Payment Innovation in Emergency Care: A Case for Global Clinician Budgets.

The fee-for-service funding model for US emergency department (ED) clinician groups is increasingly fragile. Traditional fee-for-service payment systems offer no financial incentives to improve quality, address population health, or make value-based clinical decisions. Fee-for-service also does not support maintaining ED capacity to handle peak demand periods. In fee-for-service, clinicians rely heavily on cross-subsidization, where high reimbursement from commercial payors offsets low reimbursement from government payors and the uninsured. Although fee-for-service survived decades of steady cuts in government reimbursement rates, it is increasingly strained because of visit volatility and the effects of the No Surprises Act, which is driving down commercial reimbursement. Financial pressures on ED clinician groups and higher hospital boarding and clinical workloads are increasing workforce attrition. Here, we propose an alternative model to address some of these fundamental issues: an all-payer-funded, voluntary global budget for ED clinician services. If designed and implemented effectively, the model could support robust clinician staffing over the long term, ensure stability in clinical workload, and potentially improve equity in payments. The model could also be combined with population health programs (eg, pre-ED and post-ED telehealth, frequent ED use programs, and other innovations), offering significant payer returns and addressing quality and value. A linked program could also change hospital incentives that contribute to boarding. Strategies exist to test and refine ED clinician global budgets through existing government programs in Maryland and potentially through state-level legislation as a precursor to broader adoption.

Ultrasound and color-flow Doppler evaluation for the diagnosis of subclinical hyperthyroidism.

AIM: Clinical significance, population screening and management of subclinical hyperthyroidism (SHyper) are still debated. Although the diagnosis of subclinical hyperthyroidism is, by definition, purely a biochemical one a conventional gray-scale sonography and, more recently, color-flow Doppler sonography (CFDS) have proven to be useful in obtaining information about thyroid morphology and function in thyroid disease, such as SHyper. The objective of this study was to evaluate, using CFDS, the presence and significance of changes in intrathyroidal blood flow and velocity in patients affected by SHyper and, to evalutate the potential diagnostic role of CFDS in mild thyroid disease in absence of a significant alteration in the serum level of circulating thyroid hormones. METHODS: In this study, patients with SHyper (the case group) and euthyroid patients (the control group) were enrolled. All patients from the two groups who were affected by multinodular goiter as preoperative diagnosis, underwent total thyroidectomy. In both groups preoperative examination included a conventional grey-scale sonography, followed by CFDS. Quantitative flow evaluation was performed measuring the maximal peak systolic velocity (PSV) at the level of intrathyroid arteries and inferior thyroid artery. RESULTS: Patients with SHyper showed an increased thyroid vascularization both intranodular and peripheral and the mean PSV values were higher in case patients than in control subjects. CONCLUSION: We have shown that significant changes in thyroid vascularity and blood flow velocity are already present in patients with SHyper. CFDS is a suitable technique to identify SHyper.

Acetylation curtails nucleosome binding, not stable nucleosome remodeling, by FoxO1.

Transcriptional activity of FoxO factors is controlled through the actions of multiple growth factors signaling through protein kinase B, whereby phosphorylation of FoxO factors inhibits FoxO-mediated transactivation by promoting nuclear export. Phosphorylation of FoxO factors is enhanced by p300-mediated acetylation, which decreases their affinity for DNA. The negative effect of acetylation on FoxO DNA binding, together with nuclear FoxO mobility, is eliminated by over-expression of the de-acetylase Sirt1, suggesting that acetylation mobilizes FoxO factors in chromatin for inducible gene expression. Here, we show that acetylation significantly curtails the affinity of FoxO1 for its binding sites in nucleosomal DNA but has no effect on either stable nucleosome binding or remodeling by this factor. We suggest that, while acetylation provides a first, essential step toward mobilizing FoxO factors for inducible gene repression, additional mechanisms exist for overcoming their inherent capacity to stably bind and remodel nuclear chromatin.

Application of intravoxel incoherent motion (IVIM) magnetic resonance imaging in the evaluation of primitive brain tumours.

