Repeated hospital admission for intentional poisonings among older adults - a Swedish national register-based study.

BACKGROUND: Poisoning injuries is an increasing concern among older people, and so is the repetition of intentional poisonings. To date, few studies have documented the pattern and individual risk factors for repeated poisonings. This national study aims to shed light on the burden, pattern, and health-related risk factors of repeated intentional poisoning leading to hospitalization or death among older Swedish adults (50 years and older), with a focus on the year following a first event. METHODS: We conducted a nationwide register-based cohort study of people aged 50-100, hospitalized for intentional poisoning (ICD10: X60-69) during 2006-2016 (n = 15,219) and re-hospitalized by poisoning of any intent within a year (n = 1710), i.e., up to the end of 2017. We considered in turn, the distribution of the second poisoning in 30-day intervals stratified by intent; poisoning lethality within a month and a year; and the sex-specific association between health conditions and being re-hospitalized for intentional poisoning within one year as compared to being hospitalized only once using logistic regression (odds ratios (OR) with 95% confidence intervals (95% CI)). RESULTS: Following an intentional poisoning, re-hospitalization within a year was predominantly for a new intentional poisoning (89.7%) and occurred most typically within a month (median 4 days). Death within 30 days occurred in similar proportion for the first and second poisoning (2.3% vs. 2.1% respectively). Among both men and women, comorbidity of psychiatric illness was strongly associated with re-hospitalization for intentional poisoning (adjusted ORs = 1.70; 95% CI = 1.45-2.01 and 1.89 (95% CI = 1.60-2.19) respectively). CONCLUSION: Most re-hospitalizations within a year after intentional poisoning are also for intentional poisoning and occur most typically within days. Re-hospitalization is associated with several conditions that are characteristic of poor mental health and there are more similarities than differences between men and women in that respect.

Trends in intentional and unintentional poisonings among older adults - A national register-based study in Sweden.

BACKGROUND: Among older people intentional poisoning outnumber unintentional ones. While there are indications that time trends differ by poisoning intent, studies are scarce. We assessed how the annual prevalence of intentional and unintentional poisoning changed over time, overall and by demographic groups. METHODS: We conducted a national open cohort study of individuals aged 50-100 years, resident in Sweden during 2005-2016. Individuals were followed up in population-based registers for their demographic and health attributes from 2006-2016. Annual prevalence of hospitalization and death by poisoning intent (unintentional vs. intentional or undetermined; ICD-10 definitions) were compiled for the categories of four demographic attributes (age, sex, marital status, and birth cohort "baby boomers"). The time trends were assessed by multinomial logistic regression with year as an independent variable. RESULTS: The annual overall prevalence of hospitalization and death by intentional poisonings consistently exceeded that of unintentional poisonings. There was a significant downward trend in intentional poisonings but not in unintentional ones. This difference in trends also applied when considering men and women separately, married and unmarried people, the young-old individuals (but not the older- or oldest-old ones), and the baby boomers and non-baby boomers. The largest demographic differences within intent were found between married and unmarried people, and the smallest one between men and women. CONCLUSION: As expected, the annual prevalence of intentional poisonings considerably exceed that of unintentional ones among Swedish older people. The recent trends reveal a significant reduction of intentional poisonings, consistent across a range of demographic attributes. The scope for action regarding this preventable cause of mortality and morbidity remains considerable.

Effect of the New Nordic Diet compared with usual care on glucose control in gestational diabetes mellitus: Study protocol for the randomized controlled trial intervention with new Nordic DIet in women with GestatiOnal diabetes mellitus (iNDIGO).

BACKGROUND: Gestational diabetes mellitus (GDM) is a pregnancy complication associated with short- and long-term health consequences for mother and child. First line treatment is diet and exercise but there is a recognized knowledge gap as to what diet treatment is optimal. A healthy Nordic diet has been associated with improved health but no studies in women with GDM exist. The New Nordic Diet (NND) is an initiative with the purpose to develop a healthy Nordic diet including foods with the potential to grow in Nordic countries; including fruit, berries, vegetables, whole-grain cereal products, nuts, fish, and rapeseed oil. The purpose of the intervention with new Nordic DIet in women with GestatiOnal diabetes mellitus (iNDIGO) is to test if the NND compared with usual care improves glucose control in women with GDM. METHODS: The iNDIGO study is a randomized parallel controlled trial where 50 women with GDM will be randomized to either an NND or usual care for 14 days (30-32 weeks of gestation). Participants in the NND group will receive menus and food bags containing foods to be consumed. Primary outcome is glycemic control (time in target) measured using continuous glucose monitoring. Compliance to the dietary intervention will be tested using dietary biomarkers and adherence questionnaires. CONCLUSION: Diet treatment represents first line treatment in GDM but it remains unclear what type of diets are effective. iNDIGO is an efficacy study and will provide evidence as to whether a healthy Nordic diet can improve glucose control in women with GDM. TRIAL REGISTRATION: ClinicalTrials.gov registration Number: NCT04169243. Registered 19 November 2019, https://clinicaltrials.gov/ct2/show/NCT04169243.

