Tinkering with care: Implementing extended-release buprenorphine depot treatment for opioid dependence.

We examine how extended-release buprenorphine depot (BUP-XR) is put to use and made to work in implementation practices, attending to how care practices are challenged and adapted as a long-acting technology is introduced into service in opioid agonist treatment (OAT) in Australia. Our approach is informed by ideas in science and technology studies (STS) emphasising the irreducible entanglement of care practices and technology, and in particular the concept of 'tinkering' as a practice of adaptation. To make our analysis, we draw on qualitative interview accounts (n = 19) of service providers involved in BUP-XR implementation across five sites. Our analysis considers the disruptive novelty of BUP-XR. Tinkering to make a novel technology work in practice slows down the expectation of implementation in relation to transformative innovation, despite the promise of dramatic or rapid change. Tinkering allowed for more open relations, for new care practices that departed from the routine and familiar, opening potential for how BUP-XR could be put to use and made to work in its new situation, and as its situation evolved along-with its implementation. Flexibility and openness of altering relations was, however, at times, held in tension with inflexibility and closure. This analysis identifies a concern for what is made present and what is made absent in the altered care network affected by BUP-XR, with the multiple effects of supervised daily dosing practices thrown into relief as they become absented. Tinkering to implement BUP-XR locally connects with a broader assemblage of trial and movement in the constitution of treatment. The introduction of long-acting technologies prompts new questions about embedded implementation practices, including supervised dosing, urinalysis, the time and place of psychosocial support, and how other social aspects of care might be recalibrated in drug treatment.

Xenon tracers for cost effective laser induced fluorescence of alternative propellant Hall thrusters.

One of the limiting factors to developing plasma thrusters on alternative propellants is the cost associated with changing the diagnostic tools, which are often propellant-dependent. For laser induced fluorescence (LIF), which is typically used for ion velocity distribution measurements to determine ion trajectories and potential profiles, either new lasers need to be bought, which are tuned to the wavelength of the new element's excitation level, or a costly tunable laser is required. A method to use existing LIF setups designed for xenon on any propellant has been demonstrated on a Hall thruster operating on krypton. In the demonstration test, a small amount of xenon (0.01%-4%) was mixed with the main krypton propellant for use as a diagnostic tracer, and xenon ion velocities were measured while also monitoring changes in the mean discharge current and oscillations. High signal-to-noise ratios in LIF data acquired along the channel centerline were obtained with tracer gas fractions ≤1% that negligibly affected the thruster operation. These results and comparison of the emission spectra of xenon and other common propellants suggest that the tracer LIF method should be broadly applicable to LIF measurements in Hall thrusters operating on alternative propellants.

Deliberative Improvement of Oral Care Quality: The Horizon Europe DELIVER Project.

KNOWLEDGE TRANSFER STATEMENT: The EU DELIVER project aims to enhance the quality of oral health care through codevelopment and coproduction of solutions together with citizens/patients, providers, and policymakers. The unique multicountry nature of the project will facilitate fast-track prototype development and testing of innovative QI approaches in select countries. Reflective learning regarding the transferability of findings between different countries and settings offers unique opportunities to drive progress toward context-specific implementation of innovative oral health care QI approaches. The collective knowledge gained from the 7 European countries involved in DELIVER can also generate knowhow for improving the quality of oral health care in other countries around the globe.

A retrospective cohort study evaluating pregnancy outcomes in women with MIDD.

