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In the future, a new superconducting (SC) continuous wave (CW) high intensity heavy ion HElmholtz LInear ACcelerator (HELIAC) should provide ion beams with maximum beam energy above the Coulomb barrier for the Super Heavy Element program at GSI (Gesellschaft für Schwerionenforschung, in Engl.: Association for Heavy Ion Research). The HELIAC consists of a SC main accelerator supplied by a normal conducting injector, which comprises an electron cyclotron resonance ion source, a radio-frequency quadrupole, and two separate interdigital H-mode drift-tube linear accelerator cavities, based on an Alternating Phase Focusing (APF) scheme. Together, both cavities will accelerate ions from 300 to 1400 keV/u with only one external quadrupole triplet for transverse focusing in between. Due to the demanding requirements of the APF concept on the voltage distribution along the beam axis on the one hand and the CW operation on the other hand, the optimization of each cavity concerning RF, mechanical, and thermal properties is crucial for the successful operation of the HELIAC injector.
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The upcoming commissioning of the superconducting (SC) continuous wave Helmholtz linear accelerators first of series cryomodule is going to demand precise alignment of the four internal SC cavities and two SC solenoids. For optimal results, a beam-based alignment method is used to reduce the misalignment of the whole cryomodule, as well as its individual components. A symmetric beam of low transverse emittance is required for this method, which is to be formed by a collimation system. It consists of two separate plates with milled slits, aligned in the horizontal and vertical direction. The collimation system and alignment measurements are proposed, investigated, and realized. The complete setup of this system and its integration into the existing environment at the GSI High Charge State Injector are presented, as well as the results of the recent reference measurements.
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PURPOSE: To assess the different surgical techniques and their outcomes following tibial tubercle transfer (TTT) in patients with patellar maltracking. METHODS: A systematic search of the literature was performed in PubMed, EMBASE and Cochrane Library. Studies reporting patient-reported outcome measures (PROMs) or clinical outcome following: TTT in patients with patellar maltracking were included. Collected PROMs were Lysholm, Kujala, IKDC score, and VAS pain. Clinical outcome included reported clinical success, patient satisfaction, complications and removal of hardware (ROH). Overall pre-, post-operative and change scores were estimated using random-effects meta-analysis models. Results were reported as overall mean and per transfer direction. RESULTS: A total of 26 studies and 761 patients (818 knees, mean age 35 years, mean follow-up 5.0 years) were included. In 73% of the studies, surgery was performed after failed conservative treatment. Transfer direction was anteromedial in 76% of all procedures. Overall Lysholm score improved from 61 to 91, Kujala from 52 to 85, IKDC from 53 to 81, and VAS from 6.2 to 2.5, respectively. Clinical success was reported in 79% of patients, and 80% of patients reported to have satisfactory results. Rates of complications and ROH were 13% and 29%, respectively. CONCLUSIONS: TTT for management of patellar maltracking can lead to good results with clinically meaningful improvement, an overall clinical success of 79% and overall patient satisfaction of 80% when appreciating the underlying anatomic condition and using appropriate technique. The level of evidence was low, and large-scale prospective, comparative cohort studies with uniform outcome scales are needed to confirm these findings. LEVEL OF EVIDENCE: IV.
