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INTRODUCTION: The pharmacokinetics (PK), efficacy and safety of moroctocog alfa (AF-CC) have been demonstrated in haemophilia A patients aged ≥6 years. AIM: These studies aimed to further describe moroctocog alfa (AF-CC) experience in paediatric patients (<12 years) with severe haemophilia A (FVIII:C < 1%). METHODS: Two prospective, open-label studies enrolled patients aged <12 years: one study with 37 previously treated patients (PTPs) and another with 23 previously untreated patients (PUPs). All patients initially received 50 IU/kg of moroctocog alfa (AF-CC) to evaluate either recovery alone, or with other PK parameters (6 to <12 years) before continuing treatment for 100 exposure days (EDs) or 24 months. RESULTS: At baseline, mean (±SD) recovery ranged between 1.32 ± 0.65 (PUPs aged <2 years) and 2.13 ± 0.82 (PTPs aged 6 to <12 years). The mean (±SD) half-life was 9.12 ± 1.94 hours in PTPs aged 6 to <12 years. No new safety signals were detected in either study, 2 transient lower titre inhibitors occurred in PTPs while 8 inhibitors (3 low and 5 high titre) were detected in PUPs. Most bleeding episodes resolved with one infusion (94% [893/954]). The annualised bleeding rate (ABR) in the PTP study was 27.5 and 4.2 for patients reporting an on-demand and routine prophylaxis regimen at baseline, respectively. In the PUP study, the overall ABR was 5.9. CONCLUSION: Moroctocog alfa (AF-CC) had expected PK findings (lower recovery in young children compared with older children) along with being safe and efficacious in a population of young severe haemophilia A patients.
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Factor VIII/uso terapéutico , Hemofilia A/tratamiento farmacológico , Niño , Preescolar , Factor VIII/efectos adversos , Factor VIII/inmunología , Femenino , Hemofilia A/inmunología , Humanos , Lactante , Recién Nacido , Masculino , Estudios Prospectivos , SeguridadRESUMEN
INTRODUCTION: A room temperature stable formulation of recombinant activated factor VII (NovoSeven® ), allowing convenient storage and therefore improved treatment access, has been developed. Bioequivalence to the previous NovoSeven® was demonstrated in healthy humans, leading to European approval (2008). Although no confirmed cases of neutralising antibodies to rFVIIa in patients with haemophilia A or B have been observed with the original formulation, changes in formulation or storage condition may alter immunogenicity. AIM: SMART-7™ was designed to investigate the safety of NovoSeven® in a real-world setting in patients with haemophilia A or B with inhibitors. METHODS: Study medication was not provided by the sponsor, and treatment was at the discretion of the treating physician, in accordance with the local label. Patient baseline information was collected at enrolment. Information on safety, drug exposure and bleeding episodes was collected and FVII antibody screening was encouraged at baseline and performed at the investigator's discretion. RESULTS: Fifty-one patients were enrolled and 31 completed the study. Forty-one adverse events (AEs) were reported in 23 patients; 25 AEs in 14 patients were serious. No thromboembolic events were observed. Although four cases of reduced therapeutic response were reported, FVII antibody screening was negative. Forty-eight patients experienced 618 bleeding episodes and 93.4% of 609 evaluated bleeds were stopped by treatment. Of the 538 bleeding episodes treated with NovoSeven® monotherapy, 94.2% stopped by end of treatment. CONCLUSION: Data collected during the SMART-7™ study revealed no treatment-related safety issues and no FVII-binding antibodies for patients treated with NovoSeven® under real-world conditions.
