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Fibrodysplasia ossificans progressiva (FOP) is a rare disease characterized by heterotopic ossification (HO) in connective tissues and painful flare-ups. In the phase 2 LUMINA-1 trial, adult patients with FOP were randomized to garetosmab, an activin A-blocking antibody (n = 20) or placebo (n = 24) in period 1 (28 weeks), followed by an open-label period 2 (28 weeks; n = 43). The primary end points were safety and for period 1, the activity and size of HO lesions. All patients experienced at least one treatment-emergent adverse event during period 1, notably epistaxis, madarosis and skin abscesses. Five deaths (5 of 44; 11.4%) occurred in the open-label period and, while considered unlikely to be related, causality cannot be ruled out. The primary efficacy end point in period 1 (total lesion activity by PET-CT) was not met (P = 0.0741). As the development of new HO lesions was suppressed in period 1, the primary efficacy end point in period 2 was prospectively changed to the number of new HO lesions versus period 1. No placebo patients crossing over to garetosmab developed new HO lesions (0% in period 2 versus 40.9% in period 1; P = 0.0027). Further investigation of garetosmab in FOP is ongoing. ClinicalTrials.gov identifier NCT03188666 .
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Miositis Osificante , Osificación Heterotópica , Adulto , Humanos , Miositis Osificante/tratamiento farmacológico , Miositis Osificante/patología , Tomografía Computarizada por Tomografía de Emisión de Positrones , Osificación Heterotópica/patologíaRESUMEN
OBJECTIVES: To report the impact of continued burosumab treatment on clinical laboratory tests of efficacy, patient-reported outcomes (PROs) and ambulatory function in adults with X-linked hypophosphataemia who continued from a 96-week phase 3 study into a 48-week open-label extension. METHODS: Eligible participants from the phase 3 study continued on the burosumab regimen received at the end of the phase 3 study for a further 48 weeks (n=31). Some (not all) received compassionate burosumab treatment between the two studies (a period of 6-18 months). The primary efficacy outcome was fasting serum phosphate concentration; secondary outcomes were serum 1,25 dihydroxyvitamin D concentration, renal phosphate reabsorption, PROs and ambulatory function. RESULTS: Improvements in fasting serum phosphate, serum 1,25 dihydroxyvitamin D and renal phosphate reabsorption at 96 weeks were maintained through the 48-week extension. Improvements were also maintained in stiffness and physical function measured using the Western Ontario and McMaster Universities Osteoarthritis Index, pain and fatigue endpoints measuring using the Brief Pain Inventory short-form and Brief Pain Inventory, respectively, and in ambulatory function (6-Minute Walk Test).A post-hoc exploratory analysis exploring outcomes in participants who discontinued burosumab treatment between the studies (n=7) and those who received at least one dose (n=23) indicated that the benefits of burosumab on clinical laboratory tests of efficacy, PROs and ambulatory function may be lost when treatment is interrupted but recover over time when treatment is reinstated. CONCLUSION: Continued treatment with burosumab appears necessary for sustained clinical benefit. TRIAL REGISTRATION NUMBERS: Phase 3: NCT02526160; open-label extension: NCT03920072.
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Raquitismo Hipofosfatémico Familiar , Adulto , Humanos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Raquitismo Hipofosfatémico Familiar/tratamiento farmacológico , Dolor , FosfatosRESUMEN
OBJECTIVE: Osteoporosis is underdiagnosed and undertreated, although severe complications of osteoporotic fractures, including vertebral fractures, are well known. This study sought to assess the feasibility and results of an opportunistic screening of vertebral fractures and osteoporosis in a large database of lumbar or abdominal CT scans. MATERIAL AND METHODS: Data were analysed from CT scans obtained in 35 hospitals from patients aged 60 years or older and stored in a Picture Archiving and Communication System in Assistance-Publique-Hôpitaux de Paris, from 2007 to 2013. Dedicated software was used to analyse the presence or absence of at least 1 vertebral fracture (VF), and the radiodensity of the lumbar vertebrae was measured Hounsfield Units (HUs). A simulated T-score was calculated. RESULTS: Data were analysed from 152 268 patients [mean age (S.D.) = 73.2 (9.07) years]. Success rates for VF assessment and HUs measurements were 82 and 87%, respectively. The prevalence of VFs was 24.5% and increased with age. Areas under the receiver operating characteristic curves for the detection of VFs were 0.61 and 0.62 for the mean HUs of the lumbar vertebrae and the L1 HUs, respectively. In patients without VFs, HUs decreased with age, similarly in males and females. The prevalence of osteoporosis (sT-score ≤ -2.5) was 23.8% and 36.5% in patients without and with VFs, respectively. CONCLUSION: It is feasible on a large scale to screen for VFs and osteoporosis during opportunistic screening in patients 60 years or older having lumbar or abdominal CT.
