Are COPD self-management mobile applications effective? A systematic review and meta-analysis.

The burden of chronic obstructive pulmonary disease (COPD) to patients and health services is steadily increasing. Self-management supported by mobile device applications could improve outcomes for people with COPD. Our aim was to synthesize evidence on the effectiveness of mobile health applications compared with usual care. A systematic review was conducted to identify randomized controlled trials. Outcomes of interest included exacerbations, physical function, and Quality of Life (QoL). Where possible, outcome data were pooled for meta-analyses. Of 1709 citations returned, 13 were eligible trials. Number of exacerbations, quality of life, physical function, dyspnea, physical activity, and self-efficacy were reported. Evidence for effectiveness was inconsistent between studies, and the pooled effect size for physical function and QoL was not significant. There was notable variation in outcome measures used across trials. Developing a standardized outcome-reporting framework for digital health interventions in COPD self-management may help standardize future research.

How point-of-care HbA1c testing changes the behaviour of people with diabetes and clinicians - a qualitative study.

AIM: To explore adults with diabetes and clinician views of point-of-care HbA1c testing. METHODS: Adults with diabetes and HbA1c ≥ 58 mmol/mol (7.5%) receiving HbA1c point-of-care testing in primary care were invited to individual interviews. Participants were interviewed twice, once prior to point-of-care testing and once after 6 months follow-up. Clinicians were interviewed once. A thematic framework based on an a priori framework was used to analyse the data. RESULTS: Fifteen participants (eight women, age range 30-70 years, two Asians, 13 white Europeans) were interviewed. They liked point-of-care testing and found the single appointment more convenient than usual care. Receiving the test result at the appointment helped some people understand how some lifestyle behaviours affected their control of diabetes and motivated them to change behaviours. Receiving an immediate test result reduced the anxiety some people experience when waiting for a result. People thought there was little value in using point-of-care testing for their annual review. Clinicians liked the point-of-care testing but expressed concerns about costs. CONCLUSIONS: This work suggests that several features of point-of-care testing may encourage behavioural change. It helped some people to link their HbA1c result to recent lifestyle behaviours, thereby motivating behavioural change and reinforcing healthy lifestyle choices.

Transforming mental well-being for people with diabetes: research recommendations from Diabetes UK's 2019 Diabetes and Mental Well-Being Workshop.

AIMS: To identify key gaps in the research evidence base that could help to improve the mental well-being of people with diabetes, and to provide recommendations to researchers and research funders on how best to address them. METHODS: A 2-day international research workshop was conducted, bringing together research experts in diabetes and in mental health, people living with diabetes and healthcare professionals. RESULTS: The following key areas needing increased financial investment in research were identified: understanding the mechanisms underlying depression; understanding the multifactorial impact of social stigma; improving the language used by healthcare professionals; supporting people who find it difficult to engage with their diabetes; supporting significant others; supporting people with diabetes and eating disorders; improving models of care by learning from best practice; the potential benefits of screening and managing diabetes distress in routine diabetes care pathways; primary prevention of mental health issues at the time of diagnosis of diabetes; establishing the effectiveness of diabetes therapies on mood and other mental health issues; and understanding the impact of current diabetes technologies on mental health. Research recommendations as to how to address each of these priority areas were also developed. CONCLUSIONS: This inaugural position statement outlines recommendations to address the urgent unmet need related to the mental well-being of people living with diabetes, and calls on the research community and funders to develop research programmes and strategies to reduce this need.

Timings for HbA1c testing in people with diabetes are associated with incentive payments: an analysis of UK primary care data.

AIMS: Guidelines recommend testing HbA1c every 3-6 months in people with diabetes. In the United Kingdom (UK), primary care clinics are financially incentivized to monitor HbA1c at least annually and report proportions of patients meeting targets on 31 March. We explored the hypothesis that this reporting deadline may be associated with over-frequent or delayed HbA1c testing. METHODS: This analysis used HbA1c results from 100 000 people with diabetes during 2005-2014 in the Clinical Practice Research Datalink UK primary care database. Logistic regression was used to explore whether the four months prior to the deadline for quality reporting (December to March) or individual's previous HbA1c were aligned with retesting HbA1c within 60 days or > 1 year from the previous test, and identify other factors associated with the timing of HbA1c testing. RESULTS: Retesting HbA1c within 60 days or > 1 year was more common in December to March compared with other months of the year (odds ratio 1.06, 95% confidence interval 1.04-1.08 for retesting within 60 days). Those with higher HbA1c were more likely to have a repeat test within 60 days and less likely to have a repeat test > 1 year from the previous test. CONCLUSIONS: We have found that retesting HbA1c within 60 days and > 1 year from the previous test was more common in December to March compared with the other months of the year. This work suggests that both practice-centred administrative factors and patient-centred considerations may be influencing diabetes care in the UK.

