Pregnancy and COVID-19.

There are many unknowns for pregnant women during the coronavirus disease 2019 (COVID-19) pandemic. Clinical experience of pregnancies complicated with infection by other coronaviruses e.g., Severe Acute Respiratory Syndrome (SARS) and Middle Eastern Respiratory Syndrome, has led to pregnant woman being considered potentially vulnerable to severe SARS-CoV-2 infection. Physiological changes during pregnancy have a significant impact on the immune system, respiratory system, cardiovascular function, and coagulation. These may have positive or negative effects on COVID-19 disease progression. The impact of SARS-CoV-2 in pregnancy remains to be determined, and a concerted, global effort is required to determine the effects on implantation, fetal growth and development, labor, and neonatal health. Asymptomatic infection presents a further challenge regarding service provision, prevention, and management. Besides the direct impacts of the disease, a plethora of indirect consequences of the pandemic adversely affect maternal health, including reduced access to reproductive health services, increased mental health strain, and increased socioeconomic deprivation. In this review, we explore the current knowledge of COVID-19 in pregnancy and highlight areas for further research to minimize its impact for women and their children.

Automated Insulin Delivery in Women with Pregnancy Complicated by Type 1 Diabetes.

BACKGROUND: Hybrid closed-loop insulin therapy has shown promise for management of type 1 diabetes during pregnancy; however, its efficacy is unclear. METHODS: In this multicenter, controlled trial, we randomly assigned pregnant women with type 1 diabetes and a glycated hemoglobin level of at least 6.5% at nine sites in the United Kingdom to receive standard insulin therapy or hybrid closed-loop therapy, with both groups using continuous glucose monitoring. The primary outcome was the percentage of time in the pregnancy-specific target glucose range (63 to 140 mg per deciliter [3.5 to 7.8 mmol per liter]) as measured by continuous glucose monitoring from 16 weeks' gestation until delivery. Analyses were performed according to the intention-to-treat principle. Key secondary outcomes were the percentage of time spent in a hyperglycemic state (glucose level >140 mg per deciliter), overnight time in the target range, the glycated hemoglobin level, and safety events. RESULTS: A total of 124 participants with a mean (±SD) age of 31.1±5.3 years and a mean baseline glycated hemoglobin level of 7.7±1.2% underwent randomization. The mean percentage of time that the maternal glucose level was in the target range was 68.2±10.5% in the closed-loop group and 55.6±12.5% in the standard-care group (mean adjusted difference, 10.5 percentage points; 95% confidence interval [CI], 7.0 to 14.0; P<0.001). Results for the secondary outcomes were consistent with those of the primary outcome; participants in the closed-loop group spent less time in a hyperglycemic state than those in the standard-care group (difference, -10.2 percentage points; 95% CI, -13.8 to -6.6); had more overnight time in the target range (difference, 12.3 percentage points; 95% CI, 8.3 to 16.2), and had lower glycated hemoglobin levels (difference, -0.31 percentage points; 95% CI, -0.50 to -0.12). Little time was spent in a hypoglycemic state. No unanticipated safety problems associated with the use of closed-loop therapy during pregnancy occurred (6 instances of severe hypoglycemia, vs. 5 in the standard-care group; 1 instance of diabetic ketoacidosis in each group; and 12 device-related adverse events in the closed-loop group, 7 related to closed-loop therapy). CONCLUSIONS: Hybrid closed-loop therapy significantly improved maternal glycemic control during pregnancy complicated by type 1 diabetes. (Funded by the Efficacy and Mechanism Evaluation Program; AiDAPT ISRCTN Registry number, ISRCTN56898625.).

Plasma steroid concentrations reflect acute disease severity and normalise during recovery in people hospitalised with COVID-19.

