The role of serial radiographs in the management of pediatric torus fractures.

OBJECTIVES: To assess the utility of radiographs taken immediately after the application of a cast in the management of pediatric torus (or buckle) fractures and to determine the need for serial radiographs taken at follow-up visits. DESIGN: Retrospective medical record review; survey questionnaire of a panel of experts. SETTING: The pediatric emergency department (PED) and the pediatric orthopedic clinic at an urban, tertiary care hospital. PATIENTS: All children with torus fractures referred to the pediatric orthopedic clinic for follow-up visits between February 1995 and February 1997. MAIN OUTCOME MEASURES: The number of patients whose postcast studies was obtained in the PED; number of follow-up visits and studies conducted at the pediatric orthopedic clinic; usual regional practices as extracted from a panel of experts by survey questionnaire. RESULTS: Of 70 patients, 46 (66%) were evaluated by a single, precast study in the PED, and 24 (34%) were evaluated by both precast and postcast studies in the PED. The time range of the first follow-up study was the first to fifth week after the patient's injury. The range of the number of follow-up studies for each patient was 0 to 5. Our cohort's total radiology charges for 70 patients were $27251. Regional directors of pediatric orthopedic surgery unanimously agreed that postcast studies in the PED are unnecessary. The range of the number of follow-up studies they obtained is 0 to 3 per patient. CONCLUSIONS: Postcast studies of torus fractures are unnecessary. Multiple radiographs taken during follow-up visits, especially early in the healing process, do not change fracture management. Relying on the clinical examination, perhaps combined with a single follow-up study, is a more appropriate regimen for the management of pediatric torus fractures and translates into a cost savings of over $ 10000 for our 70 patients.     

Successful use of caplacizumab in a case of refractory acquired thrombotic thrombocytopenic purpura following subacute thyroiditis

Acquired thrombotic thrombocytopenic purpura (aTTP) is a rare condition mainly characterized by microangiopathic hemolytic anemia, thrombocytopenia, reported in approximately three cases per one million adults per year. Some reports describing co-occurrence of aTTP and other autoimmune disorders, as Graves’ thyroiditis, are reported. To the best of our knowledge this is the first report describing co-occurrence of subacute thyroiditis and aTTP. The patient was refractory to conventional therapy with plasma exchange, steroids and rituximab but was successfully treated with the addition of caplacizumab, an anti‐VWF bivalent variable‐domain‐only immunoglobulin fragment that inhibits interaction between VWF multimers and platelets.     

Effective tools to manage biosimilars prescription: The Italian experience

IntroductionBiosimilars represent both a clinical and a financial opportunity. However, low biosimilar penetration has been observed across Europe. Italy has registered a high and increasing biosimilars uptake, but not uniform across regions.ObjectivesThe paper aims to describe different managerial tools that can be leveraged to exploit the biosimilars’ potential. A focus on Italy and the Tuscany region will be specifically carried out. Furthermore, this research is intended to propose some preliminary considerations about the most effective measures to support biosimilars’ uptake.MethodsThis article is based on both desk research and on action research. A desk research was carried out to explore the existing international and national literature on the measures implemented to promote biosimilars’ penetration. The action research concerned a longitudinal cooperation project between the Management and Health Laboratory of Scuola Superiore Sant'Anna of Pisa and the Drugs and Appropriateness Policy Sector of Tuscany Region. The activity saw the direct involvement of the Management and Health Laboratory in supporting the regional pharmaceutical governance in managing biosimilars’ penetration.ResultsSeveral demand and supply side policies to foster biosimilar penetration have been implemented both at national and regional levels. In Italy, most regions have adopted specific biosimilar policies at different moments and with heterogeneous contents. The Tuscan Regional Health System implemented three main measures: formal top-down, bottom-up and “mixed” measures. The strategy was effective in increasing biosimilar uptake. The success is probably associated with its comprehensive approach and to the coherence of the different measures it was composed of.     

Treatment of B-cell non-Hodgkin's lymphoma with anti CD 20 monoclonal antibody Rituximab

Rituximab is a chimeric anti CD-20 monoclonal antibody containing human IgG1 kappa constant regions, with murine variable regions. The anti-lymphoma effects of Rituximab are probably due to complement and antibody-dependent cell-mediated cytotoxicity, and induction of apoptosis. Phase II trials have demonstrated a strong activity of rituximab alone in indolent B non-Hodgkin lymphoma, especially in patients with follicular lymphoma. The most utilized dose-schedule is 375 mg/m(2) weekly x 4. The association with chemotherapy or with interferon-alpha increases Rituximab efficacy. More recently, Rituximab have showed activity also in diffuse large cell lymphoma, mantle cell lymphoma and in other B-malignancies. Good results have also been obtained utilizing Rituximab for in vivo purging. However, we are still far from having found a definite position for Rituximab in the treatment of lymphoproliferative disorders. The aim of future studies should be to develop new strategies that will hopefully produce the most effective Rituximab-based regimens in order to find the Rituximab key position in the treatment of B-malignancies     

Role of Dopamine D1 Receptors and Extracellular Signal Regulated Kinase in the Motivational Properties of Acetaldehyde as Assessed by Place Preference Conditioning

