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1.
Nature ; 596(7871): 221-226, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-34381232

RESUMEN

Research on magnetic confinement of high-temperature plasmas has the ultimate goal of harnessing nuclear fusion for the production of electricity. Although the tokamak1 is the leading toroidal magnetic-confinement concept, it is not without shortcomings and the fusion community has therefore also pursued alternative concepts such as the stellarator. Unlike axisymmetric tokamaks, stellarators possess a three-dimensional (3D) magnetic field geometry. The availability of this additional dimension opens up an extensive configuration space for computational optimization of both the field geometry itself and the current-carrying coils that produce it. Such an optimization was undertaken in designing Wendelstein 7-X (W7-X)2, a large helical-axis advanced stellarator (HELIAS), which began operation in 2015 at Greifswald, Germany. A major drawback of 3D magnetic field geometry, however, is that it introduces a strong temperature dependence into the stellarator's non-turbulent 'neoclassical' energy transport. Indeed, such energy losses will become prohibitive in high-temperature reactor plasmas unless a strong reduction of the geometrical factor associated with this transport can be achieved; such a reduction was therefore a principal goal of the design of W7-X. In spite of the modest heating power currently available, W7-X has already been able to achieve high-temperature plasma conditions during its 2017 and 2018 experimental campaigns, producing record values of the fusion triple product for such stellarator plasmas3,4. The triple product of plasma density, ion temperature and energy confinement time is used in fusion research as a figure of merit, as it must attain a certain threshold value before net-energy-producing operation of a reactor becomes possible1,5. Here we demonstrate that such record values provide evidence for reduced neoclassical energy transport in W7-X, as the plasma profiles that produced these results could not have been obtained in stellarators lacking a comparably high level of neoclassical optimization.

2.
J Endocrinol Invest ; 47(1): 141-147, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37306894

RESUMEN

PURPOSE: Sexual dysfunctions are often experienced by male patients with acromegaly, due to a combination of hypogonadism and other comorbidities, but are a scarcely investigated complication. Erectile dysfunction is also closely related to cardiovascular diseases through endothelial dysfunction. Therefore, this project aimed to assess the prevalence of erectile dysfunction in a population of acromegalic men and evaluate its association with cardio-metabolic disorders, also exploring associations with androgen and estrogen receptor gene polymorphisms. METHODS: Sexually active men aged 18-65 with previous diagnosis of acromegaly were recruited. Clinical and laboratory data were retrospectively collected. Each patient also provided a blood sample for AR and ERß gene polymorphisms analyses and filled out the IIEF-15 questionnaire. RESULTS: Twenty men with previous diagnosis of acromegaly (mean age 48.4 ± 10.0 years) were recruited. 13/20 subjects (65%) had erectile dysfunction, but only four had a concurrent biochemical hypogonadism, with no significant correlation with IIEF-15 scores. Total testosterone negatively correlated with sexual intercourse satisfaction domain (ρ = - 0.595; p = 0.019) and general satisfaction domain (ρ = - 0.651; p = 0.009). IGF-1 levels negatively correlated with biochemical hypogonadism (ρ = - 0.585; p = 0.028). The number of CAG and CA repeats in AR and ERß receptors genes was not significantly associated with IIEF-15 scores or with GH/IGF-1 levels, but a negative correlation between CA repeats and the presence of cardiomyopathy (ρ = - 0.846; p = 0.002) was present. CONCLUSIONS: Men with acromegaly have a high prevalence of erectile dysfunction, but it does not appear to be correlated with treatments, testosterone levels and AR/ER-beta signaling. Nonetheless, a shorter CA polymorphic trait (ERbeta) is associated with the presence of cardiomyopathy. If confirmed, these data may suggest an association between an incorrect hormonal balance and increased cardiovascular risk in acromegaly subjects.


