Treatment entry and return to opioid use outcomes from a pre-release methadone program in a Malaysian prison: towards improved HIV treatment outcomes

Within prison, a high prevalence of people living with human immunodeficiency virus (HIV) and opioid use disorder exist. Return to opioid use is common among people released from incarceration. Regardless of incarceration length, an estimated 85% of individuals return to opioid use within one year. Return to opioid use is associated with significant harms. Methadone may reduce return to opioid use and benefit people living with HIV and opioid use disorder due to increasing antiretroviral therapy (ART) adherence, engagement with healthcare services and reducing the risk of HIV transmission. This thesis utilises data from Project Harapan, a pre-release methadone maintenance treatment (MMT) program conducted between 2010 and 2013 in Malaysia. The overarching aim of this thesis was to explore different aspects of the pre-release MMT program among a sample of 310 men living with HIV and opioid use disorder in Malaysia’s largest male prison. This thesis comprises four studies. The first study describes the association between knowledge and attitudes and the choice to initiate pre- release MMT. Uncertainty towards methadone may be associated with MMT-related hesitancy and lower proportions of men choosing to initiate pre-release MMT. The second study uses the behavioural model for vulnerable populations as a framework to explore the association between other factors connected to healthcare utilisation and the choice to initiate pre-release MMT. Findings suggest being of Hindu faith, being prescribed (yet not taking) ART, currently being on ART during incarceration and having a more severe craving for heroin were associated with lower proportions of men choosing to initiate pre-release MMT. The third study demonstrates the impact of pre- release MMT initiation on return to opioid use following release from incarceration. The findings reveal that reductions in opioid use in the first 12 months post-release may be associated with the initiation of pre-release MMT. With HIV-related mortality closely linked with people living with HIV and opioid use disorder, the fourth study reports on a global scoping review of HIV/AIDS, hepatitis and tuberculosis-related mortality among people who experience incarceration. Globally, it remains difficult to locate good-quality infectious disease-related mortality data for prisons. Given the paucity, we located data to suggest the highest number of reported deaths over a 20-year period were attributable to HIV/AIDS (n=3,305), followed by TB (n=2,892), HCV (n=189), HIV/TB co-infection (n=173) and HBV (n=9). Increased investment to improve the reporting of key mortality indicators is urgently required. This research resulted in one published manuscript, two accepted conference abstracts and three manuscripts awaiting submission post the conference embargo period. Thesis conclusions refer to men who experience incarceration in Malaysia in a study conducted between 2010 and 2013. Globally, evidence supports the effectiveness of pre-release MMT on reducing opioid-related harms yet given the paucity of such data among men living with HIV and opioid use disorder who experience incarceration in Malaysia, no such evidence existed, and the effectiveness remained unknown. Therefore, these findings make a significant contribution to the literature in relation to this previously hidden population. This thesis demonstrates that opioid-related harms can be reduced when individuals initiate pre-release MMT. Working towards optimising MMT uptake and supporting individuals to pursue effective treatment for opioid use disorder may prevent opioid-related harms and poor HIV treatment outcomes experienced by this vulnerable population

Alcohol use disorders: a mental health not a moral issue

The prevalence of alcohol use disorders (AUD) and associated alcohol related harm amongst women in the community can compromise their mental and physical health (Foster et al. 2014)

Medication adherence: process for implementation

Improving medication adherence is a critically important, but often enigmatic objective of patients, providers, and the overall health care system. Increasing medication adherence has the potential to reduce health care costs while improving care quality, patient satisfaction and health outcomes. While there are a number of papers that describe the benefits of medication adherence in terms of cost, safety, outcomes, or quality of life, there are limited reviews that consider how best to seamlessly integrate tools and processes directed at improving medication adherence. We will address processes for implementing medication adherence interventions with the goal of better informing providers and health care systems regarding the safe and effective use of medications

Medication adherence: process for implementation

Improving medication adherence is a critically important, but often enigmatic objective of patients, providers, and the overall health care system. Increasing medication adherence has the potential to reduce health care costs while improving care quality, patient satisfaction and health outcomes. While there are a number of papers that describe the benefits of medication adherence in terms of cost, safety, outcomes, or quality of life, there are limited reviews that consider how best to seamlessly integrate tools and processes directed at improving medication adherence. We will address processes for implementing medication adherence interventions with the goal of better informing providers and health care systems regarding the safe and effective use of medications

