Diabetic autonomic neuropathy does not impede improvement in hypoglycaemia awareness in adults: Sub-study results from the HypoCOMPaSS trial.

AIMS: Impaired awareness of hypoglycaemia (IAH) increases the risk of severe hypoglycaemia in people with type 1 diabetes mellitus (T1DM). IAH can be reversed through meticulous avoidance of hypoglycaemia. Diabetic autonomic neuropathy (DAN) has been proposed as an underlying mechanism contributing to IAH; however, data are inconsistent. The aim of this study was to examine the effects of cardiac autonomic neuropathy (CAN) on IAH reversibility inT1DM. METHODS: Participants with T1DM and IAH (Gold score ≥4) recruited to the HypoCOMPaSS (24-week 2 × 2 factorial randomised controlled) trial were included. All underwent screening for cardiac autonomic function testing at baseline and received comparable education and support aimed at avoiding hypoglycaemia and improving hypoglycaemia awareness. Definite CAN was defined as the presence of ≥2 abnormal cardiac reflex tests. Participants were grouped according to their CAN status, and changes in Gold score were compared. RESULTS: Eighty-three participants (52 women [62.7%]) were included with mean age (SD) of 48 (12) years and mean HbA1c of 66 (13) mmol/mol (8.2 [3.3] %). The mean duration of T1DM was 29 (13) years. The prevalence of CAN was low with 5/83 (6%) participants having definite autonomic neuropathy with 11 (13%) classified with possible/early neuropathy. All participants, regardless of the autonomic function status, showed a mean improvement in Gold score of ≥1 (mean improvement -1.2 [95% CI -0.8, -1.6]; p < 0.001). CONCLUSIONS: IAH can be improved in people with T1DM, and a long duration of disease, with and without cardiac autonomic dysfunction. These data suggest that CAN is not a prime driver for modulating IAH reversibility.

Becoming what you are seeking: Building Relational Self-Awareness in emerging adults.

Emerging adults are attempting to navigate a rapidly shifting and immensely complicated landscape of modern love, often without meaningful sex and relationship education. Although individually oriented relationship education programs for emerging adults make a difference in the knowledge, attitudes, and beliefs of the recipients (Simpson et al., Journal of Youth and Adolescence, 2018, 47, 477) and most emerging adults report they yearn for relationship education (Weissbourd et al., The talk: How adults can promote young people's healthy relationships and prevent misogyny and sexual harassment, 2017), these programs are not widely available. Educators who are working with emerging adults in a classroom or psychoeducational setting are well-positioned to help emerging adults identify and enact healthy and purposeful relational and sexual choices. The first part of the paper orients readers to the "topography" of the modern love landscape by describing four macro cultural themes that impact the intimate lives of emerging adults. The second part of the paper introduces relationship educators to Relational Self-Awareness (Solomon, Loving Bravely: 20 lessons of self-discovery to help you get the love you want, New Harbinger, 2017), an integrative approach to helping emerging adults understand the self-in-relationship. Each of the five pillars of Relational Self-Awareness is defined and operationalized, and specific recommendations are provided for how educators can integrate these pillars into their existing curricula. Clinical implications and future directions are offered.

Los adultos emergentes están intentando orientarse ante un panorama de amor moderno rápidamente cambiante e inmensamente complicado, generalmente sin sexo significativo ni educación sobre las relaciones. Aunque los programas de educación sobre las relaciones para adultos emergentes con orientación individual marcan una diferencia en el conocimiento, las actitudes y las creencias de los destinatarios (Simpson et al., 2018), y la mayoría de los adultos emergentes informan que desean recibir educación sobre las relaciones (Weissbourd et al., 2017), estos programas no son ampliamente accesibles. Los educadores que trabajan con adultos emergentes en un aula o en un entorno psicoeducativo están bien posicionados para ayudarlos a identificar y a adoptar elecciones sexuales y relacionales saludables y significativas. La primera parte del artículo guía a los lectores por la "topografía" del panorama del amor moderno mediante la descripción de cuatro temas macroculturales que repercuten en las vidas íntimas de los adultos emergentes. En la segunda parte del artículo se presenta la autoconciencia relacional (Solomon, 2017) a los educadores sobre relaciones, un enfoque integrador para ayudar a los adultos emergentes a comprender el yo en las relaciones. Se definen y se operacionalizan cada uno de los cinco pilares de la autoconciencia relacional, y se dan recomendaciones específicas sobre cómo los educadores pueden integrar estos pilares en sus planes de estudio existentes. Se comentan las consecuencias clínicas y las futuras direcciones del estudio.

