Tokophobia and fear of birth: a workshop consensus statement on current issues and recommendations for future research.

Objective: To discuss and develop a statement on the current state of the evidence and opinion in Fear of Childbirth (FoC) and Tokophobia (Tocophobia), and to provide recommendations. Background: A group met in 2019 to discuss the state of clinical and academic knowledge relating to FoC/Tokophobia. Five key areas were agreed as the focus of the meeting. Methods: 12 internationally acknowledged experts, in this or a closely related area (e.g. PTSD) met to discuss their understanding of the evidence for FoC/ Tokophobia and current practice. The consensus described in this paper constitutes the expression of the general opinion of the participants and does not necessarily imply unanimity. Keys points: Work focussed on tokophobia is recent and there remains a wide range of issues, which were addressed in the workshop including complexity in defining prevalence, a theoretical lack of understanding, which creates challenge for robust assessment and the identification of risk factors. An improved aetiological and developmental understanding of the tokophobia is required to underpin appropriate, effective and evidence-based interventions. Evaluation of pathways of care and relevant interventions, should be a focus of future research. Conclusion: Significant gaps remain within the FoC/tokophobia knowledge base. Further research is necessary.

STRAWB2 (Stress and Wellbeing After Childbirth): a randomised controlled trial of targeted self-help materials to prevent post-traumatic stress disorder following childbirth.

OBJECTIVES: To test whether providing psychological self-help materials would significantly lower the incidence of post-traumatic stress disorder (PTSD) at 6-12 weeks postnatally. DESIGN: Open-label randomised controlled trial, with blinded outcome assessment. SETTING: Community midwifery services in two National Health Service (NHS) trusts in the North West. SAMPLE: A cohort of 2419 women receiving normal NHS postnatal care. METHODS: Midwives screened women for traumatic birth experience; 678 women who screened positively (28.1%) were randomly allocated to self-help with usual care (n = 336) or to usual care alone (n = 342). The self-help materials were a leaflet and online film designed to prevent the development of PTSD after trauma exposure through explaining how to manage early psychological responses. MAIN OUTCOME MEASURE: The primary outcome was a composite of diagnostic and subdiagnostic PTSD at 6-12 weeks postnatally using the gold-standard Clinician-Administered PTSD Scale (CAPS-5) interview. RESULTS: Of the 678 women correctly randomised plus the nine women randomised in error, 478 (70.5%) were followed up. Diagnostic or subdiagnostic PTSD rates at follow-up did not differ between groups who received self-help (26.7%, 65/243) or usual care alone (26.2%, 64/244) (intention-to-treat analysis: RR 1.02, 95% CI 0.68-1.53). Findings remained consistent in the per-protocol analysis (RR 1.04, 95% CI 0.85-1.27). Women viewed the materials very positively. There were no adverse effects. Health economic micro-costing indicated implementation would be very low cost. CONCLUSIONS: Many women experience a traumatic birth and risk developing PTSD, but self-help strategies without professional support are insufficient and should not be routinely introduced. TWEETABLE ABSTRACT: Self-help information alone does not reduce the number of women developing PTSD after a traumatic childbirth.

Using Google Earth to Assess Shade for Sun Protection in Urban Recreation Spaces: Methods and Results.

Shade in public spaces can lower the risk of and sun burning and skin cancer. However, existing methods of auditing shade require travel between sites, and sunny weather conditions. This study aimed to evaluate the feasibility of free computer software-Google Earth-for assessing shade in urban open spaces. A shade projection method was developed that uses Google Earth street view and aerial images to estimate shade at solar noon on the summer solstice, irrespective of the date of image capture. Three researchers used the method to separately estimate shade cover over pre-defined activity areas in a sample of 45 New Zealand urban open spaces, including 24 playgrounds, 12 beaches and 9 outdoor pools. Outcome measures included method accuracy (assessed by comparison with a subsample of field observations of 10 of the settings) and inter-rater reliability. Of the 164 activity areas identified in the 45 settings, most (83%) had no shade cover. The method identified most activity areas in playgrounds (85%) and beaches (93%) and was accurate for assessing shade over these areas (predictive values of 100%). Only 8% of activity areas at outdoor pools were identified, due to a lack of street view images. Reliability for shade cover estimates was excellent (intraclass correlation coefficient of 0.97, 95% CI 0.97-0.98). Google Earth appears to be a reasonably accurate and reliable and shade audit tool for playgrounds and beaches. The findings are relevant for programmes focused on supporting the development of healthy urban open spaces.