Asunto(s)
Acromegalia , Cardiomiopatías , Disfunción Eréctil , Hipogonadismo , Humanos , Masculino , Adulto , Persona de Mediana Edad , Andrógenos , Disfunción Eréctil/epidemiología , Disfunción Eréctil/genética , Acromegalia/complicaciones , Acromegalia/genética , Factor I del Crecimiento Similar a la Insulina/genética , Estudios Retrospectivos , Receptor beta de Estrógeno/genética , Testosterona , Hipogonadismo/complicaciones , Hipogonadismo/epidemiología , Hipogonadismo/genética , Polimorfismo Genético , Estrógenos
3.
Rev Neurol (Paris) ; 180(4): 290-297, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38508955

RESUMEN

The 2017 International League Against Epilepsy (ILAE) classification suggested that the term "genetic generalized epilepsies" (GGEs) should be used for the broad group of epilepsies with so-called "generalized" seizure types and "generalized" spike-wave activity on EEG, based on a presumed genetic etiology. Within this framework, idiopathic generalized epilepsies (IGEs) are described as a subset of GGEs and include only four epileptic syndromes: childhood absence epilepsy, juvenile absence epilepsy, juvenile myoclonic epilepsy, and epilepsy with generalized tonic-clonic seizures alone. The recent 2022 ILAE definition of IGEs is based on the current state of knowledge and reflects a community consensus and is designed to evolve as knowledge advances. The term "frontiers of IGEs" refers to the actual limits of our understanding of these four syndromes. Indeed, among patients presenting with a syndrome compatible with the 2022 definition of IGEs, we still observe a significant proportion of patients presenting with specific clinical features, refractory seizures, or drug-resistant epilepsies. This leads to the discussion of the boundaries of IGEs and GGEs, or what is accepted within a clinical spectrum of a definite IGE. Here, we discuss several entities that have been described in the literature for many years and that may either constitute rare features of IGEs or a distinct differential diagnosis. Their recognition by clinicians may allow a more individualized approach and improve the management of patients presenting with such entities.


Asunto(s)
Epilepsia Refractaria , Epilepsia Generalizada , Humanos , Epilepsia Generalizada/diagnóstico , Epilepsia Generalizada/fisiopatología , Epilepsia Refractaria/diagnóstico , Epilepsia Refractaria/fisiopatología , Epilepsia Refractaria/tratamiento farmacológico , Epilepsia Refractaria/etiología , Electroencefalografía , Anticonvulsivantes/uso terapéutico , Niño , Epilepsia Tipo Ausencia/diagnóstico , Epilepsia Tipo Ausencia/fisiopatología , Epilepsia Tipo Ausencia/tratamiento farmacológico
4.
Rev Neurol (Paris) ; 2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38866657

RESUMEN

BACKGROUND: Previous studies showed the efficacy of epilepsy surgery in carefully selected children with epilepsy associated with tuberous sclerosis complex. However, how this selection is conducted, and the characteristics of the patients brought to surgery are still poorly described. By conducting a multicentric retrospective cohort study covering the practice of the last twenty years, we describe the paths leading to epilepsy surgery in children with epilepsy associated with tuberous sclerosis complex. METHODS: We identified 84 children diagnosed with tuberous sclerosis complex and epilepsy by matching two exhaustive registries of genetic diseases and subsequent medical records reviews within two French neuropediatric and epilepsy centers. Demographic, clinical, longitudinal, and diagnostic and surgical procedures data were collected. RESULTS: Forty-six percent of the children were initially drug-resistant and 19% underwent resective surgery, most often before the age of four. Stereotactic electroencephalography was performed prior to surgery in 44% of cases. Fifty-seven and 43% of patients remained seizure-free one and ten years after surgery, respectively. In addition, 52% of initially drug-resistant patients who did not undergo surgery were seizure-free at the last follow-up. The number of anti-seizure medications required decreased in 50% of cases after surgery. Infantile spasms, intellectual disability, autism spectrum disorder or severe behavioral disorders were not contraindications to surgery but were associated with a higher rate of complications and a lower rate of seizure freedom after surgery. CONCLUSION: Despite the assumption of complex multifocal epilepsy and practical difficulties in young children with tuberous sclerosis complex, successful surgery results are comparable with other populations of patients with drug-resistant epilepsy, and a spontaneous evolution to drug-sensitive epilepsy may occur in non-operated patients.

