Credit Valley Hospital

PURPOSE OF REVIEW: There is an increasing interest and availability of micro-invasive glaucoma surgery (MIGS) procedures. It is important that this increase is supported by sound, peer-reviewed evidence. This article will define MIGS, review relevant publications in the period of annual review and discuss future directions. RECENT FINDINGS: The results of the pivotal trial comparing a trabecular micro-bypass stent (iStent, Glaukos Corporation, Laguna Hills, CA, USA) combined with phacoemulsification to phacoemulsification alone showed a significantly higher percentage of patients with unmedicated intraocular pressure (IOP) ≤ 21 mmHg, and a comparable safety profile. Initial results are published regarding a second-generation micro-bypass stent (iStent inject, Glaukos Corporation, Laguna Hills, CA, USA), a canalicular scaffold (Hydrus, Ivantis Inc., Irvine, CA, USA) and an ab interno suprachoroidal microstent (CyPass, Transcend Medical, Menlo Park, CA, USA), showing a decrease in mean postoperative IOP. Phaco-Trabectome (Ab interno trabeculectomy Trabectome, NeoMedix Inc., Tustin, CA, USA) was compared to phacotrabeculectomy and showed less IOP reduction, less postoperative complications, and a similar success rate. Similar success rates were found with the comparison of excimer laser trabeculostomy (ELT, AIDA, Glautec AG, Nurnberg, Germany) and selective laser trabeculoplasty. A number of publications review the importance of the location of implantable devices, intraoperative gonioscopy, cost-effectiveness and quality-of-life studies, and randomized clinical trials. SUMMARY: MIGS procedures offer reduction in IOP, decrease in dependence on glaucoma medications and an excellent safety profile. Their role within our glaucoma treatment algorithm continues to be clarified and differs from the role of more invasive glaucoma surgeries such as trabeculectomy or glaucoma drainage devices.

Published population estimates of the prevalence of chronic pain have been highly variable due, in part, to differences in definitions and study methodologies. Designing health care delivery models that address chronic pain and reduce its impact, however, require accurate, up‐to‐date prevalence data. This article first reviews studies that examined the prevalence of chronic pain both internationally and in Canada. The ensuing sections describe a telephone‐based survey of a well‐defined population of adults using a detailed and sequential definition of chronic pain, and well‐validated and reliable data collection tools for establishing the prevalence of chronic pain in Canada. BACKGROUND: While chronic pain appears to be relatively common, published population prevalence estimates have been highly variable, partly due to differences in the definition of chronic pain and in survey methodologies. OBJECTIVES: To estimate the prevalence of chronic pain in Canada using clear case definitions and a validated survey instrument. METHODS: A telephone survey was administered to a representative sample of adults from across Canada using the same screening questionnaire that had been used in a recent large, multicountry study conducted in Europe. RESULTS: The prevalence of chronic pain prevalence for adults older than 18 years of age was 18.9%. This was comparable with the overall mean reported using identical survey questions and criteria for chronic pain used in the European study. Chronic pain prevalence was greater in older adults, and females had a higher prevalence at older ages compared with males. Approximately one‐half of those with chronic pain reported suffering for more than 10 years. Approximately one‐third of those reporting chronic pain rated the intensity in the very severe range. The lower back was the most common site of chronic pain, and arthritis was the most frequently named cause. CONCLUSIONS: A consensus is developing that there is a high prevalence of chronic pain within adult populations living in industrialized nations. Recent studies have formulated survey questions carefully and have used large samples. Unfortunately, a substantial proportion of Canadian adults continue to live with chronic pain that is longstanding and severe.

