A kilonova as the electromagnetic counterpart to a gravitational-wave source.

Gravitational waves were discovered with the detection of binary black-hole mergers and they should also be detectable from lower-mass neutron-star mergers. These are predicted to eject material rich in heavy radioactive isotopes that can power an electromagnetic signal. This signal is luminous at optical and infrared wavelengths and is called a kilonova. The gravitational-wave source GW170817 arose from a binary neutron-star merger in the nearby Universe with a relatively well confined sky position and distance estimate. Here we report observations and physical modelling of a rapidly fading electromagnetic transient in the galaxy NGC 4993, which is spatially coincident with GW170817 and with a weak, short γ-ray burst. The transient has physical parameters that broadly match the theoretical predictions of blue kilonovae from neutron-star mergers. The emitted electromagnetic radiation can be explained with an ejected mass of 0.04 ± 0.01 solar masses, with an opacity of less than 0.5 square centimetres per gram, at a velocity of 0.2 ± 0.1 times light speed. The power source is constrained to have a power-law slope of -1.2 ± 0.3, consistent with radioactive powering from r-process nuclides. (The r-process is a series of neutron capture reactions that synthesise many of the elements heavier than iron.) We identify line features in the spectra that are consistent with light r-process elements (atomic masses of 90-140). As it fades, the transient rapidly becomes red, and a higher-opacity, lanthanide-rich ejecta component may contribute to the emission. This indicates that neutron-star mergers produce gravitational waves and radioactively powered kilonovae, and are a nucleosynthetic source of the r-process elements.

Early Magnesium Treatment After Aneurysmal Subarachnoid Hemorrhage: Individual Patient Data Meta-Analysis.

BACKGROUND AND PURPOSE: Delayed cerebral ischemia (DCI) is an important cause of poor outcome after aneurysmal subarachnoid hemorrhage (SAH). Trials of magnesium treatment starting <4 days after symptom onset found no effect on poor outcome or DCI in SAH. Earlier installment of treatment might be more effective, but individual trials had not enough power for such a subanalysis. We performed an individual patient data meta-analysis to study whether magnesium is effective when given within different time frames within 24 hours after the SAH. METHODS: Patients were divided into categories according to the delay between symptom onset and start of the study medication: <6, 6 to 12, 12 to 24, and >24 hours. We calculated adjusted risk ratios with corresponding 95% confidence intervals for magnesium versus placebo treatment for poor outcome and DCI. RESULTS: We included 5 trials totaling 1981 patients; 83 patients started treatment<6 hours. For poor outcome, the adjusted risk ratios of magnesium treatment for start <6 hours were 1.44 (95% confidence interval, 0.83-2.51); for 6 to 12 hours 1.03 (0.65-1.63), for 12 to 24 hours 0.84 (0.65-1.09), and for >24 hours 1.06 (0.87-1.31), and for DCI, <6 hours 1.76 (0.68-4.58), for 6 to 12 hours 2.09 (0.99-4.39), for 12 to 24 hours 0.80 (0.56-1.16), and for >24 hours 1.08 (0.88-1.32). CONCLUSIONS: This meta-analysis suggests no beneficial effect of magnesium treatment on poor outcome or DCI when started early after SAH onset. Although the number of patients was small and a beneficial effect cannot be definitively excluded, we found no justification for a new trial with early magnesium treatment after SAH.

The accuracy of patient-reported measures for GI symptoms: a comparison of real time and retrospective reports.

BACKGROUND: Obtaining accurate information about gastrointestinal (GI) symptoms is critical to achieving the goals of clinical research and practice. The accuracy of patient data is especially important for functional GI disorders (e.g., IBS) whose symptoms lack a biomarker and index illness severity and treatment response. Retrospective patient-reported data are vulnerable to forgetting and various cognitive biases whose impact has not been systematically studied in patients with GI disorders. The aim of this study was to document the accuracy of patient-reported GI symptoms over a reporting period (1 week) most representative of the time frame used in research and clinical care. METHODS: Subjects were 273 Rome III-diagnosed IBS patients (mean age = 39 years, 89% F) who completed end of day GI symptom ratings for 7 days using an electronic diary. On Day 8, Subjects recalled the frequency and/or intensity of IBS symptoms over the past 7 days. Reports were then compared against a validation criterion based on aggregated end of day ratings. KEY RESULTS: At the group level, subjects recalled most accurately abdominal pain and urgency intensity at their worst, urgency days, and stool frequency. When data were analyzed at the individual level, a subgroup of subjects had difficulty recalling accurately symptoms that showed convergence between recall and real time reports at the group level. CONCLUSIONS & INFERENCES: Although many patients' recollection for specific GI symptoms (e.g., worst pain, stool frequency) is reasonably accurate, a non-trivial number of other symptoms (e.g., typical pain) are vulnerable to distortion from recall biases that can reduce sensitivity of detecting treatment effects in clinical and research settings.