Perceptions of European medical staff on the facilitators and barriers to physical closeness between parents and infants in neonatal units.

AIM: Studies have provided insights into factors that may facilitate or inhibit parent-infant closeness in neonatal units, but none have specifically focused on the perspectives of senior neonatal staff. The aim of this study was to explore perceptions and experiences of consultant neonatologists and senior nurses in five European countries with regard to these issues. METHODS: Six small group discussions and three-one-to-one interviews were conducted with 16 consultant neonatologists and senior nurses representing nine neonatal units from Estonia, Finland, Norway, Spain and Sweden. The interviews explored facilitators and barriers to parent-infant closeness and implications for policy and practice, and thematic analysis was undertaken. RESULTS: Participants highlighted how a humanising care agenda that enabled parent-infant closeness was an aspiration, but pointed out that neonatal units were at different stages in achieving this. The facilitators and barriers to physical closeness included socio-economic factors, cultural norms, the designs of neonatal units, resource issues, leadership, staff attitudes and practices and relationships between staff and parents. CONCLUSION: Various factors affected parent-infant closeness in neonatal units in European countries. There needs to be the political motivation, appropriate policy planning, legislation and resource allocation to increase measures that support closeness agendas in neonatal units.

Responders to insulin therapy at 18 months in adults with newly diagnosed diabetes: which insulin regimen?

OBJECTIVES: To describe baseline characteristics of responders to insulin therapy (HbA(1c) targets < 58 mmol/mol, 7.5%) at 18 months among adults with newly diagnosed diabetes. METHODS: A retrospective UK study derived from 479 general practices electronic dataset. We included all adults (age > 18 years) with newly diagnosed diabetes who required insulin therapy within 6 months of diagnosis. The data comprised insulin regimen (long-acting only; premixed insulin only; basal bolus insulin regimen), gender, Townsend quintile, baseline and an 18-month measurement of clinical and biochemical variables. Multiple imputations were undertaken and logistic regression used to assess the effect of covariates. RESULTS: A total of 1492 patients (aged 19-93 years) were analysed. Means (SD) baseline HbA(1c) and BMI were 10.3% (2.6%) and 29.6 (7.0%), respectively. Following multiple imputation for missing data, logistic regression analysis indicated important covariates to achieve HbA(1c) targets were baseline HbA(1c), lipid lowering therapy, gender and age. Including all covariates, those treated with premixed insulin were 47% more likely to achieve target HbA(1c) at 18 months than those treated with a basal-bolus regimes (adjusted OR 1.47; 95% CI 1.12-1.92, P = 0.006)) and 32% more likely than those treated with long-acting insulin was (adjusted OR 1.32; 95% CI 1.01-1.74, P = 0.044). Those with a higher baseline HbA(1c) level, on lipid-lowering therapy, women and younger patients had a lower response rate. Mean weight gain (SD) was 2.4 kg (8.5 kg) and was not influenced by treatment regimen. CONCLUSION: The use of premixed insulin regimen among newly diagnosed patients with diabetes appears to be most effective in reaching HbA(1c) target values, independent of other confounders. The appropriate choice of insulin regimen at initiation should therefore take into account various metabolic and psychosocial factors.

Efficacy of dexmedetomidine compared with midazolam for sedation in adult intensive care patients: a systematic review.

