Resolving the fibrotic niche of human liver cirrhosis at single-cell level.

Liver cirrhosis is a major cause of death worldwide and is characterized by extensive fibrosis. There are currently no effective antifibrotic therapies available. To obtain a better understanding of the cellular and molecular mechanisms involved in disease pathogenesis and enable the discovery of therapeutic targets, here we profile the transcriptomes of more than 100,000 single human cells, yielding molecular definitions for non-parenchymal cell types that are found in healthy and cirrhotic human liver. We identify a scar-associated TREM2+CD9+ subpopulation of macrophages, which expands in liver fibrosis, differentiates from circulating monocytes and is pro-fibrogenic. We also define ACKR1+ and PLVAP+ endothelial cells that expand in cirrhosis, are topographically restricted to the fibrotic niche and enhance the transmigration of leucocytes. Multi-lineage modelling of ligand and receptor interactions between the scar-associated macrophages, endothelial cells and PDGFRα+ collagen-producing mesenchymal cells reveals intra-scar activity of several pro-fibrogenic pathways including TNFRSF12A, PDGFR and NOTCH signalling. Our work dissects unanticipated aspects of the cellular and molecular basis of human organ fibrosis at a single-cell level, and provides a conceptual framework for the discovery of rational therapeutic targets in liver cirrhosis.

Associations between comorbidities and immediate and one-year outcomes following supervised exercise therapy and patient education - A cohort study of 24,513 individuals with knee or hip osteoarthritis.

OBJECTIVE: To investigate if comorbidities are associated with change in health outcomes following an 8-week exercise and education program in knee and hip osteoarthritis (OA). METHODS: We included 24,513 individuals with knee or hip OA from the Good Life with osteoArthritis in Denmark (GLA:D®). GLA:D® consists of two patient education sessions and 12 supervised exercise sessions. Before the program, individuals self-reported having one or more of 11 common comorbidities. Physical function was assessed using the 40-m Fast-Paced Walk Test (FPWT, m/sec) before and immediately after the program. Pain intensity and health-related quality of life was self-reported before, immediately after, and at 12 months post-intervention using a visual analogue scale (VAS, 0-100) and the EQ-5D-5L index (-0.624 to 1.000), respectively. Associations of comorbidity combinations with change in outcomes immediately and at 12 months was estimated using mixed linear regression. RESULTS: Individuals with OA improved on average 0.12 m/s (95%CI 0.12 to 0.13) in 40-m FPWT, -12.7 mm (95%CI -13.2 to -12.2) in VAS, and 0.039 (95%CI 0.036 to 0.041) in EQ-5D-5L from before to immediately after the intervention with minor additional improvements at 12 months. Despite that individuals with comorbidities had worse baseline scores in all outcomes than individuals without comorbidities, they had similar levels of improvement immediately and 12 months after the intervention. CONCLUSION: Comorbidities are not associated with worse nor better health outcomes following an 8-week exercise and education program in individuals with OA, suggesting exercise as a viable treatment option for individuals with OA, irrespective of comorbidities.

Short- and long-term effects of the patient education strategy-learning and coping-in cardiac rehabilitation: a randomized controlled trial (LC-REHAB).

The objectives were to assess the short- and long-term effect of the patient education strategy 'Learning and Coping' (LC) in cardiac rehabilitation (CR) on health-related quality of life, patient education impact, cardiac risk factors and lifestyle. In total, 825 patients hospitalized with ischaemic heart disease or heart failure were randomized to either LC-CR or standard CR at three Danish hospitals. Teaching approach in LC-CR was situational, inductive and reflective, with experienced patients as co-educators and supplemental interviews. Teaching approach in standard CR was structured and deductive. Outcomes were assessed immediately after CR, and after 3 months (short term), and after 3 years (long term). Between-arm differences in favour of LC-CR were SF-12 'role emotional' (3.7, 95% CI: 0.6-6.8) and MDI depression score (0.9, 0.1-1.8) immediately after CR, exercise capacity (4 W, 1-9) at 3 months and SF-12 'role physical' (4.6, 0.1-9.0) (long term). Between-arm differences in favour of controls were waist circumference (-1.7 cm, -2.3 to -1.0) immediately after CR and HeiQ domain 'Constructive attitudes and approaches' (0.11, 0.04-0.18), triglycerides (-0.12 mmol/l, -0.21 to -0.02), systolic blood pressure (-3.12 mmHg, -5.66 to -0.58) at 3 months. Adding LC strategies to CR provides inconsistent short-term results but improves 'role physical' long term.

