Burden of stroke in Italy: an economic model highlights savings arising from reduced disability following thrombolysis.

BACKGROUND: The consequences of stroke must be assessed not only in terms of incidence and mortality rates, but also in terms of disability, which may persist long after the acute phase. Thrombolysis, if timely administered, can effectively reduce post-stroke disability. AIMS: The economic model presented herein aims to evaluate, in eligible patients, the effects of alteplase on post-stroke disability and related costs over three-years. METHODS: The economic analysis was developed on the basis of four key components: clinical outcomes from international trials, economic consequences extracted from cost of illness studies, regulatory data from national and international agencies, and national epidemiological data. A population-level model estimated the difference in disability costs between patients treated with standard care versus those receiving thrombolytic therapy within 4×5 h of acute ischemic stroke. The analysis covered 36 months from discharge. RESULTS: Reduced costs related to post-stroke disability were observed in treated patients compared with those receiving standard care (control). The overall savings were €2330×15 per average patient: €1445×81 during the first 18 months, €362×25 between 18 and 24 months, and €522×09 in the 24-36 months period. The overall savings on 3174 Italian treated patients in 2013 were €7 395 907 over three-years. CONCLUSION: Our study reveals that performing thrombolytic therapy in eligible patients improves economic outcomes compared with patients receiving standard care. This model is useful for decision makers, both within and outside of the Italian national context, as a tool to assess the cost-effectiveness of thrombolysis in both short- and long-term period.

Surgical removal of small petroclival meningiomas.

UNLABELLED: Treatment of large petroclival meningiomas causing brain stem compression is surgical removal followed by radiotherapy or radiosurgery if the lesion was partially resected. The management of small petroclival meningiomas is, however, controversial. Clinical observation, radiosurgery and surgical removal are the options of treatment. The natural history of these tumours is not well known. Published series of patients treated with radiosurgery are not comparable with surgical series because the latter also includes large size tumours. In this paper we present a series of 18 patients with small petroclival meningiomas (diameter

Alternative splicing of the ErbB-4 cytoplasmic domain and its regulation by hedgehog signaling identify distinct medulloblastoma subsets.

Medulloblastoma (MB) results from aberrant development of cerebellar neurons in which altered hedgehog (Hh) signalling plays a major role. We investigated the possible influence of Hh signalling on ErbB-receptor expression in MB, in particular that of the ErbB-4 CYT-1 and CYT-2 isoforms generated by alternative splicing of the cytoplasmic domain. ErbB-4 expression was downregulated in Hh-induced MBs from Patched-1(+/-) mice. Hh signalling (reflected by enhanced expression of the Gli1 transcription factor) inhibited ErbB-4 expression in mouse cerebellar granule progenitors and human MB cells. Analysis of 26 human primary MBs revealed a subset of 11 tumors characterized by low Gli1 levels, upregulated ErbB-4 expression and increased CYT-1:CYT-2 ratios. Interestingly, CYT-1 and Gli1 levels were inversely correlated. ErbB-4 CYT-1 and CYT-2 had different phenotypic effects in cultured MB cells: in response to neuregulin treatment, CYT-2 overexpression inhibited proliferation whereas CYT-1, which includes a phosphatidylinositol 3-kinase (PI3K)-binding site that is missing in CYT-2, enhanced resistance to starvation- and etoposide-induced apoptosis by activating PI3K/Akt signalling. CYT-1:CYT-2 ratios displayed correlation with tumor histotype and ErbB-2 levels, which are established prognostic indices for MB. These findings demonstrate that low-level Hh signalling in human MB is associated with the selective maintenance of high ErbB-4 CYT-1 expression, an alteration that exerts tumor-promoting effects.

Primary central nervous system lymphomas in immunocompetent patients.

