Five-year results after total knee arthroplasty in lymphoedema and lipoedema: encouraging functional and clinical outcomes and low rates of infection.

BACKGROUND: The aim of this study was to define outcomes after total knee arthroplasty (TKA) in lymphoedema and lipoedema patients managed by a multidisciplinary team and daily compression bandaging. METHODS: A retrospective study was performed in a single centre. Between 2007 and 2018, 36 TKA procedures were performed on 28 consecutive patients with a diagnosis of lymphoedema and lipoedema. Oxford Knee Scores (OKS), EuroQol-5D (EQ-5D) scores, satisfaction scores, radiographs, and complications were obtained at the final follow-up. Patients were admitted to the hospital up to two weeks prior to surgery and remained on the ward for daily compression bandaging by the specialist lymphoedema team. RESULTS: Over the study period, 36 TKAs were performed on 28 patients (5 males, 23 females) with a mean age of 71 years (range 54-90). Of these, 30 TKAs were in patients with lymphoedema, five with lipoedema, and one with a dual diagnosis. Overall, 28 TKAs (21 patients) were available at the final follow-up with a mean follow-up time of 61 months (range 9-138). The mean BMI was 38.5 kg/m2. The mean pre-operative and post-operative Oxford Knee Score increased from 18 (range 2-38) to 29 (range 10-54); p < 0.001. EQ-5D score increased from 0.48 (range 0.15-0.80) to 0.74 (0.34-1.00) (p < 0.001). Mean post-operative satisfaction was 7.6/10 (range 2-10), with 89.3% TKAs satisfied. Complications were one (4%, 1/28) deep vein thrombosis, one superficial wound infection, one prosthetic joint infection, one stiff knee requiring manipulation, and one intra-operative femoral fracture. CONCLUSIONS: Lymphoedema and lipoedema should not be seen as barriers to TKA if adopting a multidisciplinary approach.

The role of routine groin ultrasonography in the management of inguinal hernia.

BACKGROUND: Groin ultrasonography (US) has been used as an adjunct to inguinal hernia diagnosis, but there is limited evidence as to whether its use affects surgical decision-making. The primary aim of this study was to examine whether groin US affects surgical management of inguinal hernia; the secondary goal was to estimate the frequency of groin US ordered before surgical consultation. METHODS: We performed a retrospective chart review of 400 consecutive patients aged older than 18 years referred to 1 of 4 general surgeons in Calgary, Alberta, for inguinal hernia between January 2014 and January 2015. Bilateral groin examinations were entered as separate entries into the database. Outcomes assessed included the frequency of groin US examinations performed within 1 year before the general surgery consultation, presence of inguinal hernia on clinical examination (CE), presence of inguinal hernia on groin US, and whether the hernia proceeded to herniorrhaphy. RESULTS: A total of 476 groins in the 400 patients (354 [88.5%] male; mean age 53.5 yr [standard deviation 15.2 yr]) were evaluated for a hernia during the study period. Groin US was performed before general surgery consultation in 336 cases (70.6%). Overall, 364 (76.5%) of the hernias were clinically palpable; of the 364, 220 (60.4%) had preconsultation US, even in the presence of a positive CE finding. Of the 112 groins that did not have a clinically palpable hernia, 103 (92.0%) underwent preconsultation US. Of the 476 groins, 315 (66.2%) underwent inguinal hernia repair: 310 (85.2%) of the 364 with clinically palpable hernias and 5 (4.8%) of the 103 with clinically negative findings but positive groin US findings. Surgical decision-making based on CE findings occurred in 390 cases (81.9%) overall, whereas surgery based on groin US findings alone occurred in 5 of 336 cases (1.5%). CONCLUSION: Routine groin US was frequently performed before general surgery consultation, whether a hernia was detectable on clinical examination or not. Positive groin US results alone infrequently affected whether the patient proceeded to surgery. Clinical examination findings played a larger role in surgical decision-making than groin US results. Eliminating the practice of routine groin US may provide considerable health care cost savings.

