Respiratory Symptoms Items from the COPD Assessment Test Identify Ever-Smokers with Preserved Lung Function at Higher Risk for Poor Respiratory Outcomes

Rationale: Ever-smokers without airflow obstruction scores greater than or equal to 10 on the COPD Assessment Test (CAT) still have frequent acute respiratory disease events (exacerbation-like), impaired exercise capacity, and imaging abnormalities. Identification of these subjects could provide new opportunities for targeted interventions. Objectives: We hypothesized that the four respiratory-related items of the CAT might be useful for identifying such individuals, with discriminative ability similar to CAT, which is an eight-item questionnaire used to assess chronic obstructive pulmonary disease impact, including nonrespiratory questions, with scores ranging from 0 to 40. Methods: We evaluated ever-smoker participants in the Subpopulations and Intermediate Outcomes in COPD Study without airflow obstruction (FEV1/FVC≥0.70; FVC above the lower limit of normal). Using the area under the receiver operating characteristic curve, we compared responses to both CAT and the respiratory symptom–related CAT items (cough, phlegm, chest tightness, and breathlessness) and their associations with longitudinal exacerbations. We tested agreement between the two strategies (k statistic), and we compared demographics, lung function, and symptoms among subjects identified as having high symptoms by each strategy. Results: Among 880 ever-smokers with normal lung function (mean age, 61 yr; 52% women) and using a CAT cutpoint greater than or equal to 10, we classified 51.8% of individuals as having high symptoms, 15.3% of whom experienced at least one exacerbation during 1-year follow-up. After testing sensitivity and specificity of different scores for the first four questions to predict any 1-year followup exacerbation, we selected cutpoints of 0–6 as representing a low burden of symptoms versus scores of 7 or higher as representing a high burden of symptoms for all subsequent comparisons. The four respiratory-related items with cutpoint greater than or equal to 7 selected 45.8% participants, 15.6% of whom experienced at least one exacerbation during follow-up. The two strategies largely identified the same individuals (agreement, 88.5%; k = 0.77; P \u3c 0.001), and the proportions of high-symptoms subjects who had severe dyspnea were similar between CAT and the first four CAT questions (25.9% and 26.8%, respectively), as were the proportions reporting impaired quality of life (66.9% and 70.5%, respectively) and short walking distance (22.4% and 23.1%, respectively). There was no difference in area under the receiver operating characteristic curve to predict 1-year follow-up exacerbations (CAT score ≥10, 0.66; vs. four respiratory items from CAT ≥ 7 score, 0.65; P = 0.69). Subjects identified by either method also hadmore depression/anxiety symptoms, poor sleep quality, and greater fatigue. Conclusions: Four CAT items on respiratory symptoms identified high-risk symptomatic ever-smokers with preserved spirometry as well as the CAT did. These data suggest that simpler strategies can be developed to identify these high-risk individuals in primary care

Effect of 6 months of hybrid closed-loop insulin delivery in adults with type 1 diabetes: a randomised controlled trial protocol

INTRODUCTION: Manual determination of insulin dosing largely fails to optimise glucose control in type 1 diabetes. Automated insulin delivery via closed-loop systems has improved glucose control in short-term studies. The objective of the present study is to determine the effectiveness of 6 months\u27 closed-loop compared with manually determined insulin dosing on time-in-target glucose range in adults with type 1 diabetes. METHODS AND ANALYSIS: This open-label, seven-centre, randomised controlled parallel group clinical trial will compare home-based hybrid closed-loop versus standard diabetes therapy in Australia. Adults aged ≥25 years with type 1 diabetes using intensive insulin therapy (via multiple daily injections or insulin pump, total enrolment target n=120) will undertake a run-in period including diabetes and carbohydrate-counting education, clinical optimisation and baseline data collection. Participants will then be randomised 1:1 either to 26 weeks of MiniMed 670G hybrid closed-loop system therapy (Medtronic, Northridge, CA, USA) or continuation of their current diabetes therapy. The hybrid closed-loop system delivers insulin automatically to address basal requirements and correct to target glucose level, while bolus doses for meals require user initiation and carbohydrate estimation. Analysis will be intention to treat, with the primary outcome time in continuous glucose monitoring (CGM) target range (3.9-10.0 mmol/L) during the final 3 weeks of intervention. Secondary outcomes include: other CGM parameters, HbA1c, severe hypoglycaemia, psychosocial well-being, sleep, cognition, electrocardiography, costs, quality of life, biomarkers of vascular health and hybrid closed-loop system performance. Semistructured interviews will assess the expectations and experiences of a subgroup of hybrid closed-loop users. ETHICS AND DISSEMINATION: The study has Human Research Ethics Committee approval. The study will be conducted in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice. Results will be disseminated at scientific conferences and via peer-reviewed publications

