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1.
J Orthop Res ; 2020 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-32162719

RESUMO

Spine shape changes dramatically in early life, influenced by attainment of developmental milestones such as independent walking. Whether these associations persist across life is unknown. Therefore, we investigated associations between developmental milestones and spine shape, as determined using statistical shape models (SSMs) of lumbar spine from dual-energy X-ray absorptiometry scans in 1327 individuals (688 female) at 60 to 64 years in the MRC National Survey of Health and Development. Lumbar lordosis angle (L4 inferior endplate to T12 superior endplate) was measured using the two-line Cobb method. In analyses adjusted for sex, height, lean and fat mass, socioeconomic position, and birthweight, later walking age was associated with greater lordosis described by SSM1 (regression coefficient, 0.023; 95% CI, 0.000-0.047; P = .05) and direct angle measurement. Modest associations between walking age and less variation in anterior-posterior vertebral size caudally (SSM6) were also observed (0.021; 95% CI, -0.002 to 0.044; P = .07). Sex interactions showed that later walking was associated with larger relative vertebral anterior-posterior dimensions in men (SSM3; -0.043; 95% CI, -0.075 to 0.01; P = .01) but not women (0.018; 95% CI, -0.0007 to 0.043; P = .17). Similar associations were observed between age at independent standing and SSMs but there was little evidence of association between sitting age and spine shape. Unadjusted associations between walking age and SSMs 1 and 6 remained similar after adjustment for potential confounders and mediators. This suggests that these associations may be explained by altered mechanical loading of the spine during childhood growth, although other factors could contribute. Early life motor development, particularly walking, may have a lasting effect on the features of spine morphology with clinical significance.

2.
J Clin Endocrinol Metab ; 105(4)2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32016427

RESUMO

CONTEXT: Adolescents have more small, growing follicles and larger ovaries than normal women and are prone to anovulatory cycles (ANOV). It is unknown if a higher antral follicle count (AFC) per se contributes to ANOV in early postmenarchal girls. OBJECTIVE: To determine the relationship between AMH (an AFC biomarker), other reproductive hormones, and ANOV in postmenarchal girls and to compare AMH in girls and regularly cycling adults. METHODS: A total of 23 girls (1.7 ± 0.2 years postmenarche) and 32 historic adult controls (≤34 years) underwent serial hormone measurements during 1 to 2 menstrual cycles. Girls also had pelvic ultrasounds. AMH was measured 5 times/subject using the Ansh ultrasensitive ELISA. RESULTS: Girls had higher AMH than women (5.2 ± 0.3 vs. 3.3 ± 0.4 ng/mL; P < 0.01) and girls with more ovulatory (OV) cycles tended to have lower AMH than those with ANOV (2 OV 4.5 ± 0.2, 1 OV 5.7 ± 1.1, 0 OV 6.8 ± 1.1 ng/mL; P = 0.1). In girls, AMH correlated with natural-log (ln) transformed LH (r = 0.5, P = 0.01), ln_androstenedione (r = 0.6, P = 0.003), ln_testosterone (r = 0.5, P = 0.02), and ovarian volume (r = 0.7, P < 0.01) but not with FSH, estradiol, P4, or body mass index. In women, AMH correlated with estradiol and P4 (both r = -0.4, P ≤ 0.03) but not with ln_LH or body mass index. CONCLUSIONS: In postmenarchal girls, AMH is higher than in ovulatory women and is associated with LH, androgens, and a propensity for anovulatory cycles. The cause of the transient increase in AMH and AFC during late puberty and the steps underlying the transition to a mature ovary deserve further study.

3.
Radiother Oncol ; 142: 154-161, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31563411

RESUMO

BACKGROUND AND PURPOSE: High-dose fractionated radiotherapy is often necessary to achieve long-term tumor control in several types of tumors involving or within close proximity to the brain. There is limited data to guide on optimal constraints to the adjacent nontarget brain. This investigation explored the significance of the three-dimensional (3D) dose distribution of passive scattering proton therapy to the brain with other clinicopathological factors on the development of symptomatic radiation necrosis. MATERIALS AND METHODS: All patients with head and neck, skull base, or intracranial tumors who underwent proton therapy (minimum prescription dose of 59.4 Gy(RBE)) with collateral moderate to high dose radiation exposure to the nontarget brain were retrospectively reviewed. A mixture cure model with respect to necrosis-free survival was used to derive estimates for the normal tissue complication probability (NTCP) model while adjusting for potential confounding factors. RESULTS: Of 179 identified patients, 83 patients had intracranial tumors and 96 patients had primary extracranial tumors. The optimal dose measure obtained to describe the occurrence of radiation necrosis was the equivalent uniform dose (EUD) with parameter a = 9. The best-fit parameters of logistic NTCP models revealed D50 = 57.7 Gy for intracranial tumors, D50 = 39.5 Gy for extracranial tumors, and γ50 = 2.5 for both tumor locations. Multivariable analysis revealed EUD and primary tumor location to be the strongest predictors of brain radiation necrosis. CONCLUSION: In the current clinical volumetric data analyses with multivariable modelling, EUD was identified as an independent and strong predictor for brain radiation necrosis from proton therapy.