OBJECTIVES: Primary central nervous system lymphoma (PCNSL) is a rare pathology and is most often seen in immunodeficient patients. This article presents our casuistic of PCNSL in immunocompetent patients and make a literature review on this issue with focus on recent advances, investigations, and controversies in diagnosis and management of this pathology. MATERIAL AND METHODS: Nine patients operated in the last years in our clinics are analysed in relation to sex, age, time of symptoms, procedures and adjuvant treatment. Posteriorly the results are compared with those in the preview literature. RESULTS: The age ranged from 44-68 years (middle of 66 years); 62.5% of the patients were female. The mean time of symptoms, when the diagnostic was made, was 3.2 months (range 1-6 months). The most common symptoms were hemiparesis (present in 75% of the patients) headache (37.5%) seizures (25%) and ataxia (25%). The most common localization was the parietal, frontal and temporal lobe surface with 25% of the patients for each localization. Five patients (50%) were treated with stereotactic biopsy, three with surgery (37.5%) and one (12.5%) with both of them. Five patients (62.5%) were submitted to pos-operative radiotherapy as adjuvant treatment. In relation to the histology, the most common cell type was Diffuse B Cells. CONCLUSIONS: This study demonstrated that complete surgical resection followed by radiotherapy have shown good results. In opposition to the literature, the authors regard chemotherapy as a secondary line treatment and recommend its use only in some selected cases.

Primary central nervous system lymphomas in immunocompetent patients

Objetivos. En este trabajo presentamos nuestra casuística de linfomas cerebrales primarios en pacientes immunocompetentes comparandolo con los datos previos de la literatura, con especial enfoque en los recientes avances, investigaciones, y controversias acerca del diagnóstico y manejo terapéutico de estas patologías. Material y método. Nueve pacientes operados el año pasado en nuestra clínica con diagnóstico de PCNLS son analizados en relación al sexo, edad, tiempo de sintomatología, procedimientos y tratamiento. Posteriormente, los resultados son comparados con los de la literatura. Resultados. La edad varió entre 44-68 años (media de 60,6 años); 62,5% de los pacientes fueron del sexo femenino; el tiempo medio de duración de los síntomas antes del diagnóstico de la enfermedad varió de 1-6meses, con un rango medio de 3,2 meses. Los síntomas clínicos más frecuentes fueron : hemiparesia (75%),cefalea (37,5), crisis convulsivas (25%) y ataxia (25%).Las localizaciones predominaron en las superficies delos lóbulos parietal, temporal y frontal con un 25% para cada una de las localizaciones citadas. Cinco pacientes (50%) fueron tratados con biopsia estereotáxica, tres con cirugía (37.5%) y uno (12.5%) con ambas. Cinco pacientes (62,5%) fueron sometidos a radioterapia postoperatoria como tratamiento adyuvante. En relación con el tipo histológico predominó el linfoma de células difusas tipo B. Conclusiones. Este estudio demostró que la resección quirúrgica, combinada con biopsia por esterotaxia y la radioterapia dan buenos resultados. Los autores recomiendan la quimioterapia solamente como segunda línea de tratamiento, en pacientes seleccionados

Objetctives. Primary central nervous system lymphoma(PCNSL) is a rare patology and is most often seen in immune-deficient patients. This article presents our casuistic of PCNSL in immunocompetent patients and make a literature review on this issue with focus on recent advances, investigations, and controversies in diagnosis and management of this patology. Matherial and methods. Nine patients operated in the last years in our clinics are analysed in relation to sex, age, time of symptoms, procedures and adjuvant treatment. Posteriorly the results are compared with those in the preview literature. Results. The age ranged from 44-68 years (middle of 66 years); 62,5% of the patients were female. The mean time of symptoms, when the diagnostic was made, was 3.2 months (range 1-6 months). The most common symptoms were hemiparesis (present in 75%of the patients) headache (37.5%) seizures (25%) and ataxia (25%). The most common localization was the parietal, frontal and temporal lobe surface with 25%of the patients for each localization. Five patients(50%) were treated with stereotactic biopsy, three with surgery (37.5%) and one (12.5%) with both of them. Five patients (62,5%) were submitted to pos-operative radiotherapy as adjuvant treatment. In relation to the hystology, the most common cell type was Difuse B Cells. Conclusions. This study demonstrated that complete surgical ressection followed by radiotherapy have shown good results. In opposition to the literature, the authors regards chemotherapy as a secondary line treatment and recommends its use only in some selected cases

Fibrous dysplasia in combination with aneurysmal bone cyst presenting as a subarachnoid haemorrhage.