Willingness to initiate insulin among adults with type 2 diabetes in Australian primary care: results from the Stepping Up Study

AIMS: To determine \u27hypothetical willingness\u27 to initiate insulin, and identify associated factors, among adults with type 2 diabetes (T2DM) in primary care for whom insulin is clinically indicated. METHODS: Eligible participants were adults with T2DM with an HbA1c ≥7.5% (58mmol/mol) and prescribed maximum oral hypoglycaemic agents. A total of 261 participants were recruited from 74 Victorian general practices: mean age 62±10 years; 39% (n=103) women; diabetes duration 10±6 years; HbA1c 9.0±1.3% (75±14mmol/mol). Data collected by the Stepping Up Study: demographic and clinical characteristics, \u27willingness\u27 to initiate insulin, insulin appraisals, depressive symptoms, and diabetes-related distress. A multinomial regression investigated predictors of \u27willingness\u27. RESULTS: Nineteen percent (n=50) were \u27very willing\u27 to initiate insulin, if recommended. The final regression model (R(2)=.44, χ(2)(12) 145.91, p<.001) demonstrated higher socioeconomic status and less negative attitudes to insulin were associated with increased willingness to initiate insulin. CONCLUSIONS: Among adults with T2DM for whom insulin is clinically indicated, only one in five are \u27very willing\u27 to begin insulin therapy. Independent of demographics, clinical factors and emotional wellbeing, insulin appraisals were associated with \u27willingness\u27. This study highlights the importance of addressing attitudinal barriers to insulin therapy among adults with T2DM in primary care to improve insulin receptiveness

Impact of insulin initiation on glycaemic variability and glucose profiles in a primary healthcare Type 2 diabetes cohort: Analysis of continuous glucose monitoring data from the INITIATION study

Aim: To use continuous glucose monitoring to examine the effects of insulin initiation with glargine, with or without glulisine, on glycaemic variability and glycaemia in a cohort of people with Type 2 diabetes receiving maximum oral hypoglycaemic agents in primary healthcare. Methods: We conducted a post hoc analysis of continuous glucose monitoring data from 89 participants at baseline and at 24 weeks after insulin commencement. Indicators of glycaemic variability (standard deviation, J‐index and mean amplitude of glycaemic excursion) and glycaemia (HbA1c, mean glucose, area under the glucose–time curve) were assessed. Multi‐level regression analysis was used to identify the predictors of change. Results: Complete glycaemic variability data were available for 78 participants. Of these participants, 41% were women, their mean (sd) age was 59.2 (10.4) years, the median (interquartile range) diabetes duration was 10.4 (6.5, 13.3) years and the median (interquartile range) baseline HbA1c was 82.5 (71.6, 96.7) mmol/mol [9.7 (8.7, 11.0)%]. At baseline, BMI correlated negatively with standard deviation (r = −0.30) and mean amplitude of glycaemic excursion (r = −0.26), but not with J‐index; HbA1c correlated with J‐index (r = 0.61) but not with mean amplitude of glycaemic excursion and standard deviation. After insulin initiation the mean (sd) glucose level decreased [from 12.0 (3.0) to 8.5 (1.6) mmol/l; P \u3c 0.001], as did the median (interquartile range) J‐index [from 66.9 (47.7, 95.1) to 36.9 (27.6, 49.8) mmol/l; P \u3c 0.001]. Baseline HbA1c correlated with a greater J‐index reduction (r = −0.45; P \u3c 0.001). The mean amplitude of glycaemic excursion and standard deviation values were unchanged. The baseline temporal profile, showing elevated postprandial morning glucose levels, was unchanged after insulin initiation, despite an overall reduction in glycaemia. Conclusion: Insulin initiation reduced hyperglycaemia but did not alter glycaemic variability in adults with Type 2 diabetes receiving maximum oral hypoglycaemic agents. The most significant postprandial excursions were seen in the morning, which identifies prebreakfast as the most effective target for short‐acting insulin therapy

