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OBJECTIVE: Since December 2019, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has caused a threatening situation worldwide. The new variant of SARS-CoV-2, BA.2.86, also known as Pirola, is an Omicron subvariant that causes great concern because it has been found to contain a large number of mutations. This study aims to investigate and identify the biological and clinical characteristics of this threatening new variant of SARS-CoV-2, which is BA.2.86. MATERIALS AND METHODS: This observational study was performed in the Department of Physiology, College of Medicine, King Saud University, Riyadh, Saudi Arabia. The literature was searched using the key terms including "SARSCoV-2, Omicron, BA.2.86, Pirola, epidemiology, clinical characteristics". The data on Omicron BA.2.86 were obtained from the World Health Organization (WHO), Centers for Disease Control and Prevention (CDC), the Global Initiative on Sharing All Influenza Data (GSIAD), PubMed, Web of Science, regional ministries, research institutes, and international print media. Initially, 26 documents were identified and 10 documents were included for the data analysis. The information on the prevalence and the biological characteristics of the new variant of SARS-CoV-2, Omicron BA.2.86, was recorded and synthesized for analysis. RESULTS: The Omicron BA.2.86 has been identified in 23 countries with 264 confirmed cases as of September 28, 2023. The number and distribution of these cases encompass the United Kingdom 66 (25.0%), USA 34 (12.87%), Denmark 31 (11.74%), Sweden 25 (9.46%), South Africa 20 (7.57%), Spain 20 (7.57%), France 15 (5.68%), Portugal 7 (2.65%), Japan 6 (2.27%), Canada 5 (1.89%), Thailand 5 (1.89%), Israel 5 (1.89%), Greece 5 (1.89%), Germany 3 (1.13%), Belgium 3 (1.13%), Luxembourg 3 (1.13%), Netherlands 3 (1.13%), South Korea 3 (1.13%). However, one case in each country has been reported in Australia, Italy, Iceland, Switzerland, and China. The disease has been reported more frequently in females (71.0%) than males (29.0%). To date, no deaths have been reported. The novel variant has spread more swiftly than other variants of SARS-CoV-2 and has crossed many international borders. CONCLUSIONS: The new Omicron variant BA.2.86 has affected 264 people in 23 countries. The disease is more common in females than males and mainly affects old age people (over 60 years of age). However, no deaths have been reported. The variant is spreading swiftly and transmitted more rapidly. The clinical manifestations in patients with Omicron BA.2.86 variant are not well documented and may be similar to earlier strains of COVID-19 by presenting with mild infectious symptoms, including headache, body ache, cough, fever, generalized myalgia, and severe fatigue. The global health authorities must take preventive measures to stop the outbreak of this emerging variant across the globe to minimize the disease burden. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The human monkeypox infection has become the prevalent orthopoxviral disease in humans, and has developed challenging and threatening situations worldwide. This study is aimed at exploring the global epidemiological, biological and clinical characteristics of monkeypox from 1970 to July 1, 2022. MATERIALS AND METHODS: Information about the monkeypox outbreak and its epidemiological and biological characteristics was obtained from the World Health Organization (WHO), Centers for Disease Control and Prevention (CDC) reports, Pub-Med, and Web of Science. Initially, these two leading international health organizations, and 10 documents were identified; after reviewing, we included WHO and CDC, and six documents in the analysis. RESULTS: Worldwide, from 1970 to July 1, 2022, the total number of confirmed and suspected cases of human monkeypox disease in endemic and non-endemic nations was 46,915. In endemic regions, the number of confirmed cases has been 2,805 and suspected cases have been 38,327, with a total number of 41,132. However, from May 7, 2022, to July 1, 2022, 5,783 monkeypox cases have been found in 52 non-endemic nations in Europe, the UK, the USA, Australia and the Middle East. The majority of cases have been found in the United Kingdom (1,235), Germany (1,054), Spain (800), France (498), United States (459), Portugal (402), Netherlands (288), Canada (287), Italy (192), Belgium (117), Switzerland (91), Israel (42), Ireland (39), Austria (37), Sweden (28), Brazil (21), and Denmark (20). The clinical presentation of monkeypox disease is mild symptoms, including headache, lymphadenopathy, body aches, severe weakness, and acute onset of fever above 38.5°C. A skin rash initiates as macules or papules, progresses to pustules and vesicles, ulcers, and ultimately transitions to crusted scabs. In a short period of about two months, the monkeypox cases swiftly spread in 52 non-endemic countries with an increased percentage worldwide. CONCLUSIONS: The geographic pattern of monkeypox disease spread is rapidly shifting from endemic to non-endemic regions. It now involves not only Africa but also Europe, the USA, the UK, Australia and the Middle East. The clinical characteristics of monkeypox infection are mostly mild symptoms, including headache, lymphadenopathy, body aches, severe weakness, and acute onset of fever above 38.5 degrees Centigrade. A skin rash originates as macules or papules, progresses to pustules and vesicles, ulcers, and eventually to crusted scabs. The regional and international health establishments must take priority preventive procedures to break the outbreaks of monkeypox disease across the globe. The physicians, healthcare workers, patients, and public education is of utmost importance to eradicate the disease. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has created a challenging and threatening situation worldwide. The SARS-CoV-2 embodies diverse epidemiological trends, alongside emerging and reemerging pathogenic characteristics, which have raised great public health concerns. This study aims to investigate the global prevalence, biological and clinical characteristics of Omicron, a new variant of SARS-CoV-2 that is causing concern and fear internationally. MATERIALS AND METHODS: The data on the outbreak of the new variant "Omicron" was obtained from the World Health Organization (WHO), Centers for Disease Control and Prevention (CDC), European Centre for Disease Prevention and Control (ECDC), research institutes, and global international print media. We recorded information on the prevalence, the biological and clinical characteristics of the Omicron Variant of SARS-CoV-2 from November 24 to December 9, 2021. RESULTS: Worldwide, the new variant of SARSCoV-2, Omicron, has been identified in 57 countries with 2152 confirmed cases reported on December 9, 2021, ever since the emergence of the first case of this variant dated November 24, 2021. The number of confirmed Omicron variant cases has significantly increased globally. The novel variant is spreading swiftly and has crossed many borders all around the world. This new variant has been observed to be transmitted far more rapidly than other variants of SARS-CoV-2. CONCLUSIONS: The new variant of SARS-CoV-2 has novel epidemiological and biological characteristics, making it more contagious than other variants of SARS-CoV-2. It has affected 2152 people in 57 countries in a short period of two weeks. However, the fatality rate of the SARS-CoV-2 Omicron variant has not yet been reported. The major clinical manifestations in this new variant are those of a "mild infection", including headache, body ache, muscles ache, cough, fever, generalized myalgia, and severe fatigue. It is infecting younger and middle-aged people more than previous variants. Worldwide health establishments should take immediate preventive measures to stop outbreaks of this emerging and reemerging pathogenic variant across the globe to minimize the disease burden on humanity. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Vaccinations are highly essential to control infectious diseases and epidemics. Presently, the entire world faces a challenging crisis of "Severe Acute Respiratory Diseases Coronavirus 2 (SARS-CoV-2), also known as the COVID-19 pandemic". The impact of vaccines at national levels to reduce the SARS-CoV-2 cases and deaths are unclear, and people have concerns about the effectiveness of vaccines in real-world settings. This study's objective was to examine the effect of the "Pfizer/BioNTech and Oxford/AstraZeneca" vaccines to prevent SARS-CoV-2 cases and deaths in Saudi Arabia. MATERIALS AND METHODS: In this retrospective cohort study, we collected data on SARS-CoV-2 cases and deaths from the date of the first case of SARS-CoV-2 in Saudi Arabia March 2, 2020, to the date of launching the vaccination campaign on December 14, 2020; and from December 15, 2020, to September 8, 2021. We recorded the World Health Organization data and Ministry of Health of Saudi Arabia to evaluate the impact of the "Pfizer/BioNTech, (BNT162b2 mRNA) and Oxford/AstraZeneca (AZD1222)" vaccine against SARS-CoV-2 cases and deaths before and after the vaccination campaign in Saudi Arabia. RESULTS: Saudi Arabia launched the "Pfizer/BioNTech and Oxford/AstraZeneca" vaccination campaign against SARS-CoV-2 on December 14, 2020. In Saudi Arabia, before the vaccination campaign from March 2, 2020, to December 14, 2020, the mean daily SARS-CoV-2 cases were 1235.60, daily deaths were 22.70, that significantly reduced (p=0.0001) compared to the period after the vaccination campaign from December 15, 2020, to September 8, 2021, in which the daily cases fell to 692.08, and daily deaths fell to 9.48 (p=0.0001). CONCLUSIONS: In Saudi Arabia, Pfizer/BioNTech and Oxford/AstraZeneca vaccinations significantly reduced the number of SARSCoV-2 cases and deaths after the vaccination compared to the period before the vaccination campaign at country levels. The study findings demonstrate that vaccination and adherence to nonpharmaceutical intervention can better control the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The "Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)" disease has caused a worldwide challenging and threatening pandemic (COVID-19), with huge health and economic losses. The US Food and Drug Administration, (FDA) has granted emergency use authorization for treatment with the Pfizer/BioNTech and Moderna COVID-19 vaccines. Many people have a history of a significant allergic reaction to a specific food, medicine, or vaccine; hence, people all over the world have great concerns about these two authorized vaccines. This article compares the pharmacology, indications, contraindications, and adverse effects of the Pfizer/BioNTech and Moderna vaccines. MATERIALS AND METHODS: The required documents and information were collected from the relevant databases, including Web of Science (Clarivate Analytics), PubMed, EMBASE, World Health Organization (WHO), Food and Drug Authorities (FDA) USA, Local Ministries, Health Institutes, and Google Scholar. The key terms used were: Coronavirus, SARS-COV-2, COVID-19 pandemic, vaccines, Pfizer/BioNTech vaccine, Moderna vaccine, pharmacology, benefits, allergic responses, indications, contraindications, and adverse effects. The descriptive information was recorded, and we eventually included 12 documents including research articles, clinical trials, and websites to record the required information. RESULTS: Based on the currently available literature, both vaccines are beneficial to provide immunity against SARS-CoV-2 infection. Pfizer/BioNTech Vaccine has been recommended to people 16 years of age and older, with a dose of 30 µg (0.3 m) at a cost of $19.50. It provides immunogenicity for at least 119 days after the first vaccination and is 95% effective in preventing the SARS-COV-2 infection. However, Moderna Vaccine has been recommended to people 18 years of age and older, with a dose of 50 µg (0.5 mL) at a cost of $32-37. It provides immunogenicity for at least 119 days after the first vaccination and is 94.5% effective in preventing the SARS-CoV-2 infection. However, some associated allergic symptoms have been reported for both vaccines. The COVID-19 vaccines can cause mild adverse effects after the first or second doses, including pain, redness or swelling at the site of vaccine shot, fever, fatigue, headache, muscle pain, nausea, vomiting, itching, chills, and joint pain, and can also rarely cause anaphylactic shock. The occurrence of adverse effects is reported to be lower in the Pfizer/BioNTech vaccine compared to the Moderna vaccine; however, the Moderna vaccine compared to the Pfizer vaccine is easier to transport and store because it is less temperature sensitive. CONCLUSIONS: The FDA has granted emergency use authorization for the Pfizer/BioNTech and Moderna COVID-19 vaccines. These vaccines can protect recipients from a SARS-CoV-2 infection by formation of antibodies and provide immunity against a SARS-CoV-2 infection. Both vaccines can cause various adverse effects, but these reactions are reported to be less frequent in the Pfizer/BioNTech vaccine compared to the Moderna COVID-19 vaccine; however, the Moderna vaccine compared to the Pfizer vaccine is easier to transport and store because it is less temperature sensitive. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also called COVID-19, has caused a pandemic which has swiftly involved the entire world and raised great public health concerns. The scientific community is actively exploring treatments that would potentially be effective in combating COVID-19. Hydroxychloroquine has been demonstrated to limit the replication of SARS-CoV-2 virus in vitro. In malarial pandemic countries, chloroquine is widely used to treat malaria. In malarial non-pandemic nations, chloroquine is not widely used. Chloroquine and hydroxychloroquine share similar chemical structures and mechanisms of action. The aim of this study was to indirectly investigate the efficacy of chloroquine and hydroxychloroquine for the treatment of COVID-19 by determining the prevalence of COVID-19 in malaria pandemic and non-pandemic nations. We sought evidence to support or refute the hypothesis that these drugs could show efficacy in the treatment of COVID-19. MATERIALS AND METHODS: We reviewed in vitro studies, in vivo studies, original studies, clinical trials, and consensus reports, that were conducted to evaluate the antiviral activities of chloroquine and hydroxychloroquine. The studies on “COVID-19 and its allied treatment were found from World Health Organization (WHO), ISI-Web of Science, PubMed, EMBASE, Scopus, Google Scholar, and clinical trial registries. The search was based on keywords: antiviral drugs, chloroquine, hydroxychloroquine, COVID-19, COVID-19 treatment modalities, and coronavirus. In addition, we analyzed the prevalence of COVID-19 in malaria pandemic and non-pandemic countries. The review and analyses were performed on March 28, 2020. RESULTS: For this study, we identified a total of 09 published articles: 03 clinical trials with sample size 150; 03 in vitro studies and 03 expert consensus reports. These studies were all suggestive that chloroquine and hydroxychloroquine can successfully treat COVID-19 infections. We found that COVID-19 infections are highly pandemic in countries where malaria is least pandemic and are least pandemic in nations where malaria is highly pandemic. CONCLUSIONS: Chloroquine and hydroxychloroquine have antiviral characteristics in vitro. The findings support the hypothesis that these drugs have efficacy in the treatment of COVID-19. People are currently using these drugs for malaria. It is reasonable, given the hypothetical benefit of these two drugs, that they are now being tested in clinical trials to assess their effectiveness to combat this global health crisis. [ABSTRACT FROM AUTHOR]