Patients in Intensive Care Unit (ICU) often require sedatives which commonly include midazolam and the more recently developed α2-receptor agonist, dexmedetomidine. It was our aim to compare the sedative and clinical effectiveness of dexmedetomidine vs midazolam in adults admitted to ICU, using an objective appraisal of randomized control trials. Medline, Embase, SCOPUS, Web of Knowledge, Cinhal, the United States National Library of Medicine, and the Cochrane Database of Systematic Reviews were searched using keywords: 'dexmedetomidine', 'midazolam', and 'intensive care'. These were limited to human studies and adults (>18 yr old). Six randomized controlled trials were found and were critically appraised using a standardized appraisal method. Two papers described the time spent by each intervention group within a specified target sedation range and both found no statistically significant difference between midazolam and dexmedetomidine (P=0.18 and P=0.15). A third paper found no statistically significant difference in the length of time that patients were sedated within a target zone (P=0.445). Two additional pilot studies did not report P values as they were insufficiently statistically powered. A final paper found that, of the eight occasions measured, patients on dexmedetomidine were more often within the target sedation range than patients on midazolam. The sedative benefits of dexmedetomidine vs midazolam remain inconclusive. While some secondary outcomes showed clinical effectiveness of dexmedetomidine, more research is needed to validate the findings of these studies.

Using a venous thromboembolism checklist significantly improves VTE prevention: a junior doctor led intervention.

AIMS: Given that venous thromboembolic disease is a significant cause of morbidity and mortality, the aim of this study was to increase the rate of VTE risk assessment performed by junior doctors in the acute setting. We also wanted to increase the rates of prescription of thromboembolic preventative measures in those patients whom the assessment identified as being high risk. METHODS: A survey of all patients admitted to three medical wards over a 3-week period was performed to determine whether VTE risk assessment had been performed, and whether prescription of prophylactic measures had been carried out where appropriate. A prompt sheet was subsequently attached to the drug card, and the survey repeated to assess impact on risk assessment and prescription rates. RESULTS: Use of the prompt sheet significantly increased the percentage of patients being appropriately prescribed VTE prophylaxis. CONCLUSIONS/MESSAGE FOR THE CLINIC: Most physicans are aware of the risk of VTE to inpatients, but because of human factors throughout the daily ward activities, VTE assessment can be missed. A simple intervention such as a VTE assessment prompt sheet on the front of the drug card can significantly improve VTE assessment and therefore patient safety.

Impact of war on veteran life span: natural experiment involving combat versus non-combat exposed military personnel.

INTRODUCTION: There is still uncertainty around the impact of combat exposure on the life span of war veterans. Therefore we made use of a natural experiment to study the impact on veteran life span of combat versus non-combat exposure in World War II (WW2). METHODS: The combat-exposed military personnel were derived from a random (10%) sample of the military roll of the 28th (Maori) Battalion from New Zealand. One non-combat cohort was the 15th Reinforcements of this same Battalion, since the war ended before they reached the front line. The other non-combat cohort were Maori personnel who were only involved in Jayforce, which occupied Japan at the end of the WW2. Data on life span were mainly derived from an official repository of birth and death records, but supplemented with other sources, including military files. RESULTS: When comparing life spans of service veterans, there was no statistically significant reduction for the average life span of the 234 combat-exposed veterans in our sample from the 28th (Maori) Battalion (66.7 years), relative to the Maori veterans from two non-combat cohorts: the 132 personnel in the 15th Reinforcements (67.2 years) and the 147 personnel in Jayforce (66.9 years). CONCLUSIONS: Despite a very high level of wounding in the combat-exposed group (48%), there were no statistically significant reductions in life span between this group and comparable non-combat exposed veterans. This finding contrasts to life span reductions found in a similar study of New Zealand veterans of WW1.

Identifying abnormalities in symbiotic development between Trifolium spp. and Rhizobium leguminosarum bv. trifolii leading to sub-optimal and ineffective nodule phenotypes.

