Development of a group structured education programme to support safe exercise in people with Type 1 diabetes: the EXTOD education programme.

AIM: To develop a structured education programme for individuals with Type 1 diabetes who are engaging in regular exercise. METHOD: A multidisciplinary team of experts in supporting exercise and physical activity for people with Type 1 diabetes, alongside researchers with experience of developing self-management education, developed an exercise programme using the Medical Research Council framework. The programme was informed by a review of the evidence relating to Type 1 diabetes and exercise, the behaviour change literature (including the behaviour change taxonomy), and qualitative interviews with stakeholders. The programme and supporting resources were refined using an iterative process of testing, delivery and collecting feedback from participants and the wider development team. RESULTS: The outcome of the intervention development was the design of a feasible and acceptable intervention for people with Type 1 diabetes to support safe exercise. The pilot allowed refinement of the intervention prior to testing in a two-site feasibility randomized controlled trial. Key findings from the pilot informed minor restructuring of the timetable (timings and order) and adaptation of supporting educational materials (participant handbook and teaching materials). CONCLUSION: The 'EXercise in people with Type One Diabetes' (EXTOD) education programme has been developed using robust methodology for the generation of educational interventions. It now needs testing in a randomized controlled trial.

The Microalbuminuria Education Medication and Optimisation (MEMO) study: 4 years follow-up of multifactorial intervention in high-risk individuals with type 2 diabetes.

AIMS: The Microalbuminuria Education Medication and Optimisation (MEMO) study, revealed improved cardiovascular risk and glycaemic control with 18 months of intensive multifactorial intervention in high-risk people with type 2 diabetes, without any increase in severe hypoglycaemia. Our aim was to assess longer-term outcomes at 4-year follow-up in these participants. METHODS: Some 189 individuals with type 2 diabetes and microalbuminuria were recruited from a multi-ethnic population in Leicestershire, UK. The intervention group (n = 95) received multifactorial intervention with self-management education, and the control group (n = 94) received usual care. The primary outcome was change in HbA1c , and secondary outcomes were blood pressure (BP), cholesterol, microalbuminuria, estimated GFR, cardiovascular risk scores and major adverse cardiovascular events. RESULTS: Some 130 participants (68.7%), mean (sd) age 60.8 (10.4) years, duration of diabetes 11.5 (9.7) years, completed 4 years of follow-up. Mean change [95% confidence intervals (CI)] in HbA1c over 4 years was greater with intensive intervention compared with control (-3 mmol/mol, 95% CI -4.95,-1.11; -0.4%, 95% CI -0.67,-0.15; P = 0.002). Significant improvements over the 4 years were also seen in systolic BP (-7.3 mmHg, 95% CI -11.1, -3.5; P < 0.001), diastolic BP (-2.9 mmHg, 95% CI -5.4, -0.3; P = 0.026), cholesterol (-0.3 mmol/l, 95% CI -0.52,-0.12; P = 0.002), and 10-year coronary heart disease (-5.3, 95% CI -8.2,-2.3; P < 0.001) and stroke risk (-4.4, 95% CI -7.5, -1.3; P < 0.001). CONCLUSION: Multifactorial intervention with structured diabetes self-management education compared with usual diabetes care has benefits for cardio-metabolic risk factor profile. There was no increase in severe hypoglycaemia and cardiovascular mortality despite intensive glycaemic control, although the study was not powered to assess these outcomes.

Walking Away from Type 2 diabetes: a cluster randomized controlled trial.

