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1.
Lancet ; 398(10300): 583-598, 2021 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-34370970

RESUMO

BACKGROUND: Tirzepatide is a novel dual glucose-dependent insulinotropic polypeptide and GLP-1 receptor agonist under development for the treatment of type 2 diabetes. We aimed to assess the efficacy and safety of tirzepatide versus titrated insulin degludec in people with type 2 diabetes inadequately controlled by metformin with or without SGLT2 inhibitors. METHODS: In this open-label, parallel-group, multicentre (122 sites), multinational (13 countries), phase 3 study, eligible participants (aged ≥18 years) had a baseline glycated haemoglobin (HbA1c) of 7·0-10·5%, body-mass index of at least 25 kg/m2, stable weight, and were insulin-naive and treated with metformin alone or in combination with an SGLT2 inhibitor for at least 3 months before screening. Participants were randomly assigned (1:1:1:1), using an interactive web-response system, to once-weekly subcutaneous injection of tirzepatide (5, 10, or 15 mg) or once-daily subcutaneous injection of titrated insulin degludec, and were stratified by country, HbA1c, and concomitant use of oral antihyperglycaemic medications. Tirzepatide was initially given at 2·5 mg and the dose was escalated by 2·5 mg every 4 weeks until the assigned dose was reached. Insulin degludec was initially given at 10 U per day and was titrated once weekly to a fasting self-monitored blood glucose of less than 5·0 mmol/L (<90 mg/dL), following a treat-to-target algorithm, for 52 weeks. The primary efficacy endpoint was non-inferiority of tirzepatide 10 mg or 15 mg, or both, versus insulin degludec in mean change from baseline in HbA1c at week 52. Key secondary efficacy endpoints were non-inferiority of tirzepatide 5 mg versus insulin degludec in mean change from baseline in HbA1c at week 52, superiority of all doses of tirzepatide versus insulin degludec in mean change from baseline in HbA1c and bodyweight, and the proportion of participants achieving HbA1c of less than 7·0% (<53 mmol/mol) at week 52. We used a boundary of 0·3% to establish non-inferiority in HbA1c difference between treatments. Efficacy and safety analyses were assessed in the modified intention-to-treat population (all participants who received at least one dose of study drug). This trial is registered with ClinicalTrials.gov, number NCT03882970, and is complete. FINDINGS: Between April 1 and Nov 15, 2019, we assessed 1947 participants for eligibility, 1444 of whom were randomly assigned to treatment. The modified intention-to-treat population was 1437 participants from the tirzepatide 5 mg (n=358), tirzepatide 10 mg (n=360), tirzepatide 15 mg (n=359), and insulin degludec (n=360) groups. From a mean baseline HbA1c of 8·17% (SD 0·91), the reductions in HbA1c at week 52 were 1·93% (SE 0·05) for tirzepatide 5 mg, 2·20% (0·05) for tirzepatide 10 mg, and 2·37% (0·05) for tirzepatide 15 mg, and 1·34% (0·05) for insulin degludec. The non-inferiority margin of 0·3% was met. The estimated treatment difference (ETD) versus insulin degludec ranged from -0·59% to -1·04% for tirzepatide (p<0·0001 for all tirzepatide doses). The proportion of participants achieving a HbA1c of less than 7·0% (<53 mmol/mol) at week 52 was greater (p<0·0001) in all three tirzepatide groups (82%-93%) versus insulin degludec (61%). At week 52, from a baseline of 94·3 kg (SD 20·1), all three tirzepatide doses decreased bodyweight (-7·5 kg to -12·9 kg), whereas insulin degludec increased bodyweight by 2·3 kg. The ETD versus insulin degludec ranged from -9·8 kg to -15·2 kg for tirzepatide (p<0·0001 for all tirzepatide doses). The most common adverse events in tirzepatide-treated participants were mild to moderate gastrointestinal events that decreased over time. A higher incidence of nausea (12-24%), diarrhoea (15-17%), decreased appetite (6-12%), and vomiting (6-10%) was reported in participants treated with tirzepatide than in those treated with insulin degludec (2%, 4%, 1%, and 1%, respectively). Hypoglycaemia (<54 mg/dL or severe) was reported in five (1%), four (1%), and eight (2%) participants on tirzepatide 5, 10, and 15 mg, respectively, versus 26 (7%) on insulin degludec. Treatment discontinuation due to an adverse event was more common in the tirzepatide groups than in the insulin degludec group. Five participants died during the study; none of the deaths were considered by the investigators to be related to the study treatment. INTERPRETATION: In patients with type 2 diabetes, tirzepatide (5, 10, and 15 mg) was superior to titrated insulin degludec, with greater reductions in HbA1c and bodyweight at week 52 and a lower risk of hypoglycaemia. Tirzepatide showed a similar safety profile to that of GLP-1 receptor agonists. FUNDING: Eli Lilly and Company.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Polipeptídeo Inibidor Gástrico/administração & dosagem , Hipoglicemiantes/administração & dosagem , Insulina de Ação Prolongada/uso terapêutico , Metformina/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Feminino , Hemoglobina A Glicada/efeitos dos fármacos , Humanos , Injeções Subcutâneas , Internacionalidade , Masculino , Pessoa de Meia-Idade
2.
N Engl J Med ; 385(6): 503-515, 2021 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-34170647