Sex-Dependent Shared and Nonshared Genetic Architecture Across Mood and Psychotic Disorders.

BACKGROUND: Sex differences in incidence and/or presentation of schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) are pervasive. Previous evidence for shared genetic risk and sex differences in brain abnormalities across disorders suggest possible shared sex-dependent genetic risk. METHODS: We conducted the largest to date genome-wide genotype-by-sex (G×S) interaction of risk for these disorders using 85,735 cases (33,403 SCZ, 19,924 BIP, and 32,408 MDD) and 109,946 controls from the PGC (Psychiatric Genomics Consortium) and iPSYCH. RESULTS: Across disorders, genome-wide significant single nucleotide polymorphism-by-sex interaction was detected for a locus encompassing NKAIN2 (rs117780815, p = 3.2 × 10-8), which interacts with sodium/potassium-transporting ATPase (adenosine triphosphatase) enzymes, implicating neuronal excitability. Three additional loci showed evidence (p < 1 × 10-6) for cross-disorder G×S interaction (rs7302529, p = 1.6 × 10-7; rs73033497, p = 8.8 × 10-7; rs7914279, p = 6.4 × 10-7), implicating various functions. Gene-based analyses identified G×S interaction across disorders (p = 8.97 × 10-7) with transcriptional inhibitor SLTM. Most significant in SCZ was a MOCOS gene locus (rs11665282, p = 1.5 × 10-7), implicating vascular endothelial cells. Secondary analysis of the PGC-SCZ dataset detected an interaction (rs13265509, p = 1.1 × 10-7) in a locus containing IDO2, a kynurenine pathway enzyme with immunoregulatory functions implicated in SCZ, BIP, and MDD. Pathway enrichment analysis detected significant G×S interaction of genes regulating vascular endothelial growth factor receptor signaling in MDD (false discovery rate-corrected p < .05). CONCLUSIONS: In the largest genome-wide G×S analysis of mood and psychotic disorders to date, there was substantial genetic overlap between the sexes. However, significant sex-dependent effects were enriched for genes related to neuronal development and immune and vascular functions across and within SCZ, BIP, and MDD at the variant, gene, and pathway levels.

Dual-mobility bearings in complex revision hip arthroplasty.

BACKGROUND: Revision total hip arthroplasty (rTHA) is associated with an increased dislocation risk. Dual-mobility (DM) bearings have been used to address this issue. Such constructs offer increased range of motion and enhanced stability whilst avoiding some issues associated with fully-constrained devices. DM bearings have been used in our unit since 2013. METHODS: All rTHA cases since 2013 were reviewed using the following criteria: (1) use of a DM bearing; (2) extensive soft tissue or bone loss resulting from ARMD, infection or multiple revisions, or requiring custom or megaprosthetic reconstruction; (3) minimum 2-month follow-up. RESULTS: 52 cases were identified with a median of 2 previous operations (range 1-6) and mean follow-up of 14 (2-41) months. The Novae-Stick component was used in 50 cases, the Avantage in 2 and the Trident MDM in 1 case. 19 required acetabular reconstruction using trabecular metal and four required custom acetabular components. 19 required femoral reconstruction with a proximal or total femoral replacement.Postoperatively, 8 patients (15.4%) sustained a dislocation at a mean of 1.6 (range 1-3) months. 3 (5.8%) requiring re-revision. 1 required excision arthroplasty and 2 a constrained liner, 1 of which went on to have further instability. There were no intraprosthetic dislocations. CONCLUSIONS: Dual-mobility components are a viable option in the complex rTHA setting. Early dislocations can occur but the rate of instability is acceptable in this high-risk group.

Breast cancer polygenic risk scores: a 12-month prospective study of patient reported outcomes and risk management behavior.

