RESUMO
AIMS: Gestational diabetes (GDM) is associated with the development of postpartum (PP) glucose intolerance. Plasma glycated CD59 (pGCD59) is an emerging biomarker for the detection of hyperglycaemia. The aim of this study was to assess the ability of PP pGCD59 to predict the development of PP GI as defined by the 2 h 75 g OGTT using the ADA criteria, in a cohort of women diagnosed with prior GDM in the index pregnancy using the 2 h 75 g OGTT at 24-28 weeks of gestation according to the World Health Organization (WHO) 2013 criteria. METHODS: Of the 2017 pregnant women recruited prospectively 140 women with gestational diabetes had samples for pGCD59 taken PP at the time of the OGTT. The ability of pGCD59 to predict the results of the PP OGTT was assessed using nonparametric receiver operating characteristic (ROC) curves. RESULTS: Women with PP glucose intolerance had significantly higher PP pGCD59 levels compared to women with normal glucose tolerance PP (3.8 vs. 2.7 SPU). PP pGCD59 identified women who developed glucose intolerance PP with an AUC of 0.80 (95% CI: 0.70-0.91). A PP pGCD59 cut-off value of 1.9 SPU generated a sensitivity of 100% (95% CI: 83.9-100), specificity of 16.9% (95% CI: 9.8-26.3), positive predictive value of 22.1% (95% CI: 21.0-22.6), and negative predictive value of 100% (95% CI: 87.4-100). PP fasting plasma glucose generated an AUC of 0.96 (95% CI: 0.89-0.99) for the identification of PP glucose intolerance. CONCLUSION: Our study found that PP pGCD9 may be a promising biomarker to identify women not requiring PP glucose intolerance screening using the traditional OGTT. While the diagnostic accuracy of pGCD59 is good, fasting plasma glucose remains a better test for the identification of PP glucose intolerance.
Assuntos
Diabetes Gestacional , Intolerância à Glucose , Feminino , Gravidez , Humanos , Diabetes Gestacional/diagnóstico , Intolerância à Glucose/diagnóstico , Intolerância à Glucose/epidemiologia , Estudos Prospectivos , Glicemia , Teste de Tolerância a Glucose , Estudos Retrospectivos , Período Pós-Parto , Biomarcadores , Antígenos CD59RESUMO
AIM: Many challenges exist in determining true rates of adherence to antihypertensive medications among individuals in a clinic setting. For the first time, we aimed to compare patient-reported antihypertensive adherence with objective evidence using mass spectrometry spot urinalysis in a tertiary referral clinic setting. METHODS: A prospective observational single-centre cohort study was performed in a tertiary referral hypertension clinic, encompassing antihypertensive initiation and persistence. Patients were referred with apparent treatment-resistant hypertension or for suspected secondary causes. Participants completed a self-reported assessment of antihypertensive adherence and provided a spot urine sample. The presence of antihypertensive medications and/or their respective metabolites was evaluated using high-performance liquid chromatography tandem mass spectrometry. Patients were determined to be adherent if they demonstrated both self-reported adherence and objective mass spectrometry evidence. RESULTS: Of all 105 eligible participants initially recruited, 73 (69.5%) met the eligibility criteria. Only 27.4% (95% confidence interval 0.2-0.4) of participants demonstrated true adherence to their self-reported antihypertensives, despite 75.3% (0.6-0.8) reporting adherence. Greatest medication adherence was achieved with angiotensin II receptor blockers (61%), with calcium-channel blockers and mineralocorticoid antagonists demonstrating least adherence (38%). CONCLUSION: In patients attending a tertiary hypertension clinic, the combined use of spot urine mass spectrometry and self-reporting identifies higher rates of nonadherence when compared to either modality alone. Both techniques should be combined for more accurate detection of medication adherence.
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Anti-Hipertensivos , Hipertensão , Humanos , Anti-Hipertensivos/uso terapêutico , Estudos Prospectivos , Estudos de Coortes , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Adesão à Medicação , Espectrometria de Massas , Encaminhamento e Consulta , Medidas de Resultados Relatados pelo PacienteRESUMO
AIMS: The purpose of this study was to assess the clinical performance and user acceptance of capillary blood samples prepared remotely using the MiniCollect® capillary blood collection device as an alternative to blood collection by venepuncture for glycated haemoglobin (HbA1c ) analysis. METHODS: Following written informed consent, a cross-sectional study was conducted in individuals aged ≥18 years with any type of diabetes who routinely self-monitor their blood glucose. Eligible participants recruited whilst attending their routine clinical appointments were required to provide a venous blood sample, prepare a capillary blood sample at home (remotely) and complete a bespoke questionnaire. HbA1c in whole blood collected in ethylenediaminetetraacetic acid was determined by capillary electrophoresis on the Sebia Capillary's 3 Tera analyser following standard operating procedure. RESULTS: HbA1c results from both venous and capillary collection demonstrated good agreement. Passing-Bablok regression: y = 0 + 1x (p = 0.18), Spearman correlation r = 0.986, p < 0.0001. The Bland-Altman difference plot provided a mean difference of 0.3 mmol/mol (2.2%). Over half of the participants found the MiniCollect device easy to use. The majority of participants were in favour of the remote capillary blood collection service and would use it if routinely available. CONCLUSION: The home collection of capillary blood for HbA1c determination is a valuable and convenient alternative to standard venous blood collection as it provides an opportunity to support routine HbA1c monitoring, whilst mitigating the transmission of SARS-CoV-2. This service would additionally allow individuals to attend clinic visits with a HbA1c value, ensuring optimal continuance of patient care for individuals with diabetes.