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Osteotomia/métodos , Luxação Patelar/cirurgia , Articulação Patelofemoral/cirurgia , Tíbia/cirurgia , Adulto , Feminino , Humanos , Instabilidade Articular/cirurgia , Escore de Lysholm para Joelho , Masculino , Pessoa de Meia-Idade , Medição da Dor , Patela/cirurgia , Síndrome da Dor Patelofemoral/cirurgia , Medidas de Resultados Relatados pelo Paciente , Período Pós-Operatório , Resultado do Tratamento , Adulto JovemRESUMO
AIMS: Patellofemoral arthroplasty (PFA) has experienced significant improvements in implant survivorship with second generation designs. This has renewed interest in PFA as an alternative to total knee arthroplasty (TKA) for younger active patients with isolated patellofemoral osteoarthritis (PF OA). We analysed the cost-effectiveness of PFA versus TKA for the management of isolated PF OA in the United States-based population. PATIENTS AND METHODS: We used a Markov transition state model to compare cost-effectiveness between PFA and TKA. Simulated patients were aged 60 (base case) and 50 years. Lifetime costs (2015 United States dollars), quality-adjusted life year (QALY) gains and incremental cost-effectiveness ratio (ICER) were calculated from a healthcare payer perspective. Annual rates of revision were derived from the National Joint Registry for England, Wales, Northern Ireland and the Isle of Man. Deterministic and probabilistic sensitivity analysis was performed for all parameters against a $50 000/QALY willingness to pay. RESULTS: PFA was more expensive ($49 811 versus $46 632) but more effective (14.3 QALYs versus 13.3 QALYs) over a lifetime horizon. The ICER associated with the additional effectiveness of PFA was $3097. The model was mainly sensitive to utility values, with PFA remaining cost-effective when its utility exceeded that of TKA by at least 1.0%. PFA provided incremental benefits at no increased cost when annual rates of revision decreased by 24.5%. CONCLUSIONS: Recent improvements in rates of implant of survival have made PFA an economically beneficial joint-preserving procedure in younger patients, delaying TKA until implant failure or tibiofemoral OA progression. The present study quantified the minimum required marginal benefit for PFA to be cost-effective compared with TKA and identified survivorship targets for PFA to become both less expensive and more effective. These benchmarks might be used to assess clinical outcomes of PFA from an economic standpoint within the United States healthcare system. Cite this article: Bone Joint J 2017;99-B:1028-36.
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Artroplastia do Joelho/economia , Custos de Cuidados de Saúde , Osteoartrite do Joelho/cirurgia , Avaliação de Resultados em Cuidados de Saúde/economia , Sistema de Registros , Idoso , Idoso de 80 Anos ou mais , Artroplastia do Joelho/métodos , Análise Custo-Benefício , Inglaterra , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Irlanda do Norte , Osteoartrite do Joelho/economia , País de GalesRESUMO
PURPOSE: During anterior cruciate ligament (ACL) reconstruction, authors have suggested inserting the femoral tunnel at the biomechanically relevant direct fibres, but this higher position can cause more impingement. Therefore, we aimed to assess ACL graft impingement at the femoral notch for ACL reconstruction at both the direct and indirect tunnel positions. METHODS: A virtual model was created for twelve cadaveric knees with computed tomography scanning in which a virtual graft was placed at direct and indirect tunnel positions of the anteromedial bundle (AM), posterolateral bundle (PL) or centre of the both bundles (C). In these six tunnel positions, the volume (mm3) and mid-point location of impingement (°) were measured at different flexion angles. RESULTS: Generally, more impingement was seen with the indirect position compared with the direct position although this was only significant at 90° of flexion for the AM position (97 ± 28 vs. 76 ± 20 mm3, respectively; p = 0.046). The direct tunnel position impinged higher at the notch, whereas the indirect position impinged more towards the lateral wall, but this was only significant at 90° of flexion for the AM (24 ± 5° vs. 34 ± 4°, respectively; p < 0.001) and C position (34 ± 5° vs. 42 ± 5°, respectively; p = 0.003). CONCLUSION: In this cadaveric study, the direct tunnel position did not cause more impingement than the indirect tunnel position. Based on these results, graft impingement is not a limitation to reconstruct the femoral tunnel at the insertion of the biomechanically more relevant direct fibres.
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Reconstrução do Ligamento Cruzado Anterior/efeitos adversos , Reconstrução do Ligamento Cruzado Anterior/métodos , Complicações Pós-Operatórias/etiologia , Adulto , Idoso , Ligamento Cruzado Anterior/cirurgia , Feminino , Fêmur/cirurgia , Humanos , Articulação do Joelho/cirurgia , Masculino , Pessoa de Meia-Idade , Amplitude de Movimento Articular , Transplantes/cirurgiaRESUMO
PURPOSE: Historically poor results of survivorship and functional outcomes of patellofemoral arthroplasty (PFA) have been reported in the setting of isolated patellofemoral osteoarthritis. More recently, however, fairly good results of PFA were reported, but the current status of PFA outcomes is unknown. Therefore, a systematic review was performed to assess overall PFA survivorship and functional outcomes. METHODS: A search was performed using PubMed, Embase and Cochrane systems, and the registries were searched. Twenty-three cohort studies and one registry reported survivorship using Kaplan-Meier curve, while 51 cohort studies reported functional outcomes of PFA. RESULTS: Twelve studies were level II studies, while 45 studies were level III or IV studies. Heterogeneity was mainly seen in type of prosthesis and year the cohort started. Nine hundred revisions in 9619 PFAs were reported yielding 5-, 10-, 15- and 20-year PFA survivorships of 91.7, 83.3, 74.9 and 66.6 %, respectively, and an annual revision rate of 2.18. Functional outcomes were reported in 2587 PFAs with an overall score of 82.2 % of the maximum score. KSS and Knee Function Score were 87.5 and 81.6 %, respectively. CONCLUSION: This systematic review showed that fairly good results of PFA survivorship and functional outcomes were reported at short- and midterm follow-up in the setting of isolated patellofemoral osteoarthritis. Heterogeneity existed mainly in prosthesis design and year the cohort started. CLINICAL RELEVANCE: These results provide a clear overview of the current status of PFA in the setting of isolated patellofemoral osteoarthritis. LEVEL OF EVIDENCE: IV.