Promotion of mental health in young adults via mobile phone app: study protocol of the ECoWeB (emotional competence for well-being in Young adults) cohort multiple randomised trials.

BACKGROUND: Promoting well-being and preventing poor mental health in young people is a major global priority. Building emotional competence (EC) skills via a mobile app may be an effective, scalable and acceptable way to do this. However, few large-scale controlled trials have examined the efficacy of mobile apps in promoting mental health in young people; none have tailored the app to individual profiles. METHOD/DESIGN: The Emotional Competence for Well-Being in Young Adults cohort multiple randomised controlled trial (cmRCT) involves a longitudinal prospective cohort to examine well-being, mental health and EC in 16-22 year olds across 12 months. Within the cohort, eligible participants are entered to either the PREVENT trial (if selected EC scores at baseline within worst-performing quartile) or to the PROMOTE trial (if selected EC scores not within worst-performing quartile). In both trials, participants are randomised (i) to continue with usual practice, repeated assessments and a self-monitoring app; (ii) to additionally receive generic cognitive-behavioural therapy self-help in app; (iii) to additionally receive personalised EC self-help in app. In total, 2142 participants aged 16 to 22 years, with no current or past history of major depression, bipolar disorder or psychosis will be recruited across UK, Germany, Spain, and Belgium. Assessments take place at baseline (pre-randomisation), 1, 3 and 12 months post-randomisation. Primary endpoint and outcome for PREVENT is level of depression symptoms on the Patient Health Questionnaire-9 at 3 months; primary endpoint and outcome for PROMOTE is emotional well-being assessed on the Warwick-Edinburgh Mental Wellbeing Scale at 3 months. Depressive symptoms, anxiety, well-being, health-related quality of life, functioning and cost-effectiveness are secondary outcomes. Compliance, adverse events and potentially mediating variables will be carefully monitored. CONCLUSIONS: The trial aims to provide a better understanding of the causal role of learning EC skills using interventions delivered via mobile phone apps with respect to promoting well-being and preventing poor mental health in young people. This knowledge will be used to develop and disseminate innovative evidence-based, feasible, and effective Mobile-health public health strategies for preventing poor mental health and promoting well-being. TRIAL REGISTRATION: ClinicalTrials.gov ( www.clinicaltrials.org ). Number of identification: NCT04148508 November 2019.

Effects of the patient education strategy 'Learning and Coping' in cardiac rehabilitation on readmissions and mortality: a randomized controlled trial (LC-REHAB).

We assessed the effects of the patient education strategy 'Learning and Coping' (LC) in cardiac rehabilitation (CR) on mortality and readmissions by exploring results from the LC-REHAB trial. In all, 825 patients with ischaemic heart disease or heart failure were randomized to the intervention arm (LC-CR) or the control arm (standard CR) at three hospitals in Denmark. LC-CR was situational and inductive, with experienced patients as co-educators supplemented with two individual interviews. Group-based training and education hours were the same in both arms. Outcomes were time to death or readmission, length of stay and absolute number of deaths or readmissions. No between-arm differences were found in time to death, first readmission, or length of stay. Within 30 days after completion of CR, the absolute number of all-cause readmissions was 117 in the LC arm and 146 in the control arm, adjusted odds ratio 78 (95% CI: 0.61-1.01), P = 0.06. This trend diminished over time. Adding LC strategies to standard CR showed a short term but no significant long-term effect on mortality or readmissions. However, the study was not powered to detect differences in mortality and morbidity. Thus, a risk of overseeing a true effect was present.

Exercise to preserve ß-cell function in recent-onset Type 1 diabetes mellitus (EXTOD) - a randomized controlled pilot trial.

