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1.
Genet Med ; 26(4): 101074, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38243783

RESUMO

PURPOSE: Diagnostic delay in monogenic disease is reportedly common. We conducted a scoping review investigating variability in study design, results, and conclusions. METHODS: We searched the academic literature on January 17, 2023, for original peer reviewed journals and conference articles that quantified diagnostic delay in monogenic disease. We abstracted the reported diagnostic delay, relevant study design features, and definitions. RESULTS: Our search identified 259 articles quantifying diagnostic delay in 111 distinct monogenetic diseases. Median reported diagnostic delay for all studies collectively in monogenetic diseases was 5.0 years (IQR 2-10). There was major variation in the reported delay within individual monogenetic diseases. Shorter delay was associated with disorders of childhood metabolism, immunity, and development. The majority (67.6%) of articles that studied delay reported an improvement with calendar time. Study design and definitions of delay were highly heterogenous. Three gaps were identified: (1) no studies were conducted in the least developed countries, (2) delay has not been studied for the majority of known, or (3) most prevalent genetic diseases. CONCLUSION: Heterogenous study design and definitions of diagnostic delay inhibit comparison across studies. Future efforts should focus on standardizing delay measurements, while expanding the research to low-income countries.


Assuntos
Diagnóstico Tardio , Projetos de Pesquisa , Humanos , Países em Desenvolvimento
2.
Mil Med ; 189(1-2): e27-e33, 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-37192200

RESUMO

INTRODUCTION: Extracorporeal membrane oxygenation (ECMO) is typically used to provide mechanical perfusion and gas exchange to critically ill patients with cardiopulmonary failure. We present a case of a traumatic high transradial amputation in which the amputated limb was placed on ECMO to allow for limb perfusion during bony fixation and preparations and coordination of orthopedic and vascular soft tissue reconstructions. MATERIALS AND METHODS: This is a descriptive single case report which underwent managment at a level 1 trauma center. Instutional review board (IRB) approval was obtained. RESULTS: This case highlights many important factors of limb salvage. First, complex limb salvage requires a well-organized, pre-planned multi-disciplinary approach to optimize patient outcomes. Second, advancements in trauma resuscitation and reconstructive techniques over the past 20 years have drastically expanded the ability of treating surgeons to preserve limbs that would have otherwise been indicated for amputation. Lastly, which will be the focus of further discussion, ECMO and EP have a role in the limb salvage algorithm to extend current timing limitations for ischemia, allow for multidisciplinary planning, and prevent reperfusion injury with increasing literature to support its use. CONCLUSIONS: ECMO is an emerging technology that may have clinical utility for traumatic amputations, limb salvage, and free flap cases. In particular, it may extend current limitations of ischemia time and reduce the incidence of ischemia reperfusion injury in proximal amputation, thus expanding the current indications for proximal limb replantation. It is clear that developing a multi-disciplinary limb salvage team with standardized treatment protocols is paramount to optimize patient outcomes and allows limb salvage to be pursued in increasingly complex cases.


Assuntos
Amputação Traumática , Oxigenação por Membrana Extracorpórea , Humanos , Oxigenação por Membrana Extracorpórea/métodos , Antebraço/cirurgia , Amputação Cirúrgica , Salvamento de Membro/métodos , Amputação Traumática/cirurgia , Amputação Traumática/complicações , Isquemia , Estudos Retrospectivos , Resultado do Tratamento
3.
Artigo em Inglês | MEDLINE | ID: mdl-37850210

