Is cannabis a gateway drug? Testing hypotheses about the relationship between cannabis use and the use of other illicit drugs

We outline and evaluate competing explanations of three relationships that have consistently been found between cannabis use and the use of other illicit drugs, namely, ( 1) that cannabis use typically precedes the use of other illicit drugs; and that ( 2) the earlier cannabis is used, and ( 3) the more regularly it is used, the more likely a young person is to use other illicit drugs. We consider three major competing explanations of these patterns: ( 1) that the relationship is due to the fact that there is a shared illicit market for cannabis and other drugs which makes it more likely that other illicit drugs will be used if cannabis is used; ( 2) that they are explained by the characteristics of those who use cannabis; and ( 3) that they reflect a causal relationship in which the pharmacological effects of cannabis on brain function increase the likelihood of using other illicit drugs. These explanations are evaluated in the light of evidence from longitudinal epidemiological studies, simulation studies, discordant twin studies and animal studies. The available evidence indicates that the association reflects in part but is not wholly explained by: ( 1) the selective recruitment to heavy cannabis use of persons with pre-existing traits ( that may be in part genetic) that predispose to the use of a variety of different drugs; ( 2) the affiliation of cannabis users with drug using peers in settings that provide more opportunities to use other illicit drugs at an earlier age; ( 3) supported by socialisation into an illicit drug subculture with favourable attitudes towards the use of other illicit drugs. Animal studies have raised the possibility that regular cannabis use may have pharmacological effects on brain function that increase the likelihood of using other drugs. We conclude with suggestions for the type of research studies that will enable a decision to be made about the relative contributions that social context, individual characteristics, and drug effects make to the relationship between cannabis use and the use of other drugs.

The effect of a reduction in heroin supply on fatal and non-fatal drug overdoses in New South Wales, Australia

Objective: To examine the impact of a sudden and dramatic decrease in heroin availability, concomitant with increases in price and decreases in purity, on fatal and non-fatal drug overdoses in New South Wales, Australia. Design and setting: Time-series analysis was conducted where possible on data on overdoses collected from NSW hospital emergency departments, the NSW Ambulance Service, and all suspected drug-related deaths referred to the NSW Coroner's court. Main outcome measures: The number of suspected drug-related deaths where heroin and other drugs were mentioned; ambulance calls to suspected opioid overdoses; and emergency department admissions for overdoses on heroin and other drugs. Results: Both fatal and non-fatal heroin overdoses decreased significantly after heroin supply reduced; the reductions were greater among younger age groups than older age groups. There were no clear increases in non-fatal overdoses with cocaine, methamphetamines or benzodiazepines recorded at hospital emergency departments after the reduction in heroin supply. Data on drug-related deaths suggested that heroin use was the predominant driver of drug-related deaths in NSW, and that when heroin supply was reduced overdose deaths were more likely to involve a wider combination of drugs. Conclusion: A reduction in heroin supply reduced heroin-related deaths, and did not result in a concomitant increase, to the same degree, in deaths relating to other drugs. Younger people were more affected by the reduction in supply.

Reflections on the development and implementation of an early warning system for ecstasy and related drug markets in Australia

Regular and systematic monitoring of drug markets provides the basis for evidence-based policy. In Australia, trends in ecstasy and related drug (ERD) markets have been monitored in selected jurisdictions since 2000 and nationally since 2003, by the Party Drugs Initiative (PDI). The PDI maximises the validity of conclusions by triangulating information from (a) interviews with regular ecstasy users (REU), (b) interviews with key experts and (c) indicator data. There is currently no other system in Australia for monitoring these markets systematically; however, the value of the PDI has been constrained by the quality of available data. Difficulties in recruiting and interviewing appropriate consumers (REU) and key experts have been experienced, but largely overcome. Limitations of available indicator data from both health and law enforcement continue to present challenges and there remains considerable scope for enhancing existing routine data collection systems, to facilitate monitoring of ERD markets. With an expanding market for ecstasy and related drugs in Australia, and in the context of indicator data that continue to be limited in scope and detail, there is a strong argument for the continued collection of annual, comparable data from a sentinel group of REU, such as those recruited for the PDI.

A survey of regular ecstasy users' knowledge and practices around determining pill content and purity: Implications for policy and practice.

