Attenuated Neural Processing of Risk in Young Adults at Risk for Stimulant Dependence

Objective

Approximately 10% of young adults report non-medical use of stimulants (cocaine, amphetamine, methylphenidate), which puts them at risk for the development of dependence. This fMRI study investigates whether subjects at early stages of stimulant use show altered decision making processing.

Methods

158 occasional stimulants users (OSU) and 50 comparison subjects (CS) performed a “risky gains” decision making task during which they could select safe options (cash in 20 cents) or gamble them for double or nothing in two consecutive gambles (win or lose 40 or 80 cents, “risky decisions”). The primary analysis focused on risky versus safe decisions. Three secondary analyses were conducted: First, a robust regression examined the effect of lifetime exposure to stimulants and marijuana; second, subgroups of OSU with >1000 (n = 42), or <50 lifetime marijuana uses (n = 32), were compared to CS with <50 lifetime uses (n = 46) to examine potential marijuana effects; third, brain activation associated with behavioral adjustment following monetary losses was probed.

Results

There were no behavioral differences between groups. OSU showed attenuated activation across risky and safe decisions in prefrontal cortex, insula, and dorsal striatum, exhibited lower anterior cingulate cortex (ACC) and dorsal striatum activation for risky decisions and greater inferior frontal gyrus activation for safe decisions. Those OSU with relatively more stimulant use showed greater dorsal ACC and posterior insula attenuation. In comparison, greater lifetime marijuana use was associated with less neural differentiation between risky and safe decisions. OSU who chose more safe responses after losses exhibited similarities with CS relative to those preferring risky options.

Discussion

Individuals at risk for the development of stimulant use disorders presented less differentiated neural processing of risky and safe options. Specifically, OSU show attenuated brain response in regions critical for performance monitoring, reward processing and interoceptive awareness. Marijuana had additive effects by diminishing neural risk differentiation.     

Economic issues for the UK biotechnology sector

This paper examines the economic prospects for the biotechnology industry, focusing on the UK position. I discuss some economic issues relating to the structure of the biotechnology industry and examine whether these factors can account for the relative success of the biotechnology sector in the UK compared to other European countries. I emphasize the importance of the science base, pharmaceutical companies and capital markets in giving the UK an advantage. Looking ahead I argue that prospects are good for the global growth of the industry due to supply and demand side factors. The UK is in a leading position in Europe but faces significant dangers, especially from the public towards biotechnology.     

An Economic Evaluation of Venous Thromboembolism Prophylaxis Strategies in Critically Ill Trauma Patients at Risk of Bleeding

Background

Critically ill trauma patients with severe injuries are at high risk for venous thromboembolism (VTE) and bleeding simultaneously. Currently, the optimal VTE prophylaxis strategy is unknown for trauma patients with a contraindication to pharmacological prophylaxis because of a risk of bleeding.

Methods and Findings

Using decision analysis, we estimated the cost effectiveness of three VTE prophylaxis strategies—pneumatic compression devices (PCDs) and expectant management alone, serial Doppler ultrasound (SDU) screening, and prophylactic insertion of a vena cava filter (VCF)—in trauma patients admitted to an intensive care unit (ICU) with severe injuries who were believed to have a contraindication to pharmacological prophylaxis for up to two weeks because of a risk of major bleeding. Data on the probability of deep vein thrombosis (DVT) and pulmonary embolism (PE), and on the effectiveness of the prophylactic strategies, were taken from observational and randomized controlled studies. The probabilities of in-hospital death, ICU and hospital discharge rates, and resource use were taken from a population-based cohort of trauma patients with severe injuries (injury severity scores >12) admitted to the ICU of a regional trauma centre. The incidence of DVT at 12 weeks was similar for the PCD (14.9%) and SDU (15.0%) strategies, but higher for the VCF (25.7%) strategy. Conversely, the incidence of PE at 12 weeks was highest in the PCD strategy (2.9%), followed by the SDU (1.5%) and VCF (0.3%) strategies. Expected mortality and quality-adjusted life years were nearly identical for all three management strategies. Expected health care costs at 12 weeks were Can$55,831 for the PCD strategy, Can$55,334 for the SDU screening strategy, and Can$57,377 for the VCF strategy, with similar trends noted over a lifetime analysis.