RESUMO

Background: The lack of trainees from underrepresented race and gender backgrounds in orthopaedic surgery fellowship training has been well reported in the literature. The purpose of this study was to investigate the demographic trends of federally sponsored military orthopaedic surgery fellows in the Army, Navy, and Air Force. We hypothesize that there has been an increase in women selected for fellowship but that there has been no change in the race demographics of military fellows over the past 2 decades. Methods: A retrospective review of all available demographic data collected by the Army, Air Force, and Navy since the beginning of tracking federally funded fellowship training in orthopaedic surgery was completed (1998-2021). Data were grouped into 4-year periods for analysis to closely mirror the military assignment cycle. Results: Three hundred sixty-two military orthopaedic surgery fellowship board selectees were included in our analysis. The proportion of women fellows increased from 3% (n = 2/69) over 2001 to 2004 to 21% (n = 17/82) during 2017 to 2020 (p < 0.05). Fellows who identified as White comprised 82% (n = 297) of the cohort during the study period. Individuals who identified as Asian were the next highest proportion of fellows at 4% (n = 16), followed by Black (n = 14, 4%) and Hispanic (n = 13, 3%). Individuals who identified as Native Hawaiian/Pacific Islander represented 1% (n = 3), and an additional 6% (n = 20) fellows identified as "other" or "undeclared." Over the 20-year study period, representation of Asian, Black, Native Hawaiian, and Hispanic fellows did not increase (p = 0.79, 0.81, 0.45, 0.34, respectively). Conclusions: Within military orthopaedics, there has been increased representation of women in fellowship training over the past 20 years. However, the proportion of fellows from underrepresented racial and ethnic groups has remained stagnant. One barrier to improving gender and race representation is the currently imprecise and inconsistent collection of demographic information. Importantly, fellowship training has a direct effect on future leadership opportunities within the military orthopaedic surgery community. A more diverse leadership may help to inspire future generations of military orthopaedic surgeons. Level of Evidence: IV.

5.
J Bone Joint Surg Am ; 104(10): 864-871, 2022 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-35142748

RESUMO

BACKGROUND: The long-term consequences of musculoskeletal trauma can be profound and can extend beyond the post-injury period. The surveillance of long-term expenditures among individuals who sustain orthopaedic trauma has been limited in prior work. We sought to compare the health-care requirements of active-duty individuals who sustained orthopaedic injuries in combat and non-combat (United States) environments using TRICARE claims data. METHODS: We identified service members who sustained combat or non-combat musculoskeletal injuries between 2007 and 2011. Combat-injured personnel were matched to those in the non-combat-injured cohort on a 1:1 basis using biologic sex, year of the injury, Injury Severity Score (ISS), and age at the index hospitalization. Health-care utilization was surveyed through 2018. The total health-care expenditures over the post-injury period were the primary outcome. These were assessed as a total overall cost and then as costs adjusted per year of follow-up. We used negative binomial regression to identify the independent association between risk factors and health-care expenditures. RESULTS: We identified 2,119 individuals who sustained combat-related orthopaedic trauma and 2,119 individuals who sustained non-combat injuries. The most common mechanism of injury within the combat-injured cohort was blast-related trauma (59%), and 418 individuals (20%) sustained an amputation. The total costs were $156,886 for the combat-injured group compared with $55,873 for the non-combat-injured group (p < 0.001). Combat-related orthopaedic injuries were associated with a 43% increase in health-care expenditures (incidence rate ratio, 1.43 [95% confidence interval, 1.19 to 1.73]). Severe ISS at presentation, ≥2 comorbidities, and amputations were also significantly associated with health-care utilization, as was junior enlisted rank, our proxy for socioeconomic status. CONCLUSIONS: Health-care requirements and associated costs are substantial among service members sustaining combat and non-combat orthopaedic trauma. Given the sociodemographic characteristics of our cohort, we believe that these results are translatable to civilians who sustain similar types of musculoskeletal trauma.


Assuntos
Traumatismos por Explosões , Militares , Doenças Musculoesqueléticas , Ortopedia , Traumatismos por Explosões/cirurgia , Gastos em Saúde , Humanos , Aceitação pelo Paciente de Cuidados de Saúde , Estudos Retrospectivos , Estados Unidos
6.
Spine (Phila Pa 1976) ; 47(7): 515-522, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-35066537