5.
Hum Reprod ; 37(9): 2012-2031, 2022 08 25.
Artículo en Inglés | MEDLINE | ID: mdl-35906919

RESUMEN

STUDY QUESTION: What outcomes should be reported in all studies investigating uterus-sparing interventions for treating uterine adenomyosis? SUMMARY ANSWER: We identified 24 specific and 26 generic core outcomes in nine domains. WHAT IS KNOWN ALREADY: Research reporting adenomyosis treatment is not patient-centred and shows wide variation in outcome selection, definition, reporting and measurement of quality. STUDY DESIGN, SIZE, DURATION: An international consensus development process was performed between March and December 2021. Participants in round one were 150 healthcare professionals, 17 researchers and 334 individuals or partners with lived experience of adenomyosis from 48 high-, middle- and low-income countries. There were 291 participants in the second round. PARTICIPANTS/MATERIALS, SETTING, METHODS: Stakeholders included active researchers in the field, healthcare professionals involved in diagnosis and treatment, and people and their partners with lived experience of adenomyosis. The core component of the process was a 2-step modified Delphi electronic survey. The Steering Committee analysed the results and created the final core outcome set (COS) in a semi-structured meeting. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 241 outcomes was identified and distilled into a 'long list' of 71 potential outcomes. The final COS comprises 24 specific and 26 generic core outcomes across nine domains, including pain, uterine bleeding, reproductive outcomes, haematology, urinary system, life impact, delivery of care, adverse events and reporting items, all with definitions provided by the Steering Committee. Nineteen of these outcomes will apply only to certain study types. Although not included in the COS, the Steering Committee recommended that three health economic outcomes should be recorded. LIMITATIONS, REASONS FOR CAUTION: Patients from continents other than Europe were under-represented in this survey. A lack of translation of the survey might have limited the active participation of people in non-English speaking countries. Only 58% of participants returned to round two, but analysis did not indicate attrition bias. There is a significant lack of scientific evidence regarding which symptoms are caused by adenomyosis and when they are related to other co-existent disorders such as endometriosis. As future research provides more clarity, the appropriate review and revision of the COS will be necessary. WIDER IMPLICATIONS OF THE FINDINGS: Implementing this COS in future studies on the treatment of adenomyosis will improve the quality of reporting and aid evidence synthesis. STUDY FUNDING/COMPETING INTEREST(S): No specific funding was received for this work. T.T. received a grant (grant number 2020083) from the South Eastern Norwegian Health Authority during the course of this work. T.T. receives personal fees from General Electrics and Medtronic for lectures on ultrasound. E.R.L. is the chairman of the Norwegian Endometriosis Association. M.G.M. is a consultant for Abbvie Inc and Myovant, receives research funding from AbbVie and is Chair of the Women's Health Research Collaborative. S.-W.G. is a board member of the Asian Society of Endometriosis and Adenomyosis, on the scientific advisory board of the endometriosis foundation of America, previous congress chair for the World Endometriosis Society, for none of which he received personal fees. E.S. received outside of this work grants for two multicentre trials on endometriosis from the National Institute for Health Research UK, the Rosetrees Trust, and the Barts and the London Charity, he is a member of the Medicines and Healthcare Products Regulatory Agency (MHRA), Medicines for Women's Health Expert Advisory Group, he is an ambassador for the World Endometriosis Society, and he received personal fees for lectures from Hologic, Olympus, Medtronic, Johnson & Johnson, Intuitive and Karl Storz. M.H. is member of the British Society for Gynaecological Endoscopy subcommittee. No other conflict of interest was declared. TRIAL REGISTRATION NUMBER: N/A.


Asunto(s)
Adenomiosis , Endometriosis , Adenomiosis/terapia , Consenso , Técnica Delphi , Endometriosis/terapia , Femenino , Humanos , Masculino , Evaluación de Resultado en la Atención de Salud , Útero
7.
J Endocrinol Invest ; 44(12): 2675-2684, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33929709

