RESUMO
OBJECTIVE: To describe clinical effectiveness of belimumab for systemic lupus erythematosus (SLE) in real-world practice in Argentina. METHODS: This retrospective, observational study analysed medical record data of patients with SLE treated with belimumab in 15 centres in Argentina. Primary endpoint: overall clinical response (assessed on a scale similar to the 6-point Physician Global Assessment) at months 6, 12, 18 and 24, all versus index (belimumab initiation). Secondary endpoints: improvement in disease activity (SELENA-SLEDAI), SLE manifestations, and corticosteroid dose change. RESULTS: Records for 81 patients (91% female) were analysed. Clinical improvements were reported for 95%, 95%, 98% and 100% patients at 6, 12, 18, and 24 months post index, respectively. Mean SELENA-SLEDAI score decreased from 11.21 at index to 4.76, 3.77, 3.86 and 2.17 at 6, 12, 18, and 24 months post index, respectively. Number of flares decreased from 1.05 at index to 0.21, 0.09, 0.22 and 0.30 at 6, 12, 18, and 24 months post index, respectively. Mean corticosteroid dose was 14.59 mg/day at index, and 6.45, 5.18, 5.17 and 4.78 mg/day at 6, 12, 18, and 24 months post index, respectively. CONCLUSIONS: Real-world patients with SLE treated with belimumab in Argentina demonstrated clinical improvements and reductions in corticosteroid dose.
Assuntos
Corticosteroides/administração & dosagem , Anticorpos Monoclonais Humanizados/administração & dosagem , Imunossupressores/administração & dosagem , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Resultado do Tratamento , Adulto , Argentina , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de DoençaRESUMO
PURPOSE: The aims of this study were to assess the prevalence of use and prescription appropriateness of drugs for peptic ulcer and gastrooesophageal reflux disease (GERD) at hospital admission and discharge. METHODS: Patients aged 65 years or more hospitalized from 2010 to 2016 in 101 Italian internal medicine and geriatric wards in the context of the REPOSI register were scrutinized to assess if they were prescribed with drugs for peptic ulcer and GERD at hospital admission and discharge. Appropriateness of prescription was assessed considering the presence of specific conditions (i.e., history of peptic ulcer or gastrointestinal hemorrhages, advanced age, Helicobacter Pylori) or gastro-toxic drug combinations, according to the criteria provided by the reimbursement rules of the Agenzia Italiana del Farmaco (NOTA 1 and 48). RESULTS: Among 4715 enrolled patients, 3899 were discharged alive. At hospital discharge, 2412 (61.9%, 95%CI: 60.3-63.4%) patients were prescribed with drugs for peptic ulcer and GERD, a 12% of increase from hospital admission. Almost half of the patients (N = 1776, 45.6%, 95%CI: 44.0-47.1%) were inappropriately prescribed or not prescribed: among the drugs for peptic ulcer and GERD users, about 60% (1444/2412) were overprescribed, and among nonusers, 22% (332/1487) were underprescribed. Among patients newly prescribed at hospital discharge, 60% (392/668) were inappropriately prescribed. The appropriateness of drugs for peptic ulcer and GERD therapy decreased by 3% from hospital admission to discharge. CONCLUSIONS: Hospitalization missed the opportunity to improve the quality of prescription of this class of drug.
Assuntos
Prescrições de Medicamentos/estatística & dados numéricos , Uso de Medicamentos/estatística & dados numéricos , Refluxo Gastroesofágico/tratamento farmacológico , Prescrição Inadequada/estatística & dados numéricos , Úlcera Péptica/tratamento farmacológico , Medicamentos sob Prescrição/uso terapêutico , Idoso , Estudos Transversais , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Itália , Masculino , Alta do Paciente/estatística & dados numéricos , PrevalênciaRESUMO
INTRODUCTION: In the second decade of the third millennium there have been dramatic developments pertaining to the availability of highly innovative drugs for hemophilia care, notwithstanding a satisfactory previous scenario. AIM: I am going to emphasize the role of 2 main categories of players: scientist physicians who produced important translational research and the pharmaceutical industry, who developed, produced and made commercially available so many improved treatment weapons stemming from the translational research of the forementioned scientist physicians. RESULTS: Pertaining to the role of scientist physicians, I chose to mention first those who were successful in the 1980 in the production of recombinant coagulation factors. In addition, those who more recently helped to produce new non substitutive therapies given by the subcutaneous route, and recombination coagulation factors with an extended half-life. CONCLUSIONS: Current miraculous progress in hemophilia therapy is stemming from the research work of outstanding scientist physicians who acted in close collaboration with small biotechnology companies, leading to the early development of innovative therapeutic products, subsequently taken to the market place by the so called Big Pharma. I shall briefly provide my views to explain the fact that large pharmaceutical companies show more and more interest in such a rare disease as the hemophilias.
