Clinical characteristics of people with intellectual disability admitted to hospital with constipation: identifying possible specific high-risk factors.

BACKGROUND: People with intellectual disabilities (ID) die on an average 20 years earlier to the general population. They have higher rates of multimorbidity and polypharmacy. Around 25% of people with ID report chronic constipation. The England Learning Disabilities Mortality Review found that nearly 25% of deaths identified constipation as a long-term health problem. However, the likely risk factors for constipation related harm are poorly enumerated. We sought to identify possible specific high-risk factors by examining the clinical characteristics of people with ID admitted to hospital with constipation. METHODS: Data of people with ID admitted with constipation in two general hospitals covering a population of 1.3 million from 2017 to 2022 were reported using the STROBE guideline for cohort studies. Collected data included age, gender, intellectual disability severity, recorded medication, presenting complaint and co-morbidities. The medication anticholinergic burden was calculated using the anticholinergic burden scale. Continuous variables were summarised by mean and standard deviation if normally distributed, with categorical variables summarised by the number and percentage in each category. RESULTS: Of 46 admissions (males 52%), 57% had moderate to profound ID, 37% had epilepsy, 41% prescribed antiseizure medication (ASM) and 45% were on laxatives. Average age was 46 years. The anticholinergic burden score mean was 2.3 and median, one. CONCLUSIONS: We can hypothesise that people with more severe ID, suffering from epilepsy and on ASM may be more at risk of developing severe constipation. Some admissions may be avoided with earlier use of laxatives in the community.

Analytic Form of the Full Two-Loop Five-Gluon All-Plus Helicity Amplitude.

We compute the full-color two-loop five-gluon amplitude for the all-plus helicity configuration. In order to achieve this, we calculate the required master integrals for all permutations of the external legs, in the physical scattering region. We verify the expected divergence structure of the amplitude and extract the finite hard function. We further validate our result by checking the factorization properties in the collinear limit. Our result is fully analytic and valid in the physical scattering region. We express it in a compact form containing logarithms, dilogarithms, and rational functions.

Abdominal Aortic Aneurysm Genetic Associations: Mostly False? A Systematic Review and Meta-analysis.

OBJECTIVE/BACKGROUND: Many associations between abdominal aortic aneurysm (AAA) and genetic polymorphisms have been reported. It is unclear which are genuine and which may be caused by type 1 errors, biases, and flexible study design. The objectives of the study were to identify associations supported by current evidence and to investigate the effect of study design on reporting associations. METHODS: Data sources were MEDLINE, Embase, and Web of Science. Reports were dual-reviewed for relevance and inclusion against predefined criteria (studies of genetic polymorphisms and AAA risk). Study characteristics and data were extracted using an agreed tool and reports assessed for quality. Heterogeneity was assessed using I(2) and fixed- and random-effects meta-analyses were conducted for variants that were reported at least twice, if any had reported an association. Strength of evidence was assessed using a standard guideline. RESULTS: Searches identified 467 unique articles, of which 97 were included. Of 97 studies, 63 reported at least one association. Of 92 studies that conducted multiple tests, only 27% corrected their analyses. In total, 263 genes were investigated, and associations were reported in polymorphisms in 87 genes. Associations in CDKN2BAS, SORT1, LRP1, IL6R, MMP3, AGTR1, ACE, and APOA1 were supported by meta-analyses. CONCLUSION: Uncorrected multiple testing and flexible study design (particularly testing many inheritance models and subgroups, and failure to check for Hardy-Weinberg equilibrium) contributed to apparently false associations being reported. Heterogeneity, possibly due to the case mix, geographical, temporal, and environmental variation between different studies, was evident. Polymorphisms in nine genes had strong or moderate support on the basis of the literature at this time. Suggestions are made for improving AAA genetics study design and conduct.

Role of carcinoembryonic antigen as a marker for colorectal liver metastases.

