Home Use of an Artificial Beta Cell in Type 1 Diabetes.

BACKGROUND: The feasibility, safety, and efficacy of prolonged use of an artificial beta cell (closed-loop insulin-delivery system) in the home setting have not been established. METHODS: In two multicenter, crossover, randomized, controlled studies conducted under free-living home conditions, we compared closed-loop insulin delivery with sensor-augmented pump therapy in 58 patients with type 1 diabetes. The closed-loop system was used day and night by 33 adults and overnight by 25 children and adolescents. Participants used the closed-loop system for a 12-week period and sensor-augmented pump therapy (control) for a similar period. The primary end point was the proportion of time that the glucose level was between 70 mg and 180 mg per deciliter for adults and between 70 mg and 145 mg per deciliter for children and adolescents. RESULTS: Among adults, the proportion of time that the glucose level was in the target range was 11.0 percentage points (95% confidence interval [CI], 8.1 to 13.8) greater with the use of the closed-loop system day and night than with control therapy (P<0.001). The mean glucose level was lower during the closed-loop phase than during the control phase (difference, -11 mg per deciliter; 95% CI, -17 to -6; P<0.001), as were the area under the curve for the period when the glucose level was less than 63 mg per deciliter (39% lower; 95% CI, 24 to 51; P<0.001) and the mean glycated hemoglobin level (difference, -0.3%; 95% CI, -0.5 to -0.1; P=0.002). Among children and adolescents, the proportion of time with the nighttime glucose level in the target range was higher during the closed-loop phase than during the control phase (by 24.7 percentage points; 95% CI, 20.6 to 28.7; P<0.001), and the mean nighttime glucose level was lower (difference, -29 mg per deciliter; 95% CI, -39 to -20; P<0.001). The area under the curve for the period in which the day-and-night glucose levels were less than 63 mg per deciliter was lower by 42% (95% CI, 4 to 65; P=0.03). Three severe hypoglycemic episodes occurred during the closed-loop phase when the closed-loop system was not in use. CONCLUSIONS: Among patients with type 1 diabetes, 12-week use of a closed-loop system, as compared with sensor-augmented pump therapy, improved glucose control, reduced hypoglycemia, and, in adults, resulted in a lower glycated hemoglobin level. (Funded by the JDRF and others; AP@home04 and APCam08 ClinicalTrials.gov numbers, NCT01961622 and NCT01778348.).

Bolusing frequency and amount impacts glucose control during hybrid closed-loop.

AIM: To compare bolus insulin delivery patterns during closed-loop home studies in adults with suboptimally [HbA1c 58-86 mmol/mol (7.5%-10%)] and well-controlled [58 mmol/mol (< 7.5%)] Type 1 diabetes. METHODS: Retrospective analysis of daytime and night-time insulin delivery during home use of closed-loop over 4 weeks. Daytime and night-time controller effort, defined as amount of insulin delivered by closed-loop relative to usual basal insulin delivery, and daytime bolus effort, defined as total bolus insulin delivery relative to total daytime insulin delivery were compared between both cohorts. Correlation analysis was performed between individual bolus behaviour (bolus effort and frequency) and daytime controller efforts, and proportion of time spent within and below sensor glucose target range. RESULTS: Individuals with suboptimally controlled Type 1 diabetes had significantly lower bolus effort (P = 0.038) and daily bolus frequency (P < 0.001) compared with those with well-controlled diabetes. Controller effort during both daytime (P = 0.007) and night-time (P = 0.005) were significantly higher for those with suboptimally controlled Type 1 diabetes. Time when glucose was within the target range (3.9-10.0 mmol/L) during daytime correlated positively with bolus effort (r = 0.37, P = 0.016) and bolus frequency (r = 0.33, P = 0.037). Time when glucose was below the target range during daytime was comparable in both groups (P = 0.36), and did not correlate significantly with bolus effort (r = 0.28, P = 0.066) or bolus frequency (r = -0.21, P = 0.19). CONCLUSION: More frequent bolusing and higher proportion of insulin delivered as bolus during hybrid closed-loop use correlated positively with time glucose was in target range. This emphasises the need for user input and educational support to benefit from this novel therapeutic modality.

Factors associated with recurrent stroke and recanalization in patients presenting with isolated symptomatic carotid occlusion.

