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OBJECTIVES: As part of the FERN feasibility study, this qualitative research aimed to explore parents' and clinicians' views on the acceptability, feasibility and design of a randomised controlled trial (RCT) of active intervention versus expectant management in monochorionic (MC) diamniotic twin pregnancies with early-onset (prior to 24 weeks) selective fetal growth restriction (sFGR). Interventions could include laser treatment or selective termination which could lead to the death or serious disability of one or both twins. DESIGN: Qualitative semi-structured interviews with parents and clinicians. Data were analysed using reflexive thematic analysis and considered against the Principles of Biomedical Ethics. PARTICIPANTS AND SETTING: We interviewed 19 UK parents experiencing (six mothers, two partners) or had recently experienced (eight mothers, three partners) early-onset sFGR in MC twin pregnancy and 14 specialist clinicians from the UK and Europe. RESULTS: Participants viewed the proposed RCT as 'ethically murky' because they believed that the management of sFGR in MC twin pregnancy should be individualised according to the type and severity of sFGR. Clinicians prioritised the gestational age, size, decrease in growth velocity, access to the placental vessels and acceptability of intervention for parents. Discussions and decision-making about selective termination appeared to cause long-term harm (maleficence). The most important outcome for parents and clinicians was 'live birth'. For clinicians, this was the live birth of at least one twin. For parents, this meant the live birth of both twins, even if this meant that their babies had neurodevelopmental impairment or disabilities. CONCLUSIONS: All three pregnancy management approaches for sFGR in MC twin pregnancy carry risks and benefits, and the ultimate goal for parents is to receive individualised care to achieve the best possible outcome for both twins. An RCT was not acceptable to parents or clinicians or seen as ethically appropriate. Alternative study designs should be considered to answer this important research question.
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Retardo del Crecimiento Fetal , Embarazo Gemelar , Investigación Cualitativa , Humanos , Femenino , Embarazo , Retardo del Crecimiento Fetal/terapia , Adulto , Ensayos Clínicos Controlados Aleatorios como Asunto/ética , Padres/psicología , Estudios de Factibilidad , Masculino , Proyectos de Investigación , Entrevistas como Asunto , Reino Unido , Espera Vigilante , Edad GestacionalRESUMEN
INTRODUCTION: Selective fetal growth restriction (sFGR) in monochorionic twin pregnancy, defined as an estimated fetal weight (EFW) of one twin <10th centile and EFW discordance ≥25%, is associated with stillbirth and neurodisability for both twins. The condition poses unique management difficulties: on the one hand, continuation of the pregnancy carries a risk of death of the smaller twin, with a high risk of co-twin demise (40%) or co-twin neurological sequelae (30%). On the other, early delivery to prevent the death of the smaller twin may expose the larger twin to prematurity, with the associated risks of long-term physical, emotional and financial costs from neurodisability, such as cerebral palsy.When there is severe and early sFGR, before viability, delivery is not an option. In this scenario, there are currently three main management options: (1) expectant management, (2) selective termination of the smaller twin and (3) placental laser photocoagulation of interconnecting vessels. These management options have never been investigated in a randomised controlled trial (RCT). The best management option is unknown, and there are many challenges for a potential RCT. These include the rarity of the condition resulting in a small number of eligible pregnancies, uncertainty about whether pregnant women will agree to participate in such a trial and whether they will agree to be randomised to expectant management or active fetal intervention, and the challenges of robust and long-term outcome measures. Therefore, the main objective of the FERN study is to assess the feasibility of conducting an RCT of active intervention vs expectant management in monochorionic twin pregnancies with early-onset (prior to 24 weeks) sFGR. METHODS