AIMS: This study aimed to investigate whether an established behavioural intervention, Walking Away from Type 2 Diabetes, is effective at promoting and sustaining increased walking activity when delivered within primary care. METHODS: Cluster randomized controlled trial involving 10 general practices recruited from Leicestershire, UK, in 2009-2010. Eight hundred and eight (36% female) individuals with a high risk of Type 2 diabetes mellitus, identified through a validated risk score, were included. Participants in five practices were randomized to Walking Away from Type 2 Diabetes, a pragmatic 3-h group-based structured education programme incorporating pedometer use with annual follow-on refresher sessions. The primary outcome was accelerometer assessed ambulatory activity (steps/day) at 12 months. Longer term maintenance was assessed at 24 and 36 months. Results were analysed using generalized estimating equation models, accounting for clustering. RESULTS: Complete accelerometer data for the primary outcome were available for 571 (71%) participants. Increases in ambulatory activity of 411 steps/day [95% confidence interval (CI): 117, 704] and self-reported vigorous-intensity physical activity of 218 metabolic equivalent min/week (95% CI: 6, 425) at 12 months were observed in the intervention group compared with control; differences between groups were not sustained at 36 months. No differences between groups were observed for markers of cardiometabolic health. Replacing missing data with multiple imputation did not affect the results. CONCLUSIONS: A pragmatic low-resource group-based structured education programme with pedometer use resulted in modest increases in ambulatory activity compared with control conditions after 12 months when implemented within a primary care setting to those at high risk of Type 2 diabetes mellitus; however, the results were not maintained over 36 months.

A Mediterranean diet improves HbA1c but not fasting blood glucose compared to alternative dietary strategies: a network meta-analysis.

BACKGROUND: Overweight or obese individuals with type 2 diabetes are encouraged to lose weight for optimal glucose management, yet many find this difficult. Determining whether alterations in dietary patterns irrespective of weight loss can aid glucose control has not been fully investigated. METHODS: We conducted a systematic review and meta-analysis aiming to determine the effects of a Mediterranean diet compared to other dietary interventions on glycaemic control irrespective of weight loss. Electronic databases were searched for controlled trials that included a Mediterranean diet intervention. The interventions included all major components of the Mediterranean diet and were carried out in free-living individuals at high risk or diagnosed with type 2 diabetes. Network meta-analysis compared all interventions with one another at the same time as maintaining randomisation. Analyses were conducted within a Bayesian framework. RESULTS: Eight studies met the inclusion criteria, seven examined fasting blood glucose (n = 972), six examined fasting insulin (n = 1330) and three examined HbA1c (n = 487). None of the interventions were significantly better than the others in lowering glucose parameters. The Mediterranean diet reduced HbA1c significantly compared to usual care but not compared to the Palaeolithic diet. CONCLUSIONS: The effect of alterations in dietary practice irrespective of weight loss on glycaemic control cannot be concluded from the present review. The need for further research in this area is apparent because no firm conclusions about relative effectiveness of interventions could be drawn as a result of the paucity of the evidence.

Raw and processed data used in the simultaneous analysis of electrical characteristics and microstructure of crystallised PEDOT:PSS based OECTs under strain.

Here is presented raw and analysed data collected during study of the evolution, with uniaxial stretching, of the electrical and microcrystalline characteristics of polystyrene sulfonate doped poly(3,4-ethylenedioxythiophene) (PEDOT:PSS) organic electrochemical transistors (OECTs). X-ray diffraction data from GIWAXS measurements of the PEDOT:PSS material, performed at the SOLEIL light source are presented in raw and partially analysed forms. Current-voltage data, collected concurrently with the GIWAXS data, are also presented, and the evolution of the transconductance of the OECT devices with stretching is shown. GIWAXS data are only examined along the qz specular reflection ridge, and scans along this ridge are extracted and presented. However, the off-specular data may also be of interest to readers and is therefore made available here in its entirety.

Carbon dioxide exchange in cotton: some anomalous fluctuations.

Anomalous depressions in carbon dioxide exchange were observed in cotton leaves that were exhibiting oscillations in transpiration under controlled conditions of environment. The depressions occurred only when leaf temperature exceeded 37.5 degrees C and when the leaf diffusive resistance was minimum. Stomatal control of the supply of carbon dioxide to the leaf does not seem to be implicated in the effect.

Photosynthetic Mechanisms and Paleoecology from Carbon Isotope Ratios in Ancient Specimens of C4 and CAM Plants.

