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1.
Cell ; 151(2): 320-32, 2012 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-23039994

RESUMO

How cells form global, self-organized structures using genetically encoded molecular rules remains elusive. Here, we take a synthetic biology approach to investigate the design principles governing cell polarization. First, using a coarse-grained computational model, we searched for all possible simple networks that can achieve polarization. All solutions contained one of three minimal motifs: positive feedback, mutual inhibition, or inhibitor with positive feedback. These minimal motifs alone could achieve polarization under limited conditions; circuits that combined two or more of these motifs were significantly more robust. With these design principles as a blueprint, we experimentally constructed artificial polarization networks in yeast, using a toolkit of chimeric signaling proteins that spatially direct the synthesis and degradation of phosphatidylinositol (3,4,5)-trisphosphate (PIP(3)). Circuits with combinatorial motifs yielded clear foci of synthetic PIP(3) that can persist for nearly an hour. Thus, by harnessing localization-regulated signaling molecules, we can engineer simple molecular circuits that reliably execute spatial self-organized programs.


Assuntos
Modelos Biológicos , Fosfatos de Fosfatidilinositol/metabolismo , Saccharomyces cerevisiae/citologia , Algoritmos , Polaridade Celular , Citosol/metabolismo , Retroalimentação Fisiológica , Fosfatos de Fosfatidilinositol/biossíntese , Biologia Sintética
2.
Am J Obstet Gynecol ; 2024 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-38768799

RESUMO

The market for technology that tracks ovulation to promote conception is rapidly expanding in the United States, targeting the growing audience of technologically proficient, reproductive-age female consumers. In this narrative review, 23 different, nonprescription wearables and devices designed to help women track their fertile window were identified as currently, commercially available in the United States. The majority of these utilize measurements of basal body temperature or combinations of various urinary hormones. This clinical opinion characterizes the scant available research validating the accuracy of these technologies. It further examines research oversight, discusses the utility of these wearables and devices to consumers, and considers these technologies through an equity lens. The discussion concludes with a call for innovation, describing promising new technologies that not only harness unique physiologic parameters to predict ovulation, but also focus on cost-effectiveness with the hope of increasing access to these currently costly devices and wearables.

3.
Am J Obstet Gynecol ; 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38552817

RESUMO

BACKGROUND: Persistent pregnancies of unknown location are defined by abnormally trending serum human chorionic gonadotropin with nondiagnostic ultrasound. There is no consensus on optimal management. OBJECTIVE: This study aimed to assess the cost-effectiveness of 3 primary management strategies for persistent pregnancies of unknown location: (1) expectant management, (2) empirical 2-dose methotrexate, and (3) uterine evacuation followed by methotrexate, if indicated. STUDY DESIGN: This was a prospective economic evaluation performed concurrently with the Expectant versus Active Management for Treatment of Persistent Pregnancies of Unknown Location multicenter randomized trial that was conducted from July 2014 to June 2019. Participants were randomized 1:1:1 to expectant management, 2-dose methotrexate, or uterine evacuation. The analysis was from the healthcare sector perspective with a 6-week time horizon after randomization. Costs were expressed in 2018 US dollars. Effectiveness was measured in quality-adjusted life years and the rate of salpingectomy. Incremental cost-effectiveness ratios and cost-effectiveness acceptability curves were generated. Sensitivity analyses were performed to assess the robustness of the analysis. RESULTS: Methotrexate had the lowest mean cost ($875), followed by expectant management ($1085) and uterine evacuation ($1902) (P=.001). Expectant management had the highest mean quality-adjusted life years (0.1043), followed by methotrexate (0.1031) and uterine evacuation (0.0992) (P=.0001). The salpingectomy rate was higher for expectant management than for methotrexate (9.4% vs 1.2%, respectively; P=.02) and for expectant management than for uterine evacuation (9.4% vs 8.1%, respectively; P=.04). Uterine evacuation, with the highest costs and the lowest quality-adjusted life years, was dominated by both expectant management and methotrexate. In the base case analysis, expectant management was not cost-effective compared with methotrexate at a willingness to pay of $150,000 per quality-adjusted life year given an incremental cost-effectiveness ratio of $175,083 per quality-adjusted life year gained (95% confidence interval, -$1,666,825 to $2,676,375). Threshold analysis demonstrated that methotrexate administration would have to cost $214 (an increase of $16 or 8%) to favor expectant management. Moreover, expectant management would be favorable in lower-risk patient populations with rates of laparoscopic surgical management for ectopic pregnancy not exceeding 4% of pregnancies of unknown location. Based on the cost-effectiveness acceptability curves, the probability of expectant management being cost-effective compared with methotrexate at a willingness to pay of $150,000 per quality-adjusted life year gained was 50%. The results were dependent on the cost of surgical intervention and the expected rate of methotrexate failure. CONCLUSION: The management of pregnancies of unknown location with a 2-dose methotrexate protocol may be cost-effective compared with expectant management and uterine evacuation. Although uterine evacuation was dominated, expectant management vs methotrexate results were sensitive to modest changes in treatment costs of both methotrexate and surgical management.