Assuntos
Descoberta de Drogas/métodos , Hemofilia A/tratamento farmacológico , Hemofilia B/tratamento farmacológico , Animais , Indústria Farmacêutica , Humanos , Pesquisa Translacional BiomédicaRESUMO
INTRODUCTION: Persons with haemophilia (PWH) born before the middle 1970s have spent a substantial part of their lives without the benefits of replacement therapy, that became available on a relative large scale only during the 1970s. As a consequence, this group of PWH, although still relatively young, suffers from musculoskeletal and functional problems that are typical of old people. METHODS: We report herewith the short-term results of a project based upon a multidisciplinary training programme led by a physiotherapist and an occupational therapist, that was implemented over a period of 12 months in 40 patients with severe or moderate hemophilia A or B born before the middle 1970s and regularly followed-up at a comprehensive haemophilia treatment centre in Italy. The project was aimed to provide information and skills in order to empower the older PWH carrying physical handicaps and functional limitations that had resulted from the inadequate management in their early ages, and to enable them to cope more efficiently with their crippling disease and prevent further disabilities. RESULTS AND CONCLUSIONS: The comparison of the data obtained before and after the 12-month programme found marginal improvements, but the purpose of this programme was indeed to offer a blueprint for the future. In this respect, the level of satisfaction for the programme was very high and we expect that it will be implemented long-term by our older PWH.
Assuntos
Envelhecimento , Hemofilia A/psicologia , Avaliação de Programas e Projetos de Saúde , Idoso , Comorbidade , Exercício Físico , Hemofilia A/tratamento farmacológico , Hemofilia A/patologia , Humanos , Articulações/fisiopatologia , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/fisiologia , Terapia Ocupacional , Dor/patologia , Postura , Índice de Gravidade de DoençaRESUMO
The fifth Åland Island meeting on von Willebrand disease (VWD) was held on the Åland Islands, Finland, from 22 to 24 September 2016-90 years after the first case of VWD was diagnosed in a patient from the Åland Islands in 1926. This meeting brought together experts in the field of VWD to share knowledge and expertise on current trends and challenges in VWD. Topics included the storage and release of von Willebrand factor (VWF), epidemiology and diagnostics in VWD, treatment of VWD, angiogenesis and VWF inhibitors.
Assuntos
Doenças de von Willebrand/diagnóstico , Doenças de von Willebrand/terapia , Humanos , Doenças de von Willebrand/epidemiologia , Doenças de von Willebrand/etiologiaRESUMO
Von Willebrand disease (VWD) is an inherited haemorrhagic disorder caused by a quantitative or qualitative defect of von Willebrand factor (VWF), a multimeric plasma glycoprotein that plays a key role in platelet adhesion to the subendothelium and acts as a carrier of factor VIII (FVIII) in blood. Patients with VWD experience bleeding symptoms that are mainly localized in mucous membranes and soft tissues, and their severity depends on the degree of the primary reduction in VWF and the secondary deficiency of FVIII in plasma. Because VWD patients are also at increased risk of perioperative bleeding, a prophylactic treatment aimed to correct the dual haemostatic defect (i.e. VWF and FVIII) is warranted. This review summarizes knowledge on the current management of patients undergoing major surgery, focusing on the peri-surgical laboratory monitoring of replacement therapy with VWF/FVIII concentrates. We suggest to monitor plasma levels of FVIII coagulant activity in the postoperative period rather than a surrogate maker of platelet-binding VWF activity as the ristocetin cofactor assay and its recent modifications.