Conclusions

The attributable mortality due to PE in trauma patients with severe injuries is low relative to other causes of mortality. Prophylactic placement of VCF in patients at high risk of VTE who cannot receive pharmacological prophylaxis is expensive and associated with an increased risk of DVT. Compared to the other strategies, SDU screening was associated with better clinical outcomes and lower costs. Please see later in the article for Editors'' Summary     

Different Physical Activity Subtypes and Risk of Metabolic Syndrome in Middle-Aged and Older Chinese People

Background

The prevalence of metabolic syndrome (MetS) is growing rapidly in China. Tai chi and dancing are common types of exercise among middle-aged and elderly Chinese. It remains unclear whether these activities are associated with a lower risk of MetS.

Methodology/Principal Findings

A total of 15,514 individuals (6,952 men, 8,562 women) aged 50 to 70 years from the Dongfeng-Tongji Cohort in Shiyan, China participated in a cross-sectional study. Physical activity and other lifestyle factors were assessed with semi-structured questionnaires during face-to-face interviews. MetS was defined by the current National Cholesterol Education Program/Adult treatment Panel III criteria for Asian Americans. The prevalence of MetS was 33.2% in the study population. In the multivariable-adjusted logistic regression analyses, total physical activity levels were monotonically associated with a lower odds of MetS [OR 0.75 comparing extreme quintiles, 95% confidence interval (CI) 0.66–0.86, P<0.001]. Compared with non-exercisers in a specific exercise type, jogging (OR 0.82, 95% CI 0.68–1.00, P = 0.046), tai chi (OR 0.72, 95% CI 0.60–0.88, P<0.001), and dancing (OR 0.56, 95% CI 0.47–0.67, P<0.001) were associated with significantly lower odds of MetS. Furthermore, each 1–h/week increment in tai chi and dancing was associated with a 5% (95% CI 2%–9%) and a 9% (95% CI 6%, 12%) lower risk of MetS.

Conclusions/Significance

Jogging, tai chi and dancing are associated with a significantly lower risk of having MetS in middle-aged and older Chinese. Future intervention studies should consider the role of jogging, tai chi and dancing in preventing MetS.     

HIV Infection among Young People in Northwest Tanzania: The Role of Biological,Behavioural and Socio-Demographic Risk Factors

Background

Young people are at high risk of HIV and developing appropriate prevention programmes requires an understanding of the risk factors for HIV in this age group. We investigated factors associated with HIV among participants aged 15–30 years in a 2007–8 cross-sectional survey nested within a community-randomised trial of the MEMA kwa Vijana intervention in 20 rural communities in northwest Tanzania.

Methods

We analysed data for 7259(53%) males and 6476(47%) females. Using a proximate-determinant conceptual framework and conditional logistic regression, we obtained sex-specific Odds Ratios (ORs) for the association of HIV infection with socio-demographic, knowledge, behavioural and biological factors.

Results

HSV-2 infection was strongly associated with HIV infection (females: adjOR 4.4, 95%CI 3.2–6.1; males: adjOR 4.2, 95%CI 2.8–6.2). Several socio-demographic factors (such as age, marital status and mobility), behavioural factors (condom use, number and type of sexual partnerships) and biological factors (blood transfusion, lifetime pregnancies, genital ulcers, Neisseria gonorrhoeae) were also associated with HIV infection. Among females, lifetime sexual partners (linear trend, p<0.001), ≥2 partners in the past year (adjOR 2.0, 95%CI 1.4–2.8), ≥2 new partners in the past year (adjOR 1.9 95%CI 1.2, 3.3) and concurrent partners in the past year (adjOR 1.6 95%CI 1.1, 2.4) were all associated with HIV infection.

Conclusions

Efforts must be intensified to find effective interventions to reduce HSV-2. Effective behavioural interventions focusing on reducing the number of sexual partnerships and risk behaviour within partnerships are also needed. An increase in risky sexual behaviour may occur following marriage dissolution or when a young woman travels outside of her community and interventions addressing the needs of these subgroups of vulnerable women may be important.

Trial Registration

ClinicalTrial.gov {"type":"clinical-trial","attrs":{"text":"NCT00248469","term_id":"NCT00248469"}}NCT00248469.     

