Effect of filtration on morphine and particle content of injections prepared from slow-release oral morphine tablets

<p>Abstract</p> <p>Background</p> <p>Injections of mixtures prepared from crushed tablets contain insoluble particles which can cause embolisms and other complications. Although many particles can be removed by filtration, many injecting drug users do not filter due to availability, cost or performance of filters, and also due to concerns that some of the dose will be lost.</p> <p>Methods</p> <p>Injection solutions were prepared from slow-release morphine tablets (MS Contin^®) replicating methods used by injecting drug users. Contaminating particles were counted by microscopy and morphine content analysed by liquid chromatography before and after filtration.</p> <p>Results</p> <p>Unfiltered tablet extracts contained tens of millions of particles with a range in sizes from < 5 μm to > 400 μm. Cigarette filters removed most of the larger particles (> 50 μm) but the smaller particles remained. Commercial syringe filters (0.45 and 0.22 μm) produced a dramatic reduction in particles but tended to block unless used after a cigarette filter. Morphine was retained by all filters but could be recovered by following the filtration with one or two 1 ml washes. The combined use of a cigarette filter then 0.22 μm filter, with rinses, enabled recovery of 90% of the extracted morphine in a solution which was essentially free of tablet-derived particles.</p> <p>Conclusions</p> <p>Apart from overdose and addiction itself, the harmful consequences of injecting morphine tablets come from the insoluble particles from the tablets and microbial contamination. These harmful components can be substantially reduced by passing the injection through a sterilizing (0.22 μm) filter. To prevent the filter from blocking, a preliminary coarse filter (such as a cigarette filter) should be used first. The filters retain some of the dose, but this can be recovered by following filtration with one or two rinses with 1 ml water. Although filtration can reduce the non-pharmacological harmful consequences of injecting tablets, this remains an unsafe practice due to skin and environmental contamination by particles and microorganisms, and the risks of blood-borne infections from sharing injecting equipment.</p

Peer-provided psychological intervention for Syrian refugees: results of a randomised controlled trial on the effectiveness of Problem Management Plus

Background The mental health burden among refugees in high-income countries (HICs) is high, whereas access to mental healthcare can be limited. Objective To examine the effectiveness of a peer-provided psychological intervention (Problem Management Plus; PM+) in reducing symptoms of common mental disorders (CMDs) among Syrian refugees in the Netherlands. Methods We conducted a single-blind, randomised controlled trial among adult Syrian refugees recruited in March 2019–December 2021 (No. NTR7552). Individuals with psychological distress (Kessler Psychological Distress Scale (K10) >15) and functional impairment (WHO Disability Assessment Schedule (WHODAS 2.0) >16) were allocated to PM+ in addition to care as usual (PM+/CAU) or CAU only. Participants were reassessed at 1-week and 3-month follow-up. Primary outcome was depression/anxiety combined (Hopkins Symptom Checklist; HSCL-25) at 3-month follow-up. Secondary outcomes included depression (HSCL-25), anxiety (HSCL-25), post-traumatic stress disorder (PTSD) symptoms (PTSD Checklist for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition; PCL-5), impairment (WHODAS 2.0) and self-identified problems (PSYCHLOPS; Psychological Outcomes Profiles). Primary analysis was intention-to-treat. Findings Participants (n=206; mean age=37 years, 62% men) were randomised into PM+/CAU (n=103) or CAU (n=103). At 3-month follow-up, PM+/CAU had greater reductions on depression/anxiety relative to CAU (mean difference −0.25; 95% CI −0.385 to −0.122; p=0.0001, Cohen’s d=0.41). PM+/CAU also showed greater reductions on depression (p=0.0002, Cohen’s d=0.42), anxiety (p=0.001, Cohen’s d=0.27), PTSD symptoms (p=0.0005, Cohen’s d=0.39) and self-identified problems (p=0.03, Cohen’s d=0.26), but not on impairment (p=0.084, Cohen’s d=0.21). Conclusions PM+ effectively reduces symptoms of CMDs among Syrian refugees. A strength was high retention at follow-up. Generalisability is limited by predominantly including refugees with a resident permit. Clinical implications Peer-provided psychological interventions should be considered for scale-up in HICs