How can point-of-care HbA1c testing be integrated into UK primary care consultations? - A feasibility study.

AIMS: Point-of-care (POC) HbA1c testing gives a rapid result, allowing testing and treatment decisions to take place in a single appointment. Trials of POC testing have not been shown to improve HbA1c, possibly because of how testing was implemented. This study aimed to identify key components of POC HbA1c testing and determine strategies to optimise implementation in UK primary care. METHODS: This cohort feasibility study recruited thirty patients with type 2 diabetes and HbA1c>7.5% (58mmol/mol) into three primary care clinics. Patients' clinical care included two POC HbA1c tests over six months. Data were collected on appointment duration, clinical decisions, technical performance and patient behaviour. RESULTS: Fifty-three POC HbA1c consultations took place during the study; clinical decisions were made in 30 consultations. Five POC consultations with a family doctor lasted on average 11min and 48 consultations with nurses took on average 24min. Five POC study visits did not take place in one clinic. POC results were uploaded to hospital records from two clinics. In total, sixty-three POC tests were performed, and there were 11 cartridge failures. No changes in HbA1c or patient behaviour were observed. CONCLUSIONS: HbA1c measurement with POC devices can be effectively implemented in primary care. This work has identified when these technologies might work best, as well as potential challenges. The findings can be used to inform the design of a pragmatic trial to implement POC HbA1c testing.

Short- and medium-term effects of light to moderate alcohol intake on glycaemic control in diabetes mellitus: a systematic review and meta-analysis of randomized trials.

BACKGROUND: People with diabetes are told that drinking alcohol may increase their risk of hypoglycaemia. AIMS: To report the effects of alcohol consumption on glycaemic control in people with diabetes mellitus. METHODS: Medline, EMBASE and the Cochrane Library databases were searched in 2015 to identify randomized trials that compared alcohol consumption with no alcohol use, reporting glycaemic control in people with diabetes. Data on blood glucose, HbA1c and numbers of hypoglycaemic episodes were pooled using random effects meta-analysis. RESULTS: Pooled data from nine short-term studies showed no difference in blood glucose concentrations between those who drank alcohol in doses of 16-80 g (median 20 g, 2.5 units) compared with those who did not drink alcohol at 0.5, 2, 4 and 24 h after alcohol consumption. Pooled data from five medium-term studies showed that there was no difference in blood glucose or HbA1c concentrations at the end of the study between those who drank 11-18 g alcohol/day (median 13 g/day, 1.5 units/day) for 4-104 weeks and those who did not. We found no evidence of a difference in number of hypoglycaemic episodes or in withdrawal rates between randomized groups. CONCLUSIONS: Studies to date have not provided evidence that drinking light to moderate amounts of alcohol, with or without a meal, affects any measure of glycaemic control in people with Type 2 diabetes. These results suggest that current advice that people with diabetes do not need to refrain from drinking moderate quantities of alcohol does not need to be changed; risks to those with Type 1 diabetes remain uncertain.

Perceptions and experiences of taking oral medications for the treatment of Type 2 diabetes mellitus: a systematic review and meta-synthesis of qualitative studies.

AIMS: To explore patients' perceptions and experiences of taking oral medications for the pharmacological management of Type 2 diabetes mellitus. METHODS: Cinahl, EMBASE, Medline and PsycINFO databases were searched in 2014 to identify qualitative studies exploring patients' perceptions or experiences of taking medications for the management of Type 2 diabetes. Key concepts and themes were extracted and synthesized using meta-ethnography. RESULTS: Eight studies were included. Primary study findings were synthesized to develop three higher-order constructs that moved beyond the results of individual studies. The first construct, Medications for diabetes: a necessary evil, outlines how patients' negative perceptions of medication risks co-exist with a resounding view that medications are beneficial. Passive patients but active experimenters highlights the contrast between patients' passive acceptance of medication prescriptions and the urge to actively experiment and adjust doses to optimize medication use in daily life. Finally, Taking oral medication for Type 2 diabetes: a unique context describes features specific to the Type 2 diabetes medication experience, including lack of symptoms and the perceived relationship between medication and diet, which may influence adherence. CONCLUSIONS: Medication-taking for Type 2 diabetes is a unique adherence context, which requires the development of condition-specific interventions. The present findings indicate patients understand the need for medications but adjust dosage and timing in their daily lives. This review suggests providers should acknowledge patient preferences in the development of management strategies, and highlights an opportunity to direct the motivation evident in patients' experimentation towards potentially more beneficial medication-taking behaviours.