4.
Proc Natl Acad Sci U S A ; 118(20)2021 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-33972445

RESUMO

Vital signs monitoring is a fundamental component of ensuring the health and safety of women and newborns during pregnancy, labor, and childbirth. This monitoring is often the first step in early detection of pregnancy abnormalities, providing an opportunity for prompt, effective intervention to prevent maternal and neonatal morbidity and mortality. Contemporary pregnancy monitoring systems require numerous devices wired to large base units; at least five separate devices with distinct user interfaces are commonly used to detect uterine contractility, maternal blood oxygenation, temperature, heart rate, blood pressure, and fetal heart rate. Current monitoring technologies are expensive and complex with implementation challenges in low-resource settings where maternal morbidity and mortality is the greatest. We present an integrated monitoring platform leveraging advanced flexible electronics, wireless connectivity, and compatibility with a wide range of low-cost mobile devices. Three flexible, soft, and low-profile sensors offer comprehensive vital signs monitoring for both women and fetuses with time-synchronized operation, including advanced parameters such as continuous cuffless blood pressure, electrohysterography-derived uterine monitoring, and automated body position classification. Successful field trials of pregnant women between 25 and 41 wk of gestation in both high-resource settings (n = 91) and low-resource settings (n = 485) demonstrate the system's performance, usability, and safety.


Assuntos
Monitorização Fisiológica/instrumentação , Gravidez/fisiologia , Dispositivos Eletrônicos Vestíveis , Tecnologia sem Fio/instrumentação , Feminino , Recursos em Saúde , Frequência Cardíaca Fetal , Humanos , Contração Uterina , Sinais Vitais
5.
Int J Sports Med ; 45(1): 23-32, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37562444

RESUMO

This study aimed to investigate the acute effects of autoregulated and non-autoregulated applied pressures during blood flow restriction resistance exercise to volitional fatigue on indices of arterial stiffness using the Delfi Personalized Tourniquet System. Following a randomized autoregulated or non-autoregulated blood flow restriction familiarization session, 20 physically active adults (23±5 years; 7 females) participated in three randomized treatment-order sessions with autoregulated and non-autoregulated and no blood flow restriction training. Participants performed four sets of dumbbell wall squats to failure using 20% of one repetition maximum. Blood flow restriction was performed with 60% of supine limb occlusion pressure. Testing before and post-session included an ultrasonic scan of the carotid artery, applanation tonometry, and blood pressure acquisition.Carotid-femoral pulse wave velocity increased in the non-autoregulated and no blood flow restriction training groups following exercise while carotid-radial pulse wave velocity increased in the no blood flow restriction training group (all p<0.05). Carotid-femoral pulse wave velocity exhibited an interaction effect between autoregulated and non-autoregulated blood flow restriction in favor of autoregulated blood flow restriction (p<0.05). Autoregulated blood flow restriction training does not influence indices of arterial stiffness while non-autoregulated and no blood flow restriction training increases central stiffness.