BACKGROUND: Although isoniazid (INH) is commonly used for treating tuberculosis (TB), it is also effective as preventive therapy. OBJECTIVES: The objective of this review was to estimate the effect of 6 and 12 month courses of INH for preventing TB in HIV-negative people at increased risk of developing active TB. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group trials register, the Cochrane Controlled Trials Register, Medline, Embase and reference lists of articles. We hand-searched Science Citation Index and Index Medicus. SELECTION CRITERIA: Randomised trials of INH preventive therapy for 6 months or more compared with placebo. Follow-up for a minimum of 2 years. Trials enrolling patients with current or previously treated active TB, or with known HIV infection, were excluded. Criteria were applied by two reviewers independently. DATA COLLECTION AND ANALYSIS: Trial quality was assessed by two reviewers independently, and data extracted by one reviewer using a standardized extraction form. MAIN RESULTS: Eleven trials involving 73,375 patients were included. Trials were generally of high quality. Treatment with INH resulted in a relative risk (RR) of developing active TB of 0.40, (95% confidence interval ¿CI¿ 0.31 to 0.52), over two years or longer. There was no significant difference between 6 and 12 month courses (RR of 0.44, 95% CI 0.27 to 0.73 for six months, and 0.38, 95% CI 0.28 to 0.50 for 12 months). Preventive therapy reduced deaths from TB, but this effect was not seen for all cause mortality. INH was associated with hepatotoxicity in 0.36% of people on 6 months treatment and in 0.52% of people treated for 12 months. REVIEWER'S CONCLUSIONS: Isoniazid is effective for the prevention of active TB in diverse at-risk patients, and six and 12 month regimens have a similar effect.

OBJECTIVE: To compare the efficacy of a single intraarticular corticosteroid injection, a supervised physiotherapy program, a combination of the two, and placebo in the treatment of adhesive capsulitis of the shoulder. METHODS: Ninety-three subjects with adhesive capsulitis of <1 year's duration were randomized to 1 of 4 treatment groups: group 1, corticosteroid injection (triamcinolone hexacetonide 40 mg) performed under fluoroscopic guidance followed by 12 sessions of supervised physiotherapy; group 2, corticosteroid injection alone; group 3, saline injection followed by supervised physiotherapy; or group 4, saline injection alone (placebo group). All subjects were taught a simple home exercise program. Subjects were reassessed after 6 weeks, 3 months, 6 months, and 1 year. The primary outcome measure was improvement in the Shoulder Pain and Disability Index (SPADI) score. RESULTS: At 6 weeks, the total SPADI scores had improved significantly more in groups 1 and 2 compared with groups 3 and 4 (P = 0.0004). The total range of active and passive motion increased in all groups, with group 1 having significantly greater improvement than the other 3 groups. At 3 months, groups 1 and 2 still showed significantly greater improvement in SPADI scores than group 4. There was no difference between groups 3 and 4 at any of the followup assessments except for greater improvement in the range of shoulder flexion in group 3 at 3 months. At 12 months, all groups had improved to a similar degree with respect to all outcome measures. CONCLUSION: A single intraarticular injection of corticosteroid administered under fluoroscopy combined with a simple home exercise program is effective in improving shoulder pain and disability in patients with adhesive capsulitis. Adding supervised physiotherapy provides faster improvement in shoulder range of motion. When used alone, supervised physiotherapy is of limited efficacy in the management of adhesive capsulitis.

Hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) are important causes of morbidity and mortality, with mortality rates approaching 62%. HAP and VAP are the second most common cause of nosocomial infection overall, but are the most common cause documented in the intensive care unit setting. In addition, HAP and VAP produce the highest mortality associated with nosocomial infection. As a result, evidence-based guidelines were prepared detailing the epidemiology, microbial etiology, risk factors and clinical manifestations of HAP and VAP. Furthermore, an approach based on the available data, expert opinion and current practice for the provision of care within the Canadian health care system was used to determine risk stratification schemas to enable appropriate diagnosis, antimicrobial management and nonantimicrobial management of HAP and VAP. Finally, prevention and risk-reduction strategies to reduce the risk of acquiring these infections were collated. Future initiatives to enhance more rapid diagnosis and to effect better treatment for resistant pathogens are necessary to reduce morbidity and improve survival.

