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AIMS: To undertake a Priority Setting Partnership (PSP), identifying the most important unanswered questions in type 1 diabetes in Ireland and the United Kingdom and to compare these to priorities identified in a 2011 PSP. METHODS: A steering committee (including eight individuals with lived experience/charity representatives and six clinicians) designed a survey which asked stakeholders to list three questions about type 1 diabetes. This was disseminated through social media, direct email contact, and printed posters. Following analysis, a second survey asked participants to rank these priorities in order of importance. The top questions were then carried forward to an online, 2 days final workshop where the final top 10 were ranked. RESULTS: There were 1050 responses (64% female, 78% adults living with type 1 diabetes, 9% healthcare professionals, 9% family members) to the first survey and 2937 individual questions were submitted. Sixty-five summary questions were submitted into a second survey, completed by 497 individuals (76% adults living with type 1 diabetes, 9% healthcare professionals, and 11% family members). Nineteen questions from the interim survey progressed to a final workshop, which identified the top 10 priorities through group discussion. As in 2011, there was emphasis on psychological health, diabetes-related complications, and hypoglycaemia. New themes prioritised included artificial intelligence and women's health. CONCLUSIONS: The research priorities, which have been identified using a robust and proven methodology, highlight the key concerns of those living with type 1 diabetes, their families and representatives, as well as clinicians in Ireland and the UK.
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AIM: Women with GDM display adverse lifetime cardio-metabolic health. We examined whether early metformin in GDM could impact cardio-metabolic risk factors postpartum. RESEARCH DESIGN & METHODS: EMERGE, a double-blind, placebo-controlled trial randomized pregnancies 1:1 to placebo or metformin at GDM diagnosis and followed participants from randomization until 12±4 weeks postpartum. In total 478 pregnancies were available for postpartum maternal assessment, 237 and 241 assigned to metformin and placebo respectively. Weight (kg), body mass index (BMI) (kg/m2), waist circumference (cm) and blood pressure (mmHg) were measured, infant feeding method documented and bloods drawn for a 75 gram oral glucose tolerance test, fasting insulin, C peptide and lipid analysis. RESULTS: Despite similar weight and BMI at trial randomization, participants receiving metformin had significantly lower weight (79.5±15.9 vs 82.6±16.9kg; p=0.04) and BMI (29.3(5.6) vs 30.5(5.4); p=0.018) at the postpartum visit. However no difference in weight change from randomisation to 12 weeks postpartum was observed between metformin and placebo groups. Overall 29% (n=139) of the cohort met criteria for prediabetes or diabetes, with no positive impact with metformin. There were also no differences in measurements of insulin resistance, blood pressure or lipids between groups. CONCLUSION: Early metformin use in GDM did not impact important cardio-metabolic parameters in the early postpartum period despite significant benefits in weight gain and insulin use in pregnancy.