Carbon istotope ratios of modern, 10,000-year-old, and more than 40,000-year-old Atriplex confertifolia (C(4)) material from Nevada caves indicate that the C(4) photosynthetic pathway was operating in these plants over that period. Samples of a plant with crassulacean acid metabolism, Opuntia polyacantha, were also measured, and a shift in the 8(13)C value from -21.9 per mil (more than 40,000 years ago) to -13.9 per mil (10,000 years ago) was observed. This provides unique physiological evidence to support the hypothesis that the late Pleistocene pluvial climate in the region already had become drier about 10,000 years ago.

The role of physical activity in the management of type 2 diabetes mellitus.

Physical activity and weight loss are considered cornerstones of type 2 diabetes mellitus (T2DM) management programmes. However, there is much controversy and debate surrounding the relative importance of each of these factors in the treatment of T2DM. This review provides an overview of the evidence surrounding the relative importance of physical activity and weight loss in the management of T2DM and highlights key ways of initiating physical activity behaviour change.

Homocysteine and coronary heart disease risk in the PRIME study.

INTRODUCTION: Despite recent meta-analyses suggesting that homocysteine is an independent predictor of coronary heart disease (CHD), there is debate regarding whether elevated homocysteine may be deleterious only in the presence of other risk factors, with which it acts synergistically to exert a multiplicative effect on CHD risk, emerging only as a CHD predictor in patients with pre-existing risk factors. The Prospective Epidemiological Study of Myocardial Infarction (PRIME) Study is a multicentre prospective study of 10593 men from France and Northern Ireland, investigating cardiovascular risk factors. We investigated: (1) whether higher homocysteine is associated with increased CHD risk in the PRIME case-control cohort; (2) whether homocysteine interacts synergistically with pre-existing CHD risk factors. METHODS: Homocysteine was measured in 323 participants who had developed CHD at 5-year follow-up and in 638 matched controls. RESULTS: There was no significant difference in homocysteine between cases and controls (p=0.18). Homocysteine was significantly higher in current smokers (geometric mean mumol/l (interquartile range mumol/l) 9.45 (7.43, 11.75)) compared with non-smokers (8.90 (7.32, 10.70); p=0.007). There was a significant interaction between homocysteine, smoking and CHD risk (chi2=10.29, d.f.=2, p=0.006). CONCLUSIONS: These findings suggest that elevated homocysteine is significantly associated with CHD risk in current smokers.

Antibiotic Prophylaxis Regimens in Trauma and Orthopaedic Surgery: Are We Providing Adequate Cover Against Colonizing Organisms?

UNLABELLED: Trauma, elective orthopaedics, and an aging population will result in an increasing health burden and work load. The move to surgical podiatrists in the National Health Service within the United Kingdom will shift the surgical workload away from orthopaedic surgeons. A devastating complication of foot and ankle surgery is postoperative infection. While postoperative infection is multifactorial in etiology, concomitant diabetes mellitus increases the general risk of trauma and orthopaedic surgical site infections up to 8-fold. We therefore undertook a prospective study of our unit antibiotic prophylaxis regimes. Fifty patients participated. Swabs were obtained using aseptic technique from the plantar aspect of the feet, between the toes, and subsequently cultured on agar plates. Specimens were then incubated for 48 hours before being exposed to antibiotic plates. Cultured organisms were classified as susceptible to an antibiotic regimen if susceptibility to cefuroxime, or susceptibility to either drug of the flucloxacillin/gentamicin combination, was demonstrated. Statistical analysis e was performed. A P value <.05 was considered significant. Fifty patients were recruited, 26 (52%) were male. Mean age of 53 ± 19.4 years. The cohort included 15 diabetic, of which 11 (73.3%) insulin-dependent, and 35 nondiabetic patients. Comparing flucloxacillin/gentamicin against cefuroxime overall, susceptibility was noted in 84% and 70%, respectively (P = .096). Resistance to cefuroxime was significantly higher in diabetics than in nondiabetics (53% vs 25%, P = .046). The same pattern was observed for the flucloxacillin/gentamicin regimen (33% vs 9%, P = .049). While both regimens are active against colonizing organisms in this prospective observational study, flucloxacillin and gentamicin provide greater coverage overall. We have demonstrated that the use of flucloxacillin/gentamicin provides better coverage against commensal bacterial flora compared with cefuroxime alone. This is of even greater importance in the case of the specific high-risk subgroups, such as diabetic patients. LEVELS OF EVIDENCE: Level IV: Case Series.