RESUMO

BACKGROUND: Tirzepatide is a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 (GLP-1) receptor agonist that is under development for the treatment of type 2 diabetes. The efficacy and safety of once-weekly tirzepatide as compared with semaglutide, a selective GLP-1 receptor agonist, are unknown. METHODS: In an open-label, 40-week, phase 3 trial, we randomly assigned 1879 patients, in a 1:1:1:1 ratio, to receive tirzepatide at a dose of 5 mg, 10 mg, or 15 mg or semaglutide at a dose of 1 mg. At baseline, the mean glycated hemoglobin level was 8.28%, the mean age 56.6 years, and the mean weight 93.7 kg. The primary end point was the change in the glycated hemoglobin level from baseline to 40 weeks. RESULTS: The estimated mean change from baseline in the glycated hemoglobin level was -2.01 percentage points, -2.24 percentage points, and -2.30 percentage points with 5 mg, 10 mg, and 15 mg of tirzepatide, respectively, and -1.86 percentage points with semaglutide; the estimated differences between the 5-mg, 10-mg, and 15-mg tirzepatide groups and the semaglutide group were -0.15 percentage points (95% confidence interval [CI], -0.28 to -0.03; P = 0.02), -0.39 percentage points (95% CI, -0.51 to -0.26; P<0.001), and -0.45 percentage points (95% CI, -0.57 to -0.32; P<0.001), respectively. Tirzepatide at all doses was noninferior and superior to semaglutide. Reductions in body weight were greater with tirzepatide than with semaglutide (least-squares mean estimated treatment difference, -1.9 kg, -3.6 kg, and -5.5 kg, respectively; P<0.001 for all comparisons). The most common adverse events were gastrointestinal and were primarily mild to moderate in severity in the tirzepatide and semaglutide groups (nausea, 17 to 22% and 18%; diarrhea, 13 to 16% and 12%; and vomiting, 6 to 10% and 8%, respectively). Of the patients who received tirzepatide, hypoglycemia (blood glucose level, <54 mg per deciliter) was reported in 0.6% (5-mg group), 0.2% (10-mg group), and 1.7% (15-mg group); hypoglycemia was reported in 0.4% of those who received semaglutide. Serious adverse events were reported in 5 to 7% of the patients who received tirzepatide and in 3% of those who received semaglutide. CONCLUSIONS: In patients with type 2 diabetes, tirzepatide was noninferior and superior to semaglutide with respect to the mean change in the glycated hemoglobin level from baseline to 40 weeks. (Funded by Eli Lilly; SURPASS-2 ClinicalTrials.gov number, NCT03987919.).


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Polipeptídeo Inibidor Gástrico/administração & dosagem , Peptídeos Semelhantes ao Glucagon/administração & dosagem , Hipoglicemiantes/administração & dosagem , Glicemia/análise , Diabetes Mellitus Tipo 2/sangue , Relação Dose-Resposta a Droga , Esquema de Medicação , Quimioterapia Combinada , Feminino , Polipeptídeo Inibidor Gástrico/efeitos adversos , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Peptídeos Semelhantes ao Glucagon/efeitos adversos , Hemoglobina A Glicada/análise , Humanos , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/uso terapêutico , Incretinas/uso terapêutico , Injeções Subcutâneas , Masculino , Metformina/uso terapêutico , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Perda de Peso/efeitos dos fármacos
3.
Br J Sports Med ; 2021 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-33849908