PURPOSE: To prospectively assess patient reported outcomes and risk management behavior of women choosing to receive (receivers) or decline (decliners) their breast cancer polygenic risk score (PRS). METHODS: Women either unaffected or affected by breast cancer and from families with no identified pathogenic variant in a breast cancer risk gene were invited to receive their PRS. All participants completed a questionnaire at study enrollment. Receivers completed questionnaires at two weeks and 12 months after receiving their PRS, and decliners a second questionnaire at 12 months post study enrollment. RESULTS: Of the 208 participants, 165 (79%) received their PRS. Among receivers, there were no changes in anxiety or distress following testing. However, compared to women with a low PRS, those with a high PRS reported greater genetic testing-specific distress, perceived risk, decisional regret, and less genetic testing-positive response. At 12 months, breast screening and uptake of risk-reducing strategies were consistent with current Australian guidelines of breast cancer risk management. Reasons for declining PRS included being unable to attend the appointment in person and concerns over potential emotional response. CONCLUSION: The outcomes of the study provide insight into women's responses to receiving PRS and highlight the issues that need to be addressed in the associated model of genetic counseling.

Mental health screening amongst police officers: factors associated with under-reporting of symptoms.

BACKGROUND: Mental health screening in the workplace aims to identify employees who are becoming symptomatic, in order to provide timely support and evidence-based interventions to those affected. Given the stigma associated with mental illness, accurate disclosure of mental health symptoms cannot be assumed. The present study sought to investigate factors associated with the accurate reporting of mental health symptoms amongst police officers. METHODS: A total of 90 serving police officers completed identical mental health screening surveys, one administered by the employer and the other anonymously by an independent organisation. Responses were then linked to compare differences in the number and severity of mental health symptoms reported on each questionnaire. RESULTS: Comparisons of matched self-report scores indicated that employees under-reported symptoms of mental health disorders when completing screening administered by their employer, with only 76.3% of symptoms declared. Under-reporting occurred regardless of gender and symptom type. Less senior staff (p = 0.05) and those with the most severe post-traumatic stress disorder and common mental disorder symptoms (p = 0.008) were significantly more likely to under-report symptoms. CONCLUSIONS: Employer-administered mental health screening is not able to accurately capture all mental health symptoms amongst first responders. The fact that the severity of symptoms predicted the level of under-reporting means that simple changes to cut-off values cannot correct this problem.

Clinical outcomes and dislocation rates after hip reconstruction using the Bioball system.

INTRODUCTION: Instability accounts for 1/3 of revision total hip arthroplasty (rTHA) performed in the UK. Removal of well-fixed femoral stems in rTHA is challenging with a risk of blood loss and iatrogenic damage to the femur. The Bioball universal adaptor (BUA), a modular head neck extension adaptor, provides a mechanism for optimisation of femoral offset, leg length and femoral anteversion. This can avoid the need for femoral stem revision in selected cases.The aim of this study is to present the clinical results and rate of instability following revision with this BUA at a minimum of 2 years follow-up. PATIENTS AND METHODS: A review of our prospectively collected database was performed. All patients treated with the Bioball device were included. Clinical and radiologic review were performed pre- and post-surgery. Specific enquiry for instability was made. The Oxford Hip Score (OHS), EuroQol (EQ-5D) score and WOMAC scores were calculated pre-and post-operatively. Complications were recorded. RESULTS: 32 rTHA procedures were performed using the Bioball device between 2013 and 2016. 4 patients did not wish to complete post-operative questionnaires. 2 patients (2/28, 7%) complained of recurrent dislocations following their rTHA procedure. 1 patient complained of instability but no dislocation. The median pre-operative EQ-5D was 0.195 (range -0.07-0.85), OHS was 20 (range 5-43) and WOMAC was 29.8 (range 15.5-52.3). The median EQ-5D was 0.85 (range 0.59-1), OHS was 39 (range 21-48) and WOMAC was 91.1 (range 44.5-99.2) at final follow-up. There were significant improvements in the EQ-5D (p = 0.0009), OHS (p = 0.0004) and WOMAC (p = 0.0001). CONCLUSION: The BUA is associated with significant functional improvement and relatively low dislocation rates in revision THA. It is a viable option for use in the revision setting.