Effects of interventions promoting monitoring of medication use and brief messaging on medication adherence for people with Type 2 diabetes: a systematic review of randomized trials.

AIMS: To assess the impact of interventions promoting the monitoring of medication use and brief messaging to support medication adherence in patients with Type 2 diabetes mellitus, and to investigate the extent of theory use to guide intervention development. METHODS: We systematically searched for controlled trials, published from 1990 onwards in Medline, Embase, CINAHL, PsycINFO and the Cochrane library, that evaluated interventions based on monitoring and brief messaging to support medication adherence in patients with Type 2 diabetes, to examine the effectiveness of such interventions. RESULTS: A total of 11 trials, comparing 15 interventions, were identified. Only a small minority presented a low risk of bias. Three interventions were based on delivering brief messages, six were based on monitoring medication adherence, and six used both strategies. Messaging interventions included the use of short message service text messages, web-based feedback, and messages delivered through monitoring devices. Monitoring interventions included remote self-reporting of medication and telephone calls with healthcare staff. Improvements in medication adherence were observed in six interventions, although effect sizes were generally moderate. Only two interventions improved both adherence and clinical outcomes. A meta-analysis of five trials (eight interventions) combining monitoring and messaging strategies showed that the pooled difference in medication adherence between intervention and control was moderate and not statistically significant [standardized mean difference = 0.22 (95% CI -0.05; 0.49)]. Only four trials were based on explicit theoretical frameworks. CONCLUSIONS: Although interventions based on messaging and monitoring have the potential to improve medication adherence in patients with Type 2 diabetes, evidence of their efficacy is limited and additional high-quality, theory-based research is needed.

Early (1-year) Discontinuation of Different Anti-osteoporosis Medications Compared: A Population-Based Cohort Study.

Although a number of reports suggest very low persistence with oral bisphosphonates, there is limited data on persistence with other anti-osteoporosis medications. We compare rates of early discontinuation (in the first year) with all available outpatient anti-osteoporosis drugs in Catalonia, Spain. We conducted a population-based retrospective cohort study using data from the SIDIAP database. SIDIAP contains computerized primary care records and pharmacy dispensing data for >80 % of the population of Catalonia (>5 million people). All SIDIAP participants starting an anti-osteoporosis drug between 1/1/2007 and 30/06/2011 (with 2 years wash-out) were included. We modelled persistence as the time between first prescription and therapy discontinuation (refill gap of at least 6 months) using Fine and Gray survival models with competing risk for death. We identified 127,722 patients who started any anti-osteoporosis drug in the study period. The most commonly prescribed drug was weekly alendronate (N = 55,399). 1-Year persistence ranges from 40 % with monthly risedronate to 7.7 % with daily risedronate, and discontinuation was very common [from 49.5 % (monthly risedronate) to 84.4 % (daily risedronate)] as was also switching in the first year of therapy [from 2.8 % (weekly alendronate) to 10 % (daily alendronate)]. Multivariable-adjusted models showed that only monthly risedronate had better one-year persistence than weekly alendronate and teriparatide equivalent, whilst all other therapies had worse persistence. Early discontinuation with available anti-osteoporosis oral drugs is very common. Monthly risedronate, weekly alendronate, and daily teriparatide are the drugs with the best persistence, whilst daily oral drugs have 40-60 % higher first-year discontinuation rates compared to weekly alendronate.

Estimating the effect of sulfonylurea on HbA1c in diabetes: a systematic review and meta-analysis.

