RESUMO
In postmenopausal osteoporotic women in ACTIVE, abaloparatide reduced fracture risk and increased areal bone mineral density (BMD) more than teriparatide at the hip and wrist. DXA-based 3D modeling showed significantly greater increases in hip cortical volumetric BMD with abaloparatide versus teriparatide. This may explain differences reported in aBMD by DXA. INTRODUCTION: In ACTIVE, abaloparatide (ABL) increased bone mineral density (BMD) shown by dual-energy X-ray absorptiometry (DXA) while reducing fracture incidence in postmenopausal osteoporotic women. Changes in DXA BMD with ABL, 80 µg, were significantly greater than with open-label teriparatide (TPTD), 20 µg, at cortical sites including total hip, femoral neck, and 1/3 distal radius. The purpose of this study was to better understand the relative effects of ABL and TPTD on cortical and cancellous compartments in the proximal femur. METHODS: Hip DXA images from a subset of randomly selected patients in the ACTIVE trial (n = 250/arm) were retrospectively analyzed using three-dimensional modeling methods (3D-SHAPER software) to evaluate changes from baseline at months 6 and 18. RESULTS: Similar significant increases in trabecular volumetric BMD (vBMD, + 9%) and cortical thickness (+ 1.5%) were observed with ABL and TPTD by 3D-DXA at 18 months. In contrast, only ABL significantly increased cortical vBMD versus baseline (+ 1.3%), and changes in both cortical vBMD and cortical surface BMD were significantly greater with ABL versus TPTD. In the TPTD group, changes in cortical vBMD were inversely correlated with changes in serum CTX (carboxy-terminal telopeptide of type I collagen) and PINP (procollagen type I N-terminal propeptide), suggesting that higher bone turnover may have attenuated cortical gains. CONCLUSION: These results suggest previously reported differences in areal BMD increases between ABL and TPTD may be due to differential effects on cortical vBMD. Further studies are warranted to investigate how these differences affect therapeutic impact on hip strength in postmenopausal women with osteoporosis.
Assuntos
Osteoporose Pós-Menopausa , Teriparatida , Absorciometria de Fóton , Densidade Óssea , Feminino , Humanos , Osteoporose Pós-Menopausa/tratamento farmacológico , Proteína Relacionada ao Hormônio Paratireóideo , Estudos Retrospectivos , Teriparatida/farmacologia , Teriparatida/uso terapêuticoRESUMO
We characterized patients initiating abaloparatide (ABL), teriparatide (TPTD), or denosumab (DMAB) in a real-world clinical setting from a large medical and pharmacy claims database. Differences were noted in sex, age, pathologic fractures, comorbidity index, and prior bisphosphonate use for patients initiating ABL and TPTD compared with those receiving DMAB. INTRODUCTION: To characterize patients initiating abaloparatide (ABL), teriparatide (TPTD), or denosumab (DMAB) treatment in a real-world clinical setting. METHODS: Patients aged ≥ 18 years initiating ABL, TPTD, or DMAB between May 1, 2017, and September 24, 2018 (without receiving the same drug in the previous 12 months), were identified using the OM1 Data Cloud, which contains medical and pharmacy claims from approximately 200 million US patients. The index date was the date of initial prescription or dispensing for ABL, TPTD, or DMAB during the study period. RESULTS: During the study period, 2666 patients initiated ABL, 9210 TPTD, and 116,718 DMAB. Mean age (standard deviation) was 69.2 (10.6) years for the ABL cohort, 68.6 (11.3) for TPTD, and 72.1 (10.2) for DMAB (P < 0.001; ABL vs DMAB). Proportionally more patients initiating ABL were female (95.2% ABL, 86.9% TPTD, and 91.3% DMAB, P < 0.001 ABL vs TPTD or DMAB). Nearly twice as many patients initiating ABL (19.1%) and TPTD (18.8%) had a previous pathologic/fragility fracture vs DMAB (9.6%; P < 0.001 ABL vs DMAB). Fewer patients initiating ABL (36.3%) or TPTD (39.7%) had Charlson comorbidity index of ≥ 2 vs DMAB (48.4%; P < 0.001 ABL vs DMAB). Before initiating ABL, TPTD, or DMAB, 44.3%, 33.8%, and 33.9% of patients had prior osteoporosis treatment, respectively. Bisphosphonate use was more common before initiating ABL (19.2%) or TPTD (19.6%), than before initiating DMAB (16.6%; P < 0.001 ABL vs DMAB). CONCLUSIONS: Patients initiating ABL and TPTD differed in sex, age, pathologic fractures, comorbidity index, and prior bisphosphonate use compared with those initiating DMAB.