AND ANALYSIS: The FERN study is a prospective mixed-methods feasibility study. The primary objective is to recommend whether an RCT of intervention vs expectant management of sFGR in monochorionic twin pregnancy is feasible by exploring women's preference, clinician's preference, current practice and equipoise and numbers of cases. To achieve this, we propose three distinct work packages (WPs). WP1: A Prospective UK Multicentre Study, WP2A: a Qualitative Study Exploring Parents' and Clinicians' Views and WP3: a Consensus Development to Determine Feasibility of a Trial. Eligible pregnancies will be recruited to WP1 and WP2, which will run concurrently. The results of these two WPs will be used in WP3 to develop consensus on a future definitive study. The duration of the study will be 53 months, composed of 10 months of setup, 39 months of recruitment, 42 months of data collection, and 5 months of data analysis, report writing and recommendations. The pragmatic sample size for WP1 is 100 monochorionic twin pregnancies with sFGR. For WP2, interviews will be conducted until data saturation and sample variance are achieved, that is, when no new major themes are being discovered. Based on previous similar pilot studies, this is anticipated to be approximately 15-25 interviews in both the parent and clinician groups. Engagement of at least 50 UK clinicians is planned for WP3. ETHICS AND DISSEMINATION: This study has received ethical approval from the Health Research Authority (HRA) South West-Cornwall and Plymouth Ethics Committee (REC reference 20/SW/0156, IRAS ID 286337). All participating sites will undergo site-specific approvals for assessment of capacity and capability by the HRA. The results of this study will be published in peer-reviewed journals and presented at national and international conferences. The results from the FERN project will be used to inform future studies. TRIAL REGISTRATION NUMBER: This study is included in the ISRCTN Registry (ISRCTN16879394) and the NIHR Central Portfolio Management System (CPMS), CRN: Reproductive Health and Childbirth Specialty (UKCRN reference 47201).
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Estudios de Factibilidad , Retardo del Crecimiento Fetal , Embarazo Gemelar , Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Femenino , Embarazo , Retardo del Crecimiento Fetal/terapia , Estudios Prospectivos , Gemelos Monocigóticos , Espera Vigilante , Recién NacidoRESUMEN
OBJECTIVE: To identify current practices in the management of selective fetal growth restriction (sFGR) in monochorionic diamniotic (MCDA) twin pregnancies. DESIGN: Cross-sectional survey. SETTING: International. POPULATION: Clinicians involved in the management of MCDA twin pregnancies with sFGR. METHODS: A structured, self-administered survey. MAIN OUTCOME MEASURES: Clinical practices and attitudes to diagnostic criteria and management strategies. RESULTS: Overall, 62.8% (113/180) of clinicians completed the survey; of which, 66.4% (75/113) of the respondents reported that they would use an estimated fetal weight (EFW) of <10th centile for the smaller twin and an inter-twin EFW discordance of >25% for the diagnosis of sFGR. For early-onset type I sFGR, 79.8% (75/94) of respondents expressed that expectant management would be their routine practice. On the other hand, for early-onset type II and type III sFGR, 19.3% (17/88) and 35.7% (30/84) of respondents would manage these pregnancies expectantly, whereas 71.6% (63/88) and 57.1% (48/84) would refer these pregnancies to a fetal intervention centre or would offer fetal intervention for type II and type III cases, respectively. Moreover, 39.0% (16/41) of the respondents would consider fetoscopic laser surgery (FLS) for early-onset type I sFGR, whereas 41.5% (17/41) would offer either FLS or selective feticide, and 12.2% (5/41) would exclusively offer selective feticide. For early-onset type II and type III sFGR cases, 25.9% (21/81) and 31.4% (22/70) would exclusively offer FLS, respectively, whereas 33.3% (27/81) and 32.9% (23/70) would exclusively offer selective feticide. CONCLUSIONS: There is significant variation in clinician practices and attitudes towards the management of early-onset sFGR in MCDA twin pregnancies, especially for type II and type III cases, highlighting the need for high-level evidence to guide management.