Diabetes is unique among chronic diseases because clinical outcomes are intimately tied to how the person living with diabetes reacts to and implements treatment recommendations. It is further characterised by widespread social stigma, judgement and paternalism. This physical, social and psychological burden collectively influences self-management behaviours. It is widely recognised that the individual's perspective about the impact of trying to manage the disease and the burden that self-management confers must be addressed to achieve optimal health outcomes. Standardised, rigorous assessment of mental and behavioural health status, in interaction with physical health outcomes is crucial to aid understanding of person-reported outcomes (PROs). Whilst tempting to conceptualise PROs as an issue of perceived quality of life (QoL), in fact health-related QoL is multi-dimensional and covers indicators of physical or functional health status, psychological and social well-being. This complexity is illuminated by the large number of person reported outcome measures (PROMs) that have been developed across multiple psychosocial domains. Often measures are used inappropriately or because they have been used in the scientific literature rather than based on methodological or outcome assessment rigour. Given the broad nature of psychosocial functioning/mental health, it is important to broadly define PROs that are evaluated in the context of therapeutic interventions, real-life and observational studies. This report summarises the central themes and lessons derived in the assessment and use of PROMs amongst adults with diabetes. Effective assessment of PROMs routinely in clinical research is crucial to understanding the true impact of any intervention. Selecting appropriate measures, relevant to the specific factors of PROs important in the research study will provide valuable data alongside physical health data., (© 2024 Diabetes UK.)

