Comparative risk of major cardiovascular events associated with second-line antidiabetic treatments: a retrospective cohort study using UK primary care data linked to hospitalization and mortality records.

AIMS: To examine the risk of major cardiovascular events associated with second-line diabetes therapies, in patients with type 2 diabetes, after adjusting for known cardiovascular risk factors. METHODS: This was a retrospective cohort study of patients prescribed second-line regimens between 1998 and 2011 after first-line metformin. The UK Clinical Practice Research Datalink, with linked national hospitalization and mortality data, for the period up to December 2013, was used. Inverse probability of treatment-weighted time-varying Cox regression models was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for developing a major cardiovascular event (cardiovascular death, myocardial infarction, stroke, acute coronary syndrome, unstable angina, or coronary revascularization) associated with second-line therapies. Analyses adjusted for patient demographic characteristics, comorbidities, glycated haemoglobin, socio-economic status, ethnicity, smoking status and concurrent medications. RESULTS: A total of 10 118 initiators of a second-line add-on to metformin of either a sulphonylurea (n = 6740), dipeptidyl peptidase-4 (DPP-4) inhibitor (n = 1030) or thiazolidinedione (n = 2348) were identified. After a mean (standard deviation) of 2.4 (1.9) years of follow-up, 386, 36 and 95 major cardiovascular events occurred in sulphonylurea-, DPP-4 inhibitor- and thiazolidinedione-initiators, respectively. In comparison with the metformin-sulphonylurea regimen, adjusted HRs were 0.78 (95% CI 0.55; 1.11) for the metformin-DPP-4 inhibitor regimen and 0.68 (95% CI 0.54; 0.85) for the metformin-thiazolidinedione regimen. CONCLUSIONS: Thiazolidinedione add-on treatments to metformin were associated with lower risks of major cardiovascular disease or cardiovascular death compared with sulphonylurea add-on treatment to metformin. Lower, but non-statistically significant, risks were also found with DPP-4 inhibitor add-on therapies.

A comparison of medication adherence/persistence for asthma and chronic obstructive pulmonary disease in the United Kingdom.

AIM: To describe and compare adherence and persistence with maintenance therapies in patients with asthma or chronic obstructive pulmonary disease (COPD) in the United Kingdom (UK). METHODS: A retrospective prescribing database cohort was obtained from 44 general practitioner surgeries in National Health Service Forth Valley Scotland. Patients with physician-diagnosed asthma or COPD who received maintenance therapy between January 2008 and December 2009 were included. Five classes of therapy were assessed: inhaled corticosteroids, long-acting beta-agonists, combination therapy inhalers, theophyllines and long-acting muscarinic antagonists. Adherence was calculated using the medication possession ratio (MPR) and persistence was determined using Kaplan-Meier survival analysis for the time to discontinuation (TTD) over 1 year. Two step-wise logistic regressions were performed to assess the contribution of diagnosis to adherence/persistence. RESULTS: A total of 13,322 patients were included in the analysis: 10,521 patients with asthma and 2801 patients with COPD. 25.2% of medication episodes for asthma and 45.6% of medication episodes for COPD were classified as having an adequate medication supply (MPR of 80-120%). The overall median TTD was 92 days (IQR, interquartile range: 50-186 days) for patients with asthma and 116 days (IQR: 58-259 days, comparison p < 0.001) for patients with COPD. Patients with COPD were found to be more likely to achieve an MPR of at least 80% (OR: 1.27, 95% CI: 1.15-1.40), but had a similar likelihood of persistence at 1 year to patients with asthma. CONCLUSION: Adherence and persistence with respiratory therapies in the UK is relatively low. There is suggestion that patients with COPD may display more adherent behaviours than patients with asthma.

Comprehensive sampling reveals circumpolarity and sympatry in seven mitochondrial lineages of the Southern Ocean crinoid species Promachocrinus kerguelensis (Echinodermata).