Fibrous dysplasia (FD) is a rare tumour, representing 2.5% of all bone tumours and 7% of benign tumours. Aneurysmal bone cyst (ABC) is also an uncommon pathology, usually associated with a secondary vascular lesion consisting of an arteriovenous malformation. In this article, we relate a case report of a young female with a rare combination of FD with aneurysmal bone cyst presenting as a subarachnoid haemorrhage (SAH). Despite the possibility of clinical treatment of these lesions, this report demonstrates that symptomatic lesions may be successfully managed by surgical resection. The authors' opinion is that this treatment should be individualised depending on particularities of each case, such as localisation of the lesion, biopsy results and image exams features. We also present a critical literature review of diagnostic methods and therapeutical options for both ABC and FD, with emphasis on controversial topics surrounding these issues.

Structural features of force-generating cross-bridges. A 2D-X-ray diffraction study.

In several concepts of muscle contraction it was proposed that during force generation cross-bridges assume a rigor-like conformation. However, so far 2D-X-ray diffraction patterns recorded during isometric contraction did not reveal structural features of rigor-like cross-bridges. It was therefore supposed that the number of force generating cross-bridges in isometric steady state contraction is too low to be detected in 2D-X-ray diffraction patterns. To test this concept we studied the features of 2D-X-ray diffraction patterns of different fractions of rigor-like cross-bridges by varying the concentration of the nucleotide analog ATP gamma S at high [Ca++]. Although we had a fully activated system, i.e., that weak binding cross-bridges were attached to the activated thin filament, none of the patterns was like the active pattern. Analysis of the intensity change of the actin layer lines at 1/370 A-1 and at 1/59 A-1 in diffraction patterns recorded during isometric contraction vs. relaxed and rigor conditions as well as mechanical experiments revealed that the fraction of force generating cross-bridges apparently is as high as 55-70%. Yet, in agreement with previous studies, in spite of this large fraction of force generating cross-bridges, no rigor-like features were detected in diffraction patterns recorded during isometric contraction. Moreover, the intensity distribution along the actin layer lines was clearly different in rigor compared to isometric contraction. Taken together these results provide evidence that in contrast to the above mentioned models the majority of the force generating cross-bridges seems to be in a conformation which is different from rigor.

Environmental impact of the Chernobyl accident: mutagenesis in bank voles from Sweden.

An investigation was carried out in Sweden aimed at studying the possible genetic effects of the Chernobyl fallout on wild small mammals. The bank voles (Clethrionomys glareolus Schreb.) were obtained from three differently contaminated areas in Sweden and, for control, in an area with negligible contamination by fallout. Radionuclide determinations to assess the content of 137Cs and mutagenicity tests (bone marrow micronucleus test and sperm abnormality assay) were performed. The results obtained showed a positive correlation between the increase of micronucleated polychromatic erythrocytes (MPCE/1000 PCE) and both 137Cs content in muscle and in soil contamination. The estimated doses absorbed by the animals were far lower than those required for the same effect in laboratory experiments. An explanation of this discrepancy between dose and measured biological effect is not available, yet similar results have been repeatedly reported after the Chernobyl accident and should be a matter for further discussion. An increased frequency of micronucleated cells might occur at minimal dose gradients, and the micronucleus test appears to be a valid tool to show such effects.