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Artroplastia do Joelho/métodos , Articulação Patelofemoral/cirurgia , Humanos , Articulação do Joelho/cirurgia , Osteoartrite do Joelho/cirurgia , Desenho de Prótese , Sistema de Registros , Resultado do TratamentoRESUMO
PURPOSE: The predictive role of patient-specific characteristics and radiographic parameters on medial unicompartmental knee arthroplasty (UKA) outcomes is well known, but knowledge of these predictors is lacking in lateral UKA. Therefore, purpose of this study was to assess the predictive role of these parameters on short-term functional outcomes of lateral UKA. METHODS: In this retrospective cohort study, Western Ontario and McMaster Universities Arthritis Index scores were collected at 2-year follow-up (median 2.2 years, range 2.0-4.0 years) in 39 patients who underwent lateral UKA. Patient-specific characteristics included age, BMI and gender, while radiographic parameters included osteoarthritis severity of all three compartments and both preoperative and postoperative hip-knee-ankle alignment. RESULTS: BMI, gender, age and preoperative valgus alignment were not correlated with functional outcomes, while postoperative valgus alignment was correlated with functional outcomes (0.561; p = 0.001). Postoperative valgus of 3°-7° was correlated with better outcomes than more neutral (-2° to 3° valgus) alignment (96.7 vs. 85.6; p = 0.011). Postoperative alignment was a predictor when corrected for patient-specific characteristics (regression coefficient 4.1; p < 0.001) and radiological parameters (regression coefficient 3.8; p = 0.002). CONCLUSIONS: Postoperative valgus alignment of 3°-7° was correlated with the best short-term functional outcomes in lateral UKA surgery, while patient-specific parameters and preoperative alignment were not correlated with functional outcomes. Based on these findings, a surgeon should aim for valgus alignment of 3°-7° when performing lateral UKA surgery for optimal functional outcomes. LEVEL OF EVIDENCE: Prognostic study, Level II.
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Artroplastia do Joelho/métodos , Geno Valgo/fisiopatologia , Osteoartrite do Joelho/cirurgia , Complicações Pós-Operatórias/fisiopatologia , Idoso , Estudos de Coortes , Feminino , Geno Valgo/diagnóstico por imagem , Humanos , Articulação do Joelho/cirurgia , Prótese do Joelho , Extremidade Inferior , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico por imagem , Período Pós-Operatório , Radiografia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Historically poor results of patellofemoral arthroplasty (PFA) were reported in the setting of isolated patellofemoral osteoarthritis (OA). In order to lower PFA failure rates, it is important to identify failure modes using a standardized method. In this systematic review, PFA failure modes were assessed and compared in early vs. late failures and older vs. recent studies. METHODS: Databases of PubMed, Embase and Cochrane and annual registries were searched for studies reporting PFA failures. Failure modes in studies with mean follow-up <5years were classified as early failures while >5years were classified late failures. Cohorts started before 2000 were classified as older studies and started after 2000 as recent studies. RESULTS: Thirty-nine cohort studies (10 level II and 29 level III or IV studies) and three registries were included with overall low quality of studies (GRADE criteria). A total of 938 PFA failures were included and were caused by OA progression (38%), pain (16%), aseptic loosening (14%) and patellar maltracking (10%). Pain was responsible for most early failures (31%), while OA progression was most common in late failures (46%). In older studies, OA progression was more commonly reported as failure mode than in more recent studies (53% vs. 39%, p=0.005). CONCLUSION: This level IV systematic review with low quality of studies identified OA progression and pain as major failure modes. Reviewing these studies, appropriate patient selection could prevent PFA failures in select cases. Future studies assessing the role of PFA in isolated patellofemoral OA are necessary.