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BACKGROUND: Although aspirin therapy is being increasingly advocated with the intention of risk modification for a wide range of pregnancy complications, women with prepregnancy diabetes mellitus are commonly excluded from clinical trials. OBJECTIVE: The primary aim of this study was to examine the effect of aspirin therapy on a composite measure of adverse perinatal outcome in pregnancies complicated by pregestational diabetes mellitus. STUDY DESIGN: A double-blinded, placebo-controlled randomized trial was conducted at 6 university-affiliated perinatology centers. Women with type 1 diabetes mellitus or type 2 diabetes mellitus of at least 6 months' duration were randomly allocated to 150-mg daily aspirin or placebo from 11 to 14 weeks' gestation until 36 weeks. Established vascular complications of diabetes mellitus, including chronic hypertension or nephropathy, led to exclusion from the trial. The primary outcome was a composite measure of placental dysfunction (preeclampsia, fetal growth restriction, preterm birth <34 weeks' gestation, or perinatal mortality). The planned sample size was 566 participants to achieve a 35% reduction in the primary outcome, assuming 80% statistical power. Secondary end points included maternal and neonatal outcomes and determination of insulin requirements across gestation. Data were centrally managed using ClinInfo and analyzed using SAS 9.4. The 2 treatment groups were compared using t tests or chi-square tests, as required, and longitudinal data were compared using a repeated-measures analysis. RESULTS: From February 2020 to September 2022, 191 patients were deemed eligible, 134 of whom were enrolled (67 randomized to aspirin and 67 to placebo) with a retrospective power of 64%. A total of 101 (80%) women had type 1 diabetes mellitus and 25 (20%) had type 2 diabetes mellitus. Reaching the target sample size was limited by the impact of the COVID-19 pandemic. Baseline characteristics were similar between the aspirin and placebo groups. Treatment compliance was very high and similar between groups (97% for aspirin, 94% for placebo). The risk of the composite measure of placental dysfunction did not differ between groups (25% aspirin vs 21% placebo; P=.796). Women in the aspirin group had significantly lower insulin requirements throughout pregnancy compared with the placebo group. Insulin requirements in the aspirin group increased on average from 0.7 units/kg at baseline to 1.1 units/kg by 36 weeks' gestation (an average 83% within-patient increase), and increased from 0.7 units/kg to 1.3 units/kg (a 181% within-patient increase) in the placebo group, over the same gestational period (P=.002). Serial hemoglobin A1c levels were lower in the aspirin group than in the placebo group, although this trend did not reach statistical significance. CONCLUSION: In this multicenter, double-blinded, placebo-controlled randomized trial, aspirin did not reduce the risk of adverse perinatal outcome in pregnancies complicated by prepregnancy diabetes mellitus. Compared with the placebo group, aspirin-treated patients required significantly less insulin throughout pregnancy, indicating a beneficial effect of aspirin on glycemic control. Aspirin may exert a plausible placenta-mediated effect on pregestational diabetes mellitus that is not limited to its antithrombotic properties.
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Aspirina , Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Pré-Eclâmpsia , Gravidez em Diabéticas , Humanos , Aspirina/administração & dosagem , Gravidez , Feminino , Método Duplo-Cego , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 1/complicações , Adulto , Gravidez em Diabéticas/epidemiologia , Gravidez em Diabéticas/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Pré-Eclâmpsia/prevenção & controle , Pré-Eclâmpsia/epidemiologia , Pré-Eclâmpsia/diagnóstico , Irlanda/epidemiologia , Nascimento Prematuro/prevenção & controle , Nascimento Prematuro/epidemiologia , Resultado da Gravidez/epidemiologia , Recém-Nascido , Retardo do Crescimento Fetal/epidemiologia , Retardo do Crescimento Fetal/prevenção & controle , Insulina/administração & dosagemRESUMO
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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Importance: Gestational diabetes is a common complication of pregnancy and the optimal management is uncertain. Objective: To test whether early initiation of metformin reduces insulin initiation or improves fasting hyperglycemia at gestation weeks 32 or 38. Design, Setting, and Participants: Double-blind, placebo-controlled trial conducted in 2 centers in Ireland (one tertiary hospital and one smaller regional hospital). Participants were enrolled from June 2017 through September 2022 and followed up until 12 weeks' postpartum. Participants comprised 510 individuals (535 pregnancies) diagnosed with gestational diabetes based on World Health Organization 2013 criteria. Interventions: Randomized 1:1 to either placebo or metformin (maximum dose, 2500 mg) in addition to usual care. Main Outcomes And Measures: The primary outcome was a composite of insulin initiation or a fasting glucose level of 5.1 mmol/L or greater at gestation weeks 32 or 38. Results: Among 510 participants (mean age, 34.3 years), 535 pregnancies were randomized. The primary composite outcome was not significantly different between groups and occurred in 150 pregnancies (56.8%) in the metformin group and 167 pregnancies (63.7%) in the placebo group (between-group difference, -6.9% [95% CI, -15.1% to 1.4%]; relative risk, 0.89 [95% CI, 0.78-1.02]; P = .13). Of 6 prespecified secondary maternal outcomes, 3 favored the metformin group, including time to insulin initiation, self-reported capillary glycemic control, and gestational weight gain. Secondary neonatal outcomes differed by group, with smaller neonates (lower mean birth weights, a lower proportion weighing >4 kg, a lower proportion in the >90% percentile, and smaller crown-heel length) in the metformin group without differences in neonatal intensive care needs, respiratory distress requiring respiratory support, jaundice requiring phototherapy, major congenital anomalies, neonatal hypoglycemia, or proportion with 5-minute Apgar scores less than 7. Conclusion and relevance: Early treatment with metformin was not superior to placebo for the composite primary outcome. Prespecified secondary outcome data support further investigation of metformin in larger clinical trials. Trial Registration: ClinicalTrials.gov Identifier: NCT02980276; EudraCT: 2016-001644-19.