Assuntos
Conservadores da Densidade Óssea , Osteoporose Pós-Menopausa , Idoso , Densidade Óssea , Conservadores da Densidade Óssea/uso terapêutico , Denosumab/uso terapêutico , Feminino , Humanos , Lactente , Masculino , Medicare , Proteína Relacionada ao Hormônio Paratireóideo , Teriparatida/uso terapêutico , Estados Unidos/epidemiologiaRESUMO
This study expands on previous findings that hip fracture rates may no longer be declining. We found that age- and sex-adjusted fracture rates in the US plateaued or increased through mid-2017 in a population of commercially insured and Medicare Advantage health plan enrollees, in contrast to a decline from 2007 to 2013. INTRODUCTION: The purpose of this study was to evaluate fracture trends in US commercial and Medicare Advantage health plan members aged ≥ 50 years between 2007 and 2017. METHODS: Retrospective analysis of the Optum Research Database from January 1, 2007, to May 31, 2017. RESULTS: Of 1,841,263 patients identified with an index fracture, 930,690 were case-qualifying and included in this analysis. The overall age- and sex-adjusted fracture rate decreased from 14.67/1000 person-years (py) in 2007 to 11.79/1000 py in 2013, followed by a plateau for the next 3 years and then an increase to 12.50/1000 py in mid-2017. In females aged ≥ 65 years, fracture rates declined from 27.49/1000 py in 2007 to 22.08/1000 py in 2013, then increased to 24.92/1000 py in mid-2017. Likewise, fracture rates in males aged ≥ 65 years declined from 2007 (12.00/1000 py) to 2013 (10.72/1000 py), then increased to 12.04/1000 py in mid-2017. The age- and sex-adjusted fracture rates for most fracture sites declined from 2007 to 2013 by 3.7% per year (P = 0.310). CONCLUSIONS: Following a consistent decline in fracture rate from 2007 to 2013, trends from 2014 to 2017 indicate fracture rates are no longer declining and, for some fracture types, rates are rising.
Assuntos
Fraturas do Quadril , Fraturas por Osteoporose , Adolescente , Idoso , Feminino , Fraturas do Quadril/epidemiologia , Humanos , Incidência , Masculino , Programas de Assistência Gerenciada , Medicare , Fraturas por Osteoporose/epidemiologia , Estudos Retrospectivos , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: The use of opioids in non-cancer-related pain following skeletal trauma is controversial due to the presumed risk of dose escalation and dependence. We therefore examined the pattern of opioid prescriptions, that is, those actually dispensed, in patients with femoral shaft fractures. METHODS: We analysed data from the Swedish National Hospital Discharge Register and the Swedish Prescribed Drug Register between 2005 and 2008. RESULTS: We identified 1471 patients with isolated femoral shaft fractures. The median age was 75 (16-102) years and 56% were female. In this cohort, 891 patients (61%) received dispensed opioid prescriptions during a median follow-up of 20 months (interquartile range 11-32). In the age- and sex-matched comparison cohort (7339 individuals) without fracture, 25% had opioid prescriptions dispensed during the same period. The proportions of patients receiving opioid analgesics at 6 and 12 months after the fracture were 45% (95% CI 42-49) and 36% (32-39), respectively. The median daily morphine equivalent dose (MED) was between 15 and 17 mg 1-12 months post-fracture. After 3 months, less than 5% used prescription doses higher than 20 mg MED per day. Older age (≥ 70 compared with < 70 years) was a significant predictor of earlier discontinuation of opioid use (Hazard ratio [HR] 1.9). CONCLUSION: A notable proportion of patients continued to receive dispensed prescriptions for opioids for over 6 months (45%) and more than a third of them (36%) continued treatment for at least 12 months. However, the risk of dose escalation seems to be small in opioid-naïve patients.
Assuntos
Analgésicos Opioides/uso terapêutico , Fraturas do Fêmur/complicações , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Prescrições de Medicamentos , Uso de Medicamentos , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Padrões de Prática Médica , Fatores Sexuais , Suécia/epidemiologia , Adulto JovemRESUMO
There are genetically determined differences in susceptibility to arthritis among inbred rat strains. The aim of the present study was to elucidate phenotypical differences, by determining expression of TNF and IL-1beta, two pivotal mediators of arthritis, in the highly arthritis-prone Dark Agouti (DA) rat compared to that of two arthritis-resistant rat strains, the major histocompatibility complex-homologous Piebald-Viral-Glaxo (PVG.1AV1) rat and the Brown Norway (BN) rat, assessed by immunohistochemistry. We demonstrate a distinct difference in articular cartilage, with chondrocytes expressing IL-1beta, not TNF, in the highly arthritis-prone DA rat as opposed to the two arthritis-resistant BN or PVG.1AV1 rat strains, where no cytokine expression was documented. The results were otherwise congruent among the rat strains. We observed TNF- and IL-1beta-expressing cells within the synovial lining layer in all rat strains. Other tissues studied, auricular cartilage as well as muscle, lung, thyroid gland and kidney tissue, were devoid of cytokine expression. Constitutional expression of IL-1beta in chondrocytes might facilitate initiation and perpetuation of inflammation. This may offer one explanation of why erosive arthritides are so easily induced in the DA rat and also support the hypothesis that articular chondrocytes may themselves play a major role in cartilage matrix degradation.