RESUMEN

PURPOSE: Due to relevant repercussions on reproductive medicine, we aimed to evaluate feasibility of RT-PCR as a detection method of SARS-CoV-2 RNA in seminal fluid. METHODS: A qualitative determination of the RT-PCR assays in semen was performed through different approaches: (1) efficiency of RNA extraction from sperm and seminal plasma was determined using PRM1 and PRM2 mRNA and a heterologous system as control; (2) samples obtained by diluting viral preparation from a SARS-CoV-2 panel (virus cultured in Vero E6 cell lines) were tested; (3) viral presence in different fractions of seminal fluid (whole sample, seminal plasma and post-centrifugation pellet) was evaluated. Semen samples from mild and recovered COVID-19 subjects were collected by patients referring to the Infectious Disease Department of the Policlinico Umberto I Hospital - "Sapienza" University of Rome. Control subjects were recruited at the Laboratory of Seminology-Sperm Bank "Loredana Gandini'' of the same hospital. RESULTS: The control panel using viral preparations diluted in saline and seminal fluid showed the capability to detect viral RNA presence with Ct values depending on the initial viral concentration. All tested semen samples were negative for SARS-CoV-2, regardless of the nasopharyngeal swab result or seminal fluid fraction. CONCLUSION: These preliminary data show that RT-PCR for SARS-CoV-2 RNA testing appears to be a feasible method for the molecular diagnosis of SARS-CoV-2 in seminal fluid, supported by results of the control panel. The ability to detect SARS-CoV-2 in semen is extremely important for reproductive medicine, especially in assisted reproductive technology and sperm cryopreservation.


Asunto(s)
COVID-19/diagnóstico , Patología Molecular/métodos , Semen/virología , Adulto , Animales , Chlorocebus aethiops , Estudios de Factibilidad , Humanos , Masculino , ARN Mensajero/química , ARN Viral/química , Reacción en Cadena en Tiempo Real de la Polimerasa , Técnicas Reproductivas , Células Vero
8.
Phys Rev Lett ; 125(24): 243001, 2020 Dec 11.
Artículo en Inglés | MEDLINE | ID: mdl-33412031

RESUMEN

We demonstrate a widely applicable technique to absolutely calibrate the energy scale of x-ray spectra with experimentally well-known and accurately calculable transitions of highly charged ions, allowing us to measure the K-shell Rydberg spectrum of molecular O_{2} with 8 meV uncertainty. We reveal a systematic ∼450 meV shift from previous literature values, and settle an extraordinary discrepancy between astrophysical and laboratory measurements of neutral atomic oxygen, the latter being calibrated against the aforementioned O_{2} literature values. Because of the widespread use of such, now deprecated, references, our method impacts on many branches of x-ray absorption spectroscopy. Moreover, it potentially reduces absolute uncertainties there to below the meV level.

9.
BJOG ; 127(8): 967-974, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32227676

RESUMEN

OBJECTIVE: To develop a core outcome set for endometriosis. DESIGN: Consensus development study. SETTING: International. POPULATION: One hundred and sixteen healthcare professionals, 31 researchers and 206 patient representatives. METHODS: Modified Delphi method and modified nominal group technique. RESULTS: The final core outcome set includes three core outcomes for trials evaluating potential treatments for pain and other symptoms associated with endometriosis: overall pain; improvement in the most troublesome symptom; and quality of life. In addition, eight core outcomes for trials evaluating potential treatments for infertility associated with endometriosis were identified: viable intrauterine pregnancy confirmed by ultrasound; pregnancy loss, including ectopic pregnancy, miscarriage, stillbirth and termination of pregnancy; live birth; time to pregnancy leading to live birth; gestational age at delivery; birthweight; neonatal mortality; and major congenital abnormalities. Two core outcomes applicable to all trials were also identified: adverse events and patient satisfaction with treatment. CONCLUSIONS: Using robust consensus science methods, healthcare professionals, researchers and women with endometriosis have developed a core outcome set to standardise outcome selection, collection and reporting across future randomised controlled trials and systematic reviews evaluating potential treatments for endometriosis. TWEETABLE ABSTRACT: @coreoutcomes for future #endometriosis research have been developed @jamesmnduffy.


Asunto(s)
Investigación Biomédica , Endometriosis , Consenso , Técnica Delphi , Determinación de Punto Final , Femenino , Personal de Salud , Humanos , Estudios Prospectivos , Proyectos de Investigación , Investigadores
10.
Phys Rev Lett ; 122(3): 035002, 2019 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-30735428

RESUMEN

Electron temperature gradient (ETG)-driven turbulence, despite its ultrafine scale, is thought to drive significant thermal losses in magnetic fusion devices-but what role does it play in stellarators? The first numerical simulations of ETG turbulence for the Wendelstein 7-X stellarator, together with power balance analysis from its initial experimental operation phase, suggest that the associated transport should be negligible compared to other channels. The effect, we argue, originates essentially from the geometric constraint of multiple field periods, a generic feature of stellarators.