RESUMO

STUDY DESIGN: Prospective observational study. OBJECTIVE: We present the natural history, including survival and function, among participants in the prospective observational study of spinal metastases treatment investigation. SUMMARY OF BACKGROUND DATA: Surgical treatment has been touted as a means to preserve functional independence, quality of life, and survival. Nearly all prior investigations have been limited by retrospective design and relatively short-periods of post-treatment surveillance. METHODS: This natural history study was conducted using the records of patients who were enrolled in the prospective observational study of spinal metastases treatment study (2017-2019). Eligible participants were 18 or older and presenting for treatment of spinal metastatic disease. Patients were followed at predetermined intervals (1, 3, 6, 12, and 24-mo) following treatment. We conducted cox proportional hazard regression analysis adjusting for confounders including age, biologic sex, number of comorbidities, type of metastatic lesion, neurologic symptoms at presentation, number of metastases involving the vertebral body, vertebral body collapse, New England Spinal Metastasis Score (NESMS) at presentation, and treatment strategy. RESULTS: We included 202 patients. Twenty-three percent of the population had died by 3 months following treatment initiation, 51% by 1 year, and 70% at 2 years. There was no significant difference in survival between patients treated operatively and nonoperatively (P = 0.16). No significant difference in HRQL between groups was appreciated beyond 3 months following treatment initiation. NESMS at presentation (scores of 0 [HR 5.61; 95% CI 2.83, 11.13] and 1 [HR 3.00; 95% CI 1.60, 5.63]) was significantly associated with mortality. CONCLUSION: We found that patients treated operatively and nonoperatively for spinal metastases benefitted from treatment in terms of HRQL. Two-year mortality for the cohort as a whole was 70%. When prognosticating survival, the NESMS appears to be an effective utility, particularly among patients with scores of 0 or 1.Level of Evidence: 2.


Assuntos
Neoplasias da Coluna Vertebral , Estudos de Coortes , Humanos , Estudos Prospectivos , Qualidade de Vida , Estudos Retrospectivos , Neoplasias da Coluna Vertebral/diagnóstico , Neoplasias da Coluna Vertebral/cirurgia
8.
Nat Rev Cardiol ; 17(12): 761-772, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32665641

RESUMO

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are effective antidiabetic therapies in patients with type 2 diabetes mellitus and are associated with improved glycaemic control as well as with reductions in body mass and blood pressure. In large cardiovascular outcome trials in patients with diabetes, SGLT2 inhibitors improve cardiovascular and renal outcomes, including hospitalization for heart failure, with this benefit extending to patients without diabetes who have heart failure with reduced ejection fraction. The possible mechanisms of benefit are being extensively investigated because they are unlikely to be related to improved glycaemic control. Early natriuresis with a reduction in plasma volume, a consequent rise in haematocrit, improved vascular function, a reduction in blood pressure and changes in tissue sodium handling are all likely to have a role. Additional mechanisms of SGLT2 inhibitors that might be beneficial include a reduction in adipose tissue-mediated inflammation and pro-inflammatory cytokine production, a shift towards ketone bodies as the metabolic substrate for the heart and kidneys, reduced oxidative stress, lowered serum uric acid level, reduced glomerular hyperfiltration and albuminuria, and suppression of advanced glycation end-product signalling. Further outcome trials and mechanistic studies, including in patients with heart failure with preserved ejection fraction or non-diabetic kidney disease, might identify other possible mechanisms of benefit of SGLT2-inhibitor therapy.


Assuntos
Doenças Cardiovasculares , Inibidores do Transportador 2 de Sódio-Glicose , Doenças Cardiovasculares/tratamento farmacológico , Controle Glicêmico , Humanos , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico
9.
J Hand Surg Am ; 45(8): 775.e1-775.e7, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32408998

RESUMO

PURPOSE: To determine the region of the flexor digitorum profundus (FDP) and flexor digitorum superficialis (FDS) tendons in zone 2 that, when involved by a laceration repair, will reliably catch on the A2 pulley after surgery. METHODS: Using fresh-frozen cadavers (5 hands, 20 digits), excursions of the FDP and FDS tendons were measured in relation to the A2 pulley. The C1, A3, and C2 pulleys were resected. The digit was maximally flexed by applying traction to the flexor tendon in the forearm. An 8-0 suture tag was placed in the flexor tendons immediately distal to the A2 pulley. The digit was then passively fully extended to measure tendon excursion. Measurements were repeated with 50% venting and 100% release of the A4 pulley. Reference points such as tendon insertions and flexion creases were obtained. This protocol was repeated sequentially for the index, middle, ring, and little fingers. RESULTS: For all 20 fingers, the suture placed into the FDP just distal to the A2 pulley with the finger fully flexed traveled 1.6 ± 1.9 mm distal to the proximal edge of the A4 pulley with passive extension of the finger. The mean excursion for the FDP was 24.6 ± 3.2 mm, and 16.9 ± 3.1 mm for the FDS. The mean A2 pulley length was 16.2 ± 3.5 mm, and the mean distance between the distal edge of the A2 pulley and the proximal edge of the A4 pulley was 23.0 ± 3.3 mm. Venting the A4 pulley 50% and 100% increased FDP excursion a maximum of 0.9 and 1.9 mm, respectively. CONCLUSIONS: An FDP repair proximal to the A4 pulley will slide under the A2 pulley with full active digital flexion after surgery. If the distal FDP stump lies underneath the A4 pulley with the digit fully extended, the FDP repair will not likely engage the A2 pulley with full flexion after surgery. The FDP excursion can be reliably predicted as a percentage of the A2 (distal) to the A4 (distal) pulley distance. Most importantly, the distance between the repair site and the A4 pulley approximately equals the length of the A2 pulley that requires release to avoid postoperative triggering. CLINICAL RELEVANCE: Knowledge of this high-risk region of flexor tendon repair will guide surgeons regarding the potential need for partial release of the A2 pulley.