The long-term outcome of childhood supracondylar humeral fractures: A population-based follow up study with a minimum follow up of ten years and normal matched comparisons.

AIMS: We present the clinical and radiographic outcome of 81 children with Gartland type I to III supracondylar humeral fractures at a minimum follow-up of ten years (mean 12.1 years; 10.3 to 16.1) following injury. PATIENTS AND METHODS: The clinical and functional outcomes are compared with normal age- and gender-matched individuals. The population-based study setting was first identified from the institutional registries; the rate of participation was 76%. Controls were randomly selected from Finnish National Population Registry. RESULTS: According to Flynn's criteria, most fractures (75.3%) resulted in a satisfactory ("good or excellent") outcome. Satisfactory recovery was achieved in 75.0% of type I fractures treated by closed splinting (p = 0.013). Type II fractures were associated with both satisfactory (57.7%) and unsatisfactory (42.3%) results, regardless of the type of treatment, although the numbers were small in the sub groups. Most type III fractures were treated operatively, and most (76%) had a satisfactory outcome according to Flynn's criteria (p = 0.015). Compared with none among the normal subjects, flexion of the elbow was reduced by > 10° at long-term follow-up in 20 cases (24.7%, p < 0.001) and 9 (11.1%) had a reduced flexion of > 15° (p = 0.004). In patients who had sustained a type III fracture, the carrying angle was decreased by 35.7% (from 9.8° to 6.3°; p = 0.048). All patients achieved an excellent Mayo Elbow Performance Score (mean 96.4 points). CONCLUSION: The long-term outcome of extension-type supracondylar humeral fractures is generally good, but not exclusively benign, with the potential for long-term pain and ulnar nerve sensitivity, and a decrease in grip strength and range of movement in type II and type III fractures. Bony remodelling cannot be relied upon to correct any residual deformity. In particular, type II fractures have impaired long-term recovery and justify individual consideration in their treatment. Cite this article: Bone Joint J 2016;98-B:1410-17.

Biomarkers of inflammation in major vascular surgery: a prospective randomised trial.

BACKGROUND: Surgery induces inflammation and pro-inflammatory cytokines are associated with post-operative complications. In cardiac surgery, it has been shown that volatile anaesthetics have cardioprotective properties. We explored whether sevoflurane affects the pro-inflammatory response favourably compared with total intravenous anaesthesia (TIVA) after surgery. METHODS: We measured monocyte chemotactic protein 1 (MCP-1), matrix metalloproteinase 9 (MMP-9), C-reactive protein (CRP), vascular cell adhesion molecule 1 (VCAM-1), interleukin (IL)-6 and IL-8 perioperatively and evaluated if the anaesthetic regimen affected these mediators. Our hypothesis was that sevoflurane-based anaesthesia is associated with a reduced release of biomarkers of inflammation compared with TIVA with propofol/remifentanil. RESULTS: In the total population, MCP-1, MMP-9, IL-6 and IL-8 increased 30 min after arrival intensive care unit, compared with before surgery (P < 0.001), whereas CRP and VCAM-1 transiently declined (P < 0.001). From 30 min after arrival intensive care unit to 1st post-operative day, MCP-1 and IL-6 levels declined (P < 0.001), CRP and VCAM-1 increased (P < 0.001), whereas MMP-9 and IL-8 were not significantly altered. Pre-operatively there were no significant differences in any variables between the two anaesthetic groups. Lower levels of MCP-1 and IL-8 (P < 0.001) and higher levels of IL-6 and MMP-9 (P = 0.003) were found in the sevoflurane group, compared with the TIVA group 30 min post-operatively. CRP and VCAM-1 levels did not differ. There were no significant differences between the two anaesthetic groups before surgery or at 1st post-operative day. CONCLUSION: We found an inflammatory response during the observation period, which was modified by the anaesthetic regimen in the early phase. This short-lasting difference is probably too short to support a cardioprotective effect of sevoflurane compared with TIVA in open abdominal aortic surgery.