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Background: When cardiac implantable electronic device infection occurs, standard therapy is usually total system extraction. Transvenous lead extraction is preferable to open heart surgical extraction, unless contraindicated because of the presence of very large vegetations on the intravenous leads according to the European Society of Cardiology guidelines. Extraction of transvenous leads with vegetations risks distal embolism resulting in obstruction and/or infection in the pulmonary arteries. Catheter aspiration of vegetations or thrombi has been performed prior to transvenous lead extraction using a partial veno-venous extracorporeal bypass circuit. We report the use of a single-access aspiration system using the Inari FlowTriever 24 French system to debulk a defibrillator lead before percutaneous extraction. Case summary: A 79-year-old male presented with fever 18 years after his first implantable cardioverter defibrillator implant and 9 years after his most recent pulse generator change. Two large vegetations were identified on his transvenous defibrillator lead on the atrial aspect, near the tricuspid annulus, which were aspirated using the Inari Medical 24Fr FlowTriever aspiration catheter. We describe anatomical considerations during the approach and a technique to localize the vegetations based on a combination of fluoroscopy and transoesophageal echocardiogram guidance. Discussion: This case demonstrates the safe and effective use of the Inari Medical 24Fr FlowTriever aspiration catheter in debulking a defibrillator lead before transvenous lead extraction. This method uses a single venous puncture and is not dependent on extracorporeal bypass. Apart from reducing complexity, this technique may be advantageous in patients where anticoagulation needs to be minimised.
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OBJECTIVE: Severe early-onset fetal growth restriction (FGR) causes stillbirth, neonatal death and neurodevelopmental impairment. Poor maternal spiral artery remodelling maintains vasoactive responsiveness but is susceptible to treatment with sildenafil, a phosphodiesterase type 5 (PDE5) inhibitor, which may improve perinatal outcomes. DESIGN: Superiority, double-blind randomised controlled trial. SETTING: A total of 20 UK fetal medicine units. POPULATION: Pregnancies affected by FGR, defined as an abdominal circumference below the tenth centile with absent end-diastolic flow in the umbilical artery between 22+0 and 29+6 weeks of gestation. METHODS: Treatment with sildenafil (25 mg three times/day) or placebo until delivery or 32 weeks of gestation. MAIN OUTCOME MEASURES: All infants alive at hospital discharge were assessed for cardiovascular function and cognitive, speech/language and neuromotor impairment at 2 years of age. The primary outcome was survival without cerebral palsy or neurosensory impairment, or a Bayley-III composite score of >85. RESULTS: In total, 135 women were randomised between November 2014 and July 2016 (70 to sildenafil and 65 to placebo). We previously published that there was no improvement in time to delivery or perinatal outcomes with sildenafil. In all, 75 babies (55.5%) were discharged alive, with 61 infants eligible for follow-up (32 sildenafil and 29 placebo). One infant died (placebo), three mothers declined and ten mothers were uncontactable. There was no difference in neurodevelopment or blood pressure following treatment with sildenafil. Infants who received sildenafil had a larger head circumference at 2 years of age (median difference 49.2 cm, IQR 46.4-50.3, vs 47.2 cm, 95% CI 44.7-48.9 cm). CONCLUSIONS: Sildenafil therapy did not prolong pregnancy or improve perinatal outcomes and did not improve infant neurodevelopment in FGR survivors. Therefore, sildenafil should not be prescribed for this condition.
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PURPOSE: To report the first interim analysis of the STRIKE-PE study, evaluating the safety and effectiveness of computer assisted vaccum thrombectomy (CAVT) for the treatment of acute pulmonary embolism (PE). MATERIALS AND METHODS: This prospective, international, multicenter study will enroll 600 adult patients with acute PE of ≤14 days and a right ventricle (RV)-to-left ventricle (LV) ratio of ≥0.9 who receive first-line endovascular treatment with CAVT using the Indigo Aspiration System (Penumbra, Alameda, California). Primary endpoints are change in RV/LV ratio and incidence of composite major adverse events (MAEs) within 48 hours. Secondary endpoints include functional and quality-of-life (QoL) assessments. RESULTS: The first 150 consecutive patients were treated with 12F catheter CAVT. Mean age was 61.3 years, 54.7% were men, 94.7% presented with intermediate-risk PE, and 5.3% presented with high-risk PE. Median thrombectomy and procedure times were 33.5 minutes and 70.0 minutes, respectively, resulting in a mean reduction in systolic pulmonary artery pressure of 16.3% (P < .001). Mean RV/LV ratio decreased from 1.39 to 1.01 at 48 hours, a 25.7% reduction (P < .001). Four (2.7%) patients experienced a composite MAE within 48 hours. At 90-day follow-up, patients exhibited statistically significant improvements in the Borg dyspnea scale score and QoL measures, and the New York Heart Association class distribution returned to that reported before the index PE. CONCLUSIONS: Interim results from the STRIKE-PE study demonstrate a significant reduction in pulmonary artery pressure and RV/LV ratio, a median thrombectomy time of 33.5 minutes, a composite MAE rate of 2.7%, and significant improvements in 90-day functional and QoL outcomes.