Pre-pregnancy care and pregnancy outcomes in type 1 diabetes mellitus: a comparison of continuous subcutaneous insulin infusion and multiple daily injection therapy.

BACKGROUND: Pre-pregnancy care improves pregnancy outcomes in type 1 diabetes mellitus (T1DM). Continuous subcutaneous insulin infusion (CSII) therapy and multiple daily injection (MDI) therapy can both be used to achieve glycaemic targets, but few data are available to compare their efficacy in pre-pregnancy care. AIM: To compare MDI and CSII in pre-pregnancy care in T1DM. METHODS: Retrospective database review of women with T1DM attending the Dublin Diabetes in Pregnancy Centre. RESULTS: 464 women with T1DM (40 treated with CSII) were included. Women attending for pre-pregnancy care had lower HbA1c levels at booking to antenatal services [52 ± 10 mmol/mol (6.9 ± 0.9 %) vs. 62 ± 16 mmol/mol (7.8 ± 1.5 %), p < 0.001], and booked at an earlier gestation (6 ± 2 vs. 8 ± 6 weeks, p < 0.001). In those who attended for pre-pregnancy care, the CSII group had lower HbA1c levels at booking than those using MDI [48 ± 8 mmol/mol (6.5 ± 0.7 %) vs. 53 ± 10 mmol/mol (7.0 ± 0.9 %), p = 0.03]. Gestational age at delivery and birth weight did not differ between groups. Caesarean section rates were associated with CSII use (p < 0.001), duration of diabetes (p = 0.002), and parity (p = 0.006). Nulliparous women using CSII with a longer history of diabetes were more likely to deliver by Caesarean section. There was no perinatal mortality. CONCLUSIONS: Pre-pregnancy care delivered by a specialist multi-disciplinary team effectively reduces HbA1c levels peri-conception. CSII use results in lower HbA1c levels in pre-pregnancy care in selected individuals and should be considered in women with T1DM planning pregnancy.

A multi-tiered intervention to address behavioural and cognitive changes after diagnosis of primary brain tumour: a feasibility study.

PURPOSE: Untreated behavioural and cognitive changes after primary brain tumour (PBT) can result in challenging behaviours (CBs), with limited documentation on treatment approaches. This study explored the feasibility of employing a Behavioural Consultancy approach to manage CBs, targeting individuals with PBT, family and treating staff. METHODS: Participants were patients and families of two hospitals and health professionals from cancer/neurological services. A single-case experimental design piloted skill-based training and environmental changes in managing socio-behavioural impairments in a person with a low grade astrocytoma. A half-day workshop to train family members (n = 7) in compensatory strategy use to manage CBs after PBT was piloted. Finally, a 1-day workshop was provided to 43 health professionals in managing CBs after PBT. For both workshops, a pre-post impact evaluation was conducted employing a purpose-designed Strategies Use Measure. RESULTS: All three interventions demonstrated positive results. The single case showed a 71% decrease in the target behaviour (time spent talking) post-intervention. Some attrition to these gains was observed at two follow-up time points (3 and 5 months). Participants from both workshops demonstrated significant post-intervention increases in perceived knowledge of Strategy Use (family members z = 2.03, p < 0.05; health professionals z = 4.95, p < 0.00; Wilcoxon signed-rank test). CONCLUSIONS: These initial studies highlight the potential of employing an integrated multi-tiered intervention based on a Behavioural Consultancy model to manage CBs after PBT.

Outcome of pregnancy in type 1 diabetes mellitus (T1DMP): results from combined diabetes-obstetrical clinics in Dublin in three university teaching hospitals (1995-2006).

OBJECTIVE: To compare the pregnancy outcomes in all T1DMP attending at combined (diabetes-obstetric) outpatients clinics in three university teaching hospitals in Dublin from 1995 to 2006 with a non-diabetic control population (C) attending at antenatal outpatient clinics at the same hospitals over the same period. METHODS: T1DMP (n = 600) were compared with control non-diabetic pregnancies (n = 142,498). RESULTS: The spontaneous abortion rate was 15% in T1DMP versus 8% in C (p < 0.0001). Perinatal mortality rate was 3.3% in T1DMP compared to 0.9% in C (p < 0.001). The incidence of foetal macrosomia was 29% in T1DMP versus 16% in C (p < 0.001). CONCLUSIONS: Pregnancy outcomes in T1DMP remain worse than in the general population despite management of T1DMP in combined obstetric/diabetes clinics in a single centre using similar management protocols. These outcomes in our study population of T1DMP in Dublin appear better than some previously reported studies.