AIM: Residual ß-cell function is present at the time of diagnosis with Type 1 diabetes. Preserving this ß-cell function reduces complications. We hypothesized that exercise preserves ß-cell function in Type 1 diabetes and undertook a pilot trial to address the key uncertainties in designing a definitive trial to test this hypothesis. METHODS: A randomized controlled pilot trial in adults aged 16-60 years diagnosed with Type 1 diabetes within the previous 3 months was undertaken. Participants were assigned to control (usual care) or intervention (exercise consultation every month), in a 1 : 1 ratio for 12 months. The primary outcomes were recruitment rate, drop out, exercise adherence [weeks with ≥ 150 min of self-reported moderate to vigorous physical activity (MVPA)], and exercise uptake in the control group. The secondary outcomes were differences in insulin sensitivity and rate of loss of ß-cell function between intervention and control at 6 and 12 months. RESULTS: Of 507 individuals who were approached, 58 (28 control, 30 intervention) entered the study and 41 completed it. Participants were largely white European males, BMI 24.8 ± 3.8 kg/m2 , HbA1c 75 ± 25 mmol/mol (9 ± 2%). Mean level of objectively measured MVPA increased in the intervention group (mean 243 to 273 min/week) and 61% of intervention participants reached the target of ≥ 150 min/week of self-reported MVPA on at least 42 weeks of the year. Physical activity levels fell slightly in the control group (mean 277 to 235 min of MVPA/week). There was exploratory evidence that intervention group became more insulin sensitive and required less insulin. However, the rate of loss of ß-cell function appeared similar between the groups, although the change in insulin sensitivity may have affected this. CONCLUSION: We show that it is possible to recruit and randomize people with newly diagnosed Type 1 diabetes to a trial of an exercise intervention, and increase and maintain their exercise levels for 12 months. Future trials need to incorporate measures of greater adherence to exercise training targets, and include more appropriate measures of ß-cell function. (Clinical Trials Registry No; ISRCTN91388505).

Productivity and species richness in longleaf pine woodlands: resource-disturbance influences across an edaphic gradient.

This study examines the complex feedback mechanisms that regulate a positive relationship between species richness and productivity in a longleaf pine-wiregrass woodland. Across a natural soil moisture gradient spanning wet-mesic to xeric conditions, two large scale manipulations over a 10-yr period were used to determine how limiting resources and fire regulate plant species diversity and productivity at multiple scales. A fully factorial experiment was used to examine productivity and species richness responses to N and water additions. A separate experiment examined standing crop and richness responses to N addition in the presence and absence of fire. Specifically, these manipulations addressed the following questions: (1) How do N and water addition influence annual aboveground net primary productivity of the midstory/overstory and ground cover? (2) How do species richness responses to resource manipulations vary with scale and among functional groups of ground cover species? (3) How does standing crop (including overstory, understory/midstory, and ground cover components) differ between frequently burned and fire excluded plots after a decade without fire? (4) What is the role of fire in regulating species richness responses to N addition? This long-term study across a soil moisture gradient provides empirical evidence that species richness and productivity in longleaf pine woodlands are strongly regulated by soil moisture. After a decade of treatment, there was an overall species richness decline with N addition, an increase in richness of some functional groups with irrigation, and a substantial decline in species richness with fire exclusion. Changes in species richness in response to treatments were scale-dependent, occurring primarily at small scales (≤10 m2 ). Further, with fire exclusion, standing crop of ground cover decreased with N addition and non-pine understory/midstory increased in wet-mesic sites. Non-pine understory/midstory standing crop increased in xeric sites with fire exclusion, but there was no influence of N addition. This study highlights the complexity of interactions among multiple limiting resources, frequent fire, and characteristics of dominant functional groups that link species richness and productivity.

Effects of pre-eclampsia and fetal growth restriction on C-type natriuretic peptide.

OBJECTIVE: To determine changes in plasma C-type natriuretic peptide (CNP), a paracrine product of the vascular endothelium, in pregnancies with vascular disorders, and relate these to time of presentation and severity. DESIGN: Retrospective nested cases and controls. SETTING: Community study, Auckland New Zealand. POPULATION: Screening for Pregnancy Endpoints (SCOPE) data and bio-bank of maternal plasma. METHODS: Maternal plasma amino terminal proCNP (NTproCNP) was measured by radioimmunoassay in early (14-16 weeks of gestation, and again at 19-21 weeks of gestation) and late (34-36 weeks of gestation) pregnancy in three groups of women (20 per group): pre-eclampsia (pre-eclampsia); gestational hypertension (GHT) with small for gestational age (SGA); and uncomplicated pregnancy. MAIN OUTCOME MEASURES: Change in NTproCNP and associations with concurrent blood pressure, time of case presentation, severity, and infant birthweight. RESULTS: Plasma NTproCNP in early pregnancy in women with vascular disorders did not differ from those found in controls. In late pregnancy, levels in pre-eclampsia (28.8 ± 2.3 pM) and in GHT with SGA (28.6 ± 4.8 pM) were significantly increased (P = 0.01 and 0.027, respectively) compared with controls (21.3 ± 1 pM). In pre-eclampsia, levels were significantly higher (P < 0.03) at 14-16 weeks of gestation in women diagnosed prior to 34 weeks of gestation. Combining all three groups, associations of NTproCNP with concurrent diastolic and mean arterial pressure were found at 34-36 weeks of gestation (r = 0.46). No significant associations were identified with birthweight. CONCLUSIONS: CNP secretion during gestation is responsive to vascular stress. Plasma NTproCNP measurements may have clinical application in late pregnancy in defining the different phenotypes associated with pre-eclampsia.