Carcinoembryonic antigen (CEA), a marker for colorectal adenocarcinoma, can monitor disease progression and treatment response. This study aims to determine the accuracy of CEA in the detection and resectability of colorectal liver metastases. Patients with primary colorectal cancer were divided into three groups: resectable hepatic metastases (group 1), unresectable metastases (group 2), and disease-free cases (group 3). The CEA concentration was recorded pre- and post-hepatectomy in group 1 and on radiological confirmation of disease state in the other groups. It was expressed as median (95% confidence interval [CI]), with predictors of concentration determined. Group 1 (n=141) had pre-operative CEA of 8.9 (4.6-13.1), with 38.1% of patients being normal. Maximum tumour diameter correlated with CEA level (r=0.41, P<0.0001). Post-hepatectomy CEA was 2.3 (1.9-2.7; P<0.0001), with 81.1% of patients being normal. Group 2 (n=158) had CEA of 20.6 (9.4-31.9). Group 3 (n=361) had CEA of 2.0 (1.8-2.2). Sensitivity of CEA pre- and post-hepatectomy was 61.2% and 69.3%, respectively, while specificity was 79.8% for both groups. Concentration was elevated in hepatic colorectal metastases but is not a marker of resectability. A CEA reduction post-resection indicates that it may be used as an indicator of treatment response, while CEA is increased by tumour burden and lesion size.

Chlamydia pneumoniae antibodies and C-reactive protein levels in patients with abdominal aortic aneurysms.

INTRODUCTION: The study aim was to assess the relationship between the presence of antibodies to Chlamydia pneumoniae and abdominal aortic aneurysm (AAA) incidence. PATIENTS AND METHODS: Consecutive AAA patients and AAA-free controls were recruited prospectively. Serum samples from both groups were examined to determine Immunoglobulin (Ig) A and IgG titres against Chlamydia pneumoniae by ELISA and C-reactive protein (CRP) concentrations. Results were expressed as mean (SD) or median (IQR) and compared using χ (2) and Mann-Whitney U tests. A P value of <0.05 was considered statistically significant. RESULTS: Each study group (AAA/nAAA) comprised 250 patients. 196 (78.7%) AAA patients had positive IgA antichlamydial antibody titres, compared to 181 (72.4%) in the control group (P = 0.008, OR 2.0, 95% CI 1.2-3.5). However, positive IgG antibody titres were similar (191 versus 203; P = 0.222, OR 0.7, 95% CI 0.4-1.3). Average CRP concentrations were higher in AAA individuals. IgA or IgG antibody titres were not related to CRP concentrations. CONCLUSIONS: These results demonstrated that the frequent incidence of Chlamydia pneumoniae antibodies within the general population makes it difficult to relate its presence to AAA development, despite the high IgA antibody titres. In addition, raised CRP concentrations in AAA patients are not related to the presence of antichlamydial antibodies.

Implications of attendance patterns in Northern Ireland for abdominal aortic aneurysm screening.

INTRODUCTION: Evidence supports the introduction of an abdominal aortic aneurysm (AAA) screening programme. The aims of this study were to estimate future disease patterns and to determine the effect of the proportion attending on the programme's cost-effectiveness. PATIENTS AND METHODS: The results of the local AAA screening programme were reviewed. Ultrasonic infrarenal aortic diameter of 30 mm was considered aneurysmal. Projected population numbers from the Department of Health and current disease prevalence were used to estimate future number of potential patients. The Multi-centre Aneurysm Screening Study (MASS) Markov model was used to calculate an incremental cost-effectiveness ratio (ICER) and 95% uncertainty intervals (UI), using a 30-year time horizon and 3.5% per annum discount, to determine the effect of attendance. RESULTS: Men were recruited from August 2004 to May 2010. 13316 were invited for a scan and 5931 (44.5%) attended. 321 AAA were diagnosed, giving a prevalence of 5.4%, while 27 large AAA (0.46%) were repaired. The annual incidence of AAA until 2021 will range from 441 to 526, with an incidence of 40-48 large AAA, with both showing a gradual increase with time. Using this attendance rate, the ICER was calculated at £2350 per life-year gained (95% UI: £1620-£4290), or £3020 per quality-adjusted life-year gained (95% UI: £2080-£5500). CONCLUSIONS: The prevalence of disease in this local AAA screening was similar to other studies. The low attendance will result in many AAA being missed, but will not impact greatly on the long-term cost-effectiveness.

Coding polymorphisms in the genes of the alternative complement pathway and abdominal aortic aneurysm.