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Embolia Pulmonar , Calidad de Vida , Trombectomía , Humanos , Femenino , Masculino , Embolia Pulmonar/fisiopatología , Embolia Pulmonar/terapia , Embolia Pulmonar/cirugía , Persona de Mediana Edad , Trombectomía/efectos adversos , Trombectomía/instrumentación , Resultado del Tratamiento , Estudios Prospectivos , Anciano , Factores de Tiempo , Recuperación de la Función , Adulto , Vacio , Estado Funcional , Factores de RiesgoRESUMEN
BACKGROUND: Over the past decade, major society guidelines have recommended the use of newer P2Y12 inhibitors over clopidogrel for those undergoing percutaneous coronary intervention for acute coronary syndrome. It is unclear what impact these recommendations had on clinical practice. METHODS AND RESULTS: All percutaneous coronary intervention procedures (n=534 210) for acute coronary syndrome in England and Wales (April 1, 2010, to March 31, 2022) were retrospectively analyzed, stratified by choice of preprocedural P2Y12 inhibitor (clopidogrel, ticagrelor, and prasugrel). Multivariable logistic regression models were used to examine odds ratios of receipt of ticagrelor and prasugrel (versus clopidogrel) over time, and predictors of their receipt. Overall, there was a significant increase in receipt of newer P2Y12 inhibitors from 2010 to 2020 (2022 versus 2010: ticagrelor odds ratio, 8.12 [95% CI, 7.67-8.60]; prasugrel odds ratio, 6.14 [95% CI, 5.53-6.81]), more so in ST-segment-elevation myocardial infarction than non-ST-segment-elevation acute coronary syndrome indication. The most significant increase in odds of receipt of prasugrel was observed between 2020 and 2022 (P<0.001), following a decline/plateau in its use in earlier years (2011-2019). In contrast, the odds of receipt of ticagrelor significantly increased in earlier years (2012-2017, Ptrend<0.001), after which the trend was stable (Ptrend=0.093). CONCLUSIONS: Over a 13-year-period, there has been a significant increase in use of newer P2Y12 inhibitors, although uptake of prasugrel use remained significantly lower than ticagrelor. Earlier society guidelines (pre-2017) were associated with the highest rates of ticagrelor use for non-ST-segment-elevation acute coronary syndrome and ST-segment-elevation myocardial infarction cases while the ISAR-REACT 5 (Prospective, Randomized Trial of Ticagrelor Versus Prasugrel in Patients With Acute Coronary Syndrome) trial and later society guidelines were associated with higher prasugrel use, mainly for ST-segment-elevation myocardial infarction indication.