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Artroplastia do Joelho , Osteoartrite do Joelho/cirurgia , Articulação Patelofemoral , Estudos de Coortes , Humanos , Sistema de Registros , Fatores de Tempo , Falha de TratamentoRESUMO
BACKGROUND: Lateral unicompartmental knee arthroplasty (UKA) and total knee arthroplasty (TKA) are both reliable treatment options for patients with isolated lateral osteoarthritis (OA). However, studies comparing both procedures are scarce. Aims of this study were to (I) compare short-term functional outcomes following lateral UKA and TKA and (II) assess the role of patient characteristics on outcomes as measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). METHODS: In this retrospective cohort study, 82 patients (48 undergoing lateral UKA and 34 undergoing TKA) were identified that presented with lateral OA and completed the WOMAC. Independent t-tests were used to compare outcomes following lateral UKA and TKA. RESULTS: Mean follow-up was 2.8 years (range: 2.0 - 5.0 years). Preoperatively, no differences between lateral UKA and TKA were seen (50.1±13.5 and 53.3±17.1, respectively, p=0.551). Postoperatively, lateral UKA patients reported better overall outcomes than TKA (90.5±11.7 vs. 81.8±17.9, p=0.017). Subgroup analysis showed better outcomes following lateral UKA than TKA in patients younger than 75 years (92.1±9.9 vs. 81.3±19.6, p=0.014) and in females (91.6±9.9 vs. 81.0±18.2, p=0.014). CONCLUSION: These findings indicate that lateral UKA has superior short-term functional outcomes compared to TKA in patients with isolated lateral OA. Better outcomes were especially seen in younger patients and females. These findings may help orthopedic surgeons choose treatment for patients presenting with lateral OA and optimize treatment for individual patients.
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Artroplastia do Joelho , Osteoartrite do Joelho/cirurgia , Fatores Etários , Idoso , Índice de Massa Corporal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Amplitude de Movimento Articular , Recuperação de Função Fisiológica , Estudos Retrospectivos , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Pathogen inactivation (PI) of platelet concentrates with extension of shelf life to 7 days requires the use of platelet additive solutions (PAS). We examined the quality of platelets resuspended in three different PAS stored for up to 7 days. MATERIALS AND METHODS: Twelve triple adult dose platelet concentrates (PC) were collected using the TrimaAccel® collection system. Each highly concentrated product was divided into three equal parts, and the additive solutions (Composol® or SSP+® or Intersol™) were added to a final concentration of 56% PAS and 44% plasma. Samples were drawn on days 1, 5 and 7 to measure pH, glucose, lactate dehydrogenase (LDH), lactate, mean platelet volume (MPV) and the aggregation response to collagen and the thrombin receptor agonist peptide-6. Further, p-selectin expression on platelets was assessed. RESULTS: No statistically significant changes were observed for pH and MPV during 7 days of storage in all PAS containing PCs, whereas glucose decreased and LDH and lactate increased over time (P < 0·05). These changes were particularly evident in Intersol PCs on days 5 and 7 compared with Composol® PCs or SSP+® PCs (P < 0·05). Platelets from Intersol PCs exhibited the highest baseline activation of p-selectin and showed reduced collagen- and TRAP-6-induced aggregation. CONCLUSION: Resuspension of platelets in Intersol for 7 days results in increased platelet activation and platelet metabolism compared with SSP+® or Composol®. Further clinical studies are needed to evaluate whether the observed differences in PAS-PCs affect the recovery rate or the life span of transfused platelets.