Variants in the genes of the alternative complement pathway are associated with risk of numerous inflammatory diseases. Abdominal aortic aneurysm is associated with inflammation and is a common cause of illness and death among European populations. This study tested 49 single nucleotide polymorphisms, including common putatively functional polymorphisms, in the genes of the alternative complement cascade (CFH, CFB, CFD, CFI, properdin, CR1, CR1L, CR2, CD46, vitronectin, C3, C5, C6, C7, C8A, C8B, C8G and C9). The study group were 434 cases with infra-renal aortic diameter ≥30 mm and 378 disease-free controls from two UK centres, all with self-reported European ancestry. There was no evidence for significant association with presence or size of aneurysm following correction for multiple testing. This study suggests that variation in the genes of the alternative pathway is not an important cause of abdominal aortic aneurysm development.

The role of microwave ablation in the management of hepatic colorectal metastases.

BACKGROUND: colorectal metastatic disease of the liver carries a significant mortality. Surgical resection improves prognosis in suitable patients. Microwave ablation is a recent innovative technique for the management of hepatic cancer. The aim of this study was to review the relevant literature regarding its safety and efficacy. METHODS: a literature search was performed using Pubmed, Athens, Medline and Google Scholar search engine. The following key words were used - thermal ablation, microwave ablation, liver, colorectal cancer, colorectal liver metastases - singly or in combination. To ensure an up-to-date literature search, the search has been restricted to the last ten years from 2000 to date inclusively, and the search was restricted to English language articles. To maximize this search backward chaining of reference lists from retrieved papers was also undertaken. CONCLUSIONS: microwave ablation adds another potential treatment modality to the hepatic surgeon armament. It can be performed safely and has an acceptably low complication rate.

Risk stratification as a means of reducing the burden of follow-up after completion of initial treatment for breast cancer.

INTRODUCTION: Little evidence exists regarding the optimum frequency or duration of follow-up for patients with breast cancer. The aim of this study was to assess the effectiveness of a risk-stratified follow-up programme. METHODS: Patients treated surgically for primary breast cancer from January 2000 to September 2006 were recorded on a BASO database. Follow-up was stratified according to risk of relapse as determined by the Nottingham Prognostic Index (NPI). Patients were assigned to high, moderate or low risk groups. The date of recurrence, time from primary diagnosis and site of relapse were obtained from the database. Review of case notes was used to confirm the method of detection. RESULTS: 1303 women had surgery for primary breast cancer in the study period. Median follow-up was 40 months. Overall survival rate was 96.9% (90.4% high, 97.3% moderate, 99.5% low). Disease free survival was 94.1% (84.1% high, 94.7% moderate, 98.1% low). Seventy-seven recurrences were detected with 39 (51%) in the high risk group, 27 (35%) in the moderate risk group and 11 (14%) in the low risk group. Detection rate at a scheduled appointment was 0.27% overall (low risk 0.14%, moderate risk 0.27%, high risk 0.45%). CONCLUSIONS: NPI correlates with risk of recurrent disease. Scheduled follow-up yielded few recurrences, suggesting early discharge with open access to clinics could be a safe alternative. This type of follow-up may reduce demand on specialist clinics without significantly affecting patient care or overall survival.

Determinants of radiation exposure during EVAR.

OBJECTIVES: Endovascular aneurysm repair (EVAR) is an established method of aortic aneurysm repair, in favourable anatomical configurations. It does however expose patients to radiation. The study aim was to determine if the aneurysm neck morphology influenced radiation exposure. PATIENTS AND METHODS: All elective and emergency EVAR patients were identified. Elective patients had a bifurcated stent-graft deployed, while emergency patients were repaired with an aorto-uni-iliac stent-graft and fem-fem crossover bypass. Proximal and distal aortic neck diameters, neck length, neck angles and sac diameter were recorded, with the radiation dose, screening time and contrast volume. The two subgroups of elective and emergency patients were compared and correlation between anatomical and radiological parameters calculated by using Pearson's correlation coefficient. RESULTS: 320 (270 male) elective patients and 64 (55 male) emergency patients from October 1998 to October 2008 underwent EVAR. The mean proximal (p = 0.004) and distal (p = 0.01) neck diameters were smaller and mean sac diameter (p < 0.0001) was greater in emergencies. No difference between groups existed in the neck length (p = 0.36) and suprarenal diameter (p = 0.30), sagittal (p = 0.05) and coronal (p = 0.62) neck angles. The screening time (p = 0.053) and contrast volume (p = 0.04) were lower, with a slightly higher radiation dose (p = 0.12) in emergencies. There was no definite correlation between the seven anatomical and three radiological parameters. CONCLUSION: While radiation exposure is different in emergency patients, this is thought due to surgical technique rather than the aneurysm neck morphology.