Use of Longitudinal Dose-Response Modeling to Support the Efficacy and Tolerability of Alitretinoin in Severe Refractory Chronic Hand Eczema (CHE).

Longitudinal dose-response analyses of alitretinoin (an investigational agent in the US) were conducted to supplement results from phase III studies in severe, refractory chronic hand eczema, with objectives to address several outstanding development issues (e.g., optimal dose, possible factors affecting efficacy and/or tolerability). Models were fitted to the physicians' global assessment score and triglycerides over time. Five hundred trials were simulated to evaluate the relevance of findings. Analyses clarified that the optimal dose of alitretinoin was 30 mg once daily, where response rates were ∼10% over placebo at 12 weeks and increased by 5-7% over placebo for every 4 weeks thereafter, for up to 24 weeks. Elderly subjects had higher magnitudes of efficacy and an increased probability of high triglycerides. Results from analyses sufficiently addressed the development issues, thereby adding to the weight of evidence supporting the efficacy and safety of alitretinoin in the treatment of severe, refractory chronic hand eczema.

Carbon isotope ratio measurements of succulent plants in southern Africa.

Succulent plants representing 16 families and a variety of growth forms originating from winter, summer, and year-round rainfall regimes in southern Africa were analyzed for carbon isotope ratios. Most families had species with δ13C values indicative of CAM, particularly those from winter and year-round rainfall regimes. Plants with δ13C values intermediate between CAM and C3, indicating flexible photosynthetic pathways, were generally leafy perennials subject to seasonal tissue dehydration. Reproductive tissue tended to have less negative δ13C values than vegetative tissue on the same plant, indicating drought-season origin of the former.

Variable carbon isotope ratios of Dudleya species growing in natural environments.

Measurements are reported of carbon isotope ratios of Dudleya species growing in natural plant communities. Considerable variation in the δ13C values are interpreted as indicating substantial flexibility of the photosynthetic pathways between C3 and CAM. The variability in photosynthetic pathway was in response to genetic factors, stage of plant development, life-form, and environmental conditions. Species active during drought periods have less carbon isotope fractionation than species that are summer-dormant. Summer-active species from drier habitats have less negative δ13C values than those from more mesic sites. On the same plant, leaf tissue had more negative δ13C values than tissue from the inflorescence. The less negative carbon isotope ratios are indicative of an increased proportion of exogenous CO2 fixed in dark vs light. The ecological significance of these results is discussed.

Multifactorial intervention in individuals with type 2 diabetes and microalbuminuria: the Microalbuminuria Education and Medication Optimisation (MEMO) study.

AIMS: To determine whether tighter cardiovascular risk factor control with structured education in individuals with type 2 diabetes (T2DM) and microalbuminuria benefits cardiovascular risk factors. METHODS: Participants from a multiethnic population, recruited from primary care and specialist clinics were randomised to intensive intervention with structured patient (DESMOND model) education (n=94) or usual care by own health professional (n=95). PRIMARY OUTCOME: change in HbA1c at 18months. SECONDARY OUTCOMES: changes in blood pressure (BP), cholesterol, albuminuria, proportion reaching risk factor targets, modelled cardiovascular risk scores. RESULTS: Mean (SD) age and diabetes duration of participants were 61.5 (10.5) and 11.5 (9.3) years, respectively. At 18months, intensive intervention showed significant improvements in HbA1c (7.1(1.0) vs. 7.8(1.4)%, p<0.0001), systolic BP (129(16) vs. 139(17) mmHg, p<0.0001), diastolic BP (70(11) vs. 76(12) mmHg, p<0.001), total cholesterol (3.7(0.8) vs. 4.1(0.9) mmol/l, p=0.001). Moderate and severe hypoglycaemia was 11.2 vs. 29.0%; p=0.001 and 0 vs. 6.3%; p=0.07, respectively. More intensive participants achieved ≥3 risk factor targets with greater reductions in cardiovascular risk scores. CONCLUSIONS: Intensive intervention showed greater improvements in metabolic control and cardiovascular risk profile with lower rates of moderate and severe hypoglycaemia. Intensive glycaemic interventions should be underpinned by structured education promoting self-management in T2DM.

