Impact of a physician - critical care practitioner pre-hospital service in Wales on trauma survival: a retrospective analysis of linked registry data.

The Emergency Medical Retrieval and Transfer Service for Wales launched in 2015. This service delivers senior pre-hospital doctors and advanced critical care practitioners to the scene of time-critical life- and limb-threatening incidents to provide advanced decision-making and pre-hospital clinical care. The impact of the service on 30-day mortality was evaluated retrospectively using a data linkage system. The study included patients who sustained moderate-to-severe blunt traumatic injuries (injury severity score ≥ 9) between 27 April 2015 and 30 November 2018. The association between pre-hospital management by the Emergency Medical Retrieval and Transfer Service and 30-day mortality was assessed using multivariable logistic regression. In total, data from 4035 patients were analysed, of which 412 (10%) were treated by the Emergency Medical Retrieval and Transfer Service. A greater proportion of patients treated by the Emergency Medical Retrieval and Transfer Service had an injury severity score ≥ 16 and Glasgow coma scale ≤ 12 (288 (70%) vs. 1435 (40%) and 126 (31%) vs. 325 (9%), respectively). The unadjusted 30-day mortality rate was 11.7% for patients managed by the Emergency Medical Retrieval and Transfer Service compared with 9.6% for patients managed by standard pre-hospital care services. However, after adjustment for differences in case-mix, the 30-day mortality rate for patients treated by the Emergency Medical Retrieval and Transfer Service was 37% lower (adjusted odds ratio 0.63 (95%CI 0.41-0.97); p = 0.037). The introduction of an emergency medical retrieval service was associated with a reduction in 30-day mortality for patients with blunt traumatic injury.

Development of a registration framework to validate MRI with histology for prostate focal therapy.

PURPOSE: Focal therapy has been proposed as an alternative method to whole-gland treatment for prostate cancer when aiming to reduce treatment side effects. The authors recently validated a radiobiological model which takes into account tumor location and tumor characteristics including tumor cell density, Gleason score, and hypoxia in order to plan optimal dose distributions for focal therapy. The authors propose that this model can be informed using multiparametric MRI (mpMRI) and in this study present a registration framework developed to map prostate mpMRI and histology data, where histology will provide the "ground truth" data regarding tumor location and biology. The authors aim to apply this framework to a growing database to develop a prostate biological atlas which will enable MRI based planning for prostate focal therapy treatment. METHODS: Six patients scheduled for routine radical prostatectomy were used in this proof-of-concept study. Each patient underwent mpMRI scanning prior to surgery, after which the excised prostate specimen was formalin fixed and mounted in agarose gel in a custom designed sectioning box. T2-weighted MRI of the specimen in the sectioning box was acquired, after which 5 mm sections of the prostate were cut and histology sections were microtomed. A number of image processing and registration steps were used to register histology images with ex vivo MRI and deformable image registration (DIR) was applied to 3D T2w images to align the in vivo and ex vivo MRI data. Dice coefficient metrics and corresponding feature points from two independent annotators were selected in order to assess the DIR accuracy. RESULTS: Images from all six patients were registered, providing histology and in vivo MRI in the ex vivo MRI frame of reference for each patient. Results demonstrated that their DIR methodology to register in vivo and ex vivo 3D T2w MRI improved accuracy in comparison with an initial manual alignment for prostates containing features which were readily visible on MRI. The average estimated uncertainty between in vivo MRI and histology was 3.3 mm, which included an average error of 3.1 mm between in vivo and ex vivo MRI after applying DIR. The mean dice coefficient for the prostate contour between in vivo and ex vivo MRI increased from 0.83 before DIR to 0.93 after DIR. CONCLUSIONS: The authors have developed a registration framework for mapping in vivo MRI data of the prostate with histology by implementing a number of processing steps and ex vivo MRI of the prostate specimen. Validation of DIR was challenging, particularly in prostates with few or mostly linear rather than spherical shaped features. Refinement of their MR imaging protocols to improve the data quality is currently underway which may improve registration accuracy. Additional mpMRI sequences will be registered within this framework to quantify prostate tumor location and biology.

Improving Multiple Sclerosis Plaque Detection Using a Semiautomated Assistive Approach.