AIMS: The most common pathogenic mitochondrial mutation associated with mitochondrial disease is m.3243A>G. Increased obstetric complications, such as spontaneous abortion, gestational diabetes (GDM), preterm delivery, and preeclampsia, have been reported in women carrying this mutation. We aimed to determine the fetal and maternal outcomes in pregnant women with mitochondrial disease. METHODS: We retrospectively studied the obstetric and perinatal outcomes in 88 pregnancies of 26 women with genetically confirmed mitochondrial disease (m.3243A>G in the MTTL1 gene (n = 25); m.12258C>A in the MT-TS2 gene (n = 1)). Outcomes included pregnancy related complications, mode of delivery, gestational age at delivery and birthweight. RESULTS: Mean heteroplasmy rate was 18%. The miscarriage rate was higher than background at 25%. 21 pregnancies (24%) were complicated by GDM; 9 pregnancies (13.6%) had a preterm delivery and 2 of them (3%) an extreme premature delivery < 32 weeks. One woman had preeclampsia and one had a postpartum hemorrhage. The caesarean section (CS) rate was 20%. For every unit increase in maternal heteroplasmy levels there was a 26% increased risk of undergoing an assisted operative vaginal delivery (OR 1.26, 95% CI 1.04-1.53, P = 0.002, Bonferroni corrected P = 0.005) and an 18% increased risk of undergoing a CS (OR 1.18, 95% CI 1.01-1.39, P = 0.01, Bonferroni corrected P = 0.03) compared to a spontaneous vaginal delivery. There was a statistical significant correlation between maternal and offspring heteroplasmy levels. Spearman correlation rho = 0.96, 95% CI 0.78-0.99, P = 0.0002. CONCLUSION: Women with mitochondrial disease appear to have more frequent obstetric complications including miscarriage and GDM. Pre-pregnancy diagnosis of m.3243A>G will enable the counseling of women and increase awareness of possible obstetric complications.

tRNA-derived fragments are altered in diabetes.

AIMS: Maternally inherited diabetes and deafness (MIDD) is a rare form of adult-onset diabetes that can be difficult to diagnose due to its variable clinical phenotype. Transfer RNA-derived small fragments are a novel, emerging class of small non-coding RNAs (sncRNAs) that have significant potential as serum biomarkers due to their stress-induced generation, abundance, stability and ease of detection. METHODS: We investigated the levels of tiRNA 5'ValCAC (alone and in combination with miR-23b-3p) identified from small RNA sequencing studies in serum samples from healthy controls, type 1 diabetes, type 2 diabetes and MIDD subjects. RESULTS: Serum levels of 5'ValCAC were reduced in MIDD and type 2 diabetes subjects compared to controls. Type 2 diabetes subjects had higher serum levels of miR-23b-3p compared to all other subjects. Receiver Operating Characteristic analysis showed the potential of 5'ValCAC and miR-23b-3p as MIDD biomarkers, with the combination showing excellent separation from type 2 diabetes subjects. CONCLUSIONS: This is the first report showing altered serum levels of tiRNAs in diabetes subjects. The combined use of 5'ValCAC and miR-23b-3p as serum biomarkers could potentially differentiate between MIDD subjects and type 2 diabetes subjects.

Water turbidity affects the establishment of Neochetina eichhorniae (Warner) (Coleoptera: Curculionidae): Implications for biological control of water hyacinth.

Water hyacinth is the target of nine biological control agents in South Africa including Neochetina eichhorniae (Warner) and Neochetina bruchi (Hustache) (Coleoptera: Curculionidae). These two weevils have also been released against water hyacinth in Rwanda, but failed to control the weed invasion, possibly due to high turbidity in the country's water bodies. This study therefore aimed to investigate the effect of water turbidity on the establishment and performance of N. eichhorniae in Rwanda. Turbidity levels were measured over two seasons in four Rwandan rivers and two lakes. The results were then used to benchmark laboratory trials to test the effect of turbidity on the weevils' development. Water hyacinth plants were maintained at four turbidity levels: Clear water (2 Nephelometric Turbidity Units (NTU): low (85 NTU), medium (600 NTU) and high (1500 NTU). Each treatment plant was inoculated with three N. eichhorniae larvae, while control plants were free of larvae. Plant growth was measured weekly for three months, while adult weevil emergence was recorded from the 56th day of the experiment. The number of adults emerging from the treatment plants grown in the clear water, low, medium and high turbidity levels were 24, 21, 12 and 0, respectively. Larval feeding was greater on plants growing in clear water and the low turbidity, compared to the medium and high turbidity treatments. These results indicate that N. eichhorniae may not establish or perform well in water bodies with high levels of turbidity, which in turn enhances the growth of water hyacinth, allowing compensatory growth for weevil feeding.

Key predictors and burden of meticillin-resistant Staphylococcus aureus infection in comparison with meticillin-susceptible S. aureus infection in an Australian hospital setting.

