Young adult drug interventions: a social marketing systematic review and research agenda

Purpose This paper aims to report on the first comprehensive, social marketing systematic review of interventions targeting illicit drug use by young adults. Design/methodology/approach A total of 3,169 papers were screened, with 20 relevant empirical studies meeting the eligibility criteria for the systematic review. These were analysed according to Andreasen’s (2002) and NSMC’s (2006) social marketing benchmarks. Findings The findings provide evidence regarding the efficacy of behavioural and clinical interventions targeting individuals and groups, including motivational, life skills training, cognitive behavioural therapy, comprehensive health and social risk assessments and buprenorphine treatment interventions. Further, results evidence that there is yet to be an intervention which has implemented the full marketing mix, and limited studies have used the social marketing benchmarks of exchange and competition. Originality/value To the best of the authors’ knowledge, this study is the first to conduct a comprehensive systematic review and provide key recommendations outlining the potential for social marketing to support the improved uptake and efficacy of interventions. A research agenda is also put forward to direct future social marketing scholarship in the area of young adult drug interventions.

The Cross Marks the Spot: The Emerging Role of JmjC Domain-Containing Proteins in Myeloid Malignancies

Histone methylation tightly regulates chromatin accessibility, transcription, proliferation, and cell differentiation, and its perturbation contributes to oncogenic reprogramming of cells. In particular, many myeloid malignancies show evidence of epigenetic dysregulation. Jumonji C (JmjC) domain-containing proteins comprise a large and diverse group of histone demethylases (KDMs), which remove methyl groups from lysines in histone tails and other proteins. Cumulating evidence suggests an emerging role for these demethylases in myeloid malignancies, rendering them attractive targets for drug interventions. In this review, we summarize the known functions of Jumonji C (JmjC) domain-containing proteins in myeloid malignancies. We highlight challenges in understanding the context-dependent mechanisms of these proteins and explore potential future pharmacological targeting.

Comparative Effect of Antihypertensive Drugs in Improving Arterial Stiffness in Hypertensive Adults (RIGIPREV Study). A Protocol for Network Meta-Analysis

(1) Background: Arterial stiffness is closely and bi-directionally related to hypertension and is understood as both a cause and a consequence of hypertension. Several studies suggest that antihypertensive drugs may reduce arterial stiffness. Therefore, effective prescription of antihypertensive drugs should consider both blood pressure and arterial stiffness. The aim of this protocol is to provide a review comparing the effects of different types of antihypertensive drug interventions on the reduction of arterial stiffness in hypertensive subjects. (2) Methods: The literature search will be performed through the MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Web of Science databases. Randomised clinical trials assessing the effect of antihypertensive drug interventions on arterial stiffness measured in subjects with hypertension will be included. A frequentist network meta-analysis will be performed to determine the comparative effects of different antihypertensive drugs. (3) Results: The findings of this study will be published in a peer-reviewed journal. (4) Conclusions: This study will provide evidence for health care professionals on the efficacy of different antihypertensive drugs in decreasing arterial stiffness; in addition, it will analyse the efficacy of the drugs not only in terms of arterial stiffness but also in terms of blood pressure treatment.

Drug Delivery Challenges in Brain Disorders across the Blood–Brain Barrier: Novel Methods and Future Considerations for Improved Therapy

Due to the physiological and structural properties of the blood–brain barrier (BBB), the delivery of drugs to the brain poses a unique challenge in patients with central nervous system (CNS) disorders. Several strategies have been investigated to circumvent the barrier for CNS therapeutics such as in epilepsy, stroke, brain cancer and traumatic brain injury. In this review, we summarize current and novel routes of drug interventions, discuss pharmacokinetics and pharmacodynamics at the neurovascular interface, and propose additional factors that may influence drug delivery. At present, both technological and mechanistic tools are devised to assist in overcoming the BBB for more efficient and improved drug bioavailability in the treatment of clinically devastating brain disorders.

The Cost-Effectiveness of Non-Drug Interventions That Reduce Nursing Home Admissions for People With Dementia

Although people generally want to age in their community, individuals living with dementia are likely to move to a nursing home. In randomized trials, psychosocial interventions reduce the risk of people living with dementia transitioning to a nursing home, but the cost-effectiveness of these interventions is unknown. We used an evidence-based mathematical model to simulate a place of residence (community or nursing home) for people living with dementia. Our model also predicts time caregiving, health care costs, and quality of life. We modeled the reduction in nursing home rate (i.e., hazard ratio (HR) treatment effect) identified from two trials of non-drug interventions for people living with dementia and their caregiver. Using trial data, we account for the disease stage of when interventions are implemented. Specifically, we modeled MIND (HR: 0.63; 18-month effect), an in-home intervention for people with mild-moderate dementia, and the NYU Caregiver Intervention (HR: 0.53; 42-month effect), which is for people with moderate dementia. We evaluated each intervention’s cost-effectiveness relative to usual care for the duration of the intervention from a societal perspective. The MIND and NYU Caregiver Intervention resulted in $23,900, and $6,600 costs savings relative to usual care, respectively. The model predicted an improvement in the quality of life for people living with dementia for both interventions. The largest cost saving was attributed to reductions in family nursing home spending. Medicare and Medicaid received modest cost savings but are likely to be tasked with paying for these interventions.