Anabolic Therapy and Optimal Treatment Sequences for Patients With Osteoporosis at High Risk for Fracture

Objective: Provide an update regarding anabolic medications for osteoporosis, which are often considered to be the last resort for patients with osteoporosis, after multiple fractures have already occurred and other medications have already been administered.Methods: Literature review and discussion.Results: Recent pivotal trial data for anabolic agents and randomized trials comparing anabolic and antiresorptive medications suggest that three anabolic agents (teriparatide, abaloparatide, and romosozumab) reduce nonvertebral and vertebral fractures faster and to a greater extent than potent antiresorptive treatments. Furthermore, bone density accrual is maximized when patients are given anabolic agents first, followed by potent antiresorptive therapy. Since total hip bone density during or after osteoporosis treatment has emerged as an excellent surrogate for future fracture risk, attaining a greater hip bone mineral density is a treatment goal for high-risk osteoporosis patients.Conclusion: This review defines the highest-risk patients and summarizes the rationale for the evolving role of anabolic therapy in the management of postmenopausal women at high risk for fracture.Abbreviations: ACTIVE = Abaloparatide Comparator Trial in Vertebral Endpoints; ARCH = Active Controlled Fracture Study in Postmenopausal Women with Osteoporosis at High Risk; BMD = bone mineral density; FRAME = Fracture Study in Postmenopausal Women with Osteoporosis; FRAX = Fracture Risk Assessment Tool; PTH = parathyroid hormone; TBS = trabecular bone score     

The Government of Kenya's Cash Transfer Program Reduces the Risk of Sexual Debut among Young People Age 15-25

The aim of this study is to assess whether the Government of Kenya''s Cash Transfer for Orphans and Vulnerable Children (Kenya CT-OVC) can reduce the risk of HIV among young people by postponing sexual debut. The program provides an unconditional transfer of US$20 per month directly to the main caregiver in the household. An evaluation of the program was implemented in 2007–2009 in seven districts. Fourteen Locations were randomly assigned to receive the program and fourteen were assigned to a control arm. A sample of households was enrolled in the evaluation in 2007. We revisited these households in 2011 and collected information on sexual activity among individuals between 15–25 years of age. We used logistic regression, adjusted for the respondent''s age, sex and relationship to caregiver, the age, sex and schooling of the caregiver and whether or not the household lived in Nairobi at baseline, to compare rates of sexual debut among young people living in program households with those living in control households who had not yet entered the program. Our results, adjusted for these covariates, show that the program reduced the odds of sexual debut by 31 percent. There were no statistically significant effects on secondary outcomes of behavioral risk such as condom use, number of partners and transactional sex. Since the CT-OVC provides cash to the caregiver and not to the child, and there are no explicit conditions associated with receipt, these impacts are indirect, and may have been achieved by keeping young people in school. Our results suggest that large-scale national social cash transfer programs with poverty alleviation objectives may have potential positive spillover benefits in terms of reducing HIV risk among young people in Eastern and Southern Africa.     

People at Risk of Influenza Pandemics: The Evolution of Perception and Behavior

Influenza pandemics can severely impact human health and society. Understanding public perception and behavior toward influenza pandemics is important for minimizing the effects of such events. Public perception and behavior are expected to change over the course of an influenza pandemic, but this idea has received little attention in previous studies. Our study aimed to understand the dynamics of public perception and behavior over the course of the 2009 H1N1 influenza pandemic. Three consecutive cross-sectional surveys were administered among Beijing residents with random-digit dialing techniques in March 2008 and August and November 2009. Effective samples of 507, 508 and 1006 respondents were interviewed in each of the three surveys, respectively. The mean scores of risk perception were low to moderate across the three surveys. The perceived risk of infection of self was significantly lower than that of the community, revealing an optimistic bias. Longitudinally, the perceived risk of contracting H1N1 increased, whereas the perceived risk of being unable to obtain medicine and medical care once influenza permeated the community first increased and then decreased. Responsive actions toward influenza varied. Most respondents took actions that required little extra effort, such as ventilating rooms; these actions did not change over time. Comparatively, a smaller number of respondents took actions for coping with influenza, such as vaccination; however, these actions were taken by an increasing number of respondents over time. The association between risk perception and behavior was unstable. Positive, insignificant, and negative associations were obtained in the three surveys. In conclusion, the evolving patterns of risk perception and responsive behavior over the course of an influenza pandemic are sensitive to how risk and behavior are defined and scoped.     