Objective: To examine the methods used by a sample of regular ecstasy users to determine the content and purity of ecstasy pills, their knowledge of the limitations of available pill testing methods, and how pill test results would influence their drug use behaviour. Method: Data were collected from regular ecstasy users (n = 810) recruited from all eight capital cities of Australia. Data were analysed using multiple logistic regression and chi-square (chi(2)) tests of association. Open-ended responses were coded for themes. Results: The majority of the sample(84%) reported attempting to find out the content and purity of ecstasy at least some of the time, most commonly asking friends or dealers. Less than one quarter (22%) reported personal use of testing kits. There was a moderate level of awareness of the limitations of testing kits among those who reported having used them. Over half (57%) of those reporting personal use of testing kits reported that they would not take a pill if test results indicated that it contained ketamine and over three quarters (76%) reported that they would not take an "unknown" pill (producing no reaction in a reagent test). Finally, a considerable majority (63%) expressed interest in pill testing should it be more widely available. Conclusions: The majority of regular ecstasy users sampled in this Australian study report previous attempts to determine the content and purity of pills sold as ecstasy. Although only a small proportion have used testing kits, many report that they would do so if they were more widely available. The results of pill tests may influence drug use if they indicate that pills contain substances which ecstasy users do not want to ingest or are of unknown content. More detailed research examining ways in which pill testing may influence drug use is required to inform evidence-based policy. (c) 2006 Elsevier B.V. All rights reserved.

The development of an in vivo model of drug-induced terminal differentiation of Leukaemic cells

The technique of growing human leukaemic cells in diffusion chambers was developed to enable chemicals to be assessed for their ability to induce terminal differentiation. HL-60 promyelocytic leukaemia cell growth, in a lucite chamber with a Millipore filter, was optimised by use of a lateral incision site. Chambers were constructed using 0.45um filters and contained 150ul of serum-free HL-60 cells at a density of 1x106 cells/ml. The chambers were implanted into CBA/Ca mice and spontaneous terminal differentiation of the cells to granulocytes was prevented by the use of serum-free medium. Under these conditions there was an initial growth lag of 72 hours and a logarithmic phase of growth for 96 hours; the cell number reached a plateau after 168 hours of culture in vivo. The amount of drug in the plasma of the animal and in chambers that had been implanted for 5 days, was determined after a single ip injection of equitoxic doses of N-methylformamide, N-ethylformamide, tetramethylurea, N-dibutylformamide, N-tetramethylbutylformamide and hexamethylenebisacetamide. Concentrations of both TMU and HMBA were obtained in the plasma and in the chamber which were pharmacologically effective for the induction of differentiation of HL-60 cells in vitro, that is 12mM TMU and 5mM HMBA. A 4 day regime of treatment of animals implanted with chambers demonstrated that TMU and HMBA induced terminal differentiation of 50% and 35%, respectively, of the implanted HL-60 cells to granulocyte-like cells, assessed by measurement of functional and biochemical markers of maturity. None of the other agents attained concentrations in the plasma that were pharmacologically effective for the induction of differentiation of the cells in vitro and were unable to induce the terminal differentiation of the cells in vivo.

The influence of gender on perceived treatment need among a community sample of substance users

Purpose: Most individuals do not perceive a need for substance use treatment despite meeting diagnostic criteria for substance use disorders and they are least likely to pursue treatment voluntarily. There are also those who perceive a need for treatment and yet do not pursue it. This study aimed to understand which factors increase the likelihood of perceiving a need for treatment for individuals who meet diagnostic criteria for substance use disorders in the hopes to better assist with more targeted efforts for gender-specific treatment recruitment and retention. Using Andersen and Newman's (1973/2005) model of individual determinants of healthcare utilization, the central hypothesis of the study was that gender moderates the relationship between substance use problem severity and perceived treatment need, so that women with increasing problems due to their use of substances are more likely than men to perceive a need for treatment. Additional predisposing and enabling factors from Andersen and Newman's (1973/2005) model were included in the study to understand their impact on perceived need. Method: The study was a secondary data analysis of the 2010 National Survey on Drug Use and Health (NSDUH) using logistic regression. The weighted sample consisted of a total 20,077,235 American household residents (The unweighted sample was 5,484 participants). Results of the logistic regression were verified using Relogit software for rare events logistic regression due to the rare event of perceived treatment need (King & Zeng, 2001a; 2001b). Results: The moderating effect of female gender was not found. Conversely, men were significantly more likely than women to perceive a need for treatment as substance use problem severity increased. The study also found that a number of factors such as race, ethnicity, socioeconomic status, age, marital status, education, co-occurring mental health disorders, and prior treatment history differently impacted the likelihood of perceiving a need for treatment among men and women. Conclusion: Perceived treatment need among individuals who meet criteria for substance use disorders is rare, but identifying factors associated with an increased likelihood of perceiving need for treatment can help the development of gender-appropriate outreach and recruitment for social work treatment, and public health messages.