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Osteoporosis , Fracturas Osteoporóticas , Fracturas de la Columna Vertebral , Absorciometría de Fotón/métodos , Anciano , Densidad Ósea , Femenino , Humanos , Vértebras Lumbares/diagnóstico por imagen , Masculino , Osteoporosis/complicaciones , Osteoporosis/diagnóstico por imagen , Osteoporosis/epidemiología , Fracturas Osteoporóticas/diagnóstico por imagen , Fracturas Osteoporóticas/epidemiología , Fracturas Osteoporóticas/etiología , Fracturas de la Columna Vertebral/diagnóstico por imagen , Fracturas de la Columna Vertebral/epidemiología , Fracturas de la Columna Vertebral/etiología , Tomografía Computarizada por Rayos X/métodosRESUMEN
This prospective study aimed to analyze determinants that can influence bone mineral density evolution in childhood acute leukemia survivors. Patients included were selected from the long-term follow-up LEA cohort and had dual energy radiograph absorptiometry scan between 10 and 18 years and after the age of 18. All scans were centrally reviewed. Bone mineral density was measured at the lumbar spine, femoral neck, total hip, and whole body, and expressed as z-score. Eighty-nine patients (female 39, lymphoblastic leukemia 68, relapse 25, hematopoietic stem cell transplantation 44, and mean age 15.4 and 20.1 years at the first and second scans, respectively) were studied. The first and second scan z-scores were significantly correlated (P < 10-3). Mean femoral neck and total hip z-scores improved significantly between the first and second scans, whereas no significant evolution occurred at the lumbar spine and whole-body level. On the second evaluation, 14.6% of patients had z-score <-2 at the lumbar spine and 4.3% at the femoral neck level. Gender, type of leukemia, transplantation, relapse, cumulative corticosteroid doses, or growth hormone deficiency did not have any significant impact on z-score variation. Younger age at diagnosis (≤8.5 years) proved an unfavorable risk factor for z-score evolution at the lumbar spine (P = 0.041); the trend did not reach statistical significance for metabolic syndrome (P = 0.054). At the femoral neck, both were associated with unfavorable z-score evolution (P = 0.003 and 0.025, respectively). Patients treated at a younger age and those with metabolic syndrome seem to be at higher risk of bone mineral density decline and should benefit from specific interventions.
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INTRODUCTION: Reports of elevated bone mass (EBM) on routine DXA scanning are not infrequent. However, epidemiological studies of EBM are few in number and definition thresholds variable. The purpose of this study was to assess the prevalence and causes of EBM in the general population referred to a single university hospital - catering for a population of 4 million inhabitants - for DXA scanning. MATERIAL AND METHODS: DXA databases were initially searched for individuals with a bone mineral density (BMD) Z-score ≥+4 at any site in the lumbar spine or hip from April 1st, 2008 to April 30st, 2018. Two Hologic scanners were available at the Lille University Hospital (France). Prevalence of EBM was evaluated, as were causes associated with EBM. RESULTS: At the lumbar spine, 18,229 bone density tests were performed in women and 10,209 in men. At the hip, 17,390 tests were performed in women and 9857 in men. The total number of patients who had at least one bone density test was 14,745, of which 64.2% were female. Of these 14,745 patients, 211 had a Z-score ≥+4 at any site, i.e. a prevalence of 1.43% [1.25%-1.64%]. The DXA scans and medical records of 92 men and 119 women with elevated BMD were reviewed to assess causes. An artefactual cause was found in 164 patients (75%) with EBM (mostly degenerative disease of the spine), and an acquired cause of focal EBM was found in only 2 patients, both of whom had sclerotic bone metastases from prostate cancer. An acquired cause of generalized EBM was found in 32 patients (15%), the vast majority of whom had renal osteodystrophy (n = 11), followed by hematological disorders (n = 9; e.g. myeloproliferative syndromes and mastocytosis) and diffuse bone metastases from solid cancer (n = 5). Of the remaining causes, rare hereditary diseases (e.g. osteopetrosis ) and unexplained EBM were found in 10 and 6 cases respectively. CONCLUSION: The prevalence of EBM (Z-score ≥+4 at any site) was 1.43% [1.25%-1.64%]. In nearly all instances (97.1%) the explanation for EBM could be found in the medical record and through conventional investigations. This study suggests that the main cause of EBM is degenerative disease of the spine. Further studies are needed to differentiate artefactual EBM from hereditary or acquired EBM, and to investigate unexplained EBM. Genetic testing may prove useful in elucidating rare unknown causes.
