The role of the NLRP3 inflammasome in atherosclerotic disease: Systematic review and meta-analysis.

Atherosclerosis is a chronic, progressive cardiovascular disease characterized by cholesterol deposition within blood vessel walls. Recent literature has suggested that the NLRP3 [NOD (nucleotide oligomerization domain)-, LRR (leucine-rich repeat)-, and PYD (pyrin domain)-containing protein 3] inflammasome is a key mediator in the development, progression, and destabilization of atherosclerotic plaques. This review aims to evaluate the current literature on the role of NLRP3 in human atherosclerosis. This systematic review was registered on the PROSPERO database (ID = CRD42022340039) and involved the search of a total of 8 databases. Records were screened in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. A total of 20 studies were included and quality assessed using the NIH: NHLBI tool. Six were eligible for meta-analysis using RevMan 5.4.1. We identified 20 relevant articles representing 3388 participants. NLRP3 mRNA levels and downstream cytokines, interleukin (IL)-1ß and IL-18 were found to be associated with atherosclerotic disease. Fold changes in NLRP3 mRNA levels were most strongly associated with high risk atherosclerotic disease, compared to controls [0.84 (95 % CI: 0.41-1.28)]. IL-1ß mRNA fold change was more robustly associated with high-risk atherosclerotic disease [0.61 (95 % CI: 0.10-1.13)] than IL-18 [0.47 (95 % CI: 0.02-0.91)]. NLRP3, IL-1ß, and IL-18 are associated with high-risk atherosclerotic disease. However, given the scope of this review, the role of this inflammasome and its cytokine counterparts in acting as prognosticators of coronary artery disease severity is unclear. Several upstream activators such as cholesterol crystals are involved in the canonical or non-canonical activation of the NLRP3 inflammasome and its downstream cytokines. These findings highlight the necessity for further research to delineate the exact mechanisms of NLRP3 inflammasome activation and potential drug targets.

Electromechanical therapy in diabetic foot ulcers patients: A systematic review and meta-analysis.

Purpose: Diabetic foot ulcer (DFU) is one of the most devastating and troublesome consequences of diabetes. The current therapies are not always effective because of the complicated aetiology and interactions of local and systemic components in DFU. However, adjunctive therapy (electromechanical therapy) has become the latest modality in recent years, although there is a lack of significant research to support its utilization as a treatment standard. The purpose of this systematic research was to review the literature on the application of electromechanical therapies in the healing of DFUs. Methods: For this systematic review, we searched PubMed, Medline, EmBase, the Cochrane library, and Google Scholar for the most current research (1990-2022) on electromechanical therapies for DFUs. We used the PICO method (where P is population, I is intervention, C is comparator/control, and O is outcome for our study) to establish research question with the terms [Electromechanical therapy OR Laser therapy OR photo therapy OR Ultrasound therapy OR Shockwave therapy] AND [diabetic foot ulcers OR diabetes] were used as search criteria. Searches were restricted to English language articles only. Whereas, Cochrane handbook of "Systematic Reviews of Interventions" with critical appraisal for medical and health sciences checklist for systematic review was used for risk of bias assessment. There were 39 publications in this study that were deemed to be acceptable. All the suitably selected studies include 1779 patients. Results: The meta-analysis of 15 included research articles showed the overall effect was significant (P = 0.0002) thus supporting experimental groups have improvement in the DFUs healing in comparison to the control group. Conclusion: This systematic review and meta-analysis revealed electromechanical treatments are significantly viable options for patients with DFUs. Electromechanical therapy can considerably reduce treatment ineffectiveness, accelerate healing, and minimize the time it takes for complete ulcer healing. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-023-01240-2.

Extracorporeal Shockwave Therapy (ESWT) in the Management of Diabetic Foot Ulcer: A Prospective Randomized Clinical Trial.

