Codevelopment of a model of care for adults living with cystic fibrosis-related diabetes.

BACKGROUND: Cystic fibrosis (CF) related diabetes affects up to half of all adults with CF and is associated with higher morbidity and mortality. Our aim is to codevelop an ideal model of care that integrates diabetes technology and better meets the needs of adults living with the condition to improve attendance, engagement, service satisfaction, and clinical outcomes. METHODS: Using qualitative research methods, we evaluated disease perceptions, barriers, and enablers to optimal CF-related diabetes management and service delivery. Integration of continuous glucose monitoring (CGM) was also explored. An initial broad purposive consumer survey was followed by focus groups with end-users. Grounded theory approach was utilized with major problem areas identified then explored, coded, and grouped into requisites for an "ideal model of care" for adults living with CF-related diabetes. RESULTS: Two key themes emerged (i) an ideal model of care consisted of a dual-specialty service co-led by endocrinology and CF physicians and supported by diabetes educator and CF dietitian with a goal to provide consistent and personalized diabetes management and (ii) CGM was acceptable for use in adults with CF-related diabetes with many perceived benefits and should be integrated into the model of care. Barriers to optimizing glycemic control included diet, finger-prick testing, reduced access to CGM, and pulmonary exacerbations. End-user feedback on CGM was overwhelmingly positive with regard to operability. CGM was also identified as a tool that could be used to engage, educate, and empower adults living with CF-related diabetes and facilitate constructive and personalized clinical decision-making by healthcare providers. CONCLUSION: For adults living with CF, a diagnosis of diabetes is associated with increased treatment burden. Our findings suggest an "ideal model of care" for CF-related diabetes would be co-led by endocrinology services integrated within a pre-existing CF service, incorporating CGM.

Paraquat ingestion in an adult with cystic fibrosis (CF): Diagnostic and management dilemmas.

N,N'-dimethyl-4,4'bipyridinium dichloride (Paraquat) is a potent herbicide used widely in agriculture. We report the effects of an ingestion of paraquat by a 28 year old male with cystic fibrosis and the diagnostic and management challenges this posed in both the acute and longer term setting. We describe the effects of direct paraquat toxicity on the lung tissue secondary to aspiration and review the long-term sequelae of paraquat, namely osteonecrosis. Our case is the first to describe osteonecrosis of the knee in the context of paraquat toxicity. Survival following ingestion remains poor with a high associated mortality. However, timely treatment with NAC and immunosuppression may impact on survival. In those patients who do survive the acute phase post ingestion, follow-up over years may be required to detect the long-term effects of paraquat on bone health.

Effects of modulator therapies on endocrine complications in adults with cystic fibrosis: a narrative review.

Cystic fibrosis is a monogenic disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) protein, which transports chloride ions in secretory organs. Modulator therapies are small molecules that correct CFTR dysfunction and can lead to a wide range of benefits for both pulmonary and extrapulmonary complications of cystic fibrosis. With advancements in airway, antimicrobial and nutritional therapies and now introduction of modulator therapies, most people living with cystic fibrosis in Australia are now adults. For adults with cystic fibrosis, endocrine manifestations such as cystic fibrosis-related diabetes, metabolic bone disease, and reproductive health are becoming increasingly important, and emerging evidence on the endocrine effects of CFTR modulator therapies is promising and is shifting paradigms in our understanding and management of these conditions. The management of cystic fibrosis-related diabetes will likely need to pivot for high responders to modulator therapy with dietary adaptions and potential use of medications traditionally reserved for adults with type 2 diabetes, but evidence to support changing clinical care needs is currently lacking. Increased attention to diabetes-related complications screening will also be required. Increased exercise capacity due to improved lung function, nutrition and potentially direct modulator effect may have a positive impact on cystic fibrosis-related bone disease, but supporting evidence to date is limited. Fertility can improve in women with cystic fibrosis taking modulator therapy. This has important implications for pregnancy and lactation, but evidence is lacking to guide pre-conception and antenatal management. Provision of multidisciplinary clinical care remains ever-important to ensure the emergence of endocrine and metabolic complications are optimised in adults with cystic fibrosis.

Continuous glucose monitoring versus self-monitoring of blood glucose in the management of cystic fibrosis related diabetes: A systematic review and meta-analysis.