4.
J Nurs Care Qual ; 35(2): 165-170, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31464846

RESUMO

BACKGROUND: High rates of missed appointments for routine HIV care are associated with unsuppressed viremia, increasing morbidity. LOCAL PROBLEM: The Clinic no-show rate ranged between 30% and 35%, and only 69% of patients were considered retained in care within a 24-month time frame. METHODS: The Woodward Risk Prediction Tool was completed on all patients to stratify patient risk for missing the next appointment. INTERVENTIONS: All patients were offered text message along with standard phone message appointment reminders, and patients who missed appointments were called within 24 hours to reschedule. Medium-risk patients received a previsit planning call to remove barriers to appointment attendance, and high-risk patients received a home visit from the peer navigator. RESULTS: The project resulted in a 3.8% reduction rate in the overall no-show rate in the first 5 months of implementation. Using risk stratification and targeted interventions allowed valuable resources to be allocated where they were needed.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31868821

RESUMO

Few nurse practitioner programs integrate education on care of veterans into their curriculum. Because more veterans are seeking health care outside of the Veteran Affairs system, all advanced practice nurses need to be prepared to meet the unique needs of veterans with post-traumatic stress disorder (PTSD). The authors developed an education session on military-to-civilian transition and screening and treatment of veterans with PTSD. The session was provided to a convenience sample of students. Case studies were included to allow student participation and active learning. Students completed pre-education and post-education surveys to measure their comfort level in caring for this specific population and their understanding of PTSD. The participant scores on comfort level with identifying and managing PTSD after the education session were significantly increased. Placing veteran-specific education into nurse practitioner programs enhances the comfort level with identifying and managing PTSD. Adding this veteran-specific education could enhance the overall care for veterans in the civilian sector.

6.
Br J Cancer ; 121(6): 443-454, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31366999

RESUMO

BACKGROUND: Breast cancer diagnosis may be a teachable moment for lifestyle behaviour change and to prevent adjuvant therapy associated weight gain. We assessed the acceptability and effectiveness of two weight control programmes initiated soon after breast cancer diagnosis to reduce weight amongst overweight or obese women and prevent gains in normal-weight women. METHODS: Overweight or obese (n = 243) and normal weight (n = 166) women were randomised to a three-month unsupervised home (home), a supervised community weight control programme (community) or to standard written advice (control). Primary end points were change in weight and body fat at 12 months. Secondary end points included change in insulin, cardiovascular risk markers, quality of life and cost-effectiveness of the programmes. RESULTS: Forty-three percent of eligible women were recruited. Both programmes reduced weight and body fat: home vs. control mean (95% CI); weight -2.3 (-3.5, -1.0) kg, body fat -1.6 (-2.6, -0.7) kg, community vs. control; weight -2.4 (-3.6, -1.1) kg, body fat -1.4 (-2.4, -0.5) kg (all p < 0.001). The community group increased physical activity, reduced insulin, cardiovascular disease risk markers, increased QOL and was cost-effective. CONCLUSIONS: The programmes were equally effective for weight control, but the community programme had additional benefits. CLINICAL TRIAL REGISTRATION: ISRCTN68576140.