Hemoptysis associated with percutaneous transthoracic needle biopsy: Development of critical events checklist and procedure outcomes.

BACKGROUND: A percutaneous transthoracic needle biopsy (PTNB) is performed to obtain tissue for a pathologic diagnosis. A PTNB is necessary prior to the initiation of many cancer treatments. There is a risk of hemoptysis, the expectoration of blood, with the possibility for adverse, life-threatening outcomes. A critical event checklist is a cognitive aid used in an emergency to ensure critical steps are followed. To date, there are no known checklists published for management of PTNB-related, life-threatening hemoptysis. The purpose of this report is to describe the development and implementation of a critical event checklist and the adoption of the checklist into hemoptysis management. METHODS: In March 2017, a process improvement team convened to evaluate the hemoptysis response using the Plan-Do-Study-Act (PDSA) methodology. The checklist was evaluated and updated through September 2019. The team educated Interventional Radiology (IR) clinicians on the new checklist and conducted simulations on its use. A retrospective chart review was performed on hemoptysis events between the ten-year period of October 1, 2008 and September 30, 2018 to evaluate the adoption of the checklist into practice. RESULTS: There were 231 hemoptysis events occurring in 229 patients (2 with repeat biopsies). Prior to implementing the protocol and checklist, there were 166 (71.9%) hemoptysis events. After implementation there were 65 (28.1%) events. The median amount of documented blood expectorated with hemoptysis was 100 mL (IQR 20.0-300.0). Twenty-six patients were admitted after PTNB for reasons related to the hemoptysis event (11.3%). During the procedure, four (1.7%) patients with hemoptysis suffered a cardiac arrest. Prior to implementation of the protocol and critical events checklist, nurses positioned patients in the lateral decubitus (LD) position in 40 out of 162 (24.7%) cases. After implementation of the critical events checklist, nurses positioned patients in the LD position 42 out of 65 cases (64.6%) (OR=5.57(95% CI 2.99-10.367), p<0.001). DISCUSSION: Interventional Radiology nurses successfully adopted the checklist into management of hemoptysis events. The reported incidence of hemoptysis suggests a need for IR teams to prepare for and simulate hemoptysis events. Future research is needed to evaluate the change in patient outcomes before and after critical events checklist implementation.

Safety-Net Academic Hospital Experience in Following Up Noncritical Yet Potentially Significant Radiologist Recommendations.

OBJECTIVE: In this retrospective study, we identified the types of noncritical recommendations radiologists issued over a 15-day period, the percentage of noncritical radiology recommendations that were not acted on or acknowledged in the medical records, potential causes for recommendations not being acted on, and the potential risk of harm to patients. MATERIALS AND METHODS: We conducted a retrospective review of radiology reports and patient records from January 1, 2014, to January 15, 2014, at a large tertiary academic center and regional safety-net hospital. RESULTS: A total of 6851 reports were reviewed; 857 (13%) contained at least one noncritical recommendation, with 978 total recommendations. The two most common recommendations were additional imaging (63%, n = 615) and clinical correlation (23%, n = 229). The majority of radiology recommendations were followed (67%, n = 655), but 323 cases (33%) contained no evidence that recommendations were followed. Of those that were not followed, 39% (n = 126) had no documentation in the medical records of the recommendation being acknowledged. Of those, 32% (n = 40) had important findings, half of which (n = 20) could have benefited from a verbal communication (18 mass lesions, two instances of fetal death). CONCLUSION: Radiologists' recommendations contained in written reports of noncritical findings may not be consistently followed or acknowledged in the medical records. Our study shows that a few report recommendations that were not consistently followed or acknowledged contained findings that referred to potentially harmful conditions. The results triggered an investment in systems improvement at the studied institution.

Unsupervised overnight closed loop insulin delivery during free living: analysis of randomised cross-over home studies in adults and adolescents with type 1 diabetes.