OBJECTIVES: To describe revisions to the Premature Infant Pain Profile (PIPP) and initial construct validation and feasibility of the Premature Infant Pain Profile-Revised (PIPP-R). METHODS: The PIPP was revised to enhance validity and feasibility. To validate the PIPP-R, data from 2 randomized cross-over studies were utilized to: (1) calculate and compare PIPP and PIPP-R scores in extremely low gestational age infants undergoing a painful and nonpainful event (N=52; dataset #1) and (2) calculate and compare PIPP and PIPP-R scores in assessing the effectiveness of (a) sucrose, (b) non-nutritive sucking (NNS)+sucrose, and (c) facilitated tucking+NNS+sucrose during heel lance (N = 85; dataset #2). Pearson correlations between PIPP and PIPP-R scores were calculated, and Student t tests and 1-way analysis of variance were used to determine construct validity during painful and nonpainful events. To establish feasibility, a survey of 31 Neonatal Intensive Care Unit nurses was conducted. RESULTS: PIPP-R scores were significantly lower during nonpainful (mean, 8.3; SD = 2.9) compared with painful (mean, 9.9; SD=3.1; t95 = 4.51, P = 0.036) events in extremely low gestational age infants in dataset #1. In dataset #2, PIPP-R scores were significantly lower in infants 25 to 41 weeks gestation in the group receiving NNS+sucrose compared with the other 2 groups (F2,79 = 2.9, P<0.05). Overall, nurses rated the PIPP-R as feasible. DISCUSSION: Initial construct validation and feasibility of the PIPP-R was demonstrated. Further testing with infants of varying gestational ages, diagnoses, and pain conditions is required; as is exploration of PIPP-R in relation to other types of physiological and cognitive responses.

BACKGROUND: Systematic symptom reporting by patients and the use of questionnaires such as the Edmonton Symptom Assessment System (ESAS) have potential to improve clinical encounters and patient satisfaction. We review findings from published studies of the ESAS to guide use of the system and to focus research. METHODS: A systematic search for articles from 1991 through 2007 found thirty-nine peer-reviewed papers from 25 different institutions, thirty-three of which focused on patients with cancer. Observations, data, and statistics were collated according to relevance, reliability, validity, and responsiveness. RESULTS: Findings apply predominantly to symptomatic palliative patients with advanced cancer who were no longer receiving active oncologic therapies. Uncertainty about summarizing findings arises from frequent modification of the ESAS (altered items, scales, and time periods). Overall, reliability is established for daily administration. Scores are skewed, with a floor effect, but the relative order of symptoms by mean scores is similar across studies. Emotional symptoms are poorly captured by the depression and anxiety items. An equally weighted summation of scores may estimate a construct of "physical symptom distress," which in turn is related to performance status, palliative goals, quality of life, and well-being. CONCLUSIONS: The ESAS is reliable, but it has restricted validity, and its use requires a sound clinical process to help interpret scores and to give them an appropriate level of attention. Research priorities are to further develop the ESAS for assessing a greater number of important physical symptoms (and to target "physical symptom distress"), and to develop a similar instrument for emotional symptoms.

