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2.
PLoS One ; 19(2): e0297857, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38416750

RESUMEN

OBJECTIVES: To explore local induction of labour pathways in the UK National Health Service to provide insight into current practice. DESIGN: National survey. SETTING: Hospital maternity services in all four nations of the UK. SAMPLE: Convenience sample of 71 UK maternity units. METHODS: An online cross-sectional survey was disseminated and completed via a national network of obstetrics and gynaecology specialist trainees (October 2021-March 2022). Results were analysed descriptively, with associations explored using Fisher's Exact and ANOVA. MAIN OUTCOME MEASURES: Induction rates, criteria, processes, delays, incidents, safety concerns. RESULTS: 54/71 units responded (76%, 35% of UK units). Induction rate range 19.2%-53.4%, median 36.3%. 72% (39/54) had agreed induction criteria: these varied widely and were not all in national guidance. Multidisciplinary booking decision-making was not reported by 38/54 (70%). Delays reported 'often/always' in hospital admission for induction (19%, 10/54) and Delivery Suite transfer once induction in progress (63%, 34/54). Staffing was frequently reported cause of delay (76%, 41/54 'often/always'). Delays triggered incident reports in 36/54 (67%) and resulted in harm in 3/54 (6%). Induction was an area of concern (44%, 24/54); 61% (33/54) reported induction-focused quality improvement work. CONCLUSIONS: There is substantial variation in induction rates, processes and policies across UK maternity services. Delays appear to be common and are a cause of safety concerns. With induction rates likely to increase, improved guidance and pathways are critically needed to improve safety and experience of care.


Asunto(s)
Obstetricia , Medicina Estatal , Embarazo , Humanos , Femenino , Estudios Transversales , Trabajo de Parto Inducido , Reino Unido
3.
BMJ Open ; 14(1): e082835, 2024 01 18.
Artículo en Inglés | MEDLINE | ID: mdl-38238057

RESUMEN

INTRODUCTION: In the UK, 1600 babies die every year before, during or immediately after birth at 20-28 weeks' gestation. This bereavement has a similar impact on parental physical and psychological well-being to late stillbirth (>28 weeks' gestation). Improved understanding of potentially modifiable risk factors for late stillbirth (including supine going-to-sleep position) has influenced international clinical practice. Information is now urgently required to similarly inform clinical practice and aid decision-making by expectant mothers/parents, addressing inequalities in pregnancy loss between 20 and 28 weeks. METHODS AND ANALYSIS: This study focuses on what portion of risk of pregnancy loss 20-28 weeks' gestation is associated with exposures amenable to public health campaigns/antenatal care adaptation. A case-control study of non-anomalous singleton baby loss (via miscarriage, stillbirth or early neonatal death) 20+0 to 27+6 (n=316) and randomly selected control pregnancies (2:1 ratio; n=632) at group-matched gestations will be conducted. Data is collected via participant recall (researcher-administered questionnaire) and extraction from contemporaneous medical records. Unadjusted/confounder-adjusted ORs will be calculated. Exposures associated with early stillbirth at OR≥1.5 will be detectable (p<0.05, ß>0.80) assuming exposure prevalence of 30%-60%. ETHICS AND DISSEMINATION: NHS research ethical approval has been obtained from the London-Seasonal research ethics committee (23/LO/0622). The results will be presented at international conferences and published in peer-reviewed open-access journals. Information from this study will enable development of antenatal care and education for healthcare professionals and pregnant people to reduce risk of early stillbirth. TRIAL REGISTRATION NUMBER: NCT06005272.