RESUMO

OBJECTIVES: To (1) determine if wearing a cloth face mask significantly affected exercise performance and associated physiological responses, and (2) describe perceptual measures of effort and participants' experiences while wearing a face mask during a maximal treadmill test. METHODS: Randomised controlled trial of healthy adults aged 18-29 years. Participants completed two (with and without a cloth face mask) maximal cardiopulmonary exercise tests (CPETs) on a treadmill following the Bruce protocol. Blood pressure, heart rate, oxygen saturation, exertion and shortness of breath were measured. Descriptive data and physical activity history were collected pretrial; perceptions of wearing face masks and experiential data were gathered immediately following the masked trial. RESULTS: The final sample included 31 adults (age=23.2±3.1 years; 14 women/17 men). Data indicated that wearing a cloth face mask led to a significant reduction in exercise time (-01:39±01:19 min/sec, p<0.001), maximal oxygen consumption (VO2max) (-818±552 mL/min, p<0.001), minute ventilation (-45.2±20.3 L/min), maximal heart rate (-8.4±17.0 beats per minute, p<0.01) and increased dyspnoea (1.7±2.9, p<0.001). Our data also suggest that differences in SpO2 and rating of perceived exertion existed between the different stages of the CPET as participant's exercise intensity increased. No significant differences were found between conditions after the 7-minute recovery period. CONCLUSION: Cloth face masks led to a 14% reduction in exercise time and 29% decrease in VO2max, attributed to perceived discomfort associated with mask-wearing. Compared with no mask, participants reported feeling increasingly short of breath and claustrophobic at higher exercise intensities while wearing a cloth face mask. Coaches, trainers and athletes should consider modifying the frequency, intensity, time and type of exercise when wearing a cloth face mask.

4.
Proc (Bayl Univ Med Cent) ; 33(4): 674-676, 2020 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-33100567

RESUMO

A 53-year-old male mountain biker received a total artificial heart and remained in the cardiovascular intensive care unit for 56 days. To reduce functional decline caused by inactivity, he performed a six-session cycle ergometer exercise program in his hospital room. Traditional cardiac responses for exercise prescription were not applicable; therefore, a symptom-limited, monitored progression scheme in conjunction with recommendations for the artificial heart was implemented to modify duration and intensity. Over the six sessions, the patient improved his distance pedaled by 320% and functional capacity by 1 metabolic equivalent. He was subsequently discharged from the hospital and later successfully transplanted without readmission.

5.
J Org Chem ; 85(19): 12012-12023, 2020 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-32938175

RESUMO

The anthracyclines are structurally diverse anticancer natural products that bind to DNA and poison the topoisomerase II-DNA complex in cancer cells. Rational modifications in the deoxysugar functionality are especially advantageous for synthesizing drugs with improved potency. Combinatorial biosynthesis of glycosyltransferases and deoxysugar synthesis enzymes is indispensable for the generation of glycodiversified anthracyclines. This Synopsis considers recent advances in glycosyltransferase structural biology and site-directed mutagenesis, pathway engineering, and deoxysugar combinatorial biosynthesis with a focus on the generation of "new-to-nature" anthracycline analogues.


Assuntos
Produtos Biológicos , Policetídeos , Antraciclinas , Glicosilação , Glicosiltransferases/metabolismo
6.
Proc (Bayl Univ Med Cent) ; 33(3): 342-345, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32675950

RESUMO

The purpose of this study was to investigate the maximum rate-pressure product of cardiac rehabilitation participants after myocardial infarction, percutaneous coronary intervention, or both during high-intensity resistance training (HI-RT) using continuous blood pressure monitoring. Thirty-four individuals exercised on the leg press machine while being monitored with a continuous blood pressure monitor. The maximum rate-pressure product was significantly lower than the established safety threshold of 36,000 (P < 0.001), with a mean of 17,369 and standard deviation of 6634. Only 2% of observations had a value ≥36,000. These results suggest that cardiac rehabilitation patients can perform HI-RT while keeping their rate-pressure products under the safety threshold of 36,000 after myocardial infarction/percutaneous coronary intervention. Performance of HI-RT exercises contributes to return to precardiac event occupations, and continuous blood pressure monitoring may be an effective tool in evaluating the safety of HI-RT in this patient population.