Famine in the Young and Risk of Later Hospitalization for COPD and Asthma

Background

Undernutrition during critical periods of growth and development may permanently affect lung physiology and function.

Objectives

To investigate whether acute undernutrition in childhood or young adulthood increases the risk of later hospitalization for obstructive airways disease, chronic obstructive pulmonary disease (COPD), or asthma.

Methods

We studied 7,841 women from Prospect-EPIC who experienced the 1944–45 Dutch famine between ages 0 and 21. Pulmonary outcomes were measured by registered hospital admissions and exposure-blinded computed tomography (CT) in a subgroup of 295 women. With Cox proportional hazard regression we explored effects of famine exposure on risk of hospitalization for obstructive airways disease, COPD, and asthma. With logistic regression we explored effects of famine on risk of CT evidence of pulmonary disease.

Results

Risks of hospitalization for obstructive airways disease, COPD, and asthma were increased after moderate famine exposure, and significantly increased after severe famine exposure: hazard ratios for obstructive airways disease were 1.31 (95% CI: 0.97 to 1.77) and 1.57 (95% CI: 1.10 to 2.23) respectively. Associations between famine exposure and hospitalization for COPD were stronger in ever-smokers than in never-smokers.

Conclusions

Acute undernutrition in childhood or young adulthood is associated with an increased risk of later COPD and asthma hospitalization, possibly through increased sensitivity for tobacco smoke.     

Peer-based Education and the Integration of HIV and Sexual and Reproductive Health Services for Young People in Vietnam: Evidence from a Project Evaluation

Introduction

This paper reports changes in behavioral outcomes related to the use of HIV testing service of a project that employed peer-based education strategies and integration of HIV voluntary counseling and testing (VCT) and Sexual and Reproductive Health (SRH) services targeting young people aged 15–24 across 5 provinces in Vietnam.

Methods

A pre-test/post-test, non-experimental evaluation design was used. Data were collected from cross-sectional surveys of youth and client exit interviews at project supported SRH clinics conducted at baseline and again at 24 months following implementation. The baseline samples consisted of 813 youth and 399 exit clients. The end line samples included 501 youths and 399 exit clients. Z test was used to assess changes in behavioral outcomes.

Results

Results show that there was a significant increase (p<0.05) in the percentage of youth who wanted to obtain a HIV test (from 33% to 51%), who had ever had a test (from 7.5% to 15%), and who had a repeat test in the last 12 months (from 54.5% to 67.5%). Exit client interviews found a nearly five-fold increase in the percentage of clients seeking HIV VCT in their current visit (5.0% vs. 24.5%) and almost two-fold increase in the percentage of those having their last test at a project supported clinic (9.3% vs. 17.8%). There were also positive changes in some aspects of youth HIV/AIDS knowledge, attitudes, and risk perceptions.

Conclusions

This study provides preliminary evidence regarding the benefits of the integration of HIV VCT-SRH services in terms of increased access to HIV services and testing in Vietnam. Benefits of peer-based education regarding increased HIV knowledge were also identified. Further investigations, including experimental studies with assessment of health outcomes and the uptake of HIV testing services, are required to better elucidate the effectiveness and challenges of this intervention model in Vietnam.     

Level of Young People Sexual and Reproductive Health Service Utilization and Its Associated Factors among Young People in Awabel District,Northwest Ethiopia

Background

Currently in Ethiopia, young people’s sexual and reproductive health services are limited and there is a growing issue of confidentiality and affordability of these health services. Moreover, the available services provided are not sensitive to the special needs of young people. Therefore, this study was aimed to assess young people’s sexual and reproductive health service utilization and its associated factors in Awabel district, Northwest Ethiopia.

Methods

A community based cross-sectional study was conducted among 781 randomly selected young people using a pre-tested structured questionnaires in Awabel district, Northwest Ethiopia. Data were entered into Epi data version 3.1 and analyzed using SPSS version 16.0 software.