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COVID-19 , Diabetes Mellitus , Adolescente , Adulto , COVID-19/epidemiologia , Estudos Transversais , Hemoglobinas Glicadas/análise , Humanos , Pandemias , SARS-CoV-2RESUMO
BACKGROUND: Hypernatraemia arises commonly in acute general medical admissions. Affected patients have a guarded prognosis with high rates of morbidity and mortality. Age-related physiology and physical/cognitive barriers to accessing water predispose older patients to developing hypernatraemia. This study sought to perform a descriptive retrospective review of hypernatraemic patients admitted under acute general medicine teams. METHODS: A retrospective cross-sectional study of a sample of acute medical in-patients with serum[sodium]>145 mmol/L was conducted. Patients were exclusively older(>69 years) and admitted from Nursing homes (NH)(41%) and non-NH pathways(59%). A comparison of management of NH /non-NH patients including clinical presentation, comorbidities, laboratory values, [sodium] monitoring, intravenous fluid regimes and patient outcomes was performed. RESULTS: In total, 102 consecutive patients (males, n=69(67.6%)) were included. Dementia and reduced mobility were more common in NH residents and admission serum [Sodium] higher (148 vs 142 mmol/L/p=0.003). Monitoring was inadequate: no routine bloods within the first 12h in >80% of patients in both groups. No patient had calculated free water deficit documented. More NH patients received correct fluid management (60% vs 33%/p%0.015). Incorrect fluid regimes occurred in both groups (38% vs 58%/p=0.070). Length of stay in discharged patients was lower in NH, (8(4-20) vs 20.5(9.8-49.3 days)/p=0.003). Time to death for NH residents was shorter (9(5.5-11.5) vs 16 (10.25-23.5) days/p=0.011). CONCLUSION: This study highlights suboptimal management of hypernatraemia. Implementation of hypernatraemia guidelines for general medical older inpatients are clearly required with mechanisms to confirm adherence. Health care workers require further education on diagnostic challenges of dehydration in older people and the importance of maintaining adequate hydration.
Assuntos
Hipernatremia , Idoso , Estudos Transversais , Hidratação , Hospitalização , Humanos , Hipernatremia/diagnóstico , Hipernatremia/epidemiologia , Hipernatremia/terapia , Masculino , Estudos RetrospectivosRESUMO
AIMS/HYPOTHESIS: The aim of this systematic review was to develop core outcome sets (COSs) for trials evaluating interventions for the prevention or treatment of gestational diabetes mellitus (GDM). METHODS: We identified previously reported outcomes through a systematic review of the literature. These outcomes were presented to key stakeholders (including patient representatives, researchers and clinicians) for prioritisation using a three-round, e-Delphi study. A priori consensus criteria informed which outcomes were brought forward for discussion at a face-to-face consensus meeting where the COS was finalised. RESULTS: Our review identified 74 GDM prevention and 116 GDM treatment outcomes, which were presented to stakeholders in round 1 of the e-Delphi study. Round 1 was completed by 173 stakeholders, 70% (121/173) of whom went on to complete round 2; 84% (102/121) of round 2 responders completed round 3. Twenty-two GDM prevention outcomes and 30 GDM treatment outcomes were discussed at the consensus meeting. Owing to significant overlap between included prevention and treatment outcomes, consensus meeting stakeholders agreed to develop a single prevention/treatment COS. Fourteen outcomes were included in the final COS. These consisted of six maternal outcomes (GDM diagnosis, adherence to the intervention, hypertensive disorders of pregnancy, requirement and type of pharmacological therapy for hyperglycaemia, gestational weight gain and mode of birth) and eight neonatal outcomes (birthweight, large for gestational age, small for gestational age, gestational age at birth, preterm birth, neonatal hypoglycaemia, neonatal death and stillbirth). CONCLUSIONS/INTERPRETATION: This COS will enable future GDM prevention and treatment trials to measure similar outcomes that matter to stakeholders and facilitate comparison and combination of these studies. TRIAL REGISTRATION: This study was registered prospectively with the Core Outcome Measures in Effectiveness Trials (COMET) database: http://www.comet-initiative.org/studies/details/686/.