Pregnancy in women with Type 1 and Type 2 diabetes in Dublin.

INTRODUCTION: The Confidential Enquiry into Maternal and Child Health (CEMACH) reported outcomes of pregnancies in women with pre-gestational diabetes (PGDM) in the UK (n = 3,733). This study aimed to compare CEMACH outcomes with PGDM pregnancies in Dublin. METHODS: Retrospective chart review of all PGDM pregnancies. Comparison to CEMACH are shown in brackets. RESULTS: One hundred and ten PGDM women delivered in Dublin. Thirty (27%) had T2 diabetes (vs. 27%). Fifty-nine (53%) women had a booking HbA1c less than 7% (vs. 66%). Nineteen women (17.3%) had a first trimester miscarriage (vs. 8.5%). Of the 91 remaining women, 71 (78%) women underwent induction of labour (vs. 38.9%). Fifty-four women (59.3%) were delivered by caesarean section (vs. 67.4%). Two infants (2.1%) were macrosomic (vs. 5.7%). There was one intrauterine death (0.1 vs. 0.6%) and no maternal deaths (vs. five). CONCLUSION: These results serve to underline the continued importance of multidisciplinary care for pregnant women with diabetes.

The cost of treating type 2 diabetes (CODEIRE).

Diabetes mellitus is the most common chronic metabolic disease and a major source of morbidity and mortality. Type 2 diabetes (T2D) is by far the most prevalent form of diabetes accounting for around 90% of cases worldwide. In recent years it has become apparent that a diabetes epidemic is unfolding as a result of increasing obesity, sedentary lifestyles and an ageing population. The enormity of the diabetes epidemic raises concern about the total cost to healthcare systems. This study was undertaken to investigate the direct healthcare costs of managing T2D in Ireland. Data was captured on 701 diabetes patients attending four diabetes centres. A bottom-up, prevalence-based design was used, which collected data on hospital resource use and clinical outcome measures over a 12-month period (1999/2000). The study was observational in nature, focusing on usual care of patients with T2D. Although the true prevalence of T2D in Ireland is unknown, conservative estimates are 3.9% for diagnosed diabetes and 6% for both diagnosed and undiagnosed diabetes. Using these figures the annual total direct cost was estimated at 377.2 million euro for diagnosed diabetes and 580.2 million euro for both diagnosed and undiagnosed diabetes. This corresponds to 4.1% and 6.4% of total healthcare expenditure respectively. Hospitalisations were the main driver of costs, accounting for almost half of overall costs, while ambulatory and drug costs accounted for 27% and 25% respectively. Hospitalisation costs were high because 60% of patients had developed complications. The most common microvascular and macrovascular complications were neuropathy and angina respectively. The annual cost of care for patients with microvascular and macrovascular complications were 1.8 and 2.9 times the cost of treating those without clinical evidence of complications respectively. The figure for patients with both types of complications was 3.8. This study shows that T2D is a very costly disease, largely due to the cost of and the management of complications. Many diabetes related complications are preventable, therefore it would appear a cost-effective approach for government to invest in the prevention of T2D and diabetes related complications.

Irish diabetes detection programme in general practice.

OBJECTIVES: To assess the prevalence of undiagnosed diabetes, impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) in patients over the age of 40 years attending their general practitioner (GP) in Ireland, through opportunistic screening, using a three-step screening tool involving self-determined high-risk groups, random venous plasma glucose (RVPG) measurement and oral glucose tolerance tests. DESIGN: In participating general practices, 100 consecutive patients > 40 years, completed a screening questionnaire relating to diabetes-related symptoms and risk factors. Patients with previously diagnosed diabetes were not excluded from the study and the screening instrument included a question about known diabetes. Patients without known diabetes mellitus (DM) and with at least two risk factors and/or symptoms underwent a RVPG test. Those with an RVPG above 5.5 mmol/l underwent an oral glucose tolerance test. RESULTS: Forty-one practices returned 3821 questionnaires. The prevalence of Type 2 diabetes mellitus in the study population was 9.2% (353), of whom 23.5% (83) were previously undiagnosed. DM was detected on the basis of an RVPG >11.1 mmol/l in 0.8% (32) of the studied population. DM was detected on the basis of the oral glucose tolerance test in 1.3% (51) of the population. One per cent (39) had a fasting plasma glucose (FPG) > or = 7.0 mmol/l, 0.6% (24) had a 2-h >11.0 mmol/l and 0.3% (12) had both. Diabetes would not have been detected in 12 people had the 2-h test been omitted. The prevalence rate for IFG and/or IGT was 3.9% (148). Of the 103 patients with IGT, 83 (81%) would have been missed had the GTT been omitted. CONCLUSION: Opportunistic diabetes screening in general practice using a screening questionnaire followed by RVPG testing and GTT for those above 5.5 mmol/l is feasible, with a high participation rate. The use of GTTs rather than fasting glucose testing alone improves patient identification, in particular those with IGT who are at higher cardiovascular risk.