Assuntos
Análise de Onda de Pulso , Rigidez Vascular , Adulto , Feminino , Humanos , Rigidez Vascular/fisiologia , Hemodinâmica , Pressão Sanguínea/fisiologia , Artérias Carótidas/diagnóstico por imagem , Artérias Carótidas/fisiologia
6.
Paediatr Anaesth ; 33(8): 670-672, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37102400

RESUMO

INTRODUCTION: More than 40,000 children undergo surgical interventions annually for the treatment of congenital heart defects. Intraoperative and postoperative vital sign monitoring is a cornerstone of pediatric care. METHODS: A single-arm prospective observational study was performed. Pediatric patients undergoing a procedure with a planned admission to the Cardiac Intensive Care Unit at Lurie Children's Hospital (Chicago, IL) were eligible for enrollment. Participant vital signs were monitored using standard equipment and an FDA-cleared experimental device (ANNE® ) consisting of a wireless patch positioned at the suprasternal notch and index finger or foot. The primary goal of the study was to assess real-world feasibility of wireless sensors in pediatric patients with congenital cardiac defects. RESULTS: A total of 13 patients were enrolled, ranging in age from 4 months to 16 years with a median age of 4 years. Overall, 54% (n = 7) were female and the most common anomaly in the cohort was an atrial septal defect (n = 6). The mean admission length was 3 days (range 2-6), resulting in more than 1000 h of vital sign monitoring (⟩60,000 data points). Bland-Altman plots were generated for heart rate and respiratory rate to assess beat-to-beast differences between the standard equipment and the experimental sensors. CONCLUSIONS: Novel, wireless, flexible sensors demonstrated comparable performance to standard monitoring equipment in a cohort of pediatric patients with congenital cardiac heart defects undergoing surgery.


Assuntos
Cardiopatias Congênitas , Sinais Vitais , Humanos , Criança , Feminino , Pré-Escolar , Masculino , Cardiopatias Congênitas/cirurgia , Cardiopatias Congênitas/diagnóstico , Frequência Cardíaca , Taxa Respiratória , Hospitalização
7.
J Assist Reprod Genet ; 40(11): 2639-2647, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37667016

RESUMO

PURPOSE: To study the impact of undergoing an embryo transfer during the week of daylight savings time transition on live birth rates. METHODS: We performed a retrospective observational cohort study of patients undergoing embryo transfer at an academic infertility practice during the week of spring or fall daylight savings time transition (cases), or the 2 weeks preceding and following the daylight savings transition (controls) between 2015 and 2021. The primary exposure was completion of an embryo transfer during the week of daylight savings time transition. The primary outcome was a comparison of live birth rate per embryo transfer among individuals undergoing an embryo transfer during the week of daylight savings time (DST) transition and those who did not. RESULTS: A total of 309 embryo transfers occurred during the week of daylight savings transition and 1242 embryo transfers occurred in the control group outside of the daylight savings transition week. The live birth rate after embryo transfer during DST transition weeks was 39.2% (121/309) compared to 40.8% (507/1242) (p = 0.59). When restricting the analysis to individuals (age > 37 years), the live birth rate after embryo transfer during DST transition week was 23.5% (24/102) compared to 34.8% (149/429) (p = 0.03). This difference persisted in the mixed-effects regression model demonstrating that after adjusting for relevant covariates, embryo transfer during DST transition weeks resulted in a 45% decrease in the odds of achieving a live birth. CONCLUSION: Daylight savings time transition may be associated with less favorable outcomes after embryo transfer among an older infertile patient population. Future work is needed to prospectively examine the influence of circadian rhythm disruption on reproductive outcomes.