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Diabetes Gestacional/epidemiologia , Peso ao Nascer/fisiologia , Feminino , Humanos , Recém-Nascido , Gravidez , Nascimento Prematuro/epidemiologia , Resultado do TratamentoRESUMO
After in vivo transplantation, mesenchymal stem cells (MSC) face an ischemic microenvironment, characterized by nutrient deprivation and reduced oxygen tension, which reduces their viability and thus their therapeutic potential. Therefore, MSC response to models of in vitro ischemia is of relevance for improving their survival and therapeutic efficacy. The aim of this study was to understand the survival/adaptive response mechanism that MSC use to respond to extreme culture conditions. Specifically, the effect of a long-term starvation on human bone marrow (hBM)-derived MSC cultured in a chemically defined medium (fetal bovine serum-free [SF] and human SF), either in hypoxic or normoxic conditions. We observed that hBM-MSC that were isolated and cultured in SF medium and subjected to a complete starvation for up to 75 days transiently changed their behavior and phenotype. However, at the end of that period, hBM-MSC retained their characteristics as determined by their morphology, DNA damage resistance, proliferation kinetic, and differentiation potential. This survival mode involved a quiescent state, confirmed by increased expression of cell cycle regulators p16, p27, and p57 and decreased expression of proliferating cell nuclear antigen (PCNA), Ki-67, mTOR, and Nanog. In addition, Jak/STAT (STAT6) antiapoptotic activity selected which cells conserved stemness and that supported metabolic, bioenergetic, and scavenging requirements. We also demonstrated that hBM-MSC exploited an autophagic process which induced lipid ß-oxidation as an alternative energy source. Priming MSC by concomitant starvation and culture in hypoxic conditions to induce their quiescence would be of benefit to increase MSC survival when transplanted in vivo. Stem Cells 2019;37:813-827.
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Células da Medula Óssea/efeitos dos fármacos , Hipóxia Celular/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Glucose/deficiência , Células-Tronco Mesenquimais/efeitos dos fármacos , Oxigênio/farmacologia , Células da Medula Óssea/citologia , Células da Medula Óssea/metabolismo , Ciclo Celular/efeitos dos fármacos , Ciclo Celular/genética , Diferenciação Celular/efeitos dos fármacos , Hipóxia Celular/genética , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/genética , Meios de Cultura/farmacologia , Inibidor p16 de Quinase Dependente de Ciclina/genética , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Inibidor de Quinase Dependente de Ciclina p27/genética , Inibidor de Quinase Dependente de Ciclina p27/metabolismo , Inibidor de Quinase Dependente de Ciclina p57/genética , Inibidor de Quinase Dependente de Ciclina p57/metabolismo , Humanos , Antígeno Ki-67/genética , Antígeno Ki-67/metabolismo , Metabolismo dos Lipídeos/genética , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Proteína Homeobox Nanog/genética , Proteína Homeobox Nanog/metabolismo , Cultura Primária de Células , Antígeno Nuclear de Célula em Proliferação/genética , Antígeno Nuclear de Célula em Proliferação/metabolismo , Fator de Transcrição STAT6/genética , Fator de Transcrição STAT6/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismoRESUMO
Extreme weather events including recently experienced prolonged heatwaves are predicted to increase in frequency and intensity as a result of climate change. Vulnerable groups, and particularly older persons, are at increased risk of heat-related illness and mortality. Multimodal interventions that incorporate community, primary and secondary care programmes are required. Social programmes such as early warning systems, regional heat plans and community-led initiatives that specifically target the isolated, dependent older person are protective. Establishing clear and effective communication on health promotion and preventative measures is the key. Energy-efficient building design and eco-city planning are vital to reduce the impact of heatwaves at both a population and individual level. Anticipatory strategies should be adopted to ensure ample access to fluids, target barriers to increase oral intake and allow early identification of intercurrent illness, along with regular medication reviews. Prompt management of risk factors for the development of heat-related illness and treatment of complications such as heat stroke and cardiovascular events are keys to reducing the negative health impact of extreme heat in at-risk populations. Morbidity and mortality in heatwaves should be preventable. Evidence-based interventions are available to mitigate and prevent the negative health impact of extreme heat and should be implemented in all residential settings.
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Temperatura Alta , Idoso , Idoso de 80 Anos ou mais , Humanos , Morbidade , Medição de Risco , Fatores de RiscoRESUMO
AIMS/HYPOTHESIS: Gestational diabetes mellitus (GDM) is linked with a higher lifetime risk for the development of impaired fasting glucose, impaired glucose tolerance, type 2 diabetes, the metabolic syndrome, cardiovascular disease, postpartum depression and tumours. Despite this, there is no consistency in the long-term follow-up of women with a previous diagnosis of GDM. Further, the outcomes selected and reported in the research involving this population are heterogeneous and lack standardisation. This amplifies the risk of reporting bias and diminishes the likelihood of significant comparisons between studies. The aim of this study is to develop a core outcome set (COS) for RCTs and other studies evaluating the long-term follow-up at 1 year and beyond of women with previous GDM treated with insulin and/oral glucose-lowering agents. METHODS: The study consisted of three work packages: (1) a systematic review of the outcomes reported in previous RCTs of the follow-up at 1 year and beyond of women with GDM treated with insulin and/or oral glucose-lowering agents; (2) a three-round online Delphi survey with key stakeholders to prioritise these outcomes; and (3) a consensus meeting where the final COS was decided. RESULTS: Of 3344 abstracts identified and evaluated, 62 papers were retrieved and 25/62 papers were included in this review. A total of 121 outcomes were identified and included in the Delphi survey. Delphi round 1 was emailed to 835 participants and 288 (34.5%) responded. In round 2, 190 of 288 (65.9%) participants responded and in round 3, 165 of 190 (86.8%) participants responded. In total, nine outcomes were selected and agreed for inclusion in the final COS: assessment of glycaemic status; diagnosis of type 2 diabetes since the index pregnancy; number of pregnancies since the index pregnancy; number of pregnancies with a diagnosis of GDM since the index pregnancy; diagnosis of prediabetes since the index pregnancy; BMI; post-pregnancy weight retention; resting blood pressure; and breastfeeding. CONCLUSIONS/INTERPRETATION: This study identified a COS that will help bring consistency and uniformity to outcome selection and reporting in clinical trials and other studies involving the follow-up at 1 year and beyond of women diagnosed with GDM treated with insulin and/or oral glucose-lowering agents during pregnancy.
