What factors influence concordance with medications? Findings from the U.K. Asian Diabetes study.

AIMS: To investigate concordance with medication, as assessed at baseline and at 1- and 2-year follow-up, and to examine factors associated with non-concordance in a UK-resident South-Asian population. METHODS: Data from the UK Asian Diabetes Study were analysed. Concordance with medications was assessed and recorded at three time points during the study. Multiple logistic regression was used to investigate the factors associated with non-concordance; the associations of baseline factors with year 1 concordance and baseline plus year 1 factors with year 2 concordance. RESULTS: Data for 403 patients from seven practices participating in the UK Asian Diabetes Study were analysed. The numbers of patients who were non-concordant were: 63 (16%) at baseline; 101 (25%) at year 1; and 122 (30%) at year 2. The baseline-measured variables that were significantly associated with year 1 non-concordance included diabetes duration, history of cardiovascular disease, components of the EuroQol quality of life questionnaire, the EQ-5D score, and number of medications prescribed. In multivariable analyses, the most important determinant of year 1 non-concordance was baseline non-concordance: odds ratio 13.6 (95% confidence limits 4.7, 39.9). Number of medications prescribed for blood pressure control was also significant: odds ratio 1.8 (95% confidence limits 1.4, 2.4). Similar results were observed for year 2 non-concordance. CONCLUSIONS: Non-concordance with medications was common and more likely in people prescribed more medications. The current target-driven management of risk factor levels may lead to increasing numbers and doses of medications. Considering the high cost of medications and the implications of poor health behaviours on morbidity and mortality, further investigation of prescribing behaviours and the factors affecting patient concordance are required.

Diabetes specialist intervention in general practices in areas of deprivation and ethnic diversity: A qualitative evaluation (QUAL-ECLIPSE).

AIM: To assess patients' and healthcare professionals' perspectives of a specialist-led Diabetes Risk-based Assessment Clinic (DIRAC) for people with diabetes at high risk of complications (PWDHRC) in areas of deprivation in Coventry, UK. METHODS: A qualitative evaluation of a pilot trial, comprising a specialist team intervention (DIRAC), was undertaken in seven GP practices through observations of weekly virtual or occasional face-to-face patient consultations and monthly interventionists' meetings. Semi-structured interviews were carried out post-intervention, with PWDHRC, primary care clinicians and diabetes specialists (interventionists). Thematic analyses of observations and interviews were undertaken. KEY FINDINGS: Over 12 months, 28 DIRAC clinics comprising 154 patient consultations and five interventionists' meetings, were observed. 19 interviews were undertaken, PWDHRC experienced 'culturally-sensitive care from a specialist-led clinic intervention encompassing integrated care. This model of care was recommended at GP practice level, all participants (PWDHRC, primary care clinicians and diabetes specialist interventionists) felt upskilled to deal with complex diabetes care. The EMIS and ECLIPSE technologies utilised during the intervention were perceived to positively contribute to diabetes management of PWDHRC despite reservations around cost and database. CONCLUSION: The specialist-led DIRACs were largely appreciated by study participants. These qualitative data support the trial progressing to a full-service evaluation.

Replication of 13 genome-wide association (GWA)-validated risk variants for type 2 diabetes in Pakistani populations.

AIMS/HYPOTHESIS: Recent genome-wide association (GWA) studies and subsequent replication studies have greatly increased the number of validated type 2 diabetes susceptibility variants, but most of these have been conducted in European populations. Despite the high prevalence of the disease in South Asians, studies investigating GWA-validated type 2 diabetes risk variants in this ethnic group are limited. We investigated 30 single nucleotide polymorphisms (SNPs), predominantly derived from recent GWA studies, to determine if and to what extent these variants affect type 2 diabetes risk in two Punjabi populations, originating predominantly from the District of Mirpur, Pakistan. METHODS: Thirty SNPs were genotyped in 1,678 participants with type 2 diabetes and 1,584 normoglycaemic control participants from two populations; one resident in the UK and one indigenous to the District of Mirpur. RESULTS: SNPs in or near PPARG, TCF7L2, FTO, CDKN2A/2B, HHEX/IDE, IGF2BP2, SLC30A8, KCNQ1, JAZF1, IRS1, KLF14, CHCHD9 and DUSP9 displayed significant (p < 0.05) associations with type 2 diabetes, with similar effect sizes to those seen in European populations. A constructed genetic risk score was associated with type 2 diabetes (p = 5.46 × 10(-12)), BMI (p = 2.25 × 10(-4)) and age at onset of diabetes (p = 0.002). CONCLUSIONS/INTERPRETATION: We have demonstrated that 13 variants confer an increased risk of type 2 diabetes in our Pakistani populations; to our knowledge this is the first time that SNPs in or near KCNQ1, JAZF1, IRS1, KLF14, CHCHD9 and DUSP9 have been significantly associated with the disease in South Asians. Large-scale studies and meta-analyses of South Asian populations are needed to further confirm the effect of these variants in this ethnic group.