OBJECTIVE: Endocrine systems are disrupted in acute illness, and symptoms reported following coronavirus disease 2019 (COVID-19) are similar to those found with clinical hormone deficiencies. We hypothesised that people with severe acute COVID-19 and with post-COVID symptoms have glucocorticoid and sex hormone deficiencies. DESIGN/PATIENTS: Samples were obtained for analysis from two UK multicentre cohorts during hospitalisation with COVID-19 (International Severe Acute Respiratory Infection Consortium/World Health Organisation [WHO] Clinical Characterization Protocol for Severe Emerging Infections in the UK study), and at follow-up 5 months after hospitalisation (Post-hospitalisation COVID-19 study). MEASUREMENTS: Plasma steroids were quantified by liquid chromatography-mass spectrometry. Steroid concentrations were compared against disease severity (WHO ordinal scale) and validated symptom scores. Data are presented as geometric mean (SD). RESULTS: In the acute cohort (n = 239, 66.5% male), plasma cortisol concentration increased with disease severity (cortisol 753.3 [1.6] vs. 429.2 [1.7] nmol/L in fatal vs. least severe, p < .001). In males, testosterone concentrations decreased with severity (testosterone 1.2 [2.2] vs. 6.9 [1.9] nmol/L in fatal vs. least severe, p < .001). In the follow-up cohort (n = 198, 62.1% male, 68.9% ongoing symptoms, 165 [121-192] days postdischarge), plasma cortisol concentrations (275.6 [1.5] nmol/L) did not differ with in-hospital severity, perception of recovery, or patient-reported symptoms. Male testosterone concentrations (12.6 [1.5] nmol/L) were not related to in-hospital severity, perception of recovery or symptom scores. CONCLUSIONS: Circulating glucocorticoids in patients hospitalised with COVID-19 reflect acute illness, with a marked rise in cortisol and fall in male testosterone. These findings are not observed 5 months from discharge. The lack of association between hormone concentrations and common post-COVID symptoms suggests steroid insufficiency does not play a causal role in this condition.

Impact of COVID-19 on gestational diabetes pregnancy outcomes in the UK: A multicentre retrospective cohort study.

OBJECTIVE: To determine the impact of implementing emergency care pathway(s) for screening, diagnosing and managing women with gestational diabetes (GDM) during COVID-19. DESIGN: Retrospective multicentre cohort. SETTING: Nine National Health Service (NHS) Hospital Trusts/Health boards in England and Scotland. POPULATION: 4915 women with GDM pre-pandemic (1 April 2018 to 31 March 2020), and 3467 women with GDM during the pandemic (1 May 2020 to 31 March 2021). METHODS: We examined clinical outcomes for women with GDM prior to and during the pandemic following changes in screening methods, diagnostic testing, glucose thresholds and introduction of virtual care for monitoring of antenatal glycaemia. MAIN OUTCOME MEASURES: Intervention at birth, perinatal mortality, large-for-gestational-age infants and neonatal unit admission. RESULTS: The new diagnostic criteria more often identified GDM women who were multiparous, had higher body mass index (BMI) and greater deprivation, and less frequently had previous GDM (all p < 0.05). During COVID, these women had no differences in the key outcome measures. Of the women, 3% were identified with pre-existing diabetes at antenatal booking. Where OGTT continued during COVID, but virtual care was introduced, outcomes were also similar pre- and during the pandemic. CONCLUSIONS: Using HbA1c and fasting glucose identified a higher risk GDM population during the pandemic but this had minimal impact on pregnancy outcomes. The high prevalence of undiagnosed pre-existing diabetes suggests that women with GDM risk factors should be offered HbA1c screening in early pregnancy.

Socioeconomic characteristics and postoperative outcomes of patients undergoing prenatal vs. postnatal repair of myelomeningoceles.

PURPOSE: To investigate differences in sociodemographic characteristics and short-term outcomes between patients undergoing prenatal versus postnatal myelomeningocele repair. METHODS: Patients who underwent myelomeningocele repair at our institution were stratified based on prenatal or postnatal timing of repair. Baseline characteristics and outcomes were compared. Multivariate analysis was performed to identify whether prenatal repair was a predictor of outcomes independent of socioeconomic measures. RESULTS: 49 patients underwent postnatal repair, and 30 underwent prenatal repair. Patients who underwent prenatal repair were more likely to have private insurance (73.3% vs. 42.9%, p = 0.03) and live farther from the hospital where they received their repair (251.5 ± 447.4 vs. 72.5 ± 205.6 miles, p = 0.02). Patients who underwent prenatal repair had shorter hospital stays (14.3 ± 22.7 days vs. 25.3 ± 20.1 days, p = 0.03), fewer complications (13.8% vs. 42.9%, p = 0.01), fewer 30-day ED visits (0.0% vs. 34.0%, p < 0.001), lower CSF diversion rates (13.8% vs. 38.8%, p = 0.02), and better functional status at 3-months (13.3% vs. 57.1% delayed, p = 0.009), 6-months (20.0% vs. 56.7% delayed, p = 0.03), and 1-year (29.4% vs. 70.6% delayed, p = 0.007). On multivariate analysis, prenatal repair was an independent predictor of inpatient complication (OR(95%CI): 0.19(0.05-0.75), p = 0.02) and 3-month (OR(95%CI): 0.14(0.03-0.80) p = 0.03), 6-month (OR(95%CI): 0.12(0.02-0.73), p = 0.02), and 1-year (OR(95%CI): 0.19(0.05-0.80), p = 0.02) functional status. CONCLUSION: Prenatal repair for myelomeningocele is associated with better outcomes and developmental functional status. However, patients receiving prenatal closure are more likely to have private health insurance and live farther from the hospital, suggesting potential barriers to care.