Diabetic foot ulcer (DFU) is the most common cause of prolonged hospitalization with a high cost of care due to unsatisfactory outcomes with the current mode of therapy. Extracorporeal shockwave therapy (ESWT) is a new technology in the care of nonhealing wounds. The study's main objective was to compare the healing parameters of DFUs between patients undergoing the standard of care (SOC) alone and ESWT + SOC. The secondary objective was to assess inflammatory markers in both study groups. The study was designed as a single-center, randomized trial to provide evidence on the effects of ESWT on DFU healing. Informed consent was obtained from all participants before enrolment. Forty-eight participants were recruited, enrolled, and randomly allocated into the 2 study groups. Twenty-five patients were allocated to the ESWT + SOC group, and 23 patients were allocated into the SOC-only group for a treatment period of 6 weeks. The univariate binary analysis showed more patients with healed DFU in the ESWT + SOC group than the SOC-only group at 6 weeks, though the difference did not reach statistical significance (OR = 3.2, p = .07). The adjusted multivariate binary analysis confirmed this finding; however, the effect size did not reach statistical significance at 6 weeks (OR = 3.9, p = .08). The level of circulating inflammatory markers was similar in both groups of patients. It is the author's opinion that there is a potential benefit of ESWT on diabetic wound healing with further research warranted to determine its role in treatment of DFU. A larger trial with a more extended treatment period is, however, needed to substantiate our findings.

The effectiveness of mindfulness-based stress reduction (MBSR) on the mental health, HbA1C, and mindfulness of diabetes patients: A systematic review and meta-analysis of randomised controlled trials.

The clinically standardised mindfulness-based stress reduction (MBSR) has been utilised as an intervention for improving mental health among diabetes patients The present study aimed to assess the effectiveness of mindfulness-based stress reduction (MBSR) on the mental health, haemoglobin A1c (HbA1C), and mindfulness of diabetes patients. A systematic review and meta-analysis approach was employed to review randomised controlled trials published in the English language between the inception of eight databases to July 2022. Eleven articles from 10 studies, with a combined sample size of 718 participants, were included in the systematic review, and nine studies were included in the meta-analysis. In the meta-analysis, outcomes at post-intervention and follow-up were compared between the MBSR intervention and control groups with an adjustment of the baseline values. The results showed that MBSR demonstrated effects at post-intervention and follow-up (in a period between one to 12 months with a mean length of 4.3 months) in reducing anxiety and depressive symptoms, and enhancing mindfulness, with large effect sizes. However, the effect of MBSR on reducing stress was observed at follow-up, but not at post-intervention. Effects of MBSR on HbA1C were not detected at post-intervention and follow-up. The findings suggest that MBSR appears to be an effective treatment for improving mental health conditions and mindfulness in people with diabetes. The measurement of cortisol is recommended to be used as a biological measure to evaluate the effectiveness of MBSR in diabetes patients in future research.

Effects of vildagliptin on wound healing and markers of inflammation in patients with type 2 diabetic foot ulcer: a prospective, randomized, double-blind, placebo-controlled, single-center study.

INTRODUCTION: Diabetic foot ulcers (DFU) are one of the leading long-term complications experienced by patients with diabetes. Dipeptidyl Peptidase 4 inhibitors (DPP4is) are a class of antihyperglycemic medications prescribed to patients with diabetes to manage glycaemic control. DPP4is may also have a beneficial effect on DFU healing. This study aimed to determine vildagliptin's effect on inflammatory markers and wound healing. TRIAL DESIGN: Prospective, randomized, double-blind, placebo-controlled, single-center study. METHODS: Equal number of participants were randomized into the treatment and placebo groups. The treatment was for 12 weeks, during which the participants had regular visits to the podiatrist, who monitored their DFU sizes using 3D camera, and blood samples were taken at baseline, six weeks, and 12 weeks during the study for measurement of inflammatory markers. In addition, demographic characteristics, co-morbidities, DFU risk factors, and DFU wound parameters were recorded. RESULTS: 50 participants were recruited for the study, with 25 assigned to placebo and 25 to treatment group. Vildagliptin treatment resulted in a statistically significant reduction of HBA1c (p < 0.02) and hematocrit (p < 0.04), total cholesterol (p < 0.02), LDL cholesterol (p < 0.04), and total/HDL cholesterol ratio (P < 0.03) compared to the placebo group. Also, vildagliptin had a protective effect on DFU wound healing, evidenced by the odds ratio (OR) favoring the intervention of 11.2 (95% CI 1.1-113.5; p < 0.04) and the average treatment effect on the treated (ATET) for vildagliptin treatment group showed increased healing by 35% (95%CI; 10-60, p = 0.01) compared to placebo with the model adjusted for microvascular complications, smoking, amputation, dyslipidemia, peripheral vascular disease (PVD) and duration of diabetes. CONCLUSIONS: Vildagliptin treatment was effective in healing DFU in addition to controlling the diabetes. Our findings support the use of DPP4is as a preferred option for treating ulcers in patients with diabetes. Further studies on a larger population are warranted to confirm our findings and understand how DPP4is could affect inflammation and DFU healing.