Impact of acute hyperglycaemia on endothelial function and retinal vascular reactivity in patients with Type 2 diabetes.

AIM: In diabetes, endothelial dysfunction and an altered retinal blood flow have been reported and precede overt macrovascular and microvascular disease. Furthermore, an association between postprandial hyperglycaemia, retinopathy and cardiovascular disease has been observed. METHODS: Endothelial function and retinal vascular reactivity have been measured in baseline conditions in 10 healthy control subjects and 21 patients with Type 2 diabetes. In the patients with Type 2 diabetes, endothelial function and retinal vascular reactivity have been also measured every hour, for 4 h, during an oral glucose tolerance test. Endothelial function has been evaluated by measuring flow-mediated vasodilation of the brachial artery, while retinal vascular reactivity has been measured using a retinal vessel analyser, during a flicker. RESULTS: At 1 and 2 h after glucose ingestion, endothelial function decreased (P<0.05), while retinal vascular reactivity increased, even at 3 h (P<0.05), vs. the baseline values. CONCLUSION: Our data highlight that acute hyperglycaemia impacts on endothelial function simultaneously at both macrovascular and at microvascular levels, inducing functional change, which could contribute towards explaining the clinical evidence of a strong association between postprandial hyperglycaemia, cardiovascular disease and retinopathy.

An FTO variant is associated with Type 2 diabetes in South Asian populations after accounting for body mass index and waist circumference.

AIMS: A common variant, rs9939609, in the FTO (fat mass and obesity) gene is associated with adiposity in Europeans, explaining its relationship with diabetes. However, data are inconsistent in South Asians. Our aim was to investigate the association of the FTO rs9939609 variant with obesity, obesity-related traits and Type 2 diabetes in South Asian individuals, and to use meta-analyses to attempt to clarify to what extent BMI influences the association of FTO variants with diabetes in South Asians. METHODS: We analysed rs9939609 in two studies of Pakistani individuals: 1666 adults aged ≥40 years from the Karachi population-based Control of Blood Pressure and Risk Attenuation (COBRA) study and 2745 individuals of Punjabi ancestry who were part of a Type 2 diabetes case-control study (UK Asian Diabetes Study/Diabetes Genetics in Pakistan; UKADS/DGP). The main outcomes were BMI, waist circumference and diabetes. Regression analyses were performed to determine associations between FTO alleles and outcomes. Summary estimates were combined in a meta-analysis of 8091 South Asian individuals (3919 patients with Type 2 diabetes and 4172 control subjects), including those from two previous studies. RESULTS: In the 4411 Pakistani individuals from this study, the age-, sex- and diabetes-adjusted association of FTO variant rs9939609 with BMI was 0.45 (95%CI 0.24-0.67) kg/m(2) per A-allele (P=3.0 × 10(-5) ) and with waist circumference was 0.88 (95% CI 0.36-1.41) cm per A-allele (P=0.001). The A-allele (30% frequency) was also significantly associated with Type 2 diabetes [per A-allele odds ratio (95%CI) 1.18 (1.07-1.30); P=0.0009]. A meta-analysis of four South Asian studies with 8091 subjects showed that the FTO A-allele predisposes to Type 2 diabetes [1.22 (95%CI 1.14-1.31); P=1.07 × 10(-8) ] even after adjusting for BMI [1.18 (95%CI 1.10-1.27); P=1.02 × 10(-5) ] or waist circumference [1.18 (95%CI 1.10-1.27); P=3.97 × 10(-5) ]. CONCLUSIONS: The strong association between FTO genotype and BMI and waist circumference in South Asians is similar to that observed in Europeans. In contrast, the strong association of FTO genotype with diabetes is only partly accounted for by BMI.

Sodium in the dermis colocates to glycosaminoglycan scaffold, with diminishment in type 2 diabetes mellitus.