Early Routine Use of Upper GI Contrast Series Post Paraesophageal Hernia Repair: A Single Institution Consecutive Case Series.

INTRODUCTION: There is conflicting evidence with regard to the routine use of upper gastrointestinal contrast series in detecting early complications post paraesophageal hernia repair (PEHR). METHODS: All cases booked for a PEHR between January 2007 and September 2015 were identified using hospital records. Standard demographic, operation, and imaging data were extracted. RESULTS: We retrospectively identified 391 PEHR cases between January 2007 and September 2015. The mean age at the index operation was 66.7 years with a female predominance. The majority of index operations were elective and completed for a large paraesophageal hernia. Contrast studies were reported as normal in 70.6%, a leak in 0.3%, an obstruction in 27.9%, and early recurrence in 1.0%. Reoperation was required in 1.8% of cases. CONCLUSION: Routine upper gastrointestinal contrast studies post-PEHR changed management in 0.8% of cases and were unhelpful in determining the need for early reoperation in 57.1% of cases requiring reoperation.

Sleeve gastrectomy and hypertension: a systematic review of long-term outcomes.

INTRODUCTION: Bariatric surgery has been shown to be a safe and durable intervention for patients struggling with obesity and metabolic syndrome, including hypertension. Buchwald et al. reported hypertension resolution rates in 67.1% and improvement in 78.5% following aggregate bariatric surgery. The laparoscopic sleeve gastrectomy (LSG) is becoming increasingly utilized as a primary bariatric surgery, but lacks long-term outcome data. There are a growing number of studies reporting outcome data beyond 5 years. OBJECTIVE: This study aims to systematically evaluate the efficacy of laparoscopic sleeve gastrectomy on hypertension amongst obese patients. MATERIALS AND METHODS: A comprehensive literature search was conducted through Medline, Embase, Scopus, Web of Science, Dare, Cochrane library, and HTA database. The search terms used were broad: sleeve gastrectomy AND hypertension OR blood pressure. Adult patients undergoing LSG with follow-up hypertension outcome results of at least 5 years were included. Revisional surgeries were excluded. Two independent reviewers were used. RESULTS: Fourteen studies were included in this systematic review, which included 3550 subjects in total. Mean age was 41.1 ± 10.7 years. Mean pre-operative BMI and weight were 47.7 ± 8.83 kg/m2 and 272.8 ± 48.4 lb, respectively. Pre-operative prevalence of hypertension was 36.5% (range 6.7-91%) which dropped to 14.79% (range 0-33.3%) at approximately 5-year follow-up. Hypertension resolved in 62.17% (range 0-100%) of patients and improved in 35.7% (range 13.3-76.9%) at a mean of 5.35 years of follow-up. CONCLUSION: From this systematic review, LSG is an effective intervention for bariatric patients with hypertension. In addition to the observed reduction in the incidence of hypertension, it is likely that LSG may lead to additional health system benefits such as cost savings due to reductions in antihypertensive medications. Further prospective studies should include estimates of cost savings associated with reductions in chronic antihypertensive medication usage.

Comprehensive cross-disorder analyses of CNTNAP2 suggest it is unlikely to be a primary risk gene for psychiatric disorders.