7.
J Manag Care Spec Pharm ; 26(7): 839-847, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32584684

RESUMO

BACKGROUND: Few studies have examined patient characteristics and treatment patterns of high-dose insulin therapy (> 200 units/day) among patients with type 2 diabetes mellitus (T2DM). OBJECTIVE: To understand patient characteristics, dosing, adherence, and persistence related to high-dose insulin therapy. METHODS: This was a retrospective observational study that used administrative claims from a large national health plan. Patients were identified who had been diagnosed with T2DM and who were aged 18-89 years, enrolled in a commercial or Medicare Advantage Prescription Drug plan, newly initiated on a total daily dose (TDD) > 200 units of insulin between January 2011 and August 2015. Patients were required to be enrolled 6 months before and 12 months after the index date. Patients were categorized to Regimen-100 if treated with U-100 insulin only or Regimen-500 if treated with U-500R with or without U-100. Baseline demographic and clinical characteristics were evaluated. An adjustment factor for the days supply was calculated as the ratio of median time between insulin claims, and median pharmacy reported days supply for each insulin prescription. Adjusted days supply, quantity, and concentration were used to calculate TDD for each quarter after the index date. Adherence was measured as the proportion of days covered (PDC) for each regimen. Persistence was measured in 2 ways: the percentage of patients remaining on index medications in each quarter and the proportion of patients who maintained TDD > 200 units during all 4 quarters of the 12-month post-index period. RESULTS: We identified 2,339 patients newly titrated up to TDD > 200 units on either Regimen-100 (2,062, 88.2%) or Regimen-500 (277, 11.8%). Patients on Regimen-500 were slightly younger with higher prevalence of comorbidities. The mean TDD (SD) for Regimen-100 decreased from 228.6 (36.0) units during the first quarter to 194.2 (181.4) units during the last quarter. The mean TDD (SD) for Regimen-500 increased from 294.2 (102.2) units in the first quarter to 304.8 (281.6) units in last quarter. The average adherence to the high-dose insulin regimen was 68.2% (30.7; median 72.6%) for the Regimen-100 cohort and 75.5% (27.0; median 85.2%) for the Regimen-500 cohort. In the Regimen-100 and Regimen-500 cohorts, 45.3% and 55.2% had a PDC ≥ 80%, respectively. Only 23.0% and 51.6% of patients maintained TDD > 200 units for the Regimen-100 and Regimen-500 cohorts, respectively, throughout the 4 quarters after the index date. CONCLUSIONS: We observed that many patients did not maintain high-dose insulin use over time, especially those on standard U-100 insulin only. This dosing pattern appears to reflect the differences in patient characteristics, insulin needs, and adherence/persistence behavior between those on Regimen-100 and those on Regimen-500. DISCLOSURES: This study was supported by funding from Eli Lilly and Company to Humana as a collaborative research project involving employees of both companies. Chen, Brown, Fan, Taylor, and He are employees of Eli Lilly and Company. Nair and Meah are employees of Humana, which received funding to complete this research. Siadaty was an employee of Humana at the time of this study.


Assuntos
Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Revisão da Utilização de Seguros , Adesão à Medicação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Diabetes Mellitus Tipo 2/epidemiologia , Relação Dose-Resposta a Droga , Feminino , Humanos , Revisão da Utilização de Seguros/tendências , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
8.
Neuropsychol Rehabil ; 30(9): 1829-1851, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31046586

RESUMO

There is currently a need to identify feasible and effective interventions to help older individuals suffering from memory loss maintain functional independence and quality of life. To improve upon paper and pencil memory notebook interventions, the Digital Memory Notebook (DMN) application (app) was developed iteratively with persons with cognitive impairment. In this paper we detail a manual-based intervention for training use of the DMN app. A series of three case studies are described to illustrate the clinical process of the DMN intervention, the key components of the intervention and participants' perceptions of the intervention. The Reliable Change Index was applied to pre/post intervention scores that examined everyday memory lapses, daily functioning, coping self-efficacy, satisfaction with life, and quality of life with standardized measures. Following the intervention, two of three participants self-reported a clinically significant reduction in everyday memory lapses and improved everyday functioning. One participant reported clinically significant change in quality of life. All participants demonstrated clinically significant changes in their ability to cope with problems and build self-efficacy. Furthermore, all participants scored in the normative range post-intervention on the measure of satisfaction with life. Clinical observations and participant feedback were used for refinement of the DMN intervention (ClinicalTrials.gov NCT03453554).


Assuntos
Disfunção Cognitiva/reabilitação , Remediação Cognitiva , Transtornos da Memória/reabilitação , Idoso , Remediação Cognitiva/instrumentação , Remediação Cognitiva/métodos , Computadores de Mão , Humanos , Aplicativos Móveis , Avaliação de Resultados da Assistência ao Paciente , Design de Software
9.
Disabil Rehabil Assist Technol ; 15(4): 421-431, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-30907223