BACKGROUND: Dietary sodium intake mismatches urinary sodium excretion over prolonged periods. Our aims were to localize and quantify electrostatically bound sodium within human skin using triple-quantum-filtered (TQF) protocols for MRI and magnetic resonance spectroscopy (MRS) and to explore dermal sodium in type 2 diabetes mellitus (T2D). METHODS: We recruited adult participants with T2D (n = 9) and euglycemic participants with no history of diabetes mellitus (n = 8). All had undergone lower limb amputations or abdominal skin reduction surgery for clinical purposes. We used 20 µm in-plane resolution 1H MRI to visualize anatomical skin regions ex vivo from skin biopsies taken intraoperatively, 23Na TQF MRI/MRS to explore distribution and quantification of freely dissolved and bound sodium, and inductively coupled plasma mass spectrometry to quantify sodium in selected skin samples. RESULTS: Human dermis has a preponderance (>90%) of bound sodium that colocalizes with the glycosaminoglycan (GAG) scaffold. Bound and free sodium have similar anatomical locations. T2D associates with a severely reduced dermal bound sodium capacity. CONCLUSION: We provide the first evidence to our knowledge for high levels of bound sodium within human dermis, colocating to the GAG scaffold, consistent with a dermal "third space repository" for sodium. T2D associates with diminished dermal electrostatic binding capacity for sodium.

Randomized clinical trial of different bandage regimens after foam sclerotherapy for varicose veins.

BACKGROUND: This trial compared outcomes after foam sclerotherapy in patients wearing compression bandaging for 24 h or 5 days after treatment. METHODS: Consecutive patients with primary uncomplicated varicose veins were randomized after foam sclerotherapy treatment. The primary endpoint was 6-week Aberdeen Varicose Vein Severity Score (AVVSS) and Burford pain score. RESULTS: Some 124 legs were randomized, 61 to 24 h and 63 to 5 days of bandaging. Target vein occlusion rates at 6-week duplex imaging were 90 and 89 per cent respectively (P = 0.842). There was no significant difference in phlebitis after 2 weeks (P = 0.445) or skin discoloration after 6 weeks (46 versus 40 per cent; P = 0.546). There was no significant difference in the change in AVVSS from baseline to 2 weeks (-0.29 versus -0.80; P = 0.717) or to 6 weeks (-5.89 versus -5.14; 95 per cent confidence interval (c.i.) for the difference -3.29 to 1.80; P = 0.563), or in change in Burford pain score from baseline to 2 weeks (-9.04 versus -2.80; P = 0.248) or to 6 weeks (-17.32 versus -8.46; 95 per cent c.i. for the difference -19.06 to 1.33; P = 0.088), or in change in Short Form 36 score from baseline to 6 weeks (2.02 versus 1.74; P = 0.903). CONCLUSION: There was no advantage to compression bandaging for more than 24 h when thromboembolus deterrent stockings were worn for the remainder of 14 days. REGISTRATION NUMBER: NCT00991497 (http://www.clinicaltrials.gov).

Randomised clinical trial of foam sclerotherapy for patients with a venous leg ulcer.

OBJECTIVES: To assess whether routine use of foam sclerotherapy, in addition to four-layer compression bandaging, could speed up the healing of venous ulcers. DESIGN: Randomised controlled trial involving patients recruited from a nurse-led leg ulcer clinic. A total of 315 new patients were assessed, and eleven patients were identified from follow-up clinics. METHODS: Inclusion criteria were: patients with an active venous leg ulcer, in the presence of superficial truncal venous incompetence and without total deep venous incompetence on duplex imaging. Patients were randomised to four-layer compression bandages alone (control) or with additional foam sclerotherapy to incompetent superficial truncal veins. The primary endpoint was ulcer healing 24 weeks after randomisation. RESULTS: It was only possible to recruit 40 patients who were suitable for analysis: 22 control, 18 additional foam sclerotherapy. There was no complication from the foam treatment and at six months the target vein was occluded in 9 of 11 evaluable patients that had foam. One patient died before 24 weeks from an unrelated cause. At 24 weeks, 17 of 20 (85% - 1 died) in the control group and 12 of 13 (92%) patients with additional foam sclerotherapy had ulcer healing (P=0.72, log rank testing). CONCLUSION: This trial failed to recruit sufficient patients for formal comparison, but foam sclerotherapy was feasible as an adjunct to compression therapy for venous ulceration. TRIAL REGISTRATION: Eudra CT 2005-001551-38.