Assuntos
Coeficiente de Natalidade , Infertilidade , Gravidez , Feminino , Humanos , Idoso , Adulto , Fertilização in vitro , Taxa de Gravidez , Estudos Retrospectivos , Transferência Embrionária/métodos , Nascido Vivo/epidemiologia , Infertilidade/epidemiologia , Infertilidade/terapia
8.
J Strength Cond Res ; 37(2): 315-321, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-35916876

RESUMO

ABSTRACT: Morgan, B, Mirza, AM, Gimblet, CJ, Ortlip, AT, Ancalmo, J, Kalita, D, Pellinger, TK, Walter, JM, and Werner, TJ. Effect of an 11-week resistance training program on arterial stiffness in young women. J Strength Cond Res 37(2): 315-321, 2023-The current investigation was conducted to determine the effect of 2 resistance training models on indices of arterial stiffness in young, healthy women. Twenty-four women, untrained college students, aged 18-22 years were randomized into 1 of 3 groups: control (CON) group ( n = 8), high-intensity (HI) resistance exercise group ( n = 8), and high-volume (HV) resistance exercise group ( n = 8). Subjects randomized to resistance training groups were required to perform strength training exercises 3-5 days a week for 11 weeks. The exercise regimen consisted of 2-3 sets of 3-8 repetitions (80-90% of 1 repetition maximum [1RM]) for the HI group and 3-4 sets of 10-15 repetitions (50-70% of 1RM) for the HV group. All subjects were instructed to continue their normal diet and avoid cardiovascular exercise during the study. After the intervention, there was a significant increase in carotid femoral pulse wave velocity (PWV) (6.39 ± 0.73 to 8.40 ± 2.31 m·s -1 ; p < 0.05) and carotid radial PWV (9.77 ± 1.74 to 12.58 ± 2.09 m·s -1 ; p < 0.05) in the CON group alone. Both the HI and HV groups increased their maximum squat (36.6 ± 7.9 vs. 41.3 ± 31.8 percent change; p < 0.05), bench press (34.4 ± 12.6 vs. 23.4 ± 11.1 percent change; p < 0.05), and seated row (22.0 ± 12.6 vs. 21.9 ± 12.5 percent change; p < 0.05), respectively. Our findings support the use of resistance training exercise without undue impact on vascular compliance in otherwise healthy women.


Assuntos
Treinamento Resistido , Rigidez Vascular , Humanos , Feminino , Análise de Onda de Pulso , Exercício Físico , Coração , Força Muscular , Músculo Esquelético
9.
Clin Obstet Gynecol ; 65(1): 68-75, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-35045027

RESUMO

Uterus transplantation (UTx) provides a new pathway to parenthood for patients with absolute uterine factor infertility. The application of reproductive technologies, such as in vitro fertilization, embryo cryopreservation, and frozen embryo transfers, for this unique population, is particularly nuanced and continually evolving. There are important pretransplant and posttransplant reproductive considerations for physicians and patients anticipating UTx. As with any rapidly evolving medical innovation, efforts to consolidate experiences and knowledge by centers offering UTx is paramount.


Assuntos
Infertilidade Feminina , Criopreservação , Transferência Embrionária , Feminino , Fertilização in vitro , Humanos , Infertilidade Feminina/terapia , Útero/transplante
10.
J Assist Reprod Genet ; 38(12): 3069-3075, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34739643

RESUMO

PURPOSE: To compare pregnancy and birth outcomes after frozen embryo transfers (FETs) among White, Black, and Asian women and evaluate the effect of patient, protocol, and cycle characteristics on success. METHODS: A retrospective chart review identified women who underwent an autologous FET at an academic fertility center between January 2013 and March 2020. RESULTS: White, Black, and Asian women completed 1,181 (71.7%), 230 (14.0%), and 235 (14.3%) cycles, respectively. Black women were significantly less likely to achieve a positive hCG level (AOR 0.66, 95% CI 0.49-0.90), clinical pregnancy (AOR 0.71, 95% CI 0.53-0.97), and live birth (AOR 0.65, 95% CI 0.47-0.89) compared to White women after adjusting for possible confounders. There were no differences in the aforementioned outcomes when looking at cycles completed by Asian versus White women. When comparing outcomes by endometrial preparation protocol, significant differences were seen amongst the three groups for live birth rates following natural cycle FETs (52.36%, 25.81%, and 44.19% for White, Black, and Asian women, respectively, p = 0.02), a difference not appreciated after programmed FETs. CONCLUSION: Black race is associated with significantly worse pregnancy and live birth rates following FET when compared to White race. Additionally, significant differences in live birth rates among White, Black, and Asian women exist following natural cycle FET versus programmed FET. These disparities in success are not only important for patient counseling, but also when determining management strategies to improve fertility rates among minority women.