7.
Int J Radiat Oncol Biol Phys ; 105(1): 90-95, 2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-31128146

RESUMO

PURPOSE: Definitive chemoradiation with concurrent 5-fluorouracil (5-FU)/mitomycin C (MMC) is an effective treatment for localized anal cancer, but it is associated with significant acute long-term treatment-related toxicity. Pencil beam scanning proton beam (PBS-PT) radiation therapy may potentially reduce this toxicity. This is a multi-institutional pilot study evaluating the feasibility of definitive concurrent chemoradiation with PBS-PT in combination with 5-FU and MMC for carcinoma of the anal canal. METHODS AND MATERIALS: Patients were enrolled on a National Cancer Institute-sponsored, prospective, multi-institutional, single-arm pilot study (NCT01858025). Key eligibility criteria included Eastern Cooperative Oncology Group 0 to 2, age ≥18 years, histologically confirmed invasive squamous cell carcinoma of the anal canal, and clinically staged T1-4, N0-3 disease. Patients were treated with PBS-PT per Radiation Therapy Oncology Group 0529 dose schema and concurrent 5-FU/MMC on day 1 and 29. The primary objective of this study was to determine feasibility of PBS-PT with concurrent 5-FU/MMC, defined as grade 3+ dermatologic toxicity less than 48% (reported grade 3+ dermatologic toxicity from Radiation Therapy Oncology Group 98-11). Secondary objectives were to determine the rates of overall grade 3+ toxicities, clinical complete response rate, and disease outcomes. RESULTS: Between February 2014 and April 2017, we enrolled 25 patients into our study, all of whom were analyzed. Twenty-three patients (92%) completed treatment per protocol, and 2 patients died on treatment. Median time to completion of treatment was 42 days (range, 38-49). The grade 3+ radiation dermatitis rate was 24%. Median follow-up is 27 months (range, 21-50) among the 21 patients still alive. The overall rate of clinical complete response was 88%. The 2-year local failure, colostomy-free survival, progression-free survival, and overall survival are 12%, 72%, 80%, and 84%, respectively. CONCLUSIONS: In our prospective, multi-institutional pilot study of PBS-PT with concurrent 5-FU/MMC, PBS-PT was found to be feasible. A phase 2 study of proton beam radiation therapy is currently underway.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Ânus/terapia , Carcinoma de Células Escamosas/terapia , Quimiorradioterapia/métodos , Terapia com Prótons/métodos , Radiodermatite/patologia , Idoso , Canal Anal , Neoplasias do Ânus/patologia , Carcinoma de Células Escamosas/patologia , Quimiorradioterapia/efeitos adversos , Colostomia , Estudos de Viabilidade , Feminino , Fluoruracila/administração & dosagem , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Mitomicina/administração & dosagem , Projetos Piloto , Intervalo Livre de Progressão , Estudos Prospectivos , Terapia com Prótons/efeitos adversos , Dosagem Radioterapêutica
8.
J Gastrointest Oncol ; 10(1): 155-160, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30788171

RESUMO

Secondary esophageal cancers from prior thoracic radiation therapy are rare but challenging cases to deliver standard combined modality therapy as part of a curative approach. In patients with prior exposure to cardiopulmonary-toxic chemotherapy or radiotherapy, management requires meticulous multidisciplinary evaluation given the morbidity associated with surgery in the previously irradiated thorax and re-irradiation of the spinal cord, heart, and lungs. Oftentimes, suboptimal treatment regimens, either with compromised radiation coverage, attenuated chemotherapy doses, or exclusion of surgery, are required to avoid significant toxicity. The physical properties inherent to protons allow for optimal coverage of tumor while achieving remarkably low dose to surrounding normal tissue compared to standard photon treatment. Proton therapy has been studied across various disease sites and may facilitate treatment intensification for radiation-associated esophageal tumors. While no comparative studies have evaluated the efficacy and safety of protons versus photons for esophageal cancer, three cases of radiation-associated esophageal cancer presented in this series are exemplary to highlight the benefit of protons in this unique clinical circumstance. The technical considerations in planning, including passively scattered versus pencil-beam scanning technique, as well as the clinical course and tolerance to treatment, are discussed, which may guide consideration of this advanced treatment modality in this disease site.

9.
Int J Radiat Oncol Biol Phys ; 103(3): 654-668, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30712708

RESUMO

PURPOSE: Radiation-related toxicity in nasopharyngeal carcinoma (NPC) is common. There are no well-established guidelines for clinical target volume (CTV) delineation with long-term follow-up. Current consensus continues to rely heavily on bony landmarks and fixed margins around the gross tumor volume (GTV), an approach used to define fields in the conventional 2- and 3-dimensional radiation therapy era. METHODS AND MATERIALS: We retrospectively evaluated patients with newly diagnosed nonmetastatic NPC treated with definitive radiation therapy using a technique of CTV delineation based on individual tumor extent and the orderly stepwise pattern of tumor spread. Dosimetric comparisons were made between national protocol HN001 and our contouring strategies on a representative early- and advanced-stage NPC. The primary endpoints were patterns of failure and local control; secondary endpoints included regional control and survival, estimated using the Kaplan-Meier method. RESULTS: Between 1999 and 2013, 73 patients (88% with stage 3-4 disease) were treated with median follow-up of 90 months for surviving patients. Median dose to GTV was 70 Gy. Four patients developed local recurrence and 1 patient developed regional recurrence. All locoregional recurrences occurred within the high-dose GTV. The 5-year local control, regional control, and overall survival was 94% (95% confidence interval [CI], 85%-98%), 99% (95% CI, 90%-100%), and 84% (95% CI, 73%-91%), respectively. Compared with HN001, our contouring strategy resulted in 62% and 36% reduction in CTV for T1 and T4 disease, respectively. In the T1 tumor, the reduction of doses to the contralateral parotid, optic nerve, and cochlea were 54%, 50%, 34% respectively. In the T4 case, there was a decrease of optic chiasm dose of 46% and contralateral optic nerve of 37%. There were 10 grade 3 toxicities. There was no grade 2 or higher xerostomia and no grade 4/5 toxicity. CONCLUSIONS: Our long-term experience with individualized CTV delineation based on stepwise patterns of spread results in excellent local control, with no recurrence outside the GTV.


