describe here a new device, permitting adjustable ligation of the vertical vein, which permits us to avoid multiple reoperations.
Patients and methods
In five patients, aged 2, 4, 3, 4, and 3 months respectively, and undergoing rechannelling of totally anomalous pulmonary venous connection with an unligated vertical vein, were treated with a device permitting adjusted ligation of the vertical vein over the course of postoperative congestive cardiac failure.
There was no early or late death. Postoperatively, all ligatures were tightened gradually over a period of 24 to 96 hours, maintaining stable haemodynamics. At a mean follow-up of 55.40 months, there was no evidence of congestive heart failure in any patient, the clinical risk score varying from zero to 2, and no requirement of anti-failure medications. Computed tomographic angiograms during follow-up revealed absence of flow through the vertical vein, and ruled out distortion of the left upper pulmonary and left brachiocephalic veins.
Use of a percutaneously adjustable device to ligate the vertical vein allows gradual tightening or loosening of the ligature under optimal physiologic conditions, without re-opening the sternum, or having to resort to another thoracotomy once the reactive components of pulmonary hypertension disappear.