Asunto(s)
Aborto Espontáneo , Mortinato , Recién Nacido , Humanos , Femenino , Embarazo , Mortinato/epidemiología , Mortinato/psicología , Estudios de Casos y Controles , Madres , Atención Prenatal , Encuestas y Cuestionarios
4.
Nature ; 626(8000): 836-842, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38267582

RESUMEN

HIV can infect non-dividing cells because the viral capsid can overcome the selective barrier of the nuclear pore complex and deliver the genome directly into the nucleus1,2. Remarkably, the intact HIV capsid is more than 1,000 times larger than the size limit prescribed by the diffusion barrier of the nuclear pore3. This barrier in the central channel of the nuclear pore is composed of intrinsically disordered nucleoporin domains enriched in phenylalanine-glycine (FG) dipeptides. Through multivalent FG interactions, cellular karyopherins and their bound cargoes solubilize in this phase to drive nucleocytoplasmic transport4. By performing an in vitro dissection of the nuclear pore complex, we show that a pocket on the surface of the HIV capsid similarly interacts with FG motifs from multiple nucleoporins and that this interaction licences capsids to penetrate FG-nucleoporin condensates. This karyopherin mimicry model addresses a key conceptual challenge for the role of the HIV capsid in nuclear entry and offers an explanation as to how an exogenous entity much larger than any known cellular cargo may be able to non-destructively breach the nuclear envelope.


Asunto(s)
Proteínas de la Cápside , Glicina , VIH , Carioferinas , Imitación Molecular , Proteínas de Complejo Poro Nuclear , Poro Nuclear , Fenilalanina , Humanos , Transporte Activo de Núcleo Celular , Proteínas de la Cápside/química , Proteínas de la Cápside/metabolismo , Difusión , Dipéptidos/química , Dipéptidos/metabolismo , Glicina/metabolismo , VIH/química , VIH/metabolismo , Técnicas In Vitro , Proteínas Intrínsecamente Desordenadas/química , Proteínas Intrínsecamente Desordenadas/metabolismo , Carioferinas/metabolismo , Poro Nuclear/química , Poro Nuclear/metabolismo , Poro Nuclear/virología , Proteínas de Complejo Poro Nuclear/química , Proteínas de Complejo Poro Nuclear/metabolismo , Permeabilidad , Fenilalanina/metabolismo , Solubilidad , Internalización del Virus , Cápside/química , Cápside/metabolismo
6.
Psychol Med ; 54(3): 447-456, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37927223

RESUMEN

Debate is ongoing on the efficacy of cognitive behavior therapy (CBT) for myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS). With an individual patient data (IPD) meta-analysis we investigated whether the effect of CBT varied by patient characteristics. These included post-exertional malaise (PEM), a central feature of ME/CFS according to many. We searched for randomized controlled trials similar with respect to comparison condition, outcomes and treatment-protocol. Moderation on fatigue severity (Checklist Individual Strength, subscale fatigue severity), functional impairment (Sickness Impact Profile-8) and physical functioning (Short Form-36, subscale physical functioning) was investigated using linear mixed model analyses and interaction tests. PROSPERO (CRD42022358245). Data from eight trials (n = 1298 patients) were pooled. CBT showed beneficial effects on fatigue severity (ß = -11.46, 95% CI -15.13 to -7.79); p < 0.001, functional impairment (ß = -448.40, 95% CI -625.58 to -271.23); p < 0.001; and physical functioning (ß = 9.64, 95% CI 3.30 to 15.98); p < 0.001. The effect of CBT on fatigue severity varied by age (pinteraction = 0.003), functional impairment (pinteraction = 0.045) and physical activity pattern (pinteraction = 0.027). Patients who were younger, reported less functional impairments and had a fluctuating activity pattern benefitted more. The effect on physical functioning varied by self-efficacy (pinteraction = 0.025), with patients with higher self-efficacy benefitting most. No other moderators were found. It can be concluded from this study that CBT for ME/CFS can lead to significant reductions of fatigue, functional impairment, and physical limitations. There is no indication patients meeting different case definitions or reporting additional symptoms benefit less from CBT. Our findings do not support recent guidelines in which evidence from studies not mandating PEM was downgraded.