11.
Phys Rev Lett ; 123(2): 025002, 2019 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-31386539

RESUMEN

For the first time, the optimized stellarator Wendelstein 7-X has operated with an island divertor. An operation regime in hydrogen was found in which the total plasma radiation approached the absorbed heating power without noticeable loss of stored energy. The divertor thermography recorded simultaneously a strong reduction of the heat load on all divertor targets, indicating almost complete power detachment. This operation regime was stably sustained over several energy confinement times until the preprogrammed end of the discharge. The plasma radiation is mainly due to oxygen and is located at the plasma edge. This plasma scenario is reproducible and robust at various heating powers, plasma densities, and gas fueling locations. These experimental results show that the island divertor concept actually works and displays good power dissipation potential, producing a promising exhaust concept for the stellarator reactor line.

12.
BJOG ; 126(12): 1482-1490, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31359560

RESUMEN

OBJECTIVE: To quantify the effect of different methodological decisions on the identification of potential core outcomes to inform the development of recommendations for future core coutcome set developers. DESIGN: Mixed methods study. SETTING: A core outcome set for pre-eclampsia was used as an exemplar. SAMPLE: A long list of potential core outcomes was developed by undertaking a systematic review of pre-eclampsia trials and performing a thematic analysis of in-depth patient interviews. METHODS: Specific methods used to generate long lists of potential core outcomes were evaluated. RESULTS: Different methodological decisions had a substantial impact on the identification of potential core outcomes. Extracting outcomes from published pre-eclampsia trials was an effective way of identifying 48 maternal, eight fetal, 25 neonatal outcomes, and eight patient-reported outcomes. Limiting the extraction of outcomes to primary outcomes or outcomes commonly reported in pre-eclampsia trials reduced the number and diversity of potential core outcomes identified. Thematic analysis of in-depth patient interviews ensured an additional five patient reported outcomes and six outcomes related to future child health were identified. CONCLUSIONS: Future core outcome set developers should use quantitative and qualitative methods when developing a long list of potential core outcomes. TWEETABLE ABSTRACT: @OfficialNIHR research published in @BJOGtweets informs new recommendations for future @coreoutcomes developers.


Asunto(s)
Técnicas de Apoyo para la Decisión , Evaluación de Resultado en la Atención de Salud/estadística & datos numéricos , Preeclampsia/diagnóstico , Diagnóstico Prenatal , Femenino , Humanos , Evaluación de Resultado en la Atención de Salud/tendencias , Embarazo
13.
BJOG ; 125(5): 556-564, 2018 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-28755422

RESUMEN

BACKGROUND: The development of clinical guidelines requires standardised methods informed by robust evidence synthesis. OBJECTIVES: We evaluated the methodological quality of endometriosis guidelines, mapped their recommendations, and explored the relationships between recommendations and research evidence. SEARCH STRATEGY: We searched EMBASE, MEDLINE, and PubMed from inception to February 2016. SELECTION CRITERIA: We included guidelines related to the diagnosis and management of endometriosis. DATA COLLECTION AND ANALYSIS: The search strategy identified 879 titles and abstracts. We include two international and five national guidelines. Four independent authors assessed the methodological quality of the included guidelines, using the Appraisal of Guidelines for Research & Evaluation (AGREE-II) instrument, and systematically extracted the guideline recommendations and supporting research evidence. MAIN RESULTS: One hundred and fifty-two different recommendations were made. Ten recommendations (7%) were comparable across guidelines. The European Society of Human Reproduction and Embryology was objectively evaluated as the highest quality guideline (methodological quality score: 88/100). There was substantial variation between the supporting evidence presented by individual guidelines for comparable recommendations. Forty-two recommendations (28%) were not supported by research evidence. No guideline followed the standardised guideline development methods (AGREE-II). CONCLUSIONS: There is substantial variation in the recommendations and methodological quality of endometriosis guidelines. Future guidelines should be developed with reference to high-quality methods in consultation with key stakeholders, including women with endometriosis, ensuring that their scope can truly inform clinical practice and eliminate unwarranted and unjustified variations in clinical practice. TWEETABLE ABSTRACT: #Endometriosis guidelines vary in recommendations and quality. @EndometriosisUK.


