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1.
Nature ; 580(7802): 227-231, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32269351

RESUMO

Atmospheric carbon dioxide enrichment (eCO2) can enhance plant carbon uptake and growth1-5, thereby providing an important negative feedback to climate change by slowing the rate of increase of the atmospheric CO2 concentration6. Although evidence gathered from young aggrading forests has generally indicated a strong CO2 fertilization effect on biomass growth3-5, it is unclear whether mature forests respond to eCO2 in a similar way. In mature trees and forest stands7-10, photosynthetic uptake has been found to increase under eCO2 without any apparent accompanying growth response, leaving the fate of additional carbon fixed under eCO2 unclear4,5,7-11. Here using data from the first ecosystem-scale Free-Air CO2 Enrichment (FACE) experiment in a mature forest, we constructed a comprehensive ecosystem carbon budget to track the fate of carbon as the forest responded to four years of eCO2 exposure. We show that, although the eCO2 treatment of +150 parts per million (+38 per cent) above ambient levels induced a 12 per cent (+247 grams of carbon per square metre per year) increase in carbon uptake through gross primary production, this additional carbon uptake did not lead to increased carbon sequestration at the ecosystem level. Instead, the majority of the extra carbon was emitted back into the atmosphere via several respiratory fluxes, with increased soil respiration alone accounting for half of the total uptake surplus. Our results call into question the predominant thinking that the capacity of forests to act as carbon sinks will be generally enhanced under eCO2, and challenge the efficacy of climate mitigation strategies that rely on ubiquitous CO2 fertilization as a driver of increased carbon sinks in global forests.


Assuntos
Atmosfera/química , Dióxido de Carbono/análise , Dióxido de Carbono/metabolismo , Sequestro de Carbono , Florestas , Árvores/metabolismo , Biomassa , Eucalyptus/crescimento & desenvolvimento , Eucalyptus/metabolismo , Aquecimento Global/prevenção & controle , Modelos Biológicos , New South Wales , Fotossíntese , Solo/química , Árvores/crescimento & desenvolvimento
2.
J Urol ; 211(2): 241-255, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37922370

RESUMO

PURPOSE: The treated natural history of nonmetastatic plasmacytoid variant of bladder cancer (PV-BCa) is poorly understood owing to its rarity. We sought to examine the disease recurrence and metastasis patterns in this select group of patients in order to identify opportunities for intervention. MATERIALS AND METHODS: We conducted a natural language processing algorithm-augmented retrospective chart review of 56 consecutive patients who were treated with curative intent for nonmetastatic PV-BCa at our institution between 1998 and 2018. Kaplan-Meier and multivariable Cox regression methods were used for survival analyses. RESULTS: The stage at presentation was: ≤ cT2N0 in 22 (39.3%), cT3N0 in 15 (26.8%), cT4N0 in 13 (23.2%), and ≥ cN1 in 6 patients (10.7%). Forty-nine patients (87.5%) received chemotherapy, and 42 (75%) were able to undergo the planned surgery. Notably, only 4 patients (7.2%) had pT0 stage, while 22 (52.4%) had pN+ disease at the time of surgery. At 36-month follow-up, 28.4% of patients (95% CI: 22.1%-34.5%) were alive and 22.2% (95% CI: 16.1%-28.5%) were free of metastatic disease. The benefit of surgical extirpation was stage specific: successful completion of surgery was associated with improved metastasis-free survival (at 36 months 32.4% vs 0%, log-rank P < .001) in patients with localized or locally advanced disease (≤cT2N0/cT3N0); however, in patients with regionally advanced disease (cT4N0/≥cN1), consolidative surgery following chemotherapy was not associated with improved metastasis-free survival (12.5% vs 10% at 36 months, log-rank P = .49). The median time to metastasis from primary treatment end was 6.5 months (IQR: 2.9-14.7). The predominant site of recurrence/metastasis was the peritoneum (76.1%), either in isolation or along with extraperitoneal lesions. Salvage immunotherapy in these patients significantly reduced the risk of death (HR = 0.11, P = .001). CONCLUSIONS: PV-BCa is a disease with high lethality. Despite multimodal treatment, a vast majority of patients develop atypical intraperitoneal metastasis soon after therapy and rapidly succumb to it. Clinical trials evaluating utility of hyperthermic intraperitoneal chemotherapy and/or immunotherapy may be warranted in this high-risk population.