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Síndrome Coronario Agudo , Clopidogrel , Intervención Coronaria Percutánea , Guías de Práctica Clínica como Asunto , Clorhidrato de Prasugrel , Antagonistas del Receptor Purinérgico P2Y , Ticagrelor , Humanos , Síndrome Coronario Agudo/tratamiento farmacológico , Síndrome Coronario Agudo/cirugía , Síndrome Coronario Agudo/terapia , Intervención Coronaria Percutánea/tendencias , Antagonistas del Receptor Purinérgico P2Y/uso terapéutico , Masculino , Femenino , Ticagrelor/uso terapéutico , Clorhidrato de Prasugrel/uso terapéutico , Anciano , Persona de Mediana Edad , Estudios Retrospectivos , Gales , Clopidogrel/uso terapéutico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Pautas de la Práctica en Medicina/tendencias , Inglaterra , Adhesión a Directriz/tendencias , Infarto del Miocardio con Elevación del ST/tratamiento farmacológico , Infarto del Miocardio con Elevación del ST/terapia , Infarto del Miocardio con Elevación del ST/cirugía , Infarto del Miocardio sin Elevación del ST/tratamiento farmacológico , Infarto del Miocardio sin Elevación del ST/cirugía , Infarto del Miocardio sin Elevación del ST/terapia , Factores de Tiempo , Resultado del TratamientoRESUMEN
This systematic review and meta-analysis was conducted to assess the randomized controlled trial (RCT) evidence available for renal denervation (RDN) in uncontrolled arterial hypertension. Twenty-five RCTs met the eligibility criteria for the systematic review, and 16 RCTs were included in the meta-analysis. The results of the random effects meta-analysis estimated a mean difference of -8.5âmmHg [95% confidence interval (CI) -13.5 to -3.6] for office SBP, -3.6âmmHg (95% CI -5.2 to -2.0) for 24âh SBP and -3.9âmmHg (95% CI -5.6 to -2.2) for ambulatory daytime SBP in favour of RDN compared with control (medication and/or sham-only) at primary follow-up. Similarly favourable results were observed across a range of prespecified subgroup analyses, including treatment-resistant hypertension. This meta-analysis suggests that the use of RDN in uncontrolled hypertension leads to consistent reductions in blood pressure. Reductions appear to be statistically consistent in the presence or absence of medications and in populations resistant to the use of three medications.
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Hipertensión , Riñón , Humanos , Hipertensión/cirugía , Hipertensión/fisiopatología , Riñón/inervación , Presión Sanguínea , Desnervación/métodos , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento , Antihipertensivos/uso terapéuticoRESUMEN
BACKGROUND: Catheter-based renal sympathetic denervation (RDN) reduced blood pressure (BP) in multiple randomized sham-controlled trials of patients with uncontrolled hypertension (HTN). We tested proof-of-concept for a more selective treatment strategy, exclusively targeting these areas to improve the efficiency of the procedure. METHODS: The SPYRAL DYSTAL Pilot study was designed to mirror the SPYRAL HTN-OFF MED Pivotal study, enabling comparison with a propensity score adjusted active-control group. Patients were antihypertensive medication-free for one month before undergoing BP assessment. Those with office BP of 150-180/>90 mmHg and with an ambulatory systolic BP of 140-170 mmHg were selected to undergo open label treatment, delivering energy only to the distal main renal arteries and first order branches. Patients from DYSTAL were compared with patients who underwent maximized RF RDN treatment in the prior randomized OFF MED trial at 3 months. After 3 months, patients resumed antihypertensive medications as indicated. Safety and efficacy outcomes were assessed post hoc through 12 months. RESULTS: The SPYRAL DYSTAL Pilot study treated 56 HTN patients. Baseline office systolic BP (OSBP) and 24-h ambulatory systolic BP (ASBP) were similar between DYSTAL and OFF MED patient groups. The number of ablations (32.3 ± 8.0 vs 46.6 ± 15.3, p < 0.001), procedure time (67 ± 21 min vs 99 ± 36 min; p < 0.001), and contrast volume (173 ± 77 cc vs 208 ± 96 cc; p = 0.014) were significantly lower with the simplified treatment strategy. OSBP and ASBP changes compared with baseline were -9.0 and -1.4 mmHg at 3 months, -20.3 and -13.9 mmHg at 6 months, and -20.3 and -16.6 mmHg at 12 months, respectively. During the medication up-titration phase, BP reductions among DYSTAL patients were similar to reductions observed in OFF MED through 12 months, with comparable number of drugs (1.4 and 1.5 medications, respectively (P=NS)). Two adverse events related to guidewire placement were reported. CONCLUSION: In this pilot study, focusing ablation treatment on the distal main and proximal branch renal arteries was performed, resulting in fewer RF lesions, and reduced contrast volume and procedure time. Whether BP reductions are similar between a selective vs. maximized RDN approach requires further prospective study.