Assuntos
Mãos , Tendões , Fenômenos Biomecânicos , Dedos/cirurgia , Humanos , Músculo Esquelético , Amplitude de Movimento Articular , Tendões/cirurgia
10.
Artigo em Inglês | MEDLINE | ID: mdl-32303532

RESUMO

INTRODUCTION: This prospective observational study sought to establish the glycemic, physiological and dietary demands of strenuous exercise training as part of a 9-day performance camp in a professional cycling team with type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS: Sixteen male professional cyclists with T1D on multiple daily injections (age: 27±4 years; duration of T1D: 11±5 years; body mass index: 22±2 kg/m2; glycated hemoglobin: 7%±1% (50±6 mmol/mol); maximum rate of oxygen consumption: 73±4 mL/kg/min) performed road cycle sessions (50%-90% of the anaerobic threshold, duration 1-6 hours) over 9 consecutive days. Glycemic (Dexcom G6), nutrition and physiological data were collected throughout. Glycemic data were stratified into predefined glycemic ranges and mapped alongside exercise physiology and nutritional parameters, as well as split into daytime and night-time phases for comparative analysis. Data were assessed by means of analysis of variance and paired t-tests. A p value of ≤0.05 (two-tailed) was statistically significant. RESULTS: Higher levels of antecedent hypoglycemia in the nocturnal hours were associated with greater time spent in next-day hypoglycemia overall (p=0.003) and during exercise (p=0.019). Occurrence of nocturnal hypoglycemia was associated with over three times the risk of next-day hypoglycemia (p<0.001) and a twofold risk of low glucose during cycling (p<0.001). Moreover, there was trend for a greater amount of time spent in mild hypoglycemia during the night compared with daytime hours (p=0.080). CONCLUSION: The higher prevalence of nocturnal hypoglycemia was associated with an increased risk of next-day hypoglycemia, which extended to cycle training sessions. These data highlight the potential need for additional prebed carbohydrates and/or insulin dose reduction strategies around exercise training in professional cyclists with T1D. TRIAL REGISTRATION NUMBER: DRKS00019923.


Assuntos
Diabetes Mellitus Tipo 1 , Hipoglicemia , Adulto , Glicemia , Diabetes Mellitus Tipo 1/epidemiologia , Hemoglobinas Glicadas/análise , Humanos , Hipoglicemia/epidemiologia , Hipoglicemiantes , Masculino , Adulto Jovem
11.
Diabetes Care ; 43(5): 1142-1145, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32179510

RESUMO

OBJECTIVE: To investigate factors related to glycemic management among members of a professional cycling team with type 1 diabetes over a 7-day Union Cycliste Internationale World Tour stage race. RESEARCH DESIGN AND METHODS: An observational evaluation of possible factors related to glycemic management and performance in six male professional cyclists with type 1 diabetes (HbA1c 6.4 ± 0.6%) during the 2019 Tour of California. RESULTS: In-ride time spent in euglycemia (3.9-10.0 mmol/L glucose) was 63 ± 11%, with a low percentage of time spent in level 1 (3.0-3.9 mmol/L; 0 ± 1% of time) and level 2 (<3.0 mmol/L; 0 ± 0% of time) hypoglycemia over the 7-day race. Riders spent 25 ± 9% of time in level 1 (10.1-13.9 mmol/L) and 11 ± 9% in level 2 (>13.9 mmol/L) hyperglycemia during races. Bolus insulin use was uncommon during races, despite high carbohydrate intake (76 ± 23 g ⋅ h-1). Overnight, the riders spent progressively more time in hypoglycemia from day 1 (6 ± 12% in level 1 and 0 ± 0% in level 2) to day 7 (12 ± 12% in level 1 and 2 ± 4% in level 2) (χ2[1] > 4.78, P < 0.05). CONCLUSIONS: Professional cyclists with type 1 diabetes have excellent in-race glycemia, but significant hypoglycemia during recovery overnight, throughout a 7-day stage race.