Assuntos
Recidiva Local de Neoplasia , Neoplasias da Bexiga Urinária , Humanos , Estudos Retrospectivos , Recidiva Local de Neoplasia/epidemiologia , Neoplasias da Bexiga Urinária/terapia , Neoplasias da Bexiga Urinária/patologia , Terapia Combinada , Resultado do Tratamento
3.
BJU Int ; 133(6): 638-645, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38438065

RESUMO

OBJECTIVE: To explore the data comparing single- vs multi-use catheters for clean intermittent catheterisation (CIC), consider if the widespread use of single-use catheters is warranted given the cost and environmental impact, and put forth ideas for future consideration. METHODS: A primary literature review was performed in PubMed over the past 50 years. Studies that performed comparative analysis of single- and multi-use catheters were included in our review. All studies that reported on primary data were narratively summarised. RESULTS: A total of 11 studies were identified that reported on primary data comparing single- and multi-use catheters. There was no appreciable evidence suggesting reusable multi-use catheters were inferior to single-use catheters from an infection or usability standpoint. In addition, the environmental and monetary burden of single-use catheters is significant. CONCLUSIONS: The intermittent catheter landscape in the USA has a complex past: defined by policy, shaped by industry, yet characterised by a paucity of data demonstrating superiority of single-use over multi-use catheters. We believe that the aversion to reusable catheters by many patients and healthcare professionals is unwarranted, especially given the cost and environmental impact. Moving forward, better comparative data and more sustainable practices are needed.


Assuntos
Reutilização de Equipamento , Humanos , Reutilização de Equipamento/economia , Equipamentos Descartáveis/economia , Meio Ambiente , Cateteres Urinários , Cateterismo Uretral Intermitente/instrumentação
4.
Gen Comp Endocrinol ; 351: 114479, 2024 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-38431208

RESUMO

Functions of vitellogenins have been in the limelight of fish reproductive physiology research for decades. The Vtg system of acanthomorph teleosts consists of two complete forms of Vtgs (VtgAa and VtgAb) and an incomplete form, VtgC. Insufficient uptake and processing of Vtgs and their yolk proteins lead to inadequate oocyte hydration ensuing failure in acquisition of egg buoyancy and early developmental deficiencies. This review presents a summary of our studies on utilization of multiple Vtgs in species with different egg buoyancy characteristics, as examples. Studies of moronids revealed limited degradation of all three forms of lipovitellin heavy chain derived from their three respective forms of Vtg, by which they contribute to the free amino acid pool driving oocyte hydration during oocyte maturation. In later studies, CRISPR/Cas9 was employed to invalidate zebrafish type I, type II and type III Vtgs, which are orthologs of acanthamorph VtgAa, VtgAb and VtgC, respectively. Results revealed type I Vtg to have essential developmental and nutritional functions in both late embryos and larvae. Genomic disturbance of type II Vtg led to high mortalities during the first 24 h of embryonic development. Despite being a minor form of Vtg in zebrafish and most other species, type III Vtg was also found to contribute essentially to the developmental potential of zebrafish zygotes and early embryos. Apart from severe effects on progeny survival, these studies also disclosed previously unreported regulatory effects of Vtgs on fecundity and fertility, and on embryo hatching. We recently utilized parallel reactions monitoring based liquid chromatography tandem mass spectrometry to assess the processing and utilization of lipovitellins derived from different forms of Vtg in Atlantic halibut and European plaice. Results showed the Lv heavy chain of VtgAa (LvHAa) to be consumed during oocyte maturation and the Lv light chain of VtgAb (LvLAb) to be utilized specifically during late larval stages, while all remaining YPs (LvLAa, LvHAb, LvHC, and LvLC) were utilized during or after hatching up until first feeding in halibut. In plaice, all YPs except LvHAa, which similarly to halibut supports oocyte maturation, are utilized from late embryo to late larval development up until first feeding. The collective findings from these studies affirm substantial disparity in modes of utilization of different types of Vtgs among fish species with various egg buoyancy characteristics, and they reveal previously unknown regulatory functions of Vtgs in maintenance of reproductive assets such as maternal fecundity and fertility, and in embryonic hatching. Despite the progress that has been made over the past two decades by examining multiple Vtgs and their functions, a higher complexity of these systems with much greater diversity between species in modes of Vtg utilization is now evident. Further research is needed to reveal novel ways each species has evolved to utilize these complex multiple Vtg systems and to discover unifying principles for this evolution in fishes of diverse lineages, habitats and life history characteristics.


Assuntos
Perciformes , Vitelogeninas , Animais , Vitelogeninas/metabolismo , Peixe-Zebra/metabolismo , Peixes/metabolismo , Oócitos/metabolismo , Oogênese/genética , Perciformes/metabolismo
5.
J Urol ; 209(1): 49-57, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36129376

RESUMO

PURPOSE: Our goal was to review the history of the adoption of focal therapy for breast and prostate cancer and review common barriers to implementation. MATERIALS AND METHODS: A narrative review of the literature was performed of English-language MEDLINE indexed articles of breast-conservation therapy and prostate cancer focal therapy. RESULTS: The introduction of focal therapy in breast cancer began with pioneering case series, and multiple randomized trials were performed prior to widespread adoption. Focal therapy for prostate cancer has just started the process of clinical trials with a single published randomized controlled trial. Commonly cited barriers to the adoption of prostate focal therapy include historical views of Halstedian tumor biology, tumor multifocality, over-detection, limitations in prostate imaging, and trial design end points. CONCLUSIONS: The adoption of breast-conserving therapy evolved over decades and used data from multiple large, randomized, clinical trials. Barriers to the adoption of prostate cancer local therapy are similar to those faced by breast cancer clinical trials. Completion of well-designed trials in prostate cancer focal therapy is essential for its evidence-based adoption.