Exploring the Life-Saving Potential of Naloxone : A Systematic Review and Descriptive Meta-Analysis of Take Home Naloxone (THN) Programmes for Opioid Users

Date of Acceptance: 21/09/2015 This study was funded by NHS Health Scotland. The opinions expressed in this paper as those of the authors alone and are not necessarily those of NHS Health Scotland. The funders had no role in the conduct of the research.

Exploring the Life-Saving Potential of Naloxone : A Systematic Review and Descriptive Meta-Analysis of Take Home Naloxone (THN) Programmes for Opioid Users

Date of Acceptance: 21/09/2015 This study was funded by NHS Health Scotland. The opinions expressed in this paper as those of the authors alone and are not necessarily those of NHS Health Scotland. The funders had no role in the conduct of the research.

Minimally invasive microneedles for ocular drug delivery

Introduction: Anterior and posterior segment eye diseases are highly challenging to treat, due to the barrier properties and relative inaccessibility of the ocular tissues. Topical eye drops and systemically delivered treatments result in low bioavailability. Alternatively, direct injection of medication into the ocular tissues is clinically employed to overcome the barrier properties, but injections cause significant tissue damage and are associated with a number of untoward side effects and poor patient compliance. Microneedles (MNs) has been recently introduced as a minimally invasive means for localizing drug formulation within the target ocular tissues with greater precision and accuracy than the hypodermic needles.  Areas covered: This review article seeks to provide an overview of a range of challenges that are often faced to achieve efficient ocular drug levels within targeted tissue(s) of the eye. It also describes the problems encountered using conventional hypodermic needle-based ocular injections for anterior and posterior segment drug delivery. It discusses research carried out in the field of MNs, to date.
Expert opinion: MNs can aid in localization of drug delivery systems within the selected ocular tissue. And, hold the potential to revolutionize the way drug formulations are administered to the eye. However, the current limitations and challenges of MNs application warrant further research in this field to enable its widespread clinical application.  

BAP Guidelines on the Management of Weight Gain, Metabolic Disturbances and Cardiovascular Risk Associated With Psychosis and Antipsychotic Drug Treatment

Excess deaths from cardiovascular disease are a major contributor to the significant reduction in life expectancy experienced by people with schizophrenia. Important risk factors in this are smoking, alcohol misuse, excessive weight gain and diabetes. Weight gain also reinforces service users’ negative views of themselves and is a factor in poor adherence with treatment. Monitoring of relevant physical health risk factors is frequently inadequate, as is provision of interventions to modify these. These guidelines review issues surrounding monitoring of physical health risk factors and make recommendations about an appropriate approach. Overweight and obesity, partly driven by antipsychotic drug treatment, are important factors contributing to the development of diabetes and cardiovascular disease in people with schizophrenia. There have been clinical trials of many interventions for people experiencing weight gain when taking antipsychotic medications but there is a lack of clear consensus regarding which may be appropriate in usual clinical practice. These guidelines review these trials and make recommendations regarding appropriate interventions. Interventions for smoking and alcohol misuse are reviewed, but more briefly as these are similar to those recommended for the general population. The management of impaired fasting glycaemia and impaired glucose tolerance (‘pre-diabetes’), diabetes and other cardiovascular risks, such as dyslipidaemia, are also reviewed with respect to other currently available guidelines. These guidelines were compiled following a consensus meeting of experts involved in various aspects of these problems. They reviewed key areas of evidence and their clinical implications. Wider issues relating to primary care/secondary care interfaces are discussed but cannot be resolved within guidelines such as these.