Effect of glucagon-like peptide 1 receptor agonists on albuminuria in adult patients with type 2 diabetes mellitus: A systematic review and meta-analysis.

AIMS: To determine the effect of glucagon-like peptide 1 receptor agonists (GLP-1RAs) on albuminuria in adult patients with type 2 diabetes mellitus (T2DM). METHODS: Medline Ovid, Scopus, Web of Science, EMCARE and CINAHL databases from database inception until 27 January 2022. Studies were eligible for inclusion if they were randomized controlled trials that involved treatment with a GLP-1RA in adult patients with T2DM and assessed the effect on albuminuria in each treatment arm. Data extraction was conducted independently by three individual reviewers. The PRISMA guidelines were followed regarding data extraction and quality assessment. Data were pooled using a random effects inverse variance model and all analysis was carried out with RevMan 5.4 software. The Jadad scoring tool was employed to assess the quality of evidence and risk of bias in the randomized controlled trials. RESULTS: The initial search revealed 2419 articles, of which 19 were included in this study. An additional three articles were identified from hand-searching references of included reviews. Therefore, in total, 22 articles comprising 39 714 patients were included. Meta-analysis suggested that use of GLP1-RAs was associated with a reduction in albuminuria in patients with T2DM (weighted mean difference -16.14%, 95% CI -18.42 to -13.86%; p < .0001) compared with controls. CONCLUSIONS: This meta-analysis indicates that GLP-1RAs are associated with a significant reduction in albuminuria in adult patients with T2DM when compared with placebo.

The efficacy of inflammatory markers in diagnosing infected diabetic foot ulcers and diabetic foot osteomyelitis: Systematic review and meta-analysis.

BACKGROUND: Diabetes foot ulcer (DFU) is a complication of diabetes mellitus. Accurate diagnosis of DFU severity through inflammatory markers will assist in reducing impact on quality of life. We aimed to ascertain the diagnostic test accuracy of commonly used inflammatory markers such as erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), procalcitonin (PCT), and white cell count (WCC) for the diagnosis and differentiation between DFU grades based on the International Working Group on the Diabetic Foot classification system. METHODS: This systematic review explored studies that investigated one or more of the above-listed index tests aiding in diagnosing infected DFU. This review was registered on PROSPERO database (ID = CRD42021255618) and searched 5 databases including an assessment of the references of included studies. Records were manually screened as per Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. A total of 16 studies were included which were assessed for quality using QUADAS-2 tool and meta-analysed using Meta-Disc v1.4. RESULTS: CRP had the greatest area under the curve (AUC) of 0.893 for diagnosing grade 2 DFU. This returned a pooled sensitivity and specificity of 77.4% (95% CI: 72% to 82%) and 84.3% (95% CI: 79% to 89%) respectively. In terms of diagnosing grade 3 DFU, procalcitonin had the highest AUC value of 0.844 when compared with other markers. The pooled sensitivity of PCT was calculated as 85.5% (95% CI: 79% to 90%) and specificity as 68.9% (95% CI: 63% to 75%). CONCLUSION: CRP and PCT are the best markers for diagnosing grade 2 and grade 3 DFU respectively. Other markers are also valuable when used in conjunction with clinical judgement. The findings accentuate the necessity of further research to establish standardised cut-off values for these inflammatory markers in diagnosing diabetic foot ulcers.

Ischemic heart disease and its risk factors in patients with diabetic foot ulcers: A systematic review and meta-analysis.

AIMS: There is limited literature on IHD in DFU patients. This review aimed to determine the prevalence of and risk factors of IHD in patients with DFUs. METHODS: Seven electronic databases were searched from inception to April 2021. RESULTS: The prevalence of IHD in DFU patients ranged from 6.83% to 60.61% with a pooled mean of 25.85% (95% CI, 24.28%-27.32%). Several risk factors were identified including hypertension, male gender, smoking, and peripheral vascular disease. CONCLUSION: We identified multiple risk factors for IHD requiring early interventions to increase long-term quality of life for patients with DFUs.

The IFN-γ/miniTrpRS signaling axis: An insight into the pathophysiology of osteoporosis and therapeutic potential.