Assuntos
Atletas , Ciclismo/fisiologia , Glicemia/metabolismo , Diabetes Mellitus Tipo 1/sangue , Controle Glicêmico , Adulto , Automonitorização da Glicemia , California , Comportamento Competitivo , Diabetes Mellitus Tipo 1/tratamento farmacológico , Controle Glicêmico/normas , Humanos , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Masculino , Autogestão/métodos , Fatores de Tempo
12.
Diabetes Obes Metab ; 21(2): 402-407, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30160030

RESUMO

The EDITION trials in type 2 diabetes demonstrated comparable glycaemic control with less nocturnal and anytime (24-hour) hypoglycaemia for insulin glargine 300 U/mL (Gla-300) versus glargine 100 U/mL (Gla-100). However, the predefined nocturnal window (0:00-5:59 AM) may not be the most relevant for clinical practice. This post-hoc analysis compared expansions of the predefined nocturnal interval during basal insulin treatment without prandial insulin. Patient-level, 6-month data, pooled from the EDITION 2 and 3 trials and the EDITION JP 2 trial (N = 1922, basal insulin only) were analysed. Accompanying hypoglycaemia during treatment with Gla-300 was compared to that during treatment with Gla-100, using predefined (0:00-5:59 AM) and expanded (10:00 PM-5:59 AM, 0:00-7:59 AM, 10:00 PM to pre-breakfast SMPG) windows. Confirmed (≤3.9 mmol/L [≤70 mg/dL]) or severe hypoglycaemic events were reported most frequently between 6:00 AM and 8:00 AM. Windows expanded beyond 6:00 AM included more events than other windows. The percentage of participants with at least one event was lower with Gla-300 than Gla-100 in all windows examined. Expanding the nocturnal interval allows better assessment of the risk of hypoglycaemia associated with basal insulin. The risk of nocturnal hypoglycaemia was consistently lower with Gla-300 versus Gla-100 using all four windows.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Hipoglicemia/induzido quimicamente , Hipoglicemia/epidemiologia , Insulina Glargina/administração & dosagem , Insulina Glargina/efeitos adversos , Insulina/administração & dosagem , Adulto , Ritmo Circadiano/efeitos dos fármacos , Ensaios Clínicos Fase III como Assunto/estatística & dados numéricos , Diabetes Mellitus Tipo 2/sangue , Relação Dose-Resposta a Droga , Esquema de Medicação , Quimioterapia Combinada , Feminino , Humanos , Insulina/efeitos adversos , Masculino , Estudos Multicêntricos como Assunto/estatística & dados numéricos , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo
13.
Diabetes Obes Metab ; 20(2): 448-452, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28736942

RESUMO

In this post hoc analysis we compared glycaemic control and hypoglycaemia between insulin glargine 300 U/mL (Gla-300) and glargine 100 U/mL (Gla-100) administered once daily in people with type 2 diabetes (T2DM) from the EDITION 1 (basal plus mealtime insulin) and EDITION 2 (basal insulin plus oral antihyperglycaemic drugs) trials who were previously receiving twice-daily insulin. At randomization, 16.9% and 20.0% of people in EDITION 1 and 2, respectively, were receiving twice-daily basal insulin. Glycated haemoglobin change from baseline to Month 6 was similar over 6 months with Gla-300 or Gla-100 (least squares mean difference -0.01%; 95% confidence interval [CI] -0.27 to 0.24] in EDITION 1 and 0.16%; 95% CI -0.25 to 0.57, in EDITION 2). Participants previously receiving twice-daily insulin in EDITION 1 had a lower risk of confirmed (≤3.9 mmol/L [≤70 mg/dL]) or severe hypoglycaemia with Gla-300 vs Gla-100 at night (00:00-05:59 hours), but not at any time (24 hours); in EDITION 2 the risk was reduced at night and any time (24 hours). In conclusion, Gla-300 provided similar glycaemic control with less hypoglycaemia compared with Gla-100 in people with T2DM switching from twice-daily to once-daily basal insulin.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hiperglicemia/prevenção & controle , Hipoglicemia/prevenção & controle , Hipoglicemiantes/administração & dosagem , Insulina Glargina/administração & dosagem , Administração Oral , Adulto , Glicemia/análise , Automonitorização da Glicemia , Diabetes Mellitus Tipo 2/sangue , Relação Dose-Resposta a Droga , Esquema de Medicação , Composição de Medicamentos , Monitoramento de Medicamentos , Quimioterapia Combinada/efeitos adversos , Hemoglobinas Glicadas/análise , Humanos , Hiperglicemia/fisiopatologia , Hipoglicemia/induzido quimicamente , Hipoglicemia/fisiopatologia , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/uso terapêutico , Injeções Subcutâneas , Insulina Glargina/efeitos adversos , Insulina Glargina/uso terapêutico , Análise de Intenção de Tratamento , Concentração Osmolar , Índice de Gravidade de Doença
14.
Eur J Prev Cardiol ; 23(11): NP1-NP96, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27353126
15.
Lancet Diabetes Endocrinol ; 3(9): 697-703, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26276240