The use of motivational interviews by nurses to promote health behaviors in adolescents: a scoping review protocol

Adolescents - defined as young people between 10 and 19 years of age1 - are, in general, a relatively healthy segment of the population.2 However, the developmental changes that take place during adolescence may affect their subsequent risk for diseases and for a variety of health-related behaviors. In fact, early onset of preventable health problems (e.g. obesity, malnutrition, STDs) and the engagement in health risk behaviors (e.g., sedentary life style, excessive alcohol consumption, unprotected sex) during adolescence, are likely to put them at greater risk for physical and mental health problems at a later stage in life. Moreover, health related problems and health risk behaviors may disrupt adolescents' physical and cognitive development and therefore may affect their ability to think and act in relation to decisions about their health in the future.1 In summary, health-related behaviors in adolescence, apart from their influence on the continuum of "health-disease", they also have the potential to influence future behaviors. In fact, several studies have shown that past behaviors are good predictors of future behaviors .3,4 Thus, promoting healthy practices during adolescence and taking measures to better protect young people from health risks are essential for the prevention of health problems in adulthood.5 According to the World Health Organization, the main problems affecting young people include mental health problems (such as behavioral disorders, eating disorders, suicide, anxiety or depression), the use of substances (illegal substances, alcohol and tobacco), interpersonal violence, nutrition (a proper nutrition consists of healthy eating habits and physical exercise), unintentional injuries (which are a leading cause of death and disability among young people, with road traffic injuries accounting for about 700 deaths per day), sexual and reproductive health (for example, risky sexual behaviors, early pregnancy and childbirth) and HIV (resulting from sexual transmission and drug injection).5,6 On the other hand, the number of children and youth with chronic health conditions has increased dramatically in the past four decades7 as larger numbers of chronically ill children survive beyond the age of 10.8 Despite the lack of data on adolescents' health making it difficult to determine the prevalence of chronic illnesses in this age group9, it is known that one in ten adolescents suffers from a chronic condition worldwide.10 In fact, national population based studies from Western countries show that 20-30% of teenagers have a chronic illness, defined as one that lasts longer than six months.8 The most prevalent chronic illness among adolescents is asthma and the one with the highest incidence is diabetes mellitus, particularly type II.9 Traditionally, healthcare professionals have been mainly investing in health education activities, through the transmission of knowledge with a view to creating habits, customs and behaviors, and promoting healthy lifestyles. However, empowering people does not only consist of giving them the right information11 , i.e. good information is not enough to cause people to make changes.12 The motivation or desire to change unhealthy behaviors and habits depends on many factors, namely intrinsic motivation, control over personal decisions, self-confidence and perception of effectiveness, personal ambivalence, and individualized assistance.12 Many professionals assume that supplying knowledge is sufficient for behavioral changes; however, even very good advice often fails to generate behavioral change. After all, people continue to engage in unhealthy behaviors despite clearly knowing what they should do and how to change. "What is lacking is the motivation to apply that knowledge".13, p.1233 In fact, behavioral change is a complex phenomenon with multiple determinants that also includes motivational variables. It is associated with ambivalent processes expressed in the dilemma between keeping the current status and moving on to new ways of acting. For example, telling adolescents that if they keep on engaging in a certain behavior, they are increasing the risk of developing a long-term condition such as cardiovascular disease, stroke or diabetes is rarely enough to trigger the desired behavioral change; people are more likely to change when they believe that the change is really effective and that they are able to implement it.12 Therefore, it is essential to provide specific training for "healthcare professionals to master motivational techniques, avoid confrontation with the users, and facilitate behavioral changes".14 In this context, motivating patients to make behavioral changes is also an important nursing task where change in lifestyle is a major element of patients' treatment and preventive interventions.15 One of the nurse's goals is to help improve a patient's health or help them to manage existing health conditions. Once nurses are in a position where they have to focus on accomplishing tasks and telling patients what needs to be accomplished16, the role of the nurse is expanding even more into the use of motivational strategies.17 MI is bringing nurses back to therapeutic communication and moving them closer to successful health promotion and disease management, by promoting behavior change and empowering their patients. As the nursing profession evolves, MI is seen as a challenge and the basis of nurse's interactions with individuals, families and communities.16, 17 In the same way, MI may be taken as an essential tool in the provision of nursing care to adolescents, being itself a workspace with possible therapeutic