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Densidad Ósea , Vértebras Lumbares , Absorciometría de Fotón , Femenino , Francia , Humanos , Masculino , PrevalenciaRESUMEN
OBJECTIVE: Sarcopenia has been associated with poor outcomes in various medical and surgical conditions. However, its impact in systemic necrotizing vasculitides (SNV) had never been characterized. We aimed to assess the prevalence, associated factors and prognostic impact of sarcopenia in SNV. METHODS: Patients with SNV were successively included in a prospective longitudinal study assessing comorbidities. At inclusion, we evaluated sarcopenia by assessing skeletal muscle mass index using DXA and muscle strength using handgrip strength. Vasculitis and treatments-related events were recorded and analysed using Cox models. RESULTS: One hundred and twenty patients were included. At inclusion, low handgrip strength (<30 kg for men and 20 kg for women) was identified in 28 (23%) patients, while no patient exhibited low skeletal muscle mass index (<7.23 kg/m2 for men and 5.67 kg/m2 for women). Low handgrip strength was associated with age (P <0.0001), type of vasculitis (P =0.01), vasculitis damage index (P =0.01), history of falls (P =0.0002), osteoporosis (P =0.04), low serum albumin (P =0.003) and prealbumin (P =0.0007), high CRP (P =0.001), high FRAX® tool (P =0.002) and low bone mineral density at femoral neck (P =0.0002). After median follow-up of 42 months, low handgrip strength was associated with higher risk of bone fracture [HR 4.25 (1.37-13.2), P =0.01] and serious adverse events [HR 2.80 (1.35-5.81), P =0.006]. CONCLUSION: Handgrip strength is associated in SNV with nutritional status and comorbidities such as bone disease, and seems to predict, as in other medical conditions, the risk of fracture and serious adverse events during follow-up. In contrast, assessment of skeletal muscle mass index in this population remains uncertain.
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Fracturas Óseas/epidemiología , Fuerza de la Mano , Músculo Esquelético , Sarcopenia , Vasculitis Sistémica , Absorciometría de Fotón/métodos , Anciano , Pesos y Medidas Corporales/métodos , Pesos y Medidas Corporales/estadística & datos numéricos , Densidad Ósea , Comorbilidad , Correlación de Datos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Músculo Esquelético/patología , Músculo Esquelético/fisiopatología , Estado Nutricional , Osteoporosis/epidemiología , Prevalencia , Pronóstico , Medición de Riesgo , Sarcopenia/diagnóstico , Sarcopenia/epidemiología , Vasculitis Sistémica/diagnóstico , Vasculitis Sistémica/epidemiologíaRESUMEN
We assessed bone mineral density (BMD) in a cohort of human immunodeficiency virus (HIV)-positive patients after a median of 11 years of combination antiretroviral therapy (cART) and evaluated the respective role of HIV infection and antiretroviral drugs (ARVs). A cross-sectional study of 162 participants (131 male) from the ANRS-C08 cohort was performed with bone dual-energy X-ray absorptiometry (DXA) scans and renal assessment. The window of exposure to ARVs was defined as an exposure of more than six cumulative months during the last 3 years before the DXA evaluation to account for a cumulative exposure that could affect bone remodeling. The association with low BMD (Z-score < -2) was assessed by a multiple logistic regression model. The study population was 50 years (median), hepatitis C virus (HCV) (18%), and hepatitis B virus (HBV) (8%) coinfection with HIV-RNA <50 c/mL in 89%, median CD4 of 619/mm3. Prevalence of low BMD was 18% in males and 6% in females. The factors associated with a Z-score < -2 in males were uric acid renal loss [adjusted odds ratio (aOR): 6.1; 95% confidence interval (CI): 1.2-31.5; p = .03], HCV coinfection (aOR: 4.0; 95% CI: 1.3-12.2; p = .02), and less frequent window of exposure to nevirapine (NVP) (aOR: 0.1; 95% CI: 0.02-0.6; p = .01). For the full study sample, there was a strong positive association between duration of exposure to NVP and lumbar spine Z-score (p = .004). HIV-positive patients exposed to long-term cART have a high incidence of low BMD. Tenofovir disoproxil fumarate and ritonavir-boosted protease inhibitors did not seem to be associated with increased risk of low BMD, whereas NVP exposure appeared to have an independent positive association.