Assuntos
Artrite Experimental/imunologia , Artrite Reumatoide/imunologia , Cartilagem Articular/imunologia , Interleucina-1beta/biossíntese , Animais , Artrite Experimental/genética , Artrite Reumatoide/genética , Doenças Autoimunes/genética , Doenças Autoimunes/imunologia , Predisposição Genética para Doença , Imuno-Histoquímica , Interleucina-1beta/genética , Tecido Linfoide/imunologia , Ratos , Organismos Livres de Patógenos Específicos , Membrana Sinovial/imunologia , Fator de Necrose Tumoral alfa/biossíntese , Fator de Necrose Tumoral alfa/genéticaRESUMO
OBJECTIVES: To describe the overall use and temporal trends in orthopaedic upper limb surgery associated with RA on a nation wide basis in Sweden between 1998 and 2004. METHODS: Data for all inpatient visits during 1998-2004 for patients older than 18 yrs with RA-related diagnoses were extracted from the Swedish National Hospital Discharge Registry (SNHDR). The SNHDR prospectively collects data on all hospital admissions in Sweden according to the International Classification of Diseases (ICD). Data were analysed with respect to orthopaedic surgery of the hand, elbow and shoulder. RESULTS: During the study period, 54,579 individual RA patients were admitted to a Swedish hospital and 9% of these underwent RA-related surgery of the upper limbs. The RA patient cohort underwent a total of 8251 RA-related upper limb surgical procedures. The hand (77%) was most frequently operated on, followed by the shoulder (13%) and the elbow (10%). There was a statistically significant decrease of 31% for all admissions associated with RA-related upper limb surgery during 1998-2004 (P = 0.001). Some 10% of all RA-related upper limb surgery was due to total joint arthroplasties (TJAs), mostly for the elbow (59%). During 1998-2004, all TJAs, elbow-TJAs and shoulder-TJAs had a stable occurrence. In contrast, the overall numbers of hand-TJAs significantly increased (P = 0.009). CONCLUSIONS: Rates of RA-related upper limb surgery decreased and TJAs had a stable occurrence in Sweden during 1998-2004. The findings of this study may reflect trends in disease management and health outcomes of RA patients in Sweden.
Assuntos
Artrite Reumatoide/cirurgia , Extremidade Superior/cirurgia , Adulto , Idoso , Artrite Reumatoide/epidemiologia , Artroplastia de Substituição/estatística & dados numéricos , Articulação do Cotovelo/cirurgia , Feminino , Articulação da Mão/cirurgia , Hospitalização/estatística & dados numéricos , Humanos , Tempo de Internação/estatística & dados numéricos , Tempo de Internação/tendências , Masculino , Pessoa de Meia-Idade , Procedimentos Ortopédicos/estatística & dados numéricos , Procedimentos Ortopédicos/tendências , Articulação do Ombro/cirurgia , Suécia/epidemiologiaRESUMO
OBJECTIVES: To evaluate the effects of ankle/hindfoot arthrodesis in rheumatoid arthritis (RA) patients on gait pattern of the knee and hip. METHODS: In this prospective follow-up study, 14 RA patients scheduled for ankle/hindfoot arthrodesis (talo-calcaneal, talo-navicular, calcaneo-cuboid and/or talo-crural joints) and 14 age- and sex-matched healthy controls were included. Three-dimensional gait analyses of joint angles, moments and work were performed at the index operation and after 13 months of follow-up. Each patient underwent clinical assessments of pain while walking, overall evaluation of disease activity, Health Related Quality of Life Questionnaire (EQ-5D), activity limitations, maximum walking distance, difficulty with walking surface and gait abnormality. For comparisons of pre- vs post-operative conditions, Wilcoxon's matched pairs test and Friedman ANOVA by rank test were used. RESULTS: At follow-up after ankle/hindfoot fusion surgery, RA patients demonstrated a statistically significant improvement in mean range of joint motions, moments and work in the overlying joints such as the knee and hip. Moreover, there was significantly less pain, disease activity, activity limitation, difficulty with walking surface and gait abnormality. EQ-5D and maximum walking distance were also significantly improved at follow-up. CONCLUSIONS: Our results demonstrate that ankle/hindfoot arthrodesis in RA is an effective intervention to reduce pain and to improve Health Related Quality of Life and functional ability. Moreover, the overlying leg joints experience an improvement in joint motion, muscle-generated joint moments and work during walking. Three-dimensional gait analysis may assist future investigations of the effects of orthopaedic surgery on functional mobility in RA to prevent irreversible disablement.