Intravoxel incoherent motion is a potential non-invasive diagnostic tool in brain tumours, without any clear guidelines for its evaluation yet. In our study, we compare intravoxel incoherent motion with dynamic susceptibility contrast magnetic resonance imaging in the quantification of tumour tissue blood perfusion in 28 patients affected by brain tumours, highlighting the issues encountered during the acquisition set-up and post-processing steps. Intravoxel incoherent motion is a new imaging tool and an alternative technique to dynamic susceptibility contrast-magnetic resonance imaging which is of considerable interest at present. This is partly because it does not require the use of a contrast agent and relies on the intrinsic properties of motion in the capillaries of the spins. Compared to dynamic susceptibility contrast-magnetic resonance imaging, the intravoxel incoherent motion technique is also characterised by better resolution because the gadolinium-based contrast agent bolus used in the standard technique results in a variation by more than 50% of the signal coming from the brain. Finally, intravoxel incoherent motion is more sensitive to the incoherent motion that originates from small capillary vessels, while the dynamic susceptibility contrast signal is also contaminated by the input from larger arteries and veins, which may result in an overestimation of the blood volume. Although there are limitations due to the heterogeneity of the sample considered in our study, intravoxel incoherent motion has been shown to be an accurate noninvasive radiological biomarker, useful to distinguish between low and high grade glial tumours.

Transfer of HIV-1 to human tonsillar stromal cells following cocultivation with infected lymphocytes.

The susceptibility of normal human tonsillar stromal cells (HTSCs) to infection by HIV-1 was assessed using transmission electron microscopy (TEM), immunocytochemistry, and HIV-1-specific PCR analyses. Our results demonstrate that HTSCs are efficiently infected following cocultivation with the HIV-1-infected lymphoblastoid cell line GY1. Infected stromal cells contain intracellular viral particles present as free virus or associated with phagocytic vesicles. These particles express the HIV-1-specific p24 antigen as assessed by immunocytochemical analyses using an HIV-specific anti-p24 monoclonal antibody. Moreover, PCR analysis of genomic DNA isolated from particle-bearing tonsillar stromal cells identified HIV-1-specific sequences not present in either uninfected stromal cells or parental GY1 uninfected cells. The mechanism by which HIV-1 infects HTSCs does not appear to be CD4 mediated, as none of the human tonsillar stromal cell lines express CD4 as assessed by flow cytometry, immunohistochemistry, and PCR analysis. Taken together, these results demonstrate that human tonsillar stromal cells can be infected by HIV-1, and that subsequent to infection the viral genome is reverse transcribed, and integrated into the stromal cell DNA. The infection of HTSCs may contribute to HIV-1-mediated pathogenesis indirectly as a viral reservoir or directly by structural and functional modification of the lymphoid microenvironment.

[Endometrial carcinoma with simultaneous endometrioid carcinoma of the ovary. Report of two clinical cases]. / Carcinoma dell'endometrio e simultaneo carcinoma endometrioide dell'ovaio. Presentazione di due casi clinici.

The paper reports two cases of simultaneous endometrial carcinoma and endometrioid carcinoma of the ovary. The clinical and pathological characteristics are examined. Both patients underwent radical surgery with an intraoperative examination for metastatic involvement of the lumbo-aortic, iliac and infundibulo-ovarian lymphonodes. Surgery was followed by antiblastic (cisplatin, adriamycin, cyclophosphamide), hormonal (progestogens) and immuno-modulating (thymostimulin treatment). The two patients (respectively approximately 10 and 7 years after the operation) both enjoy good health.

[Carcinoma of the vulva. Report of a case originating from Bartholin's gland]. / Carcinoma della vulva. Considerazioni su di un caso a partenza dalla ghiandola del Bartholin.