BACKGROUND AND PURPOSE: Patients with symptomatic internal carotid artery (ICA) occlusion constitute a small proportion of stroke/transient ischaemic attack patients who are at increased risk of early stroke recurrence and poor outcome. The optimal medical treatment for patients with symptomatic ICA occlusion who are ineligible for thrombolysis or thrombectomy is unknown. METHODS: Consecutive patients presenting at a single center with newly diagnosed symptomatic ICA occlusion (not involving the circle of Willis) were retrospectively reviewed. Those treated with intravenous thrombolysis or intra-arterial thrombolysis/thrombectomy were excluded. Patients were divided into two groups based on whether they experienced recurrent in-hospital stroke. RESULTS: The selected study population (n = 33) represented a small (20.4%) proportion of all newly symptomatic carotid occlusions, who nevertheless had an elevated risk of recurrent stroke during admission (24.2%). Of the variables examined (age, gender, admission National Institutes of Health Stroke Scale score, vascular risk factors, atrial fibrillation, prior stroke/transient ischaemic attack and anticoagulation within 48 h of presentation), only anticoagulation was significantly associated with a lower risk of in-hospital recurrent stroke. Anticoagulated patients showed a decreased incidence of stroke recurrence within the first week (6.7% vs. 38.9%, P = 0.032) and fewer strokes or deaths at 1 month (13.3% vs. 47.1%, P = 0.040). Hemorrhagic transformation was not observed in any patient. On follow-up imaging, ICA recanalization was significantly more frequent in anticoagulated patients (46.2% vs. 9.1%, P = 0.047). CONCLUSION: Patients with newly diagnosed symptomatic ICA occlusion (not involving the circle of Willis) represent a small but high risk subgroup of patients with carotid occlusion. Early anticoagulation was associated with fewer recurrent strokes and increased ICA recanalization. Larger scale prospective studies may be justified.

Development of performance measures for acute ischemic stroke.

BACKGROUND AND PURPOSE: The purpose of the present study was to develop and rate performance measures for hospital-based acute ischemic stroke. METHODS: A national multidisciplinary panel of 16 individuals (2 stroke specialists, 2 general neurologists, 2 internists, 2 neuroscience nurses, 2 stroke advocacy organization representatives, 1 stroke rehabilitationist, 1 family practitioner, 1 emergency room physician, 1 neuroradiologist, 1 managed care organization director, and 1 hospital association representative) from 10 medical societies or lay organizations assisted in the development of 44 potential stroke performance measures. We developed evidence summaries for each of the performance measures and graded the level of evidence associated with each measure. The panel received a summary of the literature pertaining to each measure and rated the measures by use of a modified Delphi approach for 6 dimensions of quality, including validity of evidence, feasibility, impact on outcomes, room for improvement, plausibility, and an overall rating (little reason to do, could do, should do, and must do). RESULTS: Highly rated and agreed on performance measures for the overall rating include warfarin in atrial fibrillation, antithrombotics on hospital discharge, carotid imaging in appropriate patients, and use of stroke units. Additional measures notable for high agreement were heparins for deep-vein thrombosis prophylaxis and use of a stroke protocol. Panelists rated time-related thrombolytic measures such as head CT within 25 minutes highly on the room for improvement dimension but low on the overall dimension. Neurologists tended to rate measures lower than did nonneurologists (P<0.01) for all 9 measures pertaining to thrombolytic management. CONCLUSIONS: Highly rated and agreed on performance measures exist in all domains of hospital-based stroke care.

End-stage Alzheimer's disease. Glasgow Coma Scale and the neurologic examination.

OBJECTIVE: To characterize the cognitive and neurologic features of patients with end-stage Alzheimer's disease using a standard neurologic examination and the Glasgow Coma Scale. DESIGN: Case series. SETTING: Local community nursing homes. PATIENTS: Forty patients with Alzheimer's disease were drawn from previously enrolled subjects in the Rochester Alzheimer's Disease Project with Clinical Dementia Rating scores of 3, 4, or 5. MAIN OUTCOME MEASURES: Scores on the Glasgow Coma Scale and cognitive screening examinations and the prevalence of neurologic manifestations such as primitive reflexes and extrapyramidal signs were compared across the Clinical Dementia Rating groups. RESULTS: When compared with patients in the Clinical Dementia Rating stages 3 and 4, patients with a stage 5 scored significantly lower on the Glasgow Coma Scale, with the discriminating subscales being verbal and motor responses. Primitive reflexes, myoclonus, and dyskinesia were increasingly prevalent in the more terminal stages. Cognitive screening assessments did not discriminate between groups. CONCLUSIONS: Rudimentary neurologic functions can be readily assessed and, when viewed together with the Glasgow Coma Scale, may circumvent the "floor effect" frequently encountered when using the currently available cognitive and functional scales and, thereby, better define patients with end-stage Alzheimer's disease.