Assuntos
Terapia de Reposição Hormonal/métodos , Doenças de von Willebrand/cirurgia , Hemorragia/prevenção & controle , HumanosRESUMO
INTRODUCTION: A few studies have been focused on low-titre inhibitors in patients with haemophilia A. Although several putative factors have been implicated in the development of these inhibitors, solid data are still lacking. AIM: The aim of this study was to perform a proportion meta-analysis on the incidence of low-titre inhibitors in haemophilia A. METHODS: We surveyed the PubMed database to identify studies on de novo development of low-titre inhibitors in haemophilia A patients. On the basis of these data, we carried out a proportion meta-analysis to summarize information on incidence and between-study variability. Furthermore, the following three covariates were assessed by meta-regression: (i) mild disease vs. severe haemophilia; (ii) status of previously untreated patient (PUP) as opposed to multi-transfused and (iii) type of factor VIII. RESULTS: Our literature search on PubMed extracted 340 eligible articles. From these, we selected 33 patient cohorts that were included in our meta-analysis (19 cohorts for PUPs and 14 cohorts for multi-transfused or unselected patients). The pooled incidence of low-titre inhibitors was 10.3% (95%CI: 8.3-12.5%) for studies including PUPs and 5.8% (95%CI: 2.5-10.4%) for the other studies; the difference was statistically significant (P = 0.003). Meta-regression of 31 patient cohorts found that mild disease and type of factor VIII were not associated with an increased incidence of low-titre inhibitors. CONCLUSIONS: Our results confirmed that PUPs show a higher incidence of low-titre inhibitors than the other patients. Furthermore, our data showed that mild haemophilia was not associated with an increased incidence of low-titre inhibitors.
Assuntos
Fator VIII/antagonistas & inibidores , Hemofilia A/diagnóstico , Feminino , Humanos , Incidência , Masculino , Fatores de RiscoRESUMO
The development of anti-FVIII neutralizing alloantibodies (inhibitors), occurring in about one-third of previously untreated patients (PUPs) with severe haemophilia A, depends on various genetic and environmental risk factors. Several previous studies have reported on the immunogenicity of FVIII concentrates, and due to differences in study design, study period, inhibitor testing frequency and follow-up duration the results were inconclusive. The first randomized trial on this unresolved question (SIPPET) included 251 previously untreated or minimally treated patients with severe haemophilia A treated with either a single plasma-derived FVIII (pdFVIII) containing VWF or a recombinant FVIII (rFVIII). The results showed an 87% higher rate of inhibitor development for rFVIII than pdFVIII during the first 50 exposure days of treatment. These results generated interest by patient organizations, physicians and regulatory agencies. This manuscript summarizes answers to the main questions that arose after the full publication of SIPPET.
Assuntos
Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Fator VIII/imunologia , Hemofilia A/tratamento farmacológico , Humanos , Isoanticorpos/imunologia , Isoanticorpos/uso terapêutico , Risco , Estatística como AssuntoRESUMO
INTRODUCTION: Patients with haemophilia B who develop factor IX (FIX) neutralizing antibodies (inhibitors) after FIX infusion are at high risk of hypersensitivity reactions upon FIX re-exposure, but the underlying mechanisms are incompletely understood. AIM: To investigate biomechanisms of FIX hypersensitivity. METHODS: A cellular antigen stimulation test (CAST) was employed to evaluate leukotriene C4 (LTC4) release from basophils stimulated by FIX in three treated children with haemophilia B, one of whom developed FIX inhibitor and experienced anaphylaxis following FIX re-exposure. Anti-FIX IgE and IgG antibodies and markers of complement activation (C5b9, C3d and iC3b) were measured in plasma, the last also after FIX infusion. Ten healthy children served as controls. RESULTS: The patient who developed anti-FIX inhibitors and anaphylaxis had a nonsense mutation in FIX gene (p.Arg298Stop) and, compared to controls, had higher plasma levels of specific anti-FIX IgE (2.285 vs 0.084 OD492 nm ), with marked LTC4 release from his FIX-stimulated basophils (519.8 vs 39.9 pg/mL). Further, he had higher plasma levels of anti-FIX IgG of all the four subclasses (total IgG 1.180 vs 0.120 OD492 nm ) with FIX neutralizing activity (1.5 BU); mild complement activation occurred during FIX-induced anaphylaxis (C5b9 increased from 258.5 to 351.1 ng/mL). The same parameters were normal in the two patients who tolerated FIX infusion. CONCLUSION: In the patient with haemophilia B who experienced anaphylaxis after FIX, but not in the patients with haemophilia B who tolerated FIX, the CAST assay showed FIX-induced LTC4 release, which was associated with high plasma levels of specific anti-FIX IgE and IgG antibodies.