BACKGROUND: The closed-loop system (artificial pancreas) delivers insulin in a glucose-responsive manner by the use of a control algorithm that automatically directs insulin delivery, based on real-time sensor glucose concentrations. Results from hospital-based studies have shown improved overnight glucose control and reduced risk of hypoglycaemia in type 1 diabetes. We aimed to assess whether unsupervised closed-loop systems can provide a realistic treatment option in patients with type 1 diabetes. METHODS: We combined data from two open-label, phase 2, randomised, cross-over, unsupervised home trials of people with type 1 diabetes, one in 24 adults (mean age 43 years [SD 12], HbA1c 8·0% [0·9]) and the other in 16 adolescents (15·6 [3·6], 8·1 [0·8]). In each trial, after training on study devices, participants were allocated to two periods of sensor-augmented pump therapy either with or without overnight closed loop that used a model predictive control algorithm to direct insulin delivery. Allocation sequence was done with a computer-generated random code. Each period lasted 4 weeks in adults and 3 weeks in adolescents. Primary outcome for both trials was time when sensor glucose was in the target range (3·9-8·0 mmol/L). Analysis was by intention to treat. Participants (or parents) gave written informed consent. The trials are registered with ClinicalTrials.gov, numbers NCT01440140 and NCT01221467. FINDINGS: Closed loop was started by participants on their own volition on 866 (89%) of 978 nights. The proportion of time when sensor glucose was in the target range between 0000 h and 0800 h was increased by a mean of 18·4% (95% CI 13·5-23·4, p<0·0001) during closed loop compared with no closed loop. Closed loop significantly reduced mean overnight sensor glucose by 0·9 mmol/L (95% CI 0·4-1·3, p=0·0001), and reduced the proportion of time when sensor glucose values were suggestive of hyperglycaemia (>8·0 mmol/L) (15·9%, 10·7-21·0; p<0·0001) and hypoglycaemia (<3·9 mmol/L) (median 0·9, IQR 0·2-2·2; p=0·014). Lower mean overnight glucose was associated with increased overnight insulin delivery (p<0·0001) without changing total daily insulin amount (p=0·84). INTERPRETATION: Extended use of overnight closed loop at home without supervision is feasible in adults and adolescents with type 1 diabetes. Clinically significant reduction in overnight glucose was observed accompanied by reduced time spent by patients in hypoglycaemia. To our knowledge, such combined effect has not been documented with any other means of intensified conventional insulin delivery. Longer term studies are warranted to assess its clinical potential. FUNDING: Diabetes UK, Juvenile Diabetes Research Foundation, NIHR Cambridge Biomedical Research Centre.

The Association of Anticoagulation Intensity with Outcomes in Hospitalized COVID-19 Patients.

Venous thromboembolism (VTE) risk is increased in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A key question was whether increased intensity of anticoagulation would help prevent VTE and improve patient outcomes, including transfer to the intensive care unit (ICU) and mortality. At the start of the coronavirus disease-19 (COVID-19) pandemic, our institution, Boston Medical Center, instituted a VTE risk stratification protocol based on patients' initial D-dimer levels, medical history, and presence of thrombosis to determine whether they should receive standard-dose prophylaxis, high-dose prophylaxis, or therapeutic anticoagulation. We performed a retrospective observational cohort study examining the association of degree of anticoagulation with outcomes in 915 hospitalized COVID-19 patients hospitalized initially on the general inpatient wards between March 1,, 2020, and June 1, 2020. Patients directly hospitalized in the ICU were excluded. Most, 813 patients (89%), in our cohort were on standard-dose prophylaxis; 32 patients (3.5%) received high-dose prophylaxis; 70 patients (7.7%), were treated with therapeutic anticoagulation. VTE occurred in 45 patients (4.9%), and the overall in-hospital mortality rate was 5.4% (49 deaths). On multivariable analysis of clinical outcomes in relation to type of anticoagulation, in the high-dose prophylaxis group, there was a trend towards increased in-hospital mortality (odds ratio 2.4 (0.8-7.5, 95% CI)) and increased ICU transfer (odds ratio 2.2 (0.9-5.7, 95% CI)). Our results suggest that patients receiving high-dose prophylaxis had more severe disease that was not mitigated by intermediate-dose anticoagulation.

Induction of IL-6 and CCL5 (RANTES) in human respiratory epithelial (A549) cells by clinical isolates of respiratory syncytial virus is strain specific.