Antimicrobial use and stewardship practices on Australian beef feedlots.

OBJECTIVE: Improving antimicrobial stewardship in the livestock sector requires an understanding of the motivations for antimicrobial use and the quantities consumed. However,detailed information on antimicrobial use in livestock sectors is lacking. This cross-sectional study aimed to better understand antimicrobial use in the beef feedlot sector in Australia. DESIGN: A self-administered questionnaire asking about antimicrobial use and reasons for use was designed and mailed to beef feedlot operators in Australia. Respondents were asked to report the percentage of animals treated, purpose of use, and disease conditions targeted for 26antimicrobial agents. RESULTS: In total, 83 of 517 (16.1%) beef feedlot operators completed the survey. Monensin (61.0%of respondents) and virginiamycin (19.5%of respondents) were the most commonly reported in-feed antimicrobials. In-feed antimicrobial agents were most frequently used by respondents for treatment of gastrointestinal diseases (52.8%). Antimicrobials were used for growth promotion by 42.1% of respondents, with most (85.7%) reporting the use of ionophores(a group of compounds not used in human medicine). Short-acting penicillin(69.1%), short-acting oxytetracycline, and tulathromycin (both 57.3%) werethe most common injectable antimicrobial agents used. Injectable antimicrobials were most frequently used to treat respiratory (72.3%) and musculoskeletal (67.5%) conditions. CONCLUSION: Overall,the use of antimicrobials was appropriate for the purpose indicated, and there was a strong preference for drugs of low-importance in human medicine. The data described here stand to be a strong influence on the implementation of an antimicrobial stewardship program in the sector.

The effects of cilostazol on exercise-induced ischaemia-reperfusion injury in patients with peripheral arterial disease.

OBJECTIVES: Cilostazol improves walking distance in peripheral arterial disease (PAD) patients. The study objectives were to assess the effects of cilostazol on walking distance, followed by the additional assessment of cilostazol on exercise-induced ischaemia-reperfusion injury in such patients. METHODS: PAD patients were prospectively recruited to a double-blinded, placebo-controlled trial. Patients were randomised to receive either cilostazol 100mg or placebo twice a day. The primary end-point was an improvement in walking distance. Secondary end-points included the assessment of oxygen-derived free-radical generation, antioxidant consumption and other markers of the inflammatory cascade. Initial and absolute claudication distances (ICDs and ACDs, respectively) were measured on a treadmill. Inflammatory response was assessed before and 30 min post-exercise by measuring lipid hydroperoxide, ascorbate, alpha-tocopherol, beta-carotene, P-selectin, intracellular and vascular cell-adhesion molecules (I-CAM and V-CAM), thromboxane B(2) (TXB(2)), interleukin-6, interleukin-10, high-sensitive C-reactive protein (hsCRP), albumin-creatinine ratio (ACR) and urinary levels of p75TNF receptor. All tests were performed at baseline and 6 and 24 weeks. RESULTS: One hundred and six PAD patients (of whom 73 were males) were recruited and successfully randomised from December 2004 to January 2006. Patients who received cilostazol demonstrated a more significant improvement in the mean percentage change from baseline in ACD (77.2% vs. 26.6% at 6 weeks, p=0.026 and 161.7% vs. 79.0% at 24 weeks, p=0.048) as compared to the placebo. Cilostazol reduced lipid hydroperoxide levels compared to a placebo-related increase before and after exercise (6 weeks: pre-exercise: -11.8% vs. +5.8%, p=0.003 and post-exercise: -12.3% vs. +13.9%, p=0.007 and 24 weeks: pre-exercise -15.5% vs. +12.0%, p=0.025 and post-exercise: -9.2% vs. +1.9%, p=0.028). beta-Carotene levels were significantly increased in the cilostazol group, compared to placebo, before exercise at 6 and 24 weeks (6 weeks: 34.5% vs. -7.4%, p=0.028; 24 weeks: 34.3% vs. 17.7%, p=0.048). Cilostazol also significantly reduced P-selectin, I-CAM and V-CAM levels at 24 weeks as compared to baseline (p<0.05). There was no difference between treatment groups for ascorbate, alpha-tocopherol, interleukin-6 and -10, hsCRP and p75TNF receptor levels. CONCLUSIONS: Cilostazol significantly improves ACD, in addition to attenuating exercise-induced ischaemia-reperfusion injury, in PAD patients.