Asunto(s)
Endometriosis/diagnóstico , Endometriosis/terapia , Guías de Práctica Clínica como Asunto/normas , Femenino , Humanos
14.
BJOG ; 125(7): 795-803, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-29030992

RESUMEN

BACKGROUND: Randomised trials and their syntheses in meta-analyses offer a unique opportunity to assess the frequency and severity of adverse reactions. OBJECTIVE: To assess safety reporting in pre-eclampsia trials. SEARCH STRATEGY: Systematic search using bibliographic databases, including Cochrane Central Register of Controlled Trials, Embase, and MEDLINE, from inception to August 2017. SELECTION CRITERIA: Randomised trials evaluating anticonvulsant or antihypertensive medication for pre-eclampsia. DATA COLLECTION AND ANALYSIS: Descriptive statistics appraising the adequacy of adverse reaction and toxicity reporting. MAIN RESULTS: We included 60 randomised trials. Six trials (10%) were registered with the International Clinical Trials Registry Platform, two registry records referred to adverse reactions, stating 'safety and toleration' and 'possible side effects' would be collected. Twenty-six trials (43%) stated the frequency of withdrawals within each study arm, and five trials (8%) adequately reported these withdrawals. Adverse reactions were inconsistently reported across eligible trials: 24 (40%) reported no serious adverse reactions and 36 (60%) reported no mild adverse reactions. The methods of definition or measurement of adverse reactions were infrequently reported within published trial reports. CONCLUSIONS: Pre-eclampsia trials regularly omit critical information related to safety. Despite the paucity of reporting, randomised trials collect an enormous amount of safety data. Developing and implementing a minimum data set could help to improve safety reporting, permitting a more balanced assessment of interventions by considering the trade-off between the benefits and harms. FUNDING: National Institute for Health Research (DRF-2014-07-051), UK; Maternity Forum, Royal Society of Medicine, UK. TWEETABLE ABSTRACT: Developing @coreoutcomes could help to improve safety reporting in #preeclampsia trials. @NIHR_DC.


Asunto(s)
Anticonvulsivantes/efectos adversos , Antihipertensivos/efectos adversos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/etiología , Seguridad del Paciente/estadística & datos numéricos , Preeclampsia/tratamiento farmacológico , Proyectos de Investigación/normas , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Femenino , Humanos , Embarazo , Ensayos Clínicos Controlados Aleatorios como Asunto
15.
Gene Ther ; 24(1): 49-59, 2017 01.
Artículo en Inglés | MEDLINE | ID: mdl-27834949

RESUMEN

Recent hemophilia B clinical trials using adeno-associated virus (AAV) gene delivery have demonstrated much lower coagulation factor IX (FIX) production in patients compared with the high levels observed in animal models and AAV capsid-specific cytotoxic T lymphocyte response elicited at high doses of AAV vectors. These results emphasize the necessity to explore effective approaches for enhancement of AAV transduction. Initially, we found that incubation of all AAV vectors with human serum enhanced AAV transduction. Complementary analytical experiments demonstrated that human serum albumin (HSA) directly interacted with the AAV capsid and augmented AAV transduction. The enhanced transduction was observed with clinical grade HSA. Mechanistic studies suggest that HSA increases AAV binding to target cells, and that the interaction of HSA with AAV does not interfere with the AAV infection pathway. Importantly, HSA incubation during vector dialysis also increased transduction. Finally, HSA enhancement of AAV transduction in a model of hemophilia B displayed greater than a fivefold increase in vector-derived circulating FIX, which improved the bleeding phenotype correction. In conclusion, incubation of HSA with AAV vectors supports a universal augmentation of AAV transduction and, more importantly, this approach can be immediately transitioned to the clinic for the treatment of hemophilia and other diseases.