AIMS/HYPOTHESIS: Sulfonylureas are widely prescribed glucose-lowering medications for diabetes, but the extent to which they improve glycaemia is poorly documented. This systematic review evaluates how sulfonylurea treatment affects glycaemic control. METHODS: Medline, EMBASE, the Cochrane Library and clinical trials registries were searched to identify double-blinded randomised controlled trials of fixed-dose sulfonylurea monotherapy or sulfonylurea added on to other glucose-lowering treatments. The primary outcome assessed was change in HbA1c, and secondary outcomes were adverse events, insulin dose and change in body weight. RESULTS: Thirty-one trials with a median duration of 16 weeks were included in the meta-analysis. Sulfonylurea monotherapy (nine trials) lowered HbA1c by 1.51% (17 mmol/mol) more than placebo (95% CI, 1.25, 1.78). Sulfonylureas added to oral diabetes treatment (four trials) lowered HbA1c by 1.62% (18 mmol/mol; 95% CI 1.0, 2.24) compared with the other treatment, and sulfonylurea added to insulin (17 trials) lowered HbA1c by 0.46% (6 mmol/mol; 95% CI 0.24, 0.69) and lowered insulin dose. Higher sulfonylurea doses did not reduce HbA1c more than lower doses. Sulfonylurea treatment resulted in more hypoglycaemic events (RR 2.41, 95% CI 1.41, 4.10) but did not significantly affect the number of other adverse events. Trial length, sulfonylurea type and duration of diabetes contributed to heterogeneity. CONCLUSIONS/INTERPRETATION: Sulfonylurea monotherapy lowered HbA1c level more than previously reported, and we found no evidence that increasing sulfonylurea doses resulted in lower HbA1c. HbA1c is a surrogate endpoint, and we were unable to examine long-term endpoints in these predominately short-term trials, but sulfonylureas appear to be associated with an increased risk of hypoglycaemic events.

Cancer outcomes and all-cause mortality in adults allocated to metformin: systematic review and collaborative meta-analysis of randomised clinical trials.

AIMS/HYPOTHESIS: Observational studies suggest that metformin may reduce cancer risk by approximately one-third. We examined cancer outcomes and all-cause mortality in published randomised controlled trials (RCTs). METHODS: RCTs comparing metformin with active glucose-lowering therapy or placebo/usual care, with minimum 500 participants and 1-year follow-up, were identified by systematic review. Data on cancer incidence and all-cause mortality were obtained from publications or by contacting investigators. For two trials, cancer incidence data were not available; cancer mortality was used as a surrogate. Summary RRs, 95% CIs and I (2)statistics for heterogeneity were calculated by fixed effects meta-analysis. RESULTS: Of 4,039 abstracts identified, 94 publications described 14 eligible studies. RRs for cancer were available from 11 RCTs with 398 cancers during 51,681 person-years. RRs for all-cause mortality were available from 13 RCTs with 552 deaths during 66,447 person-years. Summary RRs for cancer outcomes in people randomised to metformin compared with any comparator were 1.02 (95% CI 0.82, 1.26) across all trials, 0.98 (95% CI 0.77, 1.23) in a subgroup analysis of active-comparator trials and 1.36 (95% CI 0.74, 2.49) in a subgroup analysis of placebo/usual care comparator trials. The summary RR for all-cause mortality was 0.94 (95% CI 0.79, 1.12) across all trials. CONCLUSIONS/INTERPRETATION: Meta-analysis of currently available RCT data does not support the hypothesis that metformin lowers cancer risk by one-third. Eligible trials also showed no significant effect of metformin on all-cause mortality. However, limitations include heterogeneous comparator types, absent cancer data from two trials, and short follow-up, especially for mortality.

Incidence and costs of severe hypoglycaemia requiring attendance by the emergency medical services in South Central England.

AIMS: The aim was to estimate the incidence of severe hypoglycaemia requiring emergency ambulance assistance, its management and associated costs. METHODS: A retrospective observational study used routinely collected data for a 1-year period from December 2009 to November 2010 from the South Central Ambulance Service National Health Service Trust, UK. The main outcome was episodes reported by ambulance personnel and costs were estimated from published data. RESULTS: During the 1-year study period, 398,409 emergency calls were received, of which 4081 (1.02%) were coded as hypoglycaemia. The overall numbers (and annual rate) of hypoglycaemia recorded among people ≥ 15 years with presumed diabetes was 3962 (2.1%), but for those aged 15-35 years was 516 (7.5%) and for those aged ≥ 65 years was 1886 (1.9%). Of those attended, 1441 (35.3%) were taken to hospital. The estimated total cost of initial ambulance attendance and treatment at scene was £553,000; if transport to hospital was necessary, the additional ambulance costs were £223,000 plus emergency department costs of £140,000; and the cost of primary care follow-up was estimated as £61,000. The average cost per emergency call was £263. The estimated annual cost of emergency calls for severe hypoglycaemia is £13.6m for England. CONCLUSIONS: Our estimates suggest prevalence of severe hypoglycaemia attended by the emergency services is high in younger age groups and lower for older age groups, although the absolute numbers of severe events in older age groups contribute substantially to the overall costs of providing emergency assistance for hypoglycaemia.

