Open-source Artificial Pancreas Systems Are Safe and Effective When Supported In-clinic: Outcomes in 248 Consecutive Type 1 Diabetes Clients.

OBJECTIVE: Our aim in this study was to determine the safety, glycemia, and quality of life (QoL) associated with in-clinic installation and management of supported open-source artificial pancreas systems (SOSAPS) in type 1 diabetes (T1D). METHODS: This investigation is a retrospective cohort study of consecutive SOSAPS users at a Canadian diabetes centre. SOSAPS were offered to all moderately tech-savvy T1D clients on sensor-augmented multiple daily injection or pump, able to pay for hardware, and willing to sign a consent and waiver document. SOSAPS were installed and maintained by clinic staff at no cost to clients. iPhone users were assigned to either Loop (n=108) or iPhone artificial pancreas systems (iAPS; n=114) and Android users to Android-type APS (n=24). Outcomes included severe hypoglycemia and diabetic ketoacidosis (DKA), time in range (TIR) 4.0 to 10.0 mmol/L, time below range (TBR) <4 mmol/L, glucose management indicator (GMI), mean sensor glucose (MSG), change in glycated hemoglobin (A1C), and QoL. RESULTS: Two hundred forty-eight subjects (131 males, 117 females), with a mean age of 36 years and diabetes duration of 21 years, experienced 3 episodes of severe hypoglycemia and no DKA over a follow-up of 17 months. TIR rose by 16%, from 64% to 80% (p<0.0001); TBR fell by 1.0%, from 3.5% to 2.5% (p=0.001); MSG fell from 9.0 to 8.1 mmol/L (p<0.001); GMI fell from 7.3% to 6.7% (p<0.001); and A1C fell from 7.2% to 6.7% (p<0.0001). QoL scores were healthy before and improved after SOSAPS. CONCLUSIONS: Clients with T1D using SOSAPS and supported with no-cost care to the client (software, technology, and physician/physician assistant) safely achieved improved TIR, GMI, A1C, and QoL.

Additively Manufactured Surgical Implant Guides: A Review.

Static computer assisted implant surgery (s-CAIS) is an integral part of the digital workflow in implant dentistry and provides the link between the virtual planning environment and surgical field. The accuracy of s-CAIS is influenced by many cumulative factors including the fit of the template which is related to the manufacturing process. This critical review provides an overview of the current research on additively manufactured surgical implant guides.

Flash glucose monitoring in type 2 diabetes managed with basal insulin in the USA: a retrospective real-world chart review study and meta-analysis.

INTRODUCTION: Evidence supporting use of continuous glucose monitoring in type 2 diabetes treated with basal insulin is unclear. This real-world study aimed to assess the impact on glycated hemoglobin (HbA1c) of flash glucose monitoring use in adults with type 2 diabetes managed with basal insulin. RESEARCH DESIGN AND METHODS: Medical records were reviewed for adult individuals with type 2 diabetes using basal insulin for ≥1 year with or without additional antihyperglycemic medication, HbA1c 8.0%-12.0% prior to FreeStyle Libre Flash Glucose Monitoring use for ≥90 days and an HbA1c measurement recorded between 90 and 194 days after device use. Exclusion criteria included utilization of bolus insulin. Meta-analysis data are from the current study (USA) and a similar Canadian cohort. RESULTS: Medical record analysis (n=100) from 8 USA study sites showed significant HbA1c decrease of 1.4%±1.3%, from 9.4%±1.0% at baseline to 8.0%±1.2% after device use, p<0.0001 (mean±SD).Meta-analysis of medical records from USA and Canada sites (n=191) showed HbA1c significantly decreased by 1.1%±0.14% (mean±SE), from baseline 9.2%±1.0% to 8.1%±1.1%, p≤0.0001, with moderate to high heterogeneity between sites (Q=43.9, I2=74.9, p<0.0001) explained by differences in baseline HbA1c between sites.The HbA1c improvement in both groups was observed by age group, body mass index, duration of insulin use and sex at birth. CONCLUSIONS: In a real-world retrospective USA study and a meta-analysis of a larger USA and Canada cohort, HbA1c significantly reduced in basal insulin-treated type 2 diabetes, without bolus insulin initiation and following the commencement of flash glucose monitoring technology.