BACKGROUND: Gastroesophageal reflux disease (GERD) is the most prevalent acid-related disorder in Canada and is associated with significant impairment of health-related quality of life. Since the last Canadian Consensus Conference in 1996, GERD management has evolved substantially. OBJECTIVE: To develop up-to-date evidence-based recommendations relevant to the needs of Canadian health care providers for the management of the esophageal manifestations of GERD. CONSENSUS PROCESS: A multidisciplinary group of 23 voting participants developed recommendation statements using a Delphi approach; after presentation of relevant data at the meeting, the quality of the evidence, strength of recommendation and level of consensus were graded by participants according to accepted principles. OUTCOMES: GERD applies to individuals who reflux gastric contents into the esophagus causing symptoms sufficient to reduce quality of life, injury or both; endoscopy-negative reflux disease applies to individuals who have GERD and a normal endoscopy. Uninvestigated heartburn-dominant dyspepsia - characterised by heartburn or acid regurgitation - includes erosive esophagitis or endoscopy-negative reflux disease, and may be treated empirically as GERD without further investigation provided there are no alarm features. Lifestyle modifications are ineffective for frequent or severe GERD symptoms; over-the-counter antacids or histamine H2-receptor antagonists are effective for some patients with mild or infrequent GERD symptoms. Proton pump inhibitors are more effective for healing and symptom relief than histamine H2-receptor antagonists; their efficacy is proportional to their ability to reduce intragastric acidity. Response to initial therapy - a once-daily proton pump inhibitor unless symptoms are mild and infrequent (fewer than three times per week) - should be assessed at four to eight weeks. Maintenance medical therapy should be at the lowest dose and frequency necessary to maintain symptom relief; antireflux surgery is an alternative for a small proportion of selected patients. Routine testing for Helicobacter pylori infection is unnecessary before starting GERD therapy. GERD is associated with Barrett's epithelium and esophageal adenocarcinoma but the risk of malignancy is very low. Endoscopic screening for Barrett's epithelium may be considered in adults with GERD symptoms for more than 10 years; Barrett's epithelium and low-grade dysplasia generally warrant surveillance; endoscopic or surgical management should be considered for confirmed high-grade dysplasia or malignancy. CONCLUSION: Prospective studies are needed to investigate clinically relevant risk factors for the development of GERD and its complications; GERD progression, on and off therapy; optimal management strategies for typical GERD symptoms in primary care patients; and optimal management strategies for atypical GERD symptoms, Barrett's epithelium and esophageal adenocarcinoma.

INTRODUCTION: The objective is to provide guidance on the role of active surveillance (AS) as a management strategy for low-risk prostate cancer patients and to ensure that AS is offered to appropriate patients assessed by a standardized protocol. Prostate cancer is often a slowly progressive or sometimes non-progressive indolent disease diagnosed at an early stage with localized tumours that are unlikely to cause morbidity or death. Standard active treatments for prostate cancer include radiotherapy (RT) or radical prostatectomy (RP), but the harms from over diagnosis and overtreatment are of a significant concern. AS is increasingly being considered as a management strategy to avoid or delay the potential harms caused by unnecessary radical treatment. METHODS: A literature search of MEDLINE, EMBASE, the Cochrane library, guideline databases and relevant meeting proceedings was performed and a systematic review of identified evidence was synthesized to make recommendations relating to the role of AS in the management of localized prostate cancer. RESULTS: No exiting guidelines or reviews were suitable for use in the synthesis of evidence for the recommendations, but 59 reports of primary studies were identified. Due to studies being either non-comparative or heterogeneous, pooled meta-analyses were not conducted. CONCLUSION: The working group concluded that for patients with low-risk (Gleason score ≤6) localized prostate cancer, AS is the preferred disease management strategy. Active treatment (RP or RT) is appropriate for patients with intermediate-risk (Gleason score 7) localized prostate cancer. For select patients with low-volume Gleason 3+4=7 localized prostate cancer, AS can be considered.

BACKGROUND: Low maternal vitamin B(12) status may be a risk factor for neural tube defects (NTDs). Prior studies used relatively insensitive measures of B(12), did not adjust for folate levels, and were conducted in countries without folic acid food fortification. In Canada, flour has been fortified with folic acid since mid-1997. METHODS: We completed a population-based case-control study in Ontario. We measured serum holotranscobalamin (holoTC), a sensitive indicator of B(12) status, at 15 to 20 weeks' gestation. There were 89 women with an NTD and 422 unaffected pregnant controls. A low serum holoTC was defined as less than 55.3 pmol/L, the bottom quartile value in the controls. RESULTS: The geometric mean serum holoTC levels were 67.8 pmol/L in cases and 81.2 pmol/L in controls. There was a trend of increasing risk with lower levels of holoTC, reaching an adjusted odds ratio of 2.9 (95% confidence interval = 1.2-6.9) when comparing the lowest versus highest quartile. CONCLUSIONS: There was almost a tripling in the risk for NTD in the presence of low maternal B(12) status, measured by holoTC. The benefits of adding synthetic B(12) to current recommendations for periconceptional folic acid tablet supplements or folic-acid-fortified foods need to be considered. It remains to be determined what fraction of NTD cases in a universally folate-fortified environment might be prevented by higher periconceptional intake of B(12).

