An exploration of factors influencing patient outcomes of psychiatric genetic counseling

Though understanding how different characteristics of the patient and session influence outcomes of genetic counseling (GC) is important, little research data currently exits on this topic. We conducted a retrospective review of charts from patients who attended a specialist psychiatric GC clinic between February 1, 2012 and January 31, 2017. We extracted data to explore the effects of patient and sessionrelated variables on Genetic Counseling Outcome Scale scores (GCOS, validated instrument that measures empowerment). We used ANOVA to analyze the pre-, to one-month post-GC change in GCOS scores in relation to eleven variables. 307 charts were included in analysis. Overall, GCOS scores significantly increased after GC (p\u3c0.0005). No significant differences in GCOS change scores were identified with respect to: sex, ethnicity, diagnosis, mode of referral, type of appointment, genetic counseling student involvement, presence of observers or personal/family history of mental illness. Significant relationships were found between GCOS change scores and mode of delivery of GC (p=0.048, h2 = 0.020) and primary indication for the appointment (understanding recurrence risk versus other, p=0.001, h2 = 0.037). This exploratory study provides the first data on how a number of characteristics of the patient and session influence outcomes of genetic counseling. Understanding the patient and session-related factors that do seem to influence outcomes may allow for adjustment of service delivery strategies to promote the best possible outcomes

Gender Dimorphism in Aspartame-Induced Impairment of Spatial Cognition and Insulin Sensitivity

Previous studies have linked aspartame consumption to impaired retention of learned behavior in rodents. Prenatal exposure to aspartame has also been shown to impair odor-associative learning in guinea pigs; and recently, aspartame-fed hyperlipidemic zebrafish exhibited weight gain, hyperglycemia and acute swimming defects. We therefore investigated the effects of chronic lifetime exposure to aspartame, commencing in utero, on changes in blood glucose parameters, spatial learning and memory in C57BL/6J mice. Morris Water Maze (MWM) testing was used to assess learning and memory, and a random-fed insulin tolerance test was performed to assess glucose homeostasis. Pearson correlation analysis was used to investigate the associations between body characteristics and MWM performance outcome variables. At 17 weeks of age, male aspartame-fed mice exhibited weight gain, elevated fasting glucose levels and decreased insulin sensitivity compared to controls (P<0.05). Females were less affected, but had significantly raised fasting glucose levels. During spatial learning trials in the MWM (acquisition training), the escape latencies of male aspartame-fed mice were consistently higher than controls, indicative of learning impairment. Thigmotactic behavior and time spent floating directionless was increased in aspartame mice, who also spent less time searching in the target quadrant of the maze (P<0.05). Spatial learning of female aspartame-fed mice was not significantly different from controls. Reference memory during a probe test was affected in both genders, with the aspartame-fed mice spending significantly less time searching for the former location of the platform. Interestingly, the extent of visceral fat deposition correlated positively with non-spatial search strategies such as floating and thigmotaxis, and negatively with time spent in the target quadrant and swimming across the location of the escape platform. These data suggest that lifetime exposure to aspartame, commencing in utero, may affect spatial cognition and glucose homeostasis in C57BL/6J mice, particularly in males