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Factor VIIa/efectos adversos , Factor VIIa/uso terapéutico , Hemofilia A/tratamiento farmacológico , Hemofilia B/tratamiento farmacológico , Seguridad , Temperatura , Adolescente , Adulto , Anciano , Niño , Preescolar , Estabilidad de Medicamentos , Factor VIIa/farmacología , Femenino , Hemofilia A/complicaciones , Hemofilia B/complicaciones , Hemorragia/complicaciones , Humanos , Lactante , Internacionalidad , Masculino , Persona de Mediana Edad , Proteínas Recombinantes/efectos adversos , Proteínas Recombinantes/farmacología , Proteínas Recombinantes/uso terapéutico , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Development of inhibitors is the most serious complication in haemophilia A treatment. The assessment of risk for inhibitor formation in new or modified factor concentrates is traditionally performed in previously treated patients (PTPs). However, evidence on risk factors for and natural history of inhibitors has been generated mostly in previously untreated patients (PUPs). The purpose of this study was to examine cases of de novo inhibitors in PTPs reported in the scientific literature and to the EUropean HAemophilia Safety Surveillance (EUHASS) programme, and explore determinants and course of inhibitor development. METHODS: We used a case series study design and developed a case report form to collect patient level data; including detection, inhibitor course, treatment, factor VIII products used and events that may trigger inhibitor development (surgery, vaccination, immune disorders, malignancy, product switch). RESULTS: We identified 19 publications that reported 38 inhibitor cases and 45 cases from 31 EUHASS centres. Individual patient data were collected for 55/83 (66%) inhibitor cases out of 12 330 patients. The median (range) peak inhibitor titre was 4.4 (0.5-135.0), the proportion of transient inhibitors was 33% and only two cases of 12 undergoing immune tolerance induction failed this treatment. In the two months before inhibitor development, surgery was reported in nine (22%) cases, and high intensity treatment periods reported in seven (17%) cases. CONCLUSIONS: By studying the largest cohort of inhibitor development in PTPs assembled to date, we showed that inhibitor development in PTPs, is on average, a milder event than in PUPs.
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Historia Natural/métodos , Adulto , Hemofilia A/tratamiento farmacológico , Humanos , Persona de Mediana Edad , Factores de RiesgoRESUMEN
INTRODUCTION: Hereditary factor X (FX) deficiency affects 1:500 000 to 1:1 000 000 of individuals. There are few published data on the pharmacokinetics (PK) of FX for existing treatments for FX deficiency, and no specific replacement factor concentrate exists. A high-purity plasma-derived FX concentrate (pdFX) has been developed for use as replacement therapy in subjects with hereditary FX deficiency. AIM: This analysis assessed pdFX PK after a single 25 IU kg(-1) bolus dose in subjects with hereditary moderate or severe FX deficiency (plasma FX activity [FX:C] <5 IU dL(-1) ). METHODS: For a baseline PK assessment, blood samples were taken predose and at intervals up to 144 h (7 days) post dose. After ≥6 months of on-demand pdFX treatment and treatment of ≥1 bleed with pdFX, subjects underwent repeat PK assessment. Samples were assayed for plasma FX:C (measured using the clotting and chromogenic assays) and FX antigen. RESULTS: FX:C peaked at 0.4-0.5 h and subsequently declined over the course of 144 h with a biphasic decay curve. PK parameters observed at the baseline (n = 16) and repeat (n = 15) assessments were equivalent, therefore summary PK values were obtained by combining data from both visits (n = 31). The mean terminal half-life and incremental recovery of pdFX was 29.4 h and 2.00 IU dL(-1) per IU kg(-1) respectively. CONCLUSION: This is the most comprehensive PK study to date in subjects with hereditary FX deficiency. These results are consistent with the observed haemostatic efficacy of pdFX and provide the PK data required for the treatment of hereditary FX deficiency using pdFX replacement therapy.