NO BENEFIT OF INGESTING A LOW-DOSE KETONE MONOESTER SUPPLEMENT ON COGNITIVE PERFORMANCE IN TRAINED FEMALES

BACKGROUND: β-hydroxybutyrate is one of three substrates that the brain can preferentially oxidize for meeting energetic demands. Ketone monoesters (KME) allow for the rapid elevation in circulating β-hydroxybutyrate levels without following a low-carbohydrate diet or prolonged fasting and some past work with KME have shown potential to mitigate cognitive decrements in states of fatigue, but no studies have yet been conducted in a female cohort. METHODS: Following a familiarization session and a baseline session without a mental fatiguing protocol (MF), 12 trained females completed two experimental sessions, consisting of a battery of cognitive tests (psychomotor vigilance test (PVT), task-switching, incongruent flanker) performed before (PRE) and after (POST) MF. In a counter-balanced crossover design, a ketone monoester (KME, ~188 mg·kg-1 body mass) or non-caloric placebo (PLA) were ingested before MF. Markers of cognitive performance (speed and correct responses per second), blood β-hydroxybutyrate, glucose, and lactate, and subjective markers of perceived cognitive load and fatigue were collected at PRE and POST.RESULTS: KME ingestion significantly increased blood β-hydroxybutyrate (P\u3c0.001; ~1.8 mM), decreased glucose (P\u3c0.001; ~0.6 mM), and attenuated a ~34% rise in lactate at POST compared to PLA (P=0.04). MF significantly increased perceived cognitive workload and fatigue for both experimental trials in comparison to the control (P\u3c0.05) but did not impair any of the cognitive variables assessed (all P\u3e0.05). Although ingestion of a KME increased perceptions of cognitive performance compared to PLA (KME, 7.8 vs. PLA, 5.5; P=0.05), no differences were observed between groups for markers of cognition.CONCLUSION: Although changes in blood markers mimic those observed in past KME investigations, compared with PLA, KME ingestion did not affect cognitive performance following a MF protocol in trained females

ACUTE INGESTION OF A KETONE MONOESTER WITH CARBOHYDRATE IMPROVES COGNITIVE MEASURES BUT NOT PERFORMANCE IN TRAINED FEMALES

BACKGROUND: In recent years, the field of sports performance and cognitive enhancement has witnessed a growing interest in the potential benefits offered to athletes with the supplementation of exogenous ketones, specifically the ketone monoester (KME). However, the present literature has examined KME ingestion in male or mixed cohorts, with female research currently underrepresented. Thus, we examined the acute ingestion of a KME with co-ingestion of a carbohydrate (KME+CHO) compared to carbohydrate alone (CHO) on cycling performance and cognitive performance in trained females. METHODS: Using a two condition, placebo-controlled, crossover design, twelve trained females (mean ± SD: age, 23 ± 3 y; height, 1.64 ± 0.08 m; mass, 65.2 ± 12.7 kg) completed a baseline assessment of cognitive performance (psychomotor vigilance testing (PVT), task switching, and incongruent flanker), followed by 6x5-min intervals at 40%, 45%, 50%, 55%, 60%, and 65% of their maximal power output (Wmax) and then a 10-km time trial (TT), concluding with the same assessments of cognitive performance post-exercise. Participants consumed either 375 mg·kg-1 body mass of KME with a 6% CHO solution (1 g·min-1 of exercise) or CHO alone, across 3 boluses (50:25:25). RESULTS: Blood β-hydroxybutyrate concentrations averaged 1.80±0.07 mM and 0.13±0.01 mM during exercise in KME+CHO and CHO, respectively. Blood glucose decreased following drink 1 of KME+CHO (~15%; P=0.01) but not CHO alone, and lactate concentrations were significantly lower in KME+CHO at 50%, 55%, 60%, and -65%Wmax (all P\u3c0.05), compared to CHO. Despite these changes, no differences were found between conditions for TT finishing times (KME+CHO, 29.7±5.7 min; CHO, 29.6±5.7 min; P=0.92). However, only KME+CHO resulted in increases in PVT speed (~4%; P=0.01) and faster reaction times (~14%; P\u3c0.01), and speed (~15%; P\u3c0.01) and correct responses (~13%; P=0.03) in the incongruent flanker during post-testing compared to CHO alone. CONCLUSION: Acute ingestion of a KME+CHO elevated blood β-hydroxybutyrate and simultaneously lowered glucose and lactate across multiple timepoints during exercise compared to CHO alone. Although these changes did not affect physical performance, several markers of cognitive performance were improved by the addition of a KME in trained females

Respiratory Symptoms Items from the COPD Assessment Test Identify Ever-Smokers with Preserved Lung Function at Higher Risk for Poor Respiratory Outcomes

