Barriers to Physical Activity Among Patients With Type 1 Diabetes

OBJECTIVE—To determine, in an adult population with type 1 diabetes, barriers to regular physical activity using a diabetes-specific barriers measure (the Barriers to Physical Activity in Diabetes [type 1] [BAPAD1] scale) and factors associated with these barriers

Beyond Single Nucleotide Polymorphisms: CYP3A5∗3 ∗6 ∗7 Composite and ABCB1 Haplotype Associations to Tacrolimus Pharmacokinetics in Black and White Renal Transplant Recipients

Interpatient variability in tacrolimus pharmacokinetics is attributed to metabolism by cytochrome P-450 3A5 (CYP3A5) isoenzymes and membrane transport by P-glycoprotein. Interpatient pharmacokinetic variability has been associated with genotypic variants for both CYP3A5 or ABCB1. Tacrolimus pharmacokinetics was investigated in 65 stable Black and Caucasian post-renal transplant patients by assessing the effects of multiple alleles in both CYP3A5 and ABCB1. A metabolic composite based upon the CYP3A5 polymorphisms: ∗3(rs776746), ∗6(10264272), and ∗7(41303343), each independently responsible for loss of protein expression was used to classify patients as extensive, intermediate and poor metabolizers. In addition, the role of ABCB1 on tacrolimus pharmacokinetics was assessed using haplotype analysis encompassing the single nucleotide polymorphisms: 1236C \u3e T (rs1128503), 2677G \u3e T/A(rs2032582), and 3435C \u3e T(rs1045642). Finally, a combined analysis using both CYP3A5 and ABCB1 polymorphisms was developed to assess their inter-related influence on tacrolimus pharmacokinetics. Extensive metabolizers identified as homozygous wild type at all three CYP3A5 loci were found in 7 Blacks and required twice the tacrolimus dose (5.6 ± 1.6 mg) compared to Poor metabolizers [2.5 ± 1.1 mg (P \u3c 0.001)]; who were primarily Whites. These extensive metabolizers had 2-fold faster clearance (P \u3c 0.001) with 50% lower AUC∗ (P \u3c 0.001) than Poor metabolizers. No differences in C12 h were found due to therapeutic drug monitoring. The majority of blacks (81%) were classified as either Extensive or Intermediate Metabolizers requiring higher tacrolimus doses to accommodate the more rapid clearance. Blacks who were homozygous for one or more loss of function SNPS were associated with lower tacrolimus doses and slower clearance. These values are comparable to Whites, 82% of who were in the Poor metabolic composite group. The ABCB1 haplotype analysis detected significant associations of the wildtype 1236T-2677T-3435T haplotype to tacrolimus dose (P = 0.03), CL (P = 0.023), CL/LBW (P = 0.022), and AUC∗ (P = 0.078). Finally, analysis combining CYP3A5 and ABCB1 genotypes indicated that the presence of the ABCB1 3435 T allele significantly reduced tacrolimus clearance for all three CPY3A5 metabolic composite groups. Genotypic associations of tacrolimus pharmacokinetics can be improved by using the novel composite CYP3A5∗3∗4∗5 and ABCB1 haplotypes. Consideration of multiple alleles using CYP3A5 metabolic composites and drug transporter ABCB1 haplotypes provides a more comprehensive appraisal of genetic factors contributing to interpatient variability in tacrolimus pharmacokinetics among Whites and Blacks

Race and sex associations with tacrolimus pharmacokinetics in stable kidney transplant recipients