BACKGROUND AND AIMS: Legumes overcome nitrogen limitations by entering into a mutualistic symbiosis with N(2)-fixing bacteria (rhizobia). Fully compatible associations (effective) between Trifolium spp. and Rhizobium leguminosarum bv. trifolii result from successful recognition of symbiotic partners in the rhizosphere, root hair infection and the formation of nodules where N(2)-fixing bacteroids reside. Poorly compatible associations can result in root nodule formation with minimal (sub-optimal) or no (ineffective) N(2)-fixation. Despite the abundance and persistence of strains in agricultural soils which are poorly compatible with the commercially grown clover species, little is known of how and why they fail symbiotically. The aims of this research were to determine the morphological aberrations occurring in sub-optimal and ineffective clover nodules and to determine whether reduced bacteroid numbers or reduced N(2)-fixing activity is the main cause for the Sub-optimal phenotype. METHODS: Symbiotic effectiveness of four Trifolium hosts with each of four R. leguminosarum bv. trifolii strains was assessed by analysis of plant yields and nitrogen content; nodule yields, abundance, morphology and internal structure; and bacteroid cytology, quantity and activity. KEY RESULTS: Effective nodules (Nodule Function 83-100 %) contained four developmental zones and N(2)-fixing bacteroids. In contrast, Sub-optimal nodules of the same age (Nodule Function 24-57 %) carried prematurely senescing bacteroids and a small bacteroid pool resulting in reduced shoot N. Ineffective-differentiated nodules carried bacteroids aborted at stage 2 or 3 in differentiation. In contrast, bacteroids were not observed in Ineffective-vegetative nodules despite the presence of bacteria within infection threads. CONCLUSIONS: Three major responses to N(2)-fixation incompatibility between Trifolium spp. and R. l. trifolii strains were found: failed bacterial endocytosis from infection threads into plant cortical cells, bacteroid differentiation aborted prematurely, and a reduced pool of functional bacteroids which underwent premature senescence. We discuss possible underlying genetic causes of these developmental abnormalities and consider impacts on N(2)-fixation of clovers.

Differential lifespan impacts on veterans by war exposure in the First World War.

INTRODUCTION: There remains uncertainty around the impact of war on the lifespan of First World War (WW1) veterans. In particular, study comparison groups do not typically consider the 'healthy soldier effect'. METHODS: We obtained lifespan data on a random sample of 857 war-exposed New Zealand WW1 veterans and compared this with lifespans of a non-war military cohort (n=1039). This comparison was possible as the non-war-cohort arrived in Europe too late to participate in the war, allowing a 'natural experiment' that avoided the 'healthy solider effect'. RESULTS: The lifespan comparisons indicated lower mean lifespan in the war-exposed veteran cohort compared with the non-war veteran cohort (69.7 vs 71.1 years; p=0.0405). This gap persisted (range: 0.8-1.1 years) but was no longer statistically significant when only considering the non-Maori ethnic grouping (nearly all European/Pakeha personnel), when excluding additional deaths in the immediate postwar period up to 31 December 1923, and when excluding participation in any other wars. This was the case in both analysis of variance and Cox proportional hazards regression adjusting for year of birth and occupational status. Within the war-exposed cohort, there were suggestive patterns of increasing lifespan with increasing occupational status and military rank (eg, 69.5, 70.0 and 70.7 mean years as group-level occupational status progressively increased). There were also stark differences in lifespan of 8.3 years between Maori (Indigenous) and non-Maori veterans (p=0.0083). CONCLUSIONS: The pattern of reduced lifespan in war-exposed versus non-war-exposed veterans was compatible with a smaller previous New Zealand study with comparable methodology. Veterans who were Maori had significantly lower lifespans than non-Maori veterans. There are a number of feasible avenues to further improve this type of work with existing data sources.

A community standard for immunogenomic data reporting and analysis: proposal for a STrengthening the REporting of Immunogenomic Studies statement.