Netmums: a phase II randomized controlled trial of a guided Internet behavioural activation treatment for postpartum depression.

BACKGROUND: Despite the high prevalence of postnatal depression (PND), few women seek help. Internet interventions may overcome many of the barriers to PND treatment use. We report a phase II evaluation of a 12-session, modular, guided Internet behavioural activation (BA) treatment modified to address postnatal-specific concerns [Netmums Helping With Depression (NetmumsHWD)]. METHOD: To assess feasibility, we measured recruitment and attrition to the trial and examined telephone session support and treatment adherence. We investigated sociodemographic and psychological predictors of treatment adherence. Effectiveness outcomes were estimated with the Edinburgh Postnatal Depression Scale (EPDS), Generalized Anxiety Disorder-7, Work and Social Adjustment Scale, Postnatal Bonding Questionnaire, and Social Provisions Scale. RESULTS: A total of 249 women were recruited via a UK parenting site, Netmums.com. A total of 83 women meeting DSM-IV criteria for major depressive disorder were randomized to NetmumsHWD (n = 41) or treatment-as-usual (TAU; n = 42). Of the 83 women, 71 (86%) completed the EPDS at post-treatment, and 71% (59/83) at the 6-month follow-up. Women completed an average of eight out of 12 telephone support sessions and five out of 12 modules. Working women and those with less support completed fewer modules. There was a large effect size favouring women who received NetmumsHWD on depression, work and social impairment, and anxiety scores at post-treatment compared with women in the TAU group, and a large effect size on depression at 6 months post-treatment. There were small effect sizes for postnatal bonding and perceived social support. CONCLUSIONS: A supported, modular, Internet BA programme can be feasibly delivered to postpartum women, offering promise to improve depression, anxiety and functioning.

Pyrosequencing-based characterization of gastrointestinal bacteria of Atlantic salmon (Salmo salar L.) within a commercial mariculture system.

AIMS: The relationship of Atlantic salmon gastrointestinal (GI) tract bacteria to environmental factors, in particular water temperature within a commercial mariculture system, was investigated. METHODS AND RESULTS: Salmon GI tract bacterial communities commercially farmed in south-eastern Tasmania were analysed, over a 13-month period across a standard commercial production farm cycle, using 454 16S rRNA-based pyrosequencing. Faecal bacterial communities were highly dynamic but largely similar between randomly selected fish. In postsmolt, the faecal bacteria population was dominated by Gram-positive fermentative bacteria; however, by midsummer, members of the family Vibrionaceae predominated. As fish progressed towards harvest, a range of different bacterial genera became more prominent corresponding to a decline in Vibrionaceae. The sampled fish were fed two different commercial diet series with slightly different protein, lipid and digestible energy level; however, the effect of these differences was minimal. CONCLUSIONS: The overall data demonstrated dynamic hind gut communities in salmon that were related to season and fish growth phases but were less influenced by differences in commercial diets used routinely within the farm system studied. SIGNIFICANCE AND IMPACT OF THE STUDY: This study provides understanding of farmed salmon GI bacterial communities and describes the relative impact of diet, environmental and farm factors.

Fire mosaics and reptile conservation in a fire-prone region.