People with Alzheimer's disease or related dementias and diabetes mellitus (ADRD-DM) are at high risk for hypoglycemic events. Their cognitive impairment and psychosocial situation often hinder detection of hypoglycemia. Extending use and benefits of continuous glucose monitoring (CGM) to people with ADRD-DM could improve hypoglycemia detection, inform care, and reduce adverse events. However, cognitive impairment associated with ADRD presents unique challenges for CGM use. This commentary proposes applying the human-centered design process to CGM, investigating design solutions or interventions needed to integrate CGM into the health care of patients with ADRD-DM. With this process, we can identify and inform CGM designs for people with ADRD-DM, broadening CGM access, increasing detection and treatment of the silent threat posed by hypoglycemia., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Michael Weiner reports stock ownership in AbbVie Inc, Amgen Inc, Boston Scientific Corporation, Bristol-Myers Squibb Company, IBM, Integer Holdings Corp, Johnson & Johnson, Mallinckrodt PLC, Mead Johnson & Company, LLC, Medtronic, Mylan N.V., Novo Nordisk A/S, Perspecta Inc, Pfizer Inc, Roche Pharmaceuticals, Senseonics, Stryker Corp, Teva Pharmaceutical Industries Ltd, and Walgreens Boots Alliance, Inc. Rich Holden provides paid scientific advising to Cook Medical. April Savoy reports stock ownership in Pfizer Inc. and GSK (GlaxoSmithKline) Plc. David Klonoff is a consultant to Eoflow, Fractyl Health, Lifecare, Integrity, Rockley Photonics, and Thirdwayv. All other authors report no conflicts of interest.