Assuntos
Criopreservação/estatística & dados numéricos , Transferência Embrionária/estatística & dados numéricos , Grupos Raciais/estatística & dados numéricos , Adulto , Coeficiente de Natalidade , Endométrio/fisiologia , Feminino , Humanos , Nascido Vivo , Masculino , Indução da Ovulação/estatística & dados numéricos , Gravidez , Taxa de Gravidez , Estudos Retrospectivos
11.
Semin Neurol ; 40(6): 617-623, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33155183

RESUMO

Seizures affect the lives of 10% of the global population and result in epilepsy in 1 to 2% of people around the world. Current knowledge about etiology, diagnosis, and treatments for epilepsy is constantly evolving. As more is learned, appropriate and updated definitions and classification systems for seizures and epilepsy are of the utmost importance. Without proper definitions and classification, many individuals will be improperly diagnosed and incorrectly treated. It is also essential for research purposes to have proper definitions, so that appropriate populations can be identified and studied. Imprecise definitions, failure to use accepted terminology, or inappropriate use of terminology hamper our ability to study and advance the field of epilepsy. This article begins by discussing the pathophysiology and epidemiology of epilepsy, and then covers the accepted contemporary definitions and classifications of seizures and epilepsies.


Assuntos
Epilepsia , Convulsões , Epilepsia/classificação , Epilepsia/epidemiologia , Epilepsia/etiologia , Epilepsia/fisiopatologia , Humanos , Convulsões/classificação , Convulsões/epidemiologia , Convulsões/etiologia , Convulsões/fisiopatologia
12.
J Med Internet Res ; 22(12): e24328, 2020 12 09.
Artigo em Inglês | MEDLINE | ID: mdl-33245699

RESUMO

BACKGROUND: Telemedicine has been used for decades. Despite its many advantages, its uptake and rigorous evaluation of feasibility across neurology's ambulatory subspecialties has been sparse. However, the COVID-19 pandemic prompted health care systems worldwide to reconsider traditional health care delivery. To safeguard health care workers and patients, many health care systems quickly transitioned to telemedicine, including across neurology subspecialties, providing a new opportunity to evaluate this modality of care. OBJECTIVE: To evaluate the accelerated implementation of video visits in ambulatory neurology during the COVID-19 pandemic, we used mixed methods to assess adoption, acceptability, appropriateness, and perceptions of potential sustainability. METHODS: Video visits were launched rapidly in ambulatory neurology clinics of a large academic medical center. To assess adoption, we analyzed clinician-level scheduling data collected between March 22 and May 16, 2020. We assessed acceptability, appropriateness, and sustainability via a clinician survey (n=48) and semistructured interviews with providers (n=30) completed between March and May 2020. RESULTS: Video visits were adopted rapidly; overall, 65 (98%) clinicians integrated video visits into their workflow within the first 6 implementation weeks and 92% of all visits were conducted via video. Video visits were largely considered acceptable by clinicians, although various technological issues impacted their satisfaction. Video visits were reported to be more convenient for patients, families, and caregivers than in-person visits; however, access to technology, the patient's technological capacity, and language difficulties were considered barriers. Many clinicians expressed optimism about future utilization of video visits in neurology. They believed that video visits promote continuity of care and can be incorporated into their practice long-term, although several insisted that they can never replace the in-person examination. CONCLUSIONS: Video visits are an important addition to clinical care in ambulatory neurology and are anticipated to remain a permanent supplement to in-person visits, promoting patient care continuity, and flexibility for patients and clinicians alike.