Analysis of transthoracic echocardiographic data in major vascular surgery from a prospective randomised trial comparing sevoflurane and fentanyl with propofol and remifentanil anaesthesia.

The aim of this study was to define pre-operative echocardiographic data and explore if postoperative indices of cardiac function after open abdominal aortic surgery were affected by the anaesthetic regimen. We hypothesised that volatile anaesthesia would improve indices of cardiac function compared with total intravenous anaesthesia. Transthoracic echocardiography was performed pre-operatively in 78 patients randomly assigned to volatile anaesthesia and 76 to total intravenous anaesthesia, and compared with postoperative data. Pre-operatively, 16 patients (10%) had left ventricular ejection fraction < 46%. In 138 patients with normal left ventricular ejection fraction, 5/8 (62%) with left ventricular dilatation and 41/130 (33%) without left ventricular dilatation had evidence of left ventricular diastolic dysfunction (p < 0.001). Compared with pre-operative findings, significant increases in left ventricular end-diastolic volume, left atrial maximal volume, cardiac output, velocity of early mitral flow and early myocardial relaxation occurred postoperatively (all p < 0.001). The ratio of the velocity of early mitral flow to early myocardial relaxation remained unchanged. There were no significant differences in postoperative echocardiographic findings between patients anaesthetised with volatile anaesthesia or total intravenous anaesthesia. Patients had an iatrogenic surplus of approximately 4.1 l of fluid volume by the first postoperative day. N-terminal prohormone of brain natriuretic peptide increased on the first postoperative day (p < 0.001) and remained elevated after 30 days (p < 0.001) in both groups. Although postoperative echocardiographic alterations were most likely to be related to increased preload due to a substantial iatrogenic surplus of fluid, a component of peri-operative myocardial ischaemia cannot be excluded. Our hypothesis that volatile anaesthesia improved indices of cardiac function compared with total intravenous anaesthesia could not be verified.

Variability in the CIITA gene interacts with HLA in multiple sclerosis.

The human leukocyte antigen (HLA) is the main genetic determinant of multiple sclerosis (MS) risk. Within the HLA, the class II HLA-DRB1*15:01 allele exerts a disease-promoting effect, whereas the class I HLA-A*02 allele is protective. The CIITA gene is crucial for expression of class II HLA molecules and has previously been found to associate with several autoimmune diseases, including MS and type 1 diabetes. We here performed association analyses with CIITA in 2000 MS cases and up to 6900 controls as well as interaction analysis with HLA. We find that the previously investigated single-nucleotide polymorphism rs4774 is associated with MS risk in cases carrying the HLA-DRB1*15 allele (P=0.01, odds ratio (OR): 1.21, 95% confidence interval (CI): 1.04-1.40) or the HLA-A*02 allele (P=0.01, OR: 1.33, 95% CI: 1.07-1.64) and that these associations are independent of the adjacent confirmed MS susceptibility gene CLEC16A. We also confirm interaction between rs4774 and HLA-DRB1*15:01 such that individuals carrying the risk allele for rs4774 and HLA-DRB1*15:01 have a higher than expected risk for MS. In conclusion, our findings support previous data that variability in the CIITA gene affects MS risk, but also that the effect is modulated by MS-associated HLA haplotypes. These findings further underscore the biological importance of HLA for MS risk.

Colectomy for patients with ulcerative colitis and primary sclerosing cholangitis - what next?