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Coagulantes/uso terapéutico , Deficiencia del Factor X/tratamiento farmacológico , Factor X/uso terapéutico , Adolescente , Adulto , Área Bajo la Curva , Pruebas de Coagulación Sanguínea , Niño , Coagulantes/farmacocinética , Factor X/farmacocinética , Deficiencia del Factor X/congénito , Deficiencia del Factor X/patología , Femenino , Semivida , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Curva ROC , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Adulto JovenRESUMEN
INTRODUCTION: Hereditary factor X (FX) deficiency is a rare bleeding disorder affecting 1:500 000 to 1:1 000 000 of individuals. Until recently, no specific replacement factor concentrate was available. AIM: The aim of this study was to assess safety and efficacy of a new, high-purity plasma-derived FX concentrate (pdFX) in subjects with hereditary FX deficiency. METHODS: Subjects aged ≥12 years with moderate or severe FX deficiency (plasma FX activity <5 IU dL(-1) ) received 25 IU kg(-1) pdFX as on-demand treatment or short-term prophylaxis for 6 months to 2 years. Subjects assessed pdFX efficacy for each bleed; at end-of-study, investigators assessed overall pdFX efficacy. Blood samples for pharmacokinetic analysis were obtained at baseline and ≥6 months. Safety was assessed by adverse events (AEs), inhibitor development and changes in laboratory parameters. RESULTS: Sixteen enrolled subjects (six aged 12-17 years; 10 aged 18-58 years) received a total of 468 pdFX infusions. In the 187 analysed bleeds, pdFX efficacy was categorized as excellent, good, poor or unassessable in 90.9%, 7.5%, 1.1% and 0.5% of bleeds respectively; 83% of bleeds were treated with one infusion. For pdFX, mean (median; interquartile range) incremental recovery and half-life were 2.00 (2.12; 1.79-2.37) IU dL(-1) per IU kg(-1) and 29.4 (28.6; 25.8-33.1) h respectively. No serious AEs possibly related to pdFX or evidence of FX inhibitors were observed, and no hypersensitivity reactions or clinically significant trends were detected in laboratory parameters. CONCLUSION: These results demonstrate that a dose of 25 IU kg(-1) pdFX is safe and efficacious for on-demand treatment and short-term prophylaxis in subjects with moderate or severe hereditary FX deficiency.
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Deficiencia del Factor X/tratamiento farmacológico , Factor X/uso terapéutico , Adolescente , Adulto , Anticuerpos Neutralizantes/sangre , Pruebas de Coagulación Sanguínea , Niño , Factor X/efectos adversos , Factor X/farmacocinética , Deficiencia del Factor X/congénito , Deficiencia del Factor X/patología , Femenino , Semivida , Hemorragia/prevención & control , Humanos , Masculino , Menorragia/prevención & control , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Adulto JovenRESUMEN
INTRODUCTION: Limited data are available on optimal prophylaxis regimens of factor IX (FIX) replacements for patients with haemophilia B. AIM: This multicentre, open-label study evaluated the efficacy and safety of once-weekly prophylaxis with nonacog alfa compared with on-demand treatment in adolescent and adult patients. METHODS: Males aged 12-65 years with moderately severe to severe haemophilia B (FIX:C ≤ 2%) were eligible for enrolment. Patients received on-demand treatment for 26 weeks, followed by once-weekly prophylaxis of 100 IU kg(-1) for 52 weeks. The primary efficacy end point was the annualized bleeding rate (ABR). Secondary end points included response to on-demand treatment, the number of infusions used to treat bleeding events, and the incidence of less-than-expected therapeutic effect (LETE). FIX:C was measured on day 1 and at weeks 26 and 78. RESULTS: Mean (±SD) ABR was lower during prophylaxis vs. on-demand treatment [3.6 (±4.6) vs. 32.9 (±17.4) events, respectively; P < 0.0001]. The majority (88.4%) of bleeding events had excellent or good responses upon the first infusion; 82.1% of events responded to the first infusion. No incident of LETE occurred. No thrombotic events or FIX inhibitors were reported. Eight of 17 FIX:C approximately 1 week after dosing were >2 IU dL(-1) (min-max of 2.13-10.39 IU dL(-1) ). CONCLUSIONS: Once-weekly prophylaxis of 100 IU kg(-1) was associated with lower ABR compared with on-demand treatment in adolescents and adults with moderately severe to severe haemophilia B. Once-weekly prophylaxis was well tolerated, with a similar safety profile as that reported during the on-demand treatment period. Residual FIX:C may be supportive of effectiveness.