Background: The role of dopamine D₁ receptors and Extracellular signal Regulated Kinase (ERK) in the motivational properties of drugs can be studied by place‐conditioning. Recent advances have shown that the motivational properties of ethanol, determined by place‐conditioning, are mediated by its metabolic conversion into acetaldehyde. To date, the role of D₁ receptors and ERK activation in acetaldehyde‐elicited place preference has not been determined. The aim of this study was to assess the role of D₁ receptors blockade and MEK inhibition in the acquisition of acetaldehyde‐elicited conditioned place preference. Methods: Male Sprague–Dawley rats were subjected to repeated pairings with 1 compartment of the conditioning apparatus immediately following acetaldehyde (20 mg/kg i.g.) or ethanol (1 g/kg i.g.) administration. The D₁ receptor antagonist, SCH 39166 (50 μg/kg s.c.), was administered 10 minutes before acetaldehyde or ethanol administration. In order to study the role of activated ERK in the acetaldehyde‐elicited place preference, rats were administered the MEK inhibitor, PD98059 (1, 30, and 90 μg i.c.v.), 10 or 30 minutes before acetaldehyde. To verify the specificity of these effects, we also studied whether PD98059 pretreatment could affect morphine (1 mg/kg s.c.)‐elicited place preference. Results: Both acetaldehyde and ethanol elicited significant place preferences and these were prevented by pretreatment with SCH 39166. In addition, pretreatment with PD98059, dose (30 and 90 but not 1 μg i.c.v.) and time (10 but not 30 minutes before) dependently, prevented the acquisition of acetaldehyde‐ and significantly reduced the acquisition of morphine‐elicited conditioned place preference. Conclusions: These results confirm that acetaldehyde and ethanol elicit conditioned place preference and demonstrate that D₁ receptors are critically involved in these effects. Furthermore, the finding that PD98059 prevents the acquisition of acetaldehyde‐elicited conditioned place preference highlights the importance of the D₁ receptor–ERK pathway in its motivational effects.     

Insulin resistance is associated with steatosis in nondiabetic patients with genotype 1 chronic hepatitis C

Conflicting data exist regarding the relationship between hepatitis C virus genotype 1 and hepatic steatosis as well as the latter's role in the progression of fibrosis and treatment response. We assessed factors associated with hepatic steatosis in genotype 1 chronic hepatitis C and the impact of hepatic fat on fibrosis development and interferon responsiveness. Two hundred ninety-one non-diabetic patients with genotype 1 chronic hepatitis C were examined for the presence of steatosis and its correlation with clinical, virological, and biochemical data, including insulin resistance (IR), evaluated by the homeostasis model assessment (HOMA) score. Steatosis was graded as mild (1%-20% of hepatocytes involved), moderate (21%-40% of hepatocytes involved), and severe (>40% of hepatocytes involved). Steatosis was mild in 110 of 291 (37.8%) and moderate/severe in 55 of 291 (18.9%) subjects. By logistic regression, moderate/severe steatosis was independently associated with the female sex (odds ratio [OR] 2.74; 95% CI 1.40-5.35), high gamma-glutamyltransferase levels (OR 1.52; 95% CI 1.22-1.91), and HOMA-score (OR 1.076; 95% CI 1.001-1.26). By logistic regression, moderate/severe steatosis (OR 2.78; 95% CI 1.21-6.4), and platelet counts (OR 0.97; 95% CI 0.96-0.98) were independent predictors of advanced fibrosis. Patients with moderate/severe steatosis had an OR of 0.52 (95% CI 0.30-0.90) for sustained virological response compared with patients with mild/absent steatosis. In conclusion, in nondiabetic European patients with genotype 1 hepatitis C at low risk for the metabolic syndrome, the prevalence of steatosis was nearly 60%. IR is a risk factor for moderate/severe steatosis, especially in men. Moderate/severe steatosis has clinical relevance, being associated with advanced fibrosis and hyporesponsiveness to antiviral therapy.     

Post-operative rehabilitation after surgical repair of the rotator cuff

Today advances in techniques and materials for rotator cuff surgery allow the repair of a large variety of types or extensions of cuff lesions in patients from a wide range of age groups who have different kinds of jobs and participate in different kinds of sports, and who have widely different expectations in terms of recovery of functions and pain relief. A large number of factors must be taken into account before implementing a rehabilitation protocol after rotator cuff surgery. These mainly include the technique (materials and procedure) used by the surgeon. Moreover, tissue quality, retraction, fatty infiltration and time from rupture are important biological factors while the patient’s work or sport or daily activities after surgery and expectations of recovery must also be assessed. A rehabilitation protocol should also take into account the timing of biological healing of bone to tendon or tendon to tendon interface, depending on the type of rupture and repair. This timing should direct the therapist’s choice of correct passive or assisted exercise and mobilisation manoeuvres and the teaching of correct active mobilisation movements the patient has to do. Following accepted knowledge about the time of biological tissue healing, surgical technique and focused rehabilitation exercise, a conceptual protocol in four phases could be applied, tailoring the protocol for each patient. It starts with sling rest with passive small self-assisted arm motion in phase one, to prevent post-op stiffness. In phase two passive mobilisation by the patient dry or in water, integrated with scapular mobilisation and stabiliser reinforcement, are done. Phase three consists of progressive active arm mobilisation dry or in water integrated with proprioceptive exercise and “core” stabilisation. In phase four full strength recovery integrated with the recovery of work or sports movements will complete the protocol. Because of the multi-factorial aspects of the problem, the best results can be obtained through a full transfer of information from the surgeon to the therapist to optimise timing and sizing of the individual rehabilitation protocol for each patient.