Assuntos
Neoplasias da Mama , Neoplasias da Próstata , Humanos , Masculino , Neoplasias da Mama/terapia , Neoplasias da Próstata/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto
6.
New Phytol ; 237(4): 1229-1241, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36373000

RESUMO

Optimal stomatal theory predicts that stomata operate to maximise photosynthesis (Anet ) and minimise transpirational water loss to achieve optimal intrinsic water-use efficiency (iWUE). We tested whether this theory can predict stomatal responses to elevated atmospheric CO2 (eCO2 ), and whether it can capture differences in responsiveness among woody plant functional types (PFTs). We conducted a meta-analysis of tree studies of the effect of eCO2 on iWUE and its components Anet and stomatal conductance (gs ). We compared three PFTs, using the unified stomatal optimisation (USO) model to account for confounding effects of leaf-air vapour pressure difference (D). We expected smaller gs , but greater Anet , responses to eCO2 in gymnosperms compared with angiosperm PFTs. We found that iWUE increased in proportion to increasing eCO2 in all PFTs, and that increases in Anet had stronger effects than reductions in gs . The USO model correctly captured stomatal behaviour with eCO2 across most datasets. The chief difference among PFTs was a lower stomatal slope parameter (g1 ) for the gymnosperm, compared with angiosperm, species. Land surface models can use the USO model to describe stomatal behaviour under changing atmospheric CO2 conditions.


Assuntos
Magnoliopsida , Árvores , Árvores/fisiologia , Dióxido de Carbono/farmacologia , Cycadopsida , Folhas de Planta/fisiologia , Fotossíntese/fisiologia , Água/fisiologia , Estômatos de Plantas/fisiologia
7.
Plant Cell Environ ; 45(6): 1631-1646, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35319101

RESUMO

Determining the relationship between reductions in stomatal conductance (gs ) and leaf water transport during dehydration is key to understanding plant drought responses. While numerous studies have analysed the hydraulic function of woody species, minimal research has been conducted on grasses. Here, we sought to characterize hydraulic vulnerability in five widely-occurring pasture grasses (including both C3 and C4 grasses) and determine whether reductions in gs and leaf hydraulic conductance (Kleaf ) during dehydration could be attributed to xylem embolism. Using the optical vulnerability (OV) technique, we found that all species were highly resistant to xylem embolism when compared to other herbaceous angiosperms, with 50% xylem embolism (PX50 ) occurring at xylem pressures ranging from -4.4 to -6.1 MPa. We observed similar reductions in gs and Kleaf under mild water stress for all species, occurring well before PX50 . The onset of xylem embolism (PX12 ) occurred consistently after stomatal closure and 90% reduction of Kleaf . Our results suggest that factors other than xylem embolism are responsible for the majority of reductions in gs and Kleaf during drought and reductions in the productivity of pasture species under moderate drought may not be driven by embolism.


Assuntos
Secas , Embolia , Desidratação , Folhas de Planta/fisiologia , Poaceae , Xilema/fisiologia
8.
World J Urol ; 40(1): 15-19, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33432506

RESUMO

INTRODUCTION: ISUP Grade Group 1 prostate cancer is the lowest histologic grade of prostate cancer with a clinically indolent course. Removal of the term 'cancer' has been proposed and has historical precedent both in urothelial and thyroid carcinoma. METHODS: Evidence-based review identifying arguments for and against Grade Group 1 being referred to as cancer. RESULTS: Grade Group 1 has histologic evidence of tissue microinvasion and 0.3-3% rate of extraprostatic extension. Genomic evaluation suggests overlap of a minority of Grade Group 1 cancers with those of Grade Group 2. Conversely, Grade Group 1 tumors appear to have distinct genetic and genomic profiles from Grade Group 3 or higher tumors. Grade Group 1 has no documented ability for regional or distant metastasis and long-term follow up after treatment or active surveillance is safe with excellent oncologic outcomes. DISCUSSION: Grade Group 1 prostate cancer, while showing evidence of neoplasia on histology has a remarkably indolent natural history more akin to non-neoplastic precursor lesions. Consideration should be given to renaming Grade Group 1 prostate cancer, which has the potential to minimize overtreatment, treatment-related side effects, patient anxiety, and financial burden on the healthcare system.