BACKGROUND AND PURPOSE: Treating MS with disease-modifying drugs relies on accurate MR imaging follow-up to determine the treatment effect. We aimed to develop and validate a semiautomated software platform to facilitate detection of new lesions and improved lesions. MATERIALS AND METHODS: We developed VisTarsier to assist manual comparison of volumetric FLAIR sequences by using interstudy registration, resectioning, and color-map overlays that highlight new lesions and improved lesions. Using the software, 2 neuroradiologists retrospectively assessed MR imaging MS comparison study pairs acquired between 2009 and 2011 (161 comparison study pairs met the study inclusion criteria). Lesion detection and reading times were recorded. We tested inter- and intraobserver agreement and comparison with original clinical reports. Feedback was obtained from referring neurologists to assess the potential clinical impact. RESULTS: More comparison study pairs with new lesions (reader 1, n = 60; reader 2, n = 62) and improved lesions (reader 1, n = 28; reader 2, n = 39) were recorded by using the software compared with original radiology reports (new lesions, n = 20; improved lesions, n = 5); the difference reached statistical significance (P < .001). Interobserver lesion number agreement was substantial (≥1 new lesion: κ = 0.87; 95% CI, 0.79-0.95; ≥1 improved lesion: κ = 0.72; 95% CI, 0.59-0.85), and overall interobserver lesion number correlation was good (Spearman ρ: new lesion = 0.910, improved lesion = 0.774). Intraobserver agreement was very good (new lesion: κ = 1.0, improved lesion: κ = 0.94; 95% CI, 0.82-1.00). Mean reporting times were <3 minutes. Neurologists indicated retrospective management alterations in 79% of comparative study pairs with newly detected lesion changes. CONCLUSIONS: Using software that highlights changes between study pairs can improve lesion detection. Neurologist feedback indicated a likely impact on management.

Examining the effects of linking student performance and progression in a tier 2 kindergarten reading intervention.

Despite the emerging evidence base on response to intervention, there is limited research regarding how to effectively use progress-monitoring data to adjust instruction for students in Tier 2 intervention. In this study, we analyzed extant data from a series of randomized experimental studies of a kindergarten supplemental reading intervention to determine whether linking performance on formative assessments to curriculum progression improved kindergarten reading outcomes over standard implementation. We were interested in whether specific progression adjustments would enhance the effects of supplemental reading intervention. Growth-mixture modeling using data from kindergarteners (n = 136) whose intervention progression (e.g. repeat lessons, skip lessons) was adjusted every 4 weeks based on mastery data identified four latent classes characterized by unique profiles of curriculum progression adjustments. Multilevel analyses comparing the performance of students in the four classes with that of propensity matched groups whose intervention was not adjusted (n = 101) indicated positive effects of curriculum progression for (a) students whose formative assessment performance exceeded 90% and received early and sustained lesson acceleration and (b) students who initially performed below 70% on assessments and who repeated early lessons and progressed to conventional implementation. Effects of curriculum adjustments for the two smallest groups were less clear.

Audit of nutritional practice and knowledge.

An audit of nutritional practice was carried out in one NHS trust. Findings demonstrated areas for improvement, particularly in the documentation of nutritional status and in criteria for referral for specialist help. An assessment sheet and a nursing care plan were developed to assess patients' risk of being malnourished and to provide a recognised place for recording nutrition-related information.

Twelve month comparison of salmeterol and salbutamol as dry powder formulations in asthmatic patients. European Study Group.

BACKGROUND: Salmeterol is a potent selective beta 2 agonist that has been shown to have a duration of action in excess of 12 hours. In this study salmeterol and salbutamol were compared over a three month period with a further extension of nine months. METHODS: Three hundred and eighty eight patients with mild to moderate reversible airways obstruction (forced expiratory volume in one second (FEV1) > 50% predicted) were randomised to receive salmeterol (50 micrograms) twice daily or salbutamol (400 micrograms) four times daily, both by dry powder, in a double blind parallel group study. During the first three months detailed assessment of efficacy was made with recording of morning and evening peak expiratory flow rates (PEF), asthma symptoms, and bronchodilator use when necessary for the relief of symptoms. Patients continued in the study for a further nine months with the salbutamol dose reduced to 400 micrograms twice daily. Lung function was measured at the clinic and safety data were collected during this period. RESULTS: Salmeterol produced a significantly higher mean morning PEF (mean difference compared with salbutamol 21 (95% CI 12-31) l/min), and a significant reduction in mean diurnal variation in PEF (from 30 l/min at baseline to 11 34 l/min at baseline to 32 l/min during salbutamol treatment). Salmeterol also reduced day and night symptoms and use of rescue bronchodilator. FEV1 increased with both salmeterol and salbutamol treatment over the 12 month treatment period. For both treatments the number of patients reporting exacerbations of asthma and the frequency of these exacerbations remained constant during the study. Thirty six patients in the salmeterol and 49 in the salbutamol group withdrew during the 12 months of the study. CONCLUSIONS: In this study salmeterol (50 micrograms twice daily) was more effective than salbutamol (400 micrograms four times daily) in the control of asthma over three months, and more effective than salbutamol (400 micrograms twice daily) over a further nine months. Neither salmeterol nor salbutamol was associated with any worsening of control of asthma.