Lumbar intraspinal synovial cyst containing gas as a cause for low-back pain.

OBJECTIVE: To discuss intraspinal synovial cysts caused by degenerative changes involving the posterior articular facets in the lumbar spine and to provide differential considerations for patients with low-back pain. CLINICAL FEATURES: A 70-year-old man with low-back and gluteal pain demonstrating eventual progression of radiating pain into the left thigh, calf, ankle, and foot over a 5-month period. Radiographs of the lumbar spine revealed mild degenerative disk disease at L5-S1 with associated vacuum phenomena of the L5 disk. Degenerative osteophytes were present at L3, L4, and L5. Moderate posterior joint arthrosis was evident at L4-L5 and L5-S1. Computed tomography and magnetic resonance imaging studies revealed an intraspinal gas-containing synovial cyst at the left lateral aspect of the central canal at the level of the left L4-L5 facet articulation. INTERVENTION AND OUTCOME: The patient underwent surgical excision of the synovial cyst with remission of symptoms. CONCLUSION: Gas-containing intraspinal synovial cysts can be a significant finding and a causative factor in patients with low-back pain and pain radiating into the lower extremities. Both computed tomography and magnetic resonance imaging are important in defining intraspinal synovial cysts as a cause of back pain in patients whose low-back pain does not respond to chiropractic care.

Universal vs. risk factor-based screening for gestational diabetes mellitus: detection rates, gestation at diagnosis and outcome.

AIMS: Gestational diabetes mellitus (GDM) is associated with adverse maternal and fetal outcome. Screening for GDM is therefore recommended but the best screening method remains controversial. This prospective, randomized study compared a risk factor-based screening programme with a universally based one. METHODS: Subjects were randomized at booking to one of two groups: the risk factor group had a 3-h 100-g oral glucose tolerance test (OGTT) at 32 weeks if any risk factor for GDM was present; the universal group had a 50-g glucose challenge test performed and if their plasma glucose at 1 h was > or = 7.8 mmol/l, a formal 3-h 100-g OGTT was then performed. RESULTS: Universal screening detected a prevalence of GDM of 2.7%, significantly more than the 1.45% detected in the risk factor screened group (P<0.03). Universal screening facilitated earlier diagnosis than risk factor screening - mean gestation 30 +/- 2.6 weeks vs. 33 +/- 3.7 weeks (P<0.05). A higher rate of spontaneous vaginal delivery at term, and lower rates of macrosomia, Caesarean section, prematurity, pre-eclampsia and admission to neonatal intensive care unit were observed in the universally screened, early diagnosis group. CONCLUSIONS: Universal screening for GDM is superior to risk factor based screening-detecting more cases, facilitating early diagnosis and is associated with improved pregnancy outcome.

Outcome of diabetic pregnancy with spontaneous labour after 38 weeks.

One hundred and forty-eight patients with well controlled insulin dependent diabetes that were allowed to labour spontaneously from 1981 to 1994 were reviewed. There were 2 perinatal deaths, giving a perinatal mortality rate of 13.5/1000. One hundred and twenty-four patients (84 per cent) had a normal vaginal delivery, 13 (9 per cent) forceps delivery and 11 (7 per cent) caesarean section. Twenty-one infants (14 per cent) required admission to a Special Care Baby Unit. One third of infants weighed 4 Kg or more, however there was only 1 case of shoulder dystocia. We compared these results with those of the general hospital population of 1987. The 2 main differences are; 1) the Caesarean section rate in labour was higher for this diabetic group than for the general hospital population, 7 per cent versus 3.4 per cent, 2) the birth weight was heavier, 33 per cent of infants of the diabetic group weighed 4 Kg or more versus 18 per cent of the general hospital population. The other parameters were comparable. We conclude that conservative management of pregnancy in well controlled diabetic women is advantageous, resulting in a high vaginal delivery rate without an increase in shoulder dystocia, and a low perinatal morbidity and mortality rate.