Asunto(s)
Cápside/metabolismo , Dependovirus/genética , Hemofilia B/terapia , Albúmina Sérica/metabolismo , Animales , Línea Celular Tumoral , Dependovirus/metabolismo , Técnicas de Transferencia de Gen , Terapia Genética/métodos , Células HEK293 , Humanos , Ratones , Ratones Endogámicos C57BL , Unión Proteica
16.
BJOG ; 129(3): 365, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34773347
17.
BJOG ; 124(10): 1481-1489, 2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-28421657

RESUMEN

BACKGROUND: Variation in outcome collection and reporting is a serious hindrance to progress in our specialty; therefore, over 80 journals have come together to support the development, dissemination, and implementation of core outcome sets. OBJECTIVE: This study systematically reviewed and characterised registered, progressing, or completed core outcome sets relevant to women's and newborn health. SEARCH STRATEGY: Systematic search using the Core Outcome Measures in Effectiveness Trial initiative and the Core Outcomes in Women's and Newborn Health initiative databases. SELECTION CRITERIA: Registry entries, protocols, systematic reviews, and core outcome sets. DATA COLLECTION AND ANALYSIS: Descriptive statistics to describe characteristics and results. RESULTS: There were 49 core outcome sets registered in maternal and newborn health, with the majority registered in 2015 (n = 22; 48%) or 2016 (n = 16; 32%). Benign gynaecology (n = 8; 16%) and newborn health (n = 3; 6%) are currently under-represented. Twenty-four (52%) core outcome sets were funded by international (n = 1; <1%), national (n = 18; 38%), and regional (n = 4; 8%) bodies. Seven protocols were published. Twenty systematic reviews have characterised the inconsistency in outcome reporting across a broad range of relevant healthcare conditions. Four core outcome sets were completed: reconstructive breast surgery (11 outcomes), preterm birth (13 outcomes), epilepsy in pregnancy (29 outcomes), and maternity care (48 outcomes). The quantitative, qualitative, and consensus methods used to develop core outcome sets varied considerably. CONCLUSIONS: Core outcome sets are currently being developed across women's and newborn health, although coverage of topics is variable. Development of further infrastructure to develop, disseminate, and implement core outcome sets is urgently required. TWEETABLE ABSTRACT: Forty-nine women's and newborn core outcome sets registered. 50% funded. 7 protocols, 20 systematic reviews, and 4 core outcome sets published. @coreoutcomes @jamesmnduffy.


Asunto(s)
Salud del Lactante/estadística & datos numéricos , Evaluación de Resultado en la Atención de Salud , Salud de la Mujer/estadística & datos numéricos , Adolescente , Adulto , Femenino , Ginecología , Humanos , Recién Nacido , Servicios de Salud Materno-Infantil/estadística & datos numéricos , Obstetricia , Embarazo , Proyectos de Investigación , Adulto Joven
18.
BJOG ; 124(12): 1829-1839, 2017 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-28432737

RESUMEN

BACKGROUND: Standardising outcome collection and reporting in pre-eclampsia trials requires an appraisal of current outcome reporting. OBJECTIVES: To map maternal and offspring outcome reporting across randomised trials evaluating therapeutic interventions for pre-eclampsia. SEARCH STRATEGY: Randomised trials were identified by searching bibliographical databases from inception to January 2016. SELECTION CRITERIA: Randomised controlled trials. DATA COLLECTION AND ANALYSIS: We systematically extracted and categorised outcome reporting. MAIN RESULTS: Seventy-nine randomised trials, reporting data from 31 615 maternal participants and 28 172 of their offspring, were included. Fifty-five different interventions were evaluated. Included trials reported 119 different outcomes, including 72 maternal outcomes and 47 offspring outcomes. Maternal outcomes were inconsistently reported across included trials; for example, 11 trials (14%) reported maternal mortality, reporting data from 12 422 participants, and 16 trials (20%) reported cardiovascular morbidity, reporting data from 14 963 maternal participants. Forty-three trials (54%) reported fetal outcomes and 23 trials (29%) reported neonatal outcomes. Twenty-eight trials (35%) reported offspring mortality. There was poor reporting of childhood outcomes: six trials (8%) reported neurodevelopmental outcomes. Less than half of included trials reported any relevant information regarding harms for maternal participants and their offspring. CONCLUSIONS: Most randomised trials evaluating interventions for pre-eclampsia are missing information on clinically important outcomes, and in particular have neglected to evaluate efficacy and safety in the offspring of participants. Developing and implementing a minimum data set, known as a core outcome set, in future pre-eclampsia trials could help to address these issues. TWEETABLE ABSTRACT: Future #preeclampsia research requires a core outcome set to reduce #research waste. @coreoutcomes @jamesmnduffy International Prospective Register of Systematic Reviews: CRD42015015529; www.crd.york.ac.uk/PROSPERO/display_record.aspID=CRD42015015529.