Peer-provided Problem Management plus (PM+) for adult Syrian refugees: a pilot randomised controlled trial on effectiveness and cost-effectiveness

Aims Common mental disorders are highly prevalent among Syrian refugees. Problem Management Plus (PM+) is a brief, transdiagnostic, non-specialist helper delivered, psychological intervention targeting psychological distress. This single-blind pilot randomised controlled trial (RCT) on PM+ delivered by peer-refugees examined trial procedures in advance of a definitive RCT, evaluated PM+ 's acceptability and feasibility, and investigated its likely effectiveness and cost-effectiveness among Syrian refugees in the Netherlands.Methods Adult Syrian refugees (N = 60) with elevated psychological distress (Kessler Psychological Distress Scale (K10) score >15) and reduced pychosocial functioning (WHO Disability Assessment Schedule 2.0 (WHODAS) score >16) were randomised into PM+ in addition to care as usual (CAU) (PM+/CAU; n = 30) or CAU alone (n = 30). Primary outcomes were symptoms of depression and anxiety (Hopkins Symptom Checklist; HSCL-25) at 3-month follow-up. Secondary outcomes were pychosocial functioning (WHO Disability Assessment Schedule; WHODAS 2.0), symptoms of posttraumatic stress disorder (PTSD) (PTSD Checklist for DSM 5; PCL-5) and self-identified problems (Psychological Outcomes Profiles; PSYCHLOPS). Changes in service utilisation and time out of employment and/or adult education were estimated (adapted version of the Client Service Receipt Inventory; CSRI). Semi-structured interviews on the implementation of PM+ were conducted with stakeholders (i.e. six PM+ participants, five non-specialist helpers and five key informants).Results Recruitment, randomization and blinding procedures were successful. PM+ was generally perceived positively by stakeholders, especially regarding the intervention strategies, accommodation of the intervention and the helpers. Two serious adverse events not attributable to the trial were reported. At 3-month follow-up, the HSCL-25 total score was significantly lower for the PM+/CAU group (n = 30) than CAU group (n = 30) (p = 0.004; d = 0.58). Significant differences in favour of PM+/CAU were also found for WHODAS psychosocial functioning (p = 0.009, d = 0.73), PCL-5 symptoms of PTSD (p = 0.006, d = 0.66) and PSYCHLOPS self-identified problems (p = 0.005, d = 0.81). There were no significant differences in mean health service costs (p = 0.191) and the mean costs of lost productive time (p = 0.141). This suggests PM+ may potentially be cost-effective with an incremental cost from a health system perspective of €5047 (95% CI €0–€19 773) per additional recovery achieved.Conclusions Trial procedures and PM+ delivered by non-specialist peer-refugee helpers seemed acceptable, feasible and safe. Analyses indicate that PM+ may be effective in improving mental health outcomes and psychosocial functioning, and potentially cost-effective. These results support the development of a definitive RCT with a larger sample of refugees and a longer follow-up period

Cdx1 and Cdx2 have Overlapping Functions in Anteroposterior Patterning and Posterior Axis Elongation