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Diabetes Gestacional , Metformina , Adulto , Feminino , Humanos , Recém-Nascido , Gravidez , Peso ao Nascer , Diabetes Gestacional/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/uso terapêutico , Insulina/administração & dosagem , Insulina/uso terapêutico , Metformina/administração & dosagem , Metformina/efeitos adversos , Metformina/uso terapêutico , Método Duplo-CegoRESUMO
We evaluated the performance of the interoperable Cambridge hybrid closed-loop app with FreeStyle Libre 3 glucose sensor, and YpsoPump insulin pump in a real-world setting. Data from 100 users (63 adults [mean ± SD age 41.9 ± 14.0 years], 15 children [8.6 ± 5.2 years)] and 22 users of unreported age) for a period of 28 days were analyzed. Time in range (3.91- 10.0mmol/L) was 72.6 ± 11.1% overall. Time below range (<3.9mmol/L) was 3.1% (1.4-5.1) (median [interquartile range]). Auto-mode was active for 95.8% (91.8-97.9) of time. This real-world analysis suggests that the performance of Cambridge hybrid closed-loop app with this glucose sensor is comparable to other commercially available hybrid closed-loop systems.
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Metformin is used worldwide in the treatment of type 2 diabetes and has been used in the treatment of diabetes in pregnancy since the 1970s. It is highly acceptable to patients due to its ease of administration, cost and adverse effect profile. It is effective in reducing macrosomia, large-for-gestational-age infants and reduces maternal weight gain. Despite its many advantages, metformin has been associated with reductions in foetal size and has been associated with an increase in infants born small-for-gestational-age in certain cohorts. In this article, we review its efficacy, adverse effects and long-term follow-up before, during and after pregnancy for both mother and infant. We also evaluate the other forms of treatment for gestational diabetes, including oral therapies, insulin therapy and emerging treatments.
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Diabetes Mellitus Tipo 2 , Diabetes Gestacional , Metformina , Gravidez , Lactente , Feminino , Humanos , Metformina/uso terapêutico , Metformina/efeitos adversos , Hipoglicemiantes/efeitos adversos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/induzido quimicamente , Diabetes Gestacional/tratamento farmacológico , InsulinaRESUMO
OBJECTIVE: Primary hyperparathyroidism is a common endocrine disorder, with 80% of all cases usually caused by one single hyperfunctioning parathyroid adenoma. Conventional imaging modalities for the diagnostic work-up of primary hyperparathyroidism (PHPT) include ultrasound of the neck, 99mTc-sestamibi scintigraphy, and four-dimensional computed tomography (4D-CT). However, the role of other imaging modalities, such as 11C-methionine PET/CT, in the care pathway for PHPT is currently unclear. Here, we report our experience of the diagnostic utility of 11C-methionine PET/CT in a single-center patient cohort (n = 45). DESIGN: Retrospective single-center cohort study. PATIENTS AND MEASUREMENTS: The data of eligible patients that underwent 11C-methionine PET/CT between 2014 and 2022 at Addenbrooke's Hospital (Cambridge, UK) were collected and analyzed. The clinical utility of imaging modalities was determined by comparing the imaging result with histopathological and biochemical outcomes following surgery. RESULTS: In patients with persistent primary hyperparathyroidism following previous surgery, 11C-methionine PET/CT identified a candidate lesion in 6 of 10 patients (60.0%), and histologically confirmed in 5 (50.0%). 11C-methionine PET/CT also correctly identified a parathyroid adenoma in 9 out of 12 patients (75.0%) that failed to be localized on other imaging modalities. 11C-methionine PET/CT had a sensitivity of 70.0% (95% CI 55.8 - 84.2%) for the detection of parathyroid adenomas. CONCLUSIONS: This study highlights a diagnostic role for 11C-methionine PET/CT in patients that have undergone unsuccessful prior surgery or have equivocal or negative prior imaging results, aiding localization and a targeted surgical approach.