Aim: To evaluate the glycaemia risk index (GRI) and its association with other continuous glucose monitoring (CGM) metrics after initiation of an automated insulin delivery (AID) system in patients with type 1 diabetes (T1D)., Materials and Methods: Up to 90 days of CGM data before and after initiation of an AID system from 185 CGM users with T1D were collected. GRI and other CGM metrics were calculated using cgmanalysis R software and were analysed for 24 hours, for both night-time and daytime. GRI values were assigned to five GRI zones: zone A (0-20), B (21-40), C (41-60), D (61-80) and E (81-100)., Results: Compared with baseline, GRI and its components decreased significantly after AID initiation (GRI: 48.7 ± 21.8 vs. 29 ± 13; hypoglycaemia component: 2.7 ± 2.8 vs. 1.6 ± 1.7; hyperglycaemia component: 25.3 ± 14.5 vs. 15 ± 8.5; P < .001 for all). The GRI was inversely correlated with time in range before (r = -0.962) and after (r = -0.961) AID initiation (P < .001 for both). GRI was correlated with time above range (before: r = 0.906; after = 0.910; P < .001 for both), but not with time below range (P > .05). All CGM metrics improved after AID initiation during 24 hours, for both daytime and night-time (P < .001 for all). Metrics improved significantly more during night-time than daytime (P < .01)., Conclusions: GRI was highly correlated with various CGM metrics above, but not below target range, both before and after AID initiation., (© 2023 John Wiley & Sons Ltd.)

Competing Interests: We declare no competing interests

A growing number of individuals with type 1 diabetes are choosing to use "do-it-yourself" artificial pancreas systems (DIY APS) to support their diabetes self-management. Observational and self-report data of glycemic benefits of DIY APS are promising; however, without rigorous clinical trials or regulation from governing bodies, liability and user safety continue to be central concerns for stakeholders. Despite DIY APS having been used for several years now, there are no guidelines to assist users and healthcare professionals in addressing DIY APS use in routine clinical care. This commentary reports key stakeholders' perspectives presented at the annual Advanced Technologies and Treatments in Diabetes conference in February 2020. Important considerations to inform the development of clinical care guidelines are also presented to generate further debate.