Assuntos
Anafilaxia/complicações , Anticorpos Neutralizantes/imunologia , Basófilos/imunologia , Ativação do Complemento , Fator IX/imunologia , Hemofilia B/imunologia , Imunoglobulina E/imunologia , Pré-Escolar , Hemofilia B/complicações , Humanos , MasculinoRESUMO
INTRODUCTION: This report summarizes recommendations relating to haemophilia therapy arising from discussions among experts from 36 European countries during the 'Kreuth IV' meeting in May 2016. AIM: The objective of the meeting was for experts in the field of haemophilia from across Europe to draft resolutions regarding current issues relating to the treatment of haemophilia. RESULTS: Hospitals providing clinical care for people with haemophilia and related disorders are strongly recommended to seek formal designation as either European Haemophilia Treatment Centres (EHTC) or European Haemophilia Comprehensive Care Centres (EHCCC). There should be agreed national protocols or guidelines on management of the ageing patient with haemophilia. The minimum consumption of factor VIII and IX concentrate in any country should be 4 IU and 0.5 IU per capita of general population respectively. Treatment for hepatitis C with direct-acting antiviral agents should be provided to all people with haemophilia on a priority basis. Genotype analysis should be offered to all patients with severe haemophilia. Genetic counselling, when given, should encompass the recommendation that genetic relatives of the affected person be advised to seek genetic counselling. People with inhibitors should have access to bypassing agents, immune tolerance and elective surgery. National or regional tenders for factor concentrates are encouraged. Outcome data including health related quality of life should be collected. Treatment with extended half-life factors should be individualized and protection against bleeding should be improved by increasing trough levels. Steps should be taken to understand and minimize the risk of inhibitor development. CONCLUSION: It is hoped that these recommendations will help to foster equity of haemophilia care throughout Europe.
Assuntos
Fatores de Coagulação Sanguínea/uso terapêutico , Consenso , Hemofilia A/tratamento farmacológico , Europa (Continente) , HumanosRESUMO
PURPOSE: To assess the pattern of in-hospital changes in drug use in older patients from 2010 to 2016. METHODS: People aged 65 years or more acutely hospitalized in those internal medicine and geriatric wards that did continuously participate to the REgistro POliterapie Società Italiana di Medicina Interna register from 2010 to 2016 were selected. Drugs use were categorized as 0 to 1 drug (very low drug use), 2 to 4 drugs (low drug use), 5 to 9 drugs (polypharmacy), and 10 or more drugs (excessive polypharmacy). To assess whether or not prevalence of patients in relation to drug use distribution changed overtime, adjusted prevalence ratios (PRs) was estimated with log-binomial regression models. RESULTS: Among 2120 patients recruited in 27 wards continuously participating to data collection, 1882 were discharged alive and included in this analysis. The proportion of patients with very low drug use (0-1 drug) at hospital discharge increased overtime, from 2.7% in 2010 to 9.2% in 2016. Results from a log-logistic adjusted model confirmed the increasing PR of these very low drug users overtime (particularly in 2014 vs 2012, PR 1.83 95% CI 1.14-2.95). Moreover, from 2010 to 2016, there was an increasing number of patients who, on polypharmacy at hospital admission, abandoned it at hospital discharge, switching to the very low drug use group. CONCLUSION: This study shows that in internal medicine and geriatric wards continuously participating to the REgistro POliterapie Società Italiana di Medicina Interna register, the proportion of patients with a very low drug use at hospital discharge increased overtime, thus reducing the therapeutic burden in this at risk population.