The contactin-associated protein-like 2 (CNTNAP2) gene is a member of the neurexin superfamily. CNTNAP2 was first implicated in the cortical dysplasia-focal epilepsy (CDFE) syndrome, a recessive disease characterized by intellectual disability, epilepsy, language impairments and autistic features. Associated SNPs and heterozygous deletions in CNTNAP2 were subsequently reported in autism, schizophrenia and other psychiatric or neurological disorders. We aimed to comprehensively examine evidence for the role of CNTNAP2 in susceptibility to psychiatric disorders, by the analysis of multiple classes of genetic variation in large genomic datasets. In this study we used: i) summary statistics from the Psychiatric Genomics Consortium (PGC) GWAS for seven psychiatric disorders; ii) examined all reported CNTNAP2 structural variants in patients and controls; iii) performed cross-disorder analysis of functional or previously associated SNPs; and iv) conducted burden tests for pathogenic rare variants using sequencing data (4,483 ASD and 6,135 schizophrenia cases, and 13,042 controls). The distribution of CNVs across CNTNAP2 in psychiatric cases from previous reports was no different from controls of the database of genomic variants. Gene-based association testing did not implicate common variants in autism, schizophrenia or other psychiatric phenotypes. The association of proposed functional SNPs rs7794745 and rs2710102, reported to influence brain connectivity, was not replicated; nor did predicted functional SNPs yield significant results in meta-analysis across psychiatric disorders at either SNP-level or gene-level. Disrupting CNTNAP2 rare variant burden was not higher in autism or schizophrenia compared to controls. Finally, in a CNV mircroarray study of an extended bipolar disorder family with 5 affected relatives we previously identified a 131kb deletion in CNTNAP2 intron 1, removing a FOXP2 transcription factor binding site. Quantitative-PCR validation and segregation analysis of this CNV revealed imperfect segregation with BD. This large comprehensive study indicates that CNTNAP2 may not be a robust risk gene for psychiatric phenotypes.

A Shorter Circular Stapler Height at the Gastrojejunostomy during a Roux-En-Y Gastric Bypass Results in Less Strictures and Bleeding Complications.

The laparoscopic Roux-en-Y gastric bypass (LRYGB) is prone to a number of complications, most notably at the gastrojejunostomy (GJ) staple line. The circular stapler technique is a common method used to create the GJ anastomosis. Although recent studies have shown a decreased rate of anastomotic strictures with shorter stapler heights, the optimal circular stapler height to use remains controversial. We therefore completed a retrospective cohort study within the Alberta Provincial Bariatric Program (APBP) to compare outcomes between the 3.5 mm and 4.8 mm stapler heights. We identified 215 patients who had a LRYGB done between the years 2015 and 2017. 143 patients had the GJ constructed with a 3.5 mm circular stapler height, with the remaining 72 patients having the GJ fashioned with a 4.8 mm stapler height. The rate of anastomotic stricturing was lower in the 3.5 mm stapler group compared to the other cohort (3.5 versus 13.9%, resp., p=0.008). Likewise, the overall rate of bleeding complications was lower in the 3.5 mm stapler group compared to the 4.8 mm group (6.3 versus 15.3%, resp., p=0.04). The rate of anastomotic stricturing and postoperative bleeding is lower with the use of a 3.5 mm circular stapler compared to a 4.8 mm circular stapler when forming the GJ.

Identification of compounds acting as negative allosteric modulators of the LPA1 receptor.

The Lysophosphatidic Acid 1 Receptor (LPA1 receptor) has been linked to the initiation and progression of a variety of poorly treated fibrotic conditions. Several compounds that have been described as LPA1 receptor antagonists have progressed into clinical trials: 1-(4-{4-[3-methyl-4-({[(1R)-1-phenylethoxy]carbonyl}amino)-1,2-oxazol-5-yl]phenyl}phenyl)cyclopropane-1-carboxylic acid (BMS-986202) and 2-{4-methoxy-3-[2-(3-methylphenyl)ethoxy]benzamido}-2,3-dihydro-1H-indene-2-carboxylic acid (SAR-100842). We considered that as LPA1 receptor function is involved in many normal physiological processes, inhibition of specific signalling pathways associated with fibrosis may be therapeutically advantageous. We compared the binding and functional effects of a novel compound; 4-({(Cyclopropylmethyl)[4-(2-fluorophenoxy)benzoyl]amino}methyl}benzoic acid (TAK-615) with BMS-986202 and SAR-100842. Back-scattering interferometry (BSI) was used to show that the apparent affinity of TAK-615 was enhanced in the presence of LPA. The binding signal for BMS-986202 was not detected in the presence of LPA suggesting competition but interestingly the apparent affinity of SAR-100842 was also enhanced in the presence of LPA. Only BMS-986202 was able to fully inhibit the response to LPA in calcium mobilisation, ß-arrestin, cAMP, GTPγS and RhoA functional assays. TAK-615 and SAR-100842 showed different inhibitory profiles in the same functional assays. Further binding studies indicated that TAK-615 is not competitive with either SAR-100842 or BMS-986202, suggesting a different site of binding. The results generated with this set of experiments demonstrate that TAK-615 acts as a negative allosteric modulator (NAM) of the LPA1 receptor. Surprisingly we find that SAR-100842 also behaves like a NAM. BMS-986202 on the other hand behaves like an orthosteric antagonist.