Management of liver trauma.

BACKGROUND: Blunt and penetrating liver trauma is common and often presents major diagnostic and management problems. METHODS: A literature review was undertaken to determine the current consensus on investigation and management strategies. RESULTS: The liver is the most frequently injured organ following abdominal trauma. Immediate assessment with ultrasound has replaced diagnostic peritoneal lavage in the resuscitation room, but computerised tomography remains the gold standard investigation. Nonoperative management is preferred in stable patients but laparotomy is indicated in unstable patients. Damage control techniques such as perihepatic packing, hepatotomy plus direct suture, and resectional debridement are recommended. Major complex surgical procedures such as anatomical resection or atriocaval shunting are now thought to be redundant in the emergency setting. Packing is also recommended for the inexperienced surgeon to allow control and stabilisation prior to transfer to a tertiary centre. Interventional radiological techniques are becoming more widely used, particularly in patients who are being managed nonoperatively or have been stabilised by perihepatic packing. CONCLUSIONS: Management of liver injuries has evolved significantly throughout the last two decades. In the absence of other abdominal injuries, operative management can usually be avoided. Patients with more complex injuries or subsequent complications should be transferred to a specialist centre to optimise final outcome.

Smoking impairs endothelial function in human saphenous vein in an ex vivo model.

The aim of this ex vivo experimental study was to assess the effect of smoking, diabetes mellitus, and hypertension on endothelial function in human saphenous vein, a commonly used conduit for coronary and peripheral arterial bypass surgery. A segment of long saphenous vein harvested during infrainguinal bypass surgery was mounted in an organ bath for isometric tension studies. Vein rings were precontracted to submaximal contraction with phenylephrine, followed by endothelium-dependent relaxation with acetylcholine. Long saphenous vein segments were collected from 26 patients, including five females, with a mean age of 66.4 years (range 48-92). Current smokers had impaired endothelium-dependent relaxation compared to ex- and nonsmokers (10.2%, n=13, vs. 32.9%, n=13; p<0.010). However, ex-smokers and nonsmokers did not have a significant difference in relaxant responses to acetylcholine (29.1%, n=8, vs. 24.6%, n=5; p=nonsignificant [ns]). Similarly, diabetic and nondiabetic patients did not show a significant difference in endothelium-dependent relaxation (23.1%, n=10, vs. 15.6%, n=16; p=ns). The relaxant responses in hypertensive and normotensive patients were not different (20.4%, n=12, vs. 22.5%, n=14; p=ns). Smoking has a deleterious effect on the endothelial function of saphenous vein, and smoking cessation may improve the long-term durability of saphenous vein used as a bypass graft in patients undergoing arterial reconstruction.

Ultrasound is a useful adjunct to mammography in the assessment of breast tumours in all patients.

BACKGROUND: Ultrasound is the first-line breast imaging modality in younger patients and an adjunct to mammography in older patients. The objectives of this study were to evaluate the complementary value of ultrasound to mammography in breast cancer and to investigate the use of ultrasound in patients above and below the age of 50 years. METHODS: Clinical presentation and investigations for consecutive patients undergoing triple assessment at a symptomatic breast clinic were prospectively recorded between January 2000 and August 2003. Clinical data were compared with pathological findings. Patients were divided into two groups, above and below 50 years of age for subgroup analyses. RESULTS: A total of 999 of 2185 patients had both mammography and ultrasound investigations performed and constituted the study population. Subgroup analysis of the 2185 patients demonstrated that 99 of the 127 patients who were diagnosed with breast cancer had both investigations performed (median age 57.0, range: 34-89 years). Mammography was normal/benign in 14.1%, indeterminate in 29.3% and suspicious of cancer in 56.6% of patients. Adjunctive ultrasound was normal/benign in 13.1%, indeterminate in 6.1% and suspicious of cancer in 80.8% of patients. In these 99 patients, adjunctive ultrasound was more sensitive than mammogram alone (80.8% vs. 56.6%, p < 0.001). Ultrasound upgraded nine of 14 mammographically normal and 16 of 29 mammographically indeterminate X-rays to a cancer. Mammography appeared to be more sensitive in patients over 50 years compared with those patients under 50 years (62.5% vs. 45.7%, p = 0.10). The sensitivity of ultrasound was comparable between patients above and below the age of 50 years (82.8% vs. 77.1%, p = 0.60). Further subgroup analysis demonstrated a higher sensitivity with combined mammography and ultrasound compared with mammography alone in either patient group (below 50: 45.7%-->77.1% and above 50: 62.5%-->82.8%). These results also suggested that the difference in the sensitivities of mammography vs. the combined investigation approach was more marked in patients under 50 years of age (below 50 = 31.4% vs. above 50 = 20.3%). CONCLUSION: Adjunctive ultrasound assessment improves breast cancer detection in women of all ages and should be routinely used in symptomatic breast clinics.