National and sub-national HIV/AIDS-related mortality in Iran, 1990–2015: a population-based modeling study

Surveillance of HIV/AIDS mortality is crucial to evaluate a country’s response to the disease. With a modified estimation approach, this study aimed to provide more accurate estimates on deaths due to HIV/AIDS in Iran from 1990 to 2015 at national and sub-national levels. Using a comprehensive data set, death registration incompleteness and misclassification were addressed by demographical and statistical methods. Trends of mortality due to HIV/AIDS at national and sub-national levels were estimated by applying a set of models. A total of 474 men (95% uncertainty interval [UI]: 175–1332) and 256 women (95% UI: 36–1871) died due to HIV/AIDS in 2015 in Iran. Peaked in 1995, HIV/AIDS-related mortality has steadily declined among both genders. Mortality rates were remarkably higher among men than women during the period studied. At the sub-national level, the highest and the lowest annual percent change were found at 10.97 and −1.36% for women, and 4.04 and −3.47% for men, respectively. The findings of our study (731 deaths) were remarkably lower than the Joint United Nations Programme on HIV and AIDS (4000) but higher than Global Burden of Disease (339) estimates in 2015. The overall decrease in mortality due to HIV/AIDS may be attributed to the increasing burden of noncommunicable diseases; however, the role of the national and international organizations to fight HIV/AIDS should not be overlooked. To decrease HIV/AIDS mortality and to achieve international goals, evidence-based action is required. To fast-track targets, the priority must be to prevent infection, promote early diagnosis, provide access to treatment, and to ensure treatment adherence among patients. Keywords HIV, AIDS, mortality, estimation, modeling, Ira

CT colonography: optimisation, diagnostic performance and patient acceptability of reduced-laxative regimens using barium-based faecal tagging

To establish the optimum barium-based reduced-laxative tagging regimen prior to CT colonography (CTC). Ninety-five subjects underwent reduced-laxative (13 g senna/18 g magnesium citrate) CTC prior to same-day colonoscopy and were randomised to one of four tagging regimens using 20 ml 40%w/v barium sulphate: regimen A: four doses, B: three doses, C: three doses plus 220 ml 2.1% barium sulphate, or D: three doses plus 15 ml diatriazoate megluamine. Patient experience was assessed immediately after CTC and 1 week later. Two radiologists graded residual stool (1: none/scattered to 4: >50% circumference) and tagging efficacy for stool (1: untagged to 5: 100% tagged) and fluid (1: untagged, 2: layered, 3: tagged), noting the HU of tagged fluid. Preparation was good (76–94% segments graded 1), although best for regimen D (P = 0.02). Across all regimens, stool tagging quality was high (mean 3.7–4.5) and not significantly different among regimens. The HU of layered tagged fluid was higher for regimens C/D than A/B (P = 0.002). Detection of cancer (n = 2), polyps ≥6 mm (n = 21), and ≤5 mm (n = 72) was 100, 81 and 32% respectively, with only four false positives ≥6 mm. Reduced preparation was tolerated better than full endoscopic preparation by 61%. Reduced-laxative CTC with three doses of 20 ml 40% barium sulphate is as effective as more complex regimens, retaining adequate diagnostic accuracy

Medication adherence: A call for action

Poor adherence to efficacious cardiovascular related medications has led to considerable morbidity, mortality, and avoidable health care costs. This paper provides results of a recent think tank meeting in which various stakeholder groups representing key experts from consumers, community health providers, the academic community, decision-making government officials (FDA, NIH, etc), and industry scientists met to evaluate the current status of medication adherence and provide recommendations for improving outcomes. Below, we review the magnitude of the problem of medication adherence, prevalence, impact, and cost. We then summarize proven effective approaches and conclude with a discussion of recommendations to address this growing and significant public health issue of medication non adherence

Rapid spatiotemporal variations in rift structure during development of the Corinth Rift, central Greece