The impact of flash glucose monitoring on glycated hemoglobin in type 2 diabetes managed with basal insulin in Canada: A retrospective real-world chart review study.

BACKGROUND: The real-world effect of intermittently scanned continuous glucose monitoring on glucose control in type 2 diabetes treated with basal insulin is uncertain. This retrospective real-world study aimed to evaluate change in glycated hemoglobin (HbA1c) amongst adults with type 2 diabetes managed with basal insulin starting flash glucose monitoring. METHODS: Medical records were reviewed for adults with type 2 diabetes treated with basal insulin for ⩾1 year and using FreeStyle LibreTM Flash Glucose Monitoring for ⩾3 months. Prior to device use an HbA1c 8.0%-12.0% was recorded and a further HbA1c result was recorded 3-6 months (90-194 days) after starting device use. RESULTS: Medical records (n = 91) analyzed from six Canadian diabetes centers showed HbA1c significantly decreased by 0.8% ± 1.1 (mean ± SD, [p < 0.0001]) from mean baseline HbA1c 8.9% ± 0.9 to 8.1% ± 1.0 at 3-6 months after initiating flash glucose monitoring. HbA1c improvement was not independently associated with age, BMI, insulin use duration, or sex. CONCLUSION: This Canadian real-world retrospective study showed significantly reduced HbA1c following initiation of flash glucose monitoring technology to further support management of type 2 diabetes treated with basal insulin.

Exploratory examination of inflammation state, immune response and blood cell composition in a human obese cohort to identify potential markers predicting cancer risk.

Obesity has reached epidemic proportions and is often accompanied by elevated levels of pro-inflammatory cytokines that promote many chronic diseases, including cancer. However, not all obese people develop these diseases and it would be very helpful to identify those at high risk early on so that preventative measures can be instituted. We performed an extensive evaluation of the effects of obesity on inflammatory markers, on innate and adaptive immune responses, and on blood cell composition to identify markers that might be useful in distinguishing those at elevated risk of cancer. Plasma samples from 42 volunteers with a BMI>35 had significantly higher CRP, PGE2, IL-1RA, IL-6 and IL-17 levels than 34 volunteers with normal BMIs. Of the cytokines and chemokines tested, only IL-17 was significantly higher in men with a BMI>35 than women with a BMI>35. As well, only IL-17 was significantly higher in those with a BMI>35 that had type 2 diabetes versus those without type 2 diabetes. Whole blood samples from participants with a BMI>35, when challenged with E. coli, produced significantly higher levels of IL-1RA while HSV-1 challenge resulted in significantly elevated IL-1RA and VEGF, and a non-significant increase in G-CSF and IL-8 levels. T cell activation of PBMCs, via anti-CD3 plus anti-CD28, resulted in significantly higher IFNγ production from volunteers with a BMI>35. In terms of blood cells, red blood cell distribution width (RDW), monocytes, granulocytes, CD4+T cells and Tregs were all significantly higher while, natural killer (NK) and CD8+ T cells were all significantly lower in the BMI>35 cohort, suggesting that obesity may reduce the ability to kill nascent tumor cells. Importantly, however, there was considerable person-to-person variation amongst participants with a BMI>35, with some volunteers showing markedly different values from controls and others showing normal levels of many parameters measured. These person-to-person variations may prove useful in identifying those at high risk of developing cancer.

A clinical evaluation of two central venous catheter stabilization systems.

BACKGROUND: Central venous catheters (CVCs) are commonly secured with sutures which are associated with microbial colonization and infection. We report a comparison of a suture-free system with standard sutures for securing short-term CVC in an international multicentre, prospective, randomized, non-blinded, observational feasibility study. Consented critical care patients who had a CVC inserted as part of their clinical management were randomized to receive either sutures or the suture-free system to secure their CVC. The main outcome measures were CVC migration (daily measurement of catheter movement) and unplanned catheter removals. RESULTS: The per cent of unplanned CVC removal in the two study groups was 2% (suture group 2 out of 86 patients) and 6% (suture-free group 5 out of 85 patients). Both securement methods were well tolerated in terms of skin irritation. The time and ease of application and removal of either securement systems were not rated significantly different. There was also no significant difference in CVC migration between the two securement systems in exploratory univariate and multivariate analyses. Overall, 42% (36 out of 86) of the CVC secured with sutures and 56% (48 out of 85) of the CVC secured with the suture-free securement system had CVC migration of ≥ 2 mm. CONCLUSIONS: The two securement systems performed similarly in terms of CVC migration and unplanned removal of CVC; however, the feasibility study was not powered to detect statistically significant differences in these two parameters. TRIAL REGISTRATION: ISRCTN, ISRCTN13939744. Registered 9 July 2015, http://www.isrctn.com/ISRCTN13939744 .