Reduced Fractionation in Lung Cancer Patients Treated with Curative-intent Radiotherapy during the COVID-19 Pandemic.

Patients treated with curative-intent lung radiotherapy are in the group at highest risk of severe complications and death from COVID-19. There is therefore an urgent need to reduce the risks associated with multiple hospital visits and their anti-cancer treatment. One recommendation is to consider alternative dose-fractionation schedules or radiotherapy techniques. This would also increase radiotherapy service capacity for operable patients with stage I-III lung cancer, who might be unable to have surgery during the pandemic. Here we identify reduced-fractionation for curative-intent radiotherapy regimes in lung cancer, from a literature search carried out between 20/03/2020 and 30/03/2020 as well as published and unpublished audits of hypofractionated regimes from UK centres. Evidence, practical considerations and limitations are discussed for early-stage NSCLC, stage III NSCLC, early-stage and locally advanced SCLC. We recommend discussion of this guidance document with other specialist lung MDT members to disseminate the potential changes to radiotherapy practices that could be made to reduce pressure on other departments such as thoracic surgery. It is also a crucial part of the consent process to ensure that the risks and benefits of undergoing cancer treatment during the COVID-19 pandemic and the uncertainties surrounding toxicity from reduced fractionation have been adequately discussed with patients. Furthermore, centres should document all deviations from standard protocols, and we urge all colleagues, where possible, to join national/international data collection initiatives (such as COVID-RT Lung) aimed at recording the impact of the COVID-19 pandemic on lung cancer treatment and outcomes.

Enhanced diabetes care to patients of south Asian ethnic origin (the United Kingdom Asian Diabetes Study): a cluster randomised controlled trial.

BACKGROUND: Delivery of high-quality, evidence-based health care to deprived sectors of the community is a major goal for society. We investigated the effectiveness of a culturally sensitive, enhanced care package in UK general practices for improvement of cardiovascular risk factors in patients of south Asian origin with type 2 diabetes. METHODS: In this cluster randomised controlled trial, 21 inner-city practices in the UK were assigned by simple randomisation to intervention (enhanced care including additional time with practice nurse and support from a link worker and diabetes-specialist nurse [nine practices; n=868]) or control (standard care [12 practices; n=618]) groups. All adult patients of south Asian origin with type 2 diabetes were eligible. Prescribing algorithms with clearly defined targets were provided for all practices. Primary outcomes were changes in blood pressure, total cholesterol, and glycaemic control (haemoglobin A1c) after 2 years. Analysis was by intention to treat. This trial is registered, number ISRCTN 38297969. FINDINGS: We recorded significant differences between treatment groups in diastolic blood pressure (1.91 [95% CI -2.88 to -0.94] mm Hg, p=0.0001) and mean arterial pressure (1.36 [-2.49 to -0.23] mm Hg, p=0.0180), after adjustment for confounders and clustering. We noted no significant differences between groups for total cholesterol (0.03 [-0.04 to 0.11] mmol/L), systolic blood pressure (-0.33 [-2.41 to 1.75] mm Hg), or HbA1c (-0.15% [-0.33 to 0.03]). Economic analysis suggests that the nurse-led intervention was not cost effective (incremental cost-effectiveness ratio pound28 933 per QALY gained). Across the whole study population over the 2 years of the trial, systolic blood pressure, diastolic blood pressure, and cholesterol decreased significantly by 4.9 (95% CI 4.0-5.9) mm Hg, 3.8 (3.2-4.4) mm Hg, and 0.45 (0.40-0.51) mmol/L, respectively, and we recorded a small and non-significant increase for haemoglobin A1c (0.04% [-0.04 to 0.13]), p=0.290). INTERPRETATION: We recorded additional, although small, benefits from our culturally tailored care package that were greater than the secular changes achieved in the UK in recent years. Stricter targets in general practice and further measures to motivate patients are needed to achieve best possible health-care outcomes in south Asian patients with diabetes.

The promoter polymorphism -232C/G of the PCK1 gene is associated with type 2 diabetes in a UK-resident South Asian population.