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Plaquetas/efeitos dos fármacos , Preservação de Sangue/métodos , Conservantes Farmacêuticos/efeitos adversos , Adulto , Plaquetas/metabolismo , Humanos , Pessoa de Meia-Idade , Selectina-P/metabolismo , Fragmentos de Peptídeos/metabolismo , Ativação Plaquetária , Testes de Função Plaquetária , Conservantes Farmacêuticos/farmacologiaRESUMO
BACKGROUND: Unicompartmental knee arthroplasty (UKA) has gained popularity in patients with isolated unicompartmental osteoarthritis. To our knowledge no systematic review has assessed and compared survivorship of medial and lateral UKA. We performed a systematic review assessing medial and lateral UKA survivorship and comparing survivorship in cohort studies and registry-based studies. METHODS: A search was performed using PubMed, Embase and Cochrane systems. Ninety-six eligible studies reported survivorship, of which fifty-eight reported medial and sixteen reported lateral UKA survivorship. Nineteen cohort studies and seven registry-based studies reported combined medial and lateral survivorship. RESULTS: The five-year, ten-year and fifteen-year medial UKA survivorship was 93.9%, 91.7% and 88.9%, respectively. Lateral UKA survivorship was 93.2%, 91.4% and 89.4% at five-year, ten-year and fifteen-year, respectively. No statistical difference between both compartments was found. At twenty years and twenty-five years survivorship of medial UKA was 84.7% and 80%, respectively, but no studies reported lateral UKA survivorship at these follow-up intervals. Survivorship of cohort studies was not significantly higher compared to registry-based studies at five years (94.3 vs. 91.7, respectively, p=0.133) but was significantly higher at ten years (90.5 vs. 84.1, p=0.015). CONCLUSION: This is the first systematic review that shows no difference in the five-, ten- and fifteen-year survivorship of medial and lateral UKA. We found a lower survivorship in the registry-based studies compared to cohort studies.
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Artroplastia do Joelho/métodos , Articulação do Joelho/cirurgia , Prótese do Joelho , Osteoartrite do Joelho/cirurgia , Sistema de Registros , Humanos , Articulação do Joelho/fisiopatologia , Desenho de Prótese , Amplitude de Movimento Articular , Fatores de Tempo , Resultado do TratamentoRESUMO
The recognition of hips at risk of displacement in children with cerebral palsy (CP) is a difficult problem for the orthopaedic surgeon. The Gross Motor Function Classification System (GMFCS) and head-shaft angle (HSA) are prognostic factors for hip displacement. However, reference values for HSA are lacking. This study describes and compares the development of HSA in normal hips and children with CP. We selected 33 children from a retrospective cohort with unilateral developmental dysplasia of the hip (DDH) (five boys, 28 girls) and 50 children (35 boys, 15 girls) with CP with GMFCS levels II to V. HSA of normal developing hips was measured at the contralateral hip of unilateral DDH children (33 hips) and HSA of CP children was measured in both hips (100 hips). Measurements were taken from the radiographs of the children at age two, four and seven years. The normal hip HSA decreased by 2° per year (p < 0.001). In children with CP with GMFCS levels II and III HSA decreased by 0.6° (p = 0.046) and 0.9° (p = 0.049) per year, respectively. The HSA did not alter significantly in GMFCS levels IV and V. Between the ages of two and eight years, the HSA decreases in normal hips and CP children with GMFCS level, II to III but does not change in GMFCS levels IV to V. As HSA has a prognostic value for hip displacement, these reference values may help the orthopaedic surgeon to predict future hip displacement in children with CP.
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Paralisia Cerebral/complicações , Paralisia Cerebral/patologia , Luxação do Quadril/etiologia , Articulação do Quadril/crescimento & desenvolvimento , Envelhecimento/patologia , Paralisia Cerebral/diagnóstico por imagem , Paralisia Cerebral/fisiopatologia , Pré-Escolar , Feminino , Seguimentos , Luxação do Quadril/diagnóstico por imagem , Luxação do Quadril/patologia , Articulação do Quadril/anatomia & histologia , Articulação do Quadril/diagnóstico por imagem , Articulação do Quadril/patologia , Humanos , Masculino , Prognóstico , Radiografia , Valores de Referência , Estudos RetrospectivosRESUMO
A comprehensive review of physics at an [Formula: see text] linear collider in the energy range of [Formula: see text] GeV-3 TeV is presented in view of recent and expected LHC results, experiments from low-energy as well as astroparticle physics. The report focusses in particular on Higgs-boson, top-quark and electroweak precision physics, but also discusses several models of beyond the standard model physics such as supersymmetry, little Higgs models and extra gauge bosons. The connection to cosmology has been analysed as well.