Fine needle aspiration at a Regional Head and Neck Clinic: a clinically beneficial and cost-effective service.

BACKGROUND: Fine needle aspiration (FNA) is an important adjuvant to the diagnosis of a palpable lesion which often permits the complete assessment of patients. The main objective of this study was to determine the clinical benefit of a dedicated FNA service at a tertiary referral Head and Neck Clinic and to assess if such a service is cost effective. METHODS: All patients attending the Head and Neck Clinic during 2004 were prospectively assessed in this study. Patient records were analysed regarding investigative modalities including FNA, the subsequent cytology result and the requirement for further histopathological investigations. A cost analysis for all investigative procedures was performed. RESULTS: A total of 135 patients (36 males) had FNAs performed during the study period. The median age was 51.5 years (range 17-92). Patients presented with lesions of lymph nodes (n = 46), thyroid (n = 41), salivary, parotid or submandibular glands (n = 22) and other cutaneous or cystic lesions (n = 26). Cytological grading results were; C1 = 26, C2 = 93, C3 = 8, C4 = 2 and C5 = 6. Patients with lesions C3 or above normally proceeded to further investigations. The overall cost of the FNA per episode in the out-patient clinic was pound114 per episode compared to day case open biopsy per patient of pound333 and an in-patient stay per patient was pound2371. FNA provided sufficient pathological diagnosis to avoid day case surgery in 57 patients (42.2%), and inpatient surgery in 65 patients (48.1%) resulting in a total saving of pound158 372 in 2004. CONCLUSION: This study demonstrates the clinical benefit and cost-effectiveness of FNA services in a dedicated Head and Neck clinic.

Completion mastectomy after breast conserving surgery.

BACKGROUND: Breast conserving surgery (BCS) is increasingly offered to suitable patients diagnosed with early stage breast cancer. Occasionally the pathological margins on specimens following BCS are positive. The objective of this study is to assess the proportion of patients within our unit who required completion mastectomy after BCS and to determine if predictive factors could be identified to assist the breast surgeon identifying those patients at risk of positive margins following BCS. METHODS: All patients diagnosed with breast cancer between 2001 and 2005 were reviewed. Patients undergoing BCS had their histopathological specimens examined for any evidence of residual tumour at the margins of the resected specimen. These patients then proceeded to completion mastectomy if these margins were positive for residual tumour. Multinominal logistic regression was then performed on clinico-pathological factors for each of these patients to determine if predictive factors existed for determination of residual disease in the mastectomy specimen following BCS. RESULTS: Logistic regression demonstrated that size of the initial tumour was the only significant predictor for the presence of completion mastectomy residual carcinoma (CMRC) (p=0.014) and that tumours with an initial size > 2.5 cm were 15 times more likely to have a CMRC than tumours < 1.5 cm. This prediction model based on the initial tumour size had an 89.5% specificity and 52.2% sensitivity. The odds ratio for CMRC based on histological tumour type for each additional 1cm increase in size of the initial tumour was 2.82 for ductal carcinoma in situ, 2.60 for infiltrating ductal carcinoma and 2.26 for other tumours. CONCLUSION: This study demonstrates that residual disease in total mastectomy specimens following BCS increases significantly with increasing original tumour size. With current data, surgeons can inform patients of the risks of residual cancer associated with BCS with a view to increase the rate of primary mastectomies in those patients with presenting tumours greater than 2.5 cm.

Ethical Issues in the Development of Readiness Cohorts in Alzheimer's Disease Research.