Asunto(s)
Terapia Cognitivo-Conductual , Síndrome de Fatiga Crónica , Humanos , Síndrome de Fatiga Crónica/terapia , Ejercicio Físico , Terapia por Ejercicio/métodos , Terapia Cognitivo-Conductual/métodos
7.
Trials ; 24(1): 584, 2023 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-37700365

RESUMEN

BACKGROUND: Approximately one in ten women have high blood pressure during pregnancy. Hypertension is associated with adverse maternal and perinatal outcomes, and as treatment improves maternal outcomes, antihypertensive treatment is recommended. Previous trials have been unable to provide a definitive answer on which antihypertensive treatment is associated with optimal maternal and neonatal outcomes and the need for robust evidence evaluating maternal and infant benefits and risks remains an important, unanswered question for research and clinical communities. METHODS: The Giant PANDA study is a pragmatic, open-label, multicentre, randomised controlled trial of a treatment initiation strategy with nifedipine (calcium channel blocker), versus labetalol (mixed alpha/beta blocker) in 2300 women with pregnancy hypertension. The primary objective is to evaluate if treatment with nifedipine compared to labetalol in women with pregnancy hypertension reduces severe maternal hypertension without increasing fetal or neonatal death or neonatal unit admission. Subgroup analyses will be undertaken by hypertension type (chronic, gestational, pre-eclampsia), diabetes (yes, no), singleton (yes, no), self-reported ethnicity (Black, all other), and gestational age at randomisation categories (11 + 0 to 19 + 6, 20 + 0 to 27 + 6, 28 + 0 to 34 + 6 weeks). A cost-effectiveness analysis using an NHS perspective will be undertaken using a cost-consequence analysis up to postnatal hospital discharge and an extrapolation exercise with a lifetime horizon conditional on the results of the cost-consequence analysis. DISCUSSION: This trial aims to address the uncertainty of which antihypertensive treatment is associated with optimal maternal and neonatal outcomes. The trial results are intended to provide definitive evidence to inform guidelines and linked, shared decision-making tools, thus influencing clinical practice. TRIAL REGISTRATION: EudraCT number: 2020-003410-12, ISRCTN: 12,792,616 registered on 18 November 2020.


Asunto(s)
Hipertensión , Labetalol , Preeclampsia , Ursidae , Embarazo , Lactante , Recién Nacido , Animales , Femenino , Humanos , Labetalol/efectos adversos , Nifedipino/efectos adversos , Antihipertensivos/efectos adversos , Hipertensión/diagnóstico , Hipertensión/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Multicéntricos como Asunto
8.
N Z Vet J ; 71(6): 283-294, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37621178

RESUMEN

The introduction and subsequent rapid spread of Japanese encephalitis virus genotype IV across all Australian mainland states and the Northern Territory since late 2021 has increased the risk of an incursion of this mosquito-transmitted zoonotic virus disease into New Zealand, with serious implications for both animal and human health. The potential modes of entry are through introduction of infected mosquitoes as hitchhikers on ships or aircraft, windborne transfer of mosquitoes, or arrival of infected reservoir bird species. A competent vector mosquito, Culex quinquefasciatus, is endemic in New Zealand and other mosquito species may also become involved. If infection becomes established in New Zealand, the scale of transmission may be considerably less than has occurred in Australia because climatic and epidemiological factors are not so favourable. Early evidence of an incursion could come from detection of clinical disease in horses or pigs, or from human cases. Targeted surveillance to confirm or refute indications of an incursion could be undertaken by antibody detection in a number of species. Dogs have been shown to be a particularly valuable sentinel species due to their cohabitation with people and high seroconversion rate. Other novel methods of surveillance could include reverse transcriptase PCR (RT-PCR) on oronasal secretions of pigs. Should evidence of the disease be detected, prompt action would be required to vaccinate at-risk human populations and clarify the epidemiological situation with respect to mammalian hosts and mosquito vector species, including whether a new mosquito species had arrived in the country.Abbreviations: AHL: Animal Health Laboratory; JE: Japanese encephalitis disease; JEV: Japanese encephalitis virus; RT-PCR: Reverse transcriptase PCR.