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Adenoma , Hiperparatireoidismo Primário , Neoplasias das Paratireoides , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Hiperparatireoidismo Primário/diagnóstico por imagem , Hiperparatireoidismo Primário/etiologia , Neoplasias das Paratireoides/diagnóstico por imagem , Neoplasias das Paratireoides/complicações , Estudos Retrospectivos , Estudos de Coortes , Adenoma/diagnóstico , Adenoma/diagnóstico por imagem , Metionina , Tecnécio Tc 99m Sestamibi , Racemetionina , Reino Unido , Glândulas ParatireoidesRESUMO
INTRODUCTION: Type 1 diabetes mellitus occurs in one in every 275 pregnancies and can result in increased morbidity and mortality for both mother and baby. Several pregnancy complications can be reduced or prevented by attendance at pre-pregnancy care (PPC). Despite this, less than 40% of pregnant women with pre-gestational diabetes receive formal PPC. The aim of this scoping review is to identify the barriers to PPC attendance among women with type 1 diabetes. METHODS: We conducted a scoping review by searching five databases (Ebsco, Embase, Ovid and PubMed for literature and the ProQuest for any grey/unpublished literature) for studies in English between 2000 and 2022. Studies that evaluated attendance at PPC for women with type 1 diabetes were included. RESULTS: There are multiple barriers to PPC attendance, and many of these barriers have been unchanged since the 1990s. Identified barriers can be grouped under patient-centered and clinician-centered headings. Patient factors include knowledge and awareness, unplanned pregnancies, negative perceptions of healthcare and communication issues, unclear attendance pathways and logistical issues including time off work and childcare. Clinician factors include physician knowledge, time constraints and lack of comfort discussing pregnancy/contraception. CONCLUSION: This review highlights the ongoing problem of poor attendance at PPC and identifies key barriers to be addressed when developing and implementing PPC programs for women with type 1 diabetes.
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Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Complicações na Gravidez , Gravidez , Feminino , Humanos , Diabetes Mellitus Tipo 1/terapia , Cuidado Pré-Natal , GestantesRESUMO
Background Maternal opioid exposure during pregnancy has various effects on neonatal health. Buprenorphine/naloxone and methadone are examples of medications for opioid use disorder (MOUD) used for the treatment of opioid use disorder (OUD). Research comparing the impacts of these MOUD modalities on neonatal outcomes when used to treat pregnant people with OUD remains limited. We evaluated the differences in outcomes between neonates with in-utero exposure to buprenorphine/naloxone versus methadone. Methodology We performed a retrospective cohort chart review between October 15, 2008, and October 15, 2019, evaluating mother/neonate dyads at two medical centers in Michigan. The charts of female patients, aged 18+, with OUD and buprenorphine/naloxone or methadone treatment, were examined. The charts of the corresponding neonates were also examined. Multiple regression analysis was performed. Results In total, 343 mother/infant dyads were included: 99 patients were treated with buprenorphine/naloxone and 232 patients were treated with methadone. The buprenorphine/naloxone group had significant differences in maternal age, hepatitis status, asthma, gestational age in weeks, neonatal intensive care unit (NICU) length of stay (LOS), neonatal opioid withdrawal syndrome (NOWS) peak score, birth head circumference, and birth weight compared to the methadone group at baseline. Adjusted multivariable regression analysis demonstrated neonates with exposure to buprenorphine/naloxone had a NOWS peak score 3.079 points less (95% confidence interval (CI): -4.525, 1.633; p = 0.001) and NICU LOS 8.955 days less (95% CI: -14.399, -3.511; p = 0.001) than neonates exposed to methadone. Conclusions Neonates with in-utero exposure to buprenorphine/naloxone had significantly lower NOWS scores and shorter NICU LOS compared to neonates with in-utero exposure to methadone. These findings demonstrate that buprenorphine/naloxone is potentially a more favorable treatment for the reduction in metrics representing adverse neonatal outcomes in pregnant people with OUD than methadone.