Vasospasm and subsequent stroke from paraneoplastic syndrome in a pediatric patient with an intracranial mature teratoma: a case report.

Teratomas account for 18-20% of all intracranial germ cell tumors and mostly occur in the pineal region with only a few cases of pediatric sellar and suprasellar teratomas described in the literature. Here, we present a case of a child with an intracranial mature teratoma with pancreatic features causing vasospasm and subsequent stroke, found to be positive for CDKN2A-an independent variant associated with malignancy and small vessel disease leading to stroke.

Healthcare professionals' views about how pregnant women can benefit from using a closed-loop system: Qualitative study.

BACKGROUND: Interest is growing in how closed-loop systems can support attainment of within-target glucose levels amongst pregnant women with type 1 diabetes. We explored healthcare professionals' views about how, and why, pregnant women benefitted from using the CamAPS FX system during the AiDAPT trial. METHODS: We interviewed 19 healthcare professionals who supported women using closed-loop during the trial. Our analysis focused on identifying descriptive and analytical themes relevant to clinical practice. RESULTS: Healthcare professionals highlighted clinical and quality-of-life benefits to using closed-loop in pregnancy; albeit, they attributed some of these to the continuous glucose monitoring component. They emphasised that the closed-loop was not a panacea and that, to gain maximum benefit, an effective collaboration between themselves, the woman and the closed-loop was needed. Optimal performance of the technology, as they further noted, also required women to interact with the system sufficiently, but not excessively; a requirement that they felt some women had found challenging. Even where healthcare professionals felt that this balance was not achieved, they suggested that women had still benefitted from using the system. Healthcare professionals reported difficulties predicting how specific women would engage with the technology. In light of their trial experiences, healthcare professionals favoured an inclusive approach to closed-loop rollout in routine clinical care. CONCLUSIONS: Healthcare professionals recommended that closed-loop systems be offered to all pregnant women with type 1 diabetes in the future. Presenting closed-loop systems to pregnant women and healthcare teams as one pillar of a three-party collaboration may help promote optimal use.

Non-invasive imaging of functional pancreatic islet beta-cell mass in people with type 1 diabetes mellitus.

AIMS: To investigate whether manganese-enhanced magnetic resonance imaging can assess functional pancreatic beta-cell mass in people with type 1 diabetes mellitus. METHODS: In a prospective case-control study, 20 people with type 1 diabetes mellitus (10 with low (≥50 pmol/L) and 10 with very low (<50 pmol/L) C-peptide concentrations) and 15 healthy volunteers underwent manganese-enhanced magnetic resonance imaging of the pancreas following an oral glucose load. Scan-rescan reproducibility was performed in 10 participants. RESULTS: Mean pancreatic manganese uptake was 31 ± 6 mL/100 g of tissue/min in healthy volunteers (median 32 [interquartile range 23-36] years, 6 women), falling to 23 ± 4 and 13 ± 5 mL/100 g of tissue/min (p ≤ 0.002 for both) in people with type1 diabetes mellitus (52 [44-61] years, 6 women) and low or very low plasma C-peptide concentrations respectively. Pancreatic manganese uptake correlated strongly with plasma C-peptide concentrations in people with type1 diabetes mellitus (r = 0.73, p < 0.001) but not in healthy volunteers (r = -0.054, p = 0.880). There were no statistically significant correlations between manganese uptake and age, body-mass index, or glycated haemoglobin. There was strong intra-observer (mean difference: 0.31 (limits of agreement -1.42 to 2.05) mL/100 g of tissue/min; intra-class correlation, ICC = 0.99), inter-observer (-1.23 (-5.74 to 3.27) mL/100 g of tissue/min; ICC = 0.85) and scan-rescan (-0.72 (-2.9 to 1.6) mL/100 g of tissue/min; ICC = 0.96) agreement for pancreatic manganese uptake. CONCLUSIONS: Manganese-enhanced magnetic resonance imaging provides a potential reproducible non-invasive measure of functional beta-cell mass in people with type 1 diabetes mellitus. This holds major promise for investigating type 1 diabetes, monitoring disease progression and assessing novel immunomodulatory interventions.

