AiDAPT: automated insulin delivery amongst pregnant women with type 1 diabetes: a multicentre randomized controlled trial - study protocol.

BACKGROUND: Pregnant women with type 1 diabetes strive for tight glucose targets (3.5-7.8 mmol/L) to minimise the risks of obstetric and neonatal complications. Despite using diabetes technologies including continuous glucose monitoring (CGM), insulin pumps and contemporary insulin analogues, most women struggle to achieve and maintain the recommended pregnancy glucose targets. This study aims to evaluate whether the use of automated closed-loop insulin delivery improves antenatal glucose levels in pregnant women with type 1 diabetes. METHODS/DESIGN: A multicentre, open label, randomized, controlled trial of pregnant women with type 1 diabetes and a HbA1c of ≥48 mmol/mol (6.5%) at pregnancy confirmation and ≤ 86 mmol/mol (10%) at randomization. Participants who provide written informed consent before 13 weeks 6 days gestation will be entered into a run-in phase to collect 96 h (24 h overnight) of CGM glucose values. Eligible participants will be randomized on a 1:1 basis to CGM (Dexcom G6) with usual insulin delivery (control) or closed-loop (intervention). The closed-loop system includes a model predictive control algorithm (CamAPS FX application), hosted on an android smartphone that communicates wirelessly with the insulin pump (Dana Diabecare RS) and CGM transmitter. Research visits and device training will be provided virtually or face-to-face in conjunction with 4-weekly antenatal clinic visits where possible. Randomization will stratify for clinic site. One hundred twenty-four participants will be recruited. This takes into account 10% attrition and 10% who experience miscarriage or pregnancy loss. Analyses will be performed according to intention to treat. The primary analysis will evaluate the change in the time spent in the target glucose range (3.5-7.8 mmol/l) between the intervention and control group from 16 weeks gestation until delivery. Secondary outcomes include overnight time in target, time above target (> 7.8 mmol/l), standard CGM metrics, HbA1c and psychosocial functioning and health economic measures. Safety outcomes include the number and severity of ketoacidosis, severe hypoglycaemia and adverse device events. DISCUSSION: This will be the largest randomized controlled trial to evaluate the impact of closed-loop insulin delivery during type 1 diabetes pregnancy. TRIAL REGISTRATION: ISRCTN 56898625 Registration Date: 10 April, 2018.

The top 10 research priorities in diabetes and pregnancy according to women, support networks and healthcare professionals.

AIMS: To undertake a Priority Setting Partnership (PSP) to establish priorities for future research in diabetes and pregnancy, according to women with experience of pregnancy, and planning pregnancy, with any type of diabetes, their support networks and healthcare professionals. METHODS: The PSP used established James Lind Alliance (JLA) methodology working with women and their support networks and healthcare professionals UK-wide. Unanswered questions about the time before, during or after pregnancy with any type of diabetes were identified using an online survey and broad-level literature search. A second survey identified a shortlist of questions for final prioritisation at an online consensus development workshop. RESULTS: There were 466 responses (32% healthcare professionals) to the initial survey, with 1161 questions, which were aggregated into 60 unanswered questions. There were 614 responses (20% healthcare professionals) to the second survey and 18 questions shortlisted for ranking at the workshop. The top 10 questions were: diabetes technology, the best test for diabetes during pregnancy, diet and lifestyle interventions for diabetes management during pregnancy, emotional and well-being needs of women with diabetes pre- to post-pregnancy, safe full-term birth, post-natal care and support needs of women, diagnosis and management late in pregnancy, prevention of other types of diabetes in women with gestational diabetes, women's labour and birth experiences and choices and improving planning pregnancy. CONCLUSIONS: These research priorities provide guidance for research funders and researchers to target research in diabetes and pregnancy that will achieve greatest value and impact.

Mandibular implant-supported overdentures: attachment systems, and number and locations of implants--Part I.