Vaccination as an Alternative to Non-Drug Interventions to Prevent Local Resurgence of COVID-19

Background While a COVID-19 vaccine protects people from serious illness and death, it remains concern when and how to relax from the high cost strict non-pharmaceutical interventions (NPIs). Methods We developed a stochastic calculus model to identify the level of vaccine coverage that would allow safe relaxation of NPIs, and the vaccination strategies that can best achieve this level of coverage. We applied Monto Carlo simulations more than 10,000 times to remove random fluctuation effects and obtain fitted/predicted epidemic curve based on various parameters with 95% confidence interval (95% CI) at each time point. Results We found that a vaccination coverage of 50.42% was needed for the safe relaxation of NPIs, if the vaccine effectiveness was 79.34%. However, with the increasing of variants transmissibility and the decline of vaccine effectiveness for variants, the threshold for lifting NPIs would be higher. We estimated that more than 8 months were needed to achieve the vaccine coverage threshold in the combination of accelerated vaccination strategy and key groups firstly strategy. Conclusion If there are sufficient doses of vaccine then an accelerated vaccination strategy should be used, and if vaccine supply is insufficient then high-risk groups should be targeted for vaccination first. Sensitivity analyses results shown that the higher the transmission rate of the virus and the lower annual vaccine supply, the more difficult the epidemic could be under control. In conclusion, as vaccine coverage improves, the NPIs can be gradually relaxed. Until that threshold is reached, however, strict NPIs are still needed to contain the epidemic. The more transmissible SARS-CoV-2 variant lead to higher resurgence probability, which indicates the importance of accelerated vaccination and achieving the vaccine coverage earlier. Trial registration We did not involve clinical trial.

Changes in Quality-of-Life Parameters in Patients Receiving Therapeutic Interventions for Cancer-Associated Anemia: A Systematic Review

Introduction: Cancer-associated anemia (CAA) is multifactorial in etiology and can occur due to the malignancy itself or as a side effect of the treatment. The prevalence of CAA can exceed 90%. Several studies have reported positive correlations between increased hemoglobin (Hb) and improved health-related quality of life (HR-QoL) measures including fatigue scores and scores for physical, mental and social well-being. However, Hb increases and extent of improvement in HR-QoL measures varied by therapeutic interventions (Oral/intravenous iron, erythropoietin stimulating agents (ESAs), transfusions, and/or others), as did HR-QoL tools used in these studies. We conducted a systematic review to identify final target Hb levels as well as changes in Hb from baseline that resulted in significant improvement in HR-QoL parameters following interventions for CAA. We also sought to identify HR-QoL tools that effectively and comprehensively captured symptomatic improvement following Hb increases in patients with CAA. Methods: Randomized Controlled Trials (RCTs) and prospective studies which evaluated HR-QoL changes following drug interventions for CAA were identified through searches of the CINAHL Plus, Embase, PubMed, and Web of Science for articles in English from 1997-2021. Inclusion criteria were: RCT or prospective study; patients with CAA; a HR-QoL was used. Two reviewers independently screened abstracts. A third reviewer resolved disagreements. Bias assessment was performed using Joanna Briggs checklist. Results: Of the 8243 studies identified of which 1718 were duplicates and 6525 records were screened at the title and abstract level. Of the 59 full text articles reviewed, 38 articles met our eligibility criteria (Figure 1). A total of 19 RCTs and 19 prospective studies were identified. On average, studies were conducted over 14.2 ± 5.5 weeks, with a mean of 546 ± 693 study participants in each study. 23 studies provided information on the number of enrolled participants completing study. Mean study completion rates among participants was 70 ± 1 (%). A summary of HR-QoL measures utilized in the various studies is presented in Table 1. Hb changes and HR-QoL score changes were reported consistently in 30 studies and are presented in Table 2. Therapeutic interventions for CAA included ESAs (n=19; 65.5%), Oral/IV iron (n=1; 3.4%); transfusions (n=2; 6.9%), other agents used in specific conditions (luspatercept (MDS)) n=1; 3.3%, or combinations of these (n=7; 24.1%). Overall, 78% of studies that reported an Hb increase following drug interventions for CAA also reported an improvement in HR-QoL measures. Mean Hb increases was 1.9 g/dL. Median change in the most frequently used HR-QoL (FACT-An, FACT-F) was +3 points (Range: 0-4). Studies utilizing transfusions as the intervention for CAA reported the lowest final Hb (8.8 gm/dL) as well as the lowest change in Hb (Δ Hb= 1gm/dL) levels from study onset to completion. These studies also reported the least improvements in HR-QoL scores. HR-QoL tools used in transfusion-based studies were variable. With regard to other outcomes measured in the various studies, raising Hb levels by various interventions did not significantly impact bleeding scores, infections, hospitalizations, or mortality. Conclusions: Our data suggest the need to identify optimum Hb thresholds (final target Hb levels as well as changes in Hb levels from baseline) that result in meaningful improvements in HR-QoL parameters following the use of any therapeutic intervention for CAA. Specifically, studies utilizing transfusions alone as intervention for CAA may not reach the optimum threshold (>11gm/dL or a Δ Hb of greater than 2 gm/dL) to result in meaningful improvements in HR-QoL measures as has been shown in studies utilizing ESAs or iron or a combination of these agents. Further, it is imperative for studies in transfusion medicine to identify appropriate HR-QoL tool/s that comprehensively capture all aspects of well-being related to CAA. As such, studies may need to utilize more than one HR-QoL tool that gathers information on physical, social and emotional well-being before and after transfusions, while balancing the risk of questionnaire fatigue. A meta-analysis of our systematic review is ongoing and will provide additional information on data gathered thus far. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Effect of drug interventions on cerebral haemodynamics in ischaemic stroke patients