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Densidad Ósea/efectos de los fármacos , Infecciones por VIH/tratamiento farmacológico , Nevirapina/uso terapéutico , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Absorciometría de Fotón , Adulto , Estudios Transversales , Femenino , Estudios de Seguimiento , Infecciones por VIH/complicaciones , VIH-1/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de TiempoRESUMEN
BACKGROUND: Dual therapy combining integrase inhibitors and NNRTIs represents a promising regimen in ageing HIV-infected individuals with long exposure to nucleoside analogues and PIs. METHODS: The ANRS 163 ETRAL trial (NCT02212379) was a 96 week, multicentre, single-arm study evaluating the efficacy and safety of raltegravir (400 mg twice daily)/etravirine (200 mg twice daily) in individuals >45 years, on a PI-containing regimen who were integrase inhibitor and etravirine naive. The primary endpoint was the proportion of participants with virological success, defined by the absence of virological failure up to week 48. Main secondary outcomes included evolution of metabolic parameters, CD4/CD8 count, bone mineral density and inflammatory markers. The study was designed to show an efficacy >90%, assuming a success rate ≥95%, with a power of 80% and a 5% type-1 error. RESULTS: One hundred and sixty-five participants (median age 52 years, duration of ART 16.9 years, viral suppression 6.9 years and CD4 count 700 cells/mm3) were enrolled. By ITT analysis, viral suppression was maintained in 99.4% of participants (95% CIâ=â95.6%-99.9%) at week 48 and 98.7% (95% CIâ=â95.0%-99.7%) at week 96. Two virological failures occurred (week 24 and week 64) without emergence of integrase inhibitor resistance. Eight participants discontinued raltegravir/etravirine for adverse events, leading to a strategy success rate of 95.1% (95% CIâ=â90.5%-97.5%) at week 48 and 92.7% (95% CIâ=â87.5%-95.8%) at week 96. Over 96 weeks, lipid fractions improved (Pâ<â0.001), CD4/CD8 ratio increased, IFNγ-induced protein 10 (IP-10) decreased (-8.1%), soluble CD14 decreased (-27%, Pâ<â0.001) bone mineral density improved and BMI increased. CONCLUSIONS: Raltegravir plus etravirine dual therapy demonstrated durable efficacy in virologically suppressed ageing patients.
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Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , Piridazinas/uso terapéutico , Raltegravir Potásico/uso terapéutico , Terapia Antirretroviral Altamente Activa , Biomarcadores , Recuento de Linfocito CD4 , Femenino , Infecciones por VIH/transmisión , Inhibidores de Integrasa VIH/administración & dosificación , Inhibidores de Integrasa VIH/efectos adversos , Inhibidores de Integrasa VIH/uso terapéutico , Inhibidores de la Proteasa del VIH/administración & dosificación , Inhibidores de la Proteasa del VIH/efectos adversos , Inhibidores de la Proteasa del VIH/uso terapéutico , Humanos , Masculino , Cumplimiento de la Medicación , Persona de Mediana Edad , Nitrilos , Piridazinas/administración & dosificación , Piridazinas/efectos adversos , Pirimidinas , Calidad de Vida , Raltegravir Potásico/administración & dosificación , Raltegravir Potásico/efectos adversos , Inhibidores de la Transcriptasa Inversa/administración & dosificación , Inhibidores de la Transcriptasa Inversa/efectos adversos , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Factores de Tiempo , Resultado del Tratamiento , Carga ViralRESUMEN