effects regarding problems, clarification of doubts, and development of skills.18 In fact, MI may be particularly applicable in work with adolescents because of their specific developmental stage. Adolescents attempt to establish their own autonomy and identity while struggling with social interactions and moral issues, which leads to ambivalence.19 Consistent with the developmental challenges during adolescence, "MI explicitly honors autonomy, people's right and irrevocable ability to decide about their own behavior"20 while allowing the person to explore possibilities for change of risky or maladaptive behaviours.19 MI can be defined as a directive, client-centred counselling style for eliciting behavior change by helping clients to explore and resolve ambivalence. It is most centrally defined not by technique but by its spirit as a facilitative style of interpersonal relationship.21 It is a set of strategies and techniques widely used in clinical practice based on the transtheoretical model of change. The Stages of Change model describes five stages of readiness—precontemplation, contemplation, preparation, action, and maintenance—and provides a framework for understanding behavior change.22 The MI has been widely tested and applied in different areas, such as modification of addictive behaviors, interventions with offenders in the context of justice, eating disorders, promotion of therapeutic adherence among chronic patients, promotion of learning in school settings or intervention with adolescents at risk.18,23 In general, clinical practice has been adopting the perspective of motivation as something relatively immutable, i.e., the adolescent is either motivated for change/treatment and, in these conditions, the professional's role is to help him/her, or the adolescent is not motivated and then change/treatment is not feasible. Alternatively the theoretical model underlying the MI technique postulates that the individual's adherence to change/treatment depends on his/her motivation, which can change throughout the therapeutic intervention. As several studies found positive results for effects of MI24-26 and its use by health professionals is encouraged23,27 nurses may play an important role in patients' process of change. As nurses have a crucial role in clinical contexts, they can facilitate the process of ending risk behaviors and/or adopting positive health behaviors through some motivational techniques, namely with adolescents. A considerable number of systematic reviews about MI already exist pointing to some benefits of its use in the treatment of a broad range of behavioral problems and diseases.13,28,29 Some of the current reviews focus on examining the effectiveness of MI for adolescents with diverse health risks/problems 30-32. However, to date there are no reviews that present and assess the evidence for the use of nurse-led MI in adolescents. Therefore, we have little knowledge of what works for whom (which adolescent subpopulation) under what circumstances (in which setting, for what problem) in relation to motivational interviewing by nurses. There is a clear need for scoping or mapping the use of MI by nurses with adolescents to identify evidence gaps and to inform opportunities for future development in nursing practice. On the other hand, information regarding nurse-led implemented and evaluated interventions, techniques and/or strategies used, contexts of application and adolescents subpopulation groups is dispersed in the literature33-36 which impedes the formulation of precise questions about the effectiveness of those interventions conducted by nurses and therefore the realization of a systematic review. In other words, it is known that different kind of motivational interventions have been implemented in different contexts by nurses, however does not exist a map about all the motivational techniques and/or strategies used. Furthermore the literature does not clarify which is the role of nurses at cross professional motivational intervention implemented programs and finally the outcomes and evaluation of interventions are unclear. Thus, the practical implication of this mapping will be clarifying all these aspects. Without this clarification is not possible to proceed to the realization of a systematic review about the effectiveness of the use of motivational interviews by nurses to promote health behaviors in adolescents, in a particular context and/or health risk behavior; or regarding the effectiveness of certain technique and/or strategy of MI. Consequently, there are important questions about the nature of the evidence in this area that need to be answered before formulating a precise question of effectiveness. This scoping review aims to respond to these questions. An initial search of the JBI Database of Systematic Reviews & Implementation Reports, Cochrane Database of Systematic Reviews, , Database of promoting health effectiveness reviews (DoPHER), The Campbell Library, Medline and CINAHL, has revealed that currently there is no Scoping Review (published or in progress) on the subject. In this context, this scoping review will examine and map the published and unpublished research around the use of MI by nurses implemented and evaluated to promote health behaviors in adolescents; to establish its current extent, range and nature and identify its feasibility, outcomes and gaps in the evidence defining research priorities in this field. This scoping review will be informed by the JBI methodology37 that suggests a five stage methodological framework for conducting scoping reviews which includes: identifying the research question, searching for relevant studies, selecting studies, charting data, collating, summarizing and reporting the results.