Gene set enrichment analysis and expression pattern exploration implicate an involvement of neurodevelopmental processes in bipolar disorder.

BACKGROUND: Bipolar disorder (BD) is a common and highly heritable disorder of mood. Genome-wide association studies (GWAS) have identified several independent susceptibility loci. In order to extract more biological information from GWAS data, multi-locus approaches represent powerful tools since they utilize knowledge about biological processes to integrate functional sets of genes at strongly to moderately associated loci. METHODS: We conducted gene set enrichment analyses (GSEA) using 2.3 million single-nucleotide polymorphisms, 397 Reactome pathways and 24,025 patients with BD and controls. RNA expression of implicated individual genes and gene sets were examined in post-mortem brains across lifespan. RESULTS: Two pathways showed a significant enrichment after correction for multiple comparisons in the GSEA: GRB2 events in ERBB2 signaling, for which 6 of 21 genes were BD associated (PFDR = 0.0377), and NCAM signaling for neurite out-growth, for which 11 out of 62 genes were BD associated (PFDR = 0.0451). Most pathway genes showed peaks of RNA co-expression during fetal development and infancy and mapped to neocortical areas and parts of the limbic system. LIMITATIONS: Pathway associations were technically reproduced by two methods, although they were not formally replicated in independent samples. Gene expression was explored in controls but not in patients. CONCLUSIONS: Pathway analysis in large GWAS data of BD and follow-up of gene expression patterns in healthy brains provide support for an involvement of neurodevelopmental processes in the etiology of this neuropsychiatric disease. Future studies are required to further evaluate the relevance of the implicated genes on pathway functioning and clinical aspects of BD.

Microarray analysis of bone marrow lesions in osteoarthritis demonstrates upregulation of genes implicated in osteochondral turnover, neurogenesis and inflammation.

OBJECTIVE: Bone marrow lesions (BMLs) are well described in osteoarthritis (OA) using MRI and are associated with pain, but little is known about their pathological characteristics and gene expression. We evaluated BMLs using novel tissue analysis tools to gain a deeper understanding of their cellular and molecular expression. METHODS: We recruited 98 participants, 72 with advanced OA requiring total knee replacement (TKR), 12 with mild OA and 14 non-OA controls. Participants were assessed for pain (using Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)) and with a knee MRI (using MOAKS). Tissue was then harvested at TKR for BML analysis using histology and tissue microarray. RESULTS: The mean (SD) WOMAC pain scores were significantly increased in advanced OA 59.4 (21.3) and mild OA 30.9 (20.3) compared with controls 0.5 (1.28) (p<0.0001). MOAKS showed all TKR tissue analysed had BMLs, and within these lesions, bone marrow volume was starkly reduced being replaced by dense fibrous connective tissue, new blood vessels, hyaline cartilage and fibrocartilage. Microarray comparing OA BML and normal bone found a significant difference in expression of 218 genes (p<0.05). The most upregulated genes included stathmin 2, thrombospondin 4, matrix metalloproteinase 13 and Wnt/Notch/catenin/chemokine signalling molecules that are known to constitute neuronal, osteogenic and chondrogenic pathways. CONCLUSION: Our study is the first to employ detailed histological analysis and microarray techniques to investigate knee OA BMLs. BMLs demonstrated areas of high metabolic activity expressing pain sensitisation, neuronal, extracellular matrix and proinflammatory signalling genes that may explain their strong association with pain.