BACKGROUND AND AIMS: Primary sclerosing cholangitis (PSC) occurs in 2%-8% of patients who suffer from ulcerative colitis (UC). For patients who require colectomy, ileal pouch-anal anastomosis (IPAA) or ileorectal anastomosis (IRA) is employed to preserve continence.We evaluated the outcomes after IPAA and IRA for patients with UC-PSC, using patients with UC but without PSC as controls (UC-only group). PATIENTS: In a case-control study conducted at Sahlgrenska University Hospital, Sweden, patients with UC-PSC (N=48; 31 IPAA and 17 IRA) were compared to patients with UC only (N=113; 62 IPAA and 51 IRA). Functional outcomes (Öresland score), pouchitis, surgical complications, and failure were evaluated. RESULTS: For patients with IPAA, the median Öresland scores were similar for the two groups: 5 (range, 0-13) for the UC-PSC group and 5 for the UC-only group (range, 0-12; p>0.05). However, the IRA scores were significantly different at 7 (range, 2-11) and 3 (range, 0-11) for the respective groups (p=0.005). Pouchitis was more frequent in patients with UC-PSC. Complication rates did not differ. For patients with IPAA, the failure rate was 16% for those in the UC-PSC group versus 6% for those in the UC-only group (p>0.05); the corresponding results for IRA were 53% versus 22% (p=0.03). CONCLUSIONS: For cases of IPAA, pouchitis seems to be more common in patients with UC-PSC. However, the functional outcomes and failure rates are unaffected by concurrent PSC. For patients with UC-PSC, functional outcome is poor and the failure rate is high after IRA.

Ulnar nerve morbidity as a long-term complication of pediatric supracondylar humeral fracture.

BACKGROUND: Supracondylar humeral fractures are common in children. We studied long-term ulnar nerve symptoms secondary to these fractures and analyzed the treatment for ulnar neuropathy. MATERIALS AND METHODS: The cohort included 91 patients with a supracondylar humeral fracture in childhood, on average 12 years previously, in the geographic catchment area. All the cases were reexamined in regard to ulnar nerve morbidity. Cases with secondary ulnar neuropathy were treated nonoperatively and operatively. RESULTS: Ulnar neuropathy was present in four cases (4.4 %). They all had suffered from a dislocated fracture, and they had been operated primarily. Another three patients had slight ulnar nerve symptoms. Hence, the total prevalence of secondary ulnar nerve morbidity was 7.7 %. A jumping nerve was seen in 9.9 %; 51.6 % had a diminished axial angle. CONCLUSIONS: We report a defined pattern of long-term ulnar nerve morbidity after pediatric supracondylar humeral fracture. The prevalence of neuropathy is alarming in the young population (<25 years of age).

Risk of obstetric anal sphincter lacerations among obese women.

OBJECTIVE: To assess the risk for obstetric anal sphincter lacerations in relation to maternal obesity among primiparous women in Sweden. DESIGN: A population-based study. SETTING: Sweden. POPULATION: All women with vaginal delivery and singleton pregnancy in Sweden in the years 2003-2008 (n = 210,678). METHODS: The Medical Birth Registry, the National Board of Health and Welfare, was used to identify cases of rupture and body mass index (BMI) classes. The population was categorised into four classes with BMI of <25, 25 to <30, 30 to <35 and >35 kg/m². MAIN OUTCOME MEASURES: Odds ratios were estimated with 95% confidence intervals. In order to estimate the effect of BMI on obstetric anal sphincter lacerations, with possible confounders accounted for, uni- and multivariate logistic regressions were performed. RESULTS: In total, 8958 (4.25%) cases of anal sphincter lacerations (grade III-IV) occurred; increasing BMI showed a significant near-dose-response type of protective effect against grade III-IV lacerations when compared with women with BMI <25 kg/m²: BMI 25 to <30 kg/m², 0.89; BMI 30 to <35 kg/m², 0.84; BMI > 35 kg/m², 0.70. CONCLUSION: Overweight and obesity were associated with a decreased risk for obstetric anal sphincter lacerations.

Different fatty acid pattern in breast milk of obese compared to normal-weight mothers.

INTRODUCTION: The aim of this study was to investigate the fatty acid (FA) pattern in breast milk of obese mothers and their neonates' plasma compared to those of normal weight mothers. PATIENTS AND METHODS: This was an observational study of 41 obese and 41 normal weight pregnant women. Twenty-nine obese women participating in a weight reduction program were investigated for comparison. FAs were analyzed in breast milk collected at 3 and 10 days and one and two months postnatally and in infant's plasma 3 days after birth. RESULTS AND CONCLUSIONS: The concentration of long-chain n-3 FA were lower and the ratio n-6/n-3 FA higher in neonates and in consecutive samples of breast milk of obese mothers compared to normal weight mothers. The obese mothers that participated in an intervention program with general dietary advice had FA concentrations approaching that of the normal-weight mothers. The study indicates importance of dietary advice in pregnancy.