Assuntos
Glicemia/análise , Diabetes Gestacional/terapia , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Algoritmos , Índice de Massa Corporal , Atenção à Saúde , Técnica Delphi , Feminino , Seguimentos , Intolerância à Glucose , Humanos , Insulina/sangue , Obstetrícia/organização & administração , Gravidez , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do TratamentoRESUMO
OBJECTIVE: To describe clinical practice experience of 11 C-Metomidate PET/CT as an adjunct to adrenal vein sampling (AVS) in the lateralization of aldosterone-producing adenomas (APA) in primary aldosteronism (PA). CONTEXT: Accurate lateralization of APA in the setting of PA offers the potential for surgical cure and improved long-term cardiovascular outcomes. Challenges associated with AVS, the current gold standard lateralization modality, mean that only a small proportion of potentially eligible patients currently make it through to surgery. This has prompted consideration of alternative strategies for lateralization, including the application of novel molecular PET tracers such as 11 C-Metomidate. DESIGN: Clinical Service Evaluation/Retrospective audit. PATIENTS: Fifteen individuals with a confirmed diagnosis of PA, undergoing lateralization with 11 C-Metomidate PET/CT prior to final clinical decision on surgical vs medical management. MEASUREMENTS: All patients underwent screening aldosterone renin ratio (ARR), followed by confirmatory testing with the seated saline infusion test, according to Endocrine Society Clinical Practice Guidelines. Adrenal glands were imaged using dedicated adrenal CT. 11 C-Metomidate PET/CT was undertaken due to equivocal or failed AVS. Management outcomes were assessed by longitudinal measurement of blood pressure, ARR, number of hypertensive medications following adrenalectomy or institution of medical therapy. RESULTS: We describe the individual lateralization and clinical outcomes for 15 patients with PA. CONCLUSION: 11 C-Metomidate PET/CT in conjunction with adrenal CT and AVS provided useful information which aided clinical decision-making for PA within a multidisciplinary hypertension clinic.
Assuntos
Tomada de Decisão Clínica , Etomidato/análogos & derivados , Hiperaldosteronismo/diagnóstico , Hiperaldosteronismo/terapia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Compostos Radiofarmacêuticos , Adulto , Humanos , Hiperaldosteronismo/tratamento farmacológico , Hiperaldosteronismo/cirurgiaRESUMO
The aldosterone to renin ratio (ARR) is recommended for case detection of primary aldosteronism (PA). Several factors including medications can undermine its diagnostic accuracy. The objective was to explore the effect of Sodium Glucose Co-Transporter-2 Inhibition on the ARR in patients with type 2 diabetes mellitus (T2DM) who were prescribed a Sodium Glucose Co-Transporter-2 Inhibitor (SGLT-2i) as part of routine clinical care. The primary outcomes were intra-individual changes in aldosterone, renin and ARR. Participants were recruited at routine diabetes outpatient visits as part of a prospective longitudinal study. Eligible participants were prescribed standard doses of empagliflozin and sampled at baseline (pre-SGLT-2i) and at their next routine outpatient visit (post-SGLT-2i). After a mean of 198 (±87) days on SGLT-2i treatment (n=20), there was a significant reduction in HbA1c, BMI, eGFR and serum triglycerides and a significant increase in serum creatinine and sodium. Compared with baseline, there was a significant increase in median direct renin concentration (mIU/l) [40.3 (6.2-249.5) vs. 70.2 (7.0, 551.0) (p=0.005)] and no significant change in median plasma aldosterone concentration (pmol/l) [296 (101, 685) vs. 273 (101, 794) (p=0.541)] with a significant reduction in median ARR (pmol/mIU) [6.9 (0.6-70.7) vs. 5.3 (0.2-39.3) (p=0.007)]. The proportion of participants with a screen positive ARR decreased from 20% (pre-SGLT-2i) to 5% (post-SGLT-2i) (p=0.248). Although performed in a relatively small cohort of medically complex patients, the study indicates that SGLT-2i therapy has the potential to cause false-negative screening for PA in the setting of T2DM. Future confirmatory studies should include patients with confirmed PA.