Studies of antihypertensive drug persistence and adherence in the Glasgow Blood Pressure Clinic

Hypertension (HTN) is a major risk factor for cardiovascular diseases including stroke, coronary heart disease (CHD), chronic renal failure, peripheral vascular disease, myocardial infarction, congestive heart failure and premature death. The prevalence of HTN in Scotland is very high and although a high proportion of the patients receive antihypertensive medications, blood pressure (BP) control is very low. Recommendations for starting a specific antihypertensive class have been debated between various guidelines over the years. Some guidelines and HTN studies have preferred to start with a combination of an antihypertensive class instead of using a single therapy, and they have found greater BP reductions with combination therapies than with monotherapy. However, it has been shown in several clinical trials that 20% to 35% of hypertensive patients could not achieve the target BP, even though they received more than three antihypertensive medications. Several factors were found to affect BP control. Adherence and persistence were considered as the factors contributing the most to uncontrolled hypertension. Other factors such as age, sex, body mass index (BMI), alcohol intake, baseline systolic BP (SBP), and the communication between physicians and patients have been shown to be associated with uncontrolled BP and resistant hypertension. Persistence, adherence and compliance are interchangeable terms and have been used in the literature to describe a patient’s behaviour with their antihypertensive drugs and prescriptions. The methods used to determine persistence and adherence, as well as the inclusion and exclusion criteria, vary between persistence and adherence studies. The prevalence of persistence and adherence have varied between these studies, and were determined to be high in some studies and low in others. The initiation of a specific antihypertensive class has frequently been associated with an increase or decrease in adherence and persistence. The tolerability and efficacy of the initial antihypertensive class have been the most common methods of explaining this association. There are also many factors that suggest a relationship with adherence and persistence. Some factors in previous studies, such as age, were frequently associated with adherence and persistence. On the other hand, relationships with certain factors have varied between the studies. The associations of age, sex, alcohol use, smoking, baseline systolic blood pressure (SBP) and diastolic BP (DBP), the presence of comorbidities, an increase in the number of pills and the relationship between patients and physicians with adherence and persistence have been the most commonly investigated factors. Most studies have defined persistence in terms of a patient still taking medication after a period of time. A medication possession ratio (MPR) ≥ 80 has been used to define compliance. Either of these terminologies, or both, have been used to estimate adherence. In this study, I used the same definition for persistence to identify patients who have continued with their initial treatment, and used persistence and MPR to define patients who adhered to their initial treatment. The aim of this study was to estimate the prevalence of persistence and adherence in Scotland. Also, factors that could have had an effect on persistence and adherence were studied. The number of antihypertensive drugs taken by patients during the study and factors that led to an increase in patients being on a combination therapy were also evaluated. The prevalence of resistance and BP control were determined by taking the BP after the last drug had been taken by persistent patients during five follow-up studies. The relationship of factors such as age, sex, BMI, alcohol use, smoking, estimated glomerular filtration rate (eGFR), and albumin levels with BP reductions for each antihypertensive class were determined. Information Services Division (ISD) data, which includes all antihypertensive drugs, were collected from pharmacies in Scotland and linked to the Glasgow Blood Pressure Clinic (GBPC) database. This database also includes demographic characteristics, BP readings and clinical results for all patients attending the GBPC. The case notes for patients who attended the GBPC were reviewed and all new antihypertensive drugs that were prescribed between visits, BP before and after taking drugs, and any changes in the hypertensive drugs were recorded. A total of 4,232 hypertensive patients were included in the first study. The first study showed that angiotensin converting enzyme inhibitor (ACEI) and beta-blockers (BB) were the most prescribed antihypertensive classes between 2004 and 2013. Calcium channel blockers (CCB), thiazide diuretics and angiotensin receptor blockers (ARB) followed ACEI and BB as the most prescribed drugs during the same period. The prescription trend of the antihypertensive class has changed over the years with an increase in prescriptions for ACEI and ARB and a decrease in prescriptions for BB and diuretics. I observed a difference in antihypertensive class prescriptions by age, sex, SBP and BMI. For example, CCB, thiazide diuretics and alpha-blockers were more likely to be prescribed to older patients, while ACEI, ARB or BB were more commonly prescribed for younger patients. In a second study, 4,232 and 3,149 hypertensive patients were included to investigate the prevalence of persistence in the Scottish population in 1- and 5-year studies, respectively. The prevalence of persistence in the 1-year study was 