Diabetes mellitus is a chronic illness in the United States affecting nearly 120 million adults, as well as increasing in children under the age of 18. Diabetes was also the 7th leading cause of death in the United States with 270 K deaths in 2017. Diabetes is best managed by tight glycemic control, as achieving near-normal glucose levels is key to reduce the risk of microvascular complications. Currently, continuous glucose monitoring (CGM) systems have been recognized as the ideal monitoring systems for glycemic control of diabetic patients. Briefly, a CGM system measures blood glucose levels in subcutaneous tissue by attaching a CGM sensor to the skin, allowing the users to make appropriate modifications to their medical interventions according to experience or empirically derived algorithms. The principles of the glucose sensing employed in the current commercially available CGM systems are mainly electrochemical, and employ the gold standard enzyme, glucose oxidase, as the glucose sensing molecule with the combination of hydrogen peroxide monitoring or with the combination of redox mediator harboring hydrogel. Recently, by employing an abiotic synthetic receptor harboring a fluorescent probe combined with a fluorescent detection system, a chronic CGM was commercialized. In addition, the development of less or non-invasive monitoring sensors targeting glucose in tears, sweat, saliva and urine have become of great interest although their clinical relevancy is still controversial. This review article introduces current and future technological aspects of CGM systems, the flagship technology in biosensor research, which was initiated, matured and is still growing in North America., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: Hepatic-directed vesicle insulin (HDV) uses a hepatocyte-targeting moiety passively attaching free insulin, improving subcutaneous insulin's hepatic biodistribution. We assessed HDV-insulin lispro (HDV-L) versus insulin lispro (LIS) in type 1 diabetes (T1D)., Research Design and Methods: Insulin Liver Effect (ISLE-1) was a 26-week, phase 2b, multicenter, randomized, double-blind, noninferiority trial., Results: Among 176 randomized participants (HDV-L n = 118, LIS n = 58), the difference in change from baseline A1C was 0.09% (95% CI -0.18% to 0.35%), confirming noninferiority (prespecified margin ≤0.4%). Overall, there were no statistically significant differences between treatments for hypoglycemia or insulin dosing. However, baseline A1C modified the treatment group effect (interaction P < 0.001) on clinically apparent hypoglycemia designated by treatment-blinded investigators as severe. Thus, at higher baseline A1C, there was less hypoglycemia and lower insulin dosing with similar A1C outcomes during HDV-L versus LIS, whereas greater risk of hypoglycemia despite similar A1C outcomes and insulin doses was observed with lower baseline A1C. Among poorly controlled participants (A1C ≥8.5%), incidence rates of severe hypoglycemia in the HDV-L and LIS arms were 69 and 97 events/100 person-years, respectively ( P = 0.03), whereas with A1C <8.5%, respective rates were 191 and 21 events/100 person-years ( P = 0.001). Similar A1C-dependent trends in hypoglycemia were seen with continuous glucose monitoring. Among poorly controlled participants, bolus insulin doses at end point were ∼25% lower with HDV-L ( P = 0.02), despite similar A1C outcomes; in better-controlled participants, insulin doses and A1Cs were stable over time in both subgroups. No safety signals were identified., Conclusions: Hepatic biodistribution of HDV-L appears to potentiate insulin effect in T1D, with divergent clinical outcomes in hypoglycemia dependent on baseline A1C., (© 2019 by the American Diabetes Association.)

Objective: To investigate the comparability of glucose levels measured with blood gas analyzers (BGAs) and by central laboratories (CLs)., Material and Methods: Glucose measurements obtained between June 1, 2007, and March 1, 2016, at the Vanderbilt University Medical Center were reviewed. The agreement between CL and BGA results were assessed using Bland-Altman, consensus error grid (CEG), and surveillance error grid (SEG) analyses. We further analyzed the BGAs' performance against the US Food and Drug Administration (FDA) 2014 draft guidance and 2016 final guidance for blood glucose monitoring and the International Organization for Standardization (ISO) 15197:2013 standard., Results: We analyzed 2671 paired glucose measurements, including 50 pairs of hypoglycemic values (1.9%). Bland-Altman analysis yielded a mean bias of -3.1 mg/dL, with 98.1% of paired values meeting the 95% limits of agreement. In the hypoglycemic range, the mean bias was -0.8 mg/dL, with 100% of paired values meeting the 95% limits of agreement. When using CEG analysis, 99.9% of the paired values fell within the no risk zone. Similar results were found using SEG analysis. For the FDA 2014 draft guidance, our data did not meet the target compliance rate. For the FDA 2016 final guidance, our data partially met the target compliance rate. For the ISO standard, our data met the target compliance rate., Conclusion: In this study, the agreement for glucose measurement between common BGAs and CL instruments met the ISO 2013 standard. However, BGA accuracy did not meet the stricter requirements of the FDA 2014 draft guidance or 2016 final guidance. Fortunately, plotting these results on either the CEG or the SEG revealed no results in either the great or extreme clinical risk zones., (Copyright © 2017 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Background: Insulin glargine 300 U/mL (Gla-300) contains the same active ingredient as glargine 100 U/mL (Gla-100), and provides the same number of units in one-third of the volume. The SoloSTAR ® injector pen has been modified to ensure accurate administration of this reduced volume and to improve user experience., Methods: Insulin- and pen-naïve adults with type 2 diabetes (T2DM) inadequately controlled with oral antihyperglycemic drugs, who had glycated hemoglobin (HbA1c) levels of 7.0-11.0 % (53-97 mmol/mol) were studied. They received once-daily Gla-300 in this 4-week, multicenter, open-label, single-arm study (NCT02227212). Ease of use/ease of learning (the primary endpoint), glycemic control, safety, and reliability of the disposable (prefilled) Gla-300 injector pen (secondary endpoints) were evaluated., Results: At week 4, 95.0% of 40 participating subjects assessed the pen as excellent/good and none as poor/very poor; 97.5% would recommend it to others. Total Diabetes Treatment Satisfaction Questionnaire scores were stable throughout the study. Mean (SD) fasting plasma glucose levels decreased from 166.1 (35.0) mg/dL at baseline to 124.2 (41.1) mg/dL at week 4. No product technical complaints (PTCs) or adverse events (AEs) related to PTCs were reported. The number of subjects experiencing hypoglycemic events of any kind and the incidence of AEs were low. No serious AEs were reported., Conclusions: The Gla-300 injector pen is easy to use and easy to learn to use, with demonstrable reliability and high degrees of acceptance and treatment satisfaction. Once-daily Gla-300 basal insulin treatment was well tolerated and effective in pen- and insulin-naïve adult T2DM subjects.