Surgical outcomes of open and laser interstitial thermal therapy approaches for corpus callosotomy in pediatric epilepsy.

OBJECTIVE: Corpus callosotomy (CC) is a palliative surgical intervention for patients with medically refractory epilepsy that has evolved in recent years to include a less-invasive alternative with the use of laser interstitial thermal therapy (LITT). LITT works by heating a stereotactically placed laser fiber to ablative temperatures under real-time magnetic resonance imaging (MRI) thermometry. This study aims to (1) describe the surgical outcomes of CC in a large cohort of children with medically refractory epilepsy, (2) compare anterior and complete CC, and (3) review LITT as a surgical alternative to open craniotomy for CC. METHODS: This retrospective cohort study included 103 patients <21 years of age with at least 1 year follow-up at a single institution between 2003 and 2021. Surgical outcomes and the comparative effectiveness of anterior vs complete and open versus LITT surgical approaches were assessed. RESULTS: CC was the most common surgical disconnection (65%, n = 67) followed by anterior two-thirds (35%, n = 36), with a portion proceeding to posterior completion (28%, n = 10). The overall surgical complication rate was 6% (n = 6/103). Open craniotomy was the most common approach (87%, n = 90), with LITT used increasingly in recent years (13%, n = 13). Compared to open, LITT had shorter hospital stay (3 days [interquartile range (IQR) 2-5] vs 5 days [IQR 3-7]; p < .05). Modified Engel class I, II, III, and IV outcomes at last follow-up were 19.8% (n = 17/86), 19.8% (n = 17/86), 40.2% (n = 35/86), and 19.8% (n = 17/86). Of the 70 patients with preoperative drop seizures, 75% resolved postoperatively (n = 52/69). SIGNIFICANCE: No significant differences in seizure outcome between patients who underwent only anterior CC and complete CC were observed. LITT is a less-invasive surgical alternative to open craniotomy for CC, associated with similar seizure outcomes, lower blood loss, shorter hospital stays, and lower complication rates, but with longer operative times, when compared with the open craniotomy approach.

Positive maternal mental health during pregnancy and mental and behavioral disorders in children: A prospective pregnancy cohort study.

BACKGROUND: The role of positive maternal mental health during pregnancy in child mental health remains largely unknown. We investigated whether positive maternal mental health during pregnancy is associated with lower hazards of mental and behavioral disorders in children and mitigates the adverse effects of negative maternal mental health. METHODS: Among 3,378 mother-child dyads of the Prediction and Prevention of Preeclampsia and Intrauterine Growth Restriction study, mothers reported their positive mental health biweekly throughout pregnancy with the Positive and Negative Affect Schedule, the Spielberger State Anxiety Inventory Curiosity scale, and a visual analogue scale for social support, and negative mental health with the Center for Epidemiologic Studies Depression Scale. We extracted data on their mental and behavioral disorder diagnoses from a nationwide medical register. This register provided data on their children's mental and behavioral disorder diagnoses as well, from birth until 8.4-12.8 (Median = 10.2, Interquartile Range 9.7-10.8) years of age. RESULTS: A positive maternal mental health composite score during pregnancy was associated with a lower hazard of any mental and behavioral disorder among all children [Hazard Ratio (HR) = 0.79, 95% Confidence Interval (CI) 0.71 - 0.87] and among children of mothers experiencing clinically relevant depressive symptoms during pregnancy [HR = 0.80, 95%CI 0.64 - 1.00] and/or mental and behavioral disorders before or during pregnancy [HR = 0.69, 95%CI 0.55-0.86]. These associations were independent of covariates. CONCLUSIONS: Children whose mothers had more positive mental health during pregnancy were less likely to develop mental and behavioral disorders. Protective effects were seen also among children of mothers facing mental health adversities before or during pregnancy.