In order to determine the significance of trisomy mosaicism of an autosome other than chromosomes 13, 18, 20, and 21, 151 such cases diagnosed prenatally through amniocentesis were reviewed. These rare trisomy mosaicism cases include 54 from 17 cytogenetic laboratories, 34 from a previous North American mosaicism survey, and 63 from published reports. All were cases of true mosaicism with information available on pregnancy outcome, and with no evidence of biased ascertainment. There were 11 cases of 46/47, +2; 2 of 46/47, +3; 2 of 46/47, +4; 5 of 46/47, +5; 3 of 46/47, +6; 8 of 46/47, +7; 14 of 46/47, +8; 25 of 46/47, +9; 2 of 46/47, +11; 23 of 46/47, +12; 5 of 46/47, +14; 11 of 46/47, +15; 21 of 46/47, +16; 7 of 46/47, +17; 1 of 46/47, +19; and 11 of 46/47, +22. As to the risk of an abnormal outcome, the data showed a very high risk (> 60 per cent) for 46/47, +2, 46/47, +16, and 46/47, +22; a high risk (40-59 per cent) for 46/47, +5, 46/47, +9, 46/47, +14, and 46/47, +15; a moderately high risk (20-39 per cent) for 46/47, +12; a moderate risk (up to 19 per cent) for 46/47, +7 and 46/47, +7 and 46/47, +8; a low risk for 46/47, +17; and an undetermined risk, due to lack of cases, for the remaining autosomal trisomy mosaics. Most cases were evaluated at birth or at termination, so subtle abnormalities may have escaped detection and developmental retardation was not evaluated at all. Comparison of the phenotypes of prenatally diagnosed abnormal cases and postnatally diagnosed cases with the same diagnosis showed considerable concordance. Since the majority of anomalies noted are prenatally detectable with ultrasound, an ultrasound examination should be performed in all prenatally diagnosed cases. In cytogenetic confirmation studies, the data showed much higher confirmation rates in cases with abnormal outcomes than in cases with normal outcomes [81 per cent vs. 55 per cent for fibroblasts (from skin, fetal tissue, and/or cord); 88 per cent vs. 46 per cent for placental cells; 22 per cent vs. 10 per cent for blood cells]. The confirmation rate reached 85 per cent when both fibroblasts and placental tissues were studied in the same case (with trisomic cells found in one or the other, or both). Therefore, one must emphasize that both fibroblasts and placental tissues should be studied. Except for 46/47, +8 and 46/47, +9, PUBS is of limited value for prenatal diagnosis of rate trisomy mosaicism. DNA studies for UPD are suggested for certain chromosomes with established imprinting effects, such as chromosomes 7, 11, 14, and 15, and perhaps for chromosomes 2 and 16, where imprinting effects are likely.