Osteoporosis results from dysregulated bone remodeling with increased osteoclast-mediated destruction of bones. We have recently shown in vitro the truncated tryptophanyl-tRNA synthetase (mini-TrpRS)-dependent action of interferon-gamma (IFN-γ) to promote myeloid lineage multinucleation, a fundamental step in the osteoclast formation. In particular, we found that IFN-γ readily induced monocyte aggregation leading to multinuclear giant cell formation that paralleled marked upregulation of mini-TrpRS. However, blockade of mini-TrpRS with its cognate amino acid and decoy substrate D-Tryptophan prevented mini-TrpRS signaling, and markedly reduced the aggregation of monocytes and multinucleation in the presence of IFN. The cell signaling mechanism executed by mini-TrpRS appears inevitably in any inflammatory environment that involves IFN-γ with outcomes depending on the cell type involved. Here, we elaborate on these findings and discuss the potential role of the IFN-γ/mini-TrpRS signaling axis in osteoporosis pathophysiology, which may eventually materialize in a novel therapeutic perspective for this disease.

Prevalence and risk factors of lower limb amputations in patients with diabetic foot ulcers: A systematic review and meta-analysis.

BACKGROUND AND AIMS: The study aimed at determining prevalence and risk factors (RFs) of diabetic lower limb amputations (LLAs). METHODS: Electronic databases including PubMed, Medline, Web of Science, and Cochrane Library were searched from January 2003 to April 2021. RESULTS: Sixteen full-text published studies were reviewed. The prevalence of LLAs stood as high as 66%, with a combined prevalence of 19% (95% CI 10-29) using the random-effects model. The most prominent RFs for LLA were duration of diabetes mellitus (DM), age, renal impairment, and ethnic minority. Amongst Australians, Indigenous background is strongly associated with increased risk of the diabetic foot (DF) LLA. CONCLUSIONS: LLAs are considerably prevalent amongst patients with the DF and occur at even higher rates in patients with multimorbidity.

Usefulness of Procalcitonin in Diagnosing Diabetic Foot Osteomyelitis: A Pilot Study.

INTRODUCTION: Infected diabetic foot is the leading cause of hospital admissions for people with diabetes mellitus. Diabetic foot osteomyelitis (DFO) causes high morbidity and significant mortality. Current diagnostic tests for DFO are either expensive, invasive, or of low diagnostic yield. OBJECTIVE: The objective of the study was to determine whether serum levels of procalcitonin (PCT), an inflammatory marker, differ between DFO and diabetic foot ulcers without osteomyelitis (ie, cellulitis) as controls. The authors also aimed to assess the usefulness of PCT in diagnosing DFO. METHODS: A case-control study was designed comparing DFO with diabetic foot cellulitis as the control. Patients were classified as having osteomyelitis and cellulitis based on the International Working Group on the Diabetic Foot diagnostic criteria. Serum inflammatory markers PCT, adiponectin, C-reactive protein-1, osteoprotegerin (OPG), osteopontin (OPN), and interleukin 6 (IL-6) were analyzed in patients with DFO and controls. RESULTS: The median serum procalcitonin was significantly higher in the DFO group 108.5 pg/mL (range, 65.0-124.0 pg/mL) compared with 57.0 pg/mL (range, 37.2-77.0 pg/mL) controls (P = .02). Procalcitonin had a sensitivity of 79% compared with 50%, 63%, 66%, and 75% for adiponectin, OPG, OPN, and IL-6, respectively. Procalcitonin had a specificity of 70% compared with 50%, 71%, 70%, and 64%. Receiver operator characteristic curves showed a value of area under the curve of 0.73 and 0.77 for PCT and IL-6 compared with 0.4, 0.6, and 0.6 for adiponectin, OPG, and OPN, respectively. CONCLUSIONS: In this study, procalcitonin was a useful diagnostic test for DFOs and provided distinct diagnostic discrimination between DFO from cellulitis. It may serve as a useful marker for diagnosing DFO. Further studies in a larger population are needed to verify the findings.

Metabolic and Anthropometric Influences on Nerve Conduction Parameters in Patients with Peripheral Neuropathy: A Retrospective Chart Analysis.