BACKGROUND: Respiratory syncytial virus (RSV) is the major respiratory pathogen of infants and young children. During each seasonal epidemic, multiple strains of both subgroup A and B viruses circulate in the community. Like other RNA viruses, RSV genome replication is prone to errors that results in a heterogeneous population of viral strains some of which may possess differences in virulence. We sought to determine whether clinical isolates of RSV differ in their capacity to induce inflammatory cytokines IL-6 and CCL5 (previously known as RANTES [regulated upon activation, normal T-cell expressed and secreted protein]), which are known to be induced in vitro and in vivo in response to RSV, during infection of A549 cells. RESULTS: Screening of subgroup A and B isolates revealed heterogeneity among strains to induce IL-6 and CCL5. We chose two subgroup B strains, New Haven (NH)1067 and NH1125, for further analysis because of their marked differences in cytokine inducing properties and because subgroup B strains, in general, are less genetically heterogeneous as compared to subgroup A strains. At 12 and 24 hours post infection RSV strains, NH1067 and NH1125 differed in their capacity to induce IL-6 by an order of magnitude or more. The concentrations of IL-6 and CCL5 were dependent on the dose of infectious virus and the concentration of these cytokines induced by NH1125 was greater than that of those induced by NH1067 when the multiplicity of infection of NH1067 used was as much as 10-fold higher than that of NH1125. The induction of IL-6 was dependent on viable virus as infection with UV-inactivated virus did not induce IL-6. The difference in IL-6 induction most likely could not be explained by differences in viral replication kinetics. The intracellular level of RSV RNA, as determined by quantitative RT-PCR, was indistinguishable between the 2 strains though the titer of progeny virus produced by NH1125 was greater than that produced by NH1067 at 16, 24 and 36 hours but essentially equal at 48 and 72 hours. Full genome sequencing of the 2 strains revealed 193 polymorphisms and 4 insertions in NH1067 when compared to NH1125 (2 single base insertions in non-coding regions and 2 duplications of 3 and 60 bases in the RSV G gene). Of the polymorphisms, 147 occurred in coding regions and only 30 resulted in amino acid changes in 7 of the RSV genes. CONCLUSIONS: These data suggest that RSV strains may not be homogeneous with regard to pathogenesis or virulence. Identification of the genetic polymorphisms associated with variations in cytokine induction may lead to insights into RSV disease and to the development of effective antiviral agents and vaccines.

Understanding autism: how family therapists can support parents of children with autism spectrum disorders.

The number of children diagnosed with an Autism Spectrum Disorder has increased dramatically in the last 20 years. Parents of children with autism experience a variety of chronic and acute stressors that can erode marital satisfaction and family functioning. Family therapists are well-suited to help parents stay connected to each other as they create a "new normal." However, family therapists need updated information about autism, and they need to understand how family therapy can help parents of children with autism. Because having a child with autism affects multiple domains of family life, this paper explores how family therapists can utilize an integrative approach with parents, enabling them to flexibly work with the domains of action, meaning, and emotion.

"Don't lock me out": life-story interviews of family business owners facing succession.

This qualitative study used a grounded theory methodology to analyze life-story interviews obtained from 10 family business owners regarding their experiences in their businesses with the goal of understanding the complexities of family business succession. The grounded theory that emerged from this study is best understood as a potential web of constraints that can bear on the succession process. Coding of these interviews revealed four key influences, which seem to have the potential to facilitate or constrain the family business owner's approach to succession. Influence 1, "The business within," captures intrapsychic dynamics of differentiation and control. Influence 2, "The marriage," addresses how traditional gender roles shape succession. Influence 3, "The adult children," examines the role of having a natural (accidental, organic, passively groomed) successor. Influence 4, "The vision of retirement," captures the impact of owners' notions of life post-succession. Family therapists frequently encounter family systems in which the family business is facing succession. Even if succession is not the presenting problem, and even if the business owner is in the indirect (rather than direct) system, this research reminds clinicians of the importance of the family's story about the family business. Therefore, clinical implications and recommendations are included.

Predictors of Recurrent Severe Hypoglycemia in Adults With Type 1 Diabetes and Impaired Awareness of Hypoglycemia During the HypoCOMPaSS Study.