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AIM: Report the outcomes of pregnant women with type 1 and type 2 diabetes and to identify modifiable and non-modifiable factors associated with poor outcomes. METHODS: Retrospective analysis of pregnancy preparedness, pregnancy care and outcomes in the Republic of Ireland from 2015 to 2020 and subsequent multivariate analysis. RESULTS: In total 1104 pregnancies were included. Less than one third attended pre-pregnancy care (PPC), mean first trimester haemoglobin A1c was 7.2 ± 3.6% (55.5 ± 15.7 mmol/mol) and 52% received pre-conceptual folic acid. Poor preparation translated into poorer pregnancy outcomes. Livebirth rates (80%) were comparable to the background population however stillbirth rates were 8.7/1000 (four times the national rate). Congenital anomalies occurred in 42.5/1000 births (1.5 times the background rate). More than half of infants were large for gestational age and 47% were admitted to critical care. Multivariate analyses showed strong associations between non-attendance at PPC, poor glycaemic control and critical care admission (adjusted odds ratio of 1.68 (1.48-1.96) and 1.61 (1.43-1.86), p < 0.05 respectively) for women with type 1 diabetes. Smoking and teratogenic medications were also associated with critical care admission and hypertensive disorders of pregnancy. CONCLUSION: Pregnancy outcomes in women with diabetes are suboptimal. Significant effort is needed to optimize the modifiable factors identified in this study.
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Diabetes Mellitus Tipo 2 , Gravidez em Diabéticas , Estudos de Coortes , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Humanos , Irlanda/epidemiologia , Gravidez , Resultado da Gravidez/epidemiologia , Gravidez em Diabéticas/epidemiologia , Estudos RetrospectivosRESUMO
Introduction: Pregestational diabetes (PGDM) is an increasingly common and complex condition that infers risk to both mother and infant. To prevent serious morbidity, strict glycaemic control is essential. The aim of this review is to review the glucose sensing and insulin delivering technologies currently available for women with PGDM. Methods: We reviewed online databases for articles relating to technology use in pregnancy using a combination of keywords and MeSH headings. Relevant articles are included below. Results: A number of technological advancements have improved care and outcomes for women with PGDM. Real time continuous glucose monitoring (rtCGM) offers clear advantages in terms of infants size and neonatal intensive care unit admissions; and further benefits are seen when combined with continuous subcutaneous insulin delivery (insulin pump) and algorithms which continuously adjust insulin levels to glucose targets (hybrid closed loop). Other advancements including flash or intermittent scanning CGM (isCGM) and stand-alone insulin pumps do not confer as many advantages for women and their infants, however they are increasingly used outside of pregnancy and many women enter pregnancy already using these devices. Discussion: This article offers a discussion of the most commonly used technologies in pregnancy and evaluates their current and future roles.