Assuntos
Prescrições de Medicamentos/estatística & dados numéricos , Pacientes Internados , Idoso , Idoso de 80 Anos ou mais , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Medicina Interna/normas , Itália , Masculino , Polimedicação , Sistema de Registros , Fatores de RiscoRESUMO
Airborne exposure to particulate matter with diameter < 10 mcM (PM10) has been linked to an increased risk of thromboembolic events, but the mechanisms are not completely understood. The aim of this study was to evaluate the effect of PM10 phagocytosis on the release of procoagulant molecules in human differentiating macrophages, and that of PM10 inhalation in an experimental model in rats. Human monocytes were separated from the peripheral blood by the lymphoprep method, differentiated in vitro and treated with standard PM10 or vehicle. Sprague-Dawley rats were instilled intratracheally with PM10 or vehicle alone. The outcome was expression of proinflammatory genes and of tissue factor (TF). In human differentiating macrophages, PM10 exposure upregulated inflammatory genes, but most consistently induced TF mRNA and protein levels, but not TF protein inhibitor, resulting in increased TF membrane expression and a procoagulant phenotype. Differentiation towards the anti-inflammatory M2 phenotype inhibited PM10 -mediated TF expression. TF induction required phagocytosis of PM10 , whereas phagocytosis of inert particles was less effective. PM10 phagocytosis was associated with a gene expression profile consistent with intracellular retention of iron, inducing oxidative stress. Both PM10 and iron activated the stress kinases ERK1/2 pathway, involved in the induction of TF expression. In rats, alveolar exposure to PM10 was associated with pulmonary recruitment of inflammatory cells and resulted in local, but not systemic, induction of TF expression, which was sufficient to increase circulating TF levels. In conclusion, TF induction by differentiating lung macrophages, activated following phagocytosis, contributes to the increased risk of thromboembolic complications associated with PM10 exposure.
Assuntos
Macrófagos/efeitos dos fármacos , Material Particulado/toxicidade , Fagocitose/efeitos dos fármacos , Tromboplastina/biossíntese , Adulto , Animais , Diferenciação Celular/efeitos dos fármacos , Citocalasina D/farmacologia , Humanos , Ferro/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Macrófagos/fisiologia , Masculino , Ratos , Ratos Sprague-Dawley , Tromboplastina/genéticaRESUMO
Recurrent gastrointestinal bleeding is one of the most challenging complications encountered in the management of patients with von Willebrand disease (VWD). The commonest cause is angiodysplasia, but often no cause is identified due to the difficulty in making the diagnosis. The optimal treatment to prevent recurrences remains unknown. We performed a retrospective study of VWD patients with occult or angiodysplastic bleeding within the setting of the von Willebrand Disease Prophylaxis Network (VWD PN) to describe diagnostic and treatment strategies. Centres participating in the VWD PN recruited subjects under their care with a history of congenital VWD and gastrointestinal (GI) bleeding due to angiodysplasia, or cases in which the cause was not identified despite investigation. Patients with acquired von Willebrand syndrome or those for whom the GI bleeding was due to another cause were excluded. Forty-eight patients from 18 centres in 10 countries were recruited. Seven individuals had a family history of GI bleeding and all VWD types except 2N were represented. Angiodysplasia was confirmed in 38%, with video capsule endoscopy and GI tract endoscopies being the most common methods of making the diagnosis. Recurrent GI bleeding in VWD is associated with significant morbidity and required hospital admission on up to 30 occasions. Patients were treated with multiple pharmacological agents with prophylactic von Willebrand factor concentrate being the most efficient in preventing recurrence of the GI bleeding. The diagnosis and treatment of recurrent GI bleeding in congenital VWD remains challenging and is associated with significant morbidity. Prophylactic treatment with von Willebrand factor concentrate was the most effective method of preventing recurrent bleeding but its efficacy remains to be confirmed in a prospective study.
Assuntos
Hemorragia Gastrointestinal/epidemiologia , Hemorragia Gastrointestinal/etiologia , Doenças de von Willebrand/complicações , Doenças de von Willebrand/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Doenças de von Willebrand/diagnóstico , Doenças de von Willebrand/tratamento farmacológicoRESUMO
Development of inhibitory antibodies to infused factor VIII (FVIII) concentrates is the most serious unresolved complication of haemophilia A treatment. Systematic reviews suggest a twofold higher incidence of inhibitors with recombinant (rFVIII) vs. plasma-derived (pdFVIII) FVIII products, but study methodologies vary widely. The lower immunogenicity of pdFVIII concentrates is believed to derive from the presence of von Willebrand factor (VWF) which acts as protector and chaperone for FVIII. Several novel investigations reinforce the protective role of the VWF/FVIII complex in inhibitor development. At the basic science level, numerous in vitro and in vivo experiments have demonstrated that VWF-containing pdFVIII concentrates (pdFVIII/VWF) provide better protection against inhibitor neutralization than rFVIII products. Conformational aspects of the binding between VWF and FVIII are thought to prevent the 'attack' on FVIII by inhibitory antibodies. VWF/FVIII binding is 100% in pdFVIII products but only 80% in recombinant products and this 'free' FVIII may be a target for inhibitory antibodies. At the clinical level, newer strategies to prevent inhibitor development in previously untreated patients with severe haemophilia are under investigation. The concept of early prophylaxis (before the onset of a bleed) is convincing from a theoretical point of view but requires further evaluation. The Study on Inhibitors in Plasma-Product Exposed Toddlers is specifically addressing the issue of relative immunogenicity between classes of FVIII product (recombinant vs. plasma-derived). Currently nearing its target enrolment of 300 patients, this international randomized controlled trial is expected to provide some definitive answers about this ever-present clinical dilemma.