Assuntos
Articulação do Tornozelo/cirurgia , Artrite Reumatoide/cirurgia , Artrodese/métodos , Articulações do Pé/cirurgia , Marcha , Adulto , Idoso , Artrite Reumatoide/fisiopatologia , Artrite Reumatoide/reabilitação , Fenômenos Biomecânicos , Articulação do Quadril/fisiopatologia , Humanos , Articulação do Joelho/fisiopatologia , Pessoa de Meia-Idade , Estudos Prospectivos , Amplitude de Movimento Articular , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
OBJECTIVES: To analyse changes in the rates of hospital admission and use of orthopaedic surgery to the lower limbs in Swedish patients with rheumatoid arthritis between 1987 and 2001. METHODS: Data for all rheumatoid patients admitted to hospital between 1987 and 2001 were abstracted from the Swedish National Hospital Discharge Register (SNHDR). The data in the register are collected prospectively, recording all inpatient admissions throughout Sweden. The SNHDR uses the codes for diagnoses at discharge and surgical procedures according to the Swedish version of the International Classification of Diseases (ICD). RESULTS: In all, 49,802 individual patients with rheumatoid arthritis were identified, accounting for 159,888 inpatient visits. Hospital admissions for rheumatoid arthritis decreased by 42% (p<0.001) during the period 1987 to 2001. Twelve per cent of all admissions were for a rheumatoid arthritis related surgical procedure to the lower limbs; those admissions decreased markedly (by 16%) between 1987 and 1996, and by 12% between 1997 and 2001, as did the overall number of rheumatoid arthritis related surgical procedures to the lower limbs during both time periods. Between 1997 and 2001, 47% of all rheumatoid arthritis related surgical procedures were total joint arthroplasties. There was an overall trend towards reduced length of hospital stay after orthopaedic surgery to the lower limbs during the study period. CONCLUSIONS: Rates of hospital admission and rheumatoid arthritis related surgical procedures to the lower limbs in Swedish patients with rheumatoid arthritis decreased between 1987 and 2001. This may reflect trends in disease severity, management, and health outcomes of this disease in Sweden.
Assuntos
Artrite Reumatoide/cirurgia , Artroplastia/estatística & dados numéricos , Extremidade Inferior/cirurgia , Fatores Etários , Idoso , Artrite Reumatoide/epidemiologia , Artroplastia/tendências , Feminino , Hospitalização/estatística & dados numéricos , Hospitalização/tendências , Humanos , Tempo de Internação/estatística & dados numéricos , Tempo de Internação/tendências , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Fatores Sexuais , Suécia/epidemiologiaRESUMO
Bone loss represents a major unsolved problem in rheumatoid arthritis (RA). The receptor activator of nuclear factor-kappaB ligand (RANKL) is essential for the development and activation of osteoclasts, which are key mediators of bone erosions. This study was performed to determine temporal and spatial expression of RANKL compared with the potentially destructive cytokine interleukin-1beta (IL-1beta), related to progression of synovitis and joint destruction in collagen-induced arthritis (CIA), a model of RA. CIA was induced in dark agouti (DA) rats, and tissue specimens were obtained for immunohistochemical analyses at various time points before and after disease onset. Arthritis was monitored visually, and joint pathology was examined histologically. No disease-preceding expression of RANKL was detected. However, a marked increase of both RANKL- and IL-1beta-expressing cells correlated with the progression of synovial inflammation and clinical disease severity. Abundant and concomitant expression of these cytokines was detected at sites of bone erosion, where a colocalization by osteoclast-like multinuclear tartrate-resistant acid phosphatase (TRAP)+ cells was noted. In contrast to the paucity of RANKL expression in cartilage, an abundant expression of IL-1beta was demonstrated, particularly in superficial cartilage layers. These data support the hypothesis that RANKL and IL-1beta are central contributors to joint destruction in CIA.
Assuntos
Artrite Experimental/imunologia , Artrite Experimental/patologia , Artrite Reumatoide/imunologia , Artrite Reumatoide/patologia , Proteínas de Transporte/metabolismo , Interleucina-1/metabolismo , Glicoproteínas de Membrana/metabolismo , Animais , Osso e Ossos/patologia , Cartilagem Articular/patologia , Citocinas/metabolismo , Masculino , Ligante RANK , Ratos , Membrana Sinovial/patologia , Sinovite/metabolismo , Sinovite/patologiaRESUMO
OBJECTIVE: To determine if intrapatient comparisons between prediagnosis and subsequent radiological progression could be used to assess effects of DMARDs in an RA inception cohort. PATIENTS AND METHODS: 149 non-randomised patients with newly diagnosed RA in four groups were analysed: patients treated with (a) methotrexate (n = 56); (b) sulfasalazine (n = 55); (c) auranofin (n = 19); and (d) controls who were poor treatment responders (n = 19). Radiographs were quantified using the Larsen erosion score. The prediagnosis radiological progression from the onset of RA symptoms to diagnosis was calculated and compared with the observed progression rate during the first year after diagnosis while receiving DMARD treatment. RESULTS: Mean (SD) disease duration from onset of symptoms until diagnosis was 6.7 (4.0) months. Mean (SD) baseline Larsen score was 13.2 (9.3), giving a mean (SD) estimated prediagnosis progression rate of 23.6 (12.4) Larsen score units/year. Control and auranofin groups showed radiological progression after diagnosis similar to the progression predicted by prediagnosis progression rates. Patients receiving methotrexate or sulfasalazine showed a marked reduction (71% and 73%, respectively; p<0.001) in radiographic progression compared with prediagnosis progression. CONCLUSIONS: Prediagnosis rates of radiological progression can be used quantitatively to obtain information on the potential efficacy of DMARDs, and indicate that methotrexate and sulfasalazine, but not auranofin, significantly retard radiographic damage in the first year after diagnosis.
Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/diagnóstico por imagem , Artrite Reumatoide/tratamento farmacológico , Adulto , Idoso , Auranofina/uso terapêutico , Progressão da Doença , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Radiografia , Índice de Gravidade de Doença , Sulfassalazina/uso terapêutico , Resultado do TratamentoRESUMO
OBJECTIVE: The efficacy of DMARD therapy in rheumatoid arthritis (RA) can be judged by radiological analysis. This study aimed to determine the time-dependent progression of joint damage, acute-phase response, and rates of radiologic progression in early DMARD-treated RA patients over 10 years. PATIENTS AND METHODS: We evaluated outpatient records, and radiographs of hands and feet of 54 early RA patients on DMARDs for 10 years. Radiographs were quantified by the Larsen method using recently developed quantification software. RESULTS: Radiological damage attenuated, with disease progression from baseline to Year 10 [correlation coefficient (r)=0.95, probability (p)<0.001]. Radiographic scores progressed more rapidly during the first 5 years than thereafter. Cumulative erythrocyte sedimentation rate (ESR) was strongly correlated with radiological progression (p<0.001, r=0.88). CONCLUSION: Our findings reveal a higher amount of radiographic RA progression during the first years of DMARD treatment. Thus, our data provide strong evidence for the importance of both early DMARD therapy and continuous radiographic assessments in RA.
Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/patologia , Artropatias/diagnóstico por imagem , Artropatias/etiologia , Adulto , Artrite Reumatoide/complicações , Estudos de Coortes , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Radiografia , Valores de ReferênciaRESUMO
OBJECTIVES: Disease-modifying anti-rheumatic drugs (DMARDs) decrease clinical signs and symptoms in rheumatoid arthritis (RA). However, radiographic changes sometimes continue to accrue despite effective suppression of clinical symptoms by therapy. The objective of this study was to identify whether successful clinical disease-control in a Swedish early RA-inception cohort of patients led to an attenuation of radiological progression. PATIENTS AND METHODS: We analysed clinical data and radiographs of 95 patients who were on a stable treatment regimen [methotrexate (MTX), sulfasalazine (SSZ), oral gold (AUR)] or who had changed between different DMARDs during the 2-year observation period [multiple therapy failures (mTF)]. Radiographs were quantified using the modified Larsen score and 'X-Ray RheumaCoach' software. RESULTS: Clinical measures improved markedly (p <0.001) from baseline to year 2 under AUR, MTX, and SSZ therapy but not in the mTF group. Similar levels of disease control were seen for each DMARD. During this period, patients treated with AUR had a deltaLarsen score (+ 14.5+/-1.3) similar to mTF patients (+ 15.8+/-1.1) but greater than patients on MTX (+8.6+/-0.8) or SSZ (+9.1+/-0.8). CONCLUSIONS: This study confirms that radiological progression occurs despite a clinically acceptable disease control, but also shows that, given the same degree of clinical disease control, radiological progression can be different for different DMARDs.
Assuntos
Antirreumáticos/administração & dosagem , Artrite Reumatoide/diagnóstico por imagem , Artrite Reumatoide/tratamento farmacológico , Adulto , Idoso , Estudos de Coortes , Progressão da Doença , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Tiomalato Sódico de Ouro/uso terapêutico , Humanos , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Medição da Dor , Prognóstico , Radiografia , Sistema de Registros , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Sulfassalazina/uso terapêutico , Suécia , Resultado do TratamentoRESUMO
INTRODUCTION: The purpose of this retrospective analysis is to evaluate whether the combination of surgery and radiation therapy in patients with aggressive fibromatosis influences the therapeutic outcome. METHOD: Clinical, radiological and pathological results of 23 consecutive cases with histologically proven aggressive fibromatosis were retrospectively analyzed. The median follow-up was 59 months. RESULTS: Twelve patients received surgery alone for their first treatment, 10 patients had a combination of surgery and radiotherapy and 1 patient had radiochemotherapy. Of 23 patients 14 (63%) had one or more local recurrences and 9 (39%) were recurrence-free. The patients received a total of 50 treatments: 29/50 (58%) treatments were followed by a local recurrence and 21/50 (42%) were without relapse. Twenty-nine treatments with local recurrence consisted of 25/29 (86%) surgical treatments, 3/29 (10%) combinations of surgery and radiation therapy, and 1/29 (3%) radiochemotherapy. Of the patients who had only surgery for their first treatment, after one year 8 of 12 (66%) and after 5 years all patients had a local recurrence. In the group with surgery and radiotherapy, there was no recurrence after 1 year and 1 recurrence after 5 years (p = 0.0001). CONCLUSION: We recommend a complete tumor resection, without mutilating the patient. Radiation therapy in combination with surgery in contrast to surgery alone is an efficient treatment option for reducing local recurrence.