BACKGROUND: The PCK1 gene, encoding cytosolic phosphoenolpyruvate carboxykinase (PEPCK-C), has previously been implicated as a candidate gene for type 2 diabetes (T2D) susceptibility. Rodent models demonstrate that over-expression of Pck1 can result in T2D development and a single nucleotide polymorphism (SNP) in the promoter region of human PCK1 (-232C/G) has exhibited significant association with the disease in several cohorts. Within the UK-resident South Asian population, T2D is 4 to 6 times more common than in indigenous white Caucasians. Despite this, few studies have reported on the genetic susceptibility to T2D in this ethnic group and none of these has investigated the possible effect of PCK1 variants. We therefore aimed to investigate the association between common variants of the PCK1 gene and T2D in a UK-resident South Asian population of Punjabi ancestry, originating predominantly from the Mirpur area of Azad Kashmir, Pakistan. METHODS: We used TaqMan assays to genotype five tagSNPs covering the PCK1 gene, including the -232C/G variant, in 903 subjects with T2D and 471 normoglycaemic controls. RESULTS: Of the variants studied, only the minor allele (G) of the -232C/G SNP demonstrated a significant association with T2D, displaying an OR of 1.21 (95% CI: 1.03 - 1.42, p = 0.019). CONCLUSION: This study is the first to investigate the association between variants of the PCK1 gene and T2D in South Asians. Our results suggest that the -232C/G promoter polymorphism confers susceptibility to T2D in this ethnic group. TRIAL REGISTRATION: UKADS Trial Registration: ISRCTN38297969.

DPP-IV inhibition enhances the antilipolytic action of NPY in human adipose tissue.

CONTEXT: Dipeptidyl peptidase IV (DPP-IV) inactivates the incretin hormone glucagon-like peptide. It can also affect the orexigenic hormone neuropeptide Y (NPY(1-36)) which is truncated by DPP-IV to NPY(3-36), as a consequence NPY's affinity changes from receptor Y1, which mediates the antilipolytic function of NPY, to other NPY receptors. Little is known whether DPP-IV inhibitors for the treatment of type 2 diabetic (T2DM) patients could influence these pathways. AIMS: To investigate the in vitro effects of NPY with DPP-IV inhibition in isolated abdominal subcutaneous (AbdSc) adipocytes on fat metabolism, and assessment of NPY receptor and DPP-IV expression in adipose tissue (AT). METHODS: Ex vivo human AT was taken from women undergoing elective surgery (body mass index: 27.5 (mean +/- s.d.) +/- 5 kg/m2, age: 43.7 +/- 10 years, n = 36). Isolated AbdSc adipocytes were treated with human recombinant (rh)NPY (1-100 nM) with and without DPP-IV inhibitor (1 M); glycerol release and tissue distribution of DPP-IV, Y1 and Y5 messenger RNA (mRNA) were measured and compared between lean and obese subjects. RESULTS AND CONCLUSION: rhNPY reduced glycerol release, an effect that was further enhanced by co-incubation with a DPP-IV inhibitor [control: 224 (mean +/- s.e.) +/- 37 micromol/l; NPY, 100 nM: 161 +/- 27 micromol/l**; NPY 100 nM/DPP-IV inhibitor, 1 M: 127 +/- 14 micromol/l**; **p < 0.01, n = 14]. DPP-IV was expressed in AbdSc AT and omental AT with relative DPP-IV mRNA expression lower in AbdSc AT taken from obese [77 +/- 6 signal units (SU)] vs. lean subjects (186 +/- 29 SU*, n = 10). Y1 was predominantly expressed in fat and present in all fat depots but higher in obese subjects, particularly the AbdSc AT-depot (obese: 1944 +/- 111 SU vs. lean: 711 +/- 112 SU**, n = 10). NPY appears to be regulated by AT-derived DPP-IV. DPP-IV inhibitors augment the antilipolytic effect of NPY in AT. Further studies are required to show whether this explains the lack of weight loss in T2DM patients treated with DPP-IV inhibitors.

Common variants of the TCF7L2 gene are associated with increased risk of type 2 diabetes mellitus in a UK-resident South Asian population.