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Aldosterona/sangue , Compostos Benzidrílicos/farmacologia , Diabetes Mellitus Tipo 2/sangue , Glucosídeos/farmacologia , Renina/sangue , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Idoso , Compostos Benzidrílicos/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Glucosídeos/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Triglicerídeos/sangueRESUMO
BACKGROUND: Growth differentiation factor-15 (GDF-15), a stress responsive cytokine, is a promising biomarker of renal functional decline in diabetic kidney disease (DKD). This study aimed primarily to establish normative data and secondarily to evaluate the potential utility of GDF-15 in DKD using Roche Diagnostics electrochemiluminescence immunoassay (ECLIA) in an Irish Caucasian population. METHODS: Following informed consent, 188 healthy volunteers and 128 participants with diabetes (72 with and 56 without DKD) were recruited to a cross-sectional study. Baseline demographics, anthropometric measurements and laboratory measurements were recorded. Blood for GDF-15 measurement was collected into plain specimen tubes kept at room temperature and processed (centrifugation, separation of serum, freezing at -80 °C) within 1 h of phlebotomy pending batch analyses. Reference intervals were determined using the 2.5th and 97.5th percentiles for serum GDF-15 concentration. RESULTS: Of 188 healthy participants, 63 failed to meet study inclusion criteria. The reference interval for serum GDF-15 was 399 ng/L (90% confidence interval [CI]: 399-399) - 1335 ng/L (90% CI: 1152-1445). Receiver operator characteristics (ROC) curve analysis for DKD determined the area under the ROC curve to be 0.931 (95% CI: 0.893-0.959; p<0.001). The optimum GDF-15 cutoff for predicting DKD was >1136 ng/L providing a diagnostic sensitivity and specificity of 94.4% and 79%, respectively, and positive likelihood ratio of 4.5:1 (95% CI: 3.4-6.0). CONCLUSIONS: The reference interval for serum GDF-15 in a healthy Irish Caucasian population using Roche Diagnostics ECLIA was established and a preliminary determination of the potential of GDF-15 as a screening test for DKD was made. Further prospective validation with a larger DKD cohort will be required before the cutoff presented here is recommended for clinical use.
Assuntos
Diabetes Mellitus/sangue , Nefropatias Diabéticas/sangue , Fator 15 de Diferenciação de Crescimento/sangue , Adolescente , Adulto , Estudos de Coortes , Estudos Transversais/normas , Diabetes Mellitus/diagnóstico , Nefropatias Diabéticas/diagnóstico , Feminino , Fator 15 de Diferenciação de Crescimento/normas , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Valores de Referência , População Branca , Adulto JovemRESUMO
Objective: To investigate the feasibility and efficacy of localized, subtotal, cortical-sparing microwave thermal ablation (MTA) as a potential curative management for primary aldosteronism. The study investigated with equal importance the selected ablation of small volumes of adrenal cortex while sparing adjacent cortex. Method: An in-vivo study was carried out in swine (n = 8) where MTA was applied under direct visualization, to the adrenal glands at 45 W or 70 W for 60 s, using a lateral, side-firing probe and a non-penetrative approach. Animals were survived for 48 h post-procedurally. Animals were investigated for markers of histological, immunohistochemical and biochemical evidence of adrenal function and adrenal damage by assessing samples drawn intra-operatively and at the time of euthanasia. Results: Selected MTA (70 W for 60 s) successfully ablated small adrenocortical volumes (â¼0.8 cm3) characterized by coagulative necrosis and abnormal expression of functional markers (CYP11B1 and CYP17). Non-ablated, adjacent cortex was not affected and preserved normal expression of functional markers, without increased expression of markers of heat damage (HSP-70 and HMGB-1). Limited adrenal medullary damage was demonstrated histologically, clinically and biochemically. Conclusion: MTA offers potential as an efficient methodology for delivering targeted subtotal cortical-sparing adrenal ablation. Image-guided targeted MTA may also represent a safe future modality for curative management of PA, in the setting of both unilateral and bilateral disease.
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Técnicas de Ablação , Hiperaldosteronismo/terapia , Hipertermia Induzida , Micro-Ondas/uso terapêutico , Córtex Suprarrenal/cirurgia , Hormônio Adrenocorticotrópico/sangue , Aldosterona/sangue , Animais , Hidrocortisona/sangue , Hiperaldosteronismo/sangue , Masculino , Metanefrina/sangue , Normetanefrina/sangue , SuínosRESUMO
The complexity of evaluating patients for secondary treatable causes of hypertension is underappreciated. Primary aldosteronism (PA) is the most prevalent cause of secondary hypertension (3%-32% of hypertensive patients). The recent endocrine society clinical practice guideline (ESCPG), "The Management of Primary Aldosteronism: Case Detection, Diagnosis, and Treatment", differs from the previous version in the explicit recognition of PA as a major public health issue. Despite this, PA is underdiagnosed. The guidelines call on physicians to substantially ramp up the screening of hypertensive patients at risk of PA. Further, it recommends the plasma aldosterone to renin ratio (ARR), as the test of choice for screening for PA. However, the ARR is a highly variable test with reported diagnostic sensitivities and specificities ranging from 66% to 100% and 61% to 100%, respectively. Variability of the ARR can be attributed to the high degree of within-subject variation, differences in sampling protocols, laboratory assays, reporting units, the effect of medications and the population characteristics used to establish the decision thresholds. These factors render the possibility of false positive and false negative results-which have the potential to adversely impact patients. The limitations and caveats to the use of the ARR necessitate an effective clinic-laboratory interface, with specialist physician and clinical scientist collaboration for ARR result interpretation. Improvement in the diagnostic sensitivity and specificity of the ARR is predicated on harmonisation of pretesting patient preparation criteria, knowledge of the analytical methods used to derive the ratio and the method-specific threshold for PA.