Effect of PF-04634817, an Oral CCR2/5 Chemokine Receptor Antagonist, on Albuminuria in Adults with Overt Diabetic Nephropathy.

INTRODUCTION: Inflammatory cell recruitment, which is potentially mediated by the monocyte chemoattractant protein 1/C-C chemokine receptor type 2 (CCR2) system and by C-C chemokine receptor type 5 (CCR5) activity, may play a role in the development and progression of diabetic nephropathy. PF-04634817 is a dual chemokine CCR2/5 receptor antagonist that is being developed for the treatment of diabetic nephropathy. METHODS: We evaluated the efficacy of PF-04634817 compared with matching placebo for reduction of albuminuria after 12 weeks of treatment in subjects with type 2 diabetes who received standard of care (SOC; angiotensin-converting enzyme inhibitor or angiotensin receptor blocker therapy), in a randomized, double-blind, placebo-controlled, parallel-group phase 2 study. RESULTS: A total of 226 subjects who received SOC with baseline estimated glomerular filtration rates between 20 and 75 ml/min per 1.73 m2 and a baseline urinary albumin-to-creatinine ratio (UACR) of ≥300 mg/g were randomly assigned 3:1 to receive PF-04634817 (150 or 200 mg orally, once daily) or placebo. The primary analysis was Bayesian, with an informative prior for placebo response (equivalent to including an additional 80 subjects in the placebo arm). We observed a placebo-adjusted reduction in UACR of 8.2% (ratio 0.918; 95% credible interval: 0.75-1.09) at week 12 in the PF-04634817 arm. PF-04634817 appeared to be safe and well-tolerated. CONCLUSION: Despite the good safety profile shown by PF-04634817, clinical development for this indication was discontinued in light of the modest efficacy observed.

An in vitro comparison of standard cleaning to a continuous passive disinfection cap for the decontamination of needle-free connectors.

Background: The optimal decontamination method for needle-free connectors is still unresolved. The objective of this study was to determine if a continuous passive disinfection cap is as effective as standard cleaning for the microbial decontamination of injection ports of two types of needle-free connectors. Methods: The injection ports of needle-free connectors were inoculated with Staphylococcus aureus and allowed to dry. Disinfection caps containing 70% (v/v) isopropyl alcohol (IPA) were attached to the connectors for one, three or 7 days and were compared with needle-free connectors cleaned with 2% (w/v) chlorhexidine gluconate (CHG) in 70% (v/v) IPA. The number of S. aureus remaining on the injection ports was evaluated. Median log10 reductions and 95% confidence interval (CI) were calculated and data analyzed using the Mann-Whitney test. Results: The application of the disinfection cap resulted in a significantly higher reduction in S. aureus than the 2% (w/v) CHG in 70% (v/v) IPA wipe, achieving a > 5 Log10 reduction in CFU at each time point. Conclusions: The disinfection caps resulted in a significantly higher reduction in S.aureus on the injection ports when compared to the use of a 2% (w/v) CHG in 70% (v/v) IPA wipe. This offers an explanation for the lower rates of central-line associated bloodstream infection (CLABSI) associated with the use of disinfection caps reported in clinical studies.

The risk of microbial contamination associated with six different needle-free connectors.