The use of dental implants in replacing missing teeth is an integral part of restorative dental treatment. Use of conventional complete dentures is associated with several problems such as lack of denture stability, support and retention. However, when mandibular complete dentures were used with two or more implants, an improvement in the patients' psychological and social well-being could be seen. There is general consensus that removable implant-supported overdentures (RISOs) with two implants should be considered as the first-choice standard of care for an edentulous mandible. This treatment option necessitates the use of attachment systems that connect the complete denture to the implant. Nevertheless, each attachment system has its inherent advantages and disadvantages, which should be considered when choosing a system. The first part of this article provides an overview on options available to restore the mandibular edentulous arch with dental implants. Different types of attachment systems, their features and drawbacks are also reviewed.

Current and future perspectives on the utility of provocative tests of anal sphincter function: A state-of-the-art summary.

BACKGROUND: The maintenance of fecal continence depends upon coordinated interactions between the pelvic floor, anorectum, and anal sphincter complex orchestrated by central and peripheral neural activities. The current techniques to objectively measure anorectal function rely on fixed diameter catheters placed inside the anal canal with a rectal balloon to obtain measurements of anal resting and squeeze function, and rectal compliance. Until recently it had not been possible to measure the distensibility of the anal canal, or in other words its ability to resist opening against an increasing pressure, which has been proposed as the main determinant of a biological sphincter's function. Anal acoustic reflectometry (AAR) and the functional lumen imaging probe (FLIP) are two novel, provocative techniques that dynamically assess the anal sphincter complex under volume-controlled distension. In doing so, both provide information on the viscoelastic properties of the anal canal and offer new insights into its function. PURPOSE: This review details the current and potential future applications of AAR and FLIP and highlights the unanswered questions relevant to these new technologies.

Rollout of Closed-Loop Technology to Pregnant Women with Type 1 Diabetes: Healthcare Professionals' Views About Potential Challenges and Solutions.

Aims: To explore healthcare professionals' views about the training and support needed to rollout closed-loop technology to pregnant women with type 1 diabetes. Methods: We interviewed (n = 19) healthcare professionals who supported pregnant women using CamAPS FX closed-loop during the Automated insulin Delivery Amongst Pregnant women with Type 1 diabetes (AiDAPT) trial. Data were analyzed descriptively. An online workshop involving (n = 15) trial team members was used to inform recommendations. Ethics approvals were obtained in conjunction with those for the wider trial. Results: Interviewees expressed enthusiasm for a national rollout of closed-loop, but anticipated various challenges, some specific to use during pregnancy. These included variations in insulin pump and continuous glucose monitoring expertise and difficulties embedding and retaining key skills, due to the relatively small numbers of pregnant women using closed-loop. Inexperienced staff also highlighted difficulties interpreting data downloads. To support rollout, interviewees recommended providing expert initial advice training, delivered by device manufacturers together with online training resources and specific checklists for different systems. They also highlighted a need for 24 h technical support, especially when supporting technology naive women after first transitioning onto closed-loop in early pregnancy. They further recommended providing case-based meetings and mentorship for inexperienced colleagues, including support interpreting data downloads. Interviewees were optimistic that if healthcare professionals received training and support, their long-term workloads could be reduced because closed-loop lessened women's need for glycemic management input, especially in later pregnancy. Conclusions: Interviewees identified challenges and opportunities to rolling-out closed-loop and provided practical suggestions to upskill inexperienced staff supporting pregnant women using closed-loop. A key priority will be to determine how best to develop mentorship services to support inexperienced staff delivering closed-loop. Clinical Trials Registration: NCT04938557.

An Evaluation of Graphical Formats for the Summary of Activities of Daily Living (ADLs).