A case of vulvar carcinoma arising from Bartholin's gland is described. At admission the patient showed a large suppurated swelling of the left labium maior. The neoformation reached the groin of the same side. Malignant cells were detected in biopsy specimens of both the vulvar swelling and the lymphonodes. The histological test showed a vulvar carcinoma arising from Bartholin's gland. The vulvar swelling and the ulcerated lesion were removed and the patient was treated with radiotherapy, chemotherapy (bleomicina) and immunomodulant therapy (Timostimoline). Pulmonary methastases were detected eighteen months after the operation and the patient died two years later.

[Comparative clinical study of a new imidazole molecule (fluconazole) and ketaconazole in the treatment of Candida albicans vulvovaginitis]. / Studio clinico comparato tra una nuova molecola imidazolica (fluconazolo) e il ketoconazolo nella terapia della vulvovaginite da Candida albicans.

A multicentre trial was carried out in Italy with the aim of comparing the efficacy, safety and tolerability of the oral administration of fluconazole with the oral administration of ketoconazole in the treatment of patients affected by Candida vulvovaginitis. A total of 174 patients with symptomatic Candida vulvovaginitis were identified both by objective examination and cell culture tests: of these 87 were treated using a single oral administration of fluconazole (150 mg) whereas the other 87 received 2 200 mg capsules of ketoconazole daily for 5 days. Tests to assess the efficacy, safety and tolerability of both treatments were carried out approximately 7 days and 5-6 weeks from the start of therapy. The results obtained showed a success rate of 92% for fluconazole-treated patients and 83% for those treated with ketoconazole. In addition to the rapid and safe efficacy of treatment, the most important findings which emerged from this study were the extreme simplicity of use, excellent patient compliance and the complete absence of collateral effects of variations in the hematochemical and urine parameters taken into consideration caused by fluconazole.

[Brain aging and calcium antagonist drugs. A preliminary open study with nimodipine]. / Invecchiamento cerebrale e farmaci calcio-antagonisti. Studio preliminare in aperto con la nimodipina.

Forty patients aged 65-80 with minor-medium signs of brain aging were treated for 6 months with daily 90 mg doses of nimodipine. Treatment was well tolerated in that the minor side effects reported by a few of the patients never required withdrawal of the drug. Treatment proved useful, as shown by a variety of mental tests, in 69.5% of cases. In 20% conditions remained unchanged and in 9.5% further deterioration was observed. The authors conclude that nimodipine may be considered a useful therapeutic resource for phenomena of brain aging.

Epidemiology and genetics of intracranial aneurysms.

Intracranial aneurysms are acquired lesions (5-10% of the population), a fraction of which rupture leading to subarachnoid hemorrhage with devastating consequences. Until now, the exact etiology of intracranial aneurysms formation remains unclear. The low incidence of subarachnoid hemorrhage in comparison with the prevalence of unruptured IAs suggests that the vast majority of intracranial aneurysms do not rupture and that identifying those at highest risk is important in defining the optimal management. The most important factors predicting rupture are aneurysm size and site. In addition to ambiental factors (smoking, excessive alcohol consumption and hypertension), epidemiological studies have demonstrated a familiar influence contributing to the pathogenesis of intracranial aneurysms, with increased frequency in first- and second-degree relatives of people with subarachnoid hemorrhage. In comparison to sporadic aneurysms, familial aneurysms tend to be larger, more often located at the middle cerebral artery, and more likely to be multiple. Other than familiar occurrence, there are several heritable conditions associated with intracranial aneurysm formation, including autosomal dominant polycystic kidney disease, neurofibromatosis type I, Marfan syndrome, multiple endocrine neoplasia type I, pseudoxanthoma elasticum, hereditary hemorrhagic telangiectasia, and Ehlers-Danlos syndrome type II and IV. The familial occurrence and the association with heritable conditions indicate that genetic factors may play a role in the development of intracranial aneurysms. Genome-wide linkage studies in families and sib pairs with intracranial aneurysms have identified several loci on chromosomes showing suggestive evidence of linkage, particularly on chromosomes 1p34.3-p36.13, 7q11, 19q13.3, and Xp22. For the loci on 1p34.3-p36.13 and 7q11, a moderate positive association with positional candidate genes has been demonstrated (perlecan gene, elastin gene, collagen type 1 A2 gene). Moreover, 3 of the polymorphisms analyzed in 2 genes (endothelial nitric oxide synthase T786C, interleukin-6 G572C, and interleukin-6 G174C) were found to be significantly associated with ruptured/unruptured aneurysms: the endothelial nitric oxide synthase gene single-nucleotide polymorphisms increased the risk, while IL-6 G174C seemed protective. More recently, two genomic loci (endothelin receptor A and cyclin-dependent kinase inhibitor 2BAS) have been found to be significantly associated with intracranial aneurysms in the Japanese population; endothelin-1 is a potent vasoconstrictor produced by the endothelial cells. Until now, there are no diagnostic tests for specific genetic risk factors to identify patients who are at a high risk of developing intracranial aneurysms. Knowledge of the genetic determinants may be useful in order to allow clues on stopping aneurysm formation and obtain diagnostic tools for identifying individuals at increased risk. Further multicenter studies have to be carried out.