The ischaemic penumbra is sensitive to alterations in cerebral perfusion. A myriad of drugs are used in acute ischaemic stroke (AIS) management, yet their impact on cerebral haemodynamics is poorly understood. As part of the Cerebral Autoregulation Network led INFOMATAS project ( Identifying New Targets for Management and Therapy in Acute Stroke), this paper reviews some of the most common drugs a patient with AIS will come across and their potential influence on cerebral haemodynamics with a particular focus being on cerebral autoregulation (CA). We first discuss how compounds that promote clot lysis and prevent clot formation could potentially impact cerebral haemodynamics, before focusing on how the different classes of antihypertensive drugs can influence cerebral haemodynamics. We discuss the different properties of each drug and their potential impact on cerebral perfusion and CA. With emerging interest in CA status of AIS patients, either during or soon after treatment when timely reperfusion and salvageable tissue is at its most critical, the properties of these pharmacological agents may be relevant for modelling cerebral perfusion accuracy and for setting individualised treatment strategies.

Is glucose-6-phosphatase dehydrogenase deficiency associated with severe outcomes in hospitalized COVID-19 patients?

Glucose-6-phosphate dehydrogenase deficiency (G6PDd) is known to suppress the antioxidant system and is likely to aggravate severity of COVID-19, which results in a pro-oxidant response. This possible association has not been explored adequately in human studies. In this research, we report that the occurrence of non-invasive ventilation, intubation or death—all of which are indicative of severe COVID-19, are not significantly different in hospitalized COVID-19 patients with and without G6PDd (4.6 vs. 6.4%, p = 0.33). The likelihood of developing any of these severe outcomes were slightly lower in patients with G6PDd after accounting for age, nationality, presence of comorbidities and drug interventions (Odds ratio 0.40, 95% confidence intervals 0.142, 1.148). Further investigation that extends to both, hospitalized and non-hospitalized COVID-19 patients, is warranted to study this potential association.

Robust Reductions of Body Weight and Food Intake by an Oxytocin Analog in Rats

Background: Oxytocin is a hypothalamic neuropeptide that participates in the network of appetite regulation. Recently the oxytocin signaling pathway has emerged as an attractive target for treating obesity. However, the short half-life limits its development as a clinical therapeutic. Here we provide results from testing a long-lasting, potent and selective oxytocin analog ASK1476 on its efficacy to reduce food intake and body weight in comparison to the native oxytocin peptide.Methods: ASK1476 features two specific amino acid substitutions in positions 7 and 8 combined with a short polyethylene glycol spacer. Short time dose escalation experiments testing increasing doses of 3 days each were performed in diet-induced overweight (DIO) male rats assessing effects on body weight as well as changes in food intake. Furthermore, DIO rats were tested for changes in body weight, food intake, temperature, and locomotor activity over 28 days of treatment (oxytocin, ASK1476, or vehicle).Results: In dose escalation experiments, significant reductions in food intake relative to baseline were detected beginning with doses of 15 nmol/kg ASK1476 (−15.2 ± 2.3 kcal/d, p = 0.0017) and 20 nmol/kg oxytocin (−11.2.9 ± 2.4 kcal/d, p = 0.0106) with corresponding significant changes in body weight (ASK1476: −5.2 ± 0.8 g, p = 0.0016; oxytocin: −2.6 ± 0.7 g, p = 0.0326). In long-term experiments, there was no difference on body weight change between 120 nmol/kg/d ASK1476 (−71.4 ± 34.2 g, p = 0.039) and 600 nmol/kg/d oxytocin (−91.8 ± 32.2 g, p = 0.035) relative to vehicle (706.9 ± 28.3 g), indicating a stronger dose response for ASK1476. Likewise, both ASK1476 and oxytocin at these doses resulted in similar reductions in 28-day cumulative food intake (ASK1476: −562.7 ± 115.0 kcal, p = 0.0001; oxytocin: −557.1 ± 101.3 kcal, p = 0.0001) relative to vehicle treatment (2716 ± 75.4 kcal), while no effects were detected on locomotor activity or body temperature.Conclusion: This study provides proof-of-concept data demonstrating an oxytocin analog with extended in vivo stability and improved potency to reduce food intake and body weight in DIO animals which could mark a new avenue in anti-obesity drug interventions.