Assuntos
Fibromatose Agressiva/cirurgia , Adolescente , Adulto , Criança , Terapia Combinada , Intervalo Livre de Doença , Feminino , Fibromatose Agressiva/radioterapia , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/radioterapia , Recidiva Local de Neoplasia/cirurgia , Radioterapia AdjuvanteRESUMO
Plasma renin activity (PRA), active renin (AR), prorenin, and angiotensinogen were assessed in 486 hypertensive and 175 normotensive subjects with a sodium intake of 10 or 200 mEq/d during supine and upright posture and after infusion of angiotensin II. PRA and AR levels were compared in hypertensive subjects in each condition. With low sodium intake, particularly while upright, there was a significant correlation between PRA and AR. In upright subjects with low sodium intake who had a PRA of 2.4 ng/mL per hour or less (1.85 nmol.L-1.h-1 or less), the correlation was also strong. With high sodium intake, the correlation was weaker. With intermediate sodium excretion, the correlation was intermediate. Prorenin was less predictive of PRA than was AR, and angiotensinogen had a marginal role. Using PRA during sodium restriction while upright as the standard for determining renin status, the precision of AR for predicting renin status was excellent. AR may be used for surrogate assessment of the renin-angiotensin system activity when the system is activated.
Assuntos
Hipertensão/sangue , Sistema Renina-Angiotensina/fisiologia , Renina/sangue , Cloreto de Sódio na Dieta , Angiotensina II/farmacologia , Angiotensinogênio/sangue , Precursores Enzimáticos/sangue , Humanos , Hipertensão/etiologia , Ensaio Imunorradiométrico , Renina/imunologia , Reprodutibilidade dos Testes , Decúbito DorsalRESUMO
A recent 8-week, double-masked, placebo-controlled, 3 x 4 factorial-design study demonstrated that enalapril-felodipine extended-release (ER) combinations had statistically significant additive effects for reducing both sitting systolic blood pressure (SiSBP) and sitting diastolic blood pressure (SiDBP) and were generally well tolerated in hypertensive patients with SiDBPs ranging from 95 to 115 mm Hg. The present open-label study was undertaken to assess the long-term efficacy, tolerability, and safety of such combinations. Patients from the factorial study were eligible for the 1-year, open-label extension. Initially, all patients received enalapril 5 mg-felodipine ER 2.5 mg once daily; if SiDBP was not controlled (< 90 mm Hg) after 4 weeks of treatment, the dose was titrated upward at 2- to 4-week intervals to a maximum of enalapril 10 mg-felodipine ER 10 mg. Hydrochlorothiazide (HCTZ) 12.5 mg was added to the regimen of patients whose hypertension was not controlled at the highest enalapril-felodipine ER dose. A total of 507 patients were enrolled, of whom 502 were assessable. At their last study visit, 391 (78%) of the assessable patients were receiving only an enalapril-felodipine ER combination. The enalapril-felodipine ER combinations resulted in mean trough SiDBPs of 85 to 89 mm Hg (decreases of 13 to 16 mm Hg from baseline) and SiSBPs of 137 to 140 mm Hg (decreases of 13 to 21 mm Hg). Overall, 407 (81%) of the 502 assessable patients achieved an SiDBP < 90 mm Hg or a reduction from baseline > or = 10 mm Hg (responders); such a response was recorded in 331 patients (66%) taking a combination of enalapril-felodipine ER alone and 76 patients (15%) taking the combination with the addition of HCTZ 12.5 mg. Blood pressure reductions were maintained throughout the treatment period. Drug-related adverse events were relatively infrequent, often transient, usually mild, and apparently not dose related. The most frequently reported drug-related adverse events were edema/swelling, asthenia/fatigue, dizziness, cough, and headache. These results suggest that combination therapy with enalapril-felodipine ER is effective for long-term blood pressure reduction, has an excellent safety profile, and is generally well tolerated. Addition of low-dose HCTZ to the enalapril-felodipine ER combination appears to provide further blood pressure control without increasing drug-related adverse events.