Sampling at appropriate spatial scales in the Southern Ocean is logistically challenging and may influence estimates of diversity by missing intermediate representatives. With the assistance of sampling efforts especially influenced by the International Polar Year 2007-2008, we gathered nearly 1500 specimens of the crinoid species Promachocrinus kerguelensis from around Antarctica. We used phylogeographic and phylogenetic tools to assess its genetic diversity, demographic history and evolutionary relationships. Six phylogroups (A-F) identified in an earlier study are corroborated here, with the addition of one new phylogroup (E2). All phylogroups are circumpolar, sympatric and eurybathic. The phylogeny of Promachocrinus phylogroups reveals two principal clades that may represent two different cryptic species with contrasting demographic histories. Genetic diversity indices vary dramatically within phylogroups, and within populations, suggesting multiple glacial refugia in the Southern Ocean: on the Kerguelen Plateau, in the East Weddell Sea and the South Shetland Islands (Atlantic sector), and on the East Antarctic continental shelf in the Dumont d'Urville Sea and Ross Sea. The inferences of gene flow vary among the phylogroups, showing discordant spatial patterns. Phylogroup A is the only one found in the Sub-Antarctic region, although without evident connectivity between Bouvet and Kerguelen populations. The Scotia Arc region shows high levels of connectivity between populations in most of the phylogroups, and barriers to gene flow are evident in East Antarctica.

Development of the Manchester framework for the evaluation of emergency department pharmacy services.

BACKGROUND: Many countries, including the United Kingdom, have established Emergency Department (ED) pharmacy services where some ED pharmacists now work as practitioners. They provide both traditional pharmaceutical care and novel practitioner care i.e. clinical examination, yet their impact on quality of care is unknown. AIM: To develop a framework of structures, processes and potential outcome indicators to support evaluation of the quality of ED pharmacy services in future studies. METHOD: Framework components (structures, processes and potential outcome indicators) were identified in three ways: from a narrative review of relevant international literature, and separate panel meetings with ED pharmacists and then other ED healthcare professionals. Structures and processes were collated into categories developed iteratively throughout data collection, with outcome indicators collated into six domains of quality as proposed by the Institute of Medicine. These raw data were then processed e.g. outcome indicators screened for clarity i.e. those which explicitly stated what would be measured were included in the framework. RESULTS: A total of 190 structures, 533 processes, and 503 outcome indicators were identified. Through data processing a total of 153 outcome indicators were included in the final framework divided into the domains safe (32), effective (50), patient centred (18), timely (24), efficient (20) and equitable (9). CONCLUSION: The first framework specific to the quality evaluation ED pharmacy services, service evaluators should validate potential outcome indicators prior to their use. The minimum expected of a high-quality service should also be defined to enable interpretation of relevant measurements.

Message in a Bottle-Metabarcoding enables biodiversity comparisons across ecoregions.

BACKGROUND: Traditional biomonitoring approaches have delivered a basic understanding of biodiversity, but they cannot support the large-scale assessments required to manage and protect entire ecosystems. This study used DNA metabarcoding to assess spatial and temporal variation in species richness and diversity in arthropod communities from 52 protected areas spanning 3 Canadian ecoregions. RESULTS: This study revealed the presence of 26,263 arthropod species in the 3 ecoregions and indicated that at least another 3,000-5,000 await detection. Results further demonstrate that communities are more similar within than between ecoregions, even after controlling for geographical distance. Overall α-diversity declined from east to west, reflecting a gradient in habitat disturbance. Shifts in species composition were high at every site, with turnover greater than nestedness, suggesting the presence of many transient species. CONCLUSIONS: Differences in species composition among their arthropod communities confirm that ecoregions are a useful synoptic for biogeographic patterns and for structuring conservation efforts. The present results also demonstrate that metabarcoding enables large-scale monitoring of shifts in species composition, making it possible to move beyond the biomass measurements that have been the key metric used in prior efforts to track change in arthropod communities.

DNA barcoding highlights a cryptic species of grenadier Macrourus in the Southern Ocean.

Although three species of the genus Macrourus are recognized in the Southern Ocean, DNA sequencing of the mitochondrial COI gene revealed four well-supported clades. These barcode data suggest the presence of an undescribed species, a conclusion supported by meristic and morphometric examination of specimens.

Molecular and morphological evidence supports the species status of the Mahachai fighter Betta sp. Mahachai and reveals new species of Betta from Thailand.