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Diabetes Mellitus Tipo 1 , Gravidez em Diabéticas , Gravidez , Recém-Nascido , Feminino , Humanos , Hipoglicemiantes/uso terapêutico , Diabetes Mellitus Tipo 1/tratamento farmacológico , Automonitorização da Glicemia , Controle Glicêmico , Glicemia , Insulina/uso terapêutico , Gravidez em Diabéticas/terapiaRESUMO
CONTEXT AND AIM: Metformin has been used in pregnancy since the 1970s. It is cheap, widely available and is acceptable to women. Despite its increasing use, controversy remains surrounding its benefits and risks. Metformin effectively reduces hyperglycaemia for the mother during pregnancy and it reduces rates of macrosomia and neonatal hypoglycaemia. However, concern exists surrounding an increase in the rate of SGA births and obesity in childhood. We aim to review the evidence and expert opinion behind metformin in pregnancy through to the post-partum period. METHODS: We performed a literature review of relevant studies from online databases using a combination of keywords. We also searched the references of retrieved articles for pertinent studies. RESULTS: There is strong evidence that metformin is safe in early pregnancy with no risk of congenital malformations. If used throughout pregnancy, it is likely to lead to reduced maternal weight gain and reduced insulin dose in women with type 2 diabetes. In infants, metformin reduces hypoglycaemia and macrosomia but may increase the rate of infants born SGA. There is some evidence of an increased risk of obesity and altered fat distribution in offspring. Metformin appears well tolerated in pregnancy and is more acceptable to women than insulin therapy. CONCLUSION: Due to increasing rates of maternal obesity, GDM and type 2 diabetes, metformin use in pregnancy is increasing. Overall, it appears safe and effective but further research is needed to examine mechanisms linking metformin to obesity reported during childhood in some follow-up studies.
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Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Gestacional/tratamento farmacológico , Hiperglicemia/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Metformina/administração & dosagem , Obesidade Infantil/induzido quimicamente , Administração Oral , Criança , Diabetes Gestacional/prevenção & controle , Feminino , Ganho de Peso na Gestação/efeitos dos fármacos , Humanos , Hiperglicemia/prevenção & controle , Hipoglicemia/induzido quimicamente , Hipoglicemia/prevenção & controle , Hipoglicemiantes/efeitos adversos , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional , Insulina/administração & dosagem , Metformina/efeitos adversos , Gravidez , Resultado da Gravidez , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
INTRODUCTION: Diabetes mellitus is the most common metabolic complication of pregnancy and its prevalence worldwide is rising. The number of randomised controlled trials (RCTs) being conducted in people with diabetes is also increasing. Many studies preferentially publish findings on clinical endpoints and do not report patient-reported outcomes (PROs). In studies that do include PROs, PRO reporting is often of poor quality. METHODS: We will conduct this systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Using a combination of medical subject headings and keywords (combined using Boolean operators), we will search web-based databases (PubMed, Cochrane and EMBASE) for RCTs published in English between 2013 and 2021. Two reviewers will review titles and abstracts. We will review the full texts of any relevant abstracts and extract the following data: date of publication or recruitment period, journal of publication, country of study, multicentre or single centre, population and number of participants, type of intervention, frequency of PRO assessment and type of PRO (or PRO measurement) used. We will also record if the PRO was a primary, secondary or exploratory outcome. We will exclude reviews, observational studies, unpublished data for example, conference abstracts and trial protocols. Any published RCT that includes data on a PRO as a primary or secondary outcome will then be compared against the Consolidated Standards of Reporting Trials-Patient-Reported Outcome extension checklist, a structured and approved framework for the publication of results of PROs. ETHICS AND DISSEMINATION: Ethical approval to conduct this study was obtained from the ethics committee at Galway University Hospitals on 24 March 2021 (CA 2592). We aim to publish our findings in a peer-reviewed journal and present our findings at national and international conferences. SYSTEMATIC REVIEW REGISTRATION: This systematic review was registered prospectively with the International Prospective Register of Systematic Reviews (PROSPERO). Registration number CRD42021234917.