Worse glycaemic control in LADA patients than in those with type 2 diabetes, despite a longer time on insulin therapy.

AIMS/HYPOTHESIS: Our aim was to study whether glycaemic control differs between individuals with latent autoimmune diabetes in adults (LADA) and patients with type 2 diabetes, and whether it is influenced by time on insulin therapy. METHODS: We performed a retrospective study of 372 patients with LADA (205 men and 167 women; median age 54 years, range 35-80 years) from Swedish cohorts from Skåne (n = 272) and Västerbotten (n = 100). Age- and sex-matched patients with type 2 diabetes were included as controls. Data on the use of oral hypoglycaemic agents (OHAs), insulin and insulin-OHA combination therapy was retrieved from the medical records. Poor glycaemic control was defined as HbA(1c) ≥7.0% (≥53 mmol/mol) at follow-up. RESULTS: The individuals with LADA and with type 2 diabetes were followed for an average of 107 months. LADA patients were leaner than type 2 diabetes patients at diagnosis (BMI 27.7 vs 31.0 kg/m(2); p < 0.001) and follow-up (BMI 27.9 vs 30.2 kg/m(2); p < 0.001). Patients with LADA had been treated with insulin for longer than those with type 2 diabetes (53.3 vs 28.8 months; p < 0.001). There was no significant difference between the patient groups with regard to poor glycaemic control at diagnosis, but more patients with LADA (67.8%) than type 2 diabetes patients (53.0%; p < 0.001) had poor glycaemic control at follow-up. Patients with LADA had worse glycaemic control at follow-up compared with participants with type 2 diabetes (OR = 1.8, 95% CI 1.2, 2.7), adjusted for age at diagnosis, HbA(1c), BMI at diagnosis, follow-up time and duration of insulin treatment. CONCLUSIONS/INTERPRETATION: Individuals with LADA have worse glycaemic control than patients with type 2 diabetes despite a longer time on insulin therapy.

Age-dependent variation of genotypes in MHC II transactivator gene (CIITA) in controls and association to type 1 diabetes.

The major histocompatibility complex class II transactivator (CIITA) gene (16p13) has been reported to associate with susceptibility to multiple sclerosis, rheumatoid arthritis and myocardial infarction, recently also to celiac disease at genome-wide level. However, attempts to replicate association have been inconclusive. Previously, we have observed linkage to the CIITA region in Scandinavian type 1 diabetes (T1D) families. Here we analyze five Swedish T1D cohorts and a combined control material from previous studies of CIITA. We investigate how the genotype distribution within the CIITA gene varies depending on age, and the association to T1D. Unexpectedly, we find a significant difference in the genotype distribution for markers in CIITA (rs11074932, P=4 × 10(-5) and rs3087456, P=0.05) with respect to age, in the collected control material. This observation is replicated in an independent cohort material of about 2000 individuals (P=0.006, P=0.007). We also detect association to T1D for both markers, rs11074932 (P=0.004) and rs3087456 (P=0.001), after adjusting for age at sampling. The association remains independent of the adjacent T1D risk gene CLEC16A. Our results indicate an age-dependent variation in CIITA allele frequencies, a finding of relevance for the contrasting outcomes of previously published association studies.

Minor amputation in patients with diabetes mellitus and severe foot ulcers achieves good outcomes.

OBJECTIVE: To analyse the outcome of minor amputations (through, or distal to, the ankle joint) in patients with diabetes. METHOD: All diabetic patients in a defined population undergoing one or more minor amputation between 1982 and 2006 were investigated according to a standardised protocol and were followed until final outcome (healing or death). A total of 410 consecutive amputations in 309 patients with a median age of 73 (32-93) years were identified. RESULTS: In 94% of amputations, deep infection (39%) and/or gangrene (55%) was present. Severe peripheral vascular disease or critical limb ischaemia was present in 61% of amputations. 261/410 (64%) of the amputations healed at a level below the ankle joint; 69/410 (17%) healed after a re-amputation above the ankle joint; in 76/410 of amputations (19%), the patient died before healing could occur. In surviving patients, 79% of the amputations healed below the ankle. Median healing time for amputations that healed below the ankle was 26 (2-250) weeks; 21% of amputations required a re-amputation above the ankle. None of the analysed parameters excluded the possibility of healing below the ankle. CONCLUSION: In this population-based survey, the goal of avoiding major amputation was achieved in almost two thirds of minor amputations, but at the price of long healing times. In almost all amputations, the patient had deep infection and/or gangrene. In spite of this, 64% of all amputations, and 79% of amputations in surviving patients, healed at a level below the ankle. This indicates that minor amputations in these patients are worthwhile. DECLARATION OF INTEREST: None.