Rationale: Ever-smokers without airflow obstruction scores greater than or equal to 10 on the COPD Assessment Test (CAT) still have frequent acute respiratory disease events (exacerbation-like), impaired exercise capacity, and imaging abnormalities. Identification of these subjects could provide new opportunities for targeted interventions. Objectives: We hypothesized that the four respiratory-related items of the CAT might be useful for identifying such individuals, with discriminative ability similar to CAT, which is an eight-item questionnaire used to assess chronic obstructive pulmonary disease impact, including nonrespiratory questions, with scores ranging from 0 to 40. Methods: We evaluated ever-smoker participants in the Subpopulations and Intermediate Outcomes in COPD Study without airflow obstruction (FEV1/FVC≥0.70; FVC above the lower limit of normal). Using the area under the receiver operating characteristic curve, we compared responses to both CAT and the respiratory symptom–related CAT items (cough, phlegm, chest tightness, and breathlessness) and their associations with longitudinal exacerbations. We tested agreement between the two strategies (k statistic), and we compared demographics, lung function, and symptoms among subjects identified as having high symptoms by each strategy. Results: Among 880 ever-smokers with normal lung function (mean age, 61 yr; 52% women) and using a CAT cutpoint greater than or equal to 10, we classified 51.8% of individuals as having high symptoms, 15.3% of whom experienced at least one exacerbation during 1-year follow-up. After testing sensitivity and specificity of different scores for the first four questions to predict any 1-year followup exacerbation, we selected cutpoints of 0–6 as representing a low burden of symptoms versus scores of 7 or higher as representing a high burden of symptoms for all subsequent comparisons. The four respiratory-related items with cutpoint greater than or equal to 7 selected 45.8% participants, 15.6% of whom experienced at least one exacerbation during follow-up. The two strategies largely identified the same individuals (agreement, 88.5%; k = 0.77; P \u3c 0.001), and the proportions of high-symptoms subjects who had severe dyspnea were similar between CAT and the first four CAT questions (25.9% and 26.8%, respectively), as were the proportions reporting impaired quality of life (66.9% and 70.5%, respectively) and short walking distance (22.4% and 23.1%, respectively). There was no difference in area under the receiver operating characteristic curve to predict 1-year follow-up exacerbations (CAT score ≥10, 0.66; vs. four respiratory items from CAT ≥ 7 score, 0.65; P = 0.69). Subjects identified by either method also hadmore depression/anxiety symptoms, poor sleep quality, and greater fatigue. Conclusions: Four CAT items on respiratory symptoms identified high-risk symptomatic ever-smokers with preserved spirometry as well as the CAT did. These data suggest that simpler strategies can be developed to identify these high-risk individuals in primary care

Glycemia, treatment satisfaction, cognition, and sleep quality in adults and adolescents with type 1 diabetes when using a closed-loop system overnight versus sensor-augmented pump with low-glucose suspend function: a randomized crossover study

BACKGROUND: We compared glycemia, treatment satisfaction, sleep quality, and cognition using a nighttime Android-based hybrid closed-loop system (Android-HCLS) with sensor-augmented pump with low-glucose suspend function (SAP-LGS) in people with type 1 diabetes. MATERIALS AND METHODS: An open-label, prospective, randomized crossover study of 16 adults (mean [SD] age 42.1 [9.6] years) and 12 adolescents (15.2 [1.6] years) was conducted. All participants completed four consecutive nights at home with Android-HCLS (proportional integral derivative with insulin feedback algorithm; Medtronic) and SAP-LGS. PRIMARY OUTCOME: percent continuous glucose monitoring (CGM) time (00:00-08:00 h) within target range (72-144 mg/dL). Secondary endpoints: percent CGM time above target (>144 mg/dL); below target (<72 mg/dL); glycemic variability (SD); symptomatic hypoglycemia; adult treatment satisfaction; sleep quality; and cognitive function. RESULTS: The primary outcome for all participants was not statistically different between Android-HCLS and SAP-LGS (mean [SD] 59.4 [17.9]% vs. 53.1 [18]%; p = 0.14). Adults had greater percent time within target range (57.7 [18.6]% vs. 44.5 [14.5]%; p < 0.006); less time above target (42.0 [18.7]% vs. 52.6 [16.5]%; p = 0.034); lower glycemic variability (35 [10.7] mg/dL vs. 46 [10.7] mg/dL; p = 0.003); and less (median [IQR]) time below target (0.0 [0.0-0.4]% vs. 0.80 [0.0-3.9]%; p = 0.025). In adolescents, time below target was lower with Android-HCLS vs. SAP-LGS (0.0 [0.0-0.0]% vs. 1.8 [0.1-7.9]%; p = 0.011). Nocturnal symptomatic hypoglycemia was less (1 vs. 10; p = 0.007) in adolescents, but not adults (5 vs. 13; p = 0.059). In adults, treatment satisfaction increased by 10 points (p < 0.02). Sleep quality and cognition did not differ. CONCLUSIONS: Android-HCLS in both adults and adolescents reduced nocturnal hypoglycemia and, in adults, improved overnight time in target range and treatment satisfaction compared with SAP-LGS