BACKGROUND: Staphylococcus aureus is associated with significant mortality and increased burden on the healthcare system. Relatively few reliable estimates are available regarding the impact of meticillin-resistant S. aureus (MRSA) infection compared with meticillin-susceptible S. aureus (MSSA) infection. AIMS: To compare patients with MRSA infection and MSSA infection to identify differences in inpatient mortality, length of stay and costs of hospital services, and identify predictors of MRSA as a cause of S. aureus infection. METHODS: An analytical, retrospective, longitudinal study using non-identifiable linked data on adults admitted to hospitals of a health district in Australia with a diagnosis of S. aureus infection over a 10-year period. The main outcome measure was 30-day inpatient mortality. Secondary endpoints included total overnight stays, all-cause inpatient mortality, and hospitalization costs within 1 year of index admission. FINDINGS: Inpatient mortality at 30, 100 and 365 days was estimated to be significantly greater for patients with MRSA infection. The mean additional cost of MRSA infection when controlling for additional factors was $5988 and 4 nights of additional hospital stay per patient within 1 year of index admission. Key predictors of MRSA infection were: date of index admission; higher comorbidity score; greater socio-economic disadvantage; admission to hospital other than via the emergency department; older age; and prior admission to hospital within 28 days of index admission. CONCLUSIONS: MRSA infection is associated with increased inpatient mortality, costs and hospital length of stay compared with MSSA infection. Efforts are required to alleviate the additional burden of MRSA infection on patients and healthcare systems.

"You need a designated officer" - Recommendations from correctional and justice health personnel for scaling up hepatitis C treatment-as-prevention in the prison setting.

INTRODUCTION: Hepatitis C (HCV) is highly prevalent among people who are incarcerated. HCV treatment-as-prevention was implemented in the SToP-C trial in four correctional centres in New South Wales , Australia to determine whether prison-wide scale up of antiviral treatment was an effective strategy to reduce HCV incidence and prevalence in the prison setting. A qualitative assessment was undertaken with prison-based correctional and health personnel at each of the four prisons to understand operational, sociological, and cultural barriers and enablers to scale up. Informed by a framework for scaling up population health interventions, this analysis examines recommendations by correctional and justice health personnel for HCV treatment-as-prevention scale up in the prison setting. METHODS: Correctional (n=24) and justice health (n=17) personnel, including officers, nurses, and senior administrators, participated in interviews across the four prisons where SToP-C was delivered and included two maximum security, one minimum security, and one women's medium/minimum security prisons. RESULTS: Scaling up HCV treatment-as-prevention was contingent on compatibility (including sentence length), efficacy (securely funded positions for dedicated personnel and continuity of care for patients transferring between prisons), stakeholder analysis (generally the whole of prison workforce, particularly custodial officers and senior administrators), reach (reliant on peer and officer champions), and legitimised change (via dedicated officers who could instigate cultural shifts). CONCLUSION: Achieving scale up of such an intervention should be guided by an understanding of the potential barriers and enablers. This analysis showed key considerations for HCV treatment-as-prevention scale up in correctional centres.

In Vivo reflectance confocal microscopy of cutaneous acute graft-versus-host disease: concordance with histopathology and interobserver reproducibility of a glossary with representative images.

BACKGROUND: The reliability to non-invasively identify features of inflammatory dermatoses by reflectance confocal microscopy (RCM) remains unknown. Lack of formal training among RCM readers can result in inconsistent assessments, limiting clinical utility. Specific consensus terminology with representative images is necessary to ensure consistent feature-level interpretation among RCM readers. OBJECTIVES: (1) Develop a glossary with representative images of RCM features of cutaneous acute graft-versus-host disease (aGVHD) for consistent interpretation among observers, (2) assess the interobserver reproducibility among RCM readers using the glossary, and (3) determine the concordance between RCM and histopathology for aGVHD features. METHODS: Through an iterative process of refinement and discussion among five international RCM experts, we developed a glossary with representative images of RCM features of aGVHD. From April to November 2018, patients suspected of aGVHD were imaged with RCM and subsequently biopsied. 17 lesions from 12 patients had clinically and pathologically confirmed cutaneous aGVHD. For each of these lesions, four dermatopathologists and four RCM readers independently evaluated the presence of aGVHD features in scanned histopathology slides and 1.5 × 1.5 mm RCM submosaics at 4 depths (blockstacks) respectively. RCM cases were adjudicated by a fifth RCM expert. Interobserver reproducibility was calculated by mean pairwise difference (U statistic). Concordance between modalities was determined by fraction of assignments with agreement. RESULTS: We present a glossary with representative images of 18 aGVHD features by RCM. The average interobserver reproducibility among RCM readers (75%, confidence interval, CI: 71-79%) did not differ significantly from dermatopathologists (80%, 76-85%). The concordance between RCM and histopathology was 59%. CONCLUSIONS: By using the glossary, the interobserver reproducibility among RCM readers was similar to the interobserver reproducibility among dermatopathologists. There was reasonable concordance between RCM and histopathology to visualize aGVHD features. The implementation of RCM can now be advanced in a variety of inflammatory conditions with a validated glossary and representative image set.