Two regions of mitochondrial (mt) DNA, cytochrome c oxidase subunit 1 (COI) and 16S rRNA, were sequenced in nine species of Betta from Thailand and Indonesia. Most species showed little intraspecific COI variation (adjusted mean = 0.48%) including the putative species Betta sp. Mahachai, but one species (Betta smaragdina) included three lineages showing much greater divergence (7.03-13.48%) that probably represent overlooked species. These findings were confirmed by maximum likelihood analysis and Bayesian inference, which revealed well-supported corresponding monophyletic clades. Based on these results and morphological differences, the putative species Betta sp. Mahachai from central Thailand is a species distinct from other members of the B. splendens group and represents a new and hitherto undescribed species. Furthermore, this study also demonstrated the probable existence of two overlooked Betta species found in the Khorat plateau basin, illustrating the utility of mitochondrial genetic markers in the revelation of overlooked diversity.

The description and definition of Emergency Department Pharmacist Practitioners in the United Kingdom (the ENDPAPER study).

Background Due to a shortage of emergency department doctors and nurses, hospitals have started to employ pharmacists who have additional clinical skills, known as Emergency Department Pharmacist Practitioners, to help deliver services. Objective To describe, compare and define the Emergency Department Pharmacist Practitioner role. Setting UK emergency departments. Method Using a purpose developed questionnaire hosted on a tablet computer, Emergency Department Pharmacist Practitioners were asked to report their contribution to patient care and the wider emergency department over 10 work days. Main outcome measure Emergency Department Pharmacist Practitioners' work. Results Twenty Emergency Department Pharmacist Practitioners from 15 UK hospitals were recruited. Of 682 patients cared for, 4.8% (n=33) were of blue triage category (least urgent) and 4.1% (n=28) red (immediate need). Specific activities to inform patient diagnosis included clinical examinations (264/682 patients, 38.7%) and the review of investigation/test/procedure results (270, 39.6%). For treatment, EDPPs prescribed a total of 603 medicines (for administration in the ED) to 266 patients (39.0%) and performed procedures for 63 (9.2%). Eleven of the practitioners also took on the role of designated care provider (i.e. the healthcare professional with overall clinical responsibility) for at least some of their patients. From application of the care typology, all 20 practitioners carried out both 'traditional' and 'practitioner' activity and 9/20 of them sometimes provided more 'practitioner' than 'traditional' care to individual patients. Seven key role attributes were identified including how these pharmacists support patients with medical complaints and injuries of any severity and at any stage of their visit. Conclusion Emergency Department Pharmacist Practitioners combine traditional clinical pharmacy activities with more hands-on medical practise including being designated care provider. The role is versatile in that care and support provided to patients and the wider emergency department professional team is varied and therefore somewhat adaptable to situations which present.

Diabetes and lower-limb amputations in the community. A retrospective cohort study. DARTS/MEMO Collaboration. Diabetes Audit and Research in Tayside Scotland/Medicines Monitoring Unit.

OBJECTIVE: There are few U.K. data on the incidence rates of amputation in diabetic subjects compared with the nondiabetic population. RESEARCH DESIGN AND METHODS: We performed a historical cohort study of first lower-extremity amputations based in Tayside, Scotland (population 364,880) from 1 January 1993 to 31 December 1994. The Diabetes Audit and Research in Tayside Scotland (DARTS) database was used to identify a prevalence cohort of 7,079 diabetic patients on 1 January 1993. We estimated age-specific and standardized incidence rates of lower-limb amputations in the diabetic and nondiabetic cohorts. Results were compared with a previous study that evaluated lower-extremity amputations in diabetic patients in Tayside in 1980-1982. RESULTS: There were 221 subjects who underwent a total of 258 nontraumatic amputations. Of the 221 subjects, 60 (27%) patients were diabetic (93% NIDDM), and 63% were first amputations. The median duration of diabetes was 6 years (range: newly diagnosed to 41 years). Nonhealing ulceration (31%) and gangrene (29%) were the two main indications for amputation in the diabetic subjects. Of the 161 nondiabetic subjects, 140 (80%) underwent first amputations. The adjusted incidences in the diabetic and nondiabetic groups were 248 and 20 per 100,000 person-years, respectively. Tayside patients with diabetes thus had a 12.3-fold risk of an amputation compared with nondiabetic residents (95% CI 8.6-17.5). The estimated proportion of diabetic patients in the population rose from 0.81% in 1980-1982 to 1.94% in 1993-1994, whereas the absolute rate of amputation in diabetic subjects was unchanged from that in 1980-1982. CONCLUSIONS: These population-based U.K. amputation data are similar to amputation rates in the U.S. Amputation rates appear to have decreased significantly since 1980-1982. The impact of diabetes education and prevention programs that target the processes leading to amputation can now be evaluated.