OBJECTIVES: Cardiovascular (CV) events are highly prevalent in systemic necrotising vasculitides (SNV). Visceral/subcutaneous adipose tissue (VAT/SAT) ratio has been shown to be associated with CV events in various diseases. We aimed to assess the relevance of abdominal adipose tissue measurement to predict major CV events (MCVEs) in SNV. METHODS: Patients with SNV were successively included in a longitudinal study assessing MCVEs and other sequelae. Dual x-ray absorptiometry was performed to evaluate abdominal adipose tissue. Patients were prospectively followed for MCVEs, defined as myocardial infarction, unstable angina, stroke, arterial revascularisation and/or hospitalisation for or death from CV causes. RESULTS: One hundred and twenty consecutive SNV patients were included and analysed (54 males, mean age 53±18 years). High CV risk was found in 28 (23.3%) patients. In univariate analysis, age, male gender, VDI, VAT/SAT ratio and serum troponin level were significantly associated with high CV risk, whereas age and VAT/SAT ratio remained independently associated with high CV risk. Variables associated with high tertile of VAT/SAT ratio included age and metabolic risk factors. After median follow-up of 42 months, 19 (16%) patients experienced MCVEs. Hazard ratios for incident MCVEs compared with 1st tertile of VAT/SAT ratio were 7.22 (1.02-51.3; p=0.048) and 9.90 (3.15-31.2; p=0.0002) in the 2nd and 3rd tertile, respectively. CONCLUSIONS: Abdominal visceral adipose tissue is a reliable surrogate marker of CV risk and predicts incident MCVEs in SNV patients. Abdominal adipose tissue should be probably evaluated routinely in these patients to assess CV risk.
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Grasa Abdominal/metabolismo , Enfermedades Cardiovasculares , Vasculitis Sistémica/complicaciones , Tejido Adiposo/metabolismo , Adulto , Anciano , Enfermedades Cardiovasculares/diagnóstico , Femenino , Humanos , Grasa Intraabdominal , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Factores de Riesgo , Vasculitis Sistémica/metabolismoRESUMEN
Finite element models (FEM) derived from qCT-scans were developed as a clinical tool to evaluate vertebral strength. However, the high dose, time and cost of qCT-scanner are limitations for routine osteoporotic diagnosis. A new approach considers using bi-planar dual energy (BP2E) X-rays absorptiometry to build vertebral FEM using synchronized sagittal and frontal plane radiographs. The purpose of this study was to compare the performance of the areal bone mineral density (aBMD) measured from DXA, qCT-based FEM and BP2E-based FEM in predicting experimental vertebral strength. Twenty eight vertebrae from eleven lumbar spine segments were imaged with qCT, DXA and BP2E X-rays before destructively tested in anterior compression. FEM were built based on qCT and BP2E images for each vertebra. Subject-specific FEM were built based on 1) the BP2E images using 3D reconstruction and volumetric BMD distribution estimation and 2) the qCT scans using slice by slice segmentation and voxel based calibration. Linear regression analysis was performed to find the best predictor for experimental vertebral strength (Fexpe); aBMD, modeled vertebral strength and vertebral stiffness. Areal BMD was moderately correlated with Fexpe (R2 =â¯0.74). FEM calculations of vertebral strength were highly to strongly correlated with Fexpe (R2 =â¯0.84, pâ¯<â¯0.001 for BP2E model and R2 =â¯0.95, pâ¯<â¯0.001 for qCT model). The results of this study suggest that aBMD accounted for only 74% of Fexpe variability while FE models accounted for at least 84%. For anterior compressive loading on isolated vertebral bodies, simplistic loading condition aimed to replicate anterior wedge fractures, both FEM were good predictors of Fexpe. Therefore FEM based on BP2E X-rays absorptiometry could be a good alternative to replace qCT-based models in the prediction of vertebral strength. However future work should investigate the performance of the BP2E-based model in vivo in discriminating patients with and without vertebral fracture in a prospective study.