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Aldosterona/sangue , Hiperaldosteronismo/diagnóstico , Hipertensão/prevenção & controle , Renina/sangue , Biomarcadores/sangue , Humanos , Hiperaldosteronismo/sangue , Hiperaldosteronismo/complicações , Hipertensão/etiologia , Guias de Prática Clínica como Assunto , Sensibilidade e EspecificidadeRESUMO
OBJECTIVES: To evaluate the effects of ß-adrenoreceptor antagonists (ß-blockers) on the aldosterone-renin ratio (ARR) in the context of antihypertensive polypharmacy in chronic hypertension. To determine the optimal duration of ß-blocker withdrawal required to normalize the ARR. DESIGN: A prospective, longitudinal study design was employed investigating two groups whom either remained on or withdrew from ß-blocker therapy. METHODS: Hypertensive individuals taking ß-blockers and a combination of thiazide diuretics, α1-blockers, calcium channel antagonists and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker were recruited and followed over 10-12 weeks. ß-Blockers were withdrawn at the first visit. Blood pressure (BP) was measured at each visit and blood drawn serially for measurement of plasma renin activity (PRA), direct renin concentration (DRC) and aldosterone. BP was optimized by maximizing non-renin-suppressing antihypertensives. Main outcomes were ARR, DRC, PRA and aldosterone. Plasma renin activity was calculated from angiotensin I measured using radioimmunoassay (RIA), DRC was measured using chemiluminescent immunoassay assay, and aldosterone was measured using both RIA and Chemilluminescence Assay (CIL). RESULTS: False-positive ARR for primary aldosteronism (PA) occurred in 31% of patients taking ß-blockers. ARR returned to normal following ß-blocker withdrawal resulting from an increase in the DRC and PRA without affecting aldosterone. The optimum time for ß-blocker withdrawal was 2 weeks when using DRC and 3 weeks for PRA. ß-Blocker withdrawal did not adversely affect blood pressure. CONCLUSION: Raised ARR consequent to ß-blocker therapy causes false-positive screening for PA. Where ß-blockers can be safely withdrawn, this effect is reversed within 2-3 weeks depending on whether DRC or PRA is used to calculate ARR.
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Antagonistas Adrenérgicos beta/uso terapêutico , Aldosterona/sangue , Hipertensão/tratamento farmacológico , Renina/sangue , Suspensão de Tratamento , Antagonistas de Receptores Adrenérgicos alfa 1/uso terapêutico , Idoso , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Bloqueadores dos Canais de Cálcio/uso terapêutico , Doença Crônica , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Hipertensão/sangue , Hipertensão/fisiopatologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Inibidores de Simportadores de Cloreto de Sódio/uso terapêutico , Fatores de TempoRESUMO
BACKGROUND: Lifestyle modification is fundamental to obesity treatment, but few studies have described the effects of structured lifestyle programmes specifically in bariatric patients. We sought to describe changes in anthropometric and metabolic characteristics in a cohort of bariatric patients after participation in a nurse-led, structured lifestyle programme. METHODS: We conducted a retrospective, observational cohort study of adults with a body mass index (BMI) ≥ 40 kgm(-2) (or ≥ 35 kgm(-2) with significant co-morbidity) who were attending a regional bariatric service and who completed a single centre, 8-week, nurse-led multidisciplinary lifestyle modification programme. Weight, height, waist circumference, blood pressure, HbA1c, fasting glucose and lipid profiles as well as functional capacity (Incremental Shuttle Walk Test) and questionnaire-based anxiety and depression scores before and after the programme were compared in per-protocol analyses. RESULTS: Of 183 bariatric patients enrolled, 150 (81.9%) completed the programme. Mean age of completers was 47.9 ± 1.2 years. 34.7% were male. There were statistically significant reductions in weight (129.6 ± 25.9 v 126.9 ± 26.1 kg, p < 0.001), BMI (46.3 ± 8.3 v 44.9 ± 9.0 kgm(-2), p < 0.001), waist circumference (133.0 ± 17.1 v 129.3 ± 17.5 cm in women and 143.8 ± 19.0 v 135.1 ± 17.9 cm in men, both p < 0.001) as well as anxiety and depression scores, total- and LDL-cholesterol and triglyceride levels, with an increase in functional capacity (5.9 ± 1.7 v 6.8 ± 2.1 metabolic equivalents of thermogenesis (METS), p < 0.001) in completers at the end of the programme compared to the start. Blood pressure improved, with reductions in systolic and diastolic blood pressure from 135 ± 16.2 to 131.6 ± 17.1 (p = 0.009) and 84.7 ± 10.2 to 81.4 ± 10.9 mmHg (p < 0.001), respectively. The proportion of patients achieving target blood pressure increased from 50.3 to 59.3% (p = 0.04). The proportion of patients with diabetes achieving HbA1c <53 mmol/mol increased from 28.6 to 42.9%, p = 0.02. CONCLUSIONS: Bariatric patients completing an 8 week, nurse-led structured lifestyle programme had improved adiposity, fitness, lipid profiles, psychosocial health, blood pressure and glycaemia. Further assessment of this programme in a pragmatic randomised controlled trial seems warranted.