CT angiography for the detection and characterization of carotid artery bifurcation disease.

BACKGROUND AND PURPOSE: Computed tomographic angiography (CTA) is a relatively new and minimally invasive method of imaging intracranial and extracranial blood vessels. The main purpose of this study was to compare CTA to the current gold standard of arterial imaging, digital subtraction angiography (DSA), for the detection and quantification of carotid artery bifurcation stenosis. We also compared Doppler ultrasound (US) with these 2 techniques. METHODS: In a prospective study, 40 patients (80 carotid arteries) underwent CTA, US, and DSA. Patients chosen for inclusion were symptomatic with TIAs or stroke and had initial US screening that indicated >50% carotid stenosis on the side appropriate for the symptoms. Source axial, maximum intensity projection (MIP), and shaded-surface display (SSD) images were produced for each CTA study. The US, CTA, and DSA images were reviewed, with the degree of stenosis quantified and presence of ulcers determined; each type of imaging was reviewed by a separate investigator blinded to the results of the other 2 modalities. The results of CTA and US imaging were compared with the DSA images for degrees of carotid stenosis. RESULTS: CTA source axial images correlated with DSA more closely than MIP or SSD images for all degrees of stenosis. The correlation between US and DSA (0.808) was poorer than that between CTA and DSA (0.892 to 0.922). CTA performed well in the detection of mild (0% to 29%) carotid stenosis, as well as carotid occlusion, with values for sensitivity, specificity, and accuracy near 100%. In determining that a stenosis was >50% by DSA measurement, CTA was again useful, with a sensitivity, specificity, and accuracy of 89%, 91%, and 90%, respectively. While CTA was quite specific and accurate in identifying degrees of stenoses in either the 50% to 69% or the 70% to 99% ranges, in this task it was much less sensitive: 65% for 50%-69% stenosis and 73% for 70%-99% stenosis. These results did not change significantly when only the data from the most clinically relevant symptomatic arteries were analyzed. CTA was found to correlate quite well with DSA in the detection of ulcers associated with the carotid stenosis. CONCLUSIONS: CTA was found to be an excellent examination for the detection of carotid occlusion and categorization of stenosis in either the 0%-29% or >50% ranges. However, CTA was unable to reliably distinguish between moderate (50%-69%) and severe (70%-99%) stenosis, which is an important limitation in the investigation and treatment of carotid stenosis.

Selegiline and mortality in subjects with Parkinson's disease: a longitudinal community study.

OBJECTIVE: To estimate mortality by drug use in a cohort of patients with PD relative to age- and sex-matched comparators. METHODS: two longitudinal cohorts of patients with 7 and 11 years' duration of PD were constructed with matched comparators in Tayside, Scotland. Subjects were eligible for inclusion if they received a first prescription for an anti-Parkinson's drug from July 1989 to December 1995, with no PD drug prescription in the previous 6 months. Those who had previously taken a neuroleptic drug or were younger than 40 years of age were excluded. RESULTS: Overall, subjects with PD in relation to comparators had higher mortality with a rate ratio (RR) of 1.76 (95% CI 1.11, 2.81) in the 7-year cohort. There was significantly greater mortality in patients with PD who received levodopa monotherapy (RR = 2.45, 95% CI 1.42, 4.23) relative to the comparators, adjusting for previous cardiovascular drug use and diabetes. However, there was no significant difference in mortality in those with PD receiving combination therapy of selegiline with levodopa and other drugs in relation to the comparators (RR = 0.92, 95% CI 0.37, 2.31). CONCLUSIONS: Subjects with PD had twice the rate of mortality relative to age- and sex-matched comparators. However, those subjects who received selegiline at any time in combination with co-careldopa or co-beneldopa showed no significant difference in mortality compared with the comparators. Monotherapy with levodopa was associated with the highest mortality.