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Coagulantes/uso terapéutico , Factor IX/uso terapéutico , Hemofilia B/tratamiento farmacológico , Adolescente , Adulto , Anciano , Niño , Coagulantes/efectos adversos , Esquema de Medicación , Factor IX/genética , Factor IX/metabolismo , Hemorragia/epidemiología , Hemorragia/prevención & control , Humanos , Masculino , Persona de Mediana Edad , Proteínas Recombinantes/biosíntesis , Proteínas Recombinantes/genética , Proteínas Recombinantes/uso terapéutico , Trombosis/etiología , Resultado del Tratamiento , Adulto JovenRESUMEN
The ONE Registry (OR) was an international prospective observational study of on-demand recombinant factor VIIa (rFVIIa) treatment for mild to moderate bleeds in haemophilia A/B patients with inhibitors. To describe real-world use of single and multi dose rFVIIa and to compare outcomes, including effectiveness, safety, quality of life and treatment satisfaction associated with treatment. Baseline data included demographics, treatment, medical and bleed history and patient/caregiver-reported outcomes regarding bleeds. rFVIIa was prescribed according to routine practice; regimens varied and initial dose was categorized as low (LD, ≤ 120 µg kg(-1) ), intermediate (ID, >120 and <250 µg kg(-1) ) or high (HD, ≥ 250 µg kg(-1) ). OR included 102 patients and 85 (83%) reported 494 bleeds overall. Mean age was 23 years (SD 16.4), with 52% ≥ 18 years. Majority of bleeds (n = 350, 71%) involved ≥ 1 joints; 46% involved a target joint. Median initial dose was 90 µg kg(-1) in LD (range 87-120, n = 156), 174 µg kg(-1) in ID, (range 121-249, n = 127) and 270 µg kg(-1) in HD, (range 250-375, n = 211). For spontaneous bleeds, effective haemostasis rate at 9 h was 63% LD, 60% ID and 56% HD. Rates of combined partially effective/effective haemostasis was 85% LD, 96% ID and 86% HD. Median number of doses in HD was one (range 1-7), compared with two in LD (range 1-17) and ID (range 1-23). No thromboembolic events were reported in 1145 doses given. These observational data in real life are consistent with previous studies which have shown similar overall effectiveness of rFVIIa and similar effectiveness and safety across different patterns of standard initial dosing.
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Factor VIIa/antagonistas & inhibidores , Factor VIIa/uso terapéutico , Hemofilia A/tratamiento farmacológico , Internacionalidad , Sistema de Registros , Demografía , Relación Dosis-Respuesta a Droga , Factor VIIa/efectos adversos , Hemofilia A/sangre , Hemofilia A/complicaciones , Hemorragia/sangre , Hemorragia/complicaciones , Hemorragia/tratamiento farmacológico , Hemostasis/efectos de los fármacos , Humanos , Proteínas Recombinantes/efectos adversos , Proteínas Recombinantes/uso terapéutico , Resultado del TratamientoRESUMEN
Patients with haemophilia A and inhibitors are at high risk for severe bleeding, progression of joint disease and deterioration of health-related quality of life (HRQoL). To determine the impact of prophylaxis with an activated prothrombin complex concentrate (aPCC) on HRQoL, HRQoL was assessed using the Short-Form (SF)-36 Health Survey and the EQ-5D questionnaire in subjects ≥ 14 years participating in a prospective, randomized, crossover study comparing 6 months of aPCC prophylaxis with 6 months of on-demand therapy. Eighteen of 19 patients completed the survey or questionnaire before and after the on-demand therapy and prophylaxis periods. A general trend towards improved HRQoL after prophylaxis was observed for the 18 evaluable patients in all SF-36 dimensions except for vitality/energy and physical functioning. After prophylaxis, 'good responders,' defined as patients experiencing ≥ 50% reduction in bleeding, exhibited statistically and clinically significant differences in the physical component score (P = 0.021), role - physical (P = 0.042), bodily pain (P = 0.015), and social functioning (P = 0.036). Similarly, the EQ-5D health profile showed a trend towards improvement after prophylaxis in all evaluable patients. Among the good responders, improvements did not differ from those observed after on-demand treatment. EQ visual analogue scale values were slightly improved following prophylaxis for all evaluable patients and the EQ-5D utility index improved in the good responders only. During prophylaxis, patients missed significantly fewer days from school or work because of bleeding than during on-demand treatment (P = 0.01). In conclusion, by significantly reducing bleeding frequency in good responders, aPCC prophylaxis improved HRQoL compared with on-demand treatment.