RESUMO

Purpose: Memory impairment can necessitate use of external memory aids to preserve functional independence. As external aids can be difficult to learn and remember to use, technology may improve the efficacy of current rehabilitation strategies. We detail the iterative development of a digital application of a paper-and-pencil memory notebook.Methods: Twenty participants (aged 54+) of varying levels of cognitive ability were recruited for four iterations of usability testing (five participants per iteration). Each participant completed a series of tasks using the digital memory notebook (DMN), followed by questionnaires that assessed satisfaction (Questionnaire for User Interface Satisfaction) and usability ratings (Post-Study System Usability Questionnaire) for the application.Results and Conclusions: Between Iterations 2 and 5, participants demonstrated marked reductions in time to complete several types of tasks (e.g., add event, navigate interface) using the DMN. Participants in Iteration 5 also rated all subscales of both the usability and satisfaction questionnaires very highly. Faster task completion times were correlated with more favourable system ratings. However, neither task performance times nor system ratings were correlated with cognitive abilities, scheduling tool use or comfort with technology. Both the questionnaire and performance-based data indicate the final iteration of the DMN was easy to use. Furthermore, the application was user-friendly despite individual differences in cognitive ability, familiarity with scheduling tools and comfort with technology. Future work will demonstrate whether the DMN will support everyday retrospective and prospective memory lapses and increase the functional independence and quality of life for persons with cognitive impairment.Implications for rehabilitationBuilding on practice standards and user-centred design, the digital memory notebook (DMN) application is an "all-in-one" memory aid and organizational tool with an intuitive interface designed to help improve everyday functioning.The DMN's today page, to do list and calendar functions can support everyday prospective and retrospective memory abilities.The DMN's notes, journaling and motivational functions can support longer-term goal planning and mood management.The DMN's alarm functions can support learning to use the DMN and serve as reminders to support prospective memory and aid in activity completion.


Assuntos
Atividades Cotidianas , Disfunção Cognitiva/reabilitação , Computadores de Mão , Transtornos da Memória/reabilitação , Aplicativos Móveis , Interface Usuário-Computador , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários
10.
J Clin Exp Neuropsychol ; 42(1): 1-13, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31658865

RESUMO

Objective: Planning, a higher order executive functioning ability important for accomplishing complex everyday tasks, can be differentiated into initial and concurrent (online) planning. In this study, initial plans were codified to assess their impact on task execution. Cognitive correlates of initial planning and task execution were also examined.Method: One-hundred fifty-four community dwelling older adults completed a naturalistic task, called the Day Out Task (DOT), in either a planning or no planning condition. The DOT required participants to multitask and efficiently complete a series of eight subtasks, preparing for a hypothetical day out. Participants also completed a neuropsychological battery with the following cognitive constructs assessed: processing speed, cognitive flexibility, episodic memory, visuoconstructional abilities, and working memory and sequencing.Results: There were no significant differences between the planning and no planning conditions in DOT execution accuracy, efficiency or duration. However, efficiency of the initial plan was a significant predictor of task execution efficiency and initial plans that contained a higher amount of Task Relevant Associations predicted a shorter duration of task execution after controlling for age, processing speed and episodic memory. Furthermore, initial plans that had more Task Relevant Associations and task executions that took less time were associated with better working memory and sequencing ability.Discussion: Quality of the initial plan is important. Initial plans that organize task objectives in an efficient manner may lead to better task execution efficiency, while initial plans that demonstrate a detailed understanding of individual relational aspects of the tasks (i.e., higher rate of Task Relevant Associations) may result in faster task execution.


Assuntos
Envelhecimento/fisiologia , Função Executiva/fisiologia , Desempenho Psicomotor/fisiologia , Pensamento/fisiologia , Idoso , Feminino , Humanos , Masculino , Memória Episódica , Memória de Curto Prazo/fisiologia , Pessoa de Meia-Idade , Fatores de Tempo
11.
Proc (Bayl Univ Med Cent) ; 32(1): 113-115, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30956602

RESUMO

A 53-year-old female athlete with spontaneous coronary artery dissection, acute myocardial infarction, and infrarenal abdominal aortic dissection enrolled in a 6-week cardiovascular rehabilitation (CR) program. During CR sessions, the patient performed a combination of aerobic, resistance training, and core activities. In the final CR session, the patient performed reflex activities and the forced Valsalva maneuver. The patient's electrocardiogram, blood pressure, heart rate, and transient change in blood pressure over time were continuously monitored and recorded. The patient completed CR without negative symptoms or adverse events.