Assuntos
Neoplasias da Próstata/classificação , Neoplasias da Próstata/patologia , Terminologia como Assunto , Humanos , Masculino , Gradação de Tumores
9.
New Phytol ; 229(5): 2535-2547, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33217000

RESUMO

Photosynthetic water-use efficiency (WUE) describes the link between terrestrial carbon (C) and water cycles. Estimates of intrinsic WUE (iWUE) from gas exchange and C isotopic composition (δ13 C) differ due to an internal conductance in the leaf mesophyll (gm ) that is variable and seldom computed. We present the first direct estimates of whole-tree gm , together with iWUE from whole-tree gas exchange and δ13 C of the phloem (δ13 Cph ). We measured gas exchange, online 13 C-discrimination, and δ13 Cph monthly throughout spring, summer, and autumn in Eucalyptus tereticornis grown in large whole-tree chambers. Six trees were grown at ambient temperatures and six at a 3°C warmer air temperature; a late-summer drought was also imposed. Drought reduced whole-tree gm . Warming had few direct effects, but amplified drought-induced reductions in whole-tree gm . Whole-tree gm was similar to leaf gm for these same trees. iWUE estimates from δ13 Cph agreed with iWUE from gas exchange, but only after incorporating gm . δ13 Cph was also correlated with whole-tree 13 C-discrimination, but offset by -2.5 ± 0.7‰, presumably due to post-photosynthetic fractionations. We conclude that δ13 Cph is a good proxy for whole-tree iWUE, with the caveats that post-photosynthetic fractionations and intrinsic variability of gm should be incorporated to provide reliable estimates of this trait in response to abiotic stress.


Assuntos
Árvores , Água , Dióxido de Carbono , Isótopos de Carbono , Células do Mesofilo , Fotossíntese , Folhas de Planta
10.
Glob Chang Biol ; 27(12): 2970-2990, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33694242

RESUMO

Rising atmospheric [CO2 ] (Ca ) generally enhances tree growth if nutrients are not limiting. However, reduced water availability and elevated evaporative demand may offset such fertilization. Trees with access to deep soil water may be able to mitigate such stresses and respond more positively to Ca . Here, we sought to evaluate how increased vapor pressure deficit and reduced precipitation are likely to modify the impact of elevated Ca (eCa ) on tree productivity in an Australian Eucalyptus saligna Sm. plantation with access to deep soil water. We parameterized a forest growth simulation model (GOTILWA+) using data from two field experiments on E. saligna: a 2-year whole-tree chamber experiment with factorial Ca (ambient =380, elevated =620 µmol mol-1 ) and watering treatments, and a 10-year stand-scale irrigation experiment. Model evaluation showed that GOTILWA+ can capture the responses of canopy C uptake to (1) rising vapor pressure deficit (D) under both Ca treatments; (2) alterations in tree water uptake from shallow and deep soil layers during soil dry-down; and (3) the impact of irrigation on tree growth. Simulations suggest that increasing Ca up to 700 µmol mol-1 alone would result in a 33% increase in annual gross primary production (GPP) and a 62% increase in biomass over 10 years. However, a combined 48% increase in D and a 20% reduction in precipitation would halve these values. Our simulations identify high D conditions as a key limiting factor for GPP. They also suggest that rising Ca will compensate for increasing aridity limitations in E. saligna trees with access to deep soil water under non-nutrient limiting conditions, thereby reducing the negative impacts of global warming upon this eucalypt species. Simulation models not accounting for water sources available to deep-rooting trees are likely to overestimate aridity impacts on forest productivity and C stocks.


Assuntos
Solo , Água , Austrália , Dióxido de Carbono , Fertilização , Folhas de Planta , Árvores
11.
Glob Chang Biol ; 27(7): 1387-1407, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33274502

RESUMO

Ecosystems integrity and services are threatened by anthropogenic global changes. Mitigating and adapting to these changes require knowledge of ecosystem functioning in the expected novel environments, informed in large part through experimentation and modelling. This paper describes 13 advanced controlled environment facilities for experimental ecosystem studies, herein termed ecotrons, open to the international community. Ecotrons enable simulation of a wide range of natural environmental conditions in replicated and independent experimental units while measuring various ecosystem processes. This capacity to realistically control ecosystem environments is used to emulate a variety of climatic scenarios and soil conditions, in natural sunlight or through broad-spectrum lighting. The use of large ecosystem samples, intact or reconstructed, minimizes border effects and increases biological and physical complexity. Measurements of concentrations of greenhouse trace gases as well as their net exchange between the ecosystem and the atmosphere are performed in most ecotrons, often quasi continuously. The flow of matter is often tracked with the use of stable isotope tracers of carbon and other elements. Equipment is available for measurements of soil water status as well as root and canopy growth. The experiments ran so far emphasize the diversity of the hosted research. Half of them concern global changes, often with a manipulation of more than one driver. About a quarter deal with the impact of biodiversity loss on ecosystem functioning and one quarter with ecosystem or plant physiology. We discuss how the methodology for environmental simulation and process measurements, especially in soil, can be improved and stress the need to establish stronger links with modelling in future projects. These developments will enable further improvements in mechanistic understanding and predictive capacity of ecotron research which will play, in complementarity with field experimentation and monitoring, a crucial role in exploring the ecosystem consequences of environmental changes.