What motivates students to decrease or cease substance use?: A scoping review.

OBJECTIVE: The association between illicit substance use by third-level education students and their mental and physical health is well documented. The aim of this scoping review was to determine factors that contribute to student motivations to reduce or stop their use of illicit substances, and to elaborate on factors that may be pertinent for student-focused behaviour change interventions for substance use. METHOD: We searched eight databases in March 2021 using search terms based on 'students', 'illicit substance use', and 'motivations'. We identified 86 research articles that reported on third-level education students' illicit substance use and included reasons or motives for their use. RESULTS: After full-text screening, three studies were eligible for inclusion in the qualitative synthesis. The majority of studies described motives for abstention but did not describe motivation for reducing or stopping current patterns of use of illicit substances. CONCLUSION: Few studies have examined motivations of third-level education students to decrease or cease substance use. Promising avenues for research on motivations to change substance use behaviour include the social contextual factors, perceived effects on social relationships, and actions of friends and family to prompt contemplations of change.

The ratio of morning cortisol to CRP prospectively predicts first-onset depression in at-risk adolescents.

RATIONALE: Early-onset adolescent depression is related to poor prognosis and a range of psychiatric and medical comorbidities later in life, making the identification of a priori risk factors for depression highly important. Increasingly, dysregulated levels of immune and neuroendocrine markers, such as C-reactive protein (CRP) and cortisol, have been demonstrated as both precursors to and consequences of depression. However, longitudinal research with adolescent populations is limited and demonstrates mixed immuno-endocrine-depression links. OBJECTIVE: This study explored the putative bidirectional relationship between salivary measures of cortisol (Cort) and CRP, including the novel Cort:CRP ratio and depression. METHODS: Participants from the randomized control trial 'Sleep and Education: learning New Skills Early' (SENSE) Study were 122 adolescents at risk for depression (73 females) aged 12-16 years (M = 12.71 years, SD = 1.01 years) assessed at baseline (T1), post-intervention (T2), and a two-year follow-up (T3). RESULTS: Logistic regression results demonstrated that adolescents with higher T1 Cort:CRPmorn ratio levels were two-fold more likely to develop a first-onset depressive disorder from T2 to T3 as compared to adolescents with lower Cort:CRPmorn ratio levels, ß = 0.73, t (36) = 2.15, p = .04, OR = 2.08. This effect was not moderated by treatment condition (ß = -1.38, t (13) = -1.33, p = .20) and did not change when controlling for known risk factors for depression, including sex, age, body-mass index, socio-economic status, T1 anxiety disorder, nor T1 sleep disturbance, anxiety, or depressive symptoms (ß = 0.91, t (31) = 2.14, p = .04). CONCLUSION: Results highlight potential immuno-endocrine dysregulation as an underlying risk factor for adolescent first-onset depression, and may inform the development of targeted, preventative biobehavioral treatment strategies for youth depression.

Landscape and taxon age are associated with differing patterns of hybridization in two Eucalyptus (Myrtaceae) subgenera.