Assuntos
Neoplasias de Cabeça e Pescoço/radioterapia , Carcinoma Nasofaríngeo/radioterapia , Radioterapia/métodos , Adolescente , Adulto , Idoso , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Neoplasias Nasofaríngeas/radioterapia , Metástase Neoplásica , Recidiva Local de Neoplasia , Terapia com Prótons , Lesões por Radiação , Radiometria , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
10.
Radiother Oncol ; 131: 112-119, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30773177

RESUMO

INTRODUCTION: Radiation-induced optic neuropathy (RION) is a complication of radiation therapy (RT) that causes blindness. We aimed to define the tolerance of the anterior optic pathway to fractionated RT and identify risk factors for RION. MATERIALS/METHODS: Patients with chordoma or chondrosarcoma of the skull base treated with proton and photon therapy between 1983 and 2013, who received a minimum of 30 Gy (relative biologic effectiveness [RBE]) to the anterior optic pathway were assessed. Optic neuropathy with radiographic correlation occurring ≥6 months after completion of RT in the absence of tumor recurrence or other probable cause was diagnosed as RION. RESULTS: Of 514 patients, 17 developed RION. With median follow-up of 4.8 years, cumulative incidence of RION was 1% among patients receiving <59 Gy (RBE) and 5.8% among patients receiving ≥60 Gy (RBE) to the optic pathway. Higher maximum point dose to the optic pathway (subhazard ratio [SHR] = 1.2, 95% CI 1.05-1.2, p = 0.001), older age (SHR = 1.1, 95% CI 1.02-1.08, p < 0.0005), and female sex (SHR = 16.3, 95% CI 2.2-122.4, p = 0.007) were statistically significant risk factors for RION in multivariate analysis. CONCLUSION: In our study cohort, rates of RION were very low with conventionally fractionated RT up to 59 Gy. At doses ≥60 Gy, there is an increased risk of RION, with greater risk for women and older patients.


Assuntos
Doenças do Nervo Óptico/etiologia , Nervo Óptico/efeitos da radiação , Fótons/efeitos adversos , Terapia com Prótons/efeitos adversos , Lesões por Radiação/etiologia , Adulto , Idoso , Condrossarcoma/radioterapia , Cordoma/radioterapia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Fótons/uso terapêutico , Terapia com Prótons/métodos , Tolerância a Radiação , Planejamento da Radioterapia Assistida por Computador , Estudos Retrospectivos , Fatores de Risco , Neoplasias Cranianas/radioterapia
11.
J Clin Endocrinol Metab ; 104(6): 2184-2194, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-30649404

RESUMO

CONTEXT: During puberty, LH pulse frequency increases during sleep; in women, LH pulse frequency slows during sleep in the early/middle follicular phase (FP) of the menstrual cycle. The origin and significance of this developmental transition are unknown. OBJECTIVE: To determine the relationship between progesterone (P4) exposure, sleep-related slowing of LH pulses in the FP, and the intercycle FSH rise, which promotes folliculogenesis, in early postmenarchal girls. METHODS: 23 girls (gynecologic age 0.4 to 3.5 years) underwent hormone measurements and pelvic ultrasounds during two consecutive cycles and one frequent blood sampling study with concurrent polysomnography during the FP. RESULTS: Subjects demonstrated one of four patterns during cycle 1 that represent a continuum of P4 exposure: ovulatory cycles with normal or short luteal phase lengths or anovulatory cycles ± follicle luteinization. Peak serum P4 and urine pregnanediol (Pd) in cycle 1 were inversely correlated with LH pulse frequency during sleep in the FP of cycle 2 (r = -0.5; P = 0.02 for both). The intercycle FSH rise and folliculogenesis in cycle 2 were maintained after anovulatory cycles without P4 or Pd exposure or nocturnal slowing of LH pulse frequency in the FP. CONCLUSIONS: During late puberty, rising P4 levels from follicle luteinization and ovulation may promote a slower LH pulse frequency during sleep in the FP. However, a normal FSH rise and follicle growth can occur in the absence of P4-associated slowing. These studies therefore suggest that an immature LH secretory pattern during sleep is unlikely to contribute to menstrual irregularity in the early postmenarchal years.