Stroke prevention: narrowing the evidence-practice gap.

Many interventions reduce stroke risk. However, the full benefits of these interventions are not realized at current levels of utilization, as nearly all evidence-based or guideline-endorsed stroke prevention services are underused. The cause for such underuse is multifactorial and includes factors relating to both patients and providers, as well as to a health care system that has de-emphasized prevention at the expense of acute, technologically based care. Much like the evidence for stroke interventions themselves, there is a growing literature to support methods of implementing research evidence into clinical practice. There is still much to learn, however, about the effectiveness of interventions aimed at achieving changes in stroke prevention practice or the delivery of stroke prevention care. Nevertheless, there are many opportunities for providers, managed care organizations, and government to close the evidence-practice gap that exists for stroke prevention services. These opportunities exist in both the inpatient and outpatient setting, and depend on the neurologist taking a leading role in emphasizing the critical importance of risk factor identification and modification in all patients at risk for stroke.

Inaccuracy of the International Classification of Diseases (ICD-9-CM) in identifying the diagnosis of ischemic cerebrovascular disease.

In administrative databases the International Classification of Diseases, Version 9, Clinical Modification (ICD-9-CM) is often used to identify patients with specific diagnoses. However, certain conditions may not be accurately reflected by the ICD-9 codes. We assessed the accuracy of ICD-9 coding for cerebrovascular disease by comparing ICD-9 codes in an administrative database with clinical findings ascertained from medical record abstractions. We selected patients with ICD-9 diagnostic codes of 433 through 436 (in either the primary or secondary positions) from an administrative database of patients hospitalized in five academic medical centers in 1992. Medical records of the selected patients were reviewed by trained medical abstractors, and the patients' clinical conditions during the admission (stroke, TIA, asymptomatic) were recorded, as well as any history of cerebrovascular symptoms. Results of the medical record review were compared with the ICD-9 codes from the administrative database. More than 85% of those patients with the ICD-9 code 433 were asymptomatic for the index admission. More than one-third of these asymptomatic patients did not undergo either cerebral angiography or carotid endarterectomy. For ICD-9 code 434, 85% of patients were classified as having a stroke and for ICD-9 code 435, 77% had TIAs. For code 436, 77% of patients were classified as having strokes. Limiting the identifying ICD-9 code to the primary position increased the likelihood of agreement with the medical record review. The ICD-9 coding scheme may be inaccurate in the classification of patients with ischemic cerebrovascular disease. Its limitations must be recognized in the analyses of administrative databases selected by using ICD-9 codes 433 through 436.

Initial clinical experience with IV tissue plasminogen activator for acute ischemic stroke: a multicenter survey. The t-PA Stroke Survey Group.

We assessed initial clinical experience with IV tissue plasminogen activator (t-PA) treatment of acute ischemic stroke in a standardized retrospective survey of hospitals with experienced acute stroke treatment systems. The incidence of symptomatic intracerebral hemorrhage (ICH) was 6% (11 of 189 patients; 95% CI 3 to 11%), similar to that in the National Institute of Neurological Disorders and Stroke (NINDS) t-PA Stroke Study. Deviations from the NINDS protocol guidelines were identified in 30% of patients (56 of 189). The incidence of symptomatic ICH was 11% among patients with protocol deviations as compared with 4% in patients who were treated according to the NINDS protocol guidelines, suggesting that strict adherence to protocol guidelines is prudent.

Wasp sting-associated cerebral infarction: a role for cerebrovascular sympathetic innervation.

A 38-year-old man, stung repeatedly by wasps on the left face and neck, had his left internal carotid artery occluded 2 days later. A mechanism for ischemic stroke involving the sympathetic innervation of cerebral vasculature is suggested.

A controlled study of folic acid treatment in three fragile X syndrome males.

Three fragile X syndrome males were given 10 mg folic acid daily in a multiple-baseline, placebo study. Objective measures of memory skills, compliance, and behavioral appropriateness were taken during baseline, placebo, and treatment conditions. No change was evident in these variables during the drug trial. Thus, the findings shed doubt on the effectiveness of folic acid in increasing intellectual functioning or reducing behavior problems in individuals with fragile X syndrome. These results underscore the importance of operationally defined variables, double-blind observation and placebo treatment in elucidating the effects of folic acid.