OBJECTIVE: The HypoCOMPaSS study was designed to test the hypothesis that successful avoidance of biochemical hypoglycemia without compromising overall glycemic control would restore sufficient hypoglycemia awareness to prevent recurrent severe hypoglycemia in the majority of participants with established type 1 diabetes. Before starting the study, we planned to investigate associations between baseline characteristics and recurrent severe hypoglycemia over 2 years' follow-up. RESEARCH DESIGN AND METHODS: A total of 96 adults with type 1 diabetes and impaired awareness of hypoglycemia participated in a 24-week 2 × 2 factorial randomized controlled trial comparing insulin delivery and glucose monitoring modalities, with the goal of rigorous biochemical hypoglycemia avoidance. The analysis included 71 participants who had experienced severe hypoglycemia in the 12-month prestudy with confirmed absence (complete responder) or presence (incomplete responder) of severe hypoglycemia over 24 months' follow-up. RESULTS: There were 43 (61%) complete responders and 28 (39%) incomplete responders experiencing mean ± SD 1.5 ± 1.0 severe hypoglycemia events/person-year. At 24 months, incomplete responders spent no more time with glucose ≤3 mmol/L (1.4 ± 2.1% vs. 3.0 ± 4.8% for complete responders; P = 0.26), with lower total daily insulin dose (0.45 vs. 0.58 units/24 h; P = 0.01) and greater impairment of hypoglycemia awareness (Clarke score: 3.8 ± 2.2 vs. 2.0 ± 1.9; P = 0.01). Baseline severe hypoglycemia rate (16.9 ± 16.3 vs. 6.4 ± 10.8 events/person-year; P = 0.002) and fear of hypoglycemia were higher in incomplete responders. Peripheral neuropathy was more prevalent in incomplete responders (11 [39%] vs. 2 [4.7%]; P < 0.001) with a trend toward increased autonomic neuropathy. CONCLUSIONS: Recurrent severe hypoglycemia was associated with higher preintervention severe hypoglycemia rate, fear of hypoglycemia, and concomitant neuropathy.

Sustained Reduction in Severe Hypoglycemia in Adults With Type 1 Diabetes Complicated by Impaired Awareness of Hypoglycemia: Two-Year Follow-up in the HypoCOMPaSS Randomized Clinical Trial.

OBJECTIVE: Severe hypoglycemia is a feared complication of type 1 diabetes; yet, few trials have targeted prevention using optimized self-management (educational, therapeutic, and technological support). We aimed to investigate whether improved awareness and reduced severe hypoglycemia, achieved during an intensive randomized clinical trial (RCT), were sustained after return to routine care. RESEARCH DESIGN AND METHODS: Ninety-six adults with type 1 diabetes (29 ± 12 years' duration) and impaired awareness of hypoglycemia at five U.K. tertiary referral diabetes centers were recruited into a 24-week 2 × 2 factorial RCT (HypoCOMPaSS). Participants were randomized to pump (continuous subcutaneous insulin infusion [CSII]) or multiple daily injections (MDIs) and real-time continuous glucose monitoring (RT-CGM) or self-monitoring of blood glucose (SMBG), with equal education/attention to all groups. At 24 weeks, participants returned to routine care with follow-up until 24 months, including free choice of MDI/CSII; RT-CGM vs. SMBG comparison continued to 24 months. Primary outcome was mean difference (baseline to 24 months [between groups]) in hypoglycemia awareness. RESULTS: Improvement in hypoglycemia awareness was sustained (Gold score at baseline 5.1 ± 1.1 vs. 24 months 3.7 ± 1.9; P < 0.0001). Severe hypoglycemia rate was reduced from 8.9 ± 12.8 episodes/person-year over the 12 months prestudy to 0.4 ± 0.8 over 24 months (P < 0.0001). HbA1c improved (baseline 8.2 ± 3.2% [66 ± 12 mmol/mol] vs. 24 months 7.7 ± 3.1% [61 ± 10 mmol/mol]; P = 0.003). Improvement in treatment satisfaction and reduced fear of hypoglycemia were sustained. There were no significant differences between interventions at 24 months. CONCLUSIONS: Optimized insulin replacement and glucose monitoring underpinned by hypoglycemia-focused structured education should be provided to all with type 1 diabetes complicated by impaired awareness of hypoglycemia.