There is growing interest in the development of novel approaches to secondary prevention trials in Alzheimer's disease to facilitate screening and recruitment of research participants and to reduce the time and costs associated with clinical trials. Several international research collaborations are setting up research infrastructures that link existing research cohorts, studies or patient registries to establish 'trial-ready' or 'readiness' cohorts. From these cohorts, individuals are recruited into clinical trial platforms. In setting up such research infrastructures, researchers must make ethically challenging design decisions in at least three areas: re-contacting participants in existing research studies, obtaining informed consent for participation in a readiness cohort, and disclosure of Alzheimer's disease-related biomarkers. These ethical considerations have been examined by a dedicated workgroup within the European Prevention of Alzheimer's Dementia (EPAD) project, a trans-European longitudinal cohort and adaptive proof-of-concept clinical trial platform. This paper offers recommendations for the ethical management of re-contact, informed consent and risk disclosure which may be of value to other research collaborations in the process of developing readiness cohorts for prevention trials in Alzheimer's disease and other disease areas.

Endovascular repair or open repair for ruptured abdominal aortic aneurysm: a Cochrane systematic review.

OBJECTIVES: Emergency endovascular aneurysm repair (eEVAR) may improve outcomes for patients with ruptured abdominal aortic aneurysm (RAAA). The study aim was to compare the outcomes for eEVAR with conventional open surgical repair for the treatment of RAAA. SETTING: A systematic review of relevant publications was performed. Randomised controlled trials (RCTs) comparing eEVAR with open surgical repair for RAAA were included. PARTICIPANTS: 3 RCTs were included, with a total of 761 patients with RAAA. INTERVENTIONS: Meta-analysis was performed with fixed-effects models with ORs and 95% CIs for dichotomous data and mean differences with 95% CIs for continuous data. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome was short-term mortality. Secondary outcome measures included aneurysm-specific and general complication rates, quality of life and economic analysis. RESULTS: Overall risk of bias was low. There was no difference between the 2 interventions on 30-day (or in-hospital) mortality, OR 0.91 (95% CI 0.67 to 1.22; p=0.52). 30-day complications included myocardial infarction, stroke, composite cardiac complications, renal complications, severe bowel ischaemia, spinal cord ischaemia, reoperation, amputation and respiratory failure. Reporting was incomplete, and no robust conclusion was drawn. For complication outcomes that did include at least 2 studies in the meta-analysis, there was no clear evidence to support a difference between eEVAR and open repair. Longer term outcomes and cost per patient were evaluated in only a single study, thus precluding definite conclusions. CONCLUSIONS: Outcomes between eEVAR and open repair, specifically 30-day mortality, are similar. However, further high-quality trials are required, as the paucity of data currently limits the conclusions.

Psychological, behavioral and social effects of disclosing Alzheimer's disease biomarkers to research participants: a systematic review.

BACKGROUND: Current Alzheimer's disease (AD) research initiatives focus on cognitively healthy individuals with biomarkers that are associated with the development of AD. It is unclear whether biomarker results should be returned to research participants and what the psychological, behavioral and social effects of disclosure are. This systematic review therefore examines the psychological, behavioral and social effects of disclosing genetic and nongenetic AD-related biomarkers to cognitively healthy research participants. METHODS: We performed a systematic literature search in eight scientific databases. Three independent reviewers screened the identified records and selected relevant articles. Results extracted from the included articles were aggregated and presented per effect group. RESULTS: Fourteen studies met the inclusion criteria and were included in the data synthesis. None of the identified studies examined the effects of disclosing nongenetic biomarkers. All studies but one concerned the disclosure of APOE genotype and were conducted in the USA. Study populations consisted largely of cognitively healthy first-degree relatives of AD patients. In this group, disclosure of an increased risk was not associated with anxiety, depression or changes in perceived risk in relation to family history. Disclosure of an increased risk did lead to an increase in specific test-related distress levels, health-related behavior changes and long-term care insurance uptake and possibly diminished memory functioning. CONCLUSION: In cognitively healthy research participants with a first-degree relative with AD, disclosure of APOE ε4-positivity does not lead to elevated anxiety and depression levels, but does increase test-related distress and results in behavior changes concerning insurance and health. We did not find studies reporting the effects of disclosing nongenetic biomarkers and only one study included people without a family history of AD. Empirical studies on the effects of disclosing nongenetic biomarkers and of disclosure to persons without a family history of AD are urgently needed. TRIAL REGISTRATION: PROSPERO international prospective register for systematic reviews CRD42016035388 . Registered 19 February 2016.