Background: Devices employing electrochemistry-based correction algorithms (EBCAs) are optimized for patient use and require special handling procedures when tested in the laboratory. This study investigated the impact of sample handling on the results of an accuracy and hematocrit interference test performed with BG*Star, iBG*Star; OneTouch Verio Pro and Accu-Chek Aviva versus YSI Stat 2300., Methods: Venous heparinized whole blood was manipulated to contain three different blood glucose concentrations (64-74, 147-163, and 313-335 mg/dL) and three different hematocrit levels (30%, 45%, and 60%). Sample preparation was done by either a very EBCA-experienced laboratory testing team (A), a group experienced with other meters but not EBCAs (B), or a team inexperienced with meter testing (C). Team A ensured physiological pO 2 and specific sample handling requirements, whereas teams B and C did not consider pO 2 . Each sample was tested four times with each device. In a separate experiment, a different group similar to group B performed the experiment before (D1) and after (D2) appropriate sample handling training., Results: Mean absolute deviation from YSI was calculated as a metrix for all groups and devices. Mean absolute relative difference was 4.3% with team A (B: 9.2%, C: 5.2%). Team B had much higher readings and team C produced 100% of "sample composition" errors with high hematocrit levels. In a separate experiment, group D showed a result similar to group B before the training and improved significantly when considering the sample handling requirements (D1: 9.4%, D2: 4.5%, P < 0.05)., Conclusions: Laboratory performance testing of EBCA devices should only be performed by trained staff considering specific sample handling requirements. The results suggest that healthcare centers should evaluate EBCA-based devices with capillary blood from patients in accordance with the instructions for use to achieve reliable results.

Background: Using the standard venous reference for the evaluation of continuous glucose monitoring (CGM) systems could possibly negatively affect measured CGM accuracy since CGM are generally calibrated with capillary glucose and venous and capillary glucose concentrations differ. We therefore aimed to quantify the effect of using capillary versus venous glucose reference samples on estimated accuracy in capillary calibrated CGM., Methods: We evaluated 41 individuals with type 1 diabetes mellitus (T1DM) using the Dexcom G4 CGM system over 6 days. Patients calibrated their CGM devices with capillary glucose by means of the HemoCue system. During 2 visits, capillary and venous samples were simultaneously measured by HemoCue and compared to concomitantly obtained CGM readings. The mean absolute relative difference (MARD) was calculated using capillary and venous reference samples., Results: Venous glucose values were 0.83 mmol/L (15.0 mg/dl) lower than capillary values over all glycemic ranges, P < .0001. Below 4 mmol/l (72 mg/dl), the difference was 1.25 mmol/l (22.5 mg/dl), P = .0001, at 4-10 mmol/l (72-180 mg/dl), 0.67 mmol/l (12.0 mg/dl), P < .0001 and above 10 mmol/l (180 mg/dl), 0.95 mmol/l (17.1 mg/dl), P < .0001. MARD was 11.7% using capillary values as reference compared to 13.7% using venous samples, P = .037. Below 4 mmol/l (72 mg/dl) MARD was 16.6% and 31.8%, P = .048, at 4-10 mmol/l (72-180 mg/dl) 12.1% and 12.6%, P = .32, above 10 mmol/l (180 mg/dl) 8.7% and 9.2%, P = .82., Conclusion: Using capillary glucose concentrations as reference to evaluate the accuracy of CGM calibrated with capillary samples is associated with a lower MARD than using venous glucose as the reference. Capillary glucose concentrations were significantly higher than venous in all glycemic ranges., (© 2016 Diabetes Technology Society.)