Assuntos
Coagulantes/uso terapêutico , Fator VIII/uso terapêutico , Hemofilia A/tratamento farmacológico , Tolerância Imunológica/efeitos dos fármacos , Fator de von Willebrand/uso terapêutico , Inibidores dos Fatores de Coagulação Sanguínea/sangue , Coagulantes/imunologia , Substituição de Medicamentos , Fator VIII/antagonistas & inibidores , Fator VIII/imunologia , Hemofilia A/imunologia , Humanos , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/uso terapêutico , Fator de von Willebrand/antagonistas & inibidores , Fator de von Willebrand/imunologiaRESUMO
Patients with von Willebrand disease (VWD) may need orthopaedic surgery because of disabling chronic arthropathy due to recurrent joint bleeding. They may also require this surgery independently of their haemostasis disorder. Knowledge regarding the management of orthopaedic surgery in VWD is limited. Description of management of orthopaedic surgery in patients with VWD, based upon retrospective data collection and analysis of 32 orthopaedic procedures carried out over a period of 33 years in 23 patients was the aim of this study. Of 32 procedures, six were minor (three hand surgery, one foot surgery, two others) and 26 were major (seven joint replacements, nine arthroscopic procedures, two foot surgery, eight others). Twenty-two procedures were performed using replacement therapy with plasma-derived concentrates containing both factor VIII (FVIII) and von Willebrand factor (VWF). Two procedures in patients with acquired von Willebrand syndrome (AWVS) were performed using FVIII-VWF concentrates associated with intravenous immunoglobulins, or desmopressin plus tranexamic acid. Seven procedures were performed using desmopressin alone and one using intravenous immunoglobulins in AVWS. Bleeding complications occurred in seven procedures (22%). In one patient, an anti-VWF antibody was diagnosed after surgery. Anticoagulant prophylaxis of venous thromboembolism was implemented in four cases only and in two instances there was excessive bleeding. In conclusion, control of surgical haemostasis was achieved in most patients with VWD undergoing orthopaedic surgery. The control of haemostasis combined with an adequate surgical technique and early post-operative rehabilitation are warranted for the successful performance of orthopaedic surgery in VWD, which requires the involvement of specialized haemophilia centres.
Assuntos
Hemartrose/etiologia , Hemartrose/cirurgia , Procedimentos Ortopédicos , Doenças de von Willebrand/complicações , Adolescente , Adulto , Idoso , Transfusão de Sangue , Criança , Seguimentos , Hemorragia/etiologia , Hemorragia/terapia , Humanos , Pessoa de Meia-Idade , Procedimentos Ortopédicos/efeitos adversos , Procedimentos Ortopédicos/métodos , Resultado do Tratamento , Adulto Jovem , Doenças de von Willebrand/sangue , Doenças de von Willebrand/diagnósticoRESUMO
The maintenance of a correct posture in haemophilic boys might contribute to prevent joint bleeds, chronic pain and dysfunction. This single-centre study was aimed at evaluating whether or not postural alterations are more common in haemophilic than in non-haemophilic boys and whether they are related to the orthopaedic status. Posture and balance were investigated in boys with severe/moderate haemophilia (cases) and in age-matched non-haemophilic peers (controls). Thirty-five cases (89% with haemophilia A: 74% with severe disease) were included in the study and compared with 57 controls. Posture was evaluated on digital pictures of anterior, lateral and posterior views of the habitual standing position. Balance was examined with a portable force platform with eyes open and closed. The trajectory of the total body centre of force (CoF) displacement over the platform was computed by multiple planes obtaining different measures: sway area, velocity, acceleration and body loads. The joint status of cases was assessed with the Haemophilia Joint Health Score. Cases were more disharmonic than controls (52% vs. 26% in controls; P = 0.04), swayed significantly less and more slowly than controls (P < 0.05 for several parameters of CoF displacement) revealing stiffness of the musculoskeletal system. However, they were able to maintain their stance within a similar sway area. Haemophilic boys have more postural disharmonies than non-haemophilic peers, hence a global evaluation of the orthopaedic status should include also balance and posture examination to identify early dysfunction and establish a tailored physical or rehabilitation programme.