BACKGROUND: needle-free connectors are widely used in clinical practice. The aim of this study was to identify any differences between microbial ingress into six different connectors (three neutral-displacement, one negative-displacement and two anti-reflux connectors). METHODS: each connector underwent a 7-day clinical simulation involving repeated microbial contamination of the connector's injection ports with Staphylococcus aureus followed by decontamination and then saline flushes through each connector. The simulation was designed to be a surrogate marker for the potential risk of contamination in clinical practice. RESULTS: increasing numbers of S. aureus were detected in the flushes over the 7 days of sampling despite adherence to a rigorous decontamination programme. Significant differences in the number of S. aureus recovered from the saline flush of some types of connectors were also detected. Two different durations (5- and 15-second) of decontamination of the injection ports with 70% isopropyl alcohol (IPA) wipes were also investigated. There was no significant difference between the median number of S. aureus recovered in the saline flushes following a 5-second (165.5, 95% CI=93-260) or a 15-second decontamination regimen (75, 10-190). CONCLUSIONS: The findings suggest that there may be differences in the risk of internal microbial contamination with different types of connectors and that even 15 seconds of decontamination may not fully eradicate microorganisms from the injection ports of some devices.

Diabetes Nurse Case Management in a Canadian Tertiary Care Setting: Results of a Randomized Controlled Trial.

OBJECTIVES: To examine the effects of a 6-month nurse case manager (NCM) intervention compared to standard care (SC) on glycemic control and diabetes distress in a Canadian tertiary-care setting. METHODS: We recruited 140 adults with type 2 diabetes and glycated hemoglobin (A1C) levels >8% (64 mmol/mol) from 2 tertiary care facilities and randomized them to: 1) a 6-month NCM intervention in addition to SC or 2) SC by the primary endocrinologists. Assessments were conducted at baseline and at 6 months. Primary outcomes included A1C levels and diabetes distress scores (DDS). Secondary outcomes included body mass index, blood pressure, diabetes-related behaviour measures, depressive symptoms, self-motivation and perception of support. RESULTS: At the 6-month follow up, the NCM group experienced larger reductions in A1C levels of -0.73% compared to the SC group (p=0.027; n=134). The NCM group also showed an additional reduction of -0.40 (26% reduction) in DDS compared to those in the SC group (p=0.001; n=134). The NCM group had lower blood pressure, ate more fruit and vegetables, exercised more, checked their feet more frequently, were more motivated, were less depressed and perceived more support. There were no changes and no group differences in terms of body mass index, medication compliance or frequency of testing. CONCLUSIONS: Compared to SC, NCM intervention was more effective in improving glycemic control and reducing diabetes distress. It is, therefore, a viable adjunct to standard diabetes care in the tertiary care setting, particularly for patients at high risk and with poor control.

Economic impact of Tegaderm chlorhexidine gluconate (CHG) dressing in critically ill patients.

PURPOSE: To estimate the economic impact of a TegadermTM chlorhexidine gluconate (CHG) gel dressing compared with a standard intravenous (i.v.) dressing (defined as non-antimicrobial transparent film dressing), used for insertion site care of short-term central venous and arterial catheters (intravascular catheters) in adult critical care patients using a cost-consequence model populated with data from published sources. MATERIAL AND METHODS: A decision analytical cost-consequence model was developed which assigned each patient with an indwelling intravascular catheter and a standard dressing, a baseline risk of associated dermatitis, local infection at the catheter insertion site and catheter-related bloodstream infections (CRBSI), estimated from published secondary sources. The risks of these events for patients with a Tegaderm CHG were estimated by applying the effectiveness parameters from the clinical review to the baseline risks. Costs were accrued through costs of intervention (i.e. Tegaderm CHG or standard intravenous dressing) and hospital treatment costs depended on whether the patients had local dermatitis, local infection or CRBSI. Total costs were estimated as mean values of 10,000 probabilistic sensitivity analysis (PSA) runs. RESULTS: Tegaderm CHG resulted in an average cost-saving of £77 per patient in an intensive care unit. Tegaderm CHG also has a 98.5% probability of being cost-saving compared to standard i.v. dressings. CONCLUSIONS: The analyses suggest that Tegaderm CHG is a cost-saving strategy to reduce CRBSI and the results were robust to sensitivity analyses.

Randomized Trial of Two Dissemination Strategies for a Skin Cancer Prevention Program in Aquatic Settings.