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Most genetic association studies focus on binary variants. To identify the effects of multi-allelic variation of tandem repeats (TRs) on human traits, we performed direct TR genotyping and phenome-wide association studies in 168,554 individuals from the UK Biobank, identifying 47 TRs showing causal associations with 73 traits. We replicated 23 of 31 (74%) of these causal associations in the All of Us cohort. While this set included several known repeat expansion disorders, novel associations we found were attributable to common polymorphic variation in TR length rather than rare expansions and include e.g. a coding polyhistidine motif in HRCT1 influencing risk of hypertension and a poly(CGC) in the 5'UTR of GNB2 influencing heart rate. Causal TRs were strongly enriched for associations with local gene expression and DNA methylation. Our study highlights the contribution of multi-allelic TRs to the "missing heritability" of the human genome.
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There has been a scarcity of evidence about iodine nutrition knowledge among women during pregnancy and lactation. The aim of this study was to determine women's iodine knowledge and the relationship between knowledge and iodine status during pregnancy and lactation. Women were recruited from a hospital in the western part of China in the third trimester of pregnancy and followed until the end of the first week of lactation. The women's iodine status was measured by their urinary iodine concentration (UIC) and an iodine-specific, validated food frequency questionnaire (FFQ). Iodine nutrition knowledge was assessed using an iodine nutrition knowledge questionnaire. A total of 200 women (mean age of 29.0 ± 4.2 years) completed the whole study. The majority of the women did not consume enough iodine during both pregnancy and lactation (231.89 vs. 237.26 µg/day). The overall mean iodine knowledge scores in our sample of women during pregnancy and lactation were 4.77 and 4.87, indicating low iodine knowledge. The use of iodized salt and a higher education level were significantly associated with an increased iodine knowledge score. In conclusion, this study reported poor iodine nutrition knowledge in women, highlighting a public health concern. Therefore, the iodine knowledge of women should be improved, possibly via maternal health campaigns to avoid the consequences of iodine deficiency disorders in newborns.
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Yodo , Desnutrición , Embarazo , Humanos , Femenino , Recién Nacido , Adulto Joven , Adulto , Lactancia Materna , Estado Nutricional , Lactancia , Cloruro de Sodio Dietético , ChinaRESUMEN
Valvular heart disease presents a significant health burden, yet advancements in valve biology and therapeutics have been hindered by the lack of accessibility to human valve cells. In this study, we have developed a scalable and feeder-free method to differentiate human induced pluripotent stem cells (iPSCs) into endocardial cells, which are transcriptionally and phenotypically distinct from vascular endothelial cells. These endocardial cells can be challenged to undergo endothelial-to-mesenchymal transition (EndMT), after which two distinct populations emerge-one population undergoes EndMT to become valvular interstitial cells (VICs), while the other population reinforces their endothelial identity to become valvular endothelial cells (VECs). We then characterized these populations through bulk RNA-seq transcriptome analyses and compared our VIC and VEC populations to pseudobulk data generated from normal valve tissue of a 15-week-old human fetus. By increasing the accessibility to these cell populations, we aim to accelerate discoveries for cardiac valve biology and disease.