Mouse Cdx and Hox genes presumably evolved from genes on a common ancestor cluster involved in anteroposterior patterning. Drosophila caudal (cad) is involved in specifying the posterior end of the early embryo, and is essential for patterning tissues derived from the most caudal segment, the analia. Two of the three mouse Cdx paralogues, Cdx 1 and Cdx2, are expressed early in a Hox-like manner in the three germ layers. In the nascent paraxial mesoderm, both genes are expressed in cells contributing first to the most rostral, and then to progressively more caudal parts of the vertebral column. Later, expression regresses from the anterior sclerotomes, and is only maintained for Cdx1 in the dorsal part of the somites, and for both genes in the tail bud. Cdx1 null mutants show anterior homeosis of upper cervical and thoracic vertebrae. Cdx2-null embryos die before gastrulation, and Cdx2 heterozygotes display anterior transformations of lower cervical and thoracic vertebrae. We have analysed the genetic interactions between Cdx1 and Cdx2 in compound mutants. Combining mutant alleles for both genes gives rise to anterior homeotic transformations along a more extensive length of the vertebral column than do single mutations. The most severely affected Cdx1 null/Cdx2 heterozygous mice display a posterior shift of their cranio-cervical, cervico-thoracic, thoraco-lumbar, lumbo-sacral and sacro-caudal transitions. The effects of the mutations in Cdx1 and Cdx2 were co-operative in severity, and a more extensive posterior shift of the expression of three Hox genes was observed in double mutants. The alteration in Hox expression boundaries occurred early. We conclude that both Cdx genes cooperate at early stages in instructing the vertebral progenitors all along the axis, at least in part by setting the rostral expression boundaries of Hox genes. In addition, Cdx mutants transiently exhibit alterations in the extent of Hox expression domains in the spinal cord, reminding of the strong effects of overexpressing Cdx genes on Hox gene expression in the neurectoderm. Phenotypical alterations in the peripheral nervous system were observed at mid-gestation stages. Strikingly, the altered phenotype at caudal levels included a posterior truncation of the tail, mildly affecting Cdx2 heterozygotes, but more severely affecting Cdx1/Cdx2 double heterozygotes and Cdx1 null/Cdx2 heterozygotes. Mutations in Cdx1 and Cdx2 therefore also interfere with axis elongation in a cooperative way. The function of Cdx genes in morphogenetic processes during gastrulation and tail bud extension, and their relationship with the Hox genes are discussed in the light of available data in Amphioxus, C. elegans, Drosophila and mice

Effectiveness of a peer-refugee delivered psychological intervention to reduce psychological distress among adult Syrian refugees in the Netherlands: study protocol

Background: Syrian refugees face multiple hardships and adversities which put them at risk for the development of mental health problems. However, access to adequate mental health care in host countries is limited. The WHO has developed Problem Management Plus (PM+), a brief, scalable psychological intervention, delivered by non-specialist helpers, that addresses common mental disorders in people affected by adversity. This study is part of the STRENGTHS project, that aims to evaluate peer-refugee delivered psychological interventions for Syrian refugees in Europe and the Middle East. Objective: To evaluate the effectiveness and cost-effectiveness of the peer-refugee delivered PM+ intervention among Syrian refugees with elevated levels of psychological distress in the Netherlands. Methods: PM+ will be tested in a randomized controlled trial (RCT) among Arabic-speaking Syrian refugees in the Netherlands aged 18 years and above with self-reported psychological distress (Kessler Psychological Distress Scale; K10 >15) and impaired daily functioning (WHO Disability Assessment Schedule; WHODAS 2.0 >16). Participants (N = 380) will be randomized into care as usual with PM+ (CAU/PM+, n = 190) or CAU only (CAU, n = 190). Baseline, 1-week post-intervention, and 3-month and 12-month follow-up assessments will be conducted. Primary outcomes are symptoms of depression and anxiety. Secondary outcomes are functional impairment, posttraumatic stress disorder symptoms, self-identified problems, anger, health and productivity costs, and hair cortisol concentrations. A process evaluation will be carried out to evaluate treatment dose, protocol fidelity and stakeholder views on barriers and facilitators to implementing PM+. Results and Conclusions: PM+ has proved effectiveness in other populations and settings. After positive evaluation, the adapted manual and training materials for individual PM+ will be made available through the WHO to encourage further replication and scaling up. Trial registration: Trial registration Dutch Trial Registry, NL7552, registered prospectively on March 1, 2019. Medical Ethics Review Committee VU Medical Center Protocol ID 2017.320, 7 September 2017

Health service utilization and direct healthcare costs associated with obesity in older adult population in Ghana