Transitioning care for adolescents with spina bifida in the US: challenges for management.

Open spina bifida (OSB) is a common neural tube defect. Medical and surgical care involves addressing the baseline orthopedic, urologic, and neurological dysfunction as well as the changes or declines that may occur as the patient ages. Given the complexity of this disease, coordinated, multidisciplinary care involving specialists in neurosurgery, orthopedics, urology, rehabilitation and physical medicine, pediatrics, and psychology is necessary to establish and optimize baseline function. Traditionally in the US, pediatric multispecialty spina bifida clinics have provided the patient with a coordinated medical support system. Unfortunately, this coordinated, medical home has been difficult to establish during the transition from pediatric to adult care. Medical professionals must have a strong understanding of OSB to properly manage the disease and detect and prevent associated complications. In this manuscript, we (1) describe the changing needs and challenges of people living with OSB over a lifespan, (2) delineate current practices in the transition of care for people with OSB from childhood to adulthood, and (3) provide recommendations for best practices in navigating the transition process for clinicians who provide care for those afflicted with this most complex congenital abnormality of the nervous system compatible with long term survival.

Outcomes of the early endoscopic-assisted suturectomy for treatment of multisuture craniosynostosis.

To present the outcomes and adverse events associated with the endoscopic-assisted, minimally invasive suturectomy in patients with multisuture synostosis. This retrospective cohort study included children < 65 days of age who underwent endoscopic-assisted suturectomy (EAS) for multisuture craniosynostosis at a single tertiary referral center from 2013 to 2021. The primary outcome was calvarial expansion, and the secondary outcome was adverse events. The pre- and post-operative 3-dimensional brain computed tomography (CT) scan was used to calculate the intracranial volume and cephalic index. During a period of 2 years, 10 infants (10-64 days) diagnosed with multisuture synostosis underwent single-stage EAS of every affected suture in our center. The coronal suture was the most prevalent involved suture among our cases. The mean age and weight of the patients were 39 ± 17.5 days and 4.39 ± 0.8 kg, respectively. The surgical procedure took 42 ± 17.4 min of time and caused 46 ± 25.4 mL of bleeding on average. Ninety percent of the operations were considered successful (n = 9) regarding calvarial expansion. There were two complications, one requiring an open vault surgery and one repairing a leptomeningeal cyst. In the eight patients who did not necessitate further interventions, the mean pre-operative intracranial volume was 643.3 ± 189.4 cm3. The follow-up results within the average of 38.9 months after surgery showed that as age increases, the intracranial volume also increased significantly (R: 0.6, P < 0.0001), which suggests continued skull growth in patients who underwent EAS. With the low rate of intra- or post-operative complications and promising results on revising the restricted skull sutures, EAS seems both a safe and effective therapeutic modality in patients with multisuture synostosis, especially if completed in the first months after birth.

Exercise Intensity Among Older Adults Participating From Home in Remotely Delivered EnhanceFitness.

We aimed to examine exercise intensity among older adults participating from home in remotely delivered EnhanceFitness (Tele-EF). Exercise intensity was assessed through Fitbit-measured heart rate and the Borg 10-point rating of perceived exertion over 1 week of a 16-week exercise program. Outcomes included mean minutes spent at or above the heart rate reserve calculated threshold for moderate intensity and mean rating of perceived exertion. Pearson and Spearman rank correlations were used to examine associations between baseline characteristics with exercise intensity. During the 60-min classes, the 55 participants achieved moderate intensity for a mean of 21.0 min (SD = 13.5) and had a mean rating of perceived exertion of 4.9 (SD = 1.2). There were no significant associations between baseline characteristics and exercise intensity. Older adults can achieve sustained moderate-intensity exercise during Tele-EF supervised classes. Baseline physical function, physical activity, and other health characteristics did not limit ability to exercise at a moderate intensity, though further investigation is warranted.

Vegan and vegetarian males and females have higher orthorexic traits than omnivores, and are motivated in their food choice by factors including ethics and weight control.