Assuntos
Anti-Hipertensivos/uso terapêutico , Bloqueadores dos Canais de Cálcio/uso terapêutico , Enalapril/uso terapêutico , Felodipino/uso terapêutico , Hipertensão/tratamento farmacológico , Adulto , Idoso , Anti-Hipertensivos/efeitos adversos , Pressão Sanguínea/efeitos dos fármacos , Bloqueadores dos Canais de Cálcio/efeitos adversos , Método Duplo-Cego , Combinação de Medicamentos , Enalapril/efeitos adversos , Felodipino/efeitos adversos , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-IdadeRESUMO
There are anecdotal reports of early cerebrovascular complications occurring in patients with glucocorticoid-remediable aldosteronism (GRA). The issue has never been systematically evaluated. In this study, we retrospectively reviewed the International Registry for GRA to see if there was an association between cerebrovascular complications and GRA. We searched the records of 376 patients from 27 genetically proven GRA pedigrees for premature death or cerebrovascular complications. Each case was subsequently verified through the referring physician, or autopsy reports. The number of complications occurring in patients with proven GRA were compared to GRA negative subjects from the same pedigrees. There were 18 cerebrovascular events in 15 patients with proven GRA (n=167) and none in the GRA negative group (n=194; P<.001). There were an additional 15 events in 15 subjects that were suspected of having GRA based on clinical history. Seventy percent of events were hemorrhagic strokes; the overall case fatality rate was 61%. The mean (+/- SD) age at the time of the initial event was 31.7+/-11.3 years. In total, 48% of all GRA pedigrees and 18% of all GRA patients had cerebrovascular complications, which is similar to the frequency of aneurysm in adult polycystic kidney disease. GRA is associated with high morbidity and mortality from early onset of hemorrhagic stroke and ruptured intracranial aneurysms. Screening for intracranial aneurysm with magnetic resonance angiography is advised for patients with genetically proven GRA.
Assuntos
Hemorragia Cerebral/complicações , Hiperaldosteronismo/complicações , Aneurisma Intracraniano/complicações , Adulto , Idade de Início , Hemorragia Cerebral/epidemiologia , Hemorragia Cerebral/mortalidade , Feminino , Glucocorticoides/uso terapêutico , Humanos , Hiperaldosteronismo/tratamento farmacológico , Aneurisma Intracraniano/epidemiologia , Aneurisma Intracraniano/mortalidade , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
The efficacy and safety of fluvastatin in patients with moderate hypercholesterolemia was evaluated in this open-label, multicenter trial. Patients whose cholesterol did not meet National Cholesterol Education Program guidelines after an 8-week dietary stabilization period underwent a 12-week treatment period. The study population was 1776 patients ranging in age from 18 to 75 years with an average low-density lipoprotein cholesterol level for two visits of 160 to 200 mg/dL. For all patients, the mean serum level of low-density lipoprotein cholesterol showed a decrease of 21% between baseline and week 12 (177.8 +/- 19.0 to 141.0 +/- 22.7 mg/dL). Total cholesterol decreased 14% (263.3 +/- 24.3 to 224.2 +/- 12.9 mg/dL). Triglycerides decreased 14% (183.7 +/- 82.3 to 158.0 +/- 70.1 mg/dL). High-density lipoprotein cholesterol levels increased only slightly (49.7 +/- 12.1 to 51.8 +/- 12.9 mg/dL). Therapy with fluvastatin resulted in few adverse effects. No patient terminated the study prematurely because of laboratory abnormalities, although laboratory values of concern occurred in 0.3% of patients regarding serum glutamic oxaloacetic transaminase and in 0.07% regarding creatine phosphokinase. Fluvastatin is confirmed as effective and safe for the treatment of moderate hypercholesterolemia in the general-practice patient.
Assuntos
Anticolesterolemiantes/uso terapêutico , Inibidores Enzimáticos/uso terapêutico , Ácidos Graxos Monoinsaturados/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipercolesterolemia/tratamento farmacológico , Indóis/uso terapêutico , Adolescente , Adulto , Idoso , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Ácidos Graxos Monoinsaturados/efeitos adversos , Feminino , Fluvastatina , Humanos , Hipercolesterolemia/sangue , Indóis/efeitos adversos , Masculino , Pessoa de Meia-IdadeRESUMO
This multicenter, placebo-controlled, double-blind trial of factorial design evaluated the safety and efficacy of combination treatment with the angiotensin-converting enzyme inhibitor, enalapril, and the vascular selective calcium antagonist felodipine extended release (ER) in patients with essential hypertension. After a 4-week, single-blind placebo baseline period, 707 patients with sitting diastolic blood pressures (BPs) in the range of 95 to 115 mm Hg received placebo, enalapril (5 or 20 mg), felodipine ER (2.5, 5, or 10 mg), or their combinations for an 8-week double-blind treatment period. All doses of enalapril and felodipine ER had a statistically significant (p < 0.05) additive effect in reducing both systolic and diastolic BP. The trough to peak ratios for the combinations ranged from 0.63 (enalapril 5 mg-felodipine ER 2.5 mg) to 0.79 (enalapril 20 mg-felodipine ER 10 mg) and were consistent with effective BP control with 1 dose/day. Patients aged > or = 65 years demonstrated a greater reduction in diastolic BP. Combinations of enalapril-felodipine ER were associated with less drug-induced peripheral edema (4.1%) compared to felodipine ER monotherapy (10.8%). There were no serious drug-related adverse effects observed during the study. In this trial, the combination of enalapril and felodipine ER effectively lowered BP and was generally well tolerated with an excellent safety profile when used in the treatment of hypertension.