Role of pathogenic oral flora in postoperative pneumonia following brain surgery

<p>Abstract</p> <p>Background</p> <p>Post-operative pulmonary infection often appears to result from aspiration of pathogens colonizing the oral cavity. It was hypothesized that impaired periodontal status and pathogenic oral bacteria significantly contribute to development of aspiration pneumonia following neurosurgical operations. Further, the prophylactic effects of a single dose preoperative cefazolin on the oral bacteria were investigated.</p> <p>Methods</p> <p>A matched cohort of 18 patients without postoperative lung complications was compared to 5 patients who developed pneumonia within 48 hours after brain surgery. Patients waiting for elective operation of a single brain tumor underwent dental examination and saliva collection before surgery. Bacteria from saliva cultures were isolated and periodontal disease was scored according to type and severity. Patients received 15 mg/kg cefazolin intravenously at the beginning of surgery. Serum, saliva and bronchial secretion were collected promptly after the operation. The minimal inhibitory concentrations of cefazolin regarding the isolated bacteria were determined. The actual antibiotic concentrations in serum, saliva and bronchial secretion were measured by capillary electrophoresis upon completion of surgery. Bacteria were isolated again from the sputum of postoperative pneumonia patients.</p> <p>Results</p> <p>The number and severity of coexisting periodontal diseases were significantly greater in patients with postoperative pneumonia in comparison to the control group (p = 0.031 and p = 0.002, respectively). The relative risk of developing postoperative pneumonia in high periodontal score patients was 3.5 greater than in patients who had low periodontal score (p < 0.0001). Cefazolin concentration in saliva and bronchial secretion remained below detectable levels in every patient.</p> <p>Conclusion</p> <p>Presence of multiple periodontal diseases and pathogenic bacteria in the saliva are important predisposing factors of postoperative aspiration pneumonia in patients after brain surgery. The low penetration rate of cefazolin into the saliva indicates that its prophylactic administration may not be sufficient to prevent postoperative aspiration pneumonia. Our study suggests that dental examination may be warranted in order to identify patients at high risk of developing postoperative respiratory infections.</p

Sex-dimorphism in Cardiac Nutrigenomics: effect of Trans fat and/or Monosodium Glutamate consumption

<p>Abstract</p> <p>Background</p> <p>A paucity of information on biological sex-specific differences in cardiac gene expression in response to diet has prompted this present nutrigenomics investigation.</p> <p>Sexual dimorphism exists in the physiological and transcriptional response to diet, particularly in response to high-fat feeding. Consumption of <it>Trans</it>-fatty acids (TFA) has been linked to substantially increased risk of heart disease, in which sexual dimorphism is apparent, with males suffering a higher disease rate. Impairment of the cardiovascular system has been noted in animals exposed to Monosodium Glutamate (MSG) during the neonatal period, and sexual dimorphism in the growth axis of MSG-treated animals has previously been noted. Processed foods may contain both TFA and MSG.</p> <p>Methods</p> <p>We examined physiological differences and changes in gene expression in response to TFA and/or MSG consumption compared to a control diet, in male and female C57BL/6J mice.</p> <p>Results</p> <p>Heart and % body weight increases were greater in TFA-fed mice, who also exhibited dyslipidemia (P < 0.05). Hearts from MSG-fed females weighed less than males (P < 0.05). 2-factor ANOVA indicated that the TFA diet induced over twice as many cardiac differentially expressed genes (DEGs) in males compared to females (P < 0.001); and 4 times as many male DEGs were downregulated including <it>Gata4</it>, <it>Mef2d </it>and <it>Srebf2</it>. Enrichment of functional Gene Ontology (GO) categories were related to transcription, phosphorylation and anatomic structure (P < 0.01). A number of genes were upregulated in males and downregulated in females, including pro-apoptotic histone deacetylase-2 (HDAC2). Sexual dimorphism was also observed in cardiac transcription from MSG-fed animals, with both sexes upregulating approximately 100 DEGs exhibiting sex-specific differences in GO categories. A comparison of cardiac gene expression between all diet combinations together identified a subset of 111 DEGs significant only in males, 64 DEGs significant in females only, and 74 transcripts identified as differentially expressed in response to dietary manipulation in both sexes.</p> <p>Conclusion</p> <p>Our model identified major changes in the cardiac transcriptional profile of TFA and/or MSG-fed mice compared to controls, which was reflected by significant differences in the physiological profile within the 4 diet groups. Identification of sexual dimorphism in cardiac transcription may provide the basis for sex-specific medicine in the future.</p

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Recurrence numbers in genetic counselling