Asunto(s)
Enfermedades de los Perros , Virus de la Encefalitis Japonesa (Especie) , Enfermedades de los Caballos , Enfermedades de los Porcinos , Animales , Perros , Humanos , Australia/epidemiología , Enfermedades de los Perros/virología , Virus de la Encefalitis Japonesa (Especie)/genética , Enfermedades de los Caballos/virología , Caballos , Nueva Zelanda/epidemiología , ARN Viral/análisis , Sensibilidad y Especificidad , Porcinos , Enfermedades de los Porcinos/virología , Zoonosis/epidemiología
9.
ACS Cent Sci ; 9(7): 1374-1387, 2023 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-37521792

RESUMEN

Native mass spectrometry (nMS) screening of natural glycan libraries against glycan-binding proteins (GBPs) is a powerful tool for ligand discovery. However, as the glycan concentrations are unknown, affinities cannot be measured directly from natural libraries. Here, we introduce Concentration-Independent (COIN)-nMS, which enables quantitative screening of natural glycan libraries by exploiting slow mixing of solutions inside a nanoflow electrospray ionization emitter. The affinities (Kd) of detected GBP-glycan interactions are determined, simultaneously, from nMS analysis of their time-dependent relative abundance changes. We establish the reliability of COIN-nMS using interactions between purified glycans and GBPs with known Kd values. We also demonstrate the implementation of COIN-nMS using the catch-and-release (CaR)-nMS assay for glycosylated GBPs. The COIN-CaR-nMS results obtained for plant, fungal, viral, and human lectins with natural libraries containing hundreds of N-glycans and glycopeptides highlight the assay's versatility for discovering new ligands, precisely measuring their affinities, and uncovering "fine" specificities. Notably, the COIN-CaR-nMS results clarify the sialoglycan binding properties of the SARS-CoV-2 receptor binding domain and establish the recognition of monosialylated hybrid and biantennary N-glycans. Moreover, pharmacological depletion of host complex N-glycans reduces both pseudotyped virions and SARS-CoV-2 cell entry, suggesting that complex N-glycans may serve as attachment factors.

10.
Tech Coloproctol ; 27(12): 1297-1305, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37486461

RESUMEN

BACKGROUND: The optimal treatment of colorectal cancer is surgical resection and primary anastomosis. Anastomotic leak can affect up to 20% of patients and creates significant morbidity and mortality. Current diagnosis of a leak is based on clinical suspicion and subsequent radiology. Peritoneal biomarkers have shown diagnostic utility in other conditions and could be useful in providing earlier diagnosis. This pilot study was designed to assess the practical utility of peritoneal biomarkers after abdominal surgery utilising an automated immunoassay system in routine use for quantifying cytokines. METHODS: Patients undergoing an anterior resection for a rectal cancer diagnosis were recruited at University Hospital of Wales, Cardiff between June 2019 and June 2021. A peritoneal drain was placed in the proximity of the anastomosis during surgery, and peritoneal fluid was collected at days 1 to 3 post-operatively, and analysed using the Siemens IMMULITE platform for interleukin (IL)-1ß, IL-6, IL-10, CXCL8, tumour necrosis factor alpha (TNFα) and C-reactive protein (CRP). RESULTS: A total of 42 patients were recruited (22M:20F, median age 65). Anastomotic leak was detected in four patients and a further five patients had other intra-abdominal complications. The IMMULITE platform was able to provide robust and reliable results from the analysis of the peritoneal fluid. A metric based on the combination of peritoneal IL-6 and CRP levels was able to accurately diagnose three anastomotic leaks, whilst correctly classifying all negative control patients including those with other complications. CONCLUSIONS: This pilot study demonstrates that a simple immune signature in surgical drain fluid could accurately diagnose an anastomotic leak at 48 h postoperatively using instrumentation that is already widely available in hospital clinical laboratories.