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AIMS: Catheter-based radiofrequency renal denervation (RF RDN) has recently been approved for clinical use in the European Society of Hypertension guidelines and by the US FDA. This study evaluated the lifetime cost-effectiveness of RF RDN using contemporary evidence. METHODS AND RESULTS: A decision-analytic model based on multivariate risk equations projected clinical events, quality-adjusted life years (QALYs) and costs. The model consisted of seven health states: hypertension alone, myocardial infarction (MI), other symptomatic coronary artery disease, stroke, heart failure (HF), end-stage renal disease, and death. Risk reduction associated with changes in office systolic blood pressure (oSBP) was estimated based on a published meta-regression of hypertension trials. The base case effect size of -4.9 mmHg oSBP (observed vs. sham control) was taken from the SPYRAL HTN-ON MED trial of 337 patients. Costs were based on NHS England data. The incremental cost-effectiveness ratio (ICER) was evaluated against the NICE cost-effectiveness threshold of £20 000-30 000 per QALY gained. Extensive scenario and sensitivity analyses were conducted, including the ON-MED subgroup on three medications and pooled effect sizes. RF RDN resulted in a relative risk reduction in clinical events over 10 years (0.80 for stroke, 0.88 for MI, 0.72 for HF), with an increase in health benefit over a patient's lifetime, adding 0.35 QALYs at a cost of £4 763, giving an ICER of £13 482 per QALY gained. Findings were robust across tested scenarios. CONCLUSION: Catheter-based radiofrequency RDN can be a cost-effective strategy for uncontrolled hypertension in the UK, with an ICER substantially below the NICE cost-effectiveness threshold. Funding: Medtronic Inc.
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BACKGROUND: Prior clinical trials have demonstrated the efficacy of ultrasound-facilitated catheter-directed thrombolysis (USCDT) for the treatment of acute intermediate-risk pulmonary embolism (PE) using reduced thrombolytic doses and shorter infusion durations. However, utilization and safety of such strategies in broader PE populations remain unclear. The KNOCOUT PE (The EKoSoNic Registry of the Treatment and Clinical Outcomes of Patients With Pulmonary Embolism) registry is a multicenter international registry designed to study the treatment of acute PE with USCDT, with focus on safety outcomes. METHODS: The KNOCOUT PE prospective cohort included 489 patients (64 sites internationally) with acute intermediate-high or high-risk PE treated with USCDT between March 2018 and June 2020. Principal safety outcomes were independently adjudicated International Society on Thrombosis and Haemostasis major bleeding at 72 hours post-treatment and mortality within 12 months of treatment. Additional outcomes included change in right ventricular/left ventricular ratio and quality of life measures over 12 months. RESULTS: Mean alteplase (r-tPA [recombinant tissue-type plasminogen activator]) infusion duration was 10.5 hours. Mean total r-tPA dose was 18.1 mg, with 31.0% of patients receiving ≤12 mg. Major bleeding events within 72 hours occurred in 1.6% (8/489) of patients. One patient experienced worsening of a preexisting subdural hematoma after USCDT and therapeutic anticoagulation, which ultimately required surgery. All-cause mortality at 30 days was 1.0% (5/489). Improvement in PE quality of life score was observed with a 41.1% (243/489, 49.7%) and 44.2% (153/489, 31.3%) mean relative reduction by 3 and 12 months, respectively. CONCLUSIONS: In a prospective observational cohort study of patients with intermediate-high and high-risk PE undergoing USCDT, mean r-tPA dose was 18 mg, and the rates of major bleeding and mortality were low. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03426124.