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Diabetes Mellitus , Medidas de Resultados Relatados pelo Paciente , Lista de Checagem , Feminino , Humanos , Gravidez , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Revisões Sistemáticas como AssuntoRESUMO
Cushing's syndrome is a rare disorder of cortisol excess and is associated with significant morbidity and mortality. Hypercalcaemia due to hyperparathyroidism is a common condition; however, in 10% of young patients, it is associated with other endocrinopathies and occurs due to a genetic variant [e.g. multiple endocrine neoplasia (MEN) type 1 (MEN1), MEN2 or MEN4]. We report the case of a 31-year-old woman who was referred to the endocrinology out-patient service with an 8-month history of hirsutism, amenorrhoea and weight gain. Her biochemical work up was significant for adrenocorticotropic hormone (ACTH)-independent Cushing's syndrome. Radiological investigations revealed an adrenal adenoma. During investigation she was also found to have primary hyperparathyroidism due to a parathyroid adenoma. Pre-operatively, the patient was commenced on metyrapone and both her adrenal and parathyroid lesions were resected successfully. There were several concerning findings on initial examination of the parathyroid tumour, including possible extension of the tumour through the capsule and vascular invasion; however, following extensive review, it was ultimately defined as an adenoma. Given the unusual presence of two endocrinopathies in a young patient, she subsequently underwent genetic testing. Analysis of multiple genes did not reveal any pathogenic variants. The patient is currently clinically well, with a normal adjusted calcium and no clinical features of cortisol excess. She will require long-term follow up for recurrence of both hypercalcaemia and hypercortisolaemia.
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BACKGROUND: Immune checkpoint inhibitors (ICIs) are a novel class of oncological agents which are used to treat a number of malignancies. To date seven agents have been approved by the Food and Drug Administration (FDA) to treat both solid and haematological malignancies. Despite their efficacy they have been associated with a number of endocrinopathies. We report a unique case of hypophysitis, thyroiditis, severe hypercalcaemia and pancreatitis following combined ICI therapy. CASE PRESENTATION: A 46-year old Caucasian female with a background history of malignant melanoma and lung metastases presented to the emergency department with lethargy, nausea, palpitations and tremors. She had been started on a combination of nivolumab and ipilimumab 24 weeks earlier. Initial investigations revealed thyrotoxicosis with a thyroid stimulating hormone (TSH) of < 0.01 (0.38-5.33) mIU/L, free T4 of 66.9 (7-16) pmol/.L. TSH receptor and thyroperoxidase antibodies were negative. She was diagnosed with thyroiditis and treated with a beta blocker. Six weeks later she represented with polyuria and polydipsia. A corrected calcium of 3.54 (2.2-2.5) mmol/l and parathyroid hormone (PTH) of 9 (10-65) pg/ml confirmed a diagnosis of non-PTH mediated hypercalcaemia. PTH-related peptide and 1, 25-dihydroxycholecalciferol levels were within the normal range. Cross-sectional imaging and a bone scan out ruled bone metastases but did reveal an incidental finding of acute pancreatitis - both glucose and amylase levels were normal. The patient was treated with intravenous hydration and zoledronic acid. Assessment of the hypothalamic-pituitary-adrenal (HPA) axis uncovered adrenocorticotrophic hormone (ACTH) deficiency with a morning cortisol of 17 nmol/L. A pituitary Magnetic Resonance Image (MRI) was unremarkable. Given her excellent response to ICI therapy she remained on ipilimumab and nivolumab. On follow-up this patient's thyrotoxicosis had resolved without anti-thyroid mediations - consistent with a diagnosis of thyroiditis secondary to nivolumab use. Calcium levels normalised rapidly and remained normal. ACTH deficiency persisted, and she is maintained on oral prednisolone. CONCLUSION: This is a remarkable case in which ACTH deficiency due to hypophysitis; thyroiditis; hypercalcaemia and pancreatitis developed in the same patient on ipilimumab and nivolumab combination therapy. We postulate that hypercalcaemia in this case was secondary to a combination of hyperthyroidism and secondary adrenal insufficiency.