Fire influences the distribution of fauna in terrestrial biomes throughout the world. Use of fire to achieve a mosaic of vegetation in different stages of succession after burning (i.e., patch-mosaic burning) is a dominant conservation practice in many regions. Despite this, knowledge of how the spatial attributes of vegetation mosaics created by fire affect fauna is extremely scarce, and it is unclear what kind of mosaic land managers should aim to achieve. We selected 28 landscapes (each 12.6 km(2) ) that varied in the spatial extent and diversity of vegetation succession after fire in a 104,000 km(2) area in the semiarid region of southeastern Australia. We surveyed for reptiles at 280 sites nested within the 28 landscapes. The landscape-level occurrence of 9 of the 22 species modeled was associated with the spatial extent of vegetation age classes created by fire. Biogeographic context and the extent of a vegetation type influenced 7 and 4 species, respectively. No species were associated with the diversity of vegetation ages within a landscape. Negative relations between reptile occurrence and both extent of recently burned vegetation (≤10 years postfire, n = 6) and long unburned vegetation (>35 years postfire, n = 4) suggested that a coarse-grained mosaic of areas (e.g. >1000 ha) of midsuccessional vegetation (11-35 years postfire) may support the fire-sensitive reptile species we modeled. This age class coincides with a peak in spinifex cover, a keystone structure for reptiles in semiarid and arid Australia. Maintaining over the long term a coarse-grained mosaic of large areas of midsuccessional vegetation in mallee ecosystems will need to be balanced against the short-term negative effects of large fires on many reptile species and a documented preference by species from other taxonomic groups, particularly birds, for older vegetation.

Surrogate, friend or foe? The need for case studies of the use of surrogate outcomes in cost-effectiveness analyses.

We comment on a recent article by Hawkins et al. presenting different analytic approaches for the inclusion of surrogate and final outcomes in cost-effectiveness analyses. This methodological case study provides a timely and valuable contribution to build on the debate about the use of evidence based on surrogate outcomes in health technology assessment.

Where does spinal cord stimulation fit into the international guidelines for refractory painful diabetic neuropathy? a consensus statement.

BACKGROUND: Although pharmacotherapy with anticonvulsants and/or antidepressants can be effective for many people with painful diabetic neuropathy (PDN), albeit with frequent side-effects, a critical juncture occurs when neuropathic pain no longer responds to standard first- and second-step mono- and dual therapy and becomes refractory. Subsequent to these pharmacotherapeutic approaches, third-line treatment options for PDN may include opioids (short-term), capsaicin 8% patches, and spinal cord stimulation (SCS). AIM: This document summarizes consensus recommendations regarding appropriate treatment for refractory peripheral diabetic neuropathy (PDN), based on outcomes from an expert panel convened on December 10, 2022, as part of the Worldwide Initiative for Diabetes Education Virtual Global Summit, "Advances in the Management of Painful Diabetic Neuropathy." PARTICIPANTS: Nine attendees, eminent physicians and academics, comprising six diabetes specialists, two pain specialists, and one health services expert. EVIDENCE: For individuals with refractory PDN, opioids are a high-risk option that do not provide a long-term solution and should not be used. For appropriately selected individuals, SCS is an effective, safe, and durable treatment option. In particular, high-frequency (HF) SCS (10 kHz) shows strong efficacy and improves quality of life. To ensure treatment success, strict screening criteria should be used to prioritize candidates for SCS. CONSENSUS PROCESS: Each participant voiced their opinion after reviewing available data, and a verbal consensus was reached during the meeting. CONCLUSION: Globally, the use of opioids should rarely be recommended for refractory, severe PDN. Based on increasing clinical evidence, SCS, especially HF-SCS, should be considered as a treatment for PDN that is not responsive to first- or second-line monotherapy/dual therapy.

Guided self-help concreteness training as an intervention for major depression in primary care: a Phase II randomized controlled trial.

BACKGROUND: The development of widely accessible, effective psychological interventions for depression is a priority. This randomized trial provides the first controlled data on an innovative cognitive bias modification (CBM) training guided self-help intervention for depression. METHOD: One hundred and twenty-one consecutively recruited participants meeting criteria for current major depression were randomly allocated to treatment as usual (TAU) or to TAU plus concreteness training (CNT) guided self-help or to TAU plus relaxation training (RT) guided self-help. CNT involved repeated practice at mental exercises designed to switch patients from an unhelpful abstract thinking habit to a helpful concrete thinking habit, thereby targeting depressogenic cognitive processes (rumination, overgeneralization). RESULTS: The addition of CNT to TAU significantly improved depressive symptoms at post-treatment [mean difference on the Hamilton Rating Scale for Depression (HAMD) 4.28, 95% confidence interval (CI) 1.29-7.26], 3- and 6-month follow-ups, and for rumination and overgeneralization post-treatment. There was no difference in the reduction of symptoms between CNT and RT (mean difference on the HAMD 1.98, 95% CI -1.14 to 5.11), although CNT significantly reduced rumination and overgeneralization relative to RT post-treatment, suggesting a specific benefit on these cognitive processes. CONCLUSIONS: This study provides preliminary evidence that CNT guided self-help may be a useful addition to TAU in treating major depression in primary care, although the effect was not significantly different from an existing active treatment (RT) matched for structural and common factors. Because of its relative brevity and distinct format, it may have value as an additional innovative approach to increase the accessibility of treatment choices for depression.