Study Objective: This study investigated race and sex differences in tacrolimus pharmacokinetics and pharmacodynamics in stable kidney transplant recipients. Design and Setting: A cross-sectional, open-label, single center, 12-h pharmacokinetic-pharmacodynamic study was conducted. Tacrolimus pharmacokinetic parameters included area under the concentration-time curve (AUC0–12), AUC0–4, 12-h troughs (C12 h), maximum concentrations (Cmax), oral clearance (Cl), with dose-normalized AUC0–12, troughs, and Cmax with standardized adverse effect scores. Statistical models were used to analyze end points with individual covariate-adjustment including clinical factors, genotypic variants CYP3A5*3, CYP3A5*6, CYP3A5*7(CYP3A5*3*6*7) metabolic composite, and ATP binding cassette gene subfamily B member 1 (ABCB1) polymorphisms. Patients: 65 stable, female and male, Black and White kidney transplant recipients receiving tacrolimus and mycophenolic acid ≥6 months post-transplant were evaluated. Measurements and Main Results: Black recipients exhibited higher tacrolimus AUC0–12 (Race: p = 0.005), lower AUC* (Race: p \u3c 0.001; Race × Sex: p = 0.068), and higher Cl (Race: p \u3c 0.001; Sex: p = 0.066). Greater cumulative (Sex: p \u3c 0.001; Race × Sex: p = 0.014), neurologic (Sex: p = 0.021; Race × Sex: p = 0.005), and aesthetic (Sex: p = 0.002) adverse effects were found in females, with highest scores in Black women. In 84.8% of Black and 68.8% of White patients, the target AUC0–12 was achieved (p = 0.027). In 31.3% of White and 9.1% of Black recipients, AUC0–12 was \u3c100 \u3eng‧h/ml despite tacrolimus troughs in the target range (p = 0.027). The novel CYP3A5*3*6*7 metabolic composite was the significant covariate accounting for 15%–19% of tacrolimus variability in dose (p = 0.002); AUC0–12 h* (p \u3c 0.001), and Cl (p \u3c 0.001). Conclusions: Tacrolimus pharmacokinetics and adverse effects were different among stable kidney transplant recipient groups based upon race and sex with interpatient variability associated with the CYP3A5*3*6*7 metabolic composite. More cumulative, neurologic, and aesthetic adverse effects were noted among females. Tacrolimus regimens that consider race and sex may reduce adverse effects and enhance allograft outcomes by facilitating more patients to achieve the targeted AUC0–12 h

Continuity Culture: A Key Factor for Building Resilience and Sound Recovery Capabilities

This article investigates the extent to which Jordanian service organizations seek to establish continuity culture through testing, training, and updating of their business continuity plans. A survey strategy was adopted in this research. Primary and secondary data were used. Semistructured interviews were conducted with five senior managers from five large Jordanian service organizations registered with the Amman Stock Exchange. The selection of organizations was made on the basis of simple random sampling. Interviews targeted the headquarters only in order to obtain a homogenous sample. Three out of five organizations could be regarded as crisis prepared and have better chances for recovery. The other two organizations exhibited characteristics of standard practice that only emphasizes the recovery aspect of business continuity management (BCM), while paying less attention to establishing resilient cultures and embedding BCM. The findings reveal that the ability to recover following major incidents can be improved by embedding BCM in the culture of the organization and by making BCM an enterprise-wide process. This is one of few meticulous studies that have been undertaken in the Middle East and the first in Jordan to investigate the extent to which service organizations focus on embedding BCM in the organizational culture

Correlates of physical activity and sitting time in adults with type 2 diabetes attending primary health care in Oman

Abstract Background Despite evidence of the benefits of physical activity in the management of type 2 diabetes, it is poorly addressed in diabetes care. This study aimed to identify the prevalence and correlates of meeting ≥600MET-min/wk. (150 min/wk) of physical activity and sitting time in adults with type 2 diabetes in Oman. Approaches to encourage physical activity in diabetes care were explored. Methods A cross-sectional study using the Global Physical Activity Questionnaire was conducted in 17 randomly selected primary health centres in Muscat. Clinical data including co-morbidities were extracted from the health information system. Questions on physical activity preferences and approaches were included. Patients were approached if they were ≥18 years, and had been registered in the diabetes clinic for >2 years. Results The questionnaire was completed by 305 people (females 57% and males 43%). Mean age (SD) was 57 (10.8) years and mean BMI (SD) was 31.0 (6.0) kg/m2. Duration of diabetes ranged from 2 to 25 (mean 7.6) years. Hypertension (71%) and dyslipidaemia (62%) were common comorbidities. Most (58.4%) had an HbA1c ≥7% indicating poor glycaemic control (55% in males vs 61% in females). Physical activity recommendations were met by 21.6% of the participants, mainly through leisure activities. Odds of meeting the recommendations were significantly higher in males (OR 4.8, 95% CI 2.5–9.1), individuals ≤57 years (OR 3.0, 95% CI 1.6–5.9), those at active self-reported stages of change for physical activity (OR 2.2, 95% CI 1.2–4.1) and those reporting no barriers to performing physical activity (OR 2.7, 95% CI 1.4–4.9). Median (25th, 75th percentiles) sitting time was 705 (600, 780) min/d. Older age (>57 years) was associated with longer sitting time (>705 min/d) (OR 2.8, 95% CI 1.7–4.6). Preferred methods to support physical activity in routine diabetes care were consultations (38%), structured physical activity sessions (13.4%) and referrals to physical activity facilities (5.6%) delivered by a variety of health care providers. Conclusions The results suggest that intervention strategies should take account of gender, age, opportunities within daily life to promote active behaviour and readiness to change. Offering physical activity consultations is of interest to this study population, thus development and evaluation of interventions are warranted