Assuntos
Hormônio Foliculoestimulante/sangue , Hormônio Luteinizante/sangue , Progesterona/sangue , Sono , Adolescente , Criança , Feminino , Hormônio Liberador de Gonadotropina/fisiologia , Humanos , Ciclo Menstrual/fisiologia
12.
J Bone Miner Res ; 34(2): 252-261, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30347128

RESUMO

Leisure-time physical activity (LTPA) is widely recommended for the prevention of osteoporosis and fractures in older populations. However, whether the beneficial effects of LTPA on bone accumulate across life and are maintained even after reduction or cessation of regular PA in later life is unknown. We examined whether LTPA across adulthood was cumulatively associated with volumetric and areal bone mineral density (vBMD, aBMD) at ages 60 to 64 and whether associations were mediated by lean mass. Up to 1498 participants from the Medical Research Council National Survey of Health and Development were included in analyses. LTPA was self-reported at ages 36, 43, 53, and 60 to 64, and responses summed to generate a cumulative score (range 0 = inactive at all four ages to 8 = most active at all four ages). Total and trabecular vBMD were measured at the distal radius using pQCT and aBMD at the total hip and lumbar spine (L1 to L4) using DXA. Linear regression was used to test associations of the cumulative LTPA score with each bone outcome. After adjustment for height and weight, a 1-unit increase in LTPA score (95% CI) in men was associated with differences of 1.55% (0.78% to 2.31%) in radial trabecular vBMD, 0.83% (0.41% to 1.25%) in total hip aBMD, and 0.97% (0.44% to 1.49%) in spine aBMD. Among women, positive associations were seen for radial trabecular vBMD and total hip aBMD, but only among those of greater weight (LTPA × weight interaction p ≤ 0.01). In men, there was evidence to suggest that lean mass index may partly mediate these associations. These findings suggest that there are cumulative benefits of LTPA across adulthood on BMD in early old age, especially among men. The finding of weaker associations among women suggests that promotion of specific types of LTPA may be needed to benefit bone health in women. © 2018 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals, Inc.

13.
J Bone Miner Res ; 34(3): 455-463, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30496618

RESUMO

Bones' shapes and structures adapt to the muscle and reaction forces they experience during everyday movements. Onset of independent walking, at approximately 12 months, represents the first postnatal exposure of the lower limbs to the large forces associated with bipedal movements; accordingly, earlier walking is associated with greater bone strength. However, associations between early life loading and joint shape have not been explored. We therefore examined associations between walking age and hip shape at age 60 to 64 years in 1423 individuals (740 women) from the MRC National Survey of Health and Development, a nationally representative British birth cohort. Walking age in months was obtained from maternal interview at age 2 years. Ten modes of variation in hip shape (HM1 to HM10), described by statistical shape models, were ascertained from DXA images. In sex-adjusted analyses, earlier walking age was associated with higher HM1 and HM7 scores; these associations were maintained after further adjustment for height, body composition, and socioeconomic position. Earlier walking was also associated with lower HM2 scores in women only, and lower HM4 scores in men only. Taken together, this suggests that earlier walkers have proportionately larger (HM4) and flatter (HM1, HM4) femoral heads, wider (HM1, HM4, HM7) and flatter (HM1, HM7) femoral necks, a smaller neck-shaft angle (HM1, HM4), anteversion (HM2, HM7), and early development of osteophytes (HM1). These results suggest that age at onset of walking in infancy is associated with variations in hip shape in older age. Early walkers have a larger femoral head and neck and smaller neck-shaft angle; these features are associated with reduced hip fracture risk, but also represent an osteoarthritic-like phenotype. Unlike results of previous studies of walking age and bone mass, associations in this study were not affected by adjustment for lean mass, suggesting that associations may relate directly to skeletal loading in early life when joint shape changes rapidly. © 2018 American Society for Bone and Mineral Research.