BACKGROUND: Treatment of cystic fibrosis related diabetes (CFRD) can improve outcomes and use of continuous glucose monitoring (CGM) can positively impact glycemic control. We conducted a systematic review to assess current evidence on CGM compared to self-monitoring of blood glucose (SMBG) in the management of CFRD to determine its effect on glycemic, pulmonary, non-pulmonary and quality of life outcomes. METHODS: Using pre-defined selection criteria, we searched MEDLINE, Embase, CENTRAL, Evidence-Based Medicine Reviews, grey literature and six relevant journals for studies using CGM and/or SMBG in CFRD with greater than 6 weeks of follow-up and reported change in HbA1c. The primary outcome was weighted mean difference (WMD) in plasma HbA1c between CGM and SMBG groups. Secondary outcomes included exploring interrelationships between CGM metrics and effects on disease-specific pulmonary, non-pulmonary and quality of life outcomes. RESULTS: A total of 1671 references were retrieved, 862 studies screened and 124 full-texts assessed for eligibility. No studies directly compared CGM to SMBG. A meta-analysis of seventeen studies of 416 individuals (CGM = 138, SMBG = 278) found CGM group had 4.1 mmol/mol (95% CI -7.9 to -0.30, p = 0.034) lower HbA1c compared to SMBG group. Most studies demonstrated moderate-to-high risk of bias. Publication bias was also present. Heterogeneity was high and meta-regression identified duration of follow-up in SMBG group as main contributor. CONCLUSION: Our findings suggest use of CGM may be associated with improved glycemic control compared to SMBG in CFRD, however evidence of benefit on pulmonary, non-pulmonary and psychosocial outcomes are lacking.

Comparison of continuous glucose monitoring to reference standard oral glucose tolerance test for the detection of dysglycemia in cystic Fibrosis: A systematic review.

Aims: Increasing evidence for benefit of early detection of cystic fibrosis related diabetes (CFRD) coupled with limitations of current diagnostic investigations has led to interest and utilisation of continuous glucose monitoring (CGM). We conducted a systematic review to assess current evidence on CGM compared to reference standard oral glucose tolerance test for the detection of dysglycemia in people with cystic fibrosis without confirmed diabetes. Methods: MEDLINE, Embase, CENTRAL, Evidence-Based Medicine Reviews, grey literature and six relevant journals were searched for studies published after year 2000. Studies reporting contemporaneous CGM metrics and oral glucose tolerance test results were included. Outcomes on oral glucose tolerance tests were categorised into a) normal, b) abnormal (indeterminate and impaired) or c) diabetic as defined by American Diabetes Association criteria. CGM outcomes were defined as hyperglycemia (≥1 peak sensor glucose ≥ 200 mg/dL), dysglycemia (≥1 peak sensor glucose ≥ 140-199 mg/dL) or normoglycemia (all sensor glucose peaks < 140 mg/dL). CGM hyperglycemia in people with normal or abnormal glucose tolerances was used to define an arbitrary CGM-diagnosis of diabetes. The Quality Assessment of Diagnostic Accuracy Studies tool was used to assess risk of bias. Primary outcome was relative risk of an arbitrary CGM-diagnosis of diabetes compared to the oral glucose tolerance test. Results: We identified 1277 publications, of which 19 studies were eligible comprising total of 416 individuals with contemporaneous CGM and oral glucose tolerance test results. Relative risk of an arbitrary CGM-diagnosis of diabetes compared to oral glucose tolerance test was 2.92. Studies analysed were highly heterogenous, prone to bias and inadequately assessed longitudinal associations between CGM and relevant disease-specific sequela. Conclusions: A single reading > 200 mg/dL on CGM is not appropriate for the diagnosis of CFRD. Prospective studies correlating CGM metrics to disease-specific outcomes are needed to determine appropriate cut-points.

Continuous glucose monitoring indices predict poor FEV1 recovery following cystic fibrosis pulmonary exacerbations.

BACKGROUND: Little is known about the effect of dysglycemia during cystic fibrosis pulmonary exacerbation (PEx) on recovery of FEV1 percentage predicted (ppFEV1) METHODS: Continuous glucose monitoring (CGM) was commenced at the time of admission to hospital for PEx and continued for 6 weeks. The CGM indices, percentage of time glucose greater than 7.8 mmol/L (%T>7.8) and mean glucose were evaluated as predictors of absolute ppFEV1 change following treatment of PEx. RESULTS: Of the 20 participants who completed the study 13 (65%) had cystic fibrosis related diabetes (CFRD). The mean of both CGM indices were highest during the first week of pulmonary exacerbation and continued to decline over the first 4 weeks at which point they plateaued. Using multivariate regression models, factors which were predictive of maximum attained ppFEV1 change over 6 weeks were %T>7.8, mean glucose, HbA1c and preadmission ppFEV1 change from baseline. These relationships were independent of a diagnosis of CFRD, which was not associated with ppFEV1 recovery. In a longitudinal model of ppFEV1 change at weeks 1, 2 and 6, the CGM index %T>7.8 approached significance as a predictive variable. CONCLUSIONS: Hyperglycemia during PEx in adult CF patients is associated with poorer ppFEV1 recovery. Conversely, there was no association observed between CFRD diagnosis and ppFEV1 improvement, suggesting that optimization of glycemic control in CFRD patients may positively influence recovery of lung function. Further clinical trials are required to evaluate the merits of intensive glycemic control in CFRD during PEx.