Response to COVID-19 in South Korea and implications for lifting stringent interventions

Background After experiencing a sharp growth in COVID-19 cases early in the pandemic, South Korea rapidly controlled transmission while implementing less stringent national social distancing measures than countries in Europe and the US. This has led to substantial interest in their “test, trace, isolate” strategy. However, it is important to understand the epidemiological peculiarities of South Korea’s outbreak and characterise their response before attempting to emulate these measures elsewhere. Methods We systematically extracted numbers of suspected cases tested, PCR-confirmed cases, deaths, isolated confirmed cases, and numbers of confirmed cases with an identified epidemiological link from publicly available data. We estimated the time-varying reproduction number, Rt, using an established Bayesian framework, and reviewed the package of interventions implemented by South Korea using our extracted data, plus published literature and government sources. Results We estimated that after the initial rapid growth in cases, Rt dropped below one in early April before increasing to a maximum of 1.94 (95%CrI; 1.64-2.27) in May following outbreaks in Seoul Metropolitan Region. By mid-June Rt was back below one where it remained until the end of our study (July 13th). Despite less stringent “lockdown” measures, strong social distancing measures were implemented in high incidence areas and studies measured a considerable national decrease in movement in late-February. Testing capacity was swiftly increased, and protocols were in place to isolate suspected and confirmed cases quickly however we could not estimate the delay to isolation using our data. Accounting for just 10% of cases, individual case-based contact-tracing picked up a relatively minor proportion of total cases, with cluster investigations accounting for 66%. Conclusions Whilst early adoption of testing and contact-tracing are likely to be important for South Korea’s successful outbreak control, other factors including regional implementation of strong social distancing measures likely also contributed. The high volume of testing and low number of deaths suggests that South Korea experienced a small epidemic relative to other countries. Caution is needed in attempting to replicate the South Korean response in populations with larger more geographically widespread epidemics where finding, testing and isolating cases that are linked to clusters may be more difficult

“Having diabetes shouldn’t stop them”: healthcare professionals’ perceptions of physical activity in children with Type 1 diabetes

Background Healthcare professionals (HCP) working with children who have Type 1 Diabetes Mellitus (T1DM) have an important role in advising about and supporting the control of blood glucose level in relation to physical activity. Regular physical activity has known benefits for children with T1DM, but children with chronic conditions may face barriers to participation. The perceptions of HCPs were explored in an effort to understand what influences physical activity in children with T1DM and to inform the practice of those working with children who have T1DM. Methods Semi-structured interviews with 11 HCPs involved in the care of children with T1DM in the UK were conducted. Interviews were recorded, transcribed verbatim and data were analysed using thematic analysis. Results The factors perceived to influence participation in physical activity are presented as five major themes and eleven sub-themes. Themes included the positive influence of social support, the child’s motivation to be active, the potential for formal organisations such as school and diabetes clinic to support physical activity, the challenges faced by those who have T1DM and the perceived barriers to HCPs fulfilling their role of promoting physical activity. Conclusions Healthcare professionals recognised their role in helping children with T1DM and their parents to incorporate physical activity into diabetes management and everyday life, but perceived barriers to the successful fulfilment of this role. The findings highlight the potential for clinical and non-clinical supportive systems to be sensitive to these challenges and facilitate children’s regular participation in physical activity