Ketanserin and capillary flow in Raynaud's phenomenon.

The serotonin (S2) antagonist ketanserin has been proposed as a useful therapy for Raynaud's phenomenon. The present study was designed to investigate the effects of 8 weeks therapy with oral Ketanserin (40 mg tds for the last 6 weeks) on finger nailfold capillary flow velocity at rest and following cold challenge and symptom score in 30 patients with Raynaud's in a double-blind, placebo-controlled, parallel design study. The ketanserin treated group reported a 16.7% improvement in symptom score (p less than 0.05) relative to the end of the run-in phase compared with a 2.4% (NS) improvement in the placebo group. Improvement in capillary flow was confined to a significant (p less than 0.02) rise in rest flow in the ketanserin treated group but no beneficial changes were observed following cold challenge. The disparity between the subjective and objective benefits demonstrated for this drug suggest the possibility of a central action rather than one that involves the correction of a local vascular fault.

Dynamic measurement of human capillary blood pressure.

1. Capillary blood pressure was measured in man using a dynamic servo-nulling system and direct micropuncture. This enabled assessments of the normal variations in pressure which influence fluid filtration and reabsorption. 2. Seventy-eight capillaries in 19 subjects were punctured in one of three positions around the capillary loop with the hand at the level of the sternal angle. Mean pressure around the loop fell from 37.7 +/- 3.7 mmHg (arteriolar limb, mean +/- SEM, n = 12) to 19.4 +/- 1.0 mmHg (apex, n = 25) to 14.6 +/- 0.5 mmHg (venular limb, n = 41) at skin temperatures of 18.7-33.1 degrees C. These values agree closely with Landis' original studies in 1930 [E. Landis (1930) Heart, 15, 209-228]. 3. The mean filtration/reabsorption state of any particular capillary limb was not static because of cardiac, vasomotor and respiratory fluctuations in capillary pressure. From a total of 38 capillaries in which recordings were analysed for 30 s, the fluctuations in pressure were such that 27 capillaries probably had periods of both filtration and reabsorption. 4. Computerized superimposition and coherent averaging of trains of capillary pulses enabled an accurate description of the pulse waveform to be made in three capillaries. This was remarkably similar to waveforms from the radial artery, albeit at reduced amplitude (average 3.6 +/- 3.4 mmHg, mean +/- SD overall). The time for the pulse to travel between the radial artery and the finger capillary was approximately 10 ms, which implies a propagation velocity of several metres per second.(ABSTRACT TRUNCATED AT 250 WORDS)

Glucose and perinatal hypoxic-ischemic brain damage in the rat.

Seven-day postnatal rats were rendered hyperglycemic by the SC injection of 50% glucose, following which they were exposed to hypoxia with 8% oxygen. The glucose-treated animals survived more than twice as long as saline-treated littermates. Other hyperglycemic and control rat pups were subjected to hypoxia-ischemia by unilateral common carotid artery occlusion combined with 2 hours of hypoxia. Neuropathologic analysis of recovered animals at 30 days of age showed that the brains of the glucose-treated animals were no more damaged than those of the saline controls (p greater than 0.05). The finding indicates that, unlike adults, glucose supplementation and its associated hyperglycemia in the immature rat does not increase the extent of hypoxic-ischemic brain damage.

Selected soft tissue malignancies of the foot: an in-depth study with case reports.

Soft tissue malignancies represent a diagnostic and therapeutic challenge to the podiatric physician. In order to improve prognosis and increase survival rates of affected patients, prompt clinical and histologic recognition of suspect lesions is necessary. Here we present information and case reports on selected soft tissue malignancies including Kaposi's sarcoma, malignant melanoma, synovial sarcoma, and epithelioid sarcoma to aid the practitioner in recognizing these serious lesions that occur in the foot.

Moderate hyperglycemia augments ischemic brain damage: a neuropathologic study in the rat.