CT angiography for the detection of cerebral vasospasm in patients with acute subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Digital subtraction angiography (DSA) is the standard of reference for detecting cerebral vasospasm after subarachnoid hemorrhage (SAH). CT angiography (CTA) is a relatively recent method for depicting the intracranial arterial vasculature. The purpose of this study was to compare CTA and DSA in the detection and quantification of cerebral vasospasm. METHODS: Seventeen patients with SAH underwent initial CTA with or without DSA and follow-up CTA and DSA. The follow-up CTA and DSA studies were performed within 24 hours of each other and 5 to 10 days after SAH. Maximum intensity projection images were produced for each CTA. Six arterial locations were examined for spasm: the suprasellar internal carotid artery (ICA), the M1 and M2 segments of the middle cerebral artery, the A1 and A2 segments of the anterior cerebral artery, and the basilar artery. Vasospasm was categorized as none, mild (<30% luminal reduction), moderate (30% to 50% reduction), or severe (>50% reduction). RESULTS: The overall correlation between CTA and DSA was 0.757, but was better for proximal than distal locations (0.88-1.00 versus 0.152-0.446). Agreement between CTA and DSA was greater for no spasm (92%) and severe spasm (100%) than for mild (57%) or moderate (64%) spasm. CTA was highly accurate for no spasm or severe spasm in proximal locations (96%, and 100%, respectively); it was less accurate (90% and 95%, respectively) for mild or moderate spasm in these locations. For distal locations, the accuracy for absent, mild, moderate, or severe spasm was 78%, 81%, 94%, and 100%, respectively. CONCLUSION: CTA is highly sensitive, specific, and accurate in detecting no spasm or severe cerebral vasospasm in proximal arterial locations; it is less accurate for detecting mild and moderate spasm in distal locations.

Experience with computed tomographic angiography for the detection of intracranial aneurysms in the setting of acute subarachnoid hemorrhage.

OBJECTIVE: To objectively compare computed tomographic angiography (CTA) with selective digital subtraction angiography (DSA) in the detection and anatomic definition of intracranial aneurysms, particularly in the setting of acute subarachnoid hemorrhage (SAH). METHODS: In a blinded prospective study, 40 patients with known or suspected intracranial saccular aneurysms underwent both CTA and DSA, including 32 consecutive patients with SAH in whom CTA was performed after CT images were obtained diagnostic for SAH. The CT angiograms were interpreted for presence, location, and size of the aneurysms, and anatomic features, such as the number of aneurysms lobes, aneurysm neck size (< or = 4 mm), and the number of adjacent arterial branches were suggested. The images obtained with CTA were then compared with the images obtained with DSA, with the later images serving as controls. RESULTS: DSA revealed 43 aneurysms in 30 patients and ruled out intracranial aneurysms in the remaining 10 patients. For aneurysm presence alone, the sensitivity and specificity for CTA was 86 and 90%, respectively. For the presence of an aneurysms, six CT angiogram showed false negative results and one CT angiogram showed a false positive result. False negative results were usually caused by technical problems with the image, tiny aneurysm domes (< 3 mm), and unusual aneurysm locations (i.e., intracavernous carotid or posterior inferior cerebellar artery aneurysms). The results obtained with CTA were, compared with the results obtained with DSA, more than 95% accurate in determining dome and neck size of aneurysm, aneurysm lobularity, and the presence and number of adjacent arterial branches. In addition, CTA provided a three-dimensional representation of the aneurysmal lesion, which was considered useful for surgical planning. CONCLUSION: CTA is useful for rapid and relatively noninvasive detection of aneurysms in common locations, and the anatomic information provided in images showing positive results is at least equivalent to that provided by DSA. In cases of SAH in which the nonaugmented CT and CTA results indicate a clear source of bleeding and provide adequate anatomic detail, we think it is possible to forego DSA before urgent early aneurysm surgery. In all other cases, DSA is indicated.

Computed tomographic angiography versus digital subtraction angiography for the diagnosis and early treatment of ruptured intracranial aneurysms.