BACKGROUND: Recent studies have implicated variants of the transcription factor 7-like 2 (TCF7L2) gene in genetic susceptibility to type 2 diabetes mellitus in several different populations. The aim of this study was to determine whether variants of this gene are also risk factors for type 2 diabetes development in a UK-resident South Asian cohort of Punjabi ancestry. METHODS: We genotyped four single nucleotide polymorphisms (SNPs) of TCF7L2 (rs7901695, rs7903146, rs11196205 and rs12255372) in 831 subjects with diabetes and 437 control subjects. RESULTS: The minor allele of each variant was significantly associated with type 2 diabetes; the greatest risk of developing the disease was conferred by rs7903146, with an allelic odds ratio (OR) of 1.31 (95% CI: 1.11 - 1.56, p = 1.96 x 10(-3)). For each variant, disease risk associated with homozygosity for the minor allele was greater than that for heterozygotes, with the exception of rs12255372. To determine the effect on the observed associations of including young control subjects in our data set, we reanalysed the data using subsets of the control group defined by different minimum age thresholds. Increasing the minimum age of our control subjects resulted in a corresponding increase in OR for all variants of the gene (p < or= 1.04 x 10(-7)). CONCLUSION: Our results support recent findings that TCF7L2 is an important genetic risk factor for the development of type 2 diabetes in multiple ethnic groups.

Comparison of maternal ghrelin and leptin in healthy mothers and mothers with Type 1 diabetes.

AIMS: Maternal leptin affects placental growth hormone (GH), whereas ghrelin, a natural ligand of the growth-hormone-secretagogue receptor, modulates GH action. Both hormones may affect fetal growth, and dysregulation in diabetes may lead to fetal growth disturbances. The aim was to investigate changes in maternal ghrelin during pregnancy with diabetes and to establish reference leptin levels. METHODS: Twelve healthy non-diabetic (ND) and 12 pregnant women with Type 1 diabetes (T1DM) were recruited. Age and body mass index (BMI) [ND: age 29.9 +/- 4.7 years (mean +/- sd), BMI 25.2 +/- 3.7 kg/m2; T1DM: age 31 +/- 5.5 years, BMI 27 +/- 3.1 kg/m2] were similar in the groups. HbA1c in T1DM was 6.2 +/- 1.1% at 20 weeks, 6.3 +/- 1.1% at 30 weeks' gestation and 7.8 +/- 2.1% postpartum. Fasting plasma ghrelin, total leptin, free leptin (FL) and soluble leptin receptor (sOB-R) levels were measured at 20 and 30 weeks' gestation and postpartum and determined by radioimmunoassay. RESULTS: All pregnancies resulted in full-term singleton births with no differences in birth weight between groups [T1DM: 3.4 +/- 0.56 kg (mean +/- SE); ND: 3.6 +/- 0.3 kg, P = NS]. Ghrelin levels were lower in T1DM when corrected for age and mothers' weight (T1DM: 458 +/- 36 pg/ml and 432.9 +/- 26.6 pg/ml; ND: 562 +/- 52 pg/ml and 515.8 +/- 63 pg/ml at 20 and 30 weeks, respectively, P < 0.05). T1DM mothers had higher levels of sOB-R and FL levels declined at 30 weeks' gestation in T1DM (P = 0.04) but not in ND. CONCLUSION: In a population of pregnant women with expected changes in leptin levels as previously reported, ghrelin levels were lower in T1DM pregnancies at 20 and 30 weeks. This may have implications for fetal development and requires further study in diabetes, particularly in pregnancies that result in macrosomia.

Mid term results of ultrasound guided foam sclerotherapy for complicated and uncomplicated varicose veins.

OBJECTIVE: The aim was to describe the results of starting a foam sclerotherapy service, focussing on patients with complicated venous disease. METHODS: Consecutive patients undergoing ultrasound-guided foam sclerotherapy for truncal varicose veins underwent clinical and hand-held Doppler assessment at 2 weeks and venous duplex imaging at 6 months. RESULTS: One hundred and eighty-five truncal veins were treated in 165 patients. A high proportion of veins were complicated (109 CEAP classes 4-6, 76 CEAP 1-3). Ninety-one percent (168) had a single treatment session. After 2 weeks, ninety-three percent (136/147) of the truncal veins appeared occluded on hand-held Doppler examination. Ten percent (15/147) of patients had remaining visible varicosities in the lower leg. After six months, the truncal vein remained occluded in 74% (68/92), was partially occluded in 10% (9/92) and fully patent in 16% (15/92). There was no significant difference in occlusion rates between: primary (45/60-75%) and recurrent (23/32-72%) veins; CEAP 2-3 (22/30-73%) and CEAP 4-6 (46/62-74%) veins; veins with diameter <7 mm (29/38-76%) or > or =7 mm (13/23-57%). No patient had evidence of deep vein thrombosis, though nine (10%) had new segmental deep venous reflux compared with pre-treatment scans. CONCLUSION: Foam sclerotherapy was equally effective for complicated and uncomplicated varicose veins.