Assuntos
Hemartrose/etiologia , Hemofilia A/complicações , Postura , Adolescente , Estudos de Casos e Controles , Criança , Hemartrose/prevenção & controle , Hemofilia A/fisiopatologia , Humanos , Masculino , Equilíbrio PosturalRESUMO
This report summarizes recommendations relating to haemophilia therapy arising from discussions among experts from 36 European countries during the Kreuth III meeting in April 2013. To optimize the organization of haemophilia care nationally, it is recommended that a formal body be established in each country to include the relevant clinicians, national haemophilia patient organization, health ministry, paying authority and (if appropriate) regulatory authorities. The minimum factor VIII consumption level in a country should be 3 I.U. per capita. Decisions on whether to adopt a new product should not be based solely on cost. Prophylaxis for children with severe haemophilia is already recognized as the optimum therapy. Ongoing prophylaxis for individual adults should also be provided when required based on clinical decision making by the clinician in consultation with the patient. Children with inhibitors who have failed, or who are not suitable for, immune tolerance therapy should be offered prophylaxis with bypassing agents. Single factor concentrates should be used as therapy wherever possible in patients with rare bleeding disorders. Orphan drug designation for a factor concentrate should not be used to hinder the development, licencing and marketing of other products for the same condition which have demonstrably different protein modification or enhancement.
Assuntos
Fatores de Coagulação Sanguínea/uso terapêutico , Hemofilia A/tratamento farmacológico , Criança , Consenso , Europa (Continente) , Humanos , Guias de Prática Clínica como AssuntoRESUMO
Knowledge regarding the management of orthopaedic surgery in patients with rare bleeding disorders (RBDs) is limited. Retrospective data collection and analysis of 35 orthopaedic procedures (6 minor and 29 major) carried out in 22 patients with RBD between 1982 and 2013. These surgeries were performed using heterogeneous regimens of hemostatic therapy, except for seven procedures performed with no hemostatic treatment in four patients with mild factor deficiency. Of the 28 procedures carried out with hemostatic treatment, nine (32%) were performed using replacement therapy with dosages of concentrates of the deficient factor aimed to achieve perioperative plasma levels judged to be compatible with hemostasis; three (11%) using factor replacement therapy associated with fresh frozen plasma (FFP); four (14%) using recombinant activated factor VII; four (14%) using virus inactivated plasma alone; three (11%) using virus inactivated plasma associated with desmopressin; one (4%) using FFP alone; and four (14%) procedures using tranexamic acid alone. Bleeding complications occurred in 7 of 35 procedures (20%) involving five patients. Prophylaxis of venous thromboembolism was performed only in one case with no excessive bleeding, but two patients not on thromboprophylaxis developed superficial thrombophlebitis. A satisfactory control of hemostasis was achieved in most patients. In some of those characterized by mild factor deficiency (FVII, FXI) hemostatic treatment could be avoided in some instances. The control of hemostasis combined with an adequate surgical technique is needed for the successful outcome of orthopaedic surgery in RBDs that requires the involvement of specialized haemophilia centres.