Activities of Daily Living systems (ADLs) and the User Interface (UI) design principles used to implement them empowers the elderly to continue living a normal daily routine. The daily monitoring of activities for most Assisted Living (AL) systems demands/necessitates accurate daily user interaction, and the design principles for these systems often focus on the UI usability for the elder, not the caregiver/family member. This paper reviews Ambient Assisted Living (AAL) and ADLs UI designs and evaluates the usability of ADLs visualisation tools for caregivers. Results indicate that the UI presenting information in a bar graph format was the preferred option for respondents, as 60% chose this summarisation method over the alternative line graph UI, which had 38% of respondents selecting this format for information representation. Therefore, when designing Ambient Assisted Living (AAL) UIs, it is recommended that short periods of time are best presented in a pie graph format in combination with a bar graph format for representing extended timeline information to caregivers about their loved ones.

Spasm of the near reflex: A case report.

PURPOSE: Spasm of the near reflex (SNR) is a triad of miosis, excess accommodation and excess convergence. Primary SNR is most often functional in origin We aim to highlight the clinical features which distinguish primary convergence from other conditions with a similar presentation but more sinister underlying aetiology, for example bilateral abducens nerve palsy. OBSERVATIONS: There is a paucity of published data on SNR, in particular diagnostic criteria and treatment. We report a case of SNR of functional origin in an otherwise healthy young female and discuss the clinical features that differentiate this condition from similar conditions with underlying neurological origin. CONCLUSIONS AND IMPORTANCE: SNR is predominantly a clinical diagnosis, and often leads to patients undergoing unnecessary investigations and sometimes treatment. Recognising the salient features that differentiate it could potentially avoid this.

Localization of the equine IgG-binding domain in the fibrinogen-binding protein (FgBP) of Streptococcus equi subsp. equi.

Fibrinogen-binding protein (FgBP, also termed SeM) is a cell-wall-associated anti-phagocytic M-like protein of the equine pathogen Streptococcus equi subsp. equi, and binds fibrinogen (Fg) and IgG. FgBP binds Fg avidly through residues located at the extreme N terminus of the molecule, whereas the IgG-binding site is more centrally located between the A and B repeats. FgBP binds equine IgG4 and IgG7 subclasses through interaction with the CH2-CH3 interdomain region of IgG-Fc, and possesses overlapping Fc-binding sites with protein A and protein G. In this study, FgBP truncates containing defined internal deletions were used to identify a stretch of 14 aa (residues 335-348) critical for IgG binding. Protein chimeras consisting of the non-IgG-binding alpha-helical coiled-coil M5 protein fused to FgBP sequences were used to identify a minimal equine IgG-binding domain consisting of residues 329-360. Competition ELISA tests suggested that IgG does not compromise Fg binding and vice versa.

Antibody reactivity to alpha-enolase in mothers of children with congenital heart block.

OBJECTIVE: To evaluate the frequency of anti-alpha-enolase antibodies in the sera of mothers whose children have congenital heart block (CHB), given provocative results in which alpha-enolase, a membrane protein, was recognized by monoclonal antibodies reactive with the peptide p200 of 52 kDa Ro/SSA in a neonatal rat heart library. METHODS: An ELISA using a recombinant alpha-enolase protein was developed. Sera from 100 anti-Ro52+ CHB mothers in the Research Registry for Neonatal Lupus, 50 patients with systemic lupus erythematosus (SLE; 7 anti-Ro52+), and 48 healthy controls were tested for anti-alpha-enolase reactivity. RESULTS: There were no significant differences in the median values obtained from CHB mothers, patients with SLE, or controls at each of the dilutions tested. Only 7 (7%) at 1:100 dilution and 2 (2%) at 1:1000 dilution of 100 CHB sera were 3 standard deviations above the mean value obtained for controls. Preincubation with recombinant Ro52 did not inhibit anti-alpha-enolase reactivity. CONCLUSION: The low frequency of anti-alpha-enolase antibodies in the sera of CHB mothers and the absence of apparent cross-reactivity with Ro52 suggest that antibodies to Ro52 are not likely to mediate CHB via binding to alpha-enolase.