BACKGROUND AND AIMS: Hybridization is an important evolutionary process that can have a significant impact on natural plant populations. Eucalyptus species are well known for weak reproductive barriers and extensive hybridization within subgenera, but there is little knowledge of whether patterns of hybridization differ among subgenera. Here, we examine eucalypts of Western Australia's Stirling Range to investigate how patterns of hybridization are associated with landscape and taxon age between the two largest Eucalyptus subgenera: Eucalyptus and Symphyomyrtus. In doing so, we tested a hypothesis of OCBIL (old, climatically buffered, infertile landscape) theory that predicts reduced hybridization on older landscapes. METHODS: Single nucleotide polymorphism markers were applied to confirm the hybrid status, parentage and genetic structure of five suspected hybrid combinations for subg. Eucalyptus and three combinations for subg. Symphyomyrtus. KEY RESULTS: Evidence of hybridization was found in all combinations, and parental taxa were identified for most combinations. The older parental taxa assessed within subg. Eucalyptus, which are widespread on old landscapes, were identified as well-defined genetic entities and all hybrids were exclusively F1 hybrids. In addition, many combinations showed evidence of clonality, suggesting that the large number of hybrids recorded from some combinations is the result of long-term clonal spread following a few hybridization events rather than frequent hybridization. In contrast, the species in subg. Symphyomyrtus, which typically occur on younger landscapes and are more recently evolved, showed less distinction among parental taxa, and where hybridization was detected, there were high levels of introgression. CONCLUSIONS: Reduced hybridization in subg. Eucalyptus relative to extensive hybridization in subg. Symphyomyrtus affirmed the hypothesis of reduced hybridization on OCBILs and demonstrate that clade divergence times, landscape age and clonality are important drivers of differing patterns of speciation and hybridization in Eucalyptus.

Transition from child to adult health services for young people with cerebral palsy in Ireland: a mixed-methods study protocol.

INTRODUCTION: The transition from child to adult health services is a challenging and complex process for young people with cerebral palsy (CP). Poorly managed transition is associated with deterioration in health, increased hospitalisations and reduced quality of life. While international research identifies key practices that can improve the experience and outcomes of transition, there is a paucity of data in the Irish context. This research study aims to gain an insight into the experience of transition for young people with CP in Ireland. METHODS AND ANALYSIS: A convergent parallel mixed-methods design will be used to collect, analyse and interpret quantitative and qualitative data. Participants will be young people aged 16-22 years with CP, their parent(s)/carer(s) and service providers. Quantitative and qualitative data will be collected through questionnaires and interviews, respectively. Quantitative data will be reported using descriptive statistics. Where sufficient data are collected, we will examine associations between the experience of transition practices and sociodemographic and CP-related factors, respectively, using appropriate regression models. Associations between service provider characteristics and provision of key transition practices may also be explored using appropriate regression models. Qualitative data will be analysed using the Framework Method. A coding matrix based on key transitional practices identified from the literature will be used to identify convergence and divergence across study components at the integration stage. ETHICS AND DISSEMINATION: The study has been approved by the RCSI University of Medicine and Health Sciences Research Ethics Committee (REC201911010). Results will be presented to non-academic stakeholders through a variety of knowledge translation activities. Results will be published in open access, peer-reviewed journals and presented at national and international scientific conferences.

Improving Outcomes Among Young Adults with type 1 diabetes: The D1 Now Randomised Pilot Study Protocol.

BACKGROUND: Young adults (18-25 years old) living with type 1 diabetes mellitus often have sub-optimal glycaemic levels which can increase their risk of long term diabetes complications. Informed by health psychology theory and using a (public and patient involvement) young adult-centred approach, we have developed a complex intervention, entitled D1 Now, to improve outcomes in this target group. The D1 Now intervention includes three components; 1) a support-worker, 2) an interactive messaging system and 3) an agenda setting tool for use during clinic consultations. AIMS: The aim of the D1 Now pilot study is to gather and analyse acceptability and feasibility data to allow us to (1) refine the D1 Now intervention, and (2) determine the feasibility of a definitive Randomised Control Trial (RCT) of the intervention. METHODS: Diabetes clinics on the island of Ireland will be recruited and randomised to a D1 Now intervention arm or a usual care control arm. For a participant to be eligible they should be 18-25 years old and living with type 1 diabetes for at least 12 months. Participant outcomes (influenced by a Core Outcome Set) include change in HbA1c, clinic attendance, number of episodes of severe hypoglycaemia and of diabetic ketoacidosis, diabetes distress, self-management, quality of life and perceived level of control over diabetes; these will be will be measured at baseline and after 12 months follow-up for descriptive statistics only. An assessment of treatment fidelity, a health economic analysis and a qualitative sub-study will also be incorporated into the pilot study. ISRCTN (ref: ISRCTN74114336).

Fine-scale species distribution modelling and genotyping by sequencing to examine hybridisation between two narrow endemic plant species.