Assuntos
COVID-19/terapia , Neurologia/métodos , Telemedicina/métodos , Humanos
13.
Biotechnol Bioeng ; 116(6): 1449-1462, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30739333

RESUMO

For commercial protein therapeutics, Chinese hamster ovary (CHO) cells have an established history of safety, proven capability to express a wide range of therapeutic proteins and high volumetric productivities. Expanding global markets for therapeutic proteins and increasing concerns for broadened access of these medicines has catalyzed consideration of alternative approaches to this platform. Reaching these objectives likely will require an order of magnitude increase in volumetric productivity and a corresponding reduction in the costs of manufacture. For CHO-based manufacturing, achieving this combination of targeted improvements presents challenges. Based on a holistic analysis, the choice of host cells was identified as the single most influential factor for both increasing productivity and decreasing costs. Here we evaluated eight wild-type eukaryotic micro-organisms with prior histories of recombinant protein expression. The evaluation focused on assessing the potential of each host, and their corresponding phyla, with respect to key attributes relevant for manufacturing, namely (a) growth rates in industry-relevant media, (b) adaptability to modern techniques for genome editing, and (c) initial characterization of product quality. These characterizations showed that multiple organisms may be suitable for production with appropriate engineering and development and highlighted that yeast in general present advantages for rapid genome engineering and development cycles.


Assuntos
Anticorpos Monoclonais/biossíntese , Células Eucarióticas/metabolismo , Fatores Imunológicos/biossíntese , Proteínas Recombinantes/biossíntese , Anticorpos Monoclonais/genética , Biotecnologia/métodos , Fatores Imunológicos/genética , Engenharia Metabólica/métodos , Proteínas Recombinantes/genética , Tecnologia Farmacêutica/métodos
14.
Epilepsy Behav ; 93: 113-118, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30867113

RESUMO

OBJECTIVE: This study evaluates the efficacy of a modified ketogenic diet (MKD) on seizure frequency, severity, and quality of life (QOL), as well as potential complications of MKD therapy among adults with drug-resistant epilepsy (DRE). METHODS: Changes in seizure frequency, severity, QOL, and side effects were retrospectively examined among adults, ≥17 years of age, with DRE (≥2 antiepileptic drugs [AEDs]), after 3 months of MKD therapy. Attention was paid to medication or vagus nerve stimulator (VNS) changes as well to evaluate potential confounders. RESULTS: A total of 60% (n = 33) of the 55 individuals reported ≥50% seizure frequency improvement, 42 (76%) reported improvement in seizure severity, and 48 (87%) reported improvement in QOL. More patients following a modified ketogenic diet - 15 g net carbohydrate daily (MKD-15) (95%) compared with a MKD-50 (69%) reported improvement in QOL (p = 0.02). Weight among the entire sample declined from 77.5 (20) kg to 73.9 (19.0) kg (p < 0.0001), and total cholesterol (TC), low density lipoprotein (LDL), and total cholesterol:high density lipoprotein (TC:HDL) increased significantly (p = 0.03, p = 0.04, and p = 0.02, respectively). Free carnitine values were available for a select number of patients, 26 (47%) at baseline, and 7 (13%) at follow-up, of which 8 (31%) at baseline, and 2 (29%) at follow-up had carnitine deficiency (<25 nmol/mL). Constipation was noted in 5 patients (9%), and no kidney stones were reported during the study period. There were no statistical differences in number or dose changes for AED or VNS during the study period. SIGNIFICANCE: Modified ketogenic diet therapies reduce seizure frequency and severity and improve QOL among adults with DRE with few side effects outside of weight loss, a desired outcome among many adults with DRE. More restrictive MKDs may offer improved seizure severity and QOL. Modified ketogenic diet therapy increases LDL cholesterol, which may be cardioprotective if related to an increase in LDL particle size with high saturated fat intake; however, more research is needed examining LDL particle size changes among those receiving MKD therapy.