Multiple sclerosis: identification of temporal changes in brain lesions with computer-assisted detection software.

Multiple sclerosis (MS) is a chronic disease with a progressing and evolving course. Serial imaging with MRI is the mainstay in monitoring and managing MS patients. In this work we demonstrate the performance of a locally developed computer-assisted detection (CAD) software used to track temporal changes in brain MS lesions. CAD tracks changes in T2-bright MS lesions between two time points on a 3D high-resolution isotropic FLAIR MR sequence of the brain acquired at 3 Tesla. The program consists of an image-processing pipeline, and displays scrollable difference maps used as an aid to the neuroradiologist for assessing lesional change. To assess the value of the software we have compared diagnostic accuracy and duration of interpretation of the CAD-assisted and routine clinical interpretations in 98 randomly chosen, paired MR examinations from 88 patients (68 women, 20 men, mean age 43.5, age range 21-75) with a diagnosis of definite MS. The ground truth was determined by a three-expert panel. In case-wise analysis, CAD interpretation showed higher sensitivity than a clinical report (87% vs 77%, respectively). Lesion-wise analysis demonstrated improved sensitivity of CAD over a routine clinical interpretation of 40%-48%. Mean software-assisted interpretation time was 2.7 min. Our study demonstrates the potential of including CAD software in the workflow of neuroradiology practice for the detection of MS lesional change. Automated quantification of temporal change in MS lesion load may also be used in clinical research, e.g., in drug trials.

Management of unruptured brain aneurysms: retrospective analysis of a single centre experience.

Embolization is very effective in preventing bleeding of unruptured aneurysms with lower rates of mortality and morbidity than surgical treatment. Neurosurgery remains, however, a good alternative. This retrospective analysis examined data stored the digital database of Bellaria Hospital Radiology Department, evaluating patients, treatments and devices used as well as outcomes and complications. Therapy should be tailored to each individual case to offer each patient the best treatment. Out of 265 unruptured intracranial aneurysms detected, 182 were treated by embolization. 16 cases presented complications (12 only radiologically found); severe clinical consequences occurred in 3%: one ischaemia and five haemorrhages. Conservative treatment was adopted in 21 patients. Long-term follow-up is mandatory as aneurysms could increase their size and develop an irregular morphology in ten years' time. Endovascular embolization is a very effective treatment with positive outcomes in the majority of cases and a percentage of retreatments of 8%. In order to increase the number of successful cases, a multidisciplinary cooperation with neurosurgeons is strongly recommended.

Revascularized giant aneurysm of the anterior communicating artery after surgery and embolization, occluded by placement of a Leo+Baby intracranial stent. A case report.