Modern high-throughput HLA and KIR typing technologies are generating a wealth of immunogenomic data with the potential to revolutionize the fields of histocompatibility and immune-related disease association and population genetic research, much as SNP-based approaches have revolutionized association research. The STrengthening the REporting of Genetic Association studies (STREGA) statement provides community-based data reporting and analysis standards for genomic disease-association studies, identifying specific areas in which adoption of reporting guidelines can improve the consistent interpretation of genetic studies. While aspects of STREGA can be applied to immunogenomic studies, HLA and KIR research requires additional consideration, as the high levels of polymorphism associated with immunogenomic data pose unique methodological and computational challenges to the synthesis of information across datasets. Here, we outline the principle challenges to consistency in immunogenomic studies, and propose that an immunogenomic-specific analog to the STREGA statement, a STrengthening the REporting of Immunogenomic Studies (STREIS) statement, be developed as part of the 16th International HLA and Immunogenetics Workshop. We propose that STREIS extends at least four of the 22 elements of the STREGA statement to specifically address issues pertinent to immunogenomic data: HLA and KIR nomenclature, data-validation, ambiguity resolution, and the analysis of highly polymorphic genetic systems. As with the STREGA guidelines, the intent behind STREIS is not to dictate the design of immunogenomic studies, but to ensure consistent and transparent reporting of research, facilitating the synthesis of HLA and KIR data across studies.

Experiencing loneliness in parenthood: a scoping review.

AIMS: Chronic loneliness is experienced by around a third of parents, but there is no comprehensive review into how, why and which parents experience loneliness. This scoping review aimed to provide insight into what is already known about parental loneliness and give directions for further applied and methodological research. METHODS: Searches for peer-reviewed articles were undertaken in six databases: PsycINFO, Medline, CINAHL, Embase, Web of Science and Scopus, during May 2019 to February 2020. We searched for English studies which examined loneliness experienced during parenthood, including studies that involved parents with children under 16 years and living at home and excluding studies on pregnancy, childbirth or postbirth hospital care. RESULTS: From 2566 studies retrieved, 133 were included for analysis. Most studies (n = 80) examined the experience of loneliness in specific groups of parents, for example, teenage parents, parents of a disabled child. Other studies examined theoretical issues (n = 6) or health and wellbeing impacts on parents (n = 16) and their offspring (n = 17). There were 14 intervention studies with parents that measured loneliness as an outcome. Insights indicate that parental loneliness may be different to loneliness experienced in other cohorts. There is evidence that parental loneliness has direct and intergenerational impacts on parent and child mental health. Some parents (e.g. with children with chronic illness or disability, immigrant or ethnic minority parents) also appear to be at increased risk of loneliness although evidence is not conclusive. CONCLUSION: This work has identified key gaps with further international, comparative and conceptual research needed.

Genetic variation within the HLA class III influences T1D susceptibility conferred by high-risk HLA haplotypes.

Human leukocyte antigen (HLA) class II DRB1 and DQB1 represent the major type I diabetes (T1D) genetic susceptibility loci; however, other genes in the HLA region are also involved in T1D risk. We analyzed 1411 pedigrees (2865 affected individuals) from the type I diabetes genetics consortium genotyped for HLA classical loci and for 12 single-nucleotide polymorphisms (SNPs) in the class III region previously shown to be associated with T1D in a subset of 886 pedigrees. Using the transmission disequilibrium test, we compared the proportion of SNP alleles transmitted from within the high-risk DR3 and DR4 haplotypes to affected offspring. Markers rs4151659 (mapping to CFB) and rs7762619 (mapping 5' of LTA) were the most strongly associated with T1D on DR3 (P=1.2 x 10(-9) and P=2 x 10(-12), respectively) and DR4 (P=4 x 10(-15) and P=8 x 10(-8), respectively) haplotypes. They remained significantly associated after stratifying individuals in analyses for B*1801, A*0101-B*0801, DPB1*0301, DPB1*0202, DPB1*0401 or DPB1*0402. Rs7762619 and rs4151659 are in strong linkage disequilibrium (LD) (r(2)=0.82) with each other, but a joint analysis showed that the association for each SNP was not solely because of LD. Our data support a role for more than one locus in the class III region contributing to risk of T1D.

Membrane distribution and adsorptive endocytosis by C3b receptors on human polymorphonuclear leukocytes.