Type 1 diabetes mellitus, coeliac disease, and lymphoma: a report of four cases.

INTRODUCTION: Patients with Type 1 diabetes mellitus have a high prevalence of coeliac disease, symptoms of which are often mild, atypical, or absent. Untreated coeliac disease is associated with an increased risk of malignancy, particularly of lymphoma. We describe four patients with Type 1 diabetes mellitus and coeliac disease who developed lymphoma. CASE REPORTS: Two patients were male and two female. In three patients, coeliac disease and lymphoma were diagnosed simultaneously. Enteropathy-associated T cell lymphoma occurred in two patients, Hodgkin's disease in one, and B cell lymphoma in one. Response to treatment was in general poor, and three patients died soon after the diagnosis of lymphoma was made. CONCLUSION: As the relative risk of lymphoma is reduced by a gluten-free diet, a high index of suspicion for coeliac disease should exist in all Type 1 diabetic patients with unexplained constitutional or gastrointestinal symptoms.

Specialty choice, stress and personality: their relationships over time.

A longitudinal questionnaire study of 314 medical students followed up as preregistration house officers (PRHOs) and again 7 years later showed laboratory-based doctors were the least happy with their choice of career and were the most stressed now, while surgeons were the most happy with their choice and the least stressed. These differences were apparent 10 years earlier. The study also describes perceived influences on specialty choice and explores how earlier factors, such as personality as students and stress in the PRHO year, may also have influenced specialty choice.

Diabetic retinopathy in Down's syndrome.

AIM: To determine the prevalence of diabetic retinopathy in patients with Down's syndrome and diabetes mellitus. METHODS: Nine patients with Down's syndrome and diabetes mellitus were assessed. Factors recorded included type and duration of diabetes, level of diabetic control, blood pressure, urinalysis, and results of ophthalmological examination. RESULTS: The duration of diabetes ranged from 8 to 41 years (mean 17.6 years). All had satisfactory glycaemic control and blood pressure measurements on the low side of normal (mean 106.6/70 mm Hg). One patient had early background diabetic retinopathy. The remainder had no evidence of diabetic retinopathy. CONCLUSION: The low prevalence of diabetic retinopathy in these Down's syndrome patients, despite the long duration, is an interesting finding. It suggests some inherent protective factor against the development of diabetic retinopathy in this patient subgroup.

Dobutamine stress echocardiography: false positive scans in proteinuric patients with type 1 diabetes mellitus at high risk of ischaemic heart disease.

Patients with Type 1 diabetes mellitus have an increased risk of ischaemic heart disease (IHD). When diabetes is complicated by nephropathy this risk is further increased and asymptomatic IHD is common. New techniques for non-invasive cardiac evaluation are now available and one of these, Dobutamine Stress Echocardiography (DSE), was studied in subjects with Type 1 DM and nephropathy who had no evidence of IHD. DSE was performed on 18 subjects (13 male, 5 female; mean age 37.8 +/- 3.4 years), diabetes duration 23.7 +/- 1.2 years and nephropathy diagnosed for 10.9 +/- 1.3 years. There were 7 (38%) positive scans-suggesting asymptomatic IHD; 16.7% of subjects studied had a significant arrhythmia. Coronary angiography was performed in 6 of the 7 subjects with positive DSEs and was positive in only 2. These results suggest that DSE has a high rate of false positive results in Type 1 DM patients suffering from nephropathy and may limit its usefulness in these subjects.

Efficacy of combination therapy in non-insulin dependent diabetes mellitus.

Secondary failure of oral hypoglycaemic agents raises the dilemma of whether to institute therapy with insulin alone, or in combination. We reviewed our experience of combination therapy following secondary failure of oral hypoglycaemic therapy. Seventeen subjects were receiving combination therapy for 6 months or more. Such treatment was associated with a significant fall in HbA1C--from 10.7 +/- 0.38 per cent to 8.3 +/- 0.35 per cent (p < 0.01) after 6 months and remained significantly reduced at 12 months (8.7 +/- 0.34 per cent (p < 0.01)). Mean body weight, systolic and diastolic blood pressure were unchanged during treatment with adjuvant insulin therapy. Insulin therapy is a useful adjunct in the daily management of subjects with NIDDM who experience secondary failure of oral hypoglycaemic agents.