Environmental impact of the Chernobyl accident : mutagenesis in bank voles from Sweden

An investigation was carried out in Sweden aimed at studying the possible genetic effects of the Chernobyl fallout on wild small mammals. The bank voles (Clethrionomys glareolus Schreb) were obtained from three differently contaminated areas in Sweden and, for control, in an area with negligible contamination by fallout. Radionuclide determinations to asses the content of 137Cs and mutagenicity tests (bone marrow micronucleus test sperm abnormality assay) were perfomed. The results obtained showed a positive correlation between the increase of micronucleated polychromatic erythrocytes (MPCE/1000 PCE) and both 137Cs content in muscle and in soil contamination. The estimated doses absorbed by the animals were far lower than those required for the same effect in laboratory experiments. An explanation of this discrepancy between dose and measured biological effect the Chernobyl accident and should be a matter for further discussion. An increased frequency of micronucleated cells might occur at minimal dose gradients, and the mocronucleus test appears to be a valid tool to show such effects(AU)

Small mammals as biological indicators of radioactive contamination of the environment.

An investigation was carried out in Sweden aimed at studying the contamination of small mammals (orders Rodentia and Insectivora) following the Chernobyl accident. The animals were captured in three differently contaminated areas in Sweden and, for control, in an area with negligible fallout. The results obtained show that the activity in the captured animals was correlated with surface deposition. The differences between the species investigated and the influence of feeding habits on the contamination levels are discussed.

137Cs determination and mutagenicity tests in wild Mus musculus domesticus before and after the Chernobyl accident.

Wild rodents were collected alive in a suburban area to the north of Rome before, during, 6 months and 1 year after the Chernobyl accident. Radionuclide determinations to assess their content of (137)Cs and mutagenicity tests (bone-marrow micronucleus test and sperm abnormalities assay) were performed on the captured animals. The results obtained for the species Mus musculus domesticus (which was the rodent captured in highest numbers), compared with the results obtained before the fallout, showed an increase of both micronucleated polychromatic erythrocytes (MPCEs/1000 PCEs) and (137)Cs content during and after the fallout.

Development of a model for predicting pharmacy personnel requirements.

The purpose of this study was to adjust current staffing based on productivity measurement and analysis of the unit dose and sterile products area of the pharmacy, and to develop a model for predicting pharmacy personnel requirements based on Pharmacy Staffing Units (PHASUs). Time measurements of the specific pharmacy procedures were performed to define baseline procedure data. A PHASU equivalency system was developed to allow comparison of all pharmacy procedures. This system was based on the time required to complete a specific procedure divided by the time required to complete the procedure most reflective of workload, a single medication order. Pharmacy personnel requirements were forecasted using the number of unit dose orders and the number of miscellaneous sterile preparations in the sterile products area. A software package used by management engineering to predict patient days and number of admissions was used to forecast workload. The PHASU system provides a means for forecasting workload and addressing personnel requirements for the next fiscal year. Pharmacy administrative personnel must adopt a contemporary business approach to meet the challenge that pharmacy will encounter in the new health care environment.

Warfarin: a quality assurance model for concurrent drug monitoring.

Until recently, the mechanism to gain the attention of hospital decision makers on the potential implication of pharmacists' involvement in the drug use review process was missing. However, integrating clinical pharmacy services with quality assurance activities appears to provide a mechanism to reduce patient risk and cost while maintaining the quality of patient care services provided. The department of pharmacy at The Mercy Hospital of Pittsburgh, through the hospital-wide quality assurance committee (QAC) and pharmacy evaluation committee (PEC), has developed concurrent drug the reviews. The concurrent warfarin review conducted by the department of pharmacy is described in detail to illustrate the process that is followed in the development and implementation of a concurrent drug use review. The concurrent review of warfarin was initiated and, in general, criteria were met and few variations occurred. Interventions by staff pharmacists were effective in further improving compliance with certain criteria. Although it was not proven that the incidence of hemorrhage was actually decreased, the QAC felt that such an approach would serve to decrease the likelihood of hemorrhage as warfarin therapy is initiated in the hospital. Similar drug use reviews have been developed for aminoglycosides, third-generation cephalosporins, piperacillin, cefoxitin, cefazolin, vancomycin, phenytoin, and the digoxin-quinidine interaction. The objective of these reviews is also to reduce patient risk and costs associated with drug use. Therefore, in today's hospital environment, a mechanism to improve the visibility of the pharmacist's involvement in the health care process is to integrate clinical pharmacy services with quality assurance activities.