C3b receptors on human polymorphonuclear leukocytes (PMN) were nonrandomly distributed in small clusters on the plasma membranes of these cells when assessed by indirect immunofluorescence at 0 degree C using monospecific rabbit Fab' or F(ab')2 anti-C3b receptor and tetramethylrhodamine isothiocyanate (TRITC)-conjugated goat IgG anti-F(ab')2. When PMN were incubated with the bivalent anti-C3b receptor at 37 rather than at 0 degree C, almost no immunofluorescence was observed, which indicates that the C3b receptor-F(ab')2 complexes had been rendered inaccessible to TRITC-IgG anti-F(ab')2. Endocytosis of the anti-C3b receptor ligand was quantitated by measuring the binding 131I-IgG anti-F(ab')2 by PMN that had previously taken up 125I-F(ab')2 anti-C3b receptor at 0 and at 37 degree C, respectively. There was a constant 2: 1 molar ratio of anti-F(ab')2 to anti-C3b receptor with PMN that had been incubated with the first antibody at 0 degree C. In contrast, when increments of F(ab')2 anti-C3b receptor were taken up by the cells at 37 degree C, there was a dose-related decline in this molar ratio to a minimum of 0.2 molecules of anti-F(ab')2 anti-F(ab')2 bound per molecule of PMN-associated anti-C3b receptor. 125I-F(ab')2 anti-C3b receptor taken up by PMN at 37 degree C was also inaccessible to release by proteolytic treatment of the cells with pronase. The rate of endocytosis of 125I-F(ab')2 anti-C3b receptor was rapid as the PMN-bound antibody fragment became inaccessible to 131I-IgG anti-F(ab')2 within 10 min during incubation of the cells at 37 degree C. In contrast to these findings, 125I-Fab' anti-C3b receptor that was taken up by PMN at 37 degree C remained accessible to both 131I-IgG anti-F(ab')2 and to proteolytic release by pronase, which suggests that monovalent interaction of ligand with C3b receptors was not sufficient for induction of endocytosis. The requirement for multivalency was also demonstrated using the C3b-OR, the normal ligand for the C3b receptor. 125I-C3b-OR was specifically bound by PMN but remained on the cell receptor. 125I-C3b-OR was specifically bound by PMN but remained on the cell surface, as determined by its accessibility to pronase, unless it was cross-linked with F(ab')2 anti-C3. Although C3b receptors on PMN do not mediate internalization of adsorptive pinocytosis of soluble ligand indicates their potential for the clearance of C3b-bearing immune complexes without recruitment of other cell surface receptors.

How do tobacco retail displays affect cessation attempts? Findings from a qualitative study.

BACKGROUND: Tobacco retail displays promote smoking experimentation among youth; however, little is known about their effect on smokers making a quit attempt. Calls to ban tobacco retail displays would be strengthened if this measure would deter initiation and support cessation. METHODS: Semistructured in-depth interviews were conducted with 20 individuals, from two New Zealand provincial cities, who had attempted to quit smoking in the last 6 months. RESULTS: Tobacco products had high visibility, and elicited emotional and physical reactions that created on-going temptation, complicated cessation attempts and stimulated impulse purchases. Participants strongly supported banning tobacco retail displays primarily because they thought this would reduce youth initiation, promote greater consistency with smoke-free promotions and assist those attempting to quit. CONCLUSIONS: The effects of tobacco retail displays on smokers making a cessation attempt are explored. The findings are consistent with experimental and survey research, and expand a growing evidence base that supports government-mandated bans on tobacco retail displays.

Crimean-Congo hemorrhagic fever in Europe: current situation calls for preparedness.

During the last decade Crimean-Congo hemorrhagic fever (CCHF) emerged and/or re-emerged in several Balkan countries, Turkey, southwestern regions of the Russian Federation, and the Ukraine, with considerable high fatality rates. Reasons for re-emergence of CCHF include climate and anthropogenic factors such as changes in land use, agricultural practices or hunting activities, movement of livestock that may influence host-tick-virus dynamics. In order to be able to design prevention and control measures targeted at the disease, mapping of endemic areas and risk assessment for CCHF in Europe should be completed. Furthermore, areas at risk for further CCHF expansion should be identified and human, vector and animal surveillance be strengthened.

