Innovative Approaches to Educating Future Clinicians about Opioids,Pain, Addiction and Health Policy

BackgroundOpioid use disorder and overdose have reached unprecedented levels in many countries across the globe, including the United States, and pain is one of the most common reasons American adults seek healthcare. To address the interrelated public health crises of opioid use disorder and chronic pain, it is vital that clinicians practicing in diverse roles and settings possess the ability and knowledge to effectively manage pain, responsibly prescribe and monitor opioid analgesics, educate patients about harm reduction techniques, and treat opioid use disorder. However, future healthcare professionals are not receiving the training needed to competently provide this care. This gap in curriculum may lead to clinicians being unwilling and unprepared to address the current opioid and overdose crises, which requires a clinical understanding of pain and substance use disorders as well as knowledge about public health and policy interventions. To address this gap, we designed and are teaching an innovative transdisciplinary elective course titled “Opioids: From Receptors to Epidemic” for undergraduate nursing and premedical students.AimIn this paper, we present the course curriculum in detail, with the hope that educators at other institutions will design similar courses for their health professions students.     

The metabolic syndrome: what to treat, how to treat, what are the goals?

Metabolic syndrome is a cluster of risk factors for cardiovascular disease that include obesity, atherogenic dyslipidemia, raised blood pressure, and insulin resistance. The growing trend of obesity is associated with increased prevalence of metabolic syndrome. Optimizing diet and exercise are still the leading therapy for controlling the metabolic syndrome. Based on the current evidence, further emphasis should be placed on aggressive management of other metabolic risk factors such as