BACKGROUND: There is no consensus on the best technique for lung isolation for thoracic surgery. In this study, we compared the clinical performance of three bronchial blockers (BBs) available in North America with left-sided double-lumen tubes (DLTs) for lung isolation in patients undergoing left-sided thoracic surgery. METHODS: One hundred four patients undergoing left-sided thoracotomy or video-assisted thoracoscopic surgery were randomly assigned to one of the four lung isolation groups (n = 26/group). Lung isolation was with an Arndt wire-guided BB (Cook Critical Care, Bloomington, IN), a Cohen Flexi-tip BB (Cook Critical Care) or a Fuji Uni-blocker (Fuji Systems, Tokyo) or with a left-sided DLT (Mallinckrodt Medical, Cornamadde, Athlone, Westmeath, Ireland). Anesthetic management and lung isolation were performed according to a standardized protocol. Each group was randomly subdivided into two subgroups (n = 13/subgroup): immediate suction (at the time of insertion of the lung isolation device) (Subgroup I) or delayed suction (20 min after insertion of the lung separation device) (Subgroup D) according to when suction was applied to the BB suction channel or the bronchial lumen of the DLT. Using a verbal analog scale, lung collapse was assessed by the surgeons, who were blinded to the lung isolation technique. RESULTS: There was no difference among the lung isolation devices in lung collapse scores at 0 (P = 0.66), 10 (P = 0.78), or 20 min (P = 0.51) after pleural opening. The time to initial lung isolation was less for DLTs (93 +/- 62 s) than BBs (203 +/- 132) (P = 0.0001). There were no differences among the BBs in the time to lung isolation (P = 0.78). There were significantly more repositions after initial placement of the lung isolation device with BBs (35 incidents) than with DLTs (two incidents) (P = 0.009). The Arndt BB required repositioning more frequently (16 incidents) than the Cohen BB (8) or the Fuji BB (11) (P = 0.032). CONCLUSIONS: The three BBs provided equivalent surgical exposure to left-sided DLTs during left-sided open or video-assisted thoracoscopic surgery thoracic procedures. BBs required longer to position and required intraoperative repositioning more often. The Arndt BB needed to be repositioned more often than the other BBs.

Abstract Copy number variations (CNVs) are implicated across many neurodevelopmental disorders (NDDs) and contribute to their shared genetic etiology. Multiple studies have attempted to identify shared etiology among NDDs, but this is the first genome-wide CNV analysis across autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), schizophrenia (SCZ), and obsessive-compulsive disorder (OCD) at once. Using microarray (Affymetrix CytoScan HD), we genotyped 2,691 subjects diagnosed with an NDD (204 SCZ, 1,838 ASD, 427 ADHD and 222 OCD) and 1,769 family members, mainly parents. We identified rare CNVs, defined as those found in &lt;0.1% of 10,851 population control samples. We found clinically relevant CNVs (broadly defined) in 284 (10.5%) of total subjects, including 22 (10.8%) among subjects with SCZ, 209 (11.4%) with ASD, 40 (9.4%) with ADHD, and 13 (5.6%) with OCD. Among all NDD subjects, we identified 17 (0.63%) with aneuploidies and 115 (4.3%) with known genomic disorder variants. We searched further for genes impacted by different CNVs in multiple disorders. Examples of NDD-associated genes linked across more than one disorder (listed in order of occurrence frequency) are NRXN1 , SEH1L , LDLRAD4 , GNAL , GNG13 , MKRN1 , DCTN2, KNDC1 , PCMTD2 , KIF5A , SYNM , and long non-coding RNAs: AK127244 and PTCHD1-AS . We demonstrated that CNVs impacting the same genes could potentially contribute to the etiology of multiple NDDs. The CNVs identified will serve as a useful resource for both research and diagnostic laboratories for prioritization of variants.

PURPOSE: The purpose of this study was to describe the fluidics of a novel non-valved glaucoma implant designed to prevent hypotony and compare the fluidics of this device with two commonly used non-valved glaucoma devices. METHODS: The XEN 45 micro-fistula implant was designed to limit hypotony by virtue of its length and width according to the Hagen-Poiseuille equation. Flow testing was performed using a syringe pump and pressure transducer at multiple flow rates. The pressure differentials across the XEN implant, the Ex-Press implant, and 10 mm of silicone tubing from a Baerveldt implant at a physiologic flow rate (2.5 μL/min) were extrapolated. RESULTS: The XEN 45 achieved a steady-state pressure calculated at 7.56 mm Hg at 2.5 μL/min. At the same flow rate, the Ex-Press device and Baerveldt tubing reached steady-state pressures of 0.09 and 0.01 mm Hg, respectively. CONCLUSIONS: Under flow testing, the XEN micro-fistula implant was able to maintain backpressure above numerical hypotony levels without the use of complex valve systems. This is due to the XEN implant's design, derived from the principles that dictate Newtonian fluids.