Asunto(s)
Fuga Anastomótica , Neoplasias del Recto , Humanos , Anciano , Fuga Anastomótica/diagnóstico , Fuga Anastomótica/etiología , Interleucina-6 , Proyectos Piloto , Biomarcadores , Anastomosis Quirúrgica/efectos adversos , Neoplasias del Recto/complicaciones , Estudios Retrospectivos
11.
Hypertension ; 80(5): 1077-1091, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-37043613

RESUMEN

BACKGROUND: Few studies have investigated the hemodynamic mechanism whereby primary aldosteronism causes hypertension. The traditional view holds that hyperaldosteronism initiates hypertension by amplifying salt-dependent increases in cardiac output (CO) by promoting increases in sodium retention and blood volume. Systemic vascular resistance (SVR) is said to increase only as a secondary consequence of the increased CO and blood pressure. However, mounting evidence indicates that aldosterone can influence multiple pathways regulating vascular tone. We investigated the primary hemodynamic mechanism whereby hyperaldosteronism promotes salt sensitivity and initiation of salt-dependent hypertension. METHODS: In unilaterally nephrectomized male Sprague-Dawley rats given infusions of aldosterone or vehicle, we used chronically implanted arterial pressure probes and Doppler ultrasonic flow probes to continuously monitor changes in mean arterial pressure, CO, and SVR 24 hours/day, 7 days/week in response to increases in salt intake. RESULTS: In vehicle-treated control rats, switching from a low-salt diet to a high-salt diet initiated modest increases in mean arterial pressure by increasing SVR while simultaneously decreasing heart rate and CO. In aldosterone-treated rats compared with control rats, switching from a low-salt diet to a high-salt diet initiated significantly greater increases in mean arterial pressure and SVR and significantly greater decreases in heart rate and CO. CONCLUSIONS: Aldosterone promoted salt sensitivity and initiation of salt-dependent hypertension by amplifying salt-induced increases in SVR while decreasing CO. Increases in CO are not required for the initiation or maintenance of hypertension. These findings challenge the traditional view of the hemodynamic mechanisms that cause hypertension in primary aldosteronism.


Asunto(s)
Hiperaldosteronismo , Hipertensión , Masculino , Ratas , Animales , Aldosterona , Cloruro de Sodio Dietético/efectos adversos , Ratas Sprague-Dawley , Hemodinámica , Presión Sanguínea , Gasto Cardíaco , Resistencia Vascular , Hiperaldosteronismo/complicaciones
12.
Neurosci Biobehav Rev ; 147: 105068, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36738813

RESUMEN

Freezing of gait (FOG) is a common and disabling symptom in people with Parkinson's Disease (PwPD). Although cognition is thought to be worse in PwPD who freeze, a comprehensive analysis of this relationship will inform future research and clinical care. This systematic review and meta-analysis compared cognition between PwPD who do and do not exhibit FOG across a range of cognitive domains and assessed the impact of disease severity and medication status on this relationship. 145 papers (n = 9010 participants) were included in the analysis, with 144 and 138 articles meeting the criteria to assess moderating effects of disease severity and medication status, respectively. PwPD who freeze exhibited worse cognition than PwPD without FOG across global cognition, executive function/attention, language, memory, and visuospatial domains. Greater disease severity and "ON" levodopa medication status moderated the FOG status-cognition relationship in global cognitive performance but not in other cognitive domains. This meta-analysis confirmed that cognition is worse in PwPD with FOG and highlights the importance of disease severity and medication status in this relationship.