Assuntos
Transtornos da Coagulação Sanguínea/complicações , Perda Sanguínea Cirúrgica/prevenção & controle , Hemorragia/prevenção & controle , Hemostasia Cirúrgica/métodos , Hemostáticos/uso terapêutico , Procedimentos Ortopédicos , Adulto , Idoso , Transtornos da Coagulação Sanguínea/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Assistência Perioperatória , Estudos Retrospectivos , Adulto JovemRESUMO
PURPOSE: To investigate the prevalence of xanthine oxidase (XO) inhibitors prescription at admission and discharge in elderly hospital in-patients, to analyze the appropriateness of their use in relation to evidence-based indications, to evaluate the predictors of inappropriate prescription at discharge and the association with adverse events 3 months after hospital discharge. METHODS: This cross-sectional study, based upon a prospective registry, was held in 95 Italian internal medicine and geriatric hospital wards. The sample included 4035 patients aged 65 years or older at admission and 3502 at discharge. The prescription of XO inhibitors was considered appropriate in patients with diagnosis of gout, gout nephropathy, uric acid nephrolithiasis, tophi, and chemotherapy-induced hyperuricemia. In order to evaluate the predictors of inappropriate prescription of XO inhibitors, we compared the characteristics of patients considered inappropriately treated with those appropriately not treated. RESULTS: Among the 4035 patients eligible for the analysis, 467 (11.6 %) were treated with allopurinol or febuxostat at hospital admission and 461 (13.2 %) among 3502 patients discharged. At admission, 39 (8.6 %) of patients receiving XO inhibitors and 43 (9.4 %) at discharge were appropriately treated. Among those inappropriately treated, hyperuricemia, polytherapy, chronic renal failure, diabetes, obesity, ischemic cardiomyopathy, heart failure, and cardiac dysrhythmias were associated with greater prescription of XO inhibitors. Prescription of XO inhibitors was associated with a higher risk of adverse clinical events in univariate and multivariate analysis. CONCLUSIONS: Prevalence of inappropriate prescription of XO inhibitors remained almost the same at admission and discharge. Inappropriate use of these drugs is principally related to treatment of asymptomatic hyperuricemia and various cardiovascular diseases.
Assuntos
Alopurinol/efeitos adversos , Supressores da Gota/efeitos adversos , Prescrição Inadequada/estatística & dados numéricos , Tiazóis/efeitos adversos , Xantina Oxidase/antagonistas & inibidores , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Febuxostat , Feminino , Hospitais/estatística & dados numéricos , Humanos , Hiperuricemia/tratamento farmacológico , Hiperuricemia/epidemiologia , Itália/epidemiologia , Masculino , Admissão do Paciente/estatística & dados numéricos , Alta do Paciente/estatística & dados numéricos , Sistema de Registros , RiscoRESUMO
WHAT IS KNOWN AND OBJECTIVE: Inappropriate prescribing is highly prevalent for older people and has become a global healthcare concern because of its association with negative health outcomes including ADEs, hospitalization and resource utilization. Beers' criteria are widely utilized for evaluating the appropriateness of medications, and an up-to-date version has recently been published. To assess the prevalence of patients exposed to PIMs at hospital discharge according to the 2003 and 2012 versions of Beers' criteria and to evaluate the risk of adverse clinical events, re-hospitalization and all-cause mortality at 3-month follow-up. METHODS: This cross-sectional study was held in 66 Italian internal medicine and geriatric wards. The sample included 1380 inpatients aged 65 years or older. Prescriptions of PIM were analysed at hospital discharge. We considered all patients with complete 3-month follow-up. RESULTS AND DISCUSSION: The prevalence of patients receiving at least one PIM was 20·1% and 23·5% according to the 2003 and 2012 versions of the Beers' criteria, respectively. The 2012 Beers' criteria identified more patients with at least one PIM than the 2003 version, although a high percentage of those patients (72·2%) were also identified by the criteria updated in 2003. The main difference in the prevalence of patients receiving a PIM according to the two versions of Beers' criteria involved prescriptions of benzodiazepines for insomnia or agitation, chronic use of non-benzodiazepine hypnotics, prescription of antipsychotics in people with dementia and oral iron at dosage higher than 325 mg/day. Prescription of PIMs was not associated with a higher risk of adverse clinical events, re-hospitalization and all-cause mortality at 3-month follow-up in both univariate and multivariate analysis, after adjusting for age, sex and CIRS comorbidity index. WHAT IS NEW AND CONCLUSIONS: This study found no significant effect of inappropriate drug use according to Beers' criteria on health outcomes among older adults 3 month after discharge. Even though these criteria have been suggested as helpful in promoting appropriate prescribing, reducing drug-related adverse events and associated healthcare costs, to date there is no clear evidence that their application can achieve objective and quantifiable improvements in clinical outcomes. A possible explanation is that both versions of the Beers' criteria have several recognized limitations, one of the main ones being the restricted availability of some drugs in Europe or their limited prescription in everyday clinical practice.