The impact of a PCR assay for candidemia on antifungal drug prescribing in critical care: an interrupted time series pilot study.

SUMMARY OBJECTIVE: To evaluate the feasibility of conducting a definitive study to assess the impact of introducing a rapid PCR-based test for candidemia on antifungal drug prescribing. METHOD: Prospective, single centre, interrupted time series study consisting of three periods of six months' duration. The assay was available during the second period, during which the PCR assay was available for routine use by physicians Monday-Friday with guaranteed 24-h turnaround time. For each period total antifungal drug use, expressed as treatment-days, was recorded and an adjustment was made to exclude estimated use for proven candidemia. Also, during the intervention period, antifungal prescribing decisions for up to 72 h after each PCR result became available were recorded as either concordant or discordant with that result. RESULTS: While overall antifungal use remained relatively stable throughout, after adjustment for candidemia, there was a 38% reduction in use following introduction of the PCR test; however, this was nonsignificant at the 95% level. During the intervention period overall concordance between the PCR result and prescribing decisions was 84%. CONCLUSIONS: The PCR assay for candidemia was requested, prescribing decisions were generally concordant with the results produced and there was an apparent decrease in antifungal prescription, although this was sustained even after withdrawal of the intervention; these findings should be more thoroughly evaluated in a larger trial.

Paraoxonase activity and coronary heart disease risk in healthy middle-aged males: the PRIME study.

OBJECTIVE: Classic coronary heart disease (CHD) risk factors fail to explain the large gradient in CHD incidence between Northern Ireland and France. The Prospective Epidemiological Study of Myocardial Infarction (PRIME) study, a multicentre prospective study of 10,593 middle-aged males, investigated novel risk factors in these populations. We tested the hypotheses that (1) higher paraoxonase activity is associated with decreased CHD risk and (2) PON55 LL genotype is associated with increased CHD risk. METHODS: Paraoxonase activity was measured in 299 men who had developed CHD at 5-year follow-up and in 576 matched controls. DNA was available from 247 cases and 433 controls for genotyping for the PON55 polymorphism. RESULTS: There was no significant difference in paraoxonase activity between cases and controls (geometric means 73.8 and 74.2U/l; p=0.81). There was no significant difference in CHD risk between fifths of paraoxonase activity either before (p=0.55) or after adjustment for classical risk factors (p=0.58). There was no significant association between genotype and CHD risk; relative to the LL genotype, the OR (95% CI) for the LM and MM genotypes were 0.92 (0.66-1.29) and 0.83 (0.50-1.36), respectively. The frequency of the L allele in cases (66.6%) and controls (64.5%) did not differ significantly, p=0.45. CONCLUSIONS: These findings suggest that neither paraoxonase activity nor PON55 genotype is associated with CHD risk in males in the PRIME study.

The lack of carbon dioxide evolution in maize leaves in the light.

Significant carbon dioxide evolution in the light could not be betected in maize leaves held in single-leaf chambers. The leaves that were used remained attached to the plant and were kept at 30° C and with 200 w m(-2) of light incident on the leaf surface. Several experimental techniques were combined in an attempt to detect CO2 evolution from cells within the leaf; these techniques included that of passing air through, rather than over, the leaf, using different levels of O2 and obtaining CO2 response curves.

Temperature effects on the carbon-isotope ratio of C3, C 4 and crassulacean-acid-metabolism (CAM) plants.

The temperature coefficient of the δ(13)C value over the temperature range 14 to 40° has been measured for plants with different photosynthetic pathways. C3 plants (6 species) had a temperature coefficient of-0.0125‰/(o), C3 plants (5 species)-0.046‰/(o), "C4-like" CAM (2 species)-0.13‰/(o) and "C3-like" CAM (2 species)-0.019‰/(o). The relative temperature insensitivity of the δ(13)C value is in contrast with the measured temperature dependence of δ(13)C values for ribulose-diphosphate carboxylase in vitro, and to the temperature response of photosynthesis. The temperature sensitivity of the "C4-like" CAM plants was the relatively greatest; this is consistent with the evidence that high night temperature inhibits dark CO2 fixation. The same inhibition may occur in the "C3-like" CAM plants but it would not have as significant an effect on the δ(13)C value as these plants are primarily dependent on primary fixation of exogenous CO2 via the ribulose-diphosphate carboxylase reaction.