Asunto(s)
Trastornos Neurológicos de la Marcha , Enfermedad de Parkinson , Humanos , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/tratamiento farmacológico , Trastornos Neurológicos de la Marcha/etiología , Cognición , Levodopa , Marcha
13.
Behav Res Ther ; 161: 104243, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36549190

RESUMEN

BACKGROUND: Cognitive behavioural therapy (CBT) is effective in reducing fatigue across long-term conditions (LTCs). This study evaluated whether cognitive and behavioural responses to symptoms: 1) differ between LTCs and 2) moderate and/or mediate the effect of CBT on fatigue. METHOD: Data were used from four Randomized Controlled Trials testing the efficacy of CBT for fatigue in Chronic Fatigue Syndrome/ME (N = 240), Multiple Sclerosis (N = 90), Type 1 Diabetes Mellitus (N = 120) and Q-fever fatigue syndrome (N = 155). Fatigue severity, assessed with the Checklist Individual Strength, was the primary outcome. Differences in fatigue perpetuating factors, assessed with the Cognitive Behavioural Responses to Symptoms Questionnaire (CBRQ), between diagnostic groups were tested using ANCOVAs. Linear regression and mediation analyses were used to investigate moderation and mediation by CBRQ scores of the treatment effect. RESULTS: There were small to moderate differences in CBRQ scores between LTCs. Patients with higher scores on the subscales damage beliefs and avoidance/resting behaviour at baseline showed less improvement following CBT, irrespective of diagnosis. Reduction in fear avoidance, catastrophising and avoidance/resting behaviour mediated the positive effect of CBT on fatigue across diagnostic groups. DISCUSSION: The same cognitive-behavioural responses to fatigue moderate and mediate treatment outcome across conditions, supporting a transdiagnostic approach to fatigue.


Asunto(s)
Terapia Cognitivo-Conductual , Síndrome de Fatiga Crónica , Humanos , Síndrome de Fatiga Crónica/terapia , Síndrome de Fatiga Crónica/psicología , Resultado del Tratamiento , Encuestas y Cuestionarios , Cognición
14.
Int J Cardiol ; 371: 135-139, 2023 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-36181953

RESUMEN

INTRODUCTION: The Ross procedure, where a pulmonary autograft (neoaorta) replaces the aortic valve, has excellent long-term outcomes in patients with congenital aortic valve disease. However, there are reports of neoaortic dilatation and dissection. An increasing number of women are wishing to become pregnant following the Ross procedure, but little is known about the occurrence and risks of neoaortic dilatation and complications in pregnancy. We investigated neoaorta function and outcomes in pregnancy following the Ross procedure. METHODS: This retrospective study investigated women post-Ross procedure at a tertiary ACHD unit between 1997 and 2021. Imaging evaluated neoaortic root dimensions and regurgitation pre-, and post- pregnancy, compared with matched non-pregnant controls. Primary endpoints were change in neoaortic dimensions, degree of regurgitation and adverse maternal outcomes. RESULTS: Nineteen pregnancies in 12 women were included. The mean change in neoaortic root diameter post-pregnancy was 1.8 mm (SD 3.4) (p = 0.017). There was no significant change in neoaortic dimensions in matched controls during follow-up. There were no cases of dissection, arrhythmia, acute coronary syndrome, or maternal mortality. Three deliveries were pre-term, including one emergency Caesarean section due to maternal cardiac decompensation, requiring aortic root replacement post-partum but there were no neonatal deaths. CONCLUSIONS: Pregnancy following the Ross procedure is associated with neoaortic dilatation, and pregnancy is generally well tolerated. Although adverse maternal outcomes are uncommon, there are still rare cases of cardiac complications in and around the time of pregnancy. These findings emphasise the need for accessible pre-pregnancy counselling, risk stratification and careful surveillance through pregnancy by specialist cardio-obstetric multi-disciplinary teams.


Asunto(s)
Insuficiencia de la Válvula Aórtica , Estenosis de la Válvula Aórtica , Válvula Pulmonar , Humanos , Femenino , Embarazo , Insuficiencia de la Válvula Aórtica/diagnóstico por imagen , Insuficiencia de la Válvula Aórtica/cirugía , Insuficiencia de la Válvula Aórtica/etiología , Estudios Retrospectivos , Resultado del Embarazo/epidemiología , Autoinjertos , Cesárea , Trasplante Autólogo/efectos adversos , Válvula Aórtica/diagnóstico por imagen , Válvula Aórtica/cirugía , Estenosis de la Válvula Aórtica/cirugía , Dilatación Patológica , Válvula Pulmonar/diagnóstico por imagen , Válvula Pulmonar/cirugía , Estudios de Seguimiento
15.
Infect Control Hosp Epidemiol ; 44(3): 488-490, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-35403600