Results

The mean age of respondents were 17.80 (+ 2.65) years. About 41% of young people had utilized sexual and reproductive health services. Young people from families of higher family expenditure, lived with mothers, participated in peer education and lived near to a Health Center were more likely to utilize sexual and reproductive health services. Furthermore, those who had a parental discussion on sexual and reproductive health (AOR (95% C.I): 2.23 (1.43, 3.46)) and ever had sexual intercourse (AOR (95% C.I): 1.88 (1.30, 2.71)) were more likely to utilize the service than their counterparts. On the other hand, those young people lived with their father and had a primary level of educational attainment was less likely to utilize the service.

Conclusion

Utilization of sexual and reproductive health services is low which needs a great attention where; if not intervened, young people might engage in risky sexual activities. Therefore, it needs a concerted effort from all the concerned bodies to improve their service utilization and thereby reduce the burden of young people’s disease and disabilities associated with sexual and reproductive health.     

Canalization of the Polygenic Risk for Common Diseases and Traits in the UK Biobank Cohort

Since organisms develop and thrive in the face of constant perturbations due to environmental and genetic variation, species may evolve resilient genetic architectures. We sought evidence for this process, known as canalization, through a comparison of the prevalence of phenotypes as a function of the polygenic score (PGS) across environments in the UK Biobank cohort study. Contrasting seven diseases and three categorical phenotypes with respect to 151 exposures in 408,925 people, the deviation between the prevalence–risk curves was observed to increase monotonically with the PGS percentile in one-fifth of the comparisons, suggesting extensive PGS-by-Environment (PGS×E) interaction. After adjustment for the dependency of allelic effect sizes on increased prevalence in the perturbing environment, cases where polygenic influences are greater or lesser than expected are seen to be particularly pervasive for educational attainment, obesity, and metabolic condition type-2 diabetes. Inflammatory bowel disease analysis shows fewer interactions but confirms that smoking and some aspects of diet influence risk. Notably, body mass index has more evidence for decanalization (increased genetic influence at the extremes of polygenic risk), whereas the waist-to-hip ratio shows canalization, reflecting different evolutionary pressures on the architectures of these weight-related traits. An additional 10 % of comparisons showed evidence for an additive shift of prevalence independent of PGS between exposures. These results provide the first widespread evidence for canalization protecting against disease in humans and have implications for personalized medicine as well as understanding the evolution of complex traits. The findings can be explored through an R shiny app at https://canalization-gibsonlab.shinyapps.io/rshiny/.     

Cost-Effectiveness of Collaborative Care for Depression in UK Primary Care: Economic Evaluation of a Randomised Controlled Trial (CADET)

Background

Collaborative care is an effective treatment for the management of depression but evidence on its cost-effectiveness in the UK is lacking.

Aims

To assess the cost-effectiveness of collaborative care in a UK primary care setting.

Methods

An economic evaluation alongside a multi-centre cluster randomised controlled trial comparing collaborative care with usual primary care for adults with depression (n = 581). Costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICER) were calculated over a 12-month follow-up, from the perspective of the UK National Health Service and Personal Social Services (i.e. Third Party Payer). Sensitivity analyses are reported, and uncertainty is presented using the cost-effectiveness acceptability curve (CEAC) and the cost-effectiveness plane.

Results

The collaborative care intervention had a mean cost of £272.50 per participant. Health and social care service use, excluding collaborative care, indicated a similar profile of resource use between collaborative care and usual care participants. Collaborative care offered a mean incremental gain of 0.02 (95% CI: –0.02, 0.06) quality-adjusted life-years over 12 months, at a mean incremental cost of £270.72 (95% CI: –202.98, 886.04), and resulted in an estimated mean cost per QALY of £14,248. Where costs associated with informal care are considered in sensitivity analyses collaborative care is expected to be less costly and more effective, thereby dominating treatment as usual.

Conclusion

Collaborative care offers health gains at a relatively low cost, and is cost-effective compared with usual care against a decision-maker willingness to pay threshold of £20,000 per QALY gained. Results here support the commissioning of collaborative care in a UK primary care setting.     

Risk Factors for Loss to Follow-Up among People Who Inject Drugs in a Risk Reduction Program at Karachi,Pakistan. A Case-Cohort Study

Introduction

Retention of male people who inject drugs (PWIDs) is a major challenge for harm reduction programs that include sterile needle/syringe exchange in resource-limited settings like Pakistan. We assessed the risk factors for loss to follow-up among male PWIDs enrolled in a risk reduction program in Karachi, Pakistan.