Assuntos
Dieta Cetogênica/métodos , Epilepsia Resistente a Medicamentos/dietoterapia , Epilepsia Resistente a Medicamentos/psicologia , Qualidade de Vida/psicologia , Convulsões/dietoterapia , Convulsões/psicologia , Adolescente , Adulto , Criança , Dieta com Restrição de Carboidratos/métodos , Epilepsia Resistente a Medicamentos/diagnóstico , Feminino , Humanos , Masculino , Estudos Retrospectivos , Convulsões/diagnóstico , Índice de Gravidade de Doença , Resultado do Tratamento
15.
Epilepsy Behav ; 93: 119-124, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30738724

RESUMO

OBJECTIVE: Adults with drug-resistant epilepsy (DRE) are among the most challenging to treat. This study assessed whether specific subpopulations of adult patients with refractory epilepsy responded differently to modified ketogenic diet (MKD) therapy. METHODS: Changes in seizure frequency, severity, and quality of life (QOL) were retrospectively analyzed based on pre-MKD surgical history, type of epilepsy, imaging findings, and vagal nerve stimulation (VNS) history among adults, ≥17 years of age, with DRE, receiving MKD therapy for three months. Additionally, particular attention was made to medication and VNS adjustments. RESULTS: Responder rates in seizure frequency, severity, and QOL reported among those with prior surgery were 56%, 75%, and 94%, respectively. Among those with focal epilepsy: 57%, 76%, and 76% had improvements in seizure frequency, seizure severity, and QOL, respectively whereas 83% improvement was seen for all three measures in those with generalized epilepsy. Among those with abnormal imaging: just over 50% reported improvements on all measures. For those with VNS, 53%, 63%, and 95% had improvements in seizure frequency, seizure severity, and QOL, respectively. No statistical differences in seizure frequency, severity, or QOL were noted between groups based on prediet surgical history, seizure type, imaging abnormalities, or VNS history. Compared with expected improvement from medication adjustment alone, significant improvement was seen for all groups; notably, the Z-test for proportions for the surgery group, when compared with placebo responder rates at 20%, was 3.6, p < 0.001. CONCLUSIONS: Modified ketogenic diet therapies are effective in improving seizure frequency, severity, and QOL and may offer the best chance for improvement among those whose seizures have persisted despite surgical intervention and VNS therapy. All types of epilepsy respond to MKDs, and possibly those with generalized epilepsy may respond better.


Assuntos
Dieta Cetogênica/métodos , Epilepsia Resistente a Medicamentos/diagnóstico por imagem , Epilepsia Resistente a Medicamentos/dietoterapia , Vigilância da População , Estimulação do Nervo Vago/métodos , Adolescente , Adulto , Idoso , Dieta Cetogênica/tendências , Epilepsia Resistente a Medicamentos/cirurgia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Vigilância da População/métodos , Estudos Retrospectivos , Resultado do Tratamento , Estimulação do Nervo Vago/tendências , Adulto Jovem
16.
Epilepsy Behav ; 94: 151-157, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30939410