Relations between Light Level, Sucrose Concentration, and Translocation of Carbon 11 in Zea mays Leaves.

The mechanism of carbon transport in Zea mays leaves was investigated using carbon 11 which is a short lived (half-life 20.4 min) positronemitting isotope. The gamma radiation produced on annihilation allows in vivo or nondestructive measurement of the isotope and the short half-life allows many measurements of translocation to be made on the same leaf within the same day.Carbon 11 produced by the (10)B (d,n)(11)C nuclear reaction was converted to (11)CO(2), fed to a leaf as a short pulse, and assimilated during photosynthesis. The progress of the radioactive pulse along the leaf in the phloem was monitored in several positions simultaneously with counters. The counters were NaI crystals with photomultipliers and the output was amplified, passed to single channel analyzers, and the counts accumulated for 20 seconds every 30 seconds. Corrections were made for the half-life and background radiation by computer, and the results were displayed on a high speed plotter. Information derived from the corrected data included the speed of translocation, the shape of the radioactive carbon pulse, and the influence of light and distance along the leaf on these parameters. The plants were kept under controlled environment conditions during all measurements.A speed was derived from the time displacement of the midpoint of the front of the pulse, measured at two positions along the leaf. This was an apparent mean speed of translocation because it averaged a variation in speed with distance, variation in speed between or within sieve tubes, and it averaged the mean speed of all of the particles in the pulse.A wide range of speeds of translocation from 0.25 to 11 cm min(-1) was observed but most of the variability was due to the variation in light available to the leaf. For example, the speed of translocation was proportional to the light level on either the whole plant or individual leaf. Shading of the leaf established that the light effect was not localized in either the feeding area or in the portion of the leaf on which the measurements were made. It was proposed that the speed was dependent on the proportion of the leaf in the light upstream from the last counter. The speed of translocation was relatively independent of the stage of growth of the plant, age of the leaf, and the time during the diurnal light cycle.Data obtained on the level of the reducing sugars, starch, and sucrose in the leaf were related to the speed of translocation. A biphasic relationship between speed and sucrose concentration in the leaf was established and the high speeds measured during experiments only occurred when sucrose concentrations in the leaf exceeded 8% of the dry weight.The shape of the pulse loaded into and translocated in the phloem was estimated from the half-width of the pulse. The half-width was primarily determined by loading phenomena which resulted in an increase in the half-width from 2 minutes when fed to the leaf to more than 40 minutes in the phloem. In many examples, the pulse continued to broaden with distance along the leaf from the fed region. The half-width was independent of the speed but highly dependent on the light level.

Prediction of growth rate at different light levels from measured photosynthesis and respiration rates.

Light integrators with a linear response are not suitable for measuring the light climates of plants because plants are not linear integrators. It should be possible to make a quantitative allowance for this nonlinearity by using the CO(2) uptake curve of the plant. To test this, we have subjected white clover plants to different levels of constant light, comparing the rate of increase of total dry matter with the net rate of uptake of CO(2) per day. Temperature, humidity, daylength and nutrient supply were kept constant. The growth rate calculated from CO(2) uptake agreed well with the observed rate over the light levels tested (3.7-88 w.m(-2), 0.4-0.7 micron: 1 w.m(-2) = 10(3) erg . sec(-1) cm(-2)). All plants put on weight over the few days of the experiment, even those placed at light levels below their compensation point. The plants adapted their respiration rates to be a constant proportion of their growth rates. Most of the adaptation occurred within 24 hours of the light change. The adaptation of respiration has implications for models of light/growth relations in plant communities, almost all of which assume that respiration is proportional to leaf area and independent of growth rate or light level. The only model which does not is that of de Wit, and this gave good agreement with our results.