Establishing an evidence base for frequency of monitoring glycated haemoglobin levels in patients with Type 2 diabetes: projections of effectiveness from a regression model.

AIMS: Glycated haemoglobin (HbA1c) is monitored to guide treatment decisions in relation to glycaemic goals over time. Changes between two consecutive HbA1c tests result not only from deterioration or improvement in glycaemic control, but also from biovariability and measurement error. We model how this short-term variability impacts on HbA1c monitoring. METHODS: Using data from a randomized trial of non-insulin treated patients with Type 2 diabetes we fitted a random-effects model for progression and variability of HbA1c. We estimated how many tests where HbA1c ≥ 7.5% (58.5 mmol/mol) would be false-positive (underlying HbA1c < 7.5% but test ≥ 7.5% owing to variability) vs. true-positive, in people with initial HbA1c between 6.5% and 7.3% (48 mmol/mol and 56 mmol/mol). RESULTS: Participants (n = 320) had mean (SD) age 66 (10) years, BMI 31.3 (6.0) kg/m2 and median HbA1c was 7.1% (54 mmol/mol) with interquartile range 6.6% (49 mmol/mol) to 7.7% (61 mmol/mol). Mean (95% CI) change in HbA1c was 0.1% (1 mmol/mol) with 95% confidence interval 0.05% (0.5 mmol/mol) to 0.15% (2 mmol/mol) per 6 months. The minimum interval at which a true-positive test is more likely than a false positive test is 270 days for a starting HbA1c of 6.9% (52 mmol/mol) and 360 days at a starting value of 6.5% (48 mmol/mol). CONCLUSION: In patients with initial HbA1c close to treatment goal, retesting at 6 months would yield more true-positive than false-positive tests. For patients with lower initial HbA1c, retesting at 6 months would yield more false than true-positive tests. In all patients, retesting at 12 months yields more true than false-positive tests. In very few patients would retesting at 3 months be justified.

Differences in insulin treatment satisfaction following randomized addition of biphasic, prandial or basal insulin to oral therapy in type 2 diabetes.

AIM: No differences in patient health status as measured by the EuroQol-5 Dimension (EQ-5D) questionnaire were observed at 1 year between groups randomized to addition of biphasic, prandial or basal insulin to oral therapy in the treat-to-target in type 2 diabetes trial. We further investigated insulin treatment satisfaction between groups. METHODS: Seven hundred and eight patients with suboptimal glycated haemoglobin levels (7.0-10.0%) taking maximally tolerated doses of metformin and sulphonylurea were randomized to biphasic insulin aspart twice-daily, prandial insulin aspart three times daily or basal insulin detemir once-daily (twice if required). At 1 year self-completed Insulin Treatment Satisfaction Questionnaires (ITSQ) were administered. Lower scores indicated lower treatment satisfaction. We tested for differences between the three groups for the ITSQ total score and for each of the five ITSQ domain scores adjusting for age, gender, ethnicity and education. RESULTS: All 22 ITSQ subscales were completed by 554 (78.2%) patients. Their mean (s.d.) age was 61.5 (9.4) years, body weight 86.1 (16) kg and median (IQR) diabetes duration 9 (6-13) years. Sixty-five percent (358) were male. Median (IQR) 1-year ITSQ total score was lower in patients allocated to prandial therapy (76.5, 68.0-88.6) than in patients allocated to biphasic insulin (83.3, 74.2-90.2) or basal insulin (84.1, 73.5-93.2). With the exception of 'perceived glycaemic control', 1-year adjusted ITSQ scores were significantly different between groups for each of the ITSQ domains, with lower scores for prandial insulin compared with the basal or biphasic groups. Median (IQR) ITSQ scores were lower in patients with a gain in body mass index (BMI) > 1.23 kg/m² over 1 year (79.5, 69.7-89.4) compared to those with a lesser or no gain in BMI (84.1, 74.2-92.4) and in those with occurrence of hypoglycaemia (79.5, 69.7-88.6) compared to those with no hypoglycaemia (84.1, 73.7-93.2). CONCLUSION: Specific measurement of insulin treatment satisfaction identifies differences between regimens used to intensify treatment for type 2 diabetes. Impact of treatment on lifestyle needs to be considered as a factor in the choice of an insulin regimen.