Methods

We conducted a prospective cohort study among 636 HIV-uninfected male PWIDs enrolled during March-June 2009 in a harm reduction program for the estimation of incidence rate. At 24 months post-enrollment, clients who had dropped out of the program were defined as lost to follow-up and included as cases for case-cohort study.

Results

The median age of the participants was 29 years (interquartile range: 23–36). Active outreach accounted for 76% (483/636) of cohort recruits. Loss to follow-up at 24 months was 25.5% (162/636). In multivariable logistic regression, younger age (AOR: 0.97, 95% CI: 0.92–0.99, p = 0.028), clients from other provinces than Sindh (AOR: 1.49, 95% CI: 1.01–2.22, p = 0.046), having no formal education (AOR: 3.44, 95% CI: 2.35–4.90, p<0.001), a history of incarceration (AOR: 1.68, 95% CI: 1.14–2.46, p<0.008), and being homeless (AOR: 1.47, 95% CI: 1.00–2.19, p<0.049) were associated with loss to follow-up.

Conclusions

Our cohort retained 74.5% of male PWIDs in Karachi for 24 months. Its loss to follow up rate suggested substantial ongoing programmatic challenges. Programmatic enhancements are needed for the highest risk male PWIDs, i.e., younger men, men not from Sindh Province, men who are poorly educated, formerly incarcerated, and/or homeless.     

Therapeutic Application of The Kokas-Method in Music Therapy for People with Severe Disabilities

The method of Klára Kokas facilitates a deep musical understanding through the repeated listening to selected short high-quality classical masterpieces. The Kokas-method offers personality-oriented complex forms of creative, artistic expressions to explore music. Participants share their emotions by the freely improvised movements of their body, which Kokas defines as dances. Kokas started her sessions with young children, but later she extended her approach to many different groups. In order to adapt to adults with severe disabilities, the original structure of the Kokas Sessions were slightly modified and adapted to the abilities and needs of the participants. This approach, which based on the bodily responds for music with spontaneous movements, forming connections between music and bodily expression, opens a new avenue in providing meaningful and enjoyable pathways of communication strengthening the sense of belonging. In addition to fulfilling their frequently forgotten aesthetic needs, these sessions help individuals with severe disabilities to develop an emotional relationship to music, reduce challenging behavior, and encourage social interactions their self-awareness thought the bodily responses to the music. The optimal multisensory environment supports their understanding, promotes their physical and emotional well-being and keeps their motivation at a high level. The close analysis of the body movements responding to music may lead to deeper understanding of their cognitive processing.     

Evaluation of Metabolic Risk in Prepubertal Girls Versus Boys in Relation to Fitness and Physical Activity

BackgroundLow levels of cardiorespiratory fitness (CRF) and physical activity (PA) are associated with a risk of the development of metabolic syndrome. Contradictory findings are reported in the literature regarding the influence of sex and CRF and PA on metabolic changes.ObjectiveThe aim of this study was to analyze the effects of CRF and PA on lipid and carbohydrate metabolism biomarkers in boys and girls.MethodsA total of 82 prepubertal boys and 55 girls (7–12 years of age) were classified according to sex, low or high CRF, and performance or nonperformance of PA. Anthropometric and blood pressure (BP) measurements, plasma lipid profile values, glucose and insulin levels, and homeostasis model assessment for insulin resistance were analyzed.ResultsThe percentage of boys with high CRF and performance of PA was higher than that of girls (P < 0.05). When children of the same sex were compared, higher values for body mass index and waist circumference z-scores were found for boys with low CRF compared with boys with high CRF (P < 0.001) without differences between girls, and in all groups classified by PA. Systolic and diastolic BPs were higher in boys than in girls, in both CRF and PA groups (P < 0.05). In the low CRF and no PA groups, girls had higher plasma glucose, total cholesterol, and low-density lipoprotein cholesterol levels than boys, with higher high-density lipoprotein cholesterol and apolipoprotein A levels (P < 0.05).ConclusionsSex in relation to CRF and PA could affect the plasma lipid profile. These changes in girls are associated with low CRF and low levels of PA. Considering these results, we suggest the need to improve CRF and promote PA, especially in girls, to reduce metabolic risk.