12.
Ther Innov Regul Sci ; 52(2): 256-260, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29714516

RESUMO

BACKGROUND: Proprietary names are often used when prescribing drug products in the United States. The purpose of this study is to describe prescribers' use of proprietary names for generic products, branded-generic names, on prescription orders and to identify prescribing practice trends to inform the development and evaluation of new proprietary names. METHODS: To identify Abbreviated New Drug Application (ANDA) with branded-generic names approved between January 2003 and December 2012, we utilized the database provided by the FDA Office of Communications, Drugs@FDA . A national outpatient retail prescription database, IMS's Vector One: National (VONA) was used to identify prescribing trends by examining data for branded-generic names identified in Drugs@FDA as they were written on prescriptions for years 2003 to 2012, the last year of data collection for VONA. IMS Health, IMS National Sales Perspectives (IMS NSP) was used to retrieve the date that product sales were first reported (launch date). RESULTS: Our search of Drugs@FDA identified 65 distinct branded-generic names approved between January 2003 and December 2012. Data show that most of these products with branded-generic names are written on prescriptions and sold to pharmacies within a year of FDA approval. In some cases, the use of branded-generic names persists for up to 9 years after drug approval. CONCLUSION: This descriptive study confirmed that branded-generic names are used in prescribing. Thus, evaluation of orthographic and phonetic similarities between proposed proprietary names and branded-generic names is necessary when formulating and evaluating new proprietary names.


Assuntos
Prescrições de Medicamentos , Medicamentos Genéricos , Padrões de Prática Médica , Terminologia como Assunto , Aprovação de Drogas , Humanos , Médicos , Estados Unidos , United States Food and Drug Administration
13.
Diseases ; 6(2)2018 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-29783736

RESUMO

Pediatric acute lymphoblastic leukemia (ALL) represents the most common pediatric cancer diagnosis, with numbers rising gradually every year. This paper proposes a novel therapeutic agent for pediatric ALL on the basis of a failed clinical drug trial in 2006. TGN1412 was a promising therapeutic agent that yielded outstanding results in both in vitro studies and animal trials. It is a CD28 superagonist monoclonal antibody that activates T regulatory (TReg) cells in the absence of costimulation of the T cell receptor (TCR) by an antigen-presenting cell. This drug was intended as a solution to T cell deficient diseases such as B cell leukemia and autoimmune diseases such as rheumatoid arthritis. When phase I clinical trials were conducted, all volunteers that received the drug experienced severe cytokine release syndrome (CRS) and faced multiple-organ failure within hours. TGN1412 was reassessed and re-entered clinical trials as a therapeutic for rheumatoid arthritis. A new assay was developed to better quantify T cell response, and volunteers in this trial experienced no pro-inflammatory cytokine release. This essay analyzes how misinformation contributed to the failure of TGN1412 in clinical trials and how revisiting this therapeutic could yield a novel treatment for pediatric B cell leukemia.

14.
J Clin Rheumatol ; 24(8): 422-426, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29538083

RESUMO

BACKGROUND/OBJECTIVE: Despite effective therapies, rheumatoid arthritis (RA) can result in joint destruction requiring total joint arthroplasty to maintain patient function. An estimated 16% to 70% of those undergoing total joint arthroplasty of the hip or knee will receive a blood transfusion. Few studies have described risk factors for blood transfusion following total joint arthroplasty in patients with RA. The aim of this study was to identify demographic and clinical risk factors associated with receiving a blood transfusion following total joint arthroplasty among patients with RA. METHODS: A retrospective study (n = 3270) was conducted using deidentified patient health claims information from a commercially insured, US data set (2007-2009). Data analysis included descriptive statistics and multivariate logistic regression. RESULTS: Females were more likely to receive a blood transfusion (odds ratio [OR], 1.48; 95% confidence interval [CI], 1.16-1.87; p = 0.001). When compared with those in the South, patients residing the Midwest were less likely to receive a blood transfusion following total joint arthroplasty (OR, 0.56; 95% CI, 0.44-0.71). Relative to those receiving total knee arthroplasty, patients who underwent total hip arthroplasty were more likely to receive a blood transfusion (OR, 1.39; 95% CI, 1.14-1.70), and patients who underwent a total shoulder arthroplasty were less likely to receive a blood transfusion (OR, 0.14; 95% CI, 0.05-0.38; p < 0.001). Patients with a history of anemia were more likely to receive a blood transfusion compared with those who did not have this diagnosis (OR, 3.30; 95% CI, 2.62-4.14; p < 0.001). CONCLUSIONS: Risk factors for the receipt of blood transfusions among RA patients who have undergone total joint arthroplasty were identified.