Early Intervention for Diabetes in Medical and Surgical Inpatients Decreases Hyperglycemia and Hospital-Acquired Infections: A Cluster Randomized Trial.

OBJECTIVE: To investigate if early electronic identification and bedside management of inpatients with diabetes improves glycemic control in noncritical care. RESEARCH DESIGN AND METHODS: We investigated a proactive or early intervention model of care (whereby an inpatient diabetes team electronically identified individuals with diabetes and aimed to provide bedside management within 24 h of admission) compared with usual care (a referral-based consultation service). We conducted a cluster randomized trial on eight wards, consisting of a 10-week baseline period (all clusters received usual care) followed by a 12-week active period (clusters randomized to early intervention or usual care). Outcomes were adverse glycemic days (AGDs) (patient-days with glucose <4 or >15 mmol/L [<72 or >270 mg/dL]) and adverse patient outcomes. RESULTS: We included 1,002 consecutive adult inpatients with diabetes or new hyperglycemia. More patients received specialist diabetes management (92% vs. 15%, P < 0.001) and new insulin treatment (57% vs. 34%, P = 0.001) with early intervention. At the cluster level, incidence of AGDs decreased by 24% from 243 to 186 per 1,000 patient-days in the intervention arm (P < 0.001), with no change in the control arm. At the individual level, adjusted number of AGDs per person decreased from a mean 1.4 (SD 1.6) to 1.0 (0.9) days (-28% change [95% CI -45 to -11], P = 0.001) in the intervention arm but did not change in the control arm (1.8 [2.0] to 1.5 [1.8], -9% change [-25 to 6], P = 0.23). Early intervention reduced overt hyperglycemia (55% decrease in patient-days with mean glucose >15 mmol/L, P < 0.001) and hospital-acquired infections (odds ratio 0.20 [95% CI 0.07-0.58], P = 0.003). CONCLUSIONS: Early identification and management of inpatients with diabetes decreased hyperglycemia and hospital-acquired infections.

An Objective Measurement of Lacunar Infarct Location from the Middle Cerebral Artery Stem.

BACKGROUND: There is emerging interest in the relationship between neuroimaging location of lacunar infarcts and underlying stroke risk factors. Recent methods used for localization of lacunar infarcts are affected by high inter-rater variability. We used a novel algorithm-driven method that provided quantitative assessment of the distance of the lacunar infarct from the origins of the lenticulostriate arteries. METHODS: We conducted a retrospective analysis of patients who presented with lacunar infarcts between 2007 and 2011. Diffusion-weighted imaging and magnetic resonance angiography were used to manually mark the infarct lesion and the ipsilateral origins of lenticulostriate arteries. A 3-dimensional distance formula computed the distance between the infarct and the arterial region of interest. All distances were adjusted for brain volumes. Agreement testing using 2 blinded assessors was used to determine reproducibility of this method. RESULTS: One hundred and ten patients were included in our study, with a median age of 72 years (interquartile range 58-81); 67 (61%) were male and 33 (30%) had hypertension and other vascular risk factors including hypercholesterolemia 45 (41%), smoking 33 (30%), diabetes 24 (22%), ischemic heart disease 18 (16%), and atrial fibrillation 9 (8%). The agreement test for 33 patients demonstrated an intraclass correlation of .89 and Lin's correlation coefficient of .89 (95% confidence interval .816-.963). The median distance for the study cohort was 24.5 mm, with shorter median distances of 13.7 mm observed in patients with atrial fibrillation (P value < .005). CONCLUSION: Our study used a novel method to calculate a distance measurement, which has high inter-rater correlation.

Managing hyponatraemia secondary to primary polydipsia: beware too rapid correction of hyponatraemia.

We describe three cases of severe hyponatraemia in the setting of primary polydipsia that were managed in our centre in 2016. Despite receiving different solute loads, large volume diuresis and rapid correction of serum sodium occurred in all cases. Given the potentially catastrophic consequence of osmotic demyelination, we highlight the judicious use of desmopressin and hypotonic fluid infusion to mitigate sodium overcorrection in this setting.