Assuntos
Ecossistema , Ciência Ambiental , Biodiversidade , Ecologia , Solo
12.
Catheter Cardiovasc Interv ; 97(3): E411-E417, 2021 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-32633055

RESUMO

BACKGROUND: Hypoattenuating leaflet thickening (HALT), the radiographic manifestation of transcatheter heart valve thrombosis, is commonly identified following transcatheter aortic valve replacement (TAVR) and associated with increased risk of stroke and structural valve deterioration. While anticoagulation effectively resolves HALT, routine use remains controversial. We aimed to identify hemodynamic, anatomic, and comorbid predictors of HALT. METHODS: We evaluated consecutive patients with severe aortic stenosis who underwent TAVR with Edwards SAPIEN 3 bioprosthesis at a single center between June 1, 2018 and October 30, 2019. Patients on anticoagulation and those receiving valve-in-valve were excluded. Clinically driven computed tomography (CT) imaging was performed to assess for HALT at the discretion of the treating valve team. RESULTS: A total of 78 patients with a mean age of 78 ± 10 years and STS risk score 5.5 ± 3.3% were analyzed. HALT was identified in 11 (14.1%) patients. Compared to controls, those with HALT had smaller annular areas, 435 ± 57 mm2 vs. 489 ± 79 mm2 (p = .032), but received comparable size valves. In multivariate regression, valve oversizing by more than 20% was associated with increased risk of HALT, OR 23.5, 95% CI 2.5-223, (p = .006). After initiation of anticoagulation, patients with HALT had similar rates of stroke, major bleeding, and all-cause mortality out to an average of 243 days. CONCLUSIONS: In this pragmatic study of patients undergoing TAVR with SAPIEN 3 valves, we report the novel finding that oversizing by more than 20% was independently associated with increased risk of HALT. These findings warrant confirmation in larger and prospective trials.


Assuntos
Estenose da Valva Aórtica , Próteses Valvulares Cardíacas , Trombose , Substituição da Valva Aórtica Transcateter , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/cirurgia , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/cirurgia , Próteses Valvulares Cardíacas/efeitos adversos , Humanos , Estudos Prospectivos , Desenho de Prótese , Trombose/diagnóstico por imagem , Trombose/etiologia , Substituição da Valva Aórtica Transcateter/efeitos adversos , Resultado do Tratamento
13.
New Phytol ; 228(5): 1511-1523, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32531796

RESUMO

Thermoregulation of leaf temperature (Tleaf ) may foster metabolic homeostasis in plants, but the degree to which Tleaf is moderated, and under what environmental contexts, is a topic of debate. Isotopic studies inferred the temperature of photosynthetic carbon assimilation to be a constant value of c. 20°C; by contrast, leaf biophysical theory suggests a strong dependence of Tleaf on environmental drivers. Can this apparent disparity be reconciled? We continuously measured Tleaf and whole-crown net CO2 uptake for Eucalyptus parramattensis trees growing in field conditions in whole-tree chambers under ambient and +3°C warming conditions, and calculated assimilation-weighted leaf temperature (TL-AW ) across 265 d, varying in air temperature (Tair ) from -1 to 45°C. We compared these data to TL-AW derived from wood cellulose δ18 O. Tleaf exhibited substantial variation driven by Tair , light intensity, and vapor pressure deficit, and Tleaf was strongly linearly correlated with Tair with a slope of c. 1.0. TL-AW values calculated from cellulose δ18 O vs crown fluxes were remarkably consistent; both varied seasonally and in response to the warming treatment, tracking variation in Tair . The leaves studied here were nearly poikilothermic, with no evidence of thermoregulation of Tleaf towards a homeostatic value. Importantly, this work supports the use of cellulose δ18 O to infer TL-AW , but does not support the concept of strong homeothermic regulation of Tleaf.


Assuntos
Dióxido de Carbono , Eucalyptus , Árvores , Homeostase , Isótopos de Oxigênio , Fotossíntese , Folhas de Planta , Temperatura
14.
Am J Obstet Gynecol ; 222(1): 83.e1-83.e8, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31376396