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Absorciometría de Fotón , Fuerza Compresiva , Análisis de Elementos Finitos , Vértebras Lumbares/fisiología , Anciano , Anciano de 80 o más Años , Fenómenos Biomecánicos , Densidad Ósea , Femenino , Humanos , Vértebras Lumbares/diagnóstico por imagen , Masculino , Ensayo de Materiales , Persona de Mediana Edad , Tomografía Computarizada por Rayos XRESUMEN
OBJECTIVE: We aimed to compare bone mineral density (BMD) and bone remodeling markers in chronic low back pain (cLBP) patients with and without active discopathy (Modic 1 changes). DESIGN: We conducted a single center case-control exploratory study. For 18 months, all patients referred to a tertiary care physical medicine and rehabilitation department in France were consecutively screened. Patients fulfilling the inclusion criteria were prospectively enrolled. Cases were defined as cLBP patients with lumbar active discopathy detected on MRI and controls as cLBP patients without active discopathy. Bone mineral density (BMD) at the spine, femoral neck and total femur was assessed by dual-energy X-ray absorptiometry, and bone remodeling markers were assessed in fasting serum samples. Overall, 37 cLBP patients (13 cases and 24 controls) fulfilled inclusion criteria and were included. RESULTS: The median age was 42.0 years (Q1-Q3: 36.0-51.0) and mean (SD) LBP duration 72.3 (57.4) months. We found that BMD and levels of bone remodeling markers in cLBP patients did not differ with and without active discopathy. CONCLUSION: Our results do not support the association between active discopathy and systemic bone fragility.
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Densidad Ósea , Remodelación Ósea , Dolor Crónico/metabolismo , Cuello Femoral/metabolismo , Enfermedades de la Columna Vertebral/metabolismo , Columna Vertebral/metabolismo , Absorciometría de Fotón , Adulto , Estudios de Casos y Controles , Dolor Crónico/diagnóstico por imagen , Femenino , Cuello Femoral/diagnóstico por imagen , Humanos , Dolor de la Región Lumbar/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Enfermedades de la Columna Vertebral/diagnóstico por imagen , Columna Vertebral/diagnóstico por imagenRESUMEN
Background: Sparing of antiretroviral drug classes could reduce the toxicity and cost of maintenance treatment for HIV infection. Objectives: To evaluate the non-inferiority of efficacy and the safety of lopinavir/ritonavir (r) monotherapy versus a single-tablet regimen of efavirenz, emtricitabine and tenofovir (EFV/FTC/TDF) over 2 years. Methods: Adults on stable ART with plasma HIV-1 RNA viral load <50 copies/mL for the past 12 months and no documented treatment failure were randomized to receive either lopinavir/r or EFV/FTC/TDF for 2 years. The primary endpoint was the proportion of patients without treatment failure at week 96 (viral load <50 copies/mL at week 96, confirmed at week 98), without study treatment discontinuation, a new AIDS-defining illness, or death. Results: In the ITT analysis, the primary endpoint was reached by, respectively, 64% and 71% of patients in the lopinavir/r (n = 98) and EFV/FTC/TDF arms (n = 97), yielding a difference of -6.8% (lower limit of the 95% two-sided CI: -19.9%). Sanger and UltraDeep sequencing showed the occurrence of PI mutations in the lopinavir/r arm (n = 4) and of NNRTI and/or NRTI mutations in the EFV/FTC/TDF arm (n = 2). No unexpected serious clinical events occurred. Conclusions: Lopinavir/r monotherapy cannot be considered non-inferior to EFV/FTC/TDF. PI resistance rarely emerged in the lopinavir/r arm and did not undermine future PI options. Two years of lopinavir/r monotherapy had no deleterious clinical impact when compared with EFV/FTC/TDF.
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Antirretrovirales/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Lopinavir/uso terapéutico , Ritonavir/uso terapéutico , Carga Viral/efectos de los fármacos , Adulto , Femenino , Francia , VIH-1/efectos de los fármacos , Hospitales Universitarios , Humanos , Masculino , Persona de Mediana Edad , ARN Viral/sangre , Inhibidores de la Transcriptasa Inversa/uso terapéuticoRESUMEN
A finding of high bone mineral density (BMD) from routine dual-energy X-ray absorptiometry (DXA) screening is not uncommon. No consensus exists about the definition of high BMD, and T-score and/or Z-score cutoffs of ≥+2.5 or ≥+4 have been suggested. The many disorders that can result in high BMD are usually classified based on whether the BMD changes are focal vs. generalized or acquired vs. constitutional. In over half the cases, careful interpretation of the DXA report and images identifies the cause as an artefact (e.g., degenerative spinal disease, vascular calcifications, or syndesmophytes) or focal lesion (e.g., sclerotic bone metastasis or Paget's disease). Generalized acquired high BMD may be secondary to a diverse range of disorders such as fluorosis, diffuse bone sclerosis related to renal osteodystrophy, hematological diseases, and hepatitis C. Identification of the cause may require additional investigations such as imaging studies, serum tryptase assay, or serological tests for the hepatitis C virus. Finally, high BMD is a feature of many genetic diseases, most notably osteopetrosis and the disorders caused by mutations in the sclerostin gene SOST (sclerosing bone dysplasia and van Buchem disease) or in the LRP5 gene encoding the low-density lipoprotein receptor-related protein 5 (which is the Wnt co-receptor).