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Factor VIII/inmunología , Hemofilia A/tratamiento farmacológico , Hemofilia A/psicología , Isoanticuerpos/inmunología , Protrombina/administración & dosificación , Adolescente , Adulto , Anciano , Niño , Preescolar , Estudios Cruzados , Femenino , Hemofilia A/inmunología , Humanos , Isoanticuerpos/biosíntesis , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Calidad de Vida , Encuestas y Cuestionarios , Adulto JovenRESUMEN
Monitoring factor replacement treatment and observing concordance with clinical haemostasis is crucial in vital haemorrhages and major surgeries in haemophilic patients. We aimed to investigate the value of the thrombin generation assay (TGA) and thromboelastography (TEG) for monitoring haemostasis in haemophilic patients during factor replacement treatment. The study group consisted of 29 patients (21 haemophilia A, 8 haemophilia B). All the patients FVIII-inhibitor were negative. A total of 35 bleeding episodes and/or surgical interventions were evaluated. aPTT, FVIII/FIX activity, TEG and TGA tests were conducted before and after factor therapy during the bleeding episode or surgical prophylaxis of haemophilic patients. Correlations among these tests were evaluated and compared with clinical responses. No correlation was found among aPTT, factor activities and clinical outcome. There were also no correlation found between TEG parameters and clinical outcome. The only significant correlation found between TGA parameters and clinical outcome was the correlation between peak thrombin. In conclusion, we found superiority of TGA-peak thrombin over other traditional tests for monitoring haemostasis in haemophilic patients in this study.
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Factor IX/uso terapéutico , Factor VIII/uso terapéutico , Hemofilia A/tratamiento farmacológico , Hemofilia B/tratamiento farmacológico , Tromboelastografía , Trombina/análisis , Adolescente , Adulto , Inhibidores de Factor de Coagulación Sanguínea/sangre , Niño , Preescolar , Factor IX/análisis , Factor VIII/análisis , Hemostasis , Humanos , Masculino , Persona de Mediana Edad , Tiempo de Tromboplastina Parcial , Adulto JovenRESUMEN
Long used in established industrialized nations to treat patients with haemophilia and inhibitors, factor eight inhibitor bypassing activity (FEIBA) has, in recent years, been introduced into more geographically diverse settings. Data are needed on how successfully FEIBA therapy has been implemented in new regions. To determine the efficacy and safety of FEIBA for the treatment of acute bleeding and surgical haemostasis in a newly industrialized country. A multicentre registry of haemophilia A patients with inhibitors receiving FEIBA treatment was established in Turkey. With a standardized case report form, data were collected retrospectively on: patient demographics; characteristics of acute bleeding episodes and surgical interventions; FEIBA regimen; and treatment outcomes. Thirty-seven patients received a total of 112 FEIBA treatment courses, 90 for acute bleeding and 22 for surgical haemostasis. The median FEIBA dose per infusion for acute bleeding was 50 IU kg(-1), and for surgery was 100 IU kg(-1). For both acute joint and muscle/soft tissue bleeding and in surgery, haemostasis was attained in a median of two FEIBA infusions. FEIBA was judged effective in 92% of treatment courses for acute bleeding, with a 95% confidence interval (CI) of 85-97%. Rates of haemostatic efficacy did not differ significantly between anatomical sites of acute bleeding. The haemostatic efficacy rate of FEIBA in surgery was 86% (CI, 65-97%). No thromboembolic complications or other adverse events occurred during any treatment course. FEIBA has been successfully integrated into clinical practice in Turkey, with rates of haemostatic efficacy comparable to those reported in countries with a longer history of FEIBA usage.
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Factores de Coagulación Sanguínea/uso terapéutico , Pérdida de Sangre Quirúrgica/prevención & control , Coagulantes/uso terapéutico , Hemofilia A/complicaciones , Hemorragia/tratamiento farmacológico , Hemostasis Quirúrgica/métodos , Enfermedad Aguda , Adolescente , Adulto , Factores de Coagulación Sanguínea/efectos adversos , Niño , Preescolar , Coagulantes/efectos adversos , Factor VIII/inmunología , Femenino , Hemofilia A/tratamiento farmacológico , Hemofilia A/inmunología , Humanos , Lactante , Masculino , Estudios Retrospectivos , Procedimientos Quirúrgicos Operativos/métodos , Turquía , Adulto JovenRESUMEN
OBJECTIVE: After surgical correction of thoracic wall deformities, promoting neochondrogenesis in the perichondrial bed is very important for obtaining a flexible chest wall. In this experimental study, we aimed to investigate the effects of human amniotic fluid on cartilage regeneration in the costal perichondrial bed in a rabbit model. METHODS: Fifty-four adult New Zealand rabbits were divided into three groups, with 18 rabbits in each group. The third and fifth costal cartilages were excised totally on the right side and partially excised on the left side in all groups. Group 1 served as controls. All rabbits in group 1 underwent closure of the perichondrium of the third costal cartilage and closure of the perichondrium of the fifth costal cartilage with reimplantation of reshaped cartilage into the fifth costal perichondrial bed. Rabbits in group 2 underwent closure of the perichondrium of the third and fifth costal cartilages after the administration of human amniotic fluid into the perichondrial bed. Group 3 rabbits received both human amniotic fluid and underwent cartilage reimplantation. The third and fifth costal perichondriums in group 3 rabbits were closed after the administration of human amniotic fluid and the reimplantation of reshaped cartilages. Rabbits were sacrificed at two, eight and 12 weeks after operation. RESULTS: Numerical scores for the right perichondrial bed were significantly higher for group 2 compared to group 1 ( P < 0.05). But the difference was not significant for the left perichondrial bed ( P > 0.05). The diameter of chondrogenesis also did not differ significantly between left and right perichondrial bed for all groups. CONCLUSION: Our study shows that administration of human amniotic fluid into the perichondrial bed increases chondrogenesis in adult rabbits, an important finding which may contribute to improving chest wall flexibility after the surgical correction of pectus excavatum.