Providing recurrence numbers is often considered a fundamental component of genetic counselling. We sought to fill knowledge gaps regarding how often patients actively seek recurrence numbers, and how they impact patient outcomes. We conducted a retrospective chart review at a clinic where patients routinely complete the Genetic Counselling Outcomes Scale [GCOS, measuring empowerment] pre (T1)/post (T2)-appointment. Using ANCOVA we evaluated the effect on T2 GCOS score of: a) receiving recurrence numbers, and b) patient perception of recurrence numbers. Recurrence numbers were a primary indication for 134/300 patients (45%). After counselling about etiology and risk-reducing strategies, 116 patients (39%) opted to receive recurrence numbers, with most (n=64, 55%) perceiving the number to be lower than expected. There was no difference in T2 GCOS scores between those who: a) received recurrence numbers vs. those who did not, or b) perceived the number to be lower than expected vs. those with other perceptions. However, a subset of patients who did not receive recurrence numbers had larger increases in GCOS scores. Our data provide impetus to question the assumption that recurrence numbers should be routinely provided in genetic counselling, and demonstrate that in naturalistic practice optimal patient outcomes are not contingent on receipt of recurrence numbers.Medicine, Faculty ofMedical Genetics, Department ofPsychiatry, Department ofReviewedFacultyGraduat

A Discussion of the Treatment of People with an Intellectual Disability Across Healthcare and the Modernization of Learning Disability Nursing

Aims: A discussion of the treatment of people with an intellectual disability across healthcare and the modernisation of learning disability nursing. Background: Health inequalities are at the forefront of the collective mind of healthcare professionals and politicians, this paper explores why people with an intellectual disability have more health issues, die earlier and sometimes receive poor care, leading to unnecessary suffering and importantly, how this may change. Learning disability nursing has long been viewed as different and less valued, probably due to dual stigmatisation, or lack of understanding of specialist knowledge and skills required. This essential field of nursing is becoming a rare resource in our battle against health inequalities, yet internationally it is becoming recognised as crucial. Design:Discussion Paper. Data Sources:Literature and policy (1971 – 2012). Implications for Nursing:All nurses need to recognise their role in meeting the health care needs of people with an intellectual disability. Health care managers and commissioners should value the unique contribution of learning disability nurse in addressing health inequalities. Conclusion:Learning disabled people, their carers and professionals view the role of the learning disability nurse as central for effectively identifying and meeting health needs, reducing inequalities and barriers, supporting decisions around capacity, consent, best interests and advising and educating professionals. Recommendations for commissioning, nursing and services are made. Summary Statement: Why is this discussion paper needed? People with an intellectual disability have shorter life-spans and receive poor healthcare because of the barriers to good health developed in societies constructed by and for people without a disability. Internationally, the need for learning disability nurses, with their specific knowledge and skills, is being recognised in the battle against early and unnecessary deaths because of discrimination and health inequalities. Learning disability nurses and ‘Strengthening the Commitment’ lead on improving healthcare for learning disabled people and this paper raises the profile of this important health issue. What are the key findings? This discussion paper explores how most of the poor health experienced by people with an intellectual disability is about discriminating healthcare provision and crucially, not because the person has a disability. People with an intellectual disability have greater health needs than others and despite this, nonspecific health professionals often have scant understanding of their disability and health needs. Learning disability nursing as a vital resource has in recent years seen posts reducing in the NHS, with actual and commissioned numbers of registered learning disability nurses dropping. How should the findings be used to influence policy/practice/education/research? People with an intellectual disability and nonspecific staff often feel they are inadequately educated and lack appropriate skills for quality healthcare provision for learning disabled people; this has to change. Sir Johnathon Michael (2008) recommendation 1 advises that all health professionals be competent in supporting learning disabled people in a non-discriminatory way - universities and employers urgently need to adhere to this recommendation. Professionals, learning disabled people and carers state learning disability nurses are vital to acquiring human rights - increased international commissioning for learning disability nurses to enable quality healthcare, education and advice to professionals is pressing