Assuntos
Artrite Reumatoide/cirurgia , Artroplastia de Quadril/efeitos adversos , Artroplastia do Joelho/efeitos adversos , Transfusão de Sangue/métodos , Adulto , Idoso , Artrite Reumatoide/diagnóstico , Artroplastia de Quadril/métodos , Perda Sanguínea Cirúrgica , Estudos de Coortes , Bases de Dados Factuais , Feminino , Seguimentos , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Cuidados Pós-Operatórios/métodos , Falha de Prótese , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença , Resultado do Tratamento
15.
Appl Neuropsychol Adult ; 25(4): 363-365, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28388233

RESUMO

The Cognistat is a widely used neurobehavioral screening instrument that addresses functioning across multiple domains. Unlike many popular neuropsychological tests, the Cognistat does not currently assess learning efficiency for verbal material. The purpose of this study was to develop a screening method for assessing verbal learning efficiency with the Cognistat, investigate the effects of two demographic variables (age and gender) on performance, and to establish cutoff scores for impairment. Participants were 253 volunteers between the ages of 18 and 96 years. Participants were classified into two age groups: 18-64 years and 65 + years. The data revealed a significant age and gender performance difference. Implications for the present findings and for future research are presented.


Assuntos
Cognição/fisiologia , Testes Neuropsicológicos , Aprendizagem Verbal/fisiologia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valores de Referência , Fatores Sexuais , Adulto Jovem
16.
Diabetes Obes Metab ; 19(7): 953-961, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28181725

RESUMO

AIMS: To compare adherence (proportion of days covered [PDC]), persistence, and treatment patterns among patients with type 2 diabetes mellitus (T2DM) newly initiating glucagon-like peptide-1 receptor agonists (GLP-1RAs). More specifically, the main objectives were to compare dulaglutide vs exenatide once weekly and dulaglutide vs liraglutide. METHODS: Patients with T2DM newly initiating dulaglutide, albiglutide, exenatide once weekly, exenatide twice daily and liraglutide between November 2014 and April 2015 were hierarchically selected from Truven Health's MarketScan Research Databases. Propensity score matching was used to account for selection bias. Adherence to and persistence with the index GLP-1RA, and switching and augmentation patterns were assessed during the 6-month post-index period. RESULTS: Mean adherence for the matched cohorts was significantly higher for dulaglutide than for exenatide once weekly (0.72 vs 0.61; P < .0001) and liraglutide (0.71 vs 0.67; P < .0001). The percentage of patients achieving PDC ≥ 0.80 was significantly higher for dulaglutide compared with exenatide once weekly (54.2% vs 37.9%; P < .0001) and liraglutide (53.5% vs 44.3%; P < .0001). The mean (standard deviation) days on treatment for all matched patients was significantly higher for patients in the dulaglutide cohort compared with those in the exenatide once-weekly (148.4 [55.4] vs 123.6 [61.6]; P < .0001) and liraglutide cohorts (146.0 [56.9] vs 137.4 [60.1]; P < .0001). A significantly lower proportion of patients on dulaglutide discontinued treatment compared with those on exenatide once weekly (26.2% vs 48.4%; P < .0001) and those on liraglutide (28.0% vs 35.6%; P < .0001). CONCLUSIONS: Dulaglutide initiators had significantly higher adherence, were more persistent, and had lower discontinuation rates compared with initiators of exenatide once weekly or liraglutide during the 6-month follow-up period.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Peptídeos Semelhantes ao Glucagon/análogos & derivados , Hipoglicemiantes/uso terapêutico , Fragmentos Fc das Imunoglobulinas/uso terapêutico , Liraglutida/uso terapêutico , Peptídeos/uso terapêutico , Padrões de Prática Médica , Proteínas Recombinantes de Fusão/uso terapêutico , Peçonhas/uso terapêutico , Idoso , Estudos de Coortes , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/metabolismo , Esquema de Medicação , Monitoramento de Medicamentos , Prescrições de Medicamentos , Exenatida , Feminino , Seguimentos , Receptor do Peptídeo Semelhante ao Glucagon 1/metabolismo , Peptídeos Semelhantes ao Glucagon/administração & dosagem , Peptídeos Semelhantes ao Glucagon/efeitos adversos , Peptídeos Semelhantes ao Glucagon/uso terapêutico , Humanos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/efeitos adversos , Fragmentos Fc das Imunoglobulinas/administração & dosagem , Fragmentos Fc das Imunoglobulinas/efeitos adversos , Estimativa de Kaplan-Meier , Liraglutida/administração & dosagem , Liraglutida/efeitos adversos , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Peptídeos/administração & dosagem , Peptídeos/efeitos adversos , Proteínas Recombinantes de Fusão/administração & dosagem , Proteínas Recombinantes de Fusão/efeitos adversos , Estudos Retrospectivos , Estados Unidos , Peçonhas/administração & dosagem , Peçonhas/efeitos adversos
17.
Appl Neuropsychol Adult ; 23(5): 333-5, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26786807

RESUMO

The Cognistat is a widely used screening instrument for assessing cognitive functioning. However, the manualized scoring guidelines for one of the questions in the Judgment subtest appear insensitive to responses when examinees answer in light of current societal attitudes. Penalization of examinees is likely to lead to an underestimation of functional ability and a decrease in test validity. Suggestions for correcting this issue are presented.