Sleeve Gastrectomy and Type 2 Diabetes Mellitus: a Systematic Review of Long-Term Outcomes.

Long-term T2DM resolution rates are not well established following the laparoscopic sleeve gastrectomy (LSG). The aim of this paper was to systematically review the evidence on the efficacy of the LSG on long-term T2DM resolution. A comprehensive electronic literature search was conducted. Included studies reported 5-year follow-up of T2DM outcomes following the LSG. Eleven studies (n = 1354) were included in the systematic review. T2DM patients (n = 402) encompassed 29.7 % of patients. Diabetes prevalence decreased post-operatively to 20.5 % at 5 years, with diabetes resolution occurring in 60.8 % of patients. Mean plasma glucose levels and haemoglobin A1c values fell from 170.3 to 112.0 mg/dL and 8.3 to 6.7 % respectively at the 5-year mark. The LSG is an effective long-term metabolic surgery for patients with T2DM.

Prospective evaluation of gastric neurostimulation for diabetic gastroparesis in Canada.

BACKGROUND: The efficacy of gastric neurostimulation therapy for diabetic gastroparesis (GP) in a 'real-life' Canadian setting has not been assessed. AIMS: To assess changes in health-related quality of life (QoL), weekly vomiting frequency (WVF), total symptom score (TSS) and health care utilization 12 months before and after gastric neurostimulator implantation in a diabetic GP cohort. METHODS: Medication-refractory diabetic GP patients (n=7, four female, mean age 42 years) were prospectively recruited from 2008 to 2012. QoL scores were self-administered and obtained at baseline, 24 and 48 weeks postimplantion. WVF and TSS were assessed similarly. Health care usage, measured as hospitalization frequency and medication cost, was obtained six and 12 months before and after implant. Changes from baseline to six and 12 months for all outcomes were compared. RESULTS: The mean ( ± SD) QoL according to EuroQol was significantly better at 24 weeks after the baseline measurement (baseline 29 ± 5, 24 weeks 52 ± 7; P = 0.03). The mean improvement in TSS was significantly better at one year postintervention (baseline score 35 ± 5 versus 12 months 27 ± 3; P = 0.03). Changes in Short-Form 36 Health Survey and WVF were not significant. Days of GP-related hospitalization were highly variable but decreased from a median of 71 days (range 0 to 227 days) to 29 days (range two to 334 days) one year before and after surgery, respectively (P = 0.735). Outpatient medication costs did not decrease to a significant extent. CONCLUSION: Gastric neurostimulation for diabetic GP appeared to show some beneficial palliative effects overall in the present small open-label series, but the effect is highly variable among patients, and placebo effect cannot be ruled out.

Depression and the older medical patient--when and how to intervene.

Depression in the elderly, particularly those with chronic physical health problems, is a common, but complex problem. In this paper we review the research literature on both the epidemiology and management of depression in the older medical patient. After a general overview of depression in the elderly, we discuss some of the particular issues relevant to depression and co-morbid physical illness amongst elderly patients. Depression can be difficult to diagnose in medically unwell older adults, particularly when there is substantial overlap in symptomatology. The epidemiology and evidence base for the treatment of depression in a number of chronic health problems common in an older adults population are then discussed, specifically cardiac disease, cerebrovascular disease, cancer, chronic kidney disease, chronic obstructive pulmonary disease, and Parkinson's disease. For many of these conditions there is emerging evidence that treatments can be effective in reducing depressive symptoms. However, these potential benefits need to be balanced against the often-increased risk of adverse events or interactions with medical treatments. Although co-morbid depression is consistently associated with poorer medical outcomes, there is limited evidence that standard anti-depressive therapy has additional benefits in terms of physical health outcomes. Collaborative care models appear particularly well suited to medically unwell older adult patients, and may provide more generalised benefits across both mental and physical health measures.

