CONCEPTT: Continuous Glucose Monitoring in Women with Type 1 Diabetes in Pregnancy Trial: A multi-center, multi-national, randomized controlled trial - Study protocol.

BACKGROUND: Women with type 1 diabetes strive for optimal glycemic control before and during pregnancy to avoid adverse obstetric and perinatal outcomes. For most women, optimal glycemic control is challenging to achieve and maintain. The aim of this study is to determine whether the use of real-time continuous glucose monitoring (RT-CGM) will improve glycemic control in women with type 1 diabetes who are pregnant or planning pregnancy. METHODS/DESIGN: A multi-center, open label, randomized, controlled trial of women with type 1 diabetes who are either planning pregnancy with an HbA1c of 7.0 % to ≤10.0 % (53 to ≤ 86 mmol/mol) or are in early pregnancy (<13 weeks 6 days) with an HbA1c of 6.5 % to ≤10.0 % (48 to ≤ 86 mmol/mol). Participants will be randomized to either RT-CGM alongside conventional intermittent home glucose monitoring (HGM), or HGM alone. Eligible women will wear a CGM which does not display the glucose result for 6 days during the run-in phase. To be eligible for randomization, a minimum of 4 HGM measurements per day and a minimum of 96 hours total with 24 hours overnight (11 pm-7 am) of CGM glucose values are required. Those meeting these criteria are randomized to RT- CGM or HGM. A total of 324 women will be recruited (110 planning pregnancy, 214 pregnant). This takes into account 15 and 20 % attrition rates for the planning pregnancy and pregnant cohorts and will detect a clinically relevant 0.5 % difference between groups at 90 % power with 5 % significance. Randomization will stratify for type of insulin treatment (pump or multiple daily injections) and baseline HbA1c. Analyses will be performed according to intention to treat. The primary outcome is the change in glycemic control as measured by HbA1c from baseline to 24 weeks or conception in women planning pregnancy, and from baseline to 34 weeks gestation during pregnancy. Secondary outcomes include maternal hypoglycemia, CGM time in, above and below target (3.5-7.8 mmol/l), glucose variability measures, maternal and neonatal outcomes. DISCUSSION: This will be the first international multicenter randomized controlled trial to evaluate the impact of RT- CGM before and during pregnancy in women with type 1 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01788527 Registration Date: December 19, 2012

Effectiveness of prepregnancy care for women with pregestational diabetes mellitus: protocol for a systematic review of the literature and identification of a core outcomes set using a Delphi survey

BACKGROUND: Women with pregnancy complicated by pregestational diabetes experience increased rates of adverse pregnancy outcomes. Prepregnancy care is the targeted support and additional care offered to those women who are planning pregnancy and is associated with improved outcomes. However, there is significant heterogeneity in the outcomes measured and reported in studies evaluating the effects of prepregnancy care, which makes meaningful comparison difficult. The aim of this article is to present a protocol for a study to develop a Core Outcome Set (COS) for trials and other studies evaluating the effectiveness of prepregnancy care for women with pregestational diabetes mellitus. METHODS/DESIGN: This study will include a systematic review of the literature to identify outcomes that have previously been reported in studies evaluating prepregnancy care for women with pregestational diabetes. We will then prioritise these outcomes from the perspective of key stakeholders, including women with pregestational diabetes as well as clinicians, using a Delphi survey. A final consensus meeting will be held with stakeholders to review and finalise the outcomes. DISCUSSION: The expectation is that the COS will always be collected and reported in all clinical trials, audits of practice and other forms of research that involve prepregnancy care programs for women with pregestational diabetes. This will facilitate comparing and contrasting of studies and allow for combining of appropriate studies with the ultimate goal of improved patient care. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13063-015-0894-8) contains supplementary material, which is available to authorized users

Continuous glucose monitoring in pregnant women with type 1 diabetes (CONCEPTT): a multicentre international randomised controlled trial.