Assuntos
Atitude , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/psicologia , Julgamento , Testes Neuropsicológicos , Adolescente , Adulto , Idoso , Envelhecimento/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
18.
Jt Comm J Qual Patient Saf ; 42(12): 568-AP7, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-28334561

RESUMO

BACKGROUND: The use of insulin pens in the inpatient setting has continued to be a controversial decision. Insulin pens provide several advantages, but given significant reports of medication errors, several organizations have issued alerts to caution users about safety concerns. A survey was conducted to assess the prevalence of insulin pen use and current utilization trends in the inpatient setting. METHODS: The 31-question guided-logic survey was developed based on review of primary literature regarding insulin pen utilization and evaluated by a panel of medication safety experts from a variety of health care settings. The survey was sent electronically to subscribers of medication safety organizations. RESULTS: The survey was completed by 474 respondents. Approximately three fourths of respondents indicated insulin pens were on formulary at their institution (n = 332; 74%). Of those who have had insulin pens on formulary, 15% (n = 49) are no longer using them. The most common reasons for not utilizing pens were cost and safety concerns. Pens were reported to be stored in the pharmacy prior to administration (n = 230; 78%) and in a patient's bin (n = 202; 69%) afterward. More than half of respondents use two patient identifiers on the pen and label with a bar code. Approximately 30% reported that an insulin pen has been used on more than one patient at least once in their institution, while 6% were not sure. CONCLUSION: Insulin pens are widely being used in the inpatient setting. Various mitigation strategies are employed to reduce the risk of harm associated with insulin pen use. Health care professionals believe insulin pens are clinically useful and can be used safely in the inpatient setting. Many organizations and expert panels disseminate best practices in an effort to help ensure their safety. Further studies are needed to assess and validate the risk mitigation strategies identified through this research.


Assuntos
Hipoglicemiantes/administração & dosagem , Pacientes Internados , Sistemas de Infusão de Insulina , Insulina/administração & dosagem , Erros de Medicação/prevenção & controle , Agulhas , Segurança do Paciente , Formas de Dosagem , Injeções a Jato , Inquéritos e Questionários , Revisão da Utilização de Recursos de Saúde
19.
Clin Pediatr (Phila) ; 54(11): 1102-6, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25644650

RESUMO

BACKGROUND: Acid-suppressing agents have been associated with increased Clostridium difficile infection (CDI) in adults. The objective of this study was to evaluate the association of acid-suppressing therapy with the development of CDI in the pediatric population. METHODS: This was a retrospective case-control study. Children aged 1 through 17 years with a positive C difficile polymerase chain reaction (PCR) result obtained between June 1, 2008, and June 1, 2012, were randomly matched to a control population selected from patients with negative PCR. RESULTS: A total of 458 children were included. No difference was observed in acid-suppressive therapy prior to PCR in CDI-positive versus -negative patients (n = 131 [57.2%] vs n = 121 [52.8%], P = .348). Among patients receiving acid-suppressing therapy prior to obtaining a PCR, no difference was observed in proton pump inhibitor use (45% vs 46.3%, P = .843), but histamine-2 receptor antagonist (H2RA) use was greater in the CDI-positive patients (32.8% vs 14.9%, P = .001). Logistic regression analysis demonstrated that H2RA therapy at home (odds ratio = 4.6; 95% confidence interval = 1.5-14.5) was an independent CDI predictor. CONCLUSION: In this pediatric population, CDI risk in children receiving home acid-suppressive therapy with H2RAs is nearly 4.5 times greater than that of children not receiving H2RA therapy. These results suggest the need for continued monitoring and study of H2RA therapy in children.


Assuntos
Clostridioides difficile/efeitos dos fármacos , Infecções por Clostridium/epidemiologia , Antagonistas dos Receptores H2 da Histamina/efeitos adversos , Inibidores da Bomba de Prótons/efeitos adversos , Adolescente , Antiulcerosos/efeitos adversos , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Reação em Cadeia da Polimerase , Estudos Retrospectivos , Fatores de Risco
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