Balt (Montmorency, France) recently manufactured the Leo+Baby dedicated intracranial stent for arteries with a calibre between 1.5 and 3.10 mm. We describe a patient with a partially thrombosed giant sacciform aneurysm of the anterior communicating artery treated without success by surgery and coil embolization subsequently occluded by placement of a Leo+Baby stent (Balt, Montmorency, France). A 56-year-old man presented with a giant aneurysm in the anterior communicating artery region. Following successive surgical intervention and embolization procedures the patient was referred to us with a revascularized aneurysm measuring 15×9×8 cm. To stabilize the endovascular occlusion a combined treatment was scheduled with coil embolization and stent deployment after dual antiplatelet therapy started five days before the interventional procedure. Treatment was undertaken two weeks later under general anaesthesia and total heparinization. A microcatheter was inserted into the aneurysmal sac and four metal coils were released for a total of 61cm obtaining almost complete occlusion of the aneurysm from the circulation. A Leo+Baby stent (2.5×18 mm) was subsequently deployed across the aneurysm neck. At follow-up angiography two months later the aneurysm appeared substantially excluded from the arterial circulation except for a small portion in the neck. Six months later, four months after suspending antiplatelet therapy, follow-up angiography disclosed the complete exclusion of the aneurysm from the circulation. Deployment of the new ministent through the same microcatheter used to release the coils made the interventional procedure simpler and faster.

A minimally invasive treatment for lumbar disc herniation: DiscoGel® chemonucleolysis in patients unresponsive to chemonucleolysis with oxygen-ozone.

A multitude of therapies is available to treat disc herniation, ranging from conservative methods (medication and physical therapy) to minimally invasive (percutaneous) treatments and surgery. O2-O3 chemonucleolysis (O2-O3 therapy) is one of the minimally invasive treatments with the best cost/benefit ratio and lowest complication rate. Another substance recently made available exploiting the chemical properties of pure ethanol is DiscoGel®, a radiopaque gelified ethanol more viscous than absolute alcohol 8,9. The present study aimed to assess the therapeutic outcome of DiscoGel® chemonucleolysis in patients with lumbar disc herniation unresponsive to O2-O3 therapy. Thirty-two patients aged between 20 and 79 years were treated by DiscoGel® chemonucleolysis between December 2008 and January 2010. The treatment was successful (improvement in pain) in 24 out of 32 patients. DiscoGel® is safe and easy to handle and there were no complications related to product diffusivity outside the treatment site. The therapeutic success rate of DiscoGel® chemonucleolysis in patients unresponsive to O2-O3 therapy was satisfactory. Among other methods used to treat lumbar disc herniation, DiscoGel® chemonucleolysis can be deemed an intermediate procedure bridging conservative medical treatments and surgery.

Complications in the treatment of intracranial aneurysms with silk stents: an analysis of 30 consecutive patients.

Flow-diverting stents (Silk and PED) have radically changed the approach to intracranial aneurysm treatment from the use of endosaccular materials to use of an extraaneurysmal endoluminal device. However, much debate surrounds the most appropriate indications for the use of FD stents and the problems raised by several possible complications.We analysed our technical difficulties and the early (less than ten days after treatment) and late complications encountered in 30 aneurysms treated comprising 13 giant lesions, 12 large, five with maximum diameters <10 mm and one blister-like aneurysm. In our experience the primary indications for the use of FD stents can be the symptomatic intracavernous giant aneurysms. Although the extracavernous carotid siphon aneurysms have major risk of bleeding, FD stents are indicated clearly explaining the risks to the patient in case of severe mass effect. There is a very complex assessment for aneurysms of the vertebrobasilar circulation.

Staged treatment of a blood blister-like aneurysm with stent-assisted coiling followed by flow diverter in-stent insertion. A case report.

Blood blister-like aneurysms (BBLA) are rare lesions sometimes difficult to recognize and in most cases associated with diffuse subarachnoid haemorrhage and severe clinical conditions. BBLA are life-threatening because they tend to enlarge rapidly and to rebleed, and no consensus has so far been reached on the best management strategy. We describe a patient with a BBLA in the right ICA treated successful by a two-stage embolization procedure first with coils and an open cell stent (Neuroform 3) and later by further coil placement and insertion of a flow-diverting stent (Silk).

Treatment of intracranial aneurysms using flow-diverting silk stents (BALT): a single centre experience.