RESUMO

BACKGROUND: The mainstay of the management of opioid use disorder in pregnancy is with methadone or buprenorphine medication-assisted treatment. Methadone and buprenorphine are opioid agonist drugs. Naltrexone, an opioid antagonist, is also a medication-assisted treatment option; however, to date, only a few retrospective studies have reported its use in pregnancy. OBJECTIVE: Our study objective was to evaluate prospectively obstetric and newborn outcomes and the maternal/fetal effects of the use of naltrexone as a medication-assisted treatment in pregnant patients with opioid use disorder. STUDY DESIGN: We performed a prospective cohort study collecting data on all pregnant women who were treated with naltrexone medication-assisted treatment compared with pregnant women who were treated with methadone or buprenorphine medication-assisted treatment. Based on a sample size calculation, it was determined that for a power of 90, a minimum of 160 study participants (80 in each group) was needed with an alpha of .01 and an expected 60% rate of newborn infants who were treated for neonatal abstinence syndrome in the methadone or buprenorphine medication-assisted treatment group compared with a 30% rate in the naltrexone medication-assisted treatment group. In a random subset of 20 maternal/newborn dyads, blood levels for naltrexone and 6-beta-naltrexol (an active metabolite) were analyzed at delivery. RESULTS: A total of 230 patients were studied: 121 patients with naltrexone medication-assisted treatment compared with 109 patients with methadone or buprenorphine medication-assisted treatment. No differences between groups were seen regarding demographics, the use of comedications/drugs, or obstetric outcomes. For newborn outcomes, the rate of neonatal abstinence syndrome in neonates >34 weeks gestation was significantly lower in the naltrexone medication-assisted treatment group (10/119 [8.4%] vs 79/105 [75.2%]; P<.0001). Multivariate analysis demonstrated that the only significant factor for the rate of neonatal abstinence syndrome was the form of medication-assisted treatment. Of 87 patients who received naltrexone up to delivery, no neonates experienced symptoms of neonatal abstinence syndrome. No maternal relapses occurred in the 7-day no-treatment window before the initiation of naltrexone therapy. No cases of spontaneous abortion or stillbirth occurred in either group. In 64 patients who started naltrexone therapy at ≥24 weeks gestation, no changes were seen in the fetal heart monitor tracing with drug initiation. The incidence of birth anomalies was no different between the groups. Umbilical cord blood and maternal levels for naltrexone and 6-beta-naltrexol matched; no levels were elevated, and values were undetected if naltrexone was discontinued >60 hours before delivery. CONCLUSION: These study data demonstrate that, in pregnant women who choose to completely detoxify off opioid drugs during gestation, naltrexone, as a continued form of medication-assisted treatment, is a viable option for some pregnant patients who experience opioid use disorder. Naltrexone crosses the placenta, and maternal and fetal levels are concordant. Because naltrexone clears quickly from the maternal circulation, this rapid clearance needs to be addressed with patients. This is important because maternal relapse could occur in a short time-period if the oral drug is discontinued without the knowledge of their healthcare providers. Nonetheless, the drug is well-tolerated by both mother and fetus, and newborn infants do not experience symptoms of neonatal abstinence syndrome if naltrexone medication-assisted treatment is maintained to delivery.


Assuntos
Naltrexona/uso terapêutico , Antagonistas de Entorpecentes/uso terapêutico , Síndrome de Abstinência Neonatal/epidemiologia , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Complicações na Gravidez/tratamento farmacológico , Aborto Espontâneo/epidemiologia , Adulto , Analgésicos Opioides/uso terapêutico , Buprenorfina/uso terapêutico , Estudos de Casos e Controles , Feminino , Humanos , Recém-Nascido , Metadona/uso terapêutico , Naltrexona/análogos & derivados , Naltrexona/sangue , Tratamento de Substituição de Opiáceos , Gravidez , Estudos Prospectivos , Natimorto/epidemiologia , Adulto Jovem
15.
BJOG ; 127(5): 636-645, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31808248

RESUMO

OBJECTIVES: To assess feasibility of a future randomised controlled trial (RCT) of clinical and cost-effectiveness of lifestyle information and commercial weight management groups to support postnatal weight management to 12 months post-birth. DESIGN: Two-arm feasibility trial, with nested mixed-methods process evaluation. SETTING: Inner-city unit, south England. POPULATION: Women with body mass indices (BMIs) ≥25 kg/m2 at pregnancy booking or normal BMIs (18.5-24.9 kg/m2 ) identified with excessive gestational weight gain at 36 weeks of gestation. METHODS: Randomised to standard care plus commercial weight management sessions commencing 8-16 weeks postnatally or standard care only. MAIN OUTCOMES: Feasibility outcomes included assessment of recruitment, retention, acceptability and economic data collation. Primary and secondary end points included difference between groups in weight 12 months postnatally compared with booking (proposed primary outcome for a future trial), diet, physical activity, smoking, alcohol, mental health, infant feeding, NHS resource use. RESULTS: In all, 193 women were randomised: 98 intervention and 95 control; only four women had excessive gestational weight gain. A slightly greater weight change was found among intervention women at 12 months, with greatest benefit. Among women attending ten or more weight management sessions. There was >80% follow up to 12 months, low risk of contamination and no group differences in trial completion. CONCLUSION: It was feasible to recruit and retain women with BMIs ≥25 kg/m2 to an intervention to support postnatal weight management; identification of excessive gestational weight gain requires consideration. Economic modelling could inform out-of-trial costs and benefits in a future trial. A definitive trial is an important next step. TWEETABLE ABSTRACT: A feasibility RCT of postnatal weight support showed women with BMIs ≥25 kg/m2 can be recruited and followed to 12 months postnatally.