Background: Infusion sets for use with insulin pumps are recommended for use for 2 to 3 days to avoid local skin reactions, for example, to the insulin formulation and preservatives like meta-cresol. However, many patients use the catheters longer for economic reasons. We performed this study to investigate the tolerability of 2-day use of infusion sets in comparison to 4-day use in a real-world setting., Methods: This prospective randomized controlled crossover study with 2 × 3-month observation periods was performed with 24 type 1 patients. At baseline, patients were trained on the use of the infusion system (Medtronic /Mio® or inset™ II) and randomized to any of the 2 treatment sequences. Observation parameters included glycemic control, frequency and nature of device-related, and procedure-related adverse events and patient preference., Results: The per-protocol analysis was performed with 22 patients (5 men, 17 women, age 39 ± 11 years, BMI 27.0 ± 3.5 kg/m2). The number of catheter related adverse events was 290 with 2-day use versus 495 with 4-day use (P < .05). The overall number of treatment related events was 750 with 2-day use versus 934 with 4-day use (P < .001). There was no difference in glycemic control between the treatment arms. Treatment satisfaction was higher with 2-day use (very high/high satisfaction: 90.4% versus 4 day-use: 77.3%, P < .05)., Conclusion: Our results demonstrate that using the infusion sets for a longer usage period of 2-3 days resulted in a clinically relevant increase in treatment-related tolerability problems. Patients should be trained and encouraged not to use insulin pump infusion sets for a longer than the recommended time period., (© 2015 Diabetes Technology Society.)

Background: To deliver insulin glargine 300 U/mL (Gla-300), the widely used SoloSTAR(®) pen has been modified to allow for accurate and precise delivery of required insulin units in one-third of the volume compared with insulin glargine 100 U/mL, while improving usability. Here we compare the accuracy and injection force of 3 disposable insulin pens: Gla-300 SoloSTAR(®), FlexPen(®), and KwikPen™., Methods: For the accuracy assessment, 60 of each of the 3 tested devices were used for the delivery of 3 different doses (1 U, half-maximal dose, and maximal dose), which were measured gravimetrically. For the injection force assessment, 20 pens of each of the 3 types were tested twice at half-maximal and once at maximal dose, at an injection speed of 6 U/s., Results: All tested pens met the International Organization for Standardization (ISO) requirements for dosing accuracy, with Gla-300 SoloSTAR showing the lowest between-dose variation (greatest reproducibility) at all dose levels. Mean injection force was significantly lower for Gla-300 SoloSTAR than for the other 2 pens at both half maximal and maximal doses (P < .0271)., Conclusion: All tested pens were accurate according to ISO criteria, and the Gla-300 SoloSTAR pen displayed the greatest reproducibility and lowest injection force of any of the 3 tested devices., (© 2015 Diabetes Technology Society.)

Background: The functional performance of the JuniorSTAR(®) (Sanofi, Paris, France) half-unit insulin pen was evaluated through a series of specific objective tests to assess the dose accuracy, pen weight, injection force, and dialing torque., Method: Pens (n = 60) were tested under standard atmospheric conditions with 3 different types of insulins manufactured by Sanofi (insulin glargine, insulin glulisine, and biphasic insulin isophane). The dose accuracy was tested according to the ISO 11608-1:2012 standards. Injection doses of 0.010, 0.155, and 0.300 ml were evaluated. For mean weight evaluation, the pens without the cartridge were weighed on precision balances. The injection force was measured using a texture analyzer and the dialing torque was measured using a torque meter., Results: JuniorSTAR met the ISO 11608-1:2012 criteria for dose accuracy as all the delivered doses were within the predefined limits for all types of insulin tested. The mean weight of the JuniorSTAR pen was 33.4 g (SD = 0.075). The mean injection force was 6.0 N (SD = 0.8), 4.3 N (SD = 0.4), and 5.1 N (SD = 0.6) for insulin glargine, insulin glulisine, and biphasic insulin isophane, respectively. The mean dialing torque was 5.09 Ncm (SD = 0.29) and 5.88 Ncm (SD = 0.53) for setting and correcting a dose, respectively., Conclusions: Together with results from a previously reported usability survey, these results show that the JuniorSTAR reusable, half-unit pen is a lightweight and accurate device for insulin delivery with a dialing torque and injection force suitable for young people with type 1 diabetes., (© 2015 Diabetes Technology Society.)

Temperature changes on the surface of the skin lead to modifications of subcutaneous microcirculation. This phenomenon is employed in a standardized way by the InsuPad device to stabilize skin conditions before injections, which is associated with enhanced prandial insulin absorption. Three programmed warming cycles to 40°C within 50 minutes are resulting in faster insulin appearance in the plasma. Early standardized meal tolerance studies indicated a substantial improvement in postprandial glucose control when the same short-acting insulin analog dose was applied using InsuPad, and a dose reduction by 20% resulted in comparable glucose excursions. Similar results were obtained when patients applied the device under real-world conditions for 1 month. The InsuPad device was also tested in a prospective, controlled, parallel 3-month real-world study with 145 well-controlled but insulin-resistant patients with type 1 or type 2 diabetes. Patients were treated to target in both treatment arms (6.2 ± 0.5% in each group), with or without the device. However, patients with InsuPad needed 28% less prandial insulin, needed 12.5% less total insulin, and had 46% less confirmed hypoglycemic events (blood glucose < 63 mg/dL) as compared to the control group. Except for very few inflammatory or allergic skin reactions, there were no device-specific adverse events reported from these studies. In conclusion, use of InsuPad when applying prandial insulin doses may result in a safer and more efficient treatment of type 1 or type 2 diabetes., (© 2014 Diabetes Technology Society.)