RESUMO

People with epilepsy are at increased risk for neuropsychological dysfunction due to multiple factors, of which the most amendable are antiseizure medications (ASMs). Antiseizure medication effectiveness is frequently determined by tolerability. In this study, we compared the neuropsychological effects of eslicarbazepine acetate (ESL) and carbamazepine immediate-release (CBZ) using a randomized, double-blind, crossover design in healthy volunteers with a 2-week titration and 4-week maintenance phase in each treatment arm (CBZ = 400 mg BID and ESL = 800 mg qAM). Neuropsychological testing was performed at the initial visit, repeated at 1st baseline nondrug condition, end treatment #1, 2nd nondrug condition one month after treatment #1, end treatment #2, and 3rd nondrug condition one month after treatment #2. Neuropsychological testing was conducted 2 h after morning dose and included computer (i.e., dual task test, selective attention test, symbol digit, verbal memory, visuospatial memory, and 1- & 2-back continuous performance) and noncomputer tasks (i.e., Medical College of Georgia (MCG) paragraph memory, Stroop, Symbol Digit Modalities Test, Profile of Mood States). z-Scores calculated from nondrug conditions were used to compare ESL and CBZ for the 23 completers. Follow-up analyses included individual test scores and distribution of individual raw means. Mean blood levels on test day were CBZ = 8.9 µg/ml and ESL = 15.3 µg/ml. Omnibus z-score was significantly better for ESL (p = .0001). For individual measures, executive function and selective attention tests were statistically significantly better for ESL. Individual test raw means favored ESL over CBZ on 22 of 30 measures (p = .016, 2-tailed sign test). Eslicarbazepine acetate demonstrated less adverse neuropsychological effects than CBZ.


Assuntos
Anticonvulsivantes/efeitos adversos , Carbamazepina/efeitos adversos , Dibenzazepinas/efeitos adversos , Epilepsia/tratamento farmacológico , Epilepsia/psicologia , Adolescente , Adulto , Afeto/efeitos dos fármacos , Atenção/efeitos dos fármacos , Estudos Cross-Over , Método Duplo-Cego , Feminino , Voluntários Saudáveis , Humanos , Masculino , Memória/efeitos dos fármacos , Pessoa de Meia-Idade , Testes Neuropsicológicos , Desempenho Psicomotor/efeitos dos fármacos , Memória Espacial/efeitos dos fármacos , Teste de Stroop , Resultado do Tratamento , Adulto Jovem
17.
Issues Law Med ; 34(1): 77-92, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31179672

RESUMO

Between 2002 and 2016, 806 million medical devices were recalled. When approving a device, the FDA employs advisory boards organized by medical specialty (e.g. cardiovascular) to make approval recommendations. Previous work has demonstrated high numbers of recalled orthopedic and cardiovascular devices; however, no prior studies have controlled for the number of approvals by advisory board. The purpose of this study is to identify device fields at higher risk for safety problems. This study compares specialty-specific, approval-adjusted recall rates of high-risk medical devices from 2002 to 2016 by utilizing publicly available FDA data on recalls and approvals. Devices approved under general hospital (113), anesthesiology (98), and cardiovascular (98) advisory boards constituted 71% of all class I recalls. For devices approved via the more rigorous pre-market approval pathway, those under the purview of the general hospital (0.25 recalls/approval, 95% CI 0.15 - 0.41) advisory board had a significantly higher rate than average (p<0.05). For 510(k) cleared devices, microbiology (6.0 recalls/clearance, 95% CI 3.4 - 10.6), anesthesiology (0.04 recalls/clearance, 95% CI 0.03 - 0.04), general hospital (0.02 recalls/clearance, 95% CI 0.02 - 0.02), and cardiovascular (0.010 recalls/ clearance, 0.009 to 0.015) advisory boards had significantly higher recall rates than average (p<0.05). Future regulatory resources should be directed towards device areas and approval pathways that pose a higher risk for safety problems.


Assuntos
Equipamentos e Provisões/efeitos adversos , Recall de Dispositivo Médico , United States Food and Drug Administration , Estados Unidos
20.
Soc Sci Res ; 72: 170-182, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29609737

RESUMO

Using the example of the German General Social Survey, this study describes how measures of gender role attitudes can be revised. To date measures have focused on the traditional male breadwinner model. However, social developments in female labor force participation, education, and family structure suggest that a revision and adjustment of existing measures are required. First, these measures need to be supplemented with items that represent more egalitarian models of division of labor and the role of the father in the family. Second, the phrasing of existing items needs to be revised. The results of this study indicate that especially regarding the amount of working hours and the age of children, a specification is needed. This study presents a revised measure, to facilitate analyses over time. This revised measure represents two factors: one referring to traditional and one to modern gender role attitudes.

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