RESUMEN

An antimicrobial stewardship bundle was implemented in 23 community health system urgent care and primary care clinics to reduce fluoroquinolone prescribing in urinary tract infections. The percentage of urinary tract infection (UTI) visits prescribed a fluoroquinolone subsequently decreased from 17.6% to 3% in urgent care and from 23.8% to 6.8% in primary care.


Asunto(s)
Programas de Optimización del Uso de los Antimicrobianos , Infecciones Urinarias , Humanos , Fluoroquinolonas/uso terapéutico , Antibacterianos/uso terapéutico , Pacientes Ambulatorios , Infecciones Urinarias/tratamiento farmacológico , Prescripción Inadecuada/prevención & control
16.
Lancet ; 400(10361): 1426-1436, 2022 10 22.
Artículo en Inglés | MEDLINE | ID: mdl-36273481

RESUMEN

BACKGROUND: Miscarriage in the second trimester and preterm birth are significant global problems. Vaginal cervical cerclage is performed to prevent pregnancy loss and preterm birth. We aimed to determine the effectiveness of a monofilament suture thread compared with braided suture thread on pregnancy loss rates in women undergoing a cervical cerclage. METHODS: C-STICH was a pragmatic, randomised, controlled, superiority trial done at 75 obstetric units in the UK. Women with a singleton pregnancy who received a vaginal cervical cerclage due to a history of pregnancy loss or premature birth, or if indicated by ultrasound, were centrally randomised (1:1) using minimisation to receive a monofilament suture or braided suture thread for their cervical cerclage. Women and outcome assessors were masked to allocation as far as possible. The primary outcome was pregnancy loss, defined as miscarriage, stillbirth, or neonatal death in the first week of life, analysed in the intention-to-treat population (ie, all women who were randomly assigned). Safety was also assessed in the intention-to-treat population. The trial was registered with ISRCTN, ISRCTN15373349. FINDINGS: Between Aug 21, 2015, and Jan 28, 2021, 2049 women were randomly assigned to receive a monofilament suture (n=1025) or braided suture (n=1024). The primary outcome was ascertained in 1003 women in the monofilament suture group and 993 women in the braided suture group. Pregnancy loss occurred in 80 (8·0%) of 1003 women in the monofilament suture group and 75 (7·6%) of 993 women in the braided suture group (adjusted risk ratio 1·05 [95% CI 0·79 to 1·40]; adjusted risk difference 0·002 [95% CI -0·02 to 0·03]). INTERPRETATION: Monofilament suture did not reduce rate of pregnancy loss when compared with a braided suture. Clinicians should use the results of this trial to facilitate discussions around the choice of suture thread to optimise outcomes. FUNDING: National Institute of Health Research Health Technology Assessment Programme.


Asunto(s)
Aborto Espontáneo , Cerclaje Cervical , Nacimiento Prematuro , Recién Nacido , Embarazo , Femenino , Humanos , Cerclaje Cervical/métodos , Resultado del Embarazo , Nacimiento Prematuro/epidemiología , Nacimiento Prematuro/prevención & control , Aborto Espontáneo/epidemiología , Aborto Espontáneo/prevención & control , Suturas
17.
Brain Spine ; 2: 100893, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36248097

RESUMEN

•Overall electrode accuracy was 0.22+/-0.4 â€‹mm with only 3 (4%) electrodes out with 2 â€‹mm from the intended target.•Accuracy was significantly worse in the GPi versus the STN and on the second side implanted.•Inaccuracy occurred in the X (lateral) plane but was not related to pneumocephalus or brain shift.