Common variants in CNDP1 and CNDP2, and risk of nephropathy in type 2 diabetes.

AIMS/HYPOTHESIS: Several genome-wide linkage studies have shown an association between diabetic nephropathy and a locus on chromosome 18q harbouring two carnosinase genes, CNDP1 and CNDP2. Carnosinase degrades carnosine (ß-alanyl-L-histidine), which has been ascribed a renal protective effect as a scavenger of reactive oxygen species. We investigated the putative associations of genetic variants in CNDP1 and CNDP2 with diabetic nephropathy (defined either as micro- or macroalbuminuria) and estimated GFR in type 2 diabetic patients from Sweden. METHODS: We genotyped nine single nucleotide polymorphisms (SNPs) and one trinucleotide repeat polymorphism (D18S880, five to seven leucine repeats) in CNDP1 and CNDP2 in a case-control set-up including 4,888 unrelated type 2 diabetic patients (with and without nephropathy) from Sweden (Scania Diabetes Registry). RESULTS: Two SNPs, rs2346061 in CNDP1 and rs7577 in CNDP2, were associated with an increased risk of diabetic nephropathy (rs2346061 p = 5.07 × 10(-4); rs7577 p = 0.021). The latter was also associated with estimated GFR (ß = -0.037, p = 0.014), particularly in women. A haplotype including these SNPs (C-C-G) was associated with a threefold increased risk of diabetic nephropathy (OR 2.98, 95% CI 2.43-3.67, p < 0.0001). CONCLUSIONS/INTERPRETATION: These data suggest that common variants in CNDP1 and CNDP2 play a role in susceptibility to kidney disease in patients with type 2 diabetes.

Stoma-related complications and stoma size - a 2-year follow up.

AIM: The purpose of the study was to prospectively describe stoma configuration and evaluate stoma-related complications and their association with possible risk factors. METHOD: All elective patients (n = 180) operated on with a formation of colostomy, ileostomy or loop-ileostomy between 2003 and 2005 were included in the study. Follow up took place on the ward postoperatively and five times during 2 years after discharge. On these occasions the diameter and height of the stoma were recorded. Complications such as peristomal skin problems, necrosis, leakage caused by a low stoma, stenosis, granuloma formation, prolapse and peristomal hernia formation were evaluated. RESULTS: Most complications occurred 2 weeks after discharge; 53% of patients with colostomies, 79% with loop-ileostomies and 70% of patients with end-ileostomy had one or more complications. The most common complication was skin problems and it was most common in patients with end-ileostomies (60%) and loop-ileostomies (73%). Postoperatively at ward review, the most common complication was necrosis, which occurred in 20% of patients with a colostomy. Granuloma formation was most frequent in colostomies. Almost all patients with an end-ileostomy and loop-ileostomy with a height lower than 20 mm had leakage and skin problems as had half of the patients with a colostomy height lower than 5 mm. CONCLUSION: To prevent stoma-related complications, it is important to produce an adequate height of the stoma, with early and regular follow ups and adjustment of the appliance. To work closely in collaboration with the colorectal surgeons is of utmost important to provide feedback and in turn, to improve stoma outcome.

Pouch design and long-term functional outcome after ileal pouch-anal anastomosis.

BACKGROUND: Functional outcome is of utmost importance after ileal pouch-anal anastomosis. Although pouch design and construction of the anastomosis are known technical determinants of function, there are few long-term results. This retrospective study evaluated functional outcome for two different pouch designs, and for handsewn versus stapled pouch-anal anastomoses. METHODS: The analysis included 412 patients who had either a J or K pouch (double-folded J pouch), of whom 123 had a J pouch (96 handsewn and 27 stapled) and 289 had a K pouch (95 handsewn and 194 stapled). Functional outcome was evaluated by a mailed questionnaire to achieve an Oresland score (0 to 15; 15 worst). RESULTS: Mean functional scores were 6.1 for J pouches and 4.9 for K pouches (P < 0.001). Regression analysis showed that reservoir design and age at surgery were predictors of functional outcome (P < 0.001). A higher proportion of patients with a J pouch and handsewn anastomosis than with a K pouch and stapled anastomosis had a score of 8 or more, a level previously demonstrated to impact negatively on quality of life (32 versus 16 per cent; P = 0.006). CONCLUSION: The K pouch was associated with a better long-term functional outcome than the J pouch in this patient population.