RESUMO

BACKGROUND: Albiglutide is a glucagon-like peptide-1 receptor agonist, a new class of drugs used to treat type 2 diabetes. We did a prospective meta-analysis of the cardiovascular safety of albiglutide as stipulated by the US Food and Drug Administration recommendations for the assessment of new treatments for diabetes. METHODS: We did a meta-analysis of eight phase 3 trials and one phase 2b trial in which patients were randomly assigned to albiglutide, placebo, or active comparators (glimepiride, insulin glargine, insulin lispro, liraglutide, pioglitazone, or sitagliptin). The safety population included 5107 patients, of whom 2524 took albiglutide (4870 person-years) and 2583 took comparators (5213 person-years). Possible major cardiovascular events were recorded prospectively and adjudicated by an independent endpoint committee masked to treatment allocation. The primary endpoint was a composite of first occurrence of major adverse cardiovascular events (ie, cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke) or hospital admission for unstable angina. Secondary endpoints were major adverse cardiovascular events alone, all-cause mortality, silent myocardial infarction, hospital admission for heart failure, chest pain, other angina, and subdural or extradural haemorrhage. The occurrence of all other adverse events classified by the investigators as cardiovascular events were documented, but these were not adjudicated. FINDINGS: The primary endpoint was not significantly different between albiglutide and all comparators (58 events vs 58 events; hazard ratio [HR] 1·00, 95% CI 0·68-1·49, p=0·0019 for non-inferiority). Major adverse cardiovascular event alone was also not significantly different (52 events vs 53; HR, 0·99; 95% CI, 0·65-1·49). When albiglutide was compared separately with placebo or active comparators, we noted no significant differences. We detected no significant differences in the other secondary endpoints. More patients had atrial fibrillation or atrial flutter in the albiglutide group (35 [1·4%] of 2524 patients; 8·6 events per 1000 patient-years) than in the all-comparators group (16 [0·6%] of 2583 patients; 3·4 events per 1000 patient-years). INTERPRETATION: Cardiovascular events were not significantly more likely to occur with albiglutide than with all comparators. Because the upper bound of the 95% CI for major adverse cardiovascular event plus hospital admission for unstable angina was greater than 1·3, a dedicated study with a cardiovascular endpoint is underway to confirm the safety of albiglutide. FUNDING: GlaxoSmithKline.


Assuntos
Sistema Cardiovascular/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Peptídeo 1 Semelhante ao Glucagon/análogos & derivados , Incretinas/efeitos adversos , Idoso , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/epidemiologia , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Diabetes Mellitus Tipo 2/complicações , Feminino , Peptídeo 1 Semelhante ao Glucagon/efeitos adversos , Peptídeo 1 Semelhante ao Glucagon/uso terapêutico , Humanos , Incretinas/uso terapêutico , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto
16.
Lancet Diabetes Endocrinol ; 2(2): 116-24, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24622715