The impact of maternal body mass index on the phenotype of pre-eclampsia: a prospective cohort study.

OBJECTIVE: We hypothesised that among nulliparous women with pre-eclampsia, overweight or obese women would have a different phenotype of pre-eclampsia compared with normal weight women with pre-eclampsia. Specifically, they are more likely to develop term pre-eclampsia and less likely to have indicators of impaired placental perfusion, e.g. abnormal uterine artery Doppler or a small-for-gestational-age (SGA) infant. DESIGN: Prospective, multicentre, cohort SCOPE study (n = 3170). SETTING: New Zealand and Australia. POPULATION: Nulliparous women who developed pre-eclampsia. METHODS: Participants were interviewed at 14-16 weeks of gestation, uterine artery Doppler studies were performed at 19-21 weeks and pregnancy outcome was tracked prospectively. MAIN OUTCOME MEASURES: Rates of abnormal uterine artery Doppler indices, term/preterm birth and SGA infants were compared between normal, overweight and obese women with pre-eclampsia. Multivariable analysis was performed to examine the association between body mass index (BMI) and term pre-eclampsia. RESULTS: Of 178 women with pre-eclampsia, one underweight woman was excluded and 66 (37%) were normal weight, 52 (29%) were overweight and 59 (34%) were obese. Pre-eclampsia developed preterm in 26% of women and at term in 74% of women. There were no differences in the rates of term/preterm pre-eclampsia, abnormal uterine artery Doppler indices or SGA infants between BMI groups (P > 0.10). No independent association between BMI and term pre-eclampsia was found (P = 0.56). CONCLUSIONS: Among women with pre-eclampsia, those who are overweight or obese in early pregnancy are not more likely to have term pre-eclampsia compared with women with a normal BMI. Overweight and obese women require vigilant surveillance for the development of preterm as well as term pre-eclampsia.

Maternal Mid-Gestation Cytokine Dysregulation in Mothers of Children with Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is a developmental disorder characterised by deficits in social interactions and communication, with stereotypical and repetitive behaviours. Recent evidence suggests that maternal immune dysregulation may predispose offspring to ASD. Independent samples t-tests revealed downregulation of IL-17A concentrations in cases, when compared to controls, at both 15 weeks (p = 0.02), and 20 weeks (p = 0.02), which persisted at 20 weeks following adjustment for confounding variables. This adds to the growing body of evidence that maternal immune regulation may play a role in foetal neurodevelopment.

Nurse-led interventions used to improve control of high blood pressure in people with diabetes: a systematic review and meta-analysis.

BACKGROUND: Previous reviews demonstrate uncertainty about the effectiveness of nurse-led interventions in the management of hypertension. No specific reviews in diabetes have been identified. We have systematically reviewed the evidence for effectiveness of nurse-led interventions for people with diabetes mellitus. METHODS: In this systematic review and meta-analysis, searches of Medline, Embase, CINAHL and the Cochrane Central Trials register were undertaken to identify studies comparing any intervention conducted by nurses in managing hypertension in diabetes with usual doctor-led care. Additional citations were identified from papers retrieved and correspondence with authors. Outcome measures were absolute systolic and diastolic blood pressure, change in blood pressure, proportions achieving study target blood pressure and proportions prescribed anti-hypertensive medication. RESULTS: Eleven studies were identified. Interventions included adoption of treatment algorithms, nurse-led clinics and nurse prescribing. Meta-analysis showed greater reductions in blood pressure in favour of any nurse-led interventions (systolic weighted mean difference -5.8 mmHg, 95% CI -9.6 to -2.0; diastolic weighted mean difference -4.2 mmHg, 95% CI -7.6 to -0.7) compared with usual doctor-led care. No overall superiority in achievement of study targets or in the use of medication was evident for any nurse-based interventions over doctor-led care. CONCLUSIONS: There is some evidence for improved blood pressure outcomes with nurse-led interventions for hypertension in people with diabetes compared with doctor-led care. Nurse-based interventions require an algorithm to structure care and there is some preliminary evidence for better outcomes with nurse prescribing. Further work is needed to elucidate which nurse-led interventions are most effective.