14.
J Clin Endocrinol Metab ; 104(2): 613-623, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30289507

RESUMO

Context: Menstrual irregularity after menarche has been attributed to immature estrogen positive feedback activity (E+FB) but data are conflicting. Objective: To determine the hypothalamic-pituitary-ovarian contributions to menstrual irregularity in adolescents. Methods: Twenty-three healthy girls [aged 12.8 to 17.6 years; 0.4 to 3.5 years postmenarche; body mass index (BMI) percentile, 41.0 to 99.3] underwent serial hormone measurements and pelvic ultrasounds during two consecutive menstrual cycles. Hormones and follicle growth were compared with 65 adult historic controls with ovulatory cycles (OVs). Results: Girls had anovulatory cycles (ANOVs; 30%), OVs with a short luteal phase (short OVs; 22%), or OVs with normal luteal phase (normal OVs; 48%) without differences in cycle length, chronologic or gynecologic age, or BMI. Adolescents showed a spectrum of E+FB [midcycle LH adjusted for preovulatory estradiol (E2)]; only normal OV girls were comparable to adults. All OV girls had lower E2, progesterone, and gonadotropins during the luteal phase and luteal-follicular transition compared with adults. Normal OV girls also had lower follicular phase LH and FSH levels, a longer follicular phase, a slower dominant follicle growth rate, and smaller estimated preovulatory follicle size than adults. Follicular phase E2 and inhibin B levels were lower in normal OV girls than in adults even after adjusting for differences in FSH and follicle size. Conclusions: Early postmenarchal girls with normal OVs demonstrate mature E+FB but continue to have lower gonadotropin levels, diminished ovarian responsiveness, and decreased corpus luteum sex steroid synthesis compared with adults, indicating that reproductive axis maturity requires coordinated development of all components of the hypothalamic-pituitary-ovarian axis.


Assuntos
Desenvolvimento do Adolescente/fisiologia , Sistema Hipotálamo-Hipofisário/metabolismo , Menarca/fisiologia , Ciclo Menstrual/fisiologia , Ovário/metabolismo , Adolescente , Adulto , Criança , Estudos de Coortes , Estradiol , Feminino , Hormônio Foliculoestimulante/sangue , Hormônio Foliculoestimulante/metabolismo , Humanos , Inibinas/sangue , Inibinas/metabolismo , Hormônio Luteinizante/sangue , Hormônio Luteinizante/metabolismo , Ovulação/fisiologia , Progesterona/sangue , Progesterona/metabolismo
15.
Sci Rep ; 8(1): 16309, 2018 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-30397263

RESUMO

We aimed to examine whether back pain across adulthood was associated with spine shape at age 60-64 years. Data were from 1405 participants in the MRC National Survey of Health and Development, a nationally representative British birth cohort. Back pain was ascertained during nurse interviews at ages 36, 43, 53 and 60-64 years. Cumulative exposure to back pain was then derived by counting the number of ages at which back pain was reported. Statistical shape modelling was used to characterise thoracolumbar spine shape using lateral dual-energy x-ray absorptiometry images which were ascertained at age 60-64 years. Linear regression models were used to test associations of spine shape modes (SM) with: (1) cumulative exposure to back pain; (2) back pain reports during different periods of adulthood. After adjusting for sex, higher cumulative exposure to back pain across adulthood was associated with wedge-shaped L4-5 disc (lower SM4 scores) and smaller disc spaces (higher SM8 scores) in both sexes. In addition, reporting of back pain at ages 53 and/or 60-64 years was associated with smaller L4-5 disc space (lower SM6 scores) in men but not women. These findings suggest that back pain across adulthood may be associated with specific variations in spine shapes in early old age.


Assuntos
Dor nas Costas/patologia , Coluna Vertebral/patologia , Adulto , Dor nas Costas/epidemiologia , Estudos de Coortes , Inglaterra/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
16.
PLoS One ; 13(6): e0197570, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29902185

RESUMO

This study investigated associations between measures of adiposity from age 36 and spine shape at 60-64 years. Thoracolumbar spine shape was characterised using statistical shape modelling on lateral dual-energy x-ray absorptiometry images of the spine from 1529 participants of the MRC National Survey of Health and Development, acquired at age 60-64. Associations of spine shape modes with: 1) contemporaneous measures of total and central adiposity (body mass index (BMI), waist circumference (WC)) and body composition (android:gynoid fat mass ratio and lean and fat mass indices, calculated as whole body (excluding the head) lean or fat mass (kg) divided by height2 (m)2); 2) changes in total and central adiposity between age 36 and 60-64 and 3) age at onset of overweight, were tested using linear regression models. Four modes described 79% of the total variance in spine shape. In men, greater lean mass index was associated with a larger lordosis whereas greater fat mass index was associated with straighter spines. Greater current BMI was associated with a more uneven curvature in men and with larger anterior-posterior (a-p) vertebral diameters in both sexes. Greater WC and fat mass index were also associated with a-p diameter in both sexes. There was no clear evidence that gains in BMI and WC during earlier stages of adulthood were associated with spine shape but younger onset of overweight was associated with a more uneven spine and greater a-p diameter. In conclusion, sagittal spine shapes had different associations with total and central adiposity; earlier onset of overweight and prior measures of WC were particularly important.