Meta-analysis of 32 genome-wide linkage studies of schizophrenia.

A genome scan meta-analysis (GSMA) was carried out on 32 independent genome-wide linkage scan analyses that included 3255 pedigrees with 7413 genotyped cases affected with schizophrenia (SCZ) or related disorders. The primary GSMA divided the autosomes into 120 bins, rank-ordered the bins within each study according to the most positive linkage result in each bin, summed these ranks (weighted for study size) for each bin across studies and determined the empirical probability of a given summed rank (P(SR)) by simulation. Suggestive evidence for linkage was observed in two single bins, on chromosomes 5q (142-168 Mb) and 2q (103-134 Mb). Genome-wide evidence for linkage was detected on chromosome 2q (119-152 Mb) when bin boundaries were shifted to the middle of the previous bins. The primary analysis met empirical criteria for 'aggregate' genome-wide significance, indicating that some or all of 10 bins are likely to contain loci linked to SCZ, including regions of chromosomes 1, 2q, 3q, 4q, 5q, 8p and 10q. In a secondary analysis of 22 studies of European-ancestry samples, suggestive evidence for linkage was observed on chromosome 8p (16-33 Mb). Although the newer genome-wide association methodology has greater power to detect weak associations to single common DNA sequence variants, linkage analysis can detect diverse genetic effects that segregate in families, including multiple rare variants within one locus or several weakly associated loci in the same region. Therefore, the regions supported by this meta-analysis deserve close attention in future studies.

Common variants in the TCF7L2 gene help to differentiate autoimmune from non-autoimmune diabetes in young (15-34 years) but not in middle-aged (40-59 years) diabetic patients.

AIMS/HYPOTHESIS: Type 1 diabetes in children is characterised by autoimmune destruction of pancreatic beta cells and the presence of certain risk genotypes. In adults the same situation is often referred to as latent autoimmune diabetes in adults (LADA). We tested whether genetic markers associated with type 1 or type 2 diabetes could help to discriminate between autoimmune and non-autoimmune diabetes in young (15-34 years) and middle-aged (40-59 years) diabetic patients. METHODS: In 1,642 young and 1,619 middle-aged patients we determined: (1) HLA-DQB1 genotypes; (2) PTPN22 and INS variable-number tandem repeat (VNTR) polymorphisms; (3) two single nucleotide polymorphisms (rs7903146 and rs10885406) in the TCF7L2 gene; (4) glutamic acid decarboxylase (GAD) and IA-2-protein tyrosine phosphatase-like protein (IA-2) antibodies; and (5) fasting plasma C-peptide. RESULTS: Frequency of risk genotypes HLA-DQB1 (60% vs 25%, p = 9.4 x 10(-34); 45% vs 18%, p = 1.4 x 10(-16)), PTPN22 CT/TT (34% vs 26%, p = 0.0023; 31% vs 23%, p = 0.034), INS VNTR class I/I (69% vs 53%, p = 1.3 x 10(-8); 69% vs 51%, p = 8.5 x 10(-5)) and INS VNTR class IIIA/IIIA (75% vs 63%, p = 4.3 x 10(-6); 73% vs 60%, p = 0.008) was increased in young and middle-aged GAD antibodies (GADA)-positive compared with GADA-negative patients. The type 2 diabetes-associated genotypes of TCF7L2 CT/TT of rs7903146 were significantly more common in young GADA-negative than in GADA-positive patients (53% vs 43%; p = 0.0004). No such difference was seen in middle-aged patients, in whom the frequency of the CT/TT genotypes of TCF7L2 was similarly increased in GADA-negative and GADA-positive groups (55% vs 56%). CONCLUSIONS/INTERPRETATION: Common variants in the TCF7L2 gene help to differentiate young but not middle-aged GADA-positive and GADA-negative diabetic patients, suggesting that young GADA-negative patients have type 2 diabetes and that middle-aged GADA-positive patients are different from their young GADA-positive counterparts and share genetic features with type 2 diabetes.