Screening for bipolar disorder: does gender distort scores and case-finding estimates?

BACKGROUND: Gender differences in rates of bipolar disorder have been described, with most studies reporting males as over-represented in those diagnosed with a bipolar I disorder and females over-represented in those diagnosed with a bipolar II disorder. This could reflect true differences in prevalence or measurement error emerging from screening or case-finding measures. We examine the possible contribution of the latter by examining one screening measure-the Mood Swings Questionnaire (MSQ). METHODS: We analyse MSQ data from a large sample of age- and gender-matched bipolar I and bipolar II patients (and their composite group). Gender differences were examined in terms of prevalence and severity of MSQ symptoms, MSQ sub-scales scores and total MSQ scores, employing univariate and differential item functioning (DIF) analyses. RESULTS: Both male and female bipolar I patients reported higher total MSQ and higher mysticism MSQ sub-scale scores than their male and female bipolar II counterparts. There were no gender differences when bipolar I, bipolar II and composite bipolar groups were separately examined on both total and sub-scale MSQ scores, suggesting that gender does not impact on MSQ scoring. When item analyses of bipolar I and II groups were undertaken separately, a number of differences emerged, but as few were consistent across bipolar sub-types such differences could reflect chance and failure to control for multiple comparisons. The over-representation of some items in females and some in males may have contributed to the comparable total and sub-scale scores. LIMITATIONS: Large sample size and only one measure (i.e. MSQ) examined. CONCLUSION: As total and sub-scale MSQ scores were uninfluenced by gender we can conclude that this screening test is not confounded by gender and, if representative of other such screening measures, would indicate that any differential prevalence of the bipolar disorders identified in community studies possibly reflects gender differences in their occurrence rather than artefactual consequences of screening measures having a gender bias.

Characterisation of genetic variation in ST8SIA2 and its interaction region in NCAM1 in patients with bipolar disorder.

Alpha-2,8-sialyltransferase 2 (ST8SIA2) is an enzyme responsible for the transfer of polysialic acid (PSA) to glycoproteins, principally the neuronal cell adhesion molecule (NCAM1), and is involved in neuronal plasticity. Variants within ST8SIA2 have previously shown association with bipolar disorder, schizophrenia and autism. In addition, altered PSA-NCAM expression in brains of patients with schizophrenia or bipolar disorder indicates a functional dysregulation of glycosylation in mental illness. To explore the role of sequence variation affecting PSA-NCAM formation, we conducted a targeted re-sequencing study of a ∼ 100 kb region--including the entire ST8SIA2 gene and its region of interaction with NCAM1--in 48 Caucasian cases with bipolar disorder using the Roche 454 platform. We identified over 400 DNA variants, including 47 putative novel variants not described in dbSNP. Validation of a subset of variants via Sequenom showed high reliability of Roche 454 genotype calls (97% genotype concordance, with 80% of novel variants independently verified). We did not observe major loss-of-function mutations that would affect PSA-NCAM formation, either by ablating ST8SIA2 function or by affecting the ability of NCAM1 to be glycosylated. However, we identified 13 SNPs in the UTRs of ST8SIA2, a synonymous coding SNP in exon 5 (rs2305561, P207P) and many additional non-coding variants that may influence splicing or regulation of ST8SIA2 expression. We calculated nucleotide diversity within ST8SIA2 on specific haplotypes, finding that the diversity on the specific "risk" and "protective" haplotypes was lower than other non-disease-associated haplotypes, suggesting that putative functional variation may have arisen on a spectrum of haplotypes. We have identified common and novel variants (rs11074064, rs722645, 15:92961050) that exist on a spectrum of haplotypes, yet are plausible candidates for conferring the effect of risk and protective haplotypes via multiple enhancer elements. A Galaxy workflow/pipeline for sequence analysis used herein is available at: https://main.g2.bx.psu.edu/u/a-shaw-neura/p/next-generation-resources.