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BACKGROUND: Hip displacement is the second most common deformity in cerebral palsy (CP). The risk for hip displacement is related to the Gross Motor Function Classification System (GMFCS). Recently, the head-shaft angle (HSA) has been identified as a predictor for hip displacement and the aim of this study is to assess the predictive value of the HSA for hip displacement in CP. METHODS: In this retrospective cohort, we performed radiological measurements in 50 children on both hips. In children with GMFCS level II (30 hips), III (30 hips), IV (20 hips) and V (20 hips), we measured the HSA and migration percentage (MP) in three age intervals: age two years (T1), age four years (T2) and age seven years (T3). RESULTS: At T1, the HSA was larger (more valgus) in hips that will displace than in hips that will not displace (174° vs. 166°; p = 0.001) and was also larger in higher GMFCS levels (IV-V vs. II-III) (172° vs. 165°; p < 0.001). At T1, GMFCS [odds ratio (OR) 14.7; p = 0.001] and HSA (OR 1.102; p = 0.043) were predictors for hip displacement at T3, but at T2, MP (OR 1.071; p = 0.010) was the only predictor for hip displacement at T3. CONCLUSIONS: The HSA at two years is larger in hips that will displace and larger in children with higher GMFCS levels (IV-V). At age two years, GMFCS and HSA are valuable predictors for hip displacement, but at the age of four years, only MP should be used in the prediction of hip displacement. LEVEL OF EVIDENCE: Prognostic study, level II.
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AIMS: To assess initial pharmacotherapy of Type 2 diabetes with the sodium-glucose cotransporter-2 inhibitor dapagliflozin. METHODS: This double-blind, placebo-controlled trial, randomly allocated people with Type 2 diabetes aged 18-77 years and inadequate glycaemic control on diet and exercise [HbA1c 53-86 mmol/mol (7.0-10.0%)] to receive placebo (n = 75) or dapagliflozin monotherapy 2.5 mg (n = 65), 5 mg (n = 64) or 10 mg (n = 70) once daily in the morning. After 24 weeks, low-dose double-blind metformin 500 mg/day was added to the placebo group regimen (placebo+low-dose metformin group). Changes in HbA1c level, fasting plasma glucose and body weight, as well as adverse events, were assessed over 102 weeks. RESULTS: Of the 274 participants randomized, 167 completed the study (60.9%). At 102 weeks, significant differences vs placebo+low-dose metformin with dapagliflozin 5 and 10 mg were observed for HbA1c (-5.8 mmol/mol [-0.53%], P = 0.018; and -4.8 mmol/mol [-0.44%], P = 0.048), respectively); and for FPG (-0.69 mmol/L, P = 0.044; and -1.12 mmol/l, P = 0.001, respectively). For body weight, the difference between the dapagliflozin 10-mg group and the placebo+low-dose metformin group was significant (-2.60 kg; P = 0.016). Hypoglycaemic events were uncommon, with rates of 5.3% for placebo+low-dose metformin group and 0-4.6% for the dapagliflozin groups. Genital infections and urinary tract infections were more common in the dapagliflozin groups than in the placebo+low-dose metformin group. CONCLUSIONS: Dapagliflozin as monotherapy in treatment-naïve people with early Type 2 diabetes improved glycaemic control and reduced weight without increasing hypoglycaemia over 102 weeks. Dapagliflozin may provide an alternative initial pharmacotherapy in such people.
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Compostos Benzidrílicos/administração & dosagem , Diabetes Mellitus Tipo 2/tratamento farmacológico , Glucosídeos/administração & dosagem , Hipoglicemiantes/administração & dosagem , Adolescente , Adulto , Idoso , Compostos Benzidrílicos/efeitos adversos , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Diabetes Mellitus Tipo 2/sangue , Método Duplo-Cego , Esquema de Medicação , Feminino , Glucosídeos/efeitos adversos , Hemoglobinas Glicadas/metabolismo , Humanos , Hipoglicemiantes/efeitos adversos , Masculino , Metformina/administração & dosagem , Metformina/efeitos adversos , Pessoa de Meia-Idade , Inibidores do Transportador 2 de Sódio-Glicose , Resultado do Tratamento , Adulto JovemAssuntos
Coinfecção , Infecções por HIV/diagnóstico , Tuberculose Pulmonar/diagnóstico , Feminino , Humanos , MasculinoRESUMO
OBJECTIVES: To determine the yield of undetected active tuberculosis (TB), TB and human immunodeficiency virus (HIV) coinfection and the number needed to screen (NNS) to detect a case using active case finding (ACF) in an urban community in Kampala, Uganda. METHODS: In a door-to-door survey conducted in Rubaga community from January 2008 to June 2009, residents aged ≥15 years were screened for chronic cough (≥2 weeks) and tested for TB disease using smear microscopy and/or culture. Rapid testing was used to screen for HIV infection. The NNS to detect one case was calculated based on population screened and undetected cases found. RESULTS: Of 5102 participants, 3868 (75.8%) were females; the median age was 24 years (IQR 20-30). Of 199 (4%) with chronic cough, 160 (80.4%) submitted sputum, of whom 39 (24.4%, 95%CI 17.4-31.5) had undetected active TB and 13 (8.1%, 95%CI 6.7-22.9) were TB-HIV co-infected. The NNS to detect one TB case was 131 in the whole study population, but only five among the subgroup with chronic cough. CONCLUSION: ACF obtained a high yield of previously undetected active TB and TB-HIV cases. The NNS in the general population was 131, but the number needed to test in persons with chronic cough was five. These findings suggest that boosting the identification of persons with chronic cough may increase the overall efficiency of TB case detection at a community level.