18.
Neurobiol Learn Mem ; 195: 107685, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36174888

RESUMEN

This study outlines two novel protocols for examining context specific recall in animals prior to embarking on neurobiological studies. The approach is distinct from and contrasts with studies investigating associative familiarity that depend upon procedural variations of the widely used novel object recognition task. It uses an event arena in which animals are trained across numerous sessions to search for, find and dig up reward from sandwells during sample and choice trials - a prominent spatial event for a rodent. The arena could be laid out as either of two highly distinct contexts with which the animals became fully familiar throughout training. In one protocol, the location of the correct sandwell in each context remained stable across days, whereas in the other, the correct digging location varied in a counterbalanced manner across each successive session. Thus, context-specific recall of the spatial location of successful digging during choice trials was either from a stable long-term memory or could reflect context specific spatial recency of the location where reward had been available that session. Both protocols revealed effective memory recall in choice and probe tests which, at the point of test, were procedurally identical in both cases.


Asunto(s)
Memoria , Recuerdo Mental , Animales , Reconocimiento en Psicología , Percepción Visual , Recompensa
19.
NPJ Biofilms Microbiomes ; 8(1): 68, 2022 08 29.
Artículo en Inglés | MEDLINE | ID: mdl-36038607

RESUMEN

Biofilms are increasingly recognised as a critical global issue in a multitude of industries impacting health, food and water security, marine sector, and industrial processes resulting in estimated economic cost of $5 trillion USD annually. A major barrier to the translation of biofilm science is the gap between industrial practices and academic research across the biofilms field. Therefore, there is an urgent need for biofilm research to notice and react to industrially relevant issues to achieve transferable outputs. Regulatory frameworks necessarily bridge gaps between different players, but require a clear, science-driven non-biased underpinning to successfully translate research. Here we introduce a 2-dimensional framework, termed the Biofilm Research-Industrial Engagement Framework (BRIEF) for classifying existing biofilm technologies according to their level of scientific insight, including the understanding of the underlying biofilm system, and their industrial utility accounting for current industrial practices. We evidence the BRIEF with three case studies of biofilm science across healthcare, food & agriculture, and wastewater sectors highlighting the multifaceted issues around the effective translation of biofilm research. Based on these studies, we introduce some advisory guidelines to enhance the translational impact of future research.


Asunto(s)
Biopelículas , Aguas Residuales , Agua
20.
Pharmaceutics ; 14(6)2022 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-35745736

RESUMEN

Intravenous (IV) cefuroxime and cefazolin are used prophylactically in caesarean sections (CS). Currently, there are concerns regarding sub-optimal dosing in obese pregnant women compared to lean pregnant women prior to CS. The current study used a physiologically based pharmacokinetic (PBPK) approach to predict cefazolin and cefuroxime pharmacokinetics in obese pregnant women at the time of CS as well as the duration that these drug concentrations remain above a target concentration (2, 4 or 8 µg/mL or µg/g) in plasma or adipose tissue. Cefazolin and cefuroxime PBPK models were first built using clinical data in lean and in obese non-pregnant populations. Models were then used to predict cefazolin and cefuroxime pharmacokinetics data in lean and obese pregnant populations. Both cefazolin and cefuroxime models sufficiently described their total and free levels in the plasma and in the adipose interstitial fluid (ISF) in non-pregnant and pregnant populations. The obese pregnant cefazolin model predicted adipose exposure adequately at different reference time points and indicated that an IV dose of 2000 mg can maintain unbound plasma and adipose ISF concentration above 8 µg/mL for 3.5 h post dose. Predictions indicated that an IV 1500 mg cefuroxime dose can achieve unbound plasma and unbound ISF cefuroxime concentration of ≥8 µg/mL up to 2 h post dose in obese pregnant women. Re-dosing should be considered if CS was not completed within 2 h post cefuroxime administration for both lean or obese pregnant if cefuroxime concentrations of ≥8 µg/mL is required. A clinical study to measure cefuroxime adipose concentration in pregnant and obese pregnant women is warranted.

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