Assuntos
Índice de Massa Corporal , Obesidade/fisiopatologia , Sobrepeso/fisiopatologia , Coluna Vertebral/fisiopatologia , Absorciometria de Fóton , Tecido Adiposo/fisiopatologia , Adiposidade , Adulto , Composição Corporal/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/diagnóstico por imagem , Sobrepeso/diagnóstico por imagem , Coluna Vertebral/diagnóstico por imagem , Circunferência da Cintura/fisiologia
17.
Acta Oncol ; 57(9): 1259-1264, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29726722

RESUMO

PURPOSE: To investigate the effect of differences in linear energy transfer (LET) and thus the relative biological effectiveness (RBE) between passively scattered proton therapy (PS) and pencil-beam scanning intensity-modulated proton therapy (IMPT). METHODS: IMPT treatment plans were generated for six ependymoma patients, originally treated with PS, using the original plan's computed tomography image sets and beam directions, and its dose-volume values as optimization constraints. Two beam spot sizes and both single-field optimization (SFO) and multi-field optimization (MFO) techniques were used for each patient. Three-dimensional variable-RBE-weighted dose distributions were computed, using Monte Carlo calculated dose and LET distributions, and a linear dose and LET-based RBE model, and were compared between the two delivery methods. RESULTS: Increased target dose coverage and decreased mean and maximum dose to the OARs was achieved with IMPT compared to PS, for constant RBE value of 1.1. Nevertheless, the maximum variable-RBE-weighted dose to the brainstem, was increased up to 6% for the IMPT plans compared to the corresponding PS plans. CONCLUSIONS: IMPT can be dosimetrically superior to PS for ependymoma patients. However, caution should be exercised so that the increased dose conformity is not counteracted by an increase in radiobiological effect in adjacent critical structures.


Assuntos
Ependimoma/radioterapia , Transferência Linear de Energia/fisiologia , Terapia com Prótons/métodos , Planejamento da Radioterapia Assistida por Computador , Radioterapia de Intensidade Modulada , Eficiência Biológica Relativa , Calibragem , Estudos de Coortes , Relação Dose-Resposta à Radiação , Humanos , Método de Monte Carlo , Órgãos em Risco , Terapia com Prótons/efeitos adversos , Terapia com Prótons/normas , Radiometria , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/normas , Radioterapia de Intensidade Modulada/métodos , Radioterapia de Intensidade Modulada/normas
18.
Int J Radiat Oncol Biol Phys ; 100(3): 719-729, 2018 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-29413284

RESUMO

PURPOSE: Proton radiation therapy is commonly used in young children with brain tumors for its potential to reduce late effects. However, some proton series report higher rates of brainstem injury (0%-16%) than most photon series (2.2%-8.6%). We report the incidence of brainstem injury and a risk factor analysis in pediatric patients with posterior fossa primary tumors treated with proton radiation therapy at our institution. METHODS AND MATERIALS: The study included 216 consecutive patients treated between 2000 and 2015. Dosimetry was available for all but 4 patients. Grade 2 to 5 late brainstem toxicity was assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. RESULTS: The histologies include medulloblastoma (n=154, 71.3%), ependymoma (n=56, 25.9%), and atypical teratoid rhabdoid tumor (n=6, 2.8%). The median age at irradiation was 6.6 years (range, 0.5-23.1 years); median dose, 54 gray relative biological effectiveness (Gy RBE) (range, 46.8-59.4 Gy RBE); and median follow-up period, 4.2 years (range, 0.1-15.3 years) among 198 survivors. Of the patients, 83.3% received chemotherapy; 70.4% achieved gross total resection. The crude rate of injury was 2.3% in all patients, 1.9% in those with medulloblastoma, 3.6% in those with ependymoma, and 0% in those with atypical teratoid rhabdoid tumor. The 5-year cumulative incidence of injury was 2.0% (95% confidence interval, 0.7%-4.8%). The median brainstem dose (minimum dose received by 50% of brainstem) in the whole cohort was 53.6 Gy RBE (range, 16.5-56.8 Gy RBE); maximum point dose within the brainstem (Dmax), 55.2 Gy RBE (range, 48.4-60.5 Gy RBE); and mean dose, 50.4 Gy RBE (range, 21.1-56.7 Gy RBE). In the 5 patients with injury, the median minimum dose received by 50% of the brainstem was 54.6 Gy RBE (range, 50.2-55.1 Gy RBE); Dmax, 56.2 Gy RBE (range, 55.0-57.1 Gy RBE); mean dose, 51.3 Gy RBE (range, 45.4-54.4 Gy RBE); and median volume of the brainstem receiving ≥55 Gy RBE (V55), 27.4% (range, 0%-59.4%). Of the 5 patients with injury, 4 had a brainstem Dmax in the highest quartile (≥55.8 Gy RBE, P = .016) and a V55 in the highest tertile (>6.0%) of the cohort distribution (P = .047). Of the 5 patients with injury, 3 were aged >6 years (age range, 4.1-22.8 years), and 4 of 5 patients received chemotherapy and achieved gross total resection. CONCLUSIONS: The incidence of injury in pediatric patients with posterior fossa tumors is consistent with previous reports in the photon setting. Our data suggest that when Dmax and V55 are kept <55.8 Gy RBE and ≤6.0%, respectively, the 5-year rate of radiation brainstem injury would be <2%.