Experience of hypoglycaemia is associated with changes in beliefs about diabetes in patients with type 2 diabetes.

AIM: Hypoglycaemia may have a detrimental impact on quality of life for patients with Type 2 diabetes. There are few clinical studies exploring the impact of experiencing hypoglycaemia on beliefs about diabetes and health status. The aim of this study was to explore associations between experience of hypoglycaemia and changes in diabetes beliefs and self-reported health status in patients with non-insulin-treated Type 2 diabetes using a blood glucose meter. METHODS: One-year prospective cohort analysis of 226 patients recruited to a randomized trial evaluating the impact of self-monitoring of blood glucose. Self-reported hypoglycaemia over 1 year was categorized into three groups: (1) no experience of hypoglycaemia; (2) blood glucose measurements < 4 mmol/l with no associated symptoms of hypoglycaemia (grade 1); and (3) symptomatic hypoglycaemia (grade 2 and 3). Measures of beliefs about diabetes (Revised Illness Perception Questionnaire) and health status (EuroQol-5D) were assessed at baseline and 1 year. Differences in mean changes over 1 year were explored with analyses of covariance. RESULTS: There was a significant increase in mean score in beliefs about personal control (1.14; 95%CI 0.14-2.14) among those experiencing grade 1 hypoglycaemia compared with those not experiencing hypoglycaemia. There were no significant differences in changes in health status between groups, with small overall changes that were inconsistent between groups. CONCLUSIONS: This study does not provide support for a long-term adverse impact on beliefs about diabetes or health status from the experience of mild symptomatic hypoglycaemia, in well-controlled, non-insulin-treated patients with Type 2 diabetes using self-monitoring of blood glucose.

Evidence for a dose effect of renin-angiotensin system inhibition on progression of microalbuminuria in Type 2 diabetes: a meta-analysis.

AIMS: Renin-angiotensin inhibitors in Type 2 diabetes and microalbuminuria reduce renal and cardiovascular risk, but evidence supporting use of maximal tolerated dose is unclear. We aimed to determine the extent of renin-angiotensin inhibitor dose-dependent effects from randomized trials carried out in a clinical setting. METHODS: In a meta-analysis of randomized clinical trials, alternate doses of angiotensin receptor blockers or angiotensin converting enzyme inhibitors in patients with Type 2 diabetes and microalbuminuria were compared. MEDLINE, EMBASE and the Cochrane Register of Controlled Trials were searched from January 2006 to August 2010. Trials prior to January 2006 were identified from a prior systematic review. Identified outcomes were albumin excretion rate, progression and regression of albuminuria and adverse events. RESULTS: Four trials including 1051 patients compared doses of angiotensin receptor blockers. No trials compared doses of angiotensin converting enzyme inhibitor. The percentage decline in albumin excretion rate from baseline was greater with higher doses (18% higher, 95% CI 8-28%), the regression to normoalbuminuria was greater (OR 1.66, 95% CI 1.22-2.27), with less progression to macroalbuminuria (OR 0.62, CI 0.38-1.02). Adverse events were fewer with lower-dose angiotensin receptor blockers (OR 1.32, 95% CI 0.90-1.92). CONCLUSIONS: Higher-dose compared with lower-dose angiotensin receptor blockers in Type 2 diabetes with microalbuminuria are associated with significantly reduced albumin excretion rate and increased regression to normoalbuminuria. Adverse events are more frequent, but not significantly so. There is potential for trials to determine clinical cardiovascular and renal outcomes at differing doses. Our findings support current recommendations to titrate renin-angiotensin inhibitors to maximum dose whilst considering risk of adverse side effects with higher doses.

Participants' experiences of intensifying insulin therapy during the Treating to Target in Type 2 Diabetes (4-T) trial: qualitative interview study.