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Líquido Amniótico/fisiología , Regeneración Ósea/fisiología , Cartílago/trasplante , Condrogénesis/fisiología , Costillas/cirugía , Animales , Cartílago Articular/fisiología , Modelos Animales de Enfermedad , Humanos , Conejos , Procedimientos de Cirugía Plástica , Trasplante Autólogo , Resultado del TratamientoRESUMEN
OBJECTIVE: The incidence of bronchiectasis has decreased significantly in developed countries due to successful control of childhood infections. However, the surgical treatment of this disease still plays an important role in thoracic surgical practice in underdeveloped and developing countries. The aim of this retrospective study was to present our surgical experience in patients with bronchiectasis, including our surgical treatment strategies and the results of long-term follow-up. METHODS: A retrospective chart review was conducted of 339 patients who underwent surgical resection for bronchiectasis between January 1992 and December 2009. The patients' demographic features, the symptoms, etiologies and resection types, morbidity, mortality and outcomes after surgical management were analyzed. RESULTS: There were 301 (88.8â%) male and 38 (11.2â%) female patients; the average patient age was 22.4 years (range 15-50 years). The most common presenting symptoms were productive cough in 197 (58.1â%) patients. There were 21 (6.2â%) asymptomatic patients. Two hundred and thirty of the 339 patients (67.8â%) had had previous medical therapy before admission to our department. The most common etiology of bronchiectasis was childhood infections in 101 (29.8â%) patients. In most patients, bronchiectasis was found on the left side (n = 225, 66.4â%). Thirty-five patients underwent a second operation for bilateral disease. There were two (0.6â%) early postoperative mortalities including one myocardial infarction and one respiratory insufficiency. Complications occurred in 43 patients (12.7â%). The median follow-up was 13.6 months. Symptoms disappeared in 201 patients (71â%), and 66 patients (23.3â%) experienced an improvement, while 16 patients (5.7â%) continued to be symptomatic. CONCLUSION: Although improvements in medical treatment have resulted in a significant decrease in the number of patients with bronchiectasis, surgical management is still very important in developing countries. Surgical resection can be performed with acceptable morbidity and mortality rates. The aim should be the resection of all involved bronchiectatic sites, even in patients with bilateral disease, if the pulmonary reserve is adequate.