Hybridization has an important and often positive role in plant evolution. However, it can also have negative consequences for species. Two closely related species of Ornduffia are endemic to the Porongurup Range in the South West Australian Global Biodiversity Hotspot. The rare Ornduffia calthifolia is found exclusively on the summits, while O. marchantii is more widely dispersed across a greater range of elevation and is not considered threatened. Hybridisation in suitable overlapping habitat has been suspected between them for decades. Here we combine genotyping by sequencing to verify hybridisation genetically, and fine scale (2 m resolution) species distribution modelling (SDM) to test if hybrids occur in suitable intersecting habitat. From a study area of c. 4700 ha, SDM identified c. 275 ha and c. 322 ha of suitable habitat for O. calthifolia and O. marchantii, respectively. We identified range overlap between species of c. 59 ha), which enveloped 32 individuals confirmed to be hybrids. While the hybrids were at the margin of suitable habitat for O. marchantii, their preference for elevated habitat was closer to the more narrowly distributed O. calthifolia. The combination of genetic data and fine scale spatial modelling approaches enabled a better understanding of hybridisation among taxa of conservation significance. However, the level to which hybrid proliferation and competition for habitat presents as a threat to O. calthifolia is currently unknown and requires priority in conservation management given the threats from global warming and disturbance by tourism.

Focusing on fidelity: narrative review and recommendations for improving intervention fidelity within trials of health behaviour change interventions.

Background: Interventions to change behaviour have substantial potential to impact positively on individual and overall public health. Despite an increasing focus on health behaviour change intervention research, interventions do not always have the desired effect on outcomes, while others have diluted effects once implemented into real-life settings. There is little investment into understanding how or why such interventions work or do not work. Methodological inadequacies of trials of behavioural interventions have been previously suggested as a barrier to the quality and advancement of behavioural research, with intervention fidelity acknowledged as a key area for improvement. However, there is much ambiguity regarding the terminology and conceptualisation of intervention fidelity and a lack of practical guidance regarding how to address it sufficiently, particularly within trials of complex behavioural interventions. Objectives: This article outlines specific issues concerning intervention fidelity within trials of health behaviour change interventions and suggests practical considerations and specific recommendations for researchers, with examples from the literature presented. Conclusions: Recommendations pertain to (1) clarifying how fidelity is defined and conceptualised, (2) considering fidelity beyond intervention delivery, (3) considering strategies to both enhance and assess fidelity, (4) making use of existing frameworks and guidance, (5) considering the quality and comprehensiveness of fidelity assessment strategies, (6) considering the balance between fidelity and adaptation and (7) reporting the use of fidelity enhancement and assessment strategies and their results. Suggestions for future research to improve our understanding of, and ability to, address fidelity in behaviour change interventions are also provided.

Phenotype, genotype and glycaemic variability in people with activating mutations in the ABCC8 gene: response to appropriate therapy.

AIMS: To examine the phenotypic features of people identified with ABCC8-maturity-onset diabetes of the young (MODY) who were included in the adult 'Mater MODY' cohort and to establish their response to sulfonylurea therapy. METHODS: Ten participants with activating ABCC8 mutations were phenotyped in detail. A 2-hour oral glucose tolerance test was performed to establish glycaemic tolerance, with glucose, insulin and C-peptide measurements taken at baseline and 30-min intervals. Insulin was discontinued and sulfonylurea therapy initiated after genetic diagnosis of ABCC8-MODY. A blinded continuous glucose monitoring sensor was used to establish glycaemic control on insulin vs a sulfonylurea. RESULTS: The mean age at diagnosis of diabetes was 33.8 ± 11.1 years, with fasting glucose of 18.9 ± 11.5 mmol/l and a mean (range) HbA1c of 86 (51,126) mmol/mol [10.0 (6.8,13.7)%]. Following a genetic diagnosis of ABCC8-MODY three out of four participants discontinued insulin (mean duration 10.6 ± 1.69 years) and started sulfonylurea treatment. The mean (range) HbA1c prior to genetic diagnosis was 52 (43,74) mmol/mol (6.9%) and the post-treatment change was 44 (30,57) mmol/mol (6.2%; P=0.16). Retinopathy was the most common microvascular complication in this cohort, occurring in five out of 10 participants. CONCLUSIONS: Low-dose sulfonylurea therapy resulted in stable glycaemic control and the elimination of hypoglycaemic episodes attributable to insulin therapy. The use of appropriate therapy at the early stages of diabetes may decrease the incidence of complications and reduce the risks of hypoglycaemia associated with insulin therapy.