Assuntos
Ganho de Peso na Gestação , Estilo de Vida , Período Pós-Parto , Programas de Redução de Peso , Adulto , Índice de Massa Corporal , Análise Custo-Benefício , Estudos de Viabilidade , Feminino , Comportamentos Relacionados com a Saúde , Humanos , Gravidez , Reino Unido
16.
Am J Perinatol ; 37(7): 679-688, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31104311

RESUMO

OBJECTIVE: This study aimed to perform a systematic review of all studies reporting fetal outcomes following detoxification or tapering of opioid drugs during pregnancy. STUDY DESIGN: PubMed, Scopus, Medline, and Google Scholar were searched, and only manuscripts clearly reporting pregnancy/fetal outcomes involving tapering or detoxification from opioid drugs were included. Only pregnancies managed after 1980 were included (when antenatal fetal surveillance became more routine). Collected data included study design, location, years patients were managed, number of patients who were tapered or detoxified, method of tapering, and pregnancy outcome. RESULTS: A total of 14 publications met the criteria for review after evaluating more than 2,000 abstracts and 153 published manuscripts. In 1,097 pregnancies, based on mortality rate analyses and forest plots, no increased fetal risks due to tapering or detoxification from opioid drugs were identified. No increased risk of preterm delivery was found. CONCLUSION: Pregnant women with opioid use disorder who are stable in a medication-assisted treatment program with behavioral health can be informed that tapering or full detoxification from opioid drugs does not increase the fetal risk of poor pregnancy outcome. Future research needs to answer the questions on maternal and long-term newborn consequences of tapering or detoxification versus long-term newborn consequences of continued chronic in utero opioid exposure.


Assuntos
Síndrome de Abstinência Neonatal/prevenção & controle , Tratamento de Substituição de Opiáceos , Transtornos Relacionados ao Uso de Opioides/terapia , Resultado da Gravidez , Analgésicos Opioides , Feminino , Feto/efeitos dos fármacos , Humanos , Recém-Nascido , Tratamento de Substituição de Opiáceos/efeitos adversos , Gravidez , Complicações na Gravidez/terapia , Cuidado Pré-Natal
17.
Am J Perinatol ; 37(9): 924-928, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-31154665

RESUMO

OBJECTIVE: This study aimed to evaluate the psychosocial background history and confounding social factors in pregnant women with opioid use disorder (OUD). STUDY DESIGN: We performed a prospective observational cohort study of pregnant women from a dedicated obstetrical OUD clinic. Data collection came from extensive interview sessions regarding psychosocial background events and other social factors that might impact prenatal care. RESULTS: From February 1, 2017, through September 30, 2018, 411 pregnant women were evaluated and 294 (72%, 95% confidence interval [CI]: 67-76%) reported abuse of which 217 (53%, 95% CI: 48-58%) involved sexual abuse (prior to the age of 13 years in 54% of cases) and 209 (51%, 95% CI: 46-56%) involved cases of other physical abuse. Only 10% reported habitual opioid use for managing chronic pain. Only 9% had a valid driver's license with access to a car making transportation to office visits difficult. CONCLUSION: A history of abuse (mainly sexual and/or physical) appears to be the main precipitating event leading to OUD in our pregnant population. Transportation was the primary social factor limiting access to prenatal care. For primary prevention to be successful in our region, early identification of young women who have experienced abuse needs to occur followed by psychotherapy health care intervention before opioid drugs are used.


Assuntos
Analgésicos Opioides/uso terapêutico , Transtornos Relacionados ao Uso de Opioides/terapia , Complicações na Gravidez/terapia , Gestantes/psicologia , Cuidado Pré-Natal/métodos , Adulto , Dor Crônica/tratamento farmacológico , Feminino , Humanos , Tratamento de Substituição de Opiáceos , Gravidez , Cuidado Pré-Natal/estatística & dados numéricos , Estudos Prospectivos , Delitos Sexuais/estatística & dados numéricos , Centros de Tratamento de Abuso de Substâncias , Tennessee , Adulto Jovem
18.
New Phytol ; 222(3): 1313-1324, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30840319

RESUMO

Autotrophic respiration is a major driver of the global C cycle and may contribute a positive climate warming feedback through increased atmospheric concentrations of CO2 . The extent of this feedback depends on plants' ability to acclimate respiration to maintain a constant carbon use efficiency (CUE). We quantified respiratory partitioning of gross primary production (GPP) and CUE of field-grown trees in a long-term warming experiment (+3°C). We delivered a 13 C-CO2 pulse to whole tree crowns and chased that pulse in the respiration of leaves, whole crowns, roots, and soil. We also measured the isotopic composition of soil microbial biomass and the respiration rates of leaves and whole crowns. We documented homeostatic respiratory acclimation of foliar and whole-crown respiration rates; the trees adjusted to experimental warming such that leaf-level respiration rates were not increased. Experimental warming had no detectable impact on respiratory partitioning or mean residence times. Of the 13 C label acquired by the trees, aboveground respiration consumed 10%, belowground respiration consumed 40%, and the remaining 50% was retained. Experimental warming of +3°C did not alter respiratory partitioning at the scale of entire trees, suggesting that complete acclimation of respiration to warming is likely to dampen a positive climate warming feedback.