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Bronquiectasia/cirugía , Neumonectomía , Adolescente , Adulto , Bronquiectasia/complicaciones , Bronquiectasia/diagnóstico , Bronquiectasia/etiología , Bronquiectasia/mortalidad , Tos/etiología , Países en Desarrollo , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Registros Médicos , Persona de Mediana Edad , Neumonectomía/métodos , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del Tratamiento , Turquía/epidemiologíaRESUMEN
Haemophiliacs and their families consider that circumcision is a very important step to become a member of society and it is a social obligation for men in Turkey. Although bleeding risk is high, almost all haemophiliacs would like to be circumcised in Turkish society. The aim of this study was to evaluate our experience in circumcision of haemophilia patients and define efficacy, safety and complication rates of our protocol, called 'Izmir protocol'. In this study, we retrospectively reviewed medical records of 50 patients with haemophilia who underwent circumcision at our hospital according to Izmir protocol between 1996 and 2009. Oral tranexamic acid and fibrin glue were used in all children. One hour before the operation, first dose of factor concentrate was given. After reaching a plasma factor level of around 90-100%, the prepuce was incised circumferentially and excised using Gomco clamp or open technique under general anaesthesia. Intermittent injections of factor concentrate were given every 12 for 48 h. While the first two doses were given at higher amount to achieve or continue plasma factor level at 90-100%, in the last three doses, the aim was to maintain the plasma factor level at 50-60%. Forty-eight hours after the circumcision, patients were discharged. Three patients (6%) showed bleeding complication and all were resolved easily. All had at least one excuse from the protocol (Lower doses of factor concentrates was used in 2, tranexamic acid was not used in 2). Izmir protocol is safe, cheap and easy to carry out.
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Circuncisión Masculina , Hemofilia A/complicaciones , Hemofilia B/complicaciones , Antifibrinolíticos/uso terapéutico , Pérdida de Sangre Quirúrgica/prevención & control , Niño , Preescolar , Circuncisión Masculina/efectos adversos , Circuncisión Masculina/métodos , Factor IX/análisis , Factor IX/uso terapéutico , Factor VIII/análisis , Factor VIII/uso terapéutico , Adhesivo de Tejido de Fibrina/uso terapéutico , Hemofilia A/tratamiento farmacológico , Hemofilia B/tratamiento farmacológico , Hemorragia/epidemiología , Humanos , Incidencia , Lactante , Masculino , Estudios Retrospectivos , Ácido Tranexámico/uso terapéutico , TurquíaRESUMEN
This report evaluates the haemostatic efficacy of recombinant factor VIIa (rFVIIa) and activated prothrombin complex concentrate (APCC) in patients with haemophilia and high responding inhibitors who underwent major and minor surgery. Data pertaining to surgeries from 2001 to 2009 at a single centre were retrospectively analysed. During this period, 53 surgical procedures were performed in 30 haemophiliacs with high responding inhibitors. Mean age was 16.2±9.4 years. Eleven major surgeries in 4 patients, 41 radioisotope synovectomies (RS) and one circumcision classified as minor surgery in 28 patients were performed. Among the major surgery procedures, four were treated with rFVIIa, five with APCC and two with sequential use of APCC and rFVIIa. We used rFVIIa at the dosage of 80-120 µg kg(-1) every 2 h and APCC 100 IU kg(-1) every 12 h for the major surgery. When performing RS, we used rFVIIa in 18 patients with 26 target joints and APCC in 9 patients with 15 target joints. Three consecutive doses of rFVIIa (90 µg kg(-1) ) were used at 2-h intervals followed by additional three doses at 6-h intervals. The initial dose of APCC was 75 IU kg(-1) followed by a second and third dose of 50 IU kg(-1) at 12-h intervals. APCC and rFVIIa demonstrated excellent efficacy in our major and minor surgical interventions [100% (22/22) and 94% (31/33), respectively]. We had only two bleeding complications with rFVIIa. There were no thromboembolic complications. APCC and rFVIIa provide an effective and safe first line haemostatic therapy for inhibitor-positive haemophiliacs, allowing both major and minor surgery to be successfully performed.
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Factores de Coagulación Sanguínea/uso terapéutico , Pérdida de Sangre Quirúrgica/prevención & control , Factor VIIa/uso terapéutico , Hemofilia A/tratamiento farmacológico , Hemofilia A/cirugía , Hemostáticos/uso terapéutico , Adolescente , Adulto , Inhibidores de Factor de Coagulación Sanguínea/análisis , Niño , Preescolar , Hemostasis Quirúrgica , Humanos , Proteínas Recombinantes/uso terapéutico , Estudios Retrospectivos , Turquía , Adulto JovenRESUMEN
Development of inhibitors to infused factor concentrates represents a major clinical and economic challenge in the treatment of haemophilic patients. It has been shown that a delay in initiation of treatment leads to requirement of a larger number of injections to stop the bleeding but this has never been formally linked to costs associated with the bleeding. The objectives of this study were to assess the relationship between time to initiation of NovoSeven and total costs, number of doses administered and time to bleeding resolution in mild to moderate bleeding episodes. Data on time to treatment initiation, time to bleeding resolution and on all resource use related to the bleeding were extracted from medical records in Turkey for 129 bleeding episodes. Regression analysis was used to assess the impact of time to treatment on outcomes. Longer time to treatment initiation increased both total costs associated with the bleeding, the number of doses needed and the time to bleeding resolution. Treatment in hospital was associated with significantly longer time to treatment, higher costs and longer time to bleeding resolution as compared with home treatment or outpatient treatment. When controlling for other bleeding characteristics, the cost of bleedings treated in hospital was more than 150% higher. This study shows that treatment with NovoSeven should be initiated as soon as possible after the onset of bleeding in order to minimize costs and optimize outcomes. Home treatment reduces time to treatment initiation and also reduces costs related to the bleeding.