72.9%, while it was only 62.8% in the 5-year study. Those patients taking ARB and ACEI showed high rates of persistence and those taking diuretics and alpha blockers had low rates of persistence. The association of persistence with clinical characteristics was also investigated. Younger patients were more likely to totally stop their treatment before restarting their treatment with other antihypertensive drugs. Furthermore, patients who had high SBP tended to be non-persistent. In a third study, 3,085 and 1,979 patients who persisted with their treatment were included. In the first part of the study, MPR was calculated, and patients with an MPR ≥ 80 were considered as adherent. Adherence rates were 29.9% and 23.4% in the 1- and 5-year studies, respectively. Patients who initiated the study with ACEI were more likely to adhere to their treatments. However, patients who initiated the study with thiazide diuretics were less likely to adhere to their treatments. Sex, age and BMI were different between the adherence and non-adherence groups. Age was an independent factor affecting adherence rates during both the 1- and 5-year studies with older patients being more likely to be adherent. In the second part of the study, pharmacy databases were checked with patients' case notes to compare antihypertensive drugs that were collected from the pharmacy with the antihypertensive prescription given during the patient’s clinical visit. While 78.6% of the antihypertensive drugs were collected between clinical visits, 21.4% were not collected. Patients who had more days to see the doctor in the subsequent visit were more likely to not collect their prescriptions. In a fourth study, 3,085 and 1,979 persistent patients were included to calculate the number of antihypertensive classes that were added to the initial drug during the 1-year and 5-year studies, respectively. Patients who continued with treatment as a monotherapy and who needed a combination therapy were investigated during the 1- and 5-year studies. In all, 55.8% used antihypertensive drugs as a monotherapy and 44.2% used them as a combination therapy during the 1-year study. While 28.2% of patients continued with treatment without the required additional therapy, 71.8% of the patients needed additional therapy. In all, 20.8% and 46.5% of patients required three different antihypertensive classes or more during the 1-year and 5-year studies, respectively. Patients who started with ACEI, ARB and BB were more likely to continue as monotherapy and less likely to need two more antihypertensive drugs compared with those who started with alpha-blockers, non-thiazide diuretics and CCB. Older ages, high BMI levels, high SBP and high alcohol intake were independent factors that led to an increase in the probability of patients taking combination therapies. In the first part of the final study, BPs were recorded after the last drug had been taken during the 5 year study. There were 815 persistent patients who were assigned for this purpose. Of these, 39% had taken one, two or three antihypertensive classes and had controlled BP (controlled hypertension [HTN]), 29% of them took one or two antihypertensive classes and had uncontrolled BP (uncontrolled HTN), and 32% of the patients took three antihypertensive classes or more and had uncontrolled BP (resistant HTN). The initiation of an antihypertensive drug and the factors affecting BP pressure were compared between the resistant and controlled HTN groups. Patients who initiated the study with ACEI were less likely to be resistant compared with those who started with alpha blockers and non-thiazide diuretics. Older patients, and high BMI tended to result in resistant HTN. In the second part of study, BP responses for patients who initiated the study with ACEI, ARB, BB, CCB and thiazide diuretics were compared. After adjusting for risk factors, patients who initiated the study with ACEI and ARB were more respondent than those who took CCB and thiazide diuretics. In the last part of this study, the association between BP reductions and factors affecting BP were tested for each antihypertensive drug. Older patients responded better to alpha blockers. Younger patients responded better to ACEI and ARB. An increase in BMI led to a decreased reduction in patients on ACEI and diuretics (thiazide and non-thiazide). An increase in albumin levels and a decrease in eGFR led to decreases in BP reductions in patients on thiazide diuretics. An increase in eGFR decreased the BP response with ACEI. In conclusion, although a high percentage of hypertensive patients in Scotland persisted with their initial drug prescription, low adherence rates were found with these patients. Approximately half of these patients required three different antihypertensive classes during the 5 years, and 32% of them had resistant HTN. Although this study was observational in nature, the large sample size in this study represented a real HTN population, and the large pharmacy data represented a real antihypertensive population, which were collected through the support of prescription data from the GBPC database. My findings suggest that ACEI, ARB and BB are less likely to require additional therapy. However, ACEI and ARB were better tolerated than BB in that they were more likely to be persistent than BB. In addition, users of ACEI, and ARB have good BP response and low resistant HTN. Linkage patients who participated in these studies with their morbidity and mortality will provide valuable information concerning the effect of adherence on morbidity and mortality and the potential benefits of using ACEI or ARB over other drugs.