OBJECTIVE: Computed tomographic angiography (CTA) is a rapid and minimally invasive method of detecting intracranial aneurysms. We wished to determine whether CTA could replace digital subtraction angiography (DSA) in the diagnosis and operative planning of ruptured cerebral aneurysms. METHODS: In a prospective study, patients with subarachnoid hemorrhage diagnosed by plain computed tomography underwent CTA, DSA, or both. Computed tomographic scans and CTA studies were first reviewed by the treating surgeon, along with a neuroradiologist, and a decision to proceed to DSA or directly to surgery was made on the basis of the type and quality of information provided by CTA. All patients underwent postoperative DSA. RESULTS: A total of 173 patients were studied. In 24 patients, both CTA and DSA were negative for a source of subarachnoid hemorrhage. Twelve patients underwent DSA without prior CTA because a technologist capable of performing CTA was not available when the patient was evaluated. Nine patients in poor neurological condition underwent CTA, and all tested positive for aneurysms but died without surgical intervention. Of the 126 patients who underwent CTA and surgery, 65 (52%) also required preoperative DSA. The decision to proceed to DSA after CTA was influenced by aneurysm location; posterior communicating artery (62%) and posterior circulation locations (67-75%) more commonly proceeded to DSA than middle cerebral artery aneurysms (34%; 0.025 > P > 0.01). The sensitivity and specificity of CTA for the detection of all aneurysms, ruptured and unruptured, in the group of patients who underwent both types of angiograms preoperatively were 84 and 100%, respectively. In the group of 61 patients in whom aneurysm surgery was performed on the basis of CTA results alone, the sensitivity and specificity for the detection of all aneurysms, as compared with postoperative DSA, were 90 and 100%, respectively. Missed aneurysms (n = 24) were always small (<4 mm) and were usually found in patients with multiple aneurysms in whom the larger, ruptured aneurysm was identified by CTA. In one patient, the aneurysm missed by preoperative CTA would have resulted in a different operation if detected preoperatively. CONCLUSION: It is possible to proceed to ruptured aneurysm repair entirely on the basis of good-quality CTA studies that demonstrate an aneurysm consistent with the pattern of bleeding observed on plain computed tomography (48% of the patients in this series and most common middle cerebral artery aneurysms). However, detection of small unruptured aneurysms in patients with multiple lesions remains a problem.

A trial of the 21-aminosteroid U74006F in a primate model of chronic cerebral vasospasm.

The efficacy of U74006F in the prophylaxis of chronic cerebral vasospasm (VSP) was evaluated in a randomized, double-blind, placebo-controlled trial. Forty cynomolgus monkeys were divided by restricted randomization into 2 treatment groups of 20. Five animals from each treatment group were randomized into subgroups 1 and 2. The animals of subgroup 1 were studied pathologically. Brain biopsies of the animals in subgroup 2 were performed and studied with high-performance liquid chromatography (HPLC). The remaining 20 animals supplemented the number studied angiographically. Significant VSP (P less than 0.05) was detected in the majority of vessels from the clot site (right) of both treatment groups. Electron microscopy results showed positive correlation with the angiographic data. When comparing the effects of U74006F to those of the placebo at day 7, there was a significant difference (P less than 0.05) in the degree of VSP in the right extradural internal carotid and right middle cerebral arteries. This resulted from a greater degree of VSP in placebo animals. Two animals developed delayed ischemic deficits, one from each group. The infarct of the U74006F animal was smaller than the infarct in the placebo animal. Although overall changes in phosphagen levels did not reach statistical significance, HPLC analysis of the cortical biopsies did show a decrease in the ATP/ADP +/- AMP ratio of 54% in placebo animals and only 7% in animals receiving U74006F. The middle cerebral arteries of 2 animals were also studied with HPLC.(ABSTRACT TRUNCATED AT 250 WORDS)

Heparin-induced thrombocytopenia and thrombosis following subarachnoid hemorrhage. Case report.