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Diabetes Mellitus Tipo 2/terapia , Dietoterapia , Terapia por Exercício , Obesidade Mórbida/terapia , Adulto , Ansiedade/complicações , Ansiedade/psicologia , Glicemia/metabolismo , Estatura , Peso Corporal , Doenças Cardiovasculares , HDL-Colesterol/metabolismo , LDL-Colesterol/metabolismo , Estudos de Coortes , Depressão/complicações , Depressão/psicologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/psicologia , Teste de Esforço , Tolerância ao Exercício , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/complicações , Obesidade Mórbida/metabolismo , Obesidade Mórbida/psicologia , Padrões de Prática em Enfermagem , Estudos Retrospectivos , Comportamento de Redução do Risco , Resultado do Tratamento , Triglicerídeos/metabolismo , Circunferência da CinturaRESUMO
OBJECTIVE: Identify the impact of COVID-19 lockdown restrictions on the vitamin D status of individuals in the west of Ireland. DESIGN: Cross-sectional study. SETTING: Adults who had wintertime serum 25(OH)D analysis completed in Galway University Hospital. PARTICIPANTS: A total of 16,725 participants (2015-2020 (n = 13,449) and 2020-2021 (n = 3276)). Baseline demographics; sex, age, origin of the sample and the date of sample collection. RESULTS: Median serum vitamin D and serum vitamin D3 concentrations were higher in the 5-month period from October-February 2020-2021 (61 nmol/L (± 36-85 nmol/L) and 60 nmol/L (± 34-85 nmol/L)) respectively, than for the corresponding 5-month period (October-February) in 2015-2020 (53 nmol/L (± 32-78 nmol/L) and 51 nmol/L (± 30-77 nmol/L)) respectively. These changes coincided with a decline in the prevalence of deficiency. In the 5-month period October-February 2020-2021, 19.2% of the population were vitamin D deficient (< 30 nmol/L) compared to 22.5% in the corresponding 5-month period in 2015-2020, and 38.1% were vitamin D deficient (< 50 nmol/L) in the 5-month period October-February 2020-2021 compared to 46.6% in the corresponding 5-month period in 2015-2020. Males were more likely to be deficient at both thresholds (p < 0.001). For the total cohort, at the < 30 nmol/L threshold, inpatients (25.5%) and nursing home residents (34.1%) had higher prevalence of deficiency. CONCLUSIONS: Vitamin D levels were higher in the 5-month period of October-February 2020-2021, and this precipitated a decline in deficiency at both thresholds, indicating that lockdown coincided with enhanced vitamin D status. We postulate that it may be attributable to changes in diet and/or supplementation, or increased sun exposure, but further confirmatory studies are required.
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COVID-19 , Deficiência de Vitamina D , Masculino , Adulto , Humanos , Vitamina D , Irlanda/epidemiologia , Estudos Transversais , Deficiência de Vitamina D/epidemiologia , COVID-19/epidemiologia , Controle de Doenças Transmissíveis , Suplementos NutricionaisRESUMO
BACKGROUND: Adopting the WHO protocol for glucose analysis is arguably impractical in the routine clinical setting. Deviations may develop due to a lack of understanding regarding the impact of glycolysis on the accuracy of results. AIM: We sought to assess the stability of glucose in two different blood collection tubes (BCT), BD Vacutainer® FX 'Fl-Ox' and Greiner Vacuette® FC-Mix 'FC-Mix' stored at room temperature (RT:18-22°C) and 4°C over 8.5 days. METHOD: Each participant provided venous whole blood collected into 51 BCTs; 'Fl-Ox' (n = 26) and 'FC-Mix' (n = 25). One Fl-Ox sample from each participant was handled according to the WHO recommended method. The remaining BCTs were stored at 4°C/RT prior to analyses at designated study timepoints. Glucose was measured using the hexokinase assay on the Cobas® 8000 platform. RESULTS: Participants (n = 8, Male = 2) were aged 24-56 years. Plasma glucose measured in FI-Ox BCTs according to the WHO sample-handling method had a median concentration of 5.73 mmol/L (Range: 5.39-10.37 mmol/L). Glucose decreased by greater than minimal difference (>0.26 mmol/L) in blood collected into Fl-Ox and stored @4°C/RT within 24 h of phlebotomy. FC-Mix BCT maintained glucose <0.26 mmol/L @4°C over a period of 8.5 days and up to 4 days @RT when compared to the WHO recommended method. CONCLUSION: Glucose in FC-Mix BCT stored @4°C demonstrated the best agreement with results determined using the WHO specifications. When FC-Mix tubes were stored @RT, glucose was stable for 4 days. These findings suggest that the FC-Mix BCT effectively inhibits glycolysis and should be introduced into routine clinical practice.