BACKGROUND: Pregnant women with type 1 diabetes are a high-risk population who are recommended to strive for optimal glucose control, but neonatal outcomes attributed to maternal hyperglycaemia remain suboptimal. Our aim was to examine the effectiveness of continuous glucose monitoring (CGM) on maternal glucose control and obstetric and neonatal health outcomes. METHODS: In this multicentre, open-label, randomised controlled trial, we recruited women aged 18-40 years with type 1 diabetes for a minimum of 12 months who were receiving intensive insulin therapy. Participants were pregnant (≤13 weeks and 6 days' gestation) or planning pregnancy from 31 hospitals in Canada, England, Scotland, Spain, Italy, Ireland, and the USA. We ran two trials in parallel for pregnant participants and for participants planning pregnancy. In both trials, participants were randomly assigned to either CGM in addition to capillary glucose monitoring or capillary glucose monitoring alone. Randomisation was stratified by insulin delivery (pump or injections) and baseline glycated haemoglobin (HbA1c). The primary outcome was change in HbA1c from randomisation to 34 weeks' gestation in pregnant women and to 24 weeks or conception in women planning pregnancy, and was assessed in all randomised participants with baseline assessments. Secondary outcomes included obstetric and neonatal health outcomes, assessed with all available data without imputation. This trial is registered with ClinicalTrials.gov, number NCT01788527. FINDINGS: Between March 25, 2013, and March 22, 2016, we randomly assigned 325 women (215 pregnant, 110 planning pregnancy) to capillary glucose monitoring with CGM (108 pregnant and 53 planning pregnancy) or without (107 pregnant and 57 planning pregnancy). We found a small difference in HbA1c in pregnant women using CGM (mean difference -0·19%; 95% CI -0·34 to -0·03; p=0·0207). Pregnant CGM users spent more time in target (68% vs 61%; p=0·0034) and less time hyperglycaemic (27% vs 32%; p=0·0279) than did pregnant control participants, with comparable severe hypoglycaemia episodes (18 CGM and 21 control) and time spent hypoglycaemic (3% vs 4%; p=0·10). Neonatal health outcomes were significantly improved, with lower incidence of large for gestational age (odds ratio 0·51, 95% CI 0·28 to 0·90; p=0·0210), fewer neonatal intensive care admissions lasting more than 24 h (0·48; 0·26 to 0·86; p=0·0157), fewer incidences of neonatal hypoglycaemia (0·45; 0·22 to 0·89; p=0·0250), and 1-day shorter length of hospital stay (p=0·0091). We found no apparent benefit of CGM in women planning pregnancy. Adverse events occurred in 51 (48%) of CGM participants and 43 (40%) of control participants in the pregnancy trial, and in 12 (27%) of CGM participants and 21 (37%) of control participants in the planning pregnancy trial. Serious adverse events occurred in 13 (6%) participants in the pregnancy trial (eight [7%] CGM, five [5%] control) and in three (3%) participants in the planning pregnancy trial (two [4%] CGM and one [2%] control). The most common adverse events were skin reactions occurring in 49 (48%) of 103 CGM participants and eight (8%) of 104 control participants during pregnancy and in 23 (44%) of 52 CGM participants and five (9%) of 57 control participants in the planning pregnancy trial. The most common serious adverse events were gastrointestinal (nausea and vomiting in four participants during pregnancy and three participants planning pregnancy). INTERPRETATION: Use of CGM during pregnancy in patients with type 1 diabetes is associated with improved neonatal outcomes, which are likely to be attributed to reduced exposure to maternal hyperglycaemia. CGM should be offered to all pregnant women with type 1 diabetes using intensive insulin therapy. This study is the first to indicate potential for improvements in non-glycaemic health outcomes from CGM use. FUNDING: Juvenile Diabetes Research Foundation, Canadian Clinical Trials Network, and National Institute for Health Research

IMUNIZAÇÃO EM USUÁRIOS DE AGENTES BIOLÓGICOS: SERÁ QUE ESTAMOS VACINANDO ADEQUADAMENTE? AVALIAÇÃO EM AMBULATÓRIO DE ALTA COMPLEXIDADE

Introdução/Objetivo: O aumento de agentes biológicos imunossupressores dobrou o risco de infecções imunopreveníveis. Níveis subótimos de vacinação são realidade para esta população. Avaliar níveis vacinais em pacientes usando biológicos imunossupressores e suas características epidemiológicas mostra-se relevante, portanto. Métodos: Estudo descritivo transversal, incluindo pacientes ambulatoriais de hospital terciário em 2022. Usados bancos de dados dos sites governamentais SAÚDE e VACIVIDA, dos prontuários e questionários feitos em ligações aos pacientes. Resultados: Foram incluídos 142 pacientes inicialmente e do total 53.5% estavam acima de 60 anos. Mulheres foram prevalentes, mas não houve associação significativa entre gênero e vacinação. Vacina contra covid-19 estava completa em 51.5%. As demais taxas foram: Vacina dT 35.7%; hepatite B 32.9%; pneumocócica 23 27.1%; influenza 20%; febre amarela 15.7%; meningocócica 14.3%; hepatite A 5.7%; pneumocócica 13 5.7%; hemófilos B nenhum paciente; Imunidade contra HBV com proteção (antiHbs >10) 7.6%. Algumas condições favoreceram a vacinação neste estudo: Ter doença inflamatória intestinal (p: 0,001); esclerose múltipla (p: 0,003); ser acompanhado nas especialidades gastroenterologia (p: 0,001) e reumatologia (p: 0,013). Ser acompanhado na gastroenterologia reduziu a chance de ser encaminhado para vacinação (RR 0,1 IC 0,0-0,8 p: 0,021). O questionário aplicado mostrou pouco medo para vacinar (7.5%), presença significante de carteira de vacinação (64.2%) encaminhamento para vacinação pelo médico de origem (52.8%) e ótimo encaminhamento para vacina contra COVID-19 (100%). Conclusão: Ao considerar o fornecimento gratuito de imunizantes pelo Ministério da Saúde e a facilidade de realização das vacinas na própria instituição, medidas in loco para melhoria dos dados devem ser discutidas com cada equipe