AIM: To explore participants' experiences of intensifying insulin therapy during the Treating to Target in Type 2 Diabetes (4-T) trial. METHODS: In-depth interviews were conducted with 41 trial participants who had had their insulin therapy intensified during this trial. Data were analysed using an inductive, thematic approach. RESULTS: The vast majority of participants were receptive towards intensifying treatment. Whilst some were happy simply to follow health professionals' recommendations, others saw taking two types of insulin as a more effective way of controlling their diabetes. Post-intensification, participants sought to remember to take their additional injections by developing injection-related strategies and daily routines. The need to inject insulin whilst in public often arose more frequently following intensification and was a consistent source of anxiety. Those who were worried about injecting in public sought to avoid having to do so; for example, by injecting in toilets or by advancing or delaying the timing of their injections. CONCLUSIONS: IT was not increasing the number of daily injections per se which was problematic for the participants who had agreed to have their insulin therapies intensified, but the increased likelihood of having to inject insulin in public. Addressing concerns about injecting in public places may help promote adherence to intensified insulin regimens.

Optimal insulin regimens in type 2 diabetes mellitus: systematic review and meta-analyses.

AIMS/HYPOTHESIS: We compared the effect of biphasic, basal or prandial insulin regimens on glucose control, clinical outcomes and adverse events in people with type 2 diabetes. METHODS: We searched the Cochrane Library, MEDLINE, EMBASE and major American and European conference abstracts for randomised controlled trials up to October 2008. A systematic review and meta-analyses were performed. RESULTS: Twenty-two trials that randomised 4,379 patients were included. Seven trials reported both starting insulin dose and titration schedules. Hypoglycaemia definitions and glucose targets varied. Meta-analyses were performed pooling data from insulin-naive patients. Greater HbA(1c) reductions were seen with biphasic and prandial insulin, compared with basal insulin, of 0.45% (95% CI 0.19-0.70, p = 0.0006) and 0.45% (95% CI 0.16-0.73, p = 0.002), respectively, but with lesser reductions of fasting glucose of 0.93 mmol/l (95% CI 0.21-1.65, p = 0.01) and 2.20 mmol/l (95% CI 1.70-2.70, p < 0.00001), respectively. Larger insulin doses at study end were reported in biphasic and prandial arms compared with basal arms. No studies found differences in major hypoglycaemic events, but minor hypoglycaemic events for prandial and biphasic insulin were inconsistently reported as either higher than or equivalent to basal insulin. Greater weight gain was seen with prandial compared with basal insulin (1.86 kg, 95% CI 0.80-2.92, p = 0.0006). CONCLUSIONS/INTERPRETATION: Greater HbA(1c) reduction may be obtained in type 2 diabetes when insulin is initiated using biphasic or prandial insulin rather than a basal regimen, but with an unquantified risk of hypoglycaemia. Studies with longer follow-up are required to determine the clinical relevance of this finding.

Individual patient data meta-analysis of trials of self-monitoring of blood glucose in non-insulin treated type 2 diabetes: protocol for a systematic review.

BACKGROUND AND AIM OF THE STUDY: Recent trials have provided differing estimates of the benefits of self-monitoring of blood glucose (SMBG) for non-insulin treated patients with type 2 diabetes. Designing and conducting randomised trials to demonstrate the efficacy of complex interventions is challenging. Variations in the components of the intervention delivered, target population selected, and reporting methods used have limited the conclusions drawn in recent systematic reviews. We will systematically examine these factors within the trials of SMBG to enable further investigation of the data through an individual patient data analysis (IPD). METHODS/DESIGN: The IPD analysis will include data from randomised trials comparing blood glucose self-monitoring and decisions about self-management versus a control group with standardised or routine care. The data requested for each trial will include outcomes (HbA1c, blood glucose and quality of life), potential moderators of effect (e.g. demographic variables, clinical data and psychosocial factors) and intervention descriptors. The primary outcome of interest will be HbA1c. Secondary outcomes include alternative measures of glycaemia, cardiovascular risk factors, persistence with monitoring, and measures of health status, quality of life and psychosocial factors. Analysis of patient sub-groups defined by age at randomisation, gender, prior use of monitoring and health status will be carried out. An intention to treat analysis will be performed and assessed for clinical and statistical heterogeneity. DISCUSSION: With current uncertainty about the extent of benefit from SMBG for non-insulin treated patients with type 2 diabetes, this study will provide the best estimates to date of overall effectiveness, effectiveness within potential target populations, and optimal components of the intervention.