Obesity is a major risk factor for many chronic diseases and disabilities, with severe implications on morbidity and mortality among older adults. With an increasing prevalence of obesity among older adults in Ghana, it has become necessary to develop cost-effective strategies for its management and prevention. However, developing such strategies is challenging as body mass index (BMI)-specific utilization and costs required for cost-effectiveness analysis are not available in this population. Therefore, this study examines the associations between health services utilization as well as direct healthcare costs and overweight (BMI ≥25.00 and <30.00 kg/m2) and obesity (BMI ≥30.00 kg/m2) among older adults in Ghana. Data were used from a nationally representative, multistage sample of 3350 people aged 50+ years from the World Health Organization's Study on global AGEing and adult health (WHO-SAGE; 2014/15). Health service utilization was measured by the number of health facility visits over a 12-month period. Direct costs (2017 US dollars) included out-of-pocket payments and the National Health Insurance Scheme (NHIS) claims. Associations between utilization and BMI were examined using multivariable zero-inflated negative binomial regressions; and between costs and BMI using multivariable two-part regressions. Twenty-three percent were overweight and 13% were obese. Compared with normal-weight participants, overweight and obesity were associated with 75% and 159% more inpatient admissions, respectively. Obesity was also associated with 53% additional outpatient visits. One in five of the overweight and obese population had at least one chronic disease, and having chronic disease was associated with increased outpatient utilization. The average per person total costs for overweight was $78 and obesity was$132 compared with $35 for normal weight. The NHIS bore approximately 60$121 million compared with $64 million for normal weight in the entire older adult Ghanaian population. Compared with normal weight, the total costs per person associated with overweight increased by 73% and more than doubled for obesity. Even though the total prevalence of overweight and obesity was about half of that of normal weight, the sum of their cost burden was almost doubled. Implementing weight reduction measures could reduce health service utilization and costs in this population

The effectiveness of Problem Management Plus at 1-year follow-up for Syrian refugees in a high-income setting

Aims Problem Management Plus (PM+) has been effective in reducing mental health problems among refugees at three-month follow-up, but there is a lack of research on its long-term effectiveness. This study examined the effectiveness of PM+ in reducing symptoms of common mental disorders at 12-month follow-up among Syrian refugees in the Netherlands. Methods This single-blind, parallel, controlled trial randomised 206 adult Syrians who screened positive for psychological distress and impaired functioning to either PM+ in addition to care as usual (PM+/CAU) or CAU alone. Assessments were at baseline, 1 week and 3 months after the intervention and 12 months after baseline. Outcomes were psychological distress (Hopkins Symptom Checklist [HSCL-25]), depression (HSCL-25 subscale), anxiety (HSCL-25 subscale), posttraumatic stress disorder symptoms (PCL-5), functional impairment (WHODAS 2.0) and self-identified problems (PSYCHLOPS). Results In March 2019–December 2022, 103 participants were assigned to PM+/CAU and 103 to CAU of which 169 (82.0%) were retained at 12 months. Intention-to-treat analyses showed greater reductions in psychological distress at 12 months for PM+/CAU compared to CAU (adjusted mean difference −0.17, 95% CI −0.310 to −0.027; p = 0.01, Cohen’s d = 0.28). Relative to CAU, PM+/CAU participants also showed significant reductions on anxiety (−0.19, 95% CI −0.344 to −0.047; p = 0.01, d = 0.31) but not on any of the other outcomes. Conclusions PM+ is effective in reducing psychological distress and symptoms of anxiety over a period up to 1 year. Additional support such as booster sessions or additional (trauma-focused) modules may be required to prolong and consolidate benefits gained through PM+ on other mental health and psychosocial outcomes

Rapidly increasing prevalence of overweight and obesity in older Ghanaian adults from 2007-2015: Evidence from WHO-SAGE Waves 1&2

BackgroundStudies on changes in the prevalence and determinants of obesity in older adults living in sub-Saharan Africa are scarce. We examined recent changes in obesity prevalence and associated factors for older adults in Ghana between 2007/08 and 2014/15.MethodsData on adults aged 50 years and older in Ghana were drawn from the WHO SAGE 2007/08 (Wave 1; n = 4158) and 2014/15 (Wave 2; n = 1663). The weighted prevalence of obesity, overweight, normal weight and underweight, and of high central adiposity were compared in 2007/08 and 2014/15. Multinomial and binomial logistic regressions were used to examine whether the determinants of weight status based on objectively measured body mass index and waist circumference changed between the two time periods.ResultsThe prevalence of overweight (2007/08 = 19.6%, 95% CI: 18.0-21.4%; 2014/15 = 24.5%, 95% CI: 21.7-27.5%) and obesity (2007/08 = 10.2%, 95% CI: 8.9-11.7%; 2014/15 = 15.0%, 95% CI: 12.6-17.7%) was higher in 2014/15 than 2007/08 and more than half of the population had high central adiposity (2007/08 = 57.7%, 95% CI: 55.4-60.1%; 2014/15 = 66.9%, 95% CI: 63.7-70.0%) in both study periods. While the prevalence of overweight increased in both sexes, obesity prevalence was 16% lower in males and 55% higher in females comparing 2007/08 to 2014/15. Female sex, urban residence, and high household wealth were associated with higher odds of overweight/obesity and high central adiposity. Those aged 70+ years had lower odds of obesity in both study waves. In 2014/15, females who did not meet the recommended physical activity were more likely to be obese.ConclusionOver the 7-year period between the surveys, the prevalence of underweight decreased and overweight increased in both sexes, while obesity decreased in males but increased in females. The difference in obesity prevalence may point to differential impacts of past initiatives to reduce overweight and obesity, potential high-risk groups in Ghana, and the need to increase surveillance