Asunto(s)
Preeclampsia/terapia , Ensayos Clínicos Controlados Aleatorios como Asunto , Femenino , Humanos , Recién Nacido , Mortalidad Materna , Mortalidad Perinatal , Preeclampsia/mortalidad , Embarazo , Resultado del Tratamiento
19.
Reumatismo ; 69(1): 43-46, 2017 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-28535621

RESUMEN

Acute calcific tendinopathy is one of the manifestations of hydroxyapatite crystal deposition disease. While it is more frequent in the shoulder, it has been described in virtually all areas of the body, but rarely in the muscles of the hand. Its etiopathogenesis is not yet fully understood and despite being a fairly frequent condition, it is commonly misdiagnosed. The onset of the disease is usually acute and resolves spontaneously. Acute calcific tendinitis of the interosseous tendons of the hand is an uncommon site of a frequent condition. The clinical presentation is similar to other entities, thus errors in diagnosis frequently occur, resulting in over-treatment or unnecessary tests. We describe a case of acute calcific tendinitis of the interosseous muscles of the hand with a brief review of the current literature with emphasis on diagnostic imaging methods.


Asunto(s)
Calcinosis/complicaciones , Mano/patología , Músculo Esquelético/patología , Tendinopatía/complicaciones , Tendones/patología , Anciano , Calcinosis/diagnóstico por imagen , Diabetes Mellitus Tipo 2/complicaciones , Diagnóstico Diferencial , Femenino , Mano/diagnóstico por imagen , Humanos , Hipertensión/complicaciones , Músculo Esquelético/diagnóstico por imagen , Dolor/etiología , Factores de Riesgo , Tendinopatía/diagnóstico por imagen , Tendones/diagnóstico por imagen
20.
BJOG ; 123(11): 1761-8, 2016 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-27173590

RESUMEN

BACKGROUND: The development of a non-invasive and accurate diagnostic biomarker for endometriosis is urgently needed. OBJECTIVE: Evaluate the diagnostic accuracy of serum cancer antigen 125 (CA 125) for endometriosis. SEARCH STRATEGY: We searched EMBASE, MEDLINE, and Web of Science from inception to January 2016. SELECTION CRITERIA: Diagnostic accuracy studies of serum CA 125 (index test) for histologically confirmed endometriosis (reference standard) were included. DATA COLLECTION AND ANALYSIS: Two authors independently selected trials, extracted study characteristics and data. Methodological quality was assessed using Quality Assessment of Comparative Diagnostic Accuracy Studies (QUADAS-2) checklist. MAIN RESULTS: Twenty-two studies (16 cohort, six case-control), 3626 participants, were identified. Bivariate hierarchical models were used to pool accuracy data of 14 studies (2920 participants) using CA 125 ≥ 30 units/ml. Pooled specificity was 93% (95% CI 89-95%) and sensitivity 52% (95% CI 38-66%). CA 125 was significantly more sensitive for the diagnosis of moderate or severe endometriosis compared with minimal disease (63%, 95% CI 47-77% versus 24%, 95%CI 19-32%, P-value = 0.001). CONCLUSIONS: CA 125 performs well as a rule-in test facilitating expedited diagnosis and ensuring investigation and treatment can be confidently tailored for the management of endometriosis. Unfortunately, a negative test, CA 125 < 30 units/ml, is unable to rule out endometriosis. TWEETABLE ABSTRACT: Blood test CA 125: a rule-in test for the diagnosis of women presenting with symptoms of endometriosis.


Asunto(s)
Antígeno Ca-125/sangre , Endometriosis/diagnóstico , Proteínas de la Membrana/sangre , Adulto , Biomarcadores/sangre , Femenino , Humanos , Valor Predictivo de las Pruebas , Sensibilidad y Especificidad
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