OBJECTIVES: We compared 2 strategies for disseminating an evidence-based skin cancer prevention program. METHODS: We evaluated the effects of 2 strategies (basic vs enhanced) for dissemination of the Pool Cool skin cancer prevention program in outdoor swimming pools on (1) program implementation, maintenance, and sustainability and (2) improvements in organizational and environmental supports for sun protection. The trial used a cluster-randomized design with pools as the unit of intervention and outcome. The enhanced group received extra incentives, reinforcement, feedback, and skill-building guidance. Surveys were collected in successive years (2003-2006) from managers of 435 pools in 33 metropolitan areas across the United States participating in the Pool Cool Diffusion Trial. RESULTS: Both treatment groups improved their implementation of the program, but pools in the enhanced condition had significantly greater overall maintenance of the program over 3 summers of participation. Furthermore, pools in the enhanced condition established and maintained significantly greater sun-safety policies and supportive environments over time. CONCLUSIONS: This study found that more intensive, theory-driven dissemination strategies can significantly enhance program implementation and maintenance of health-promoting environmental and policy changes. Future research is warranted through longitudinal follow-up to examine sustainability.

An in vitro comparison of microbial ingress into 8 different needleless IV access devices.

There are conflicting reports of the effect needleless intravenous access devices have on rates of catheter-related bloodstream infection. The aim of this study was to identify any differences between the rates of microbial ingress into 8 different devices following contamination. Each type of device was subjected to a 7-day clinical simulation that involved repeated microbial contamination of the injection site and decontamination followed by saline flushes. Significant differences in the number of microorganisms associated with each device were detected in the saline eluates. Three positive-displacement mechanical valves were associated with the ingress of significantly fewer microorganisms compared with other devices.

Impact of patient use of an online patient portal on diabetes outcomes.

OBJECTIVE: To assess the effect of patient use of an online patient portal on diabetes outcomes. METHODS: Patients included were those with diabetes who were newly referred to a Vancouver-based tertiary care diabetologist between April 2008 and October 2012. Each patient was assessed by the diabetologist, received initial diabetes education and was referred, as necessary, for further education and self-management training. All patients who provided an e-mail address at registration were invited to open an online patient portal account. The portal provided access to diabetes education material, personal laboratory values and a messaging system allowing communication with the diabetologist and staff. Patients who logged in 1 or more times were defined as portal users (n=50); patients who never logged in to the portal were defined as non-users (n=107). A1C was measured at 2 time points: at baseline (i.e. initial, in-clinic visit) and at last follow up (visit no less than 6 months and no more than 2 years after the initial visit). Because usership is self-selected, propensity score matching was used to create comparable user/non-user groups based on available baseline covariates. RESULTS: Compared to non-users, a higher proportion of users achieved A1C ≤7% at follow up (56% vs. 32%) (p=0.031). CONCLUSION: Accessing an online patient portal is associated with improved glycemic control.

Genotypic and antimicrobial characterisation of Propionibacterium acnes isolates from surgically excised lumbar disc herniations.

The anaerobic skin commensal Propionibacterium acnes is an underestimated cause of human infections and clinical conditions. Previous studies have suggested a role for the bacterium in lumbar disc herniation and infection. To further investigate this, five biopsy samples were surgically excised from each of 64 patients with lumbar disc herniation. P. acnes and other bacteria were detected by anaerobic culture, followed by biochemical and PCR-based identification. In total, 24/64 (38%) patients had evidence of P. acnes in their excised herniated disc tissue. Using recA and mAb typing methods, 52% of the isolates were type II (50% of culture-positive patients), while type IA strains accounted for 28% of isolates (42% patients). Type III (11% isolates; 21% patients) and type IB strains (9% isolates; 17% patients) were detected less frequently. The MIC values for all isolates were lowest for amoxicillin, ciprofloxacin, erythromycin, rifampicin, tetracycline, and vancomycin (≤1 mg/L). The MIC for fusidic acid was 1-2 mg/L. The MIC for trimethoprim and gentamicin was 2 to ≥4 mg/L. The demonstration that type II and III strains, which are not frequently recovered from skin, predominated within our isolate collection (63%) suggests that the role of P. acnes in lumbar disc herniation should not be readily dismissed.