BACKGROUND AND AIMS: Nerve conduction study (NCS) measures how fast an electrical impulse moves through the nerve and is a standard technique for diagnosing and assessing neurological diseases. Despite diabetes and obesity being a common accompaniment of peripheral neuropathy, their effects on NCS patterns have not been elucidated conclusively. Our study aimed to assess several anthropometric and metabolic factors with NCS outcomes to address this gap. RESEARCH DESIGN AND METHODS: This retrospective chart analysis study was conducted on subjects who underwent NCS between 1 January 2009 and 31 December 2019 at a regional hospital. Metabolic, anthropometric, demographical and NCS data were collected from patients' health records. RESULTS: In total, 120 subjects presenting with sensorimotor peripheral neuropathy symptoms were included in the study. Age, HbA1c, urea and ESR variables were significantly negatively associated with nerve conduction outcomes (Spearman's correlation rho between -0.210 and -0.456, p < 0.038). HbA1c and age consistently had the most substantial contribution to velocity and amplitude in all regression models (beta coefficients between -0.157 and 0.516, p < 0.001). Urea also significantly account for a large amount of variance in amplitude and velocity in the lower limbs. CONCLUSION: This study suggests that the severity of sensorimotor neuropathy is influenced by glycaemic control, age and uraemia. The interpretation of NCS results must consider these factors suggesting that improved glycaemic and uraemic control may improve nerve conduction outcomes.

Cushing's disease: Does low-dose pasireotide offer a comparable efficacy and safety to high-dose?

SUMMARY: Whilst literature is expanding on pasireotide use in the management of Cushing's disease (CD), there is still currently much unknown about long-term and low-dose pasireotide use in CD. We present a 60-year-old female with residual CD after transphenoidal surgery (TSS), being successfully managed with S.C. pasireotide for over 10 years. For 6 years, her S.C. pasireotide was inadvertently administered at 360 µg twice daily (BID), almost half the recommended dose of 600 µg BID. Despite the low-dose, her urinary free cortisol (UFC) normalised within 6 months and Cushingoid features resolved. She remained in biochemical and clinical remission on the same low-dose for 6 years, before a medication audit discovered her mistaken dose and directed her to take 600 µg BID. With the higher dose 600 µg BID for the next 5 years, her glycaemia worsened without any changes in her UFC and residual tumour volume. Our case showed the continuing effectiveness and safety of treatment with S.C. pasireotide for more than 10 years, and that a low-dose regimen may be considered an option for responders by its safety profile. LEARNING POINTS: A lower dose of pasireotide may be effective in the initial treatment of CD than the recommended 600 µg BID dosage, though more studies are required to explore this. Low-dose pasireotide use has the benefit of minimising adverse effects. In the long-term, pasireotide has a sustained clinical and biochemical effect and is well tolerated.

Lower extremity amputations and long-term outcomes in diabetic foot ulcers: A systematic review.

BACKGROUND: Diabetes mellitus causes a large majority of non-traumatic major and minor amputations globally. Patients with diabetes are clinically complex with a multifactorial association between diabetic foot ulcers (DFU) and subsequent lower extremity amputations (LEA). Few studies show the long-term outcomes within the cohort of DFU-associated LEA. AIM: To highlight the long-term outcomes of LEA as a result of DFU. METHODS: PubMed/MEDLINE and Google Scholar were searched for key terms, "diabetes", "foot ulcers", "amputations" and "outcomes". Outcomes such as mortality, re-amputation, re-ulceration and functional impact were recorded. Peer-reviewed studies with adult patients who had DFU, subsequent amputation and follow up of at least 1 year were included. Non-English language articles or studies involving children were excluded. RESULTS: A total of 22 publications with a total of 2334 patients were selected against the inclusion criteria for review. The weighted mean of re-amputation was 20.14%, 29.63% and 45.72% at 1, 3 and 5 years respectively. The weighted mean of mortality at 1, 3 and 5 years were 13.62%, 30.25% and 50.55% respectively with significantly higher rates associated with major amputation, re-amputation and ischemic cardiomyopathy. CONCLUSION: Previous LEA, level of the LEA and patient comorbidities were significant risk factors contributing to re-ulceration, re-amputation, mortality and depreciated functional status.

User Retention and Engagement With a Mobile App Intervention to Support Self-Management in Australians With Type 1 or Type 2 Diabetes (My Care Hub): Mixed Methods Study.