Asunto(s)
Factor VIIa/economía , Costos de la Atención en Salud , Hemofilia A/economía , Hemofilia B/economía , Hemorragia/economía , Adolescente , Adulto , Niño , Factor VIIa/uso terapéutico , Hemofilia A/tratamiento farmacológico , Hemofilia B/tratamiento farmacológico , Hemorragia/tratamiento farmacológico , Humanos , Proteínas Recombinantes/economía , Proteínas Recombinantes/uso terapéutico , Análisis de Regresión , Estudios Retrospectivos , Factores de Tiempo , Adulto JovenRESUMEN
Radioisotope synovectomy (RS) is defined as the intra-articular injection of radioisotopic agents with the aim of fibrosis on hypertrophic synovium in the target joint. The aim of this study was to investigate genotoxic effects on lymphocytes and malign transformation induced by Yttrium(90) (Y(90)) and Rhenium(186) (Re(186)) in children with haemophilia undergone RS. Forty haemophilia patients were enrolled. The mean age was 16.4 +/- 6.2 years (range: 8-40). Y(90) was used for knees, Re(186) was used for other joints. For safety, cytogenetic analysis was performed to determine potential chromosomal changes after RS procedure at three different time points as prior to procedure, 3rd day and 90th day. For the stimulation of chromosomal breakages, diepoxybutane was used (DEB test). Chromosomal breakages (CBs) were found in 23 patients (67.6%) prior to RS. We have found CBs additionally in nine of 11 patients who had no CBs prior to RS after 3 days of radioisotope exposure. At that time, the patients who had CBs were 29 (85.2%). At day 90, only 21 patients revealed (61.7%) CBs. The mean frequency of CBs slightly but not significantly increased in the 3rd day. However, there was a significant decreasing trend between 3rd and 90th days. Radioisotope synovectomy with Y(90) and Re(186) does not seem to induce the genotoxic effects significantly on peripheral blood lymphocytes. However, CBs even after one year in the re-evaluation of four patients, significant decrease in the number of CBs between the 3rd and 90th days and de novo CBs after exposure may be accepted as warning signals for young population. It should also be pointed out that families and patients be informed properly related with historical and potential dangers of radioisotopic agents.
Asunto(s)
Rotura Cromosómica , Hemofilia A/genética , Hemofilia A/radioterapia , Hemofilia B/genética , Hemofilia B/radioterapia , Radioisótopos/efectos adversos , Radiofármacos/efectos adversos , Adolescente , Adulto , Niño , Femenino , Hemartrosis/prevención & control , Hemartrosis/radioterapia , Hemofilia A/complicaciones , Hemofilia B/complicaciones , Humanos , Inyecciones Intraarticulares , Linfocitos/efectos de la radiación , Masculino , Estudios Prospectivos , Radioisótopos/uso terapéutico , Radiofármacos/uso terapéutico , Renio/efectos adversos , Transformación Genética , Adulto Joven , Radioisótopos de Itrio/efectos adversosRESUMEN
Extra-adrenal paragangliomas are uncommon tumors arising from neuroectodermal-derived paraganglionic tissue. There are very few case reports on primary pulmonary paraganglioma in the literature. We present the case of a 21-year-old man who was treated with chemotherapy for Hodgkin's lymphoma. Only a partial response was noted so he underwent additional chemotherapy and involved field radiotherapy. PET-CT showed pathological activity in the lung parenchyma. Subsequent bronchoscopic biopsy showed paraganglioma and the patient underwent a left lower lobectomy.