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Embolia Pulmonar , Calidad de Vida , Humanos , Catéteres , Fibrinolíticos , Hemorragia/inducido químicamente , Estudios Prospectivos , Embolia Pulmonar/diagnóstico por imagen , Embolia Pulmonar/tratamiento farmacológico , Sistema de Registros , Factores de Riesgo , Terapia Trombolítica/efectos adversos , Resultado del TratamientoRESUMEN
BACKGROUND: The randomized, sham-controlled RADIANCE-HTN (A Study of the Recor Medical Paradise System in Clinical Hypertension) SOLO, RADIANCE-HTN TRIO, and RADIANCE II (A Study of the Recor Medical Paradise System in Stage II Hypertension) trials independently met their primary end point of a greater reduction in daytime ambulatory systolic blood pressure (SBP) 2 months after ultrasound renal denervation (uRDN) in patients with hypertension. To characterize the longer-term effectiveness and safety of uRDN versus sham at 6 months, after the blinded addition of antihypertensive treatments (AHTs), we pooled individual patient data across these 3 similarly designed trials. METHODS: Patients with mild to moderate hypertension who were not on AHT or with hypertension resistant to a standardized combination triple AHT were randomized to uRDN (n=293) versus sham (n=213); they were to remain off of added AHT throughout 2 months of follow-up unless specified blood pressure (BP) criteria were exceeded. In each trial, if monthly home BP was ≥135/85 mm Hg from 2 to 5 months, standardized AHT was sequentially added to target home BP <135/85 mm Hg under blinding to initial treatment assignment. Six-month outcomes included baseline- and AHT-adjusted change in daytime ambulatory, home, and office SBP; change in AHT; and safety. Linear mixed regression models using all BP measurements and change in AHT from baseline through 6 months were used. RESULTS: Patients (70% men) were 54.1±9.3 years of age with a baseline daytime ambulatory/home/office SBP of 150.5±9.8/151.0±12.4/155.5±14.4 mm Hg, respectively. From 2 to 6 months, BP decreased in both groups with AHT titration, but fewer uRDN patients were prescribed AHT (P=0.004), and fewer additional AHT were prescribed to uRDN patients versus sham patients (P=0.001). Whereas the unadjusted between-group difference in daytime ambulatory SBP was similar at 6 months, the baseline and medication-adjusted between-group difference at 6 months was -3.0 mm Hg (95% CI, -5.7, -0.2; P=0.033), in favor of uRDN+AHT. For home and office SBP, the adjusted between-group differences in favor of uRDN+AHT over 6 months were -5.4 mm Hg (-6.8, -4.0; P<0.001) and -5.2 mm Hg (-7.1, -3.3; P<0.001), respectively. There was no heterogeneity between trials. Safety outcomes were few and did not differ between groups. CONCLUSIONS: This individual patient-data analysis of 506 patients included in the RADIANCE trials demonstrates the maintenance of BP-lowering efficacy of uRDN versus sham at 6 months, with fewer added AHTs. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT02649426 and NCT03614260.
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Hipertensión , Arteria Renal , Femenino , Humanos , Masculino , Antihipertensivos/uso terapéutico , Presión Sanguínea , Monitoreo Ambulatorio de la Presión Arterial , Desnervación/efectos adversos , Desnervación/métodos , Hipertensión/diagnóstico , Hipertensión/tratamiento farmacológico , Riñón , Arteria Renal/diagnóstico por imagen , Simpatectomía/métodos , Resultado del Tratamiento , Persona de Mediana EdadRESUMEN
Breast milk iodine concentration (BMIC) is a promising indicator of iodine status in lactating women. However, there are limited data on its usefulness to reflect maternal iodine deficiency. Therefore, the aim of our study was to assess iodine concentration in breast milk and urine samples in exclusively breast-feeding women. Eligible pregnant women undergoing routine antenatal care in a large hospital in Shaanxi Province, China, were followed up from the third trimester of pregnancy until the first week of lactation. Urine samples (20 ml) were collected during pregnancy and lactation. Iodine concentration in samples was measured based on Sandell-Kolthoff reaction. Breast milk samples (5 ml) were provided during lactation. A receiver operating curve (ROC) was constructed to determine the diagnostic performance of BMIC. An iodine-specific FFQ was completed twice during pregnancy and lactation. A total of 200 women completed the study. The overall median BMIC was 89 µg/l, indicating iodine sufficiency (i.e. BMIC reference range between 60 and 465 µg/l). Women reported similar median urinary iodine concentration (UIC) during pregnancy and lactation (112 and 113 µg/l, respectively), but their iodine status differed - mild-to-moderate iodine deficiency during pregnancy and iodine sufficiency during lactation. The ROC for BMIC using UIC as a reference standard was 0·755 (95 % CI: 0·644, 0·866). In conclusion, this study demonstrated that women were iodine sufficient in the first week of lactation as assessed by UIC, which was consistent with BMIC. These findings suggested that BMIC is a useful biomarker to assess iodine status in lactating women.