A Real-World Observational Study of Gla-300 in Adults with Type 2 Diabetes Who Fast During Ramadan in the South Asia Region: A Subgroup Analysis of the ORION Study.

INTRODUCTION: In this ORION study subgroup analysis, the safety and effectiveness of insulin glargine 300 U/mL (Gla-300) was evaluated in people from the South Asia region with type 2 diabetes mellitus (T2DM) before, during, and after Ramadan, in a real-world setting. METHODS: The ORION study was a real-world, prospective, observational, non-comparative study conducted across 11 countries. The current subgroup analysis included participants from the South Asia region (India and Pakistan) who fasted during Ramadan. The primary endpoint was the percentage of participants experiencing ≥ 1 event of severe and/or symptomatic documented hypoglycemia with self-monitored plasma glucose (SMPG) ≤ 70 mg/dL during Ramadan. Secondary endpoints analyzed were changes in glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), SMPG, insulin dose, and adverse events (AEs). RESULTS: This subgroup analysis included 106 participants from the South Asia region with mean (standard deviation) age of 51.3 (10.9) years and mean number of 29.8 (4.0) fasting days. The number of severe and/or symptomatic documented hypoglycemia events was low in the pre-Ramadan (SMPG ≤ 70 mg/dL: 1 event [0.9%]; SMPG < 54 mg/dL: 1 event [0.9%]) and Ramadan periods (SMPG ≤ 70 mg/dL: 1 event [0.9%]; SMPG < 54 mg/dL: 0 events), and none in the post-Ramadan period. One participant reported severe hypoglycemia (any time of the day: nocturnal or daytime) throughout the pre-Ramadan period. A reduction in HbA1c and FPG levels was seen during the pre- to post-Ramadan period; however, a slight increase in SMPG levels was reported during this same period. Gla-300 daily dose was reduced from 21.6 (9.6) U to 20.2 (8.9) U during the pre-Ramadan to Ramadan period. The incidence of AEs was 1.9%. CONCLUSIONS: The real-world data from the ORION study indicate that Gla-300 is effective, with low risk of hypoglycemia, for the management of T2DM during Ramadan in the South Asian population. TRIAL REGISTRATION: CTRI/2019/02/017636.

Surface barrier discharges for Escherichia coli biofilm inactivation: Modes of action and the importance of UV radiation.

Cold plasma generated in air at atmospheric pressure is an extremely effective antimicrobial agent, with proven efficacy against clinically relevant bacterial biofilms. The specific mode of bacterial inactivation is highly dependent upon the configuration of the plasma source used. In this study, the mode of microbial inactivation of a surface barrier discharge was investigated against Escherichia coli biofilms grown on polypropylene coupons. Different modes of exposure were considered and it was demonstrated that the long-lived reactive species created by the plasma are not solely responsible for the observed microbial inactivation. It was observed that a synergistic interaction occurs between the plasma generated long-lived reactive species and ultraviolet (UV) photons, acting to increase the antimicrobial efficacy of the approach by an order of magnitude. It is suggested that plasma generated UV is an important component for microbial inactivation when using a surface barrier discharge; however, it is not through the conventional pathway of direct DNA damage, rather through the synergistic interaction between liquid in the biofilm matrix and long-lived chemical species created by the discharge.

Integrating an early childhood development programme into Bangladeshi primary health-care services: an open-label, cluster-randomised controlled trial.