Background: Previous studies have shown that heating the insulin injection site may accelerate insulin absorption. We investigated the pharmacological profile of insulin administered with InsuPatch, a local skin-heating device., Methods: In this randomized, crossover study carried out in 56 subjects with type 1 diabetes treated with insulin pump [mean age 32 ± 13.5 years; 23 women; HbA1c :7.8 ± 0.9% (62 ± 10 mmol/mol) (mean+/-standard deviation)]. Euglycemic glucose clamps were performed after administration of 0.15 units/kg of short-acting insulin analogues. Each subject underwent three clamp procedures: two with the InsuPatch device (day 1 and day 3) and one without the device (day 1 control). The primary endpoints were the following: (1) the change in the area under the curve (AUC) of insulin during the first 60 min post-insulin bolus on day 1 with the InsuPatch device versus day 1 control and (2) parameters to assess the safety of using the device., Results: The area under the curve of insulin during the initial 60 min (insulin AUC(0-60)) after insulin bolus was increased by 29.7 ± 7% on day 1 InsuPatch versus day 1 control (p < 0.01). Maximal post-insulin bolus concentration was 57 mU/L on day 1 InsuPatch versus 47.6 mU/L on day 1 control (p < 0.01). On day 3 InsuPatch, insulin AUC(0-60) was increased by 27.9 ± 72% versus day 1 InsuPatch (p < 0.01). Maximal insulin concentration was 70.4 mU/L versus 57 mU/L, respectively (p = 0.05)., Conclusions: The use of the heating device upon administration of short-acting insulin analogues in pump-treated type 1 diabetic patients was found to enhance insulin absorption. This heating device may therefore serve to achieve better meal insulin coverage., (Copyright © 2014 John Wiley & Sons, Ltd.)

Background: Continuous glucose monitoring (CGM) is a tool widely used in the treatment of patients with type 1 diabetes. The purpose of the current study was to evaluate whether accuracy and patient treatment satisfaction differ between the Enlite™ (Medtronic MiniMed, Inc., Northridge, CA) and Dexcom(®) (San Diego, CA) G4 PLATINUM CGM sensors., Subjects and Methods: Thirty-eight ambulatory patients with type 1 diabetes used the Dexcom G4 and Enlite sensors simultaneously for a minimum of 4 and maximum of 6 days. Patients measured capillary glucose levels with a HemoCue(®) (Ängelholm, Sweden) system six to 10 times a day. In addition, two inpatient studies were performed between Days 1-3 and 4-6., Results: The mean absolute relative difference (MARD) in blood glucose for the Dexcom G4 was significantly lower (13.9%) than for the Enlite sensor (17.8%) (P<0.0001). The corresponding MARDs for Days 1-3 were 15.0% versus 19.4% (P=0.0027) and 13.6% versus 15.9% (P=0.026) for Days 4-6. For glucose levels in the hypoglycemic range (<4.0 mmol/L), the MARD for the Dexcom G4 was 20.0% compared with 34.7% for the Enlite (P=0.0041). On a visual analog scale (VAS) (0-100), patients rated the Dexcom G4 more favorably than the Enlite in 12 out of the 13 user experience questions. For example, more patients rated their experience with the Dexcom G4 as positive (VAS, 79.7 vs. 46.6; P<0.0001) and preferred to use it in their daily lives (VAS, 79.1 vs. 42.1; P<0.0001)., Conclusions: The Dexcom G4 sensor was associated with greater overall accuracy than the Enlite sensor during initial (Days 1-3) and later (Days 4-6) use and for glucose levels in the hypoglycemic range. Patients reported a significantly more positive experience using the Dexcom G4 than the Enlite.

This paper discusses the results of a survey on the usability of a new half-unit insulin pen, JuniorSTAR ® (CE mark pending, under the responsibility of Haselmeier), in children with type 1 diabetes. Insulin pen devices have advantages over the traditional vial-and-syringe method of insulin delivery, including improved patient satisfaction and adherence, greater ease of use and superior accuracy, especially when delivering small doses of insulin. The accuracy and design of insulin pens is particularly important in the paediatric population. Young children often require half-unit adjustments. As the incidence of type 1 diabetes is expected to increase in the coming years in children less than 5 years old, a higher use of half-unit dosing pens may be anticipated. A survey with JuniorSTAR half-unit insulin pen has shown that it is easy to use, read, carry and dial back. This was confirmed by patients and also by nurses. In conclusion, the JuniorSTAR half-unit pen is well suited to the lifestyle of young people with type 1 diabetes and could help them to gain autonomy to self-inject., Competing Interests: Disclosure: David Klonoff is a consultant for Sanofi and InsuLine. Irina Nayberg is a consultant for NovoNordisk. Ivana Rabbone has no conflicts of interest to declare. Wolfgang Landgraf and Catherine Domenger are Sanofi employees. Thomas danne has received honoraria for speaking engagements from several companies involved in the diabetes field and has received grant support for the conduct of studies or scientific meetings from Abbott, Sanofi, Bayer, Roche, Boehringer, Bristol-Myers Squib, Lilly, Medtronic, DexCom and NovoNordisk.