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Densidad Ósea , Huesos/diagnóstico por imagen , Osteopetrosis/diagnóstico , Absorciometría de Fotón , Adulto , Huesos/metabolismo , Salud Global , Humanos , Incidencia , Osteopetrosis/epidemiología , Osteopetrosis/metabolismoRESUMEN
The objective of this systematic literature review is to discuss the latest French recommendation issued in 2012 that a fall within the past year should lead to bone mineral density (BMD) measurement using dual-energy X-ray absorptiometry (DXA). This recommendation rests on four facts. First, osteoporosis and fall risk are the two leading risk factors for nonvertebral fractures in postmenopausal women. Second, BMD measurement using DXA supplies significant information on the fracture risk independently from the fall risk. Thus, when a fall occurs, the fracture risk increases as BMD decreases. Third, osteoporosis drugs have been proven effective in preventing fractures only in populations with osteoporosis defined based on BMD criteria. Finally, the prevalence of osteoporosis is high in patients who fall and increases in the presence of markers for frailty (e.g., recurrent falls, sarcopenia [low muscle mass and strength], limited mobility, and weight loss), which are risk factors for both osteoporosis and falls. Nevertheless, life expectancy should be taken into account when assessing the appropriateness of DXA in fallers, as osteoporosis treatments require at least 12months to decrease the fracture risk. Another relevant factor is the availability of DXA, which may be limited due to geographic factors, patient dependency, or severe cognitive impairments, for instance. Studies are needed to better determine how the fall risk and frailty should be incorporated into the fracture risk evaluation based on BMD and the FRAX® tool.
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Accidentes por Caídas , Densidad Ósea , Osteoporosis Posmenopáusica/diagnóstico , Absorciometría de Fotón , Femenino , Humanos , Factores de RiesgoRESUMEN
OBJECTIVE: Patients with spondyloarthritis (SpA) receiving anti-TNF-α treatment have an increase in fat mass. This may be relevant to cardiovascular risk. The aim of this study was to estimate visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) changes by dual-energy x-ray absorptiometry (DEXA) in patients with SpA under anti-TNF-α therapy. METHODS: We used an ancillary protocol to an open, prospective 2-year followup study of patients with SpA. Waist circumference (WC), body weight, body mass index, VAT, and SAT were measured at baseline, 6 months, and 1 and 2 years. Univariate and multivariate analyses were performed to assess variables associated with VAT and SAT changes. RESULTS: A total of 85 patients were analyzed. Patients were 39.3 ± 11.4 years old and mean baseline Bath Ankylosing Spondylitis Disease Activity Index was 55.0 ± 20.2. Treatment was effective according to clinical and biological variables, and body weight increased by 0.9 ± 1.7 kg over 2 years. There was a significant gain in VAT after 6 months (13.7 ± 20.6 cm(2), p < 0.0001), 1 year (21.0 ± 26.6 cm(2), p < 0.0001), and after 2 years (29.1 ± 33.4 cm(2), p < 0.0001); and in SAT after 6 months (12.5 ± 27.4 cm(2), p < 0.0001), 1 year (27.1 ± 38.2 cm(2), p < 0.0001), and after 2 years (31.9 ± 53.2 cm(2), p < 0.0001). We could not find any determinant of these changes by multivariate analysis. CONCLUSION: In patients with SpA receiving anti-TNF-α therapy, there is an early significant increase in abdominal obesity with significant increase in both VAT and SAT after 1 and 2 years of treatment. Prospective studies are required to investigate the relationship between these changes and cardiovascular risk.