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Glicemia , Glucose , Humanos , Masculino , Glicemia/análise , Manejo de Espécimes/métodos , Coleta de Amostras Sanguíneas/métodos , FlebotomiaRESUMO
Context: It is not clear if the risk of abnormal glucose tolerance (AGT) is attenuated in the long-term in women diagnosed with gestational diabetes (GDM) using the World Health Organization (WHO) 2013 criteria and who have received appropriate treatment during pregnancy. Objective: We aimed to assess the long-term prevalence of AGT and other cardiovascular disease (CVD) risk factors in this cohort. Methods: A retrospective cohort follow-up study was conducted of 37 and 107 women diagnosed with and without GDM respectively using the WHO 2013 criteria between June 2010 and December 2010. Women were invited to attend our center, where they underwent a 75-g oral glucose tolerance test, blood and urine collection, body measurements, and electrocardiography. Main outcome measure included the development of AGT using the American Diabetes Association criteria. Results: Sixteen (43.2%) women with GDM compared to 5 (4.7%) women with normal glucose tolerance (NGT) at index pregnancy had AGT (P < .001). In the GDM group, 10 (27.0%), 7 (18.9%), and 4 (10.8%) women had impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and type 2 diabetes mellitus (T2DM), respectively. In the NGT group, 2 (1.9%), 3 (2.8%), and 1 (0.9%) woman had IFG, IGT, and T2DM, respectively. Women with AGT also had an unfavorable metabolic profile including obesity, hypertension, insulin resistance, and dyslipidemia. Conclusion: Women treated for GDM (WHO 2013 criteria) remain at increased risk for developing AGT and adverse CVD risk factors as early as a decade after diagnosis. Continued efforts are needed to accurately follow this population to address modifiable risk factors.
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AIMS: Diagnosis of hydatidiform mole or molar pregnancy based on morphology alone can be challenging, particularly in early gestation, necessitating the use of ancillary techniques for accurate diagnosis. We sought to adapt the VENTANA HER2 dual-colour dual-hapten in-situ hybridisation (D-DISH) assay by using the internal chromosome 17 enumeration probe to determine ploidy status. METHODS: We selected 25 products of conception, consisting of molar and non-molar cases, to validate the HER2 D-DISH assay. These cases had prior morphological assessment by a perinatal pathologist and ploidy analysis using molecular cytogenetics. Three independent observers, blinded to the original histopathological and genetic diagnosis, scored 10 representative areas on each slide. Interobserver variability was assessed by comparing the total scores of each observer using analysis of variance (ANOVA) and the kappa statistic. RESULTS: Our ploidy scoring system accurately determined the correct number of diploid and triploid conceptuses, demonstrating complete concordance with pre-existing ploidy status and the initial diagnosis. Interobserver agreement between three independent scorers was robust: ANOVA (p=0.36) and kappa statistic (0.812, p<0.001). We achieved clear separation of average nuclear signals for diploid and triploid conceptuses, which was statistically significant (p<0.05). Employing our innovative scoring system, known as the 'rule of 5', we established ploidy decision thresholds for all 25 cases. CONCLUSIONS: Our modified HER2 D-DISH ploidy assay simplifies the process of ploidy determination and improves the accuracy of morphological diagnosis of molar pregnancy. The HER2 D-DISH assay was selected for ploidy analysis due to the widespread availability of in-situ hybridisation in pathology laboratories.
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INTRODUCTION: Capillary blood collection, a technique traditionally used in diabetes care, shows promise for many applications including pregnancy monitoring. Serial measurement of serum human Chorionic Gonadotrophin (hCG) is frequently necessary for managing early pregnancy, including molar pregnancy, requiring multiple visits to a maternity hospital for blood collection by venepuncture. This proof-of-concept study aimed to assess the clinical performance and user acceptability of capillary blood samples collected remotely, as an alternative to venous blood for hCG measurement. METHODS: Women attending the early pregnancy unit who required serum hCG measurement, were invited to participate. Following informed written consent, participants were shown how to collect capillary blood samples using the Mini-Collect® collection device. Matched venous and capillary blood samples were collected in clinic for hCG comparison purposes. Participants were also supplied with a home collection kit in a prepaid return envelope. They were asked to perform a finger-prick blood collection at home using the instructions provided and to return the capillary blood sample by post within 24 h of collection, along with a completed user-satisfaction questionnaire. Statistical analysis was performed using Analyse-it® software. RESULTS: The study enrolled 71 participants and over a third of these women collected a capillary blood sample at home. The median age of participants was 33 years (range 29-36). Passing-Bablok linear regression (y = -0.037 + 1.04x) and Spearman correlation (r = 0.999, p < 0.0001), demonstrated good agreement and strong correlation between venous and capillary samples, over a broad range of hCG values (1.2 to 224,0000 IU/L). The majority of capillary samples collected remotely (39%, 27/69) had sufficient blood volume for analysis (74%, 20/27). Respondents (77%, 18/25) found the collection device easy to use and expressed willingness to use a future service if available (80%, 20/25) CONCLUSION: The study demonstrated excellent agreement between the hCG results obtained from both collection methods, suggesting that capillary blood can serve as a reliable alternative for venous hCG measurement, particularly in clinical settings requiring frequent hCG monitoring. Feedback from the study questionnaire indicates a preference for this type of follow-up among women, indicating potential improvements in compliance for blood based diagnostic tests.