Adjustment of open-loop settings to improve closed-loop results in type 1 diabetes: A multicenter randomized trial

CONTEXT: Closed-loop control (CLC) relies on an individual's open-loop insulin pump settings to initialize the system. Optimizing open-loop settings before using CLC usually requires significant time and effort. OBJECTIVE: The objective was to investigate the effects of a one-time algorithmic adjustment of basal rate and insulin to carbohydrate ratio open-loop settings on the performance of CLC. DESIGN: This study reports a multicenter, outpatient, randomized, crossover clinical trial. PATIENTS: Thirty-seven adults with type 1 diabetes were enrolled at three clinical sites. INTERVENTIONS: Each subject's insulin pump settings were subject to a one-time algorithmic adjustment based on 1 week of open-loop (i.e., home care) data collection. Subjects then underwent two 27-hour periods of CLC in random order with either unchanged (control) or algorithmic adjusted basal rate and carbohydrate ratio settings (adjusted) used to initialize the zone-model predictive control artificial pancreas controller. Subject's followed their usual meal-plan and had an unannounced exercise session. MAIN OUTCOMES AND MEASURES: Time in the glucose range was 80–140 mg/dL, compared between both arms. RESULTS: Thirty-two subjects completed the protocol. Median time in CLC was 25.3 hours. The median time in the 80–140 mg/dl range was similar in both groups (39.7% control, 44.2% adjusted). Subjects in both arms of CLC showed minimal time spent less than 70 mg/dl (median 1.34% and 1.37%, respectively). There were no significant differences more than 140 mg/dL. CONCLUSIONS: A one-time algorithmic adjustment of open-loop settings did not alter glucose control in a relatively short duration outpatient closed-loop study. The CLC system proved very robust and adaptable, with minimal (<2%) time spent in the hypoglycemic range in either arm

<strong>At-home use of a pregnancy-specific Zone-MPC closed-loop system for pregnancies complicated by type 1 diabetes: a single arm, observational multicenter study</strong>

   OBJECTIVE: There are no commercially available hybrid closed-loop insulin delivery systems customized to achieve pregnancy-specific glucose targets in the United States. This study aimed to evaluate the feasibility and performance of at-home use of a zone model predictive controller based closed-loop insulin delivery system customized for pregnancies complicated by type 1 diabetes (CLC-P). RESEARCH DESIGN AND Methods: Pregnant women with type 1 diabetes using insulin pumps were enrolled in the second or early third trimester. After study sensor wear collecting run-in data on personal pump therapy and two days of supervised training, participants used CLC-P targeting 80-110 mg/dL during the day and 80-100 mg/dL overnight running on an unlocked smartphone at home. Meals and activities were unrestricted throughout the trial. The primary outcome was the continuous glucose monitoring percentage of time in the target range 63-140 mg/dL versus run-in. Results: Ten participants (HbA1c 5.8±0.6%) used the system from mean gestational age of 23.7±3.5 weeks. Mean percentage time in range increased 14.1 percentage points, equivalent to 3.4 hours per day, compared to run-in (run-in: 64.5±16.3% versus CLC-P: 78.6±9.2%, P=0.002). During CLC-P use, there was significant decrease in both time over 140 mg/dL (P=0.033) and the hypoglycemic ranges of less than 63 mg/dL and 54 mg/dL (P=0.037 for both). Nine participants exceeded consensus goals of above 70% time in range during CLC-P use.  ConclusionS: The results show that the extended use of CLC-P at home until delivery is feasible. Larger, randomized studies are indicated to further evaluate system efficacy and pregnancy outcomes.</p