Impact of overweight and obesity on life expectancy, quality-adjusted life years and lifetime costs in the adult population of Ghana

IntroductionPrior studies have revealed the increasing prevalence of obesity and its associated health effects among ageing adults in resource poor countries. However, no study has examined the long-term and economic impact of overweight and obesity in sub-Saharan Africa. Therefore, we quantified the long-term impact of overweight and obesity on life expectancy (LE), quality-adjusted life years (QALYs) and total direct healthcare costs. Methods A Markov simulation model projected health and economic outcomes associated with three categories of body mass index (BMI): healthy weight (18.5 = 30.0 kg/m(2)) in simulated adult cohorts over a 50-year time horizon from age fifty. Costs were estimated from government and patient perspectives, discounted 3% annually and reported in 2017 US$. Mortality rates from Ghanaian lifetables were adjusted by BMI-specific all-cause mortality HRs. Published input data were used from the 2014/2015 Ghana WHO Study on global AGEing and adult health data. Internal and external validity were assessed. Results From age 50 years, average (95$619 (95% CI: 616 to 622), US$1298 (95$2057 (95% CI: 2043 to 2071) for healthy weight, overweight and obesity, respectively. QALYs and costs were lower in males. Conclusion Overweight and obesity have substantial health and economic impacts, hence the urgent need for cost-effective preventive strategies in the Ghanaian population.</div

The role of intergenerational educational mobility and household wealth in adult obesity: Evidence from Wave 2 of the World Health Organization's Study on global AGEing and adult health

BackgroundObesity has emerged as a major risk factor for non-communicable diseases in low and middle-income countries but may not follow typical socioeconomic status (SES)-related gradients seen in higher income countries. This study examines the associations between current and lifetime markers of SES and BMI categories (underweight, normal weight, overweight, obese) and central adiposity in Ghanaian adults.MethodsData from 4,464 adults (2,610 women) who participated in the World Health Organization's Study on global AGEing and adult health (SAGE) Wave 2 were examined. Multilevel multinomial and binomial logistic regression models were used to examine associations. SES markers included parental education, individual education, intergenerational educational mobility and household wealth. Intergenerational educational mobility was classified: stable-low (low parental and low individual education), stable-high (high parental and high individual education), upwardly (low parental and high individual education), or downwardly mobile (high parental and low individual education).ResultsThe prevalence of obesity (12.9%) exceeded the prevalence of underweight (7.2%) in the population. High parental and individual education were significantly associated with higher odds of obesity and central adiposity in women. Compared to the stable low pattern, stable high (obesity: OR = 3.15; 95% CI: 1.96, 5.05; central adiposity: OR = 1.75; 95% CI: 1.03, 2.98) and upwardly (obesity: OR = 1.71; 95% CI: 11.13, 2.60; central adiposity: OR = 1.60; 95% CI: 1.08, 2.37) mobile education patterns were associated with higher odds of obesity and central adiposity in women, while stable high pattern was associated with higher odds of overweight (OR = 1.88; 95% CI: 1.11, 3.19) in men. Additionally, high compared to the lowest household wealth was associated with high odds of obesity and central adiposity in both sexes.ConclusionStable high and upwardly mobile education patterns are associated with higher odds of obesity and central adiposity in women while the stable high pattern was associated with higher odds of overweight in men