The Corinth Rift, central Greece, enables analysis of early rift development as it is young (<5Ma) and highly active and its full history is recorded at high resolution by sedimentary systems. A complete compilation of marine geophysical data, complemented by onshore data, is used to develop a high-resolution chronostratigraphy and detailed fault history for the offshore Corinth Rift, integrating interpretations and reconciling previous discrepancies. Rift migration and localization of deformation have been significant within the rift since inception. Over the last circa 2Myr the rift transitioned from a spatially complex rift to a uniform asymmetric rift, but this transition did not occur synchronously along strike. Isochore maps at circa 100kyr intervals illustrate a change in fault polarity within the short interval circa 620-340ka, characterized by progressive transfer of activity from major south dipping faults to north dipping faults and southward migration of discrete depocenters at ~30m/kyr. Since circa 340ka there has been localization and linkage of the dominant north dipping border fault system along the southern rift margin, demonstrated by lateral growth of discrete depocenters at ~40m/kyr. A single central depocenter formed by circa 130ka, indicating full fault linkage. These results indicate that rift localization is progressive (not instantaneous) and can be synchronous once a rift border fault system is established. This study illustrates that development processes within young rifts occur at 100kyr timescales, including rapid changes in rift symmetry and growth and linkage of major rift faults

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes

Case Reports1. A Late Presentation of Loeys-Dietz Syndrome: Beware of TGFβ Receptor Mutations in Benign Joint Hypermobility

Background: Thoracic aortic aneurysms (TAA) and dissections are not uncommon causes of sudden death in young adults. Loeys-Dietz syndrome (LDS) is a rare, recently described, autosomal dominant, connective tissue disease characterized by aggressive arterial aneurysms, resulting from mutations in the transforming growth factor beta (TGFβ) receptor genes TGFBR1 and TGFBR2. Mean age at death is 26.1 years, most often due to aortic dissection. We report an unusually late presentation of LDS, diagnosed following elective surgery in a female with a long history of joint hypermobility. Methods: A 51-year-old Caucasian lady complained of chest pain and headache following a dural leak from spinal anaesthesia for an elective ankle arthroscopy. CT scan and echocardiography demonstrated a dilated aortic root and significant aortic regurgitation. MRA demonstrated aortic tortuosity, an infrarenal aortic aneurysm and aneurysms in the left renal and right internal mammary arteries. She underwent aortic root repair and aortic valve replacement. She had a background of long-standing joint pains secondary to hypermobility, easy bruising, unusual fracture susceptibility and mild bronchiectasis. She had one healthy child age 32, after which she suffered a uterine prolapse. Examination revealed mild Marfanoid features. Uvula, skin and ophthalmological examination was normal. Results: Fibrillin-1 testing for Marfan syndrome (MFS) was negative. Detection of a c.1270G > C (p.Gly424Arg) TGFBR2 mutation confirmed the diagnosis of LDS. Losartan was started for vascular protection. Conclusions: LDS is a severe inherited vasculopathy that usually presents in childhood. It is characterized by aortic root dilatation and ascending aneurysms. There is a higher risk of aortic dissection compared with MFS. Clinical features overlap with MFS and Ehlers Danlos syndrome Type IV, but differentiating dysmorphogenic features include ocular hypertelorism, bifid uvula and cleft palate. Echocardiography and MRA or CT scanning from head to pelvis is recommended to establish the extent of vascular involvement. Management involves early surgical intervention, including early valve-sparing aortic root replacement, genetic counselling and close monitoring in pregnancy. Despite being caused by loss of function mutations in either TGFβ receptor, paradoxical activation of TGFβ signalling is seen, suggesting that TGFβ antagonism may confer disease modifying effects similar to those observed in MFS. TGFβ antagonism can be achieved with angiotensin antagonists, such as Losartan, which is able to delay aortic aneurysm development in preclinical models and in patients with MFS. Our case emphasizes the importance of timely recognition of vasculopathy syndromes in patients with hypermobility and the need for early surgical intervention. It also highlights their heterogeneity and the potential for late presentation. Disclosures: The authors have declared no conflicts of interes