Assuntos
Anti-Hipertensivos/uso terapêutico , Bloqueadores dos Canais de Cálcio/uso terapêutico , Enalapril/uso terapêutico , Felodipino/uso terapêutico , Hipertensão/tratamento farmacológico , Idoso , Anti-Hipertensivos/administração & dosagem , Pressão Sanguínea/efeitos dos fármacos , Bloqueadores dos Canais de Cálcio/administração & dosagem , Preparações de Ação Retardada , Relação Dose-Resposta a Droga , Método Duplo-Cego , Quimioterapia Combinada , Enalapril/administração & dosagem , Felodipino/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: To investigate the hematologic and economic advantages of using iron dextran as the sole supplemental agent to safely increase and maintain hematocrit levels and iron availability while optimizing erythropoietin dosing in patients on chronic hemodialysis. DESIGN: Iron dextran 100 mg (2 ml) was administered i.v. slow push, undiluted three times per week, sometime during the last 30 minutes of each hemodialysis treatment, until a total required ml (determined by using the package insert's formula) was attained. Maintenance doses of either 25 or 50 mg per week (dependent upon body weight) were administered ongoing to compensate for dialytic and gastrointestinal blood losses. The analysis duration was 12 months. SAMPLE/SETTING: A prospective analysis was performed on 13 clinically stable hemodialysis outpatients in a rural community hospital-based dialysis facility (mean age 56.4 years ranging from 24-76; sample included 9 males, 4 females). METHODS: The means and medians were calculated for each variable: hematocrit, ferritin, transferrin saturation, and erythropoietin dose. A one-tailed paired student t test was performed on doses of erythropoietin at -1 and 6 months, -1 and 9 months, and -1 and 12 months. Cost per patient of iron dextran loading dose and maintenance, as well as cost savings from actual erythropoietin dose reductions, were calculated at 3, 9, and 12 months. Cost savings reflected the cost of iron dextran. RESULTS: After 6 months on the protocol, erythropoietin doses decreased an average of 3100 units per patient with an 8% increase in hematocrit and 66% and 78% increase in transferrin saturation and ferritin, respectively. Based on averages in actual reduced erythropoietin dosing, a savings of +5,070 per patient per year was realized. CONCLUSIONS: This analysis found the use of iron dextran in the hemodialysis setting to be an effective and economic means to maintain hematocrit values and iron availability while optimizing erythropoietin dosing.
Assuntos
Anemia Ferropriva/tratamento farmacológico , Hematínicos/uso terapêutico , Complexo Ferro-Dextran/uso terapêutico , Diálise Renal/efeitos adversos , Adulto , Idoso , Anemia Ferropriva/etiologia , Redução de Custos , Custos de Medicamentos , Eritropoetina/economia , Feminino , Hematínicos/economia , Humanos , Complexo Ferro-Dextran/economia , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
OBJECTIVES: We examined the antianginal and anti-ischemic effects of oral zatebradine, a direct sinus node inhibitor that has no blood pressure-lowering or negative inotropic effects in patients with chronic stable angina pectoris taking extended-release nifedipine. BACKGROUND: Heart rate reduction is considered an important pharmacologic mechanism for providing anginal pain relief and anti-ischemic action in patients with chronic stable angina, suggesting a benefit for sinus node-inhibiting drugs. METHODS: In a single-blind placebo run-in, randomized double-blind, placebo-controlled, multicenter study, patients already receiving extended-release nifedipine (30 to 90 mg once a day) were randomized to receive zatebradine (5 mg twice a day [n = 64]) or placebo (n = 60). All subjects had reproducible treadmill exercise-induced angina at baseline, and after randomization they performed a serial exercise test 3 h after each dose for 4 weeks. RESULTS: Zatebradine reduced rest heart rate both at 4 weeks ([mean +/- SEM] 12.9 +/- 1.23 vs. 2.3 +/- 1.6 [placebo] beats/min, p < 0.0001) and at the end of comparable stages of Bruce exercise (16.7 +/- 1.2 vs. 3.4 +/- 1.2 [placebo] beats/min, p < 0.0001). Despite the significant effects on heart rate at rest and exercise, there were no additional benefits of zatebradine from placebo baseline in measurements of total exercise duration, time to 1-mm ST segment depression or time to onset of angina. Subjects taking zatebradine also had more visual disturbances as adverse reactions. CONCLUSIONS: Zatebradine seems to provide no additional antianginal benefit to patients already receiving nifedipine, and it raises questions regarding the benefit of heart rate reduction alone as an antianginal approach to patients with chronic stable angina.