BACKGROUND: Mobile health apps are commonly used to support diabetes self-management (DSM). However, there is limited research assessing whether such apps are able to meet the basic requirements of retaining and engaging users. OBJECTIVE: This study aimed to evaluate participants' retention and engagement with My Care Hub, a mobile app for DSM. METHODS: The study employed an explanatory mixed methods design. Participants were people with type 1 or type 2 diabetes who used the health app intervention for 3 weeks. Retention was measured by completion of the postintervention survey. Engagement was measured using system log indices and interviews. Retention and system log indices were presented using descriptive statistics. Transcripts were analyzed using content analysis to develop themes interpreted according to the behavioral intervention technology theory. RESULTS: Of the 50 individuals enrolled, 42 (84%) adhered to the study protocol. System usage data showed multiple and frequent interactions with the app by most of the enrolled participants (42/50, 84%). Two-thirds of participants who inputted data during the first week returned to use the app after week 1 (36/42, 85%) and week 2 (30/42, 71%) of installation. Most daily used features were tracking of blood glucose (BG; 28/42, 68%) and accessing educational information (6/42, 13%). The interview results revealed the app's potential as a behavior change intervention tool, particularly because it eased participants' self-care efforts and improved their engagement with DSM activities such as BG monitoring, physical exercise, and healthy eating. Participants suggested additional functionalities such as extended access to historical analytic data, automated data transmission from the BG meter, and periodic update of meals and corresponding nutrients to further enhance engagement with the app. CONCLUSIONS: The findings of this short-term intervention study suggested acceptable levels of participant retention and engagement with My Care Hub, indicating that it may be a promising tool for extending DSM support and education beyond the confines of a physical clinic.

Efficacy and Acceptability of My Care Hub Mobile App to Support Self-Management in Australians with Type 1 or Type 2 Diabetes.

The aim of this study was to evaluate the preliminary efficacy and user acceptance of My Care Hub (MCH) mobile app-developed to provide evidenced-based support and education on diabetes self-management (DSM). Using a mixed-methods design, the efficacy and acceptability of MCH were measured among people with type 1 or type 2 diabetes after three weeks of intervention. The primary outcome measure was level of involvement with DSM, while the mediating factors were skills and self-efficacy for DSM. Telephone interviews were conducted to elucidate information on perceptions of the app's impact on participants' DSM and interest in future use. Statistically significant improvements were observed between pre- and post-intervention measures: DSM activities (4.55 ± 1.14 vs. 5.35 ± 0.84; p = 0.001); skills (7.10 ± 1.99 vs. 7.90 ± 1.67; p = 0.04); and self-efficacy (7.33 ±1.83 vs. 8.07 ± 1.54; p = 0.03). Multivariate analysis showed that self-efficacy had the strongest, though not significant influence on DSM. Interview findings revealed that the app reinforced knowledge and provided motivation to participate in DSM activities. The study suggested a positive impact of MCH on DSM and acceptability by patients. To confirm these promising results, further large scale and long-term studies are required.

Influence of Ethnicity on Outcomes of Diabetes Inpatient Hypoglycemia: an Australian Perspective.

AIMS: To evaluate outcomes of diabetic inpatient hypoglycemia among Aboriginal and Torres Strait Islander (ATSI) compared with Australian Caucasian patients. METHODS: A retrospective audit of diabetic patients aged > 18 years admitted at a regional hospital general ward between April 1, 2015, and March 31, 2016, was analyzed. The database contains clinical information at the time of admission and initial discharge and readmission within 4 weeks thereafter. RESULTS: A total of 1618 (of 6027) patients were admitted with diabetes representing 23.7% of the total ward admissions, of which 484 (29.9%) had inpatient hypoglycemia. Of the 91 patients with available data analyzed, ATSI origin with inpatient hypoglycemia was associated with longer length of stay (LOS) (hazard ratio [HR], 2.1, 95% confidence interval [CI], 1.2-3.5), whereas severe hypoglycemia (≤ 2.2 mmol/L) in both ATSI and non-ATSI was significantly associated with longer LOS (HR, 2.3; 95% CI, 1.2-4.2). No significant differences in LOS were found for gender, age, and Carlson comorbidity index (CCI). The adjusted model for likelihood of readmission, gender, indigenous status, and CCI were not significant risk factors for readmission to the hospital. Readmitted patients were older (50-59 years vs < 50 years, P = 0.001; 60-69 years vs < 50 years, P = 0.032; 70+ years vs < 50 years, P = 0.031). CONCLUSION: We reported high rate of inpatient hypoglycemia in our study population. Indigenous Australian diabetic patients with inpatient hypoglycemia had significantly longer LOS compared with non-Indigenous Caucasian counterparts. Further prospective studies on a larger population are needed to confirm our findings.