Perioperative stroke associated with postoperative epidural analgesia.

A patient with an epidural catheter for postoperative analgesia developed a stroke in association with a hypotensive episode resulting from a bolus of local anesthetic. After undergoing resection for femoral chondrosarcoma under epidural anesthesia, the patient received a continuous infusion of epidural morphine for postoperative analgesia. Lidocaine 1% (10 mL in divided doses) was administered through the catheter for breakthrough pain. The patient experienced a hypotensive episode and was noted to have a motor and cortical sensory deficit of the left arm and leg 8 hours after the hypotensive episode. Clinical presentation and subsequent workup were consistent with a watershed infarction. The patient recovered full neurologic function before discharge. Postoperative hypotension from epidural analgesia may be associated with stroke; however, a cause-and-effect relationship usually cannot be established with certainty.

[Calcinosis in sheep. Case report]. / Kalzinose beim Schaf. Ein Fallbericht.

A case of calcinosis outside the typical area of incidence is reported. Problems of diagnosis of the disease are illustrated and epidemiological factors are discussed.

[Recommendations for the husbandry and welfare of sheep and goats by the German Small Ruminant Veterinary Association. Part 1]. / Empfehlung für die Haltung von Schafen und Ziegen der Deutschen Gesellschaft für die Krankheiten der kleinen Wiederkäuer, Fachgruppe der DVG. Teil 1.

Recommendations for the different forms of sheep and goat husbandry based on the legal regulations are summarized. These are given in particular respect to transhumance, tending, alpine farming, and indoor housing. The requirements for pasture, housing, supply of water and food, lambing, rearing of lambs, and health management are intensively discussed. The general requirements of the extensive as well as of the intensive husbandry of sheep and goats are defined. Examples of species-specific capabilities for adaption, the limits of adaption, and signs of decompensation are provided. Compliance with these recommendations should accord the animals entrusted to our care the "five freedoms (13)": 1. Freedom from hunger and thirst, 2. freedom from discomfort, 3. freedom from pain, injury, or disease, 4. freedom to express normal behaviour, and 5. freedom from fear and distress.

[Recommendations for the husbandry and welfare of sheep and goats by the German Small Ruminant Veterinary Association. Part 2]. / Empfehlung für die Haltung von Schafen und Ziegen der Deutschen Gesellschaft für die Krankheiten der kleinen Wiederkäuer, Fachgruppe der DVG. Teil 2.

The second part of the recommendations deals with the healthcare and the regulatory framework for the husbandry of sheep and goats. The suggested concept for healthcare aims to develop an individual health plan for every flock. This health plan focuses not only on the prevention of notifiable diseases, but also on chronic and slow infections as well as on parasite monitoring. The emphasis is on early detection of diseases and prophylaxis. In conjunction with this, the handling of lameness, shearing, animal trade and quarantine as well as cleaning and disinfection in sheep and goat flocks are intensively discussed. There are detailed federal and European legal regulations concerning the transport and the physical well-being of animals. These laws are clearly presented and advice for their practical implementation is provided.

Vibrational nonequilibrium effects in the conductance of single molecules with multiple electronic states.

Vibrational nonequilibrium effects in charge transport through single-molecule junctions are investigated. Focusing on molecular bridges with multiple electronic states, it is shown that electronic-vibrational coupling triggers a variety of vibronic emission and absorption processes, which influence the conductance properties and mechanical stability of single-molecule junctions profoundly. Employing a master equation and a nonequilibrium Green's function approach, these processes are analyzed in detail for a generic model of a molecular junction and for benzenedibutanethiolate bound to gold electrodes.

Warfarin vs aspirin for symptomatic intracranial stenosis: subgroup analyses from WASID.

The WASID trial showed no advantage of warfarin over aspirin for preventing the primary endpoint of ischemic stroke, brain hemorrhage, or vascular death. In analyses of selected subgroups, there was no definite benefit from warfarin. Warfarin reduced the risk of the primary endpoint among patients with basilar artery stenosis, but there was no reduction in stroke in the basilar artery territory or benefit for vertebral artery stenosis or posterior circulation disease in general.

Pericallosal artery aneurysm originating from a "supreme anterior communicating artery".

Report on the rare case of a ruptured pericallosal aneurysm originating from an atypic communicating segment between both distal A2 arteries, called the 'supreme anterior communicating artery'. The neurosurgeon should be aware of this rare vascular anomaly that might be angiographically occult and raise unexpected intraoperative difficulties.