BACKGROUND: Evidence associating plant-based diets with the proposed 'obsessively healthy eating' eating disorder, orthorexia nervosa, has mostly focused on females. Diet motivations have seldom been assessed. AIM: To compare orthorexic tendencies between vegans/vegetarians and omnivores of both sexes, and reasons behind food choice with an English-validated Food Choice Questionnaire. METHODS: A cross-sectional survey of 444 males and females were recruited via social media, email, and Amazon MTurk; to investigate eating patterns, orthorexic tendencies using the ORTO-15 questionnaire, and eating motivations using the Food Choice Questionnaire. RESULTS: Over half of the participants were male (53.4%), younger adults (mean ± SD 37.2 ± 11.2 years), and mostly from the United States (89%). Vegan and vegetarian eating habits were reported by 15.8% of people. Vegans/vegetarians had significantly higher orthorexic tendencies than omnivores, and chose food significantly more often for Weight Control, Ethical Concern, Natural Content, and Mood reasons. People with greater orthorexic tendencies (ORTO-15 score<35) chose food significantly more often for Weight Control and Ethical Concern reasons than those with less orthorexic tendencies (ORTO-15 score 35+). CONCLUSION: This study's results are in line with the majority of the evidence that shows an association between vegan/vegetarian diets and orthorexic tendencies, but strengthens the evidence base by including more male participants. Additionally, this is the first study to use an English-validated motivation-based questionnaire that explored diet motivators in vegans/vegetarians compared to omnivories, and in those with orthorexic tendencies vs. those without orthorexic tendencies.

'Food can help numb the pain': A mixed methods exploration of disordered eating, shame and self-compassion in an international community sample of men and women.

Background: Research into disordered eating (DE), shame and self-compassion (SC) has poorly represented men, general populations and non-Western communities. Aim: To explore associations between these variables in an international community sample of men and women. Methods: An online exploratory sequential mixed methods cross-sectional survey assessed levels of (quantitative Phase 1) and perceptions of (qualitative Phase 2) eating behaviours, external shame and body image shame (BIS) and SC. Results: Phase 1: Nearly 60% of our 142 survey participants were male (82/142) and about one-third were from India (43/142). About one-third of people (41/142) had a high-level concern regarding dieting, body weight, or eating (based on Eating Attitudes Test scores), and they had significantly higher levels of external shame, BIS and (SC-related) self-judgement and overidentification - compared to the 101/142 participants with low concern. Men had healthier levels of study outcomes than women. Phase 2: Four key themes were identified using inductive thematic analysis of the responses of 55 survey participants: (T1) DE as a Psychological Issue, (T2) DE as a Social Issue, (T3) The Vicious Cycle of Shame and (T4) Seeking Help. Conclusion: In participants in Phase 1 of our study - who were mostly male - DE behaviours were related to more external shame and body image-specific shame, and to less SC. Men had healthier levels of study variables than women. In Phase 2, participants talked about a vicious cycle of pathological eating and shame.

Associations between parental type 2 diabetes risk and offspring birthweight and placental weight: a survival analysis using the Walker cohort.

AIMS/HYPOTHESIS: Low birthweight (BW) is associated with the development of type 2 diabetes. Genome-wide analyses have identified a strong genetic component to this association, with many BW-associated loci also involved in glucose metabolism. We hypothesised that offspring BW and placental weight (PW) are correlated with parental type 2 diabetes risk, reflecting the inheritance of diabetes risk alleles that also influence fetal growth. METHODS: The Walker cohort, a collection of birth records from Dundee, Scotland, from the 1950s and the 1960s was used to test this hypothesis by linking BW and PW measurements to parental health outcomes. Using data from SCI-Diabetes and the national death registry, we obtained health records for over 20,000 Walker parents. We performed Fine-Gray survival analyses of parental type 2 diabetes risk with competing risk of death, and Cox regression analyses of risk of death, independently in the maternal and paternal datasets, modelled by offspring BW and PW. RESULTS: We found significant associations between increased paternal type 2 diabetes risk and reduced offspring BW (subdistribution hazard ratio [SHR] 0.92 [95% CI 0.87, 0.98]) and PW (SHR 0.87 [95% CI 0.81, 0.94]). The association of maternal type 2 diabetes risk with offspring BW or PW was not significant. Lower offspring BW was also associated with increased risk of death in both mothers (HR 0.91 [95% CI 0.89, 0.94]) and fathers (HR 0.95 [95% CI 0.92, 0.98]), and higher offspring PW was associated with increased maternal mortality risk (HR 1.08 [95% CI 1.04, 1.13]) when adjusted for BW. CONCLUSIONS/INTERPRETATION: We identified associations between offspring BW and reduced paternal type 2 diabetes risk, most likely resulting from the independent effects of common type 2 diabetes susceptibility alleles on fetal growth, as described by the fetal insulin hypothesis. Moreover, we identified novel associations between offspring PW and reduced paternal type 2 diabetes risk, a relationship that might also be caused by the inheritance of diabetes predisposition variants. We found differing associations between offspring BW and PW and parental risk of death. These results provide novel epidemiological support for the use of offspring BW and PW as predictors for future risk of type 2 diabetes and death in mothers and fathers.