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Grasa Abdominal/efectos de los fármacos , Adiposidad/efectos de los fármacos , Anticuerpos Monoclonales/farmacología , Antirreumáticos/farmacología , Inmunoglobulina G/farmacología , Espondiloartritis/tratamiento farmacológico , Grasa Abdominal/diagnóstico por imagen , Adulto , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales/uso terapéutico , Antirreumáticos/efectos adversos , Antirreumáticos/uso terapéutico , Índice de Masa Corporal , Etanercept , Femenino , Humanos , Inmunoglobulina G/efectos adversos , Inmunoglobulina G/uso terapéutico , Infliximab , Masculino , Persona de Mediana Edad , Obesidad Abdominal/inducido químicamente , Obesidad Abdominal/diagnóstico por imagen , Estudios Prospectivos , Radiografía , Receptores del Factor de Necrosis Tumoral/uso terapéutico , Factores de Riesgo , Espondiloartritis/diagnóstico por imagen , Resultado del Tratamiento , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Circunferencia de la CinturaRESUMEN
BACKGROUND: Novel nucleoside reverse transcriptase inhibitor- and protease inhibitor-sparing strategies are needed in long-term-treated patients with lipohypertrophy. Given their potency and their excellent metabolic profile, maraviroc and raltegravir appear to be good candidates for such an approach. METHODS: This single-arm study enrolled lipohypertrophic HIV-infected patients with suppressed viraemia and an R5 tropic virus in HIV DNA; they switched from suppressive antiretroviral treatment to maraviroc plus raltegravir. The primary endpoint was the proportion of patients with treatment success at week 24, defined as no virological failure or treatment discontinuation. To ensure a success rate of at least 80%, a maximum of 10 failures were allowed for 90 patients enrolled. ClinicalTrials.gov: NCT01420523. RESULTS: A total of 44 patients were enrolled; their median age was 55 years, median nadir CD4 cell count was 210 cells/mm(3), median time on antiretroviral treatment was 15 years and median duration of viral suppression was 5.2 years. Seven patients failed maraviroc/raltegravir therapy: five had virological failure and two discontinued treatment due to serious adverse events (one had hepatitis B virus reactivation and one had hypersensitivity syndrome). At failure, raltegravir resistance mutations were detected in 3/5 patients and CXCR4 tropic virus in 2/5. Upon DSMB recommendation, the study was prematurely discontinued on 3 September 2012. Lipid profile and bone mineral density improved with a decrease from baseline values in total cholesterol (-0.56â±â0.95 mmol/L; Pâ=â0.001), low-density lipoprotein cholesterol (-0.31â±â0.81 mmol/L; Pâ=â0.039) and triglycerides (-0.59â±â1.12âmmol/L; Pâ=â0.001) and an increase in total hip bone mineral density (+0.9â±â1.5%; Pâ=â0.013) CONCLUSIONS: In long-term-experienced patients, maraviroc/raltegravir therapy lacks virological robustness despite a benefit in lipid profile and bone density.
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Fármacos Anti-VIH/uso terapéutico , Ciclohexanos/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , VIH-1 , Lipodistrofia/etiología , Pirrolidinonas/uso terapéutico , Triazoles/uso terapéutico , Terapia Antirretroviral Altamente Activa , Recuento de Linfocito CD4 , Femenino , Infecciones por VIH/complicaciones , Humanos , Masculino , Maraviroc , Persona de Mediana Edad , Raltegravir Potásico , Factores de Riesgo , Insuficiencia del Tratamiento , Carga ViralRESUMEN
UNLABELLED: The agreement for vertebral fracture (VF) diagnosis in men, between doctors is poor. OBJECTIVES: To assess the agreement for VF diagnosis, in men, on standard radiographs, between experts, before and after consensual workshop and establishing an algorithm. METHODS: The agreement between thirteen experimented rheumatologists has been calculated in thirty osteoporotic men. Then, the group discussed in a workshop and 28 other radiograph sets of osteoporotic men with follow-up radiographs and incident confirmed VF, have been reviewed. The experts identified and hierarchised 18 pathological features of vertebral deformation and established an algorithm of VF diagnosis. Eleven experts have realized a second reading of the first set of radiographs. We compared the agreement between the 2 readings without and with the algorithm. RESULTS: After consensus and the use of the algorithm the results are: number of fractured patients (with at least 1 VF) according to the experts varies from 13 to 26 patients out of 30 (13 to 28 during the first reading). The agreement between the experts at the patient level is 75% (70% at the first reading). Among the 390 vertebrae analyzed by the experts, the number of VF detected varies from 18 to 59 (18 to 98 at the first reading). The agreement between the experts at the vertebral level is 92% (89% at the first reading). The algorithm allows a good improvement of the agreement, especially for 8 of the 11 experts. Discrepancies for the VF diagnosis between experts exist. The algorithm improves the agreement.