Assuntos
Tronco Encefálico/efeitos da radiação , Neoplasias Infratentoriais/radioterapia , Terapia com Prótons/efeitos adversos , Lesões por Radiação/epidemiologia , Adolescente , Criança , Pré-Escolar , Intervalos de Confiança , Ependimoma/tratamento farmacológico , Ependimoma/mortalidade , Ependimoma/radioterapia , Feminino , Seguimentos , Humanos , Incidência , Lactente , Neoplasias Infratentoriais/tratamento farmacológico , Neoplasias Infratentoriais/mortalidade , Masculino , Meduloblastoma/tratamento farmacológico , Meduloblastoma/mortalidade , Meduloblastoma/radioterapia , Intervalo Livre de Progressão , Lesões por Radiação/mortalidade , Lesões por Radiação/patologia , Dosagem Radioterapêutica , Eficiência Biológica Relativa , Tumor Rabdoide/tratamento farmacológico , Tumor Rabdoide/mortalidade , Tumor Rabdoide/radioterapia , Medição de Risco , Teratoma/tratamento farmacológico , Teratoma/mortalidade , Teratoma/radioterapia , Adulto Jovem
19.
AANA J ; 86(5): 361-370, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31584405

RESUMO

Patient safety may be at risk when details are omitted during anesthesia handoff. The Written Handoff Anesthesia Tool (WHAT), designed by the author, was implemented to improve the quality of anesthesia handoffs in the operating room and postanesthesia care unit (PACU). The author used the Anesthesia Handoff Communication survey to evaluate Certified Registered Nurse Anesthetist (CRNA) and PACU registered nurse (RN) satisfaction with anesthesia handoff and the Targeted Solutions Tool to identify the adequacy, contributing factors, and specific patient data omitted by senders of anesthesia handoff before and after implementation of the WHAT. Adequacy of the handoff process significantly improved for CRNAto-PACU RN (P < .0001) and CRNA-to-CRNA (P < .0001) handoffs. After implementation of the WHAT, satisfaction with anesthesia handoff significantly improved for CRNAs (P < .001) and PACU RNs (P = .001). Factors contributing to inadequate handoffs and omitted patient details were identified and significantly improved for CRNA-to-PACU RN and CRNA-to-CRNA handoffs, respectfully: ineffective method (P < .001; P < .001), baseline vital signs (P = .009; P = .014), and preoperative neurologic status (P = .012; P = .004). Implementation of the WHAT led to evidence-based changes in practice, standardization, and improved anesthesia handoff communication.


Assuntos
Anestesiologia/normas , Lista de Checagem/normas , Transferência da Responsabilidade pelo Paciente/normas , Humanos , Enfermeiras Anestesistas , Melhoria de Qualidade
20.
Integr Cancer Ther ; 17(1): 131-137, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-28110564

RESUMO

Excess weight at breast cancer diagnosis and weight gain during treatment are linked to increased breast cancer specific and all-cause mortality. The Breast-Activity and Healthy Eating After Diagnosis (B-AHEAD) trial tested 2 weight loss diet and exercise programmes versus a control receiving standard written advice during adjuvant treatment. This article identifies differences in characteristics between patients recruited from the main trial site to those of the whole population from that site during the recruitment period and identifies barriers to recruitment. A total of 409 patients with operable breast cancer were recruited within 12 weeks of surgery. We compared demographic and treatment factors between women recruited from the main trial coordinating site (n = 300) to the whole breast cancer population in the center (n = 532). Uptake at the coordinating site was 42%, comparable to treatment trials in the unit (47%). Women recruited were younger (55.9 vs 61.2 years, P < .001), more likely to live in least deprived postcode areas (41.7% vs 31.6%, P = .004), and more likely to have screen-detected cancers (55.3% vs 48.7%, P = .026) than the whole breast cancer population. The good uptake highlights the interest in lifestyle change around the time of diagnosis, a challenging time in the patient pathway, and shows that recruitment at this time is feasible. Barriers to uptake among older women and women with a lower socioeconomic status should be understood and overcome in order to improve recruitment to future lifestyle intervention programs.


Assuntos
Neoplasias da Mama/terapia , Dieta Saudável , Exercício Físico , Seleção de Pacientes , Neoplasias da Mama/complicações , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/mortalidade , Dieta Redutora , Feminino , Estilo de Vida Saudável , Humanos , Estilo de Vida , Pessoa de Meia-Idade , Sobrepeso/complicações , Sobrepeso/terapia
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