The Influence of Gender on Perceived Treatment Need among a Community Sample of Substance Users

Purpose: Most individuals do not perceive a need for substance use treatment despite meeting diagnostic criteria for substance use disorders and they are least likely to pursue treatment voluntarily. There are also those who perceive a need for treatment and yet do not pursue it. This study aimed to understand which factors increase the likelihood of perceiving a need for treatment for individuals who meet diagnostic criteria for substance use disorders in the hopes to better assist with more targeted efforts for gender-specific treatment recruitment and retention. Using Andersen and Newman’s (1973/2005) model of individual determinants of healthcare utilization, the central hypothesis of the study was that gender moderates the relationship between substance use problem severity and perceived treatment need, so that women with increasing problems due to their use of substances are more likely than men to perceive a need for treatment. Additional predisposing and enabling factors from Andersen and Newman’s (1973/2005) model were included in the study to understand their impact on perceived need. Method: The study was a secondary data analysis of the 2010 National Survey on Drug Use and Health (NSDUH) using logistic regression. The weighted sample consisted of a total 20,077,235 American household residents (The unweighted sample was 5,484 participants). Results of the logistic regression were verified using Relogit software for rare events logistic regression due to the rare event of perceived treatment need (King & Zeng, 2001a; 2001b). Results: The moderating effect of female gender was not found. Conversely, men were significantly more likely than women to perceive a need for treatment as substance use problem severity increased. The study also found that a number of factors such as race, ethnicity, socioeconomic status, age, marital status, education, co-occurring mental health disorders, and prior treatment history differently impacted the likelihood of perceiving a need for treatment among men and women. Conclusion: Perceived treatment need among individuals who meet criteria for substance use disorders is rare, but identifying factors associated with an increased likelihood of perceiving need for treatment can help the development of gender-appropriate outreach and recruitment for social work treatment, and public health messages.

3D bioprinted organ models for drug screening

In recent years, 3D bioprinting has emerged as an innovative and versatile technology able to produce in vitro models that resemble the native spatial organization of organ tissues, by employing or more bioinks composed of various types of cells suspended in hydrogels. Natural and semi-synthetic hydrogels are extensively used for 3D bioprinting models since they can mimic the natural composition of the tissues, they are biocompatible and bioactive with customizable mechanical properties, allowing to support cell growth. The possibility to tailor hydrogels mechanical properties by modifying the chemical structures to obtain photo-crosslinkable materials, while maintaining their biocompatibility and biomimicry, make their use versatile and suitable to simulate a broad spectrum of physiological features. In this PhD Thesis, 3D bioprinted in vitro models with tailored mechanical properties and physiologically-like features were fabricated. AlgMa-based bioinks were employed to produce a living platform with gradient stiffness, with the aim to create an easy to handle and accessible biological tool to evaluate mechanobiology. In addition, GelMa, collagen and IPN of GelMa and collagen were used as bioinks to fabricate a proof-of-concept of 3D intestinal barrier, which include multiple cell components and multi-layered structure. A useful rheological guide to drive users to the selection of the suitable bioinks for 3D bioprinting and to correlate the model’s mechanical stability after crosslinking is proposed. In conclusion, a platform capable to reproduce models with physiological gradient stiffness was developed and the fabrication of 3D bioprinted intestinal models displaying a good hierarchical structure and cells composition was fully reported and successfully achieved. The good biological results obtained demonstrated that 3D bioprinting can be used for the fabrications of 3D models and that the mechanical properties of the external environment plays a key role on the cell pathways, viability and morphology.

Exploratory Study Of The Effect Of Lifestyle Counselling On Bone Mineral Density And Body Composition In Users Of The Contraceptive Depot-medroxyprogesterone Acetate.

To compare variations in bone mineral density (BMD) and body composition (BC) in depot-medroxyprogesterone acetate (DMPA) users and nonusers after providing counselling on healthy lifestyle habits. An exploratory study in which women aged 18 to 40 years participated: 29 new DMPA users and 25 new non-hormonal contraceptive users. All participants were advised on healthy lifestyle habits: sun exposure, walking and calcium intake. BMD and BC were assessed at baseline and 12 months later. Statistical analysis included the Mann-Whitney test or Student's t-test followed by multiple linear regression analysis. Compared to the controls, DMPA users had lower BMD at vertebrae L1 and L4 after 12 months of use. They also had a mean increase of 2 kg in total fat mass and an increase of 2.2% in body fat compared to the non-hormonal contraceptive users. BMD loss at L1 was less pronounced in DMPA users with a calcium intake ≥ 1 g/day compared to DMPA users with a lower calcium intake. DMPA use was apparently associated with lower BMD and an increase in fat mass at 12 months of use. Calcium intake ≥ 1 g/day attenuates BMD loss in DMPA users. Counselling on healthy lifestyle habits failed to achieve its aims.