RESUMO

BACKGROUND: Metformin reduces cardiovascular risk in patients with type 2 diabetes seemingly independent of lowering blood glucose concentration. We assessed the cardiovascular effects of metformin in individuals without type 2 diabetes. METHODS: We did a single-centre, double-blind, placebo-controlled trial at the Glasgow Clinical Research Facility (Glasgow, UK). We enrolled patients taking statins who did not have type 2 diabetes but who did have coronary heart disease and large waist circumferences. Participants were randomly assigned (1:1) by computer to either metformin (850 mg twice daily) or matching placebo in block sizes of four. Patients, investigators, trial staff, and statisticians were masked to treatment allocation. The primary endpoint was progression of mean distal carotid intima-media thickness (cIMT) over 18 months in the modified intention-to-treat population. Secondary endpoints were changes in carotid plaque score (in six regions), measures of glycaemia (HbA1c, fasting glucose, and insulin concentrations, and Homeostasis Model Assessment of Insulin Resistance [HOMA-IR]), and concentrations of lipids, high sensitivity C-reactive protein, and tissue plasminogen activator. The trial was registered at ClinicalTrials.gov, number NCT00723307. FINDINGS: We screened 356 patients, of whom we enrolled 173 (86 in the metformin group, 87 in the placebo group). Average age was 63 years. At baseline, mean cIMT was 0·717 mm (SD 0·129) and mean carotid plaque score was 2·43 (SD 1·55). cIMT progression did not differ significantly between groups (slope difference 0·007 mm per year, 95% CI -0·006 to 0·020; p=0·29). Change of carotid plaque score did not differ significantly between groups (0·01 per year, 95% CI -0·23 to 0·26; p=0·92). Patients taking metformin had lower HbA1c, insulin, HOMA-IR, and tissue plasminogen activator compared with those taking placebo, but there were no significant differences for total cholesterol, HDL-cholesterol, non-HDL-cholesterol, triglycerides, high sensitivity C-reactive protein, or fasting glucose. 138 adverse events occurred in 64 patients in the metformin group versus 120 in 60 patients in the placebo group. Diarrhoea and nausea or vomiting were more common in the metformin group than in the placebo group (28 vs 5). INTERPRETATION: Metformin had no effect on cIMT and little or no effect on several surrogate markers of cardiovascular disease in non-diabetic patients with high cardiovascular risk, taking statins. Further evidence is needed before metformin can be recommended for cardiovascular benefit in this population. FUNDING: Chief Scientist Office (Scotland).


Assuntos
Espessura Intima-Media Carotídea , Doença das Coronárias/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Idoso , Glicemia , Método Duplo-Cego , Feminino , Humanos , Hipoglicemiantes/efeitos adversos , Resistência à Insulina , Masculino , Metformina/efeitos adversos , Pessoa de Meia-Idade , Túnica Íntima/efeitos dos fármacos , Circunferência da Cintura
17.
Am J Ind Med ; 56(10): 1125-36, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23794247

RESUMO

BACKGROUND: A medical surveillance program was developed to identify current and former construction workers at significant risk for beryllium related disease from work at the DOE nuclear weapons facilities, and to improve surveillance among beryllium exposed workers. METHODS: Medical examinations included a medical history and a beryllium blood lymphocyte proliferation test (BeLPT). Stratified and multivariate logistic regression analyses were used to explore the risk of disease by age, race, trade, and reported work in buildings where beryllium was used. After adjusting for covariates, the risk of BeS was significantly higher among boilermakers, roofers, and sheet metal workers, as suggested in the stratified analyses. Workers identified as sensitized to beryllium were interviewed to determine whether they had been subsequently diagnosed with chronic beryllium disease. RESULTS: Between 1998 and December 31, 2010 13,810 workers received a BeLPT through the BTMed program; 189 (1.4%) were sensitized to beryllium, and 28 reported that they had had a compensation claim accepted for CBD. CONCLUSIONS: These data on former construction workers gives us additional information about the predictive value of the blood BeLPT test for detection of CBD in populations with lower total lifetime exposures and more remote exposures than that experienced by current workers in beryllium machining operations. Through this surveillance program we have identified routes of exposures to beryllium and worked with DOE site personnel to identity and mitigate those exposures which still exist, as well as helping to focus attention on the risk for beryllium exposure among current demolition workers at these facilities.


Assuntos
Beriliose/epidemiologia , Indústria da Construção/estatística & dados numéricos , Adulto , Idoso , Beriliose/diagnóstico , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Armas Nucleares , Estados Unidos/epidemiologia , United States Government Agencies
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