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.

Conditional Vasospasm-Free Survival Following Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Following aneurysmal subarachnoid hemorrhage (SAH), patients are monitored closely for vasospasm in the intensive care unit. Conditional vasospasm-free survival describes the risk of future vasospasm as a function of time elapsed without vasospasm. Conditional survival has not been applied to this clinical scenario but could improve patient counseling and intensive care unit use. The objective of this study was to characterize conditional vasospasm-free survival following SAH. METHODS: This was a single institution, retrospective cohort study of patients treated for aneurysmal SAH between 1/1/2000-6/1/2020. The primary outcome was the development of vasospasm defined by the first instance of either radiographic vasospasm on computed tomography angiography, Lindegaard Index > 3.0 by transcranial doppler ultrasonography, or vasospasm-specific intraarterial therapy. Multivariable Cox regression was performed, and conditional vasospasm-free survival curves were constructed. RESULTS: A total of 528 patients were treated for aneurysmal SAH and 309 (58.5%) developed vasospasm. Conditional survival curves suggest patients who survive to postbleed day 10 without vasospasm have a nearly 90% chance of being discharged without vasospasm. The median onset of vasospasm was postbleed day 6. Age more than 50 years was associated with a lower risk (hazard ratio [HR] = .76; 95% confidence interval [CI] 0.64-0.91; p < 0.001). Higher initial systolic blood pressure (HR = 1.18; 95% CI 1.046-1.350; p = .008), Hunt-Hess grades 4 or 5 (HR = 1.304; 95% CI 1.014-1.676), and modified Fisher scale score of 4 (HR = 1.808; 95% CI 1.198-2.728) were associated with higher vasospasm than the respective lower grades. CONCLUSION: Conditional survival provides a useful framework for counseling patients and making decisions around vasospasm risk for patients with aneurysmal SAH, while risk factor-stratified plots facilitate a patient-centric, evidence-based approach to these conversations and decisions.

Comparison of free-living physical activity data obtained from a Fitbit Zip, the Apple iPhone Health app and a modified Bouchard Activity Record.

ISSUE ADDRESSED: Physical activity tracking devices have potential to improve public health, but their data needs to be reliable. No study has compared movement data between the Fitbit Zip, Apple iPhone Health app and physical activity records in a community setting over 10 days. METHODS: University students aged 18+ years wore both a Fitbit Zip and an iPhone at/near their right waist and completed a modified Bouchard Activity Record (BAR) for 10 days in a free-living setting. Comparisons were made between the Fitbit Zip and iPhone for the number of steps and the distance travelled and between the Fitbit Zip and BAR for the minutes of activity in three different intensities. RESULTS: Eighteen students provided sufficient data for inclusion. There were strong correlations between steps per day (r = .87) and distance travelled (r = .88) between the Fitbit Zips and iPhones. However, the Fitbit Zip measured significantly more steps per day (mean 8437 vs 7303; P ≤ .001) and greater distances (mean 5.9 vs 4.9; P ≤ .001) than the iPhone. Correlations between the Fitbit Zips and the BARs were moderate for minutes of total (r = .51) and light (r = .40) activity and weak for moderate/fairly active (r = .20) and vigorous/very active (r = .25). CONCLUSIONS: There were strong correlations between the physical activity data measured by Fitbit Zips and iPhones, but the iPhone Health app significantly underestimated the number of steps per day taken and the distance travelled when compared to the Fitbit Zip. SO WHAT?: Understanding the comparability of accelerometer devices provides useful information for future pragmatic physical activity measurement.