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Hipercalcemia/induzido quimicamente , Hipofisite/induzido quimicamente , Inibidores de Checkpoint Imunológico/efeitos adversos , Pancreatite/induzido quimicamente , Tireoidite/induzido quimicamente , Quimioterapia Combinada , Feminino , Glucocorticoides/administração & dosagem , Humanos , Hipercalcemia/diagnóstico por imagem , Hipercalcemia/tratamento farmacológico , Hipofisite/diagnóstico por imagem , Hipofisite/tratamento farmacológico , Inibidores de Checkpoint Imunológico/administração & dosagem , Pessoa de Meia-Idade , Pancreatite/diagnóstico por imagem , Pancreatite/tratamento farmacológico , Tireoidite/diagnóstico por imagem , Tireoidite/tratamento farmacológicoRESUMO
This qualitative study explored the experiences of social workers, nurses, and physicians providing end-of-life care to children in a pediatric acute-care hospital setting. Findings demonstrated that participants experienced both professional and personal impacts of their work and employed various coping strategies under each of these domains. The acute-care setting was found to create unique challenges in providing end-of-life care. Implications for policy and practice include promotion of both individual and institutional-level coping strategies and supports that meet the various needs of staff. Implications for future research include a nuanced examination of differences in experiences among nurses, social workers, and physicians.
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Hospitais Pediátricos , Corpo Clínico Hospitalar/psicologia , Recursos Humanos de Enfermagem Hospitalar/psicologia , Assistentes Sociais/psicologia , Assistência Terminal/psicologia , Adulto , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Klinefelter syndrome (KS) is the most common sex-chromosomal disorder in males. Frequently under-recognized, it occurs in 1 in 500-600 male births. It is caused by the inheritance of at least one additional X chromosome from either parent. Patients often have uncommon or atypical malignancies. PATIENT: We describe the case of a 35-year-old man with 47XXY KS and previous cryptorchidism, presenting with a painful testicular mass. Histology confirmed Leydig cell hyperplasia. DISCUSSION: Cryptorchidism is an established risk factor for testicular tumours and occurs six times more commonly in KS than in the general population. Despite this, large epidemiological studies have shown a reduced burden of testicular cancer in these patients. The presentation of a hypoechoic lesion on ultrasound will prompt consideration of testicular tumours, however orchalgia represents an atypical presentation. In patients with KS, Leydig cell hyperplasia is a much more common entity and should be considered early in the differential diagnosis. LEARNING POINTS: The differential diagnosis of a testicular mass in Klinefelter syndrome includes malignancy and nodular Leydig cell hyperplasia.Diagnosis can be challenging, both radiologically and histologically.Orchalgia is atypical in Leydig cell hyperplasia.
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ISSUE ADDRESSED: Smoking rates are high among Arabic-speaking populations, particularly men, and there is limited evidence to formulate effective tobacco-control strategies in this group. This study explored smoking within an Arabic-speaking community in Sydney, focusing on men's smoking in the context of their families. METHODS: We conducted six focus groups with a total of 60 Arabic-speaking participants recruited through health workers, counsellors and community leaders in Western Sydney, Australia. The focus groups, conducted in Arabic or English, discussed smoking experiences, family issues and quit attempts. Focus group data were recorded, transcribed and analysed for emerging themes. RESULTS: Male smoking was normalised in home, social and religious settings. There was concern about children's exposure to environmental tobacco smoke (ETS), but less concern for adults, particularly wives. Smoking created conflict within families and quit attempts were often made without assistance. There was a lack of enthusiasm for telephone support services with participants suggesting free Nicotine Replacement Therapy (NRT) and programs in religious settings as potential strategies. CONCLUSIONS: Smoking is normalised in Arabic-speaking society and is socially acceptable. Strategies to de-normalise smoking, particularly among men, are critical. Ongoing ETS exposure of wives is concerning and suggests the need to empower women to control their exposure. There is an opportunity to create locally tailored interventions by engaging leaders in religious settings and to improve perceptions of telephone support services. SO WHAT?: Culturally appropriate strategies to de-normalise smoking for Arabic-speaking male smokers are needed together with novel approaches that incorporate families and involve community leaders.