Adalimumab for long-term treatment of psoriatic arthritis: 2-year data from the Adalimumab Effectiveness in Psoriatic Arthritis Trial (ADEPT).

OBJECTIVE: To evaluate the long-term effectiveness and tolerability of adalimumab in the treatment of psoriatic arthritis (PsA). METHODS: Patients with PsA who completed a 24-week, double-blind study of adalimumab versus placebo were eligible to enroll in an open-label extension study and receive adalimumab 40 mg subcutaneously every other week for up to an additional 120 weeks. At the time of this analysis, available efficacy evaluations throughout 2 years of treatment (n = 245) included American College of Rheumatology (ACR) 20%, 50% and 70% improvement scores, measures of joint disease and skin disease, disability and quality of life; modified total Sharp scores (mTSS) were available for 2.75 years of treatment for patients who received adalimumab in the 24-week study. RESULTS: After 24 weeks of double-blind treatment, the mean change in mTSS was -0.2 for the adalimumab group (N = 144) and 1.0 for the placebo group (N = 152; p<0.001), and outcomes for all individual ACR component variables were significantly improved in adalimumab compared with placebo-treated patients. Compared with 24-week responses, inhibition of radiographic progression and improvements in joint disease were maintained in most patients during long-term, open-label adalimumab treatment. Also, improvements in skin disease were maintained, with >20% of patients achieving the strict criterion of psoriasis area and severity index 100. The nature and frequency of adverse events during long-term adalimumab treatment were consistent with the safety profile during short-term treatment. CONCLUSIONS: The clinical and radiographic efficacy of adalimumab demonstrated during short-term treatment was sustained during long-term treatment. Adalimumab has a favourable risk-benefit profile in patients with PsA. TRIAL REGISTRATION NUMBER: NCT00195689.

The genetics of complex diseases.

Genetic factors influence virtually every human disorder, determining disease susceptibility or resistance and interactions with environmental factors. Our recent successes in the genetic mapping and identification of the molecular basis of mendelian traits have been remarkable. Now, attention is rapidly shifting to more-complex, and more-prevalent, genetic disorders and traits that involve multiple genes and environmental effects, such as cardiovascular disease, diabetes, rheumatoid arthritis and schizophrenia. Rather than being due to specific and relatively rare mutations, complex diseases and traits result principally from genetic variation that is relatively common in the general population. Unfortunately, despite extensive efforts by many groups, only a few genetic regions and genes involved in complex diseases have been identified. Completion of the human genome sequence will be a seminal accomplishment, but it will not provide an immediate solution to the genetics of complex traits.

Several loci in the HLA class III region are associated with T1D risk after adjusting for DRB1-DQB1.

AIM: Several studies have indicated that genes in the human leucocyte antigen (HLA) region additional to the HLA class II DRB1-DQB1 contribute to type 1 diabetes (T1D) susceptibility. The aim of this study was to assess if markers in the class III Major Histocompatibility Complex (MHC) region are associated with T1D after accounting for linkage disequilibrium (LD) with DRB1-DQB1. METHODS: We investigated 356 single nucleotide polymorphisms (SNPs) in the class III region covering 1.1 megabases in two subsets of data: 289 Human Biological Data Interchange (HBDI) Caucasian families and 597 additional Caucasian families collected by the Type 1 Diabetes Genetics Consortium (T1DGC). Analysis conditioning on DRB1-DQB1 was performed using the overall conditional genotype method. RESULTS: Thirteen SNPs replicated in both subsets of the data and showed evidence of an additional effect on disease risk. Although some of the SNPs are in tight LD with each other, at least six of the associations were not because of LD with other class III markers. The strongest association within class III markers was with rs2395106 that maps 5' to the NOTCH4 gene, which has also been implicated in susceptibility to rheumatoid arthritis. The second association was with rs707915 mapping to the MSH5 gene, in a block of six markers significantly associated with T1D after adjusting for LD with DR-DQ. In total, six-independent associations within class III were observed although results were not adjusted for LD with class I. CONCLUSIONS: Our data confirm that the class III region is involved in T1D susceptibility and suggest that more than one gene in the region is involved.