BACKGROUND: Poor development in young children in developing countries is a major problem. Child development experts are calling for interventions that aim to improve child development to be integrated into health services, but there are few robust evaluations of such programmes. Previous small Bangladeshi trials that used individual play sessions with mothers and their children (at home or in clinics), which were predominantly run by employed women, found moderate improvements on child development. We aimed to integrate an early childhood development programme into government clinics that provide primary health care and to evaluate the effects of this intervention on child cognition, language, and motor development, growth, and behaviour in a subsample of the children. METHODS: In this open-label cluster-randomised controlled trial, we recruited individuals from community clinics in Narsingdi district, Bangladesh. These clinics were randomly selected from a larger sample of eligible clinics, and they were assigned (1:1) to either deliver an intervention of 25 sessions, in which mothers of eligible children were shown how to support their child's development through play and interactions, or to deliver no intervention (control group). Participants were underweight children, defined as a weight-for-age Z score of -2 SDs of the WHO standard, who were aged 5-24 months and who lived near the clinic (defined as a walk of less than 30 min). Government health workers ran these sessions at the clinics as part of their routine work, and mothers and children attended fortnightly in pairs (instead of individual weekly home visits that were specified in the original programme). A subsample of children from each clinic was randomly selected for impact evaluation, and these children were assessed on the Bayley Scales of Infant and Toddler Development for their cognitive, language, and motor performance and for their behaviour with Wolke's ratings, before and after implementation of the intervention. The primary outcomes were the performance of this evaluation subsample on the Bayley and Wolke scales and their anthropometric measurements (weight, length or height, and head circumference) after 1 year of the intervention. This study is registered with ClinicalTrials.gov, number NCT02208531. FINDINGS: Between Nov 29, 2014, and April 30, 2015, 12 054 children in 90 clinics were screened, and between six and 25 underweight children were enrolled from each clinic. From the 2423 (20%) underweight children, we excluded 656 (27%) children who lived more than 30-min walking distance from the community clinics, and 30 (1%) children whose mothers did not consent to participate. We therefore enrolled 1737 (72%) children from these 90 clinics. After randomisation, the control group clinics included 878 (51%) children (who all received no intervention) and the intervention group clinics included 859 (49%) children (who all received the child development programme sessions). Eight children from each clinic (360 [41%] children from the control group clinics and 358 [42%] children from the intervention group clinics) were randomly selected for inclusion in the evaluation subsample. Between Feb 24, 2016, and Sept 7, 2016, 344 (96%) children in control group clinics and 343 (96%) children in intervention group clinics were assessed for the primary outcome. 16 (5%) children in the control group clinics and 15 (4%) children in the intervention group clinics did not provide all data and were not included in final analyses. An intention-to-treat analysis showed that the intervention significantly improved children's cognition (effect size 1·3 SDs, 95% CI 1·1 to 1·5; p=0·006), language (1·1 SDs, 0·9 to 1·2; p=0·01), and motor composite scores (1·2 SDs, 1·0 to 1·3; p=0·006) and behaviour ratings (ranging from 0·7 SDs, 0·5 to 0·9; p=0·02; to 1·1 SDs, 1·0 to 1·2; p=0·007), but the intervention had no significant effect on growth (p values ranged from 0·05 to 0·74). Three (1%) children in the intervention group died, but their deaths were not related to the intervention. INTERPRETATION: The extent and range of benefits of our intervention are encouraging. Health workers ran most of the sessions effectively and attendance was good, which is promising for scale-up of the intervention model. However, researchers trained and supervised the health workers, and the next step will be to determine whether the Bangladeshi ministry of health can perform these tasks. In future programmes, more attention needs to be paid to the nutrition of the children. FUNDING: Grand Challenges Canada (Saving Brains).

The generation and transport of reactive nitrogen species from a low temperature atmospheric pressure air plasma source.

The reactive chemical species generated by non-equilibrium plasma under atmospheric pressure conditions are key enablers for many emerging applications spanning the fields of biomedicine, manufacturing and agriculture. Despite showing great application potential, insight in to the underpinning reactive species generation and transport mechanisms remains scarce. This contribution focuses on the spatiotemporal behaviour of reactive nitrogen species (RNS) created and transported by an atmospheric pressure air surface barrier discharge (SBD) using both laser induced fluorescence and particle imaging velocimetry measurements combined with experimentally validated numerical modelling. It was observed that highly reactive species such as N are confined to the discharge region while less reactive species such as NO, NO2 and N2O closely followed the induced flow. The concentration of key RNS was found to be in the 10-100 ppm range at a position of 25 mm downstream of the discharge region. A close agreement between the experimental and computational results was achieved and the findings provide a valuable insight in to the role of electrohydrodynamic forces in dictating the spatiotemporal distribution of reactive chemical species beyond the plasma generation region, which is ultimately a key contributor towards downstream treatment uniformity and application efficacy.