sixty-one new continuous ambulatory peritoneal dialysis (CAPD) patients were allocated to a Y connector disinfectant (Amuchina, Italy) and 63 to standard systems (Baxter Systems II &amp; III) in a randomized clinical trial addressing peritonitis rates in 8 CAPD programs in 6 Canadian cities. In the Y connector-disinfectant group, 15 patients experienced 21 episodes of peritonitis in 452 patient-months or 1 per 21.53 patient-months. In the standard systems group, 30 patients experienced 47 episodes of peritonitis in 467 patient-months or 1 per 9.93 patient-months ( p = 0.009). The peritonitis risk reduction was 61% (95% confidence limits 27–79%). Exit-site infections occurred in 36% of each group. Prior to the development of exit -site infection, the monthly risk for peritonitis was 3.12% for the Y connector disinfectant system and 7.37% for the standard system. After an exit -site infection, these probabilities increased to 6.15% and 15.47%, respectively. Skin organisms were responsible for peritonitis in 8/21 (38%) in the Y connector-disinfectant group and 30/47 (64%) in the standard group. There were 75 days hospitalized for peritonitis in the Y connector-disinfectant group compared to 257 days for the standard group. The Y connector disinfectant system decreases the peritonitis rate through its effect on skin organisms. Exit -site infections are a major source of organisms responsible for peritonitis.

BACKGROUND: The current study builds on previous research demonstrating a link between anxiety and inhospital recurrent ischemic and arrhythmic events, by examining the effects of persistent anxiety on recurrent events 1 year later. METHODS: 913 patients with unstable angina (UA) and myocardial infarction (MI) from 12 coronary care units were recruited, and follow-up data were collected at 6 and 12 months after the event. Measures included cardiac symptomatology, healthcare utilization, the anxiety subscale of the Primary Care Evaluation of Mental Disorders , the phobic anxiety subscale of the Middlesex Hospital Questionnaire, and the Beck Depression Inventory. RESULTS: Over one third of participants with UA and MI experienced elevated anxiety at the time of the ischemic event, and these symptoms persisted for 1 year in 50% of anxious participants. Although participants with anxiety reported more atypical cardiac symptomatology, the prevalence of typical cardiac symptoms such as chest pain did not differ based on anxiety. After controlling for the severity of the coronary event, family income, sex, diabetes, and smoking, the following variables were significantly predictive of self-reported recurrent cardiac events at 6 months or 1 year: older age, family history of cardiovascular disease, greater depressive symptomatology at baseline, and anxiety at 6 months. Only 38% of anxious patients were asked about such symptoms, indicating underutilization of effective psychotherapeutic treatment. CONCLUSIONS: Over and above the effects of depressive symptomatology (among other confounding variables), nonphobic anxiety appears to have a negative effect on self-reported outcome following an ischemic coronary event. Anxiety symptomatology is underrecognized and undertreated, and examination of effects of treatment on secondary prevention must be pursued.

Neuroendocrine (NE) differentiation in prostate cancer is typically detected by immunohistochemistry as single cells in conventional adenocarcinoma. Prostatic NE tumors, such as carcinoid or small cell carcinoma, are rare and large cell NE carcinoma (LCNEC) is described only in case reports. We identified 7 cases of LCNEC and compiled their clinicopathologic characteristics. In 6 cases, there was a history of adenocarcinoma treated with hormone therapy for a mean of 2.4 years (range: 2 to 3 y). The remaining case was de novo LCNEC. LCNEC was incidentally diagnosed in palliative transurethral resection specimens in 5 cases. The mean patient age at diagnosis with LCNEC was 67 years (range: 43 to 81 y). LCNEC comprised solid sheets and ribbons of cells with abundant pale to amphophilic cytoplasm, large nuclei with coarse chromatin and prominent nucleoli along with brisk mitotic activity and foci of necrosis. In 6 cases, there were foci of admixed adenocarcinoma, 4 of which showed hormone therapy effects. LCNEC was strongly positive for CD56, CD57, chromogranin A, synaptophysin, and P504S/alpha methylacyl CoA racemase. There was strong bcl-2 overexpression, expression of MIB1, and p53 in >50% of nuclei, focally positive staining for prostate specific antigen and prostatic acid phosphatase and negative androgen receptor staining. Follow-up was available for 6 patients, all of who died with metastatic disease at mean of 7 months (range: 3 to 12 mo) after platinum-based chemotherapy. LCNEC of prostate is a distinct clinicopathologic entity that typically manifests after long-term hormonal therapy for prostatic adenocarcinoma and likely arises through clonal progression under the selection pressure of therapy.

