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SummaryBackgroundOur aim was to assess the long-term risks of death, disability, and rebleeding in patients randomly assigned to clipping or endovascular coiling after rupture of an intracranial aneurysm in the follow-up of the International Subarachnoid Aneurysm Trial (ISAT).Methods2143 patients with ruptured intracranial aneurysms were enrolled between 1994 and 2002 at 43 neurosurgical centres and randomly assigned to clipping or coiling. Clinical outcomes at 1 year have been previously reported. All UK and some non-UK centres continued long-term follow-up of 2004 patients enrolled in the original cohort. Annual follow-up has been done for a minimum of 6 years and a maximum of 14 years (mean follow-up 9 years). All deaths and rebleeding events were recorded. Analysis of rebleeding was by allocation and by treatment received. ISAT is registered, number ISRCTN49866681.Findings24 rebleeds had occurred more than 1 year after treatment. Of these, 13 were from the treated aneurysm (ten in the coiling group and three in the clipping group; log rank p=0·06 by intention-to-treat analysis). There were 8447 person-years of follow-up in the coiling group and 8177 person-years of follow-up in the clipping group. Four rebleeds occurred from a pre-existing aneurysm and six from new aneurysms. At 5 years, 11% (112 of 1046) of the patients in the endovascular group and 14% (144 of 1041) of the patients in the neurosurgical group had died (log-rank p=0·03). The risk of death at 5 years was significantly lower in the coiling group than in the clipping group (relative risk 0·77, 95% CI 0·61–0·98; p=0·03), but the proportion of survivors at 5 years who were independent did not differ between the two groups: endovascular 83% (626 of 755) and neurosurgical 82% (584 of 713). The standardised mortality rate, conditional on survival at 1 year, was increased for patients treated for ruptured aneurysms compared with the general population (1·57, 95% CI 1·32–1·82; p<0·0001).InterpretationThere was an increased risk of recurrent bleeding from a coiled aneurysm compared with a clipped aneurysm, but the risks were small. The risk of death at 5 years was significantly lower in the coiled group than it was in the clipped group. The standardised mortality rate for patients treated for ruptured aneurysms was increased compared with the general population.FundingUK Medical Research Council.

Analysis 2.4. Comparison 2 Donepezil (5 mg/day or 10 mg/day) versus placebo, Outcome 4 MMSE (change from baseline)

Previously undetected VHD affects 1 in 2 of the elderly population and is more common in lower socioeconomic classes. These unique data demonstrate the contemporary clinical and epidemiological characteristics of VHD in a large population-based cohort of older people and confirm the scale of the emerging epidemic of VHD, with widespread implications for clinicians and healthcare resources.