The development of My Care Hub Mobile-Phone App to Support Self-Management in Australians with Type 1 or Type 2 Diabetes.

Non-adherence to self-management poses a serious risk to diabetes complications. Digital behavioural change interventions have the potential to provide education and motivate users to regularly engage with self-management of diabetes. This paper describes the development of My Care Hub mobile phone application (app) aimed at supporting self-management in people with type 1 or type 2 diabetes. The development of My Care Hub involved a comprehensive process of healthy behavioural change identification, end users' needs, expert consensus, data security and privacy considerations. The app translation was a highly iterative process accompanied by usability testing and design modification. The app development process included: (1) behaviour change strategy selection; (2) users' involvement; (3) expert advisory involvement; (4) data security and privacy considerations; (5) design creation and output translation into a smartphone app and (6) two usability testings of the app prototype version. The app features include self-management activities documentation, analytics, personalized and generalized messages for diabetes self-management as well as carbohydrate components of common foods in Australia. Twelve respondents provided feedback on the usability of the app. Initially, a simplification of the documentation features of the app was identified as a need to improve usability. Overall, results indicated good user satisfaction rate.

Atypical Tibial Fracture in a 63-Year-Old Woman With Intermittent Use of Bisphosphonate Unmasking Hypophosphatasia.

We report an unusual case of atypical proximal tibial stress fracture (APTF) associated with intermittent use of bisphosphonates (BPs) and persistently low serum alkaline phosphatase (ALP) levels. We describe the case of a 63-year-old white woman who had experienced an APTF after 4 years of intermittent exposure to alendronate given for recurrent metatarsal stress fractures. BP administration was stopped after the diagnosis of the APTF. A review of her previous serum ALP levels revealed they had been consistently low. Adult hypophosphatasia (HPP) was diagnosed by the low serum ALP activity and elevated urine phosphoethanolamine levels. She was treated conservatively with analgesics. Adult HPP is an underrecognized condition associated with atypical insufficiency fractures, and BP use compounds this risk. To the best of our knowledge, we report the first case of intermittent BP exposure preceding an APTF in an adult patient with HPP, highlighting the uncommon site of the proximal tibia for BP-associated atypical insufficiency fractures, the need to screen for HPP in those with persistently low ALP levels before they begin BP therapy, and the importance of avoiding BP use in those with HPP.

Mobile application intervention to promote self-management in insulin-requiring type 1 and type 2 diabetes individuals: protocol for a mixed methods study and non-blinded randomized controlled trial.

Background: Mobile applications (apps) have proven to be useful in supporting diabetes self-care, but non-consideration of users' needs and non-inclusion of educational features are reasons for low continual use. Well-designed mobile apps that meet the needs of diabetes patients and provide ongoing self-management education and support are required. It was hypothesized that apps designed with such features can improve a range of measures including clinical outcomes, knowledge of diabetes, medication adherence, perceived ability for self-management, and quality-of-life. This may eventually facilitate a more robust and cost-effective approach for improving skills and motivation for the management of diabetes. Methods: This project will be conducted in two phases. It will initially employ a mixed methods study design to investigate the self-management needs and perceptions of diabetes patients on the use of mobile apps to support diabetes self-management. Results of the mixed methods study will inform the content and design of an app which will be employed as an intervention tool in a 12-month parallel randomized controlled trial (RCT). The RCT will compare outcomes in relation to standard-of-care alone with standard-of-care plus a mobile phone diabetes app among 150 insulin-requiring types 1 and 2 diabetes patients. The primary outcome measures are clinical parameters such as hemoglobin A1c (HbA1c), lipids, urine albumin-to-creatinine ratio, blood pressure, frequency in events of emergency hyperglycemia and hypoglycemia. Secondary outcomes include knowledge of diabetes, medication intake and adherence, perception of self-care, and quality-of-life. Discussion: Results from this study will provide empirical evidence on the usefulness of a mobile app developed based on self-management needs analysis of diabetic patients. The long-term goal is to harness knowledge gained from this study to provide evidenced-based data, which promote the scale-up or adoption of mobile applications that provide regular, ongoing education and self-management support to people living with diabetes. Trial registration: Australian New Zealand Clinical Trials Registry, ACTRN12618000065291, Registered on 17 January, 2018 (prospectively registered).