Report 26: Reduction in mobility and COVID-19 transmission

In response to the COVID-19 pandemic, countries have sought to control transmission of SARS-CoV-2 by restricting population movement through social distancing interventions, reducing the number of contacts. Mobility data represent an important proxy measure of social distancing. Here, we develop a framework to infer the relationship between mobility and the key measure of population-level disease transmission, the reproduction number (R). The framework is applied to 53 countries with sustained SARS-CoV-2 transmission based on two distinct country-specific automated measures of human mobility, Apple and Google mobility data. For both datasets, the relationship between mobility and transmission was consistent within and across countries and explained more than 85% of the variance in the observed variation in transmissibility. We quantified country-specific mobility thresholds defined as the reduction in mobility necessary to expect a decline in new infections (R<1). While social contacts were sufficiently reduced in France, Spain and the United Kingdom to control COVID-19 as of the 10th of May, we find that enhanced control measures are still warranted for the majority of countries. We found encouraging early evidence of some decoupling of transmission and mobility in 10 countries, a key indicator of successful easing of social-distancing restrictions. Easing social-distancing restrictions should be considered very carefully, as small increases in contact rates are likely to risk resurgence even where COVID-19 is apparently under control. Overall, strong population-wide social-distancing measures are effective to control COVID-19; however gradual easing of restrictions must be accompanied by alternative interventions, such as efficient contacttracing, to ensure control

State-level tracking of COVID-19 in the United States

As of 1st June 2020, the US Centers for Disease Control and Prevention reported 104,232 confirmed or probable COVID-19-related deaths in the US. This was more than twice the number of deaths reported in the next most severely impacted country. We jointly model the US epidemic at the state-level, using publicly available deathdata within a Bayesian hierarchical semi-mechanistic framework. For each state, we estimate the number of individuals that have been infected, the number of individuals that are currently infectious and the time-varying reproduction number (the average number of secondary infections caused by an infected person). We use changes in mobility to capture the impact that non-pharmaceutical interventions and other behaviour changes have on therate of transmission of SARS-CoV-2. We estimate thatRtwas only below one in 23 states on 1st June. We also estimate that 3.7% [3.4%-4.0%] of the total population of the US had been infected, with wide variation between states, and approximately 0.01% of the population was infectious. We demonstrate good 3 week model forecasts of deaths with low error and good coverage of our credible intervals

Poor glycaemic control is associated with reduced exercise performance and oxygen economy during cardio-pulmonary exercise testing in people with type 1 diabetes

BackgroundTo explore the impact of glycaemic control (HbA1c) on functional capacity during cardio-pulmonary exercise testing in people with type 1 diabetes.MethodsSixty-four individuals with type 1 diabetes (age: 34 ± 8 years; 13 females, HbA1c: 7.8 ± 1% (62 ± 13 mmol/mol), duration of diabetes: 17 ± 9 years) performed a cardio-pulmonary cycle ergometer exercise test until volitional exhaustion. Stepwise linear regression was used to explore relationships between HbA1c and cardio-respiratory data with p ≤ 0.05. Furthermore, participants were divided into quartiles based on HbA1c levels and cardio-respiratory data were analysed by one-way ANOVA. Multiple regression analysis was performed to explore the relationships between changes in time to exhaustion and cardio-respiratory data. Data were adjusted for confounder.ResultsHbA1c was related to time to exhaustion and oxygen consumption at the power output elicited at the sub-maximal threshold of the heart rate turn point (r = 0.47, R2 = 0.22, p = 0.03). Significant differences were found at time to exhaustion between QI vs. QIV and at oxygen consumption at the power output elicited at the heart rate turn point between QI vs. QII and QI vs. QIV (p < 0.05). Changes in oxygen uptake, power output and in oxygen consumption at the power output elicited at the heart rate turn point and at maximum power output explained 55% of the variance in time to exhaustion (r = 0.74, R2 = 0.55, p < 0.01).ConclusionsPoor glycaemic control is related to less economical use of oxygen at sub-maximal work rates and an earlier time to exhaustion during cardio-pulmonary exercise testing. However, exercise training could have the same potential to counteract the influence of poor glycaemic control on functional capacity