Assuntos
Dióxido de Carbono/metabolismo , Isótopos de Carbono/metabolismo , Aquecimento Global , Árvores/metabolismo , Respiração Celular , Marcação por Isótopo , Folhas de Planta/metabolismo , Raízes de Plantas/metabolismo , Solo/química
19.
New Phytol ; 222(3): 1298-1312, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30536971

RESUMO

The allocation of carbon (C) is an important component of tree physiology that influences growth and ecosystem C storage. Allocation is challenging to measure, and its sensitivity to environmental changes such as warming and altered water availability is uncertain. We exposed young Eucalyptus tereticornis trees to +3°C warming and elimination of summer precipitation in the field using whole-tree chambers. We calculated C allocation terms using detailed measurements of growth and continuous whole-crown CO2 and water exchange measurements. Trees grew from small saplings to nearly 9 m height during this 15-month experiment. Warming accelerated growth and leaf area development, and it increased the partitioning of gross primary production (GPP) to aboveground respiration and growth while decreasing partitioning below ground. Eliminating summer precipitation reduced C gain and growth but did not impact GPP partitioning. Trees utilized deep soil water and avoided strongly negative water potentials. Warming increased growth respiration, but maintenance respiration acclimated homeostatically. The increasing growth in the warmed treatment resulted in higher rates of respiration, even with complete acclimation of maintenance respiration. Warming-induced stimulations of tree growth likely involve increased C allocation above ground, particularly to leaf area development, whereas reduced water availability may not stimulate allocation to roots.


Assuntos
Eucalyptus/crescimento & desenvolvimento , Temperatura , Árvores/crescimento & desenvolvimento , Água/metabolismo , Biomassa , Carbono/metabolismo , Dióxido de Carbono/metabolismo , Respiração Celular , Secas , Folhas de Planta/fisiologia , Solo/química
20.
Neurourol Urodyn ; 38(6): 1783-1791, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31215706

RESUMO

AIMS: Sacral neuromodulation (SNM) is a standard therapy for refractory overactive bladder (OAB). Traditionally, SNM placement involves placement of an S3 lead with 1-3 weeks of testing before considering a permanent implant. Given the potential risk of bacterial contamination during testing and high success rates published by some experts, we compared the costs of traditional 2-stage against single-stage SNM placement for OAB. METHODS: We performed a cost minimization analysis using published data on 2-stage SNM success rates, SNM infection rates, and direct reimbursements from Medicare for 2017. We compared the costs associated with a 2-stage vs single-stage approach. We performed sensitivity analyses of the primary variables listed above to assess where threshold values occurred and used separate models for freestanding ambulatory surgery centers (ASC) and outpatient hospital departments (OHD). RESULTS: Based on published literature, our base case assumed a 69% SNM success rate, a 5% 2-stage approach infection rate, a 1.7% single-stage approach infection rate, and removal of 50% of non-working single-stage SNMs. In both ASC ($17 613 vs $18 194) and OHD ($19 832 vs $21 181) settings, single-stage SNM placement was less costly than 2-stage placement. The minimum SNM success rates to achieve savings with a single-stage approach occur at 65.4% and 61.3% for ASC and OHD, respectively. CONCLUSIONS: Using Medicare reimbursement, single-stage SNM placement is likely to be less costly than 2-stage placement for most practitioners. The savings are tied to SNM success rates and reimbursement rates, with reduced costs up to $5014 per case in centers of excellence (≥ 90% success).


Assuntos
Terapia por Estimulação Elétrica/economia , Bexiga Urinária Hiperativa/economia , Bexiga Urinária Hiperativa/cirurgia , Procedimentos Cirúrgicos Urológicos/economia , Idoso , Procedimentos Cirúrgicos Ambulatórios/economia , Custos e Análise de Custo , Árvores de Decisões , Terapia por Estimulação Elétrica/métodos , Feminino , Humanos , Infecções/etiologia , Infecções/psicologia , Reembolso de Seguro de Saúde/estatística & dados numéricos , Medicare/estatística & dados numéricos , Pessoa de Meia-Idade , Resultado do Tratamento , Estados Unidos , Procedimentos Cirúrgicos Urológicos/métodos
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