The authors present a case of heparin-induced thrombocytopenia and thrombosis (HITT) that occurred after aneurysmal subarachnoid hemorrhage (SAH), and they review the relevant literature. An immune-mediated syndrome, HITT is characterized by moderate thrombocytopenia and paradoxical vascular thromboses. Although it has been estimated in prospective studies that HITT occurs in between 1 and 3% of patients receiving heparin, it is underrecognized in the neurosurgical literature. In the present case, a 49-year-old woman underwent clipping of a right posterior communicating artery aneurysm after suffering a Hunt and Hess Grade III SAH. She had an uncomplicated postoperative course with good clip positioning and no vasospasm observed on a cerebral angiogram obtained on Day 7. On Day 23, the patient developed a right hemiparesis and experienced a grand mal seizure. A head computerized tomography scan revealed a hemorrhagic infarct in the left middle cerebral artery distribution. Repeated cerebral angiograms did not show vasospasm. She was thrombocytopenic (platelet count as low as 46 x 10(9)/L on Day 28 compared with 213 x 10(9)/L on Day 1) and had been receiving heparin flushes to maintain intravenous catheter patency. An assay for HITT-associated antibodies was positive. The heparin flushes were discontinued and the platelet count recovered (121 x 10(9)/L). She improved neurologically, but was left with a significant right hemiparesis at discharge. This patient had assay-proven heparin-induced thrombocytopenia despite minimal exposure to heparin. Because there was no evidence of vasospasm or other factors to account for her delayed hemorrhagic infarction, an HITT-related disorder seemed most likely. Despite a large body of literature describing HITT in nonneurosurgical patients, only three previous neurosurgical cases have been published. This case report may serve to heighten awareness of this disorder.

Effect of intrathecal thrombolytic therapy on subarachnoid clot and chronic vasospasm in a primate model of SAH.

The safety and efficacy of the thrombolytic agent tissue-type plasminogen activator (tPA) in the elimination of subarachnoid clot and prevention of chronic vasospasm were evaluated in a blind randomized placebo-controlled trial. Twenty-four monkeys were randomly assigned to one of two groups of 12. Each group underwent baseline cerebral angiography and coagulation analysis followed by right-sided craniectomy and experimental subarachnoid hemorrhage (SAH). An Ommaya reservoir was inserted with its catheter placed into the subarachnoid space. Twenty-four hours later one group (the tPA group) received 0.5 mg of tPA in 0.5 ml of buffer injected into the reservoir every 8 hours for three doses, while the second group (the placebo group) received the same volume of normal saline. On Day 7, angiography was repeated and the animals were sacrificed. One animal from the placebo group developed a delayed ischemic neurological deficit on Day 5 after SAH. Moderate to severe vasospasm (greater than 30% reduction in vessel caliber) was present on Day 7 in the internal carotid and middle cerebral arteries of the animals in the placebo group (p less than 0.01), while in the tPA group only mild narrowing of the anterior cerebral artery was seen. No significant change in coagulation status occurred in either group. All animals in the placebo group had a large amount of subarachnoid clot remaining at the time of sacrifice, but 11 of the 12 animals in the tPA group were completely free of clot. The results of electron microscopic studies of the cerebral arteries correlated with angiography, and there was no histological evidence of brain inflammation associated with the intrathecal use of tPA.

The doctor-patient relationship and prescribing patterns. A view from primary care.

The doctor-patient relationship has been described in economic terms as an 'agency relationship' where informed agents make decisions for uninformed clients. However, the decision to prescribe and the decision to accept the prescription by the patient are more complex in nature and involve many variables. Other factors, such as the 'need' for the prescription and the disease state (acute or chronic) also influence prescribing practice. Communication between the physician and patient was found to be important for rational and effective prescribing. The client can make better decisions with the relevant information, thus breaking down the agency relationship that once existed.

Hydrocephalus following aneurysmal subarachnoid haemorrhage.

Ninety-four patients with hydrocephalus following subarachnoid haemorrhage were investigated. Fourteen of these patients had temporary ventricular drains inserted, 19 had drains that were later converted to ventricular-peritoneal shunts, and 61 patients had shunts only. All patients were analysed with respect to their grade on admission, the distribution of blood on CT scan, their Glasgow Coma Score, their intracranial pressure, and the presence or absence of vasospasm on angiography. Outcome was analysed by shunt procedure and time of shunt insertion. The higher the grade on admission, the more likely it was the patient would require a shunt. Fewer patients with a good outcome required shunting as compared to those whose outcome was poor. Patients having more subarachnoid blood on CT scan tended to present with a lower Glasgow Coma Score. The outcome of patients with intraventricular haemorrhage was not obviously influenced by the insertion of a ventriculostomy. Vasospasm was not more common in patients requiring a ventriculo-peritoneal shunt, nor did early shunting in patients with hydrocephalus affect the incidence of vasospasm. The majority of patients were either shunted in the first three days or after 30 days post-SAH. The outcome was better in those patients shunted at a later date.