The Silk stent (Balt, Montmorency, France) is a retractable device designed to achieve curative reconstruction of the parent artery associated with an intracranial aneurysm. We present our initial experience with the Silk flow-diverting stent in the management and follow-up of 25 patients presenting with intracranial aneurysms.Twenty-five patients (age range, 34-81 years; 24 female) were treated with the Silk flow-diverting device. Aneurysms ranged in size from small (5), large (10) and giant (10) and included wide-necked aneurysms, multiple, nonsaccular, and recurrent intracranial aneurysms. Nine aneurysms were treated for headache, 14 for mass effect. None presented with haemorrhage. All patients were pretreated with dual antiplatelet medications for at least 72 hours before surgery and continued taking both agents for at least three months after treatment. A total of 25 Silk stents were used. Control MR angiography and/or CT angiography was typically performed prior to discharge and at one, three, six and 12 months post treatment. A follow-up digital subtraction angiogram was performed between six and 19 months post treatment.Complete angiographic occlusion or subtotal occlusion was achieved in 15 patients in a time frame from three days to 12 months. Three deaths and one major complication were encountered during the study period. Two patients, all with cavernous giant aneurysms, experienced transient exacerbations of preexisting cranial neuropathies and headache after the Silk treatment. Both were treated with corticosteroids, and symptoms resolved completely within a month.In our experience the Silk stent has proven to be a valuable tool in the endovascular treatment of intracranial giant partially thrombosed aneurysms and aneurysms of the internal carotid artery cavernous segment presenting with mass effect. The time of complete occlusion of the aneurysms and the risk of the bleeding is currently not predictable.

Role of contrast-enhanced magnetic resonance angiography in spinal dural arteriovenous fistula.

Spinal dural arteriovenous fistulae (SDAVF) are the most common vascular malformations of the spine. Although digital subtraction angiography (DSA) remains the standard of reference to diagnose and classify vascular spinal lesions, we investigated the clinical value of contrast-enhanced MR angiography (CE-MRA), equipped with TRICKS sequences, in localizing SDAVF before selective catheter angiography and possible subsequent treatment. We studied 16 consecutive patients suspected of harbouring vascular spinal cord malformations and we tried to determine the level and the side of the arterial feeder to the arteriovenous abnormality. In 12 cases the results were compared with DSA and/or possible post-operative findings. In nine cases CE-MRA correctly depicted the origin of the fistula: in particular one patient was treated surgically only on the basis of MRA results. Thanks to its elevated spatial and temporal resolution, spinal contrast-enhanced MRA using TRICKS sequences proved reliable in detecting and localizing the SDAVF arterial feeders and can be used as a guide to subsequent selective DSA examination.

The use of flow-diverting stents in the treatment of giant cerebral aneurysms: preliminary results.

The treatment of giant cerebral aneurysms has always been a challenge for neurosurgeons and neuroradiologists. Flow-diverting stents (Silk; Pipeline Embolization Device) are new endovascular devices introduced for the treatment of intracranial aneurysms without release of intrasaccular coils. They are tubular bimetallic endoluminal devices with low porosity. We have employed these stents in the Neuroradiology Unit of Bellaria Hospital (Bologna, Italy) since the end of 2008, treating nine patients with giant carotid cerebral aneurysms using nine Silk stents as soon as the device obtained the CE mark. All patients were pretreated with dual antiplatelet medications before surgery. The Silk stents were deployed through a 4F Balt introducer, which ensured an uneventful and very quick procedure. Control CT angiography or MR angiography was typically performed at discharge and one, three, six and 12 months after treatment. Post-treatment results were: four complete occlusions, three near complete occlusions (residual neck flow) with reduced volume of the aneurysm and two more than 50% reduction of intra-aneurysmal flow. A fatal hemorrhagic complication occurred in one patient, probably due to the antiplatelet treatment. The Silk stent seems a very interesting curative device to treat giant aneurysms with preservation of the parent artery and small adjacent branches. Technical improvements will certainly reduce the thrombogenic effect with the related risks.