Advanced Trauma Life Support (ATLS) and facial trauma: can one size fit all? Part 3: Hypovolaemia and facial injuries in the multiply injured patient.

Hypovolaemic shock is a common cause of morbidity and mortality following trauma, accounting for approximately 30% to 40% of trauma deaths. Life-threatening blood loss from the maxillofacial region is uncommon, but represents one of a number of possible sites which must be rapidly identified and controlled. Bleeding from the face may not be obvious especially in awake, supine patients and it poses an obvious threat to the unprotected airway. Identification requires careful assessment. Control of bleeding in the maxillofacial region requires a number of correctly sequenced techniques. Computerized tomographic imaging is now playing an increasingly important role in identifying blood loss, especially in the chest, abdomen and pelvis. This need may potentially result in the transfer of patients, with unrecognised facial injuries, outside the relative safety of the emergency department. The concepts of the 'lethal triad' and 'biologic first hit' have resulted in new strategies in managing the profoundly shocked patient, although some of these remain controversial. Debate continues over the optimal blood pressure, fluid administration and role of surgical intervention in the actively bleeding patient. These may have an impact on the timing and extent of any proposed maxillofacial repairs, and are discussed.

Maintaining standards for pressure ulcer management in care homes.

This article is based on a review carried out by the Scottish Commission for the Regulation of Care (Care Commission) in 2007, which examined pressure ulcer prevention, care and treatment for older people living in care homes in Scotland. Inspection, complaints and enforcement activity from 2002 to 2006 revealed many aspects of poor practice, as residents were either at risk of developing a pressure ulcer, or existing pressure ulcers were not being managed appropriately. The review highlighted six key areas where care homes were consistently not meeting best practice and recommendations were made to improve care.

Canagliflozin, dapagliflozin and empagliflozin monotherapy for treating type 2 diabetes: systematic review and economic evaluation.

BACKGROUND: Most people with type 2 diabetes are overweight, so initial treatment is aimed at reducing weight and increasing physical activity. Even modest weight loss can improve control of blood glucose. If drug treatment is necessary, the drug of first choice is metformin. However, some people cannot tolerate metformin, which causes diarrhoea in about 10%, and it cannot be used in people with renal impairment. This review appraises three of the newest class of drugs for monotherapy when metformin cannot be used, the sodium-glucose co-transporter 2 (SGLT2) inhibitors. OBJECTIVE: To review the clinical effectiveness and cost-effectiveness of dapagliflozin (Farxiga, Bristol-Myers Squibb, Luton, UK), canagliflozin (Invokana, Janssen, High Wycombe, UK) and empagliflozin (Jardiance, Merck & Co., Darmstadt, Germany), in monotherapy in people who cannot take metformin. SOURCES: MEDLINE (1946 to February 2015) and EMBASE (1974 to February 2015) for randomised controlled trials lasting 24 weeks or more. For adverse events, a wider range of studies was used. Three manufacturers provided submissions. METHODS: Systematic review and economic evaluation. A network meta-analysis was carried out involving the three SGLT2 inhibitors and key comparators. Critical appraisal of submissions from three manufacturers. RESULTS: We included three trials of dapagliflozin and two each for canagliflozin and empagliflozin. The trials were of good quality. The canagliflozin and dapagliflozin trials compared them with placebo, but the two empagliflozin trials included active comparators. All three drugs were shown to be effective in improving glycaemic control, promoting weight loss and lowering blood pressure (BP). LIMITATIONS: There were no head-to-head trials of the different flozins, and no long-term data on cardiovascular outcomes in this group of patients. Most trials were against placebo. The trials were done in patient groups that were not always comparable, for example in baseline glycated haemoglobin or body mass index. Data on elderly patients were lacking. CONCLUSIONS: Dapagliflozin, canagliflozin and empagliflozin are effective in improving glycaemic control, with added benefits of some reductions in BP and weight. Adverse effects are urinary and genital tract infections in a small proportion of users. In monotherapy, the three drugs do not appear cost-effective compared with gliclazide or pioglitazone, but may be competitive against sitagliptin (Januvia, Boehringer Ingelheim, Bracknell, UK). FUNDING: The National Institute for Health Research Health Technology Assessment programme.