We compared the effects of glucose injection with those of saline or mannitol on ischemic brain damage and brain water content in a four-vessel occlusion (4-VO) rat model, which simultaneously causes severe forebrain ischemia and moderate hindbrain ischemia. Glucose given before onset of ischemia was followed by severe brain injury, with necrosis of the majority of neocortical neurons and glia, substantial neuronal damage throughout the remainder of forebrain, and severe brain edema. By comparison, saline injection before forebrain ischemia resulted in only scattered ischemic damage confined to neurons and no change in the brain water content. Mannitol injection before 4-VO or D-glucose injection during or after 4-VO produced no greater forebrain damage than did the saline injection. Morphologic damage in the cerebellum, however, was increased by D-glucose injection given either before or during 4-VO. The results demonstrate that hyperglycemia before severe brain ischemia or during moderate ischemia markedly augments morphologic brain damage.

Experimental cerebral ischemia produced by extracranial vascular injury: protection with indomethacin and prostacyclin.

To determine whether the production of brain ischemia is modified by antiplatelet agents administered at the time of extracranial endothelial injury, we modified a four-vessel occlusion rat model so that an electrogenic platelet thrombus in one carotid artery produced cerebral ischemia. DC current was passed through an anode around the left carotid artery of 11 rats with preoccluded vertebral and contralateral carotid arteries. Five of six untreated rats became unresponsive because of carotid occlusion and resultant cerebral ischemia; none of five animals pretreated with indomethacin and infused with prostacyclin (PGI2) were clinically affected. Light- and electronmicroscopic studies showed arterial platelet-fibrin thrombi and ischemic brain damage in untreated rats. All rats had received radiolabeled platelets; radioactivity was increased in the electrogenically injured left carotid arteries from treated and untreated rats, but counts were reduced by more than 80% in indomethacin/PGI2-treated rats (p less than 0.01).

Hypoxic-ischemic brain injury and the vegetative state: clinical and neuropathologic correlation.

We studied 10 patients who survived for 2 to 8 weeks in a vegetative state, including 8 with cardiopulmonary failure and 2 with subarachnoid hemorrhage. Within days of onset, they regained brainstem function and awoke, but none had evidence of cognitive awareness. All patients opened their eyes within 2 weeks, and eight had roving conjugate eye movements. Pupillary and corneal responses were intact within 1 week, and seven patients had tonic oculovestibular responses (OVR) within 24 hours. By the end of 1 day, only three patients failed to move limbs in response to noxious stimuli. At postmortem, all patients had widespread ischemic neuronal damage in the cerebral hemispheres. The brainstems lacked morphologic abnormality, except that one patient had a single microinfarct in the superior colliculus.

Granulomatous angiitis of the nervous system first seen as relapsing myelopathy.

A previously healthy 19-year-old man with a painful, relapsing myelopathy died of a cerebral hemorrhage. At autopsy he was found to have granulomatous angiitis of the nervous system (GANS). This particular case of GANS is distinctive and has been reported on two previous occasions.

Selective immunodeficiency and malignant lymphoma of the central nervous system. Possible relationship to the Epstein-Barr virus.

This report presents the findings of a study of a 17-year-old male with a selective immunodeficiency to the Epstein-Barr virus, who died of a malignant lymphoma following clinical infectious mononucleosis. Autopsy findings and immunohistochemical techniques demonstrated a malignant lymphoma with B-lymphocyte characteristics which primarily involved the central nervous system (CNS). The relationship of the Epstein-Barr virus to lymphoproliferation is discussed.

The cytodiagnosis of malignant lymphomas and Hodgkin's disease in cerebrospinal, pleural and ascitic fluids.

One hundred twenty-six fluids from 98 patients with malignant lymphomas have been examined cytologically. The overall accuracy was 88 per cent with only one false positive in 126 fluids. False negatives were highest in the cerebrospinal fluid, which may reflect poor exfoliation of malignant lymphoma cells when the leptomeninges are involved. We have found exfoliative cytology to be an accurate method of diagnosing lymphomatous involvement of the leptomeninges, pleura and peritoneum and when a cytologic diagnosis of involvement by lymphoma is made it is almost as accurate as a histologic diagnosis. Nuclear characteristics and selected histochemical methods will allow classification of many types of lymphoma in bytologic preparations.

Cytology of the cerebrospinal fluid in patients with Hodgkin's disease or malignant lymphoma.

The cerebrospinal fluids (CSF) of 18 patients with Hodgkin's disease and 33 patients with malignant lymphoma were evaluated for the presence of malignant cells. The CSF cytology was correlated with the neuropathologic findings at surgery or autopsy. In the 51 patients included in the study there were seven false-negative CSF cytodiagnoses. Methods to improve detection in the false-negatives will be discussed. There were two false-positives. Explanations for the two false-positive cytodiagnoses will be presented. It is concluded that cytological examination of the CSF in patients with Hodgkin's disease and malignant lymphoma is a useful and reliable diagnostic tool.