BackgroundTreatment of hyperglycemia in women with gestational diabetes mellitus (GDM) is associated with improved maternal and neonatal outcomes and requires intensive clinical input. This is currently achieved by hospital clinic attendance every 2 to 4 weeks with limited opportunity for intervention between these visits.ObjectiveWe conducted a randomized controlled trial to determine whether the use of a mobile phone-based real-time blood glucose management system to manage women with GDM remotely was as effective in controlling blood glucose as standard care through clinic attendance.MethodsWomen with an abnormal oral glucose tolerance test before 34 completed weeks of gestation were individually randomized to a mobile phone-based blood glucose management solution (GDm-health, the intervention) or routine clinic care. The primary outcome was change in mean blood glucose in each group from recruitment to delivery, calculated with adjustments made for number of blood glucose measurements, proportion of preprandial and postprandial readings, baseline characteristics, and length of time in the study.ResultsA total of 203 women were randomized. Blood glucose data were available for 98 intervention and 85 control women. There was no significant difference in rate of change of blood glucose (–0.16 mmol/L in the intervention and –0.14 mmol/L in the control group per 28 days, P=.78). Women using the intervention had higher satisfaction with care (P=.049). Preterm birth was less common in the intervention group (5/101, 5.0% vs 13/102, 12.7%; OR 0.36, 95% CI 0.12-1.01). There were fewer cesarean deliveries compared with vaginal deliveries in the intervention group (27/101, 26.7% vs 47/102, 46.1%, P=.005). Other glycemic, maternal, and neonatal outcomes were similar in both groups. The median time from recruitment to delivery was similar (intervention: 54 days; control: 49 days; P=.23). However, there were significantly more blood glucose readings in the intervention group (mean 3.80 [SD 1.80] and mean 2.63 [SD 1.71] readings per day in the intervention and control groups, respectively; P<.001). There was no significant difference in direct health care costs between the two groups, with a mean cost difference of the intervention group compared to control of –£1044 (95% CI –£2186 to £99). There were no unexpected adverse outcomes.ConclusionsRemote blood glucocse monitoring in women with GDM is safe. We demonstrated superior data capture using GDm-health. Although glycemic control and maternal and neonatal outcomes were similar, women preferred this model of care. Further studies are required to explore whether digital health solutions can promote desired self-management lifestyle behaviors and dietetic adherence, and influence maternal and neonatal outcomes. Digital blood glucose monitoring may provide a scalable, practical method to address the growing burden of GDM around the world.Trial RegistrationClinicalTrials.gov NCT01916694; https://clinicaltrials.gov/ct2/show/NCT01916694 (Archived by WebCite at http://www.webcitat...

SummaryBackgroundPrevious analyses of the International Subarachnoid Aneurysm Trial (ISAT) cohort have reported on the risks of recurrent subarachnoid haemorrhage and death or dependency for a minimum of 5 years and up to a maximum of 14 years after treatment of a ruptured intracranial aneurysm with either neurosurgical clipping or endovascular coiling. At 1 year there was a 7% absolute and a 24% relative risk reduction of death and dependency in the coiling group compared with the clipping group, but the medium-term results showed the increased need for re-treatment of the target aneurysm in the patients given coiling. We report the long-term follow-up of patients in this UK cohort.MethodsIn ISAT, patients were randomly allocated to either neurosurgical clipping or endovascular coiling after a subarachnoid haemorrhage, assuming treatment equipoise, between Sept 12, 1994, and May 1, 2002. We followed up 1644 patients in 22 UK neurosurgical centres for death and clinical outcomes for 10·0–18·5 years. We assessed dependency as self-reported modified Rankin scale score obtained through yearly questionnaires. Data for recurrent aneurysms and rebleeding events were collected from questionnaires and from hospital and general practitioner records. The Office for National Statistics supplied data on deaths. This study is registered, number ISRCTN49866681.FindingsAt 10 years, 674 (83%) of 809 patients allocated endovascular coiling and 657 (79%) of 835 patients allocated neurosurgical clipping were alive (odds ratio [OR] 1·35, 95% CI 1·06–1·73). Of 1003 individuals who returned a questionnaire at 10 years, 435 (82%) patients treated with endovascular coiling and 370 (78%) patients treated with neurosurgical clipping were independent (modified Rankin scale score 0–2; OR 1·25; 95% CI 0·92–1·71). Patients in the endovascular treatment group were more likely to be alive and independent at 10 years than were patients in the neurosurgery group (OR 1·34, 95% CI 1·07–1·67). 33 patients had a recurrent subarachnoid haemorrhage more than 1 year after their initial haemorrhage (17 from the target aneurysm).InterpretationAlthough rates of increased dependency alone did not differ between groups, the probability of death or dependency was significantly greater in the neurosurgical group than in the endovascular group. Rebleeding was more likely after endovascular coiling than after neurosurgical clipping, but the risk was small and the probability of disability-free survival was significantly greater in the endovascular group than in the neurosurgical group at 10 years.FundingUK Medical Research Council.