Rare copy number variants (CNVs) disrupting ASTN2 or both ASTN2 and TRIM32 have been reported at 9q33.1 by genome-wide studies in a few individuals with neurodevelopmental disorders (NDDs). The vertebrate-specific astrotactins, ASTN2 and its paralog ASTN1, have key roles in glial-guided neuronal migration during brain development. To determine the prevalence of astrotactin mutations and delineate their associated phenotypic spectrum, we screened ASTN2/TRIM32 and ASTN1 (1q25.2) for exonic CNVs in clinical microarray data from 89 985 individuals across 10 sites, including 64 114 NDD subjects. In this clinical dataset, we identified 46 deletions and 12 duplications affecting ASTN2. Deletions of ASTN1 were much rarer. Deletions near the 3' terminus of ASTN2, which would disrupt all transcript isoforms (a subset of these deletions also included TRIM32), were significantly enriched in the NDD subjects (P = 0.002) compared with 44 085 population-based controls. Frequent phenotypes observed in individuals with such deletions include autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), speech delay, anxiety and obsessive compulsive disorder (OCD). The 3'-terminal ASTN2 deletions were significantly enriched compared with controls in males with NDDs, but not in females. Upon quantifying ASTN2 human brain RNA, we observed shorter isoforms expressed from an alternative transcription start site of recent evolutionary origin near the 3' end. Spatiotemporal expression profiling in the human brain revealed consistently high ASTN1 expression while ASTN2 expression peaked in the early embryonic neocortex and postnatal cerebellar cortex. Our findings shed new light on the role of the astrotactins in psychopathology and their interplay in human neurodevelopment.

A palaeomagnetic pole position, derived from a precisely dated primary remanence, with minimal uncertainties due to secular variation and structural correction, has been obtained for China’s largest dyke swarm, which trends for about 1000 km in a NNW direction across the North China craton. Positive palaeomagnetic contact tests on two dykes signify that the remanent magnetization is primary and formed during initial cooling of the intrusions. The age of one of these dykes, based on U–Pb dating of primary zircon, is 1769.1±2.5Ma. The mean palaeomagnetic direction for 19 dykes, after structural correction, is D=36°, I=−5°, k=63, α95=4°, yielding a palaeomagnetic pole at Plat=36°N, Plong=247°E, dp=2°, dm=4° and a palaeolatitude of 2.6°S. Comparison of this pole position with others of similar age from the Canadian Shield allows a continental reconstruction that is compatible with a more or less unchanged configuration of Laurentia, Siberia and the North China craton since about 1800Ma

Epilepsy represents a multifaceted group of disorders divided into two broad categories, partial and generalized, based on the seizure onset zone. The identification of the neuroanatomic site of seizure onset depends on delineation of seizure semiology by a careful history together with video-EEG, and a variety of neuroimaging technologies such as MRI, fMRI, FDG-PET, MEG, or invasive intracranial EEG recording. Temporal lobe epilepsy (TLE) is the commonest form of focal epilepsy and represents almost 2/3 of cases of intractable epilepsy managed surgically. A history of febrile seizures (especially complex febrile seizures) is common in TLE and is frequently associated with mesial temporal sclerosis (the commonest form of TLE). Seizure auras occur in many TLE patients and often exhibit features that are relatively specific for TLE but few are of lateralizing value. Automatisms, however, often have lateralizing significance. Careful study of seizure semiology remains invaluable in addressing the search for the seizure onset zone.