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Coinfecção , Infecções por HIV/diagnóstico , Tuberculose Pulmonar/diagnóstico , Adolescente , Adulto , Doença Crônica , Tosse/diagnóstico , Tosse/epidemiologia , Tosse/microbiologia , Estudos Transversais , Feminino , Infecções por HIV/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/isolamento & purificação , Valor Preditivo dos Testes , Escarro/microbiologia , Tuberculose Pulmonar/epidemiologia , Tuberculose Pulmonar/microbiologia , Uganda/epidemiologia , Saúde da População Urbana , Adulto JovemRESUMO
AIMS: Sodium-glucose co-transporter 2 (SGLT2) reabsorbs glucose and sodium in the renal proximal tubule. Dapagliflozin, an SGLT2 inhibitor, targets hyperglycaemia in type 2 diabetes by increasing renal glucose excretion. To investigate whether the parallel occurring sodium loss would have diuretic-like physiologic effects, we compared dapagliflozin and hydrochlorothiazide (HCTZ) effects on 24-h blood pressure (BP), body weight, plasma volume and glomerular filtration rate (GFR). METHODS: In this randomized, placebo-controlled, double-blind trial, 75 subjects with type 2 diabetes were assigned placebo, dapagliflozin 10 mg/day, or HCTZ 25 mg/day. Changes from baseline BP, body weight, plasma volume and GFR were assessed after 12 weeks of treatment. RESULTS: Subjects' mean age was 56 years, type 2 diabetes mellitus (T2DM) duration 6.3 years, and haemoglobin A1c (HbA1c) 7.5%. Treatment with placebo, dapagliflozin or HCTZ resulted in changes from baseline in 24-h ambulatory mean systolic blood pressure (SBP) of -0.9 (95%CI -4.2, +2.4), -3.3 (95%CI -6.8, +0.2), and -6.6 (95%CI -9.9, -3.2) mmHg, respectively at week 12, adjusted for baseline SBP. Body weight decreased with dapagliflozin and HCTZ. In a sub-study plasma volume appeared to decrease with dapagliflozin but did not change with placebo or HCTZ treatment. Dapagliflozin induced a greater reduction in GFR (-10.8%; 95%CI -14.6, -6.7) relative to placebo (-2.9%; 95% CI -6.9, +1.2) or HCTZ (-3.4%; 95%CI -7.3, +0.6). CONCLUSIONS: Dapagliflozin-induced SGLT2 inhibition for 12 weeks is associated with reductions in 24-h BP, body weight, GFR and possibly plasma volume. Cumulatively, these effects suggest that dapagliflozin may have a diuretic-like capacity to lower BP in addition to beneficial effects on glycaemic control.
Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Diuréticos/uso terapêutico , Glucosídeos/uso terapêutico , Hidroclorotiazida/uso terapêutico , Hipoglicemiantes/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose , Adolescente , Adulto , Idoso , Compostos Benzidrílicos , Glicemia/metabolismo , Pressão Sanguínea , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/epidemiologia , Diuréticos/administração & dosagem , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Glucosídeos/administração & dosagem , Humanos , Hidroclorotiazida/administração & dosagem , Hipoglicemiantes/administração & dosagem , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Redução de Peso/efeitos dos fármacosRESUMO
AIMS: Many patients with type 2 diabetes are suboptimally managed with currently available therapies. Dapagliflozin, a sodium-glucose co-transporter-2 inhibitor, has shown efficacy in reducing diabetic hyperglycaemia. This study assessed efficacy of three lower doses in recently diagnosed patients. METHODS: This phase 3, randomized, double-blind, placebo-controlled study assigned treatment-naïve patients to placebo or dapagliflozin monotherapy (1, 2.5 or 5 mg) daily for 24 weeks. Patients were antidiabetic drug-naïve with inadequate glycaemic control [haemoglobin A1c (HbA1c) ≥7.0 and ≤10.0%]. The primary efficacy endpoint was change in HbA1c from baseline. Secondary endpoints included changes in body weight and fasting plasma glucose (FPG), and proportions achieving HbA1c <7%. RESULTS: A total of 282 patients with type 2 diabetes were randomly assigned to one of four treatment groups. Baseline characteristics were similar across groups. At week 24, mean HbA1c reduction was significantly greater with dapagliflozin: -0.68% for 1 mg, -0.72% for 2.5 mg, -0.82% for 5 mg, versus 0.02% for placebo (p < 0.0001); compared to mean baseline values of 7.8-8.1%. Mean FPG reduction was significantly greater for all dapagliflozin groups versus placebo (p < 0.02), as was mean weight reduction (p < 0.003). During the treatment period, 19.1% of placebo-treated patients received rescue medication or discontinued because of poor glycaemic control versus 6.9, 4.1 and 5.9% for dapagliflozin 1, 2.5 and 5 mg, respectively. Percentages of patients experiencing ≥1 adverse event were similar across groups. CONCLUSION: Dapagliflozin at doses of 1, 2.5 and 5 mg/day is effective in reducing glycaemic levels and body weight in treatment-naïve patients with type 2 diabetes. Dapagliflozin was generally well tolerated. This insulin-independent mechanism suggests a new treatment for type 2 diabetes.
Assuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Glucosídeos/uso terapêutico , Compostos Benzidrílicos , Glicemia/efeitos dos fármacos , Canadá/epidemiologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/epidemiologia , Relação Dose-Resposta a Droga , Método Duplo-Cego , Esquema de Medicação , Feminino , Seguimentos , Glucosídeos/administração & dosagem , Hemoglobinas Glicadas/metabolismo , Humanos , Índia/epidemiologia , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Porto Rico/epidemiologia , Federação Russa/epidemiologia , África do Sul/epidemiologia , Resultado do Tratamento , Estados Unidos/epidemiologia , Redução de Peso/efeitos dos fármacosRESUMO
BACKGROUND: Combining metformin (XR) with dapagliflozin to initiate pharmacotherapy in patients with type 2 diabetes (T2D) and high baseline HbA1c may be advantageous. We conducted two randomised, double-blind, three-arm 24-week trials in treatment-naïve patients to compare dapagliflozin plus metformin, dapagliflozin alone and metformin alone. METHODS: Eligible patients had baseline HbA1c 7.5-12%. Each trial had three arms: dapagliflozin plus metformin, dapagliflozin monotherapy and metformin monotherapy. Dapagliflozin in combination and as monotherapy was dosed at 5 mg (Study 1) and 10 mg (Study 2). Metformin in combination and as monotherapy was titrated to 2000 mg. The primary endpoint was HbA1c change from baseline; secondary endpoints included change in fasting plasma glucose (FPG) and weight. RESULTS: In both trials, combination therapy led to significantly greater reductions in HbA1c compared with either monotherapy: -2.05 for dapagliflozin + metformin, -1.19 for dapagliflozin, and -1.35 for metformin (p < 0.0001) (Study 1); -1.98 for dapagliflozin + metformin, -1.45 for dapagliflozin and -1.44 for metformin (p < 0.0001) (Study 2). Combination therapy was statistically superior to monotherapy in reduction of FPG (p < 0.0001 for both studies); combination therapy was more effective than metformin for weight reduction (p < 0.0001). Dapagliflozin 10 mg was non-inferior to metformin in reducing HbA1c (Study 2). Events suggestive of genital infection were reported in 6.7%, 6.9% and 2.0% (Study 1) and 8.5%, 12.8% and 2.4% (Study 2) of patients in combination, dapagliflozin and metformin groups; events suggestive of urinary tract infection were reported in 7.7%, 7.9% and 7.5% (Study 1) and 7.6%, 11.0% and 4.3% (Study 2) of patients in the respective groups. No major hypoglycaemia was reported. CONCLUSION: In treatment-naïve patients with T2D, dapagliflozin plus metformin was generally well tolerated and effective in reducing HbA1c, FPG and weight. Dapagliflozin-induced glucosuria led to an increase in events suggestive of urinary tract and genital infections.