IntroductionFlow diversion is a new approach to the endovascular treatment of intracranial aneurysms which uses a high density mesh stent to induce sac thrombosis. These devices have been designed for the treatment of complex shaped and large size aneurysms. So far published safety and efficacy data on this approach is sparse.Material and MethodsOver 8 months, standardized clinical and angiographic data were collected on 70 patients treated with a flow diverter device (SILK flow diverter (SFD)) in 18 centres worldwide. Treatment and early follow up details were audited centrally. SFDs were deployed alone in 57 (81%) or with endosaccular coils in 10 (14%) aneurysms, which included: 44 (63%) saccular, 26 (37%) fusiform shapes and 18 (26%) small, 37 (53%) large, 15 (21%) giant sizes. Treatment outcome data up to 30 days were reported for all patients, with clinical (50 patients) and imaging (49 patients) follow up (median 119 days) data available.ResultsDifficulties in SFD deployment were reported in 15 (21%) and parent artery thrombosis in 8 (11%) procedures. Procedural complications caused stroke in 1 and serious extracranial bleeding in 3 patients; 2 of whom developed fatal pneumonias. Delayed worsening of symptoms occurred in 5 patients (3 transient, 1 permanent neurological deficit, and 1 death) and fatal aneurysm bleeding in 1 patient. Overall permanent morbidity rates were 2 (4%) and mortality 4 (8%). Statistical analysis revealed no significant association between complications and variables related to treated aneurysm morphology or rupture status.ConclusionThis series is the largest reporting outcome of the new treatment approach and provides data for future study design. Procedural difficulties in SFD deployment were frequent and anti-thrombosis prophylaxis appears to reduce the resulting clinical sequelae, but at the cost of morbidity due to extracranial bleeding. Delayed morbidity appears to be a consequence of the new approach and warrants care in selecting patients for treatment and future larger studies.

ObjectiveTo provide an overview and critical appraisal of early warning scores for adult hospital patients.DesignSystematic review.Data sourcesMedline, CINAHL, PsycInfo, and Embase until June 2019.Eligibility criteria for study selectionStudies describing the development or external validation of an early warning score for adult hospital inpatients.Results13 171 references were screened and 95 articles were included in the review. 11 studies were development only, 23 were development and external validation, and 61 were external validation only. Most early warning scores were developed for use in the United States (n=13/34, 38%) and the United Kingdom (n=10/34, 29%). Death was the most frequent prediction outcome for development studies (n=10/23, 44%) and validation studies (n=66/84, 79%), with different time horizons (the most frequent was 24 hours). The most common predictors were respiratory rate (n=30/34, 88%), heart rate (n=28/34, 83%), oxygen saturation, temperature, and systolic blood pressure (all n=24/34, 71%). Age (n=13/34, 38%) and sex (n=3/34, 9%) were less frequently included. Key details of the analysis populations were often not reported in development studies (n=12/29, 41%) or validation studies (n=33/84, 39%). Small sample sizes and insufficient numbers of event patients were common in model development and external validation studies. Missing data were often discarded, with just one study using multiple imputation. Only nine of the early warning scores that were developed were presented in sufficient detail to allow individualised risk prediction. Internal validation was carried out in 19 studies, but recommended approaches such as bootstrapping or cross validation were rarely used (n=4/19, 22%). Model performance was frequently assessed using discrimination (development n=18/22, 82%; validation n=69/84, 82%), while calibration was seldom assessed (validation n=13/84, 15%). All included studies were rated at high risk of bias.ConclusionsEarly warning scores are widely used prediction models that are often mandated in daily clinical practice to identify early clinical deterioration in hospital patients. However, many early warning scores in clinical use were found to have methodological weaknesses. Early warning scores might not perform as well as expected and therefore they could have a detrimental effect on patient care. Future work should focus on following recommended approaches for developing and evaluating early warning scores, and investigating the impact and safety of using these scores in clinical practice.Systematic review registrationPROSPERO CRD42017053324.