Predictive and explanatory factors of change in HbA1c in a 24-week observational study of 66,726 people with type 2 diabetes starting insulin analogs.

OBJECTIVE: Individualization of therapy choices requires the prediction of likely response. Predictor and explanatory factors of change in HbA1c were studied using data from a large observational study of starting insulin analog therapy (the A1chieve study). RESEARCH DESIGN AND METHODS: Univariate analyses were performed for insulin-naive people and prior insulin users in the A1chieve study. Statistically significant factors were carried forward to baseline factor-only multivariate analyses ("predictor" analysis), and separately using all significant factors ("explanatory" analysis). Power was considered in terms of the variance explained. RESULTS: Geographical region, baseline HbA1c level, lipid levels, and baseline insulin dose were the most powerful predictors of HbA1c change (mean change -2.1% [-23 mmol/mol]) observed in the univariate analysis (r2 > 0.010, P < 0.001). However, although the predictor and explanatory multivariate models explained 62-82% of the variance in HbA1c change, this was mainly associated with baseline HbA1c (r2 = 0.544-0.701) and region (r2 = 0.014-0.037). Other factors were statistically significant but had low predictive power (r2 < 0.010); in the explanatory analysis, this included end-of-study hypoglycemia (insulin-naive group), insulin dose, and health-related quality of life (r(2) < 0.001-0.006, P ≤ 0.007). CONCLUSIONS: Many factors can guide clinicians in predicting the response to starting therapy with insulin analogs, but many are interdependent and thus of poor utility. The factor explaining most of the variance in HbA1c change is baseline HbA1c level, with each increase of 1.0%-units (11 mmol/mol) providing a 0.7-0.8%-units (8-9 mmol/mol) greater fall. Other factors do not explain much of the remaining variance, even when including all end-of-trial measures.

Clinical experience with insulin detemir in patients with type 2 diabetes from the near East countries.

INTRODUCTION: This study aimed at determining the clinical safety and efficacy of insulin detemir (IDet) in combination with oral anti-diabetic drugs (OADs) in type 2 diabetes (T2D) patients from four Near East Countries (Israel, Jordan, Pakistan and Lebanon). METHODS: This prospective observational study included T2D patients previously on OADs and newly diagnosed patients initiating IDet with or without OADs, at the discretion of physicians. Safety objectives included evaluation of hypoglycemia and adverse drug reactions (ADRs) from baseline to Week 24. Efficacy outcomes included baseline to Week 24 changes in glucose control parameters (glycated hemoglobin [HbA1c], fasting plasma glucose [FPG] and post-breakfast post-prandial plasma glucose [PPPG]). Change in body weight during this period was also assessed. RESULTS: A total of 2,155 patients (mean ± SD: age 57.1 ± 11.0 years, BMI 29.4 ± 5.1 kg/m(2), average diabetes duration 9.2 ± 5.4 years) were included. IDet dose at baseline was 0.20 ± 0.09 U/kg titrated up to 0.34 ± 0.14 U/kg by Week 24. From baseline to Week 24, the total number of hypoglycemic episodes increased from 1.30 to 1.37 events/patient-year, while major hypoglycemic episodes decreased from 0.15 to 0.02 events/patient-year. A total of 9 ADRs were reported, of which one event was a serious ADR. Statistically significant improvements in glucose control were reported from baseline to Week 24 (HbA1c: 9.6 ± 1.6% vs. 7.6 ± 1.1%; FPG: 201.5 ± 59.5 mg/dL vs. 124.9 ± 31.6 mg/dL; PPPG: 264.2 ± 65.7 mg/dL vs. 167.2 ± 36.8 mg/dL; all p < 0.0001). Body weight did not change significantly after 24 weeks of IDet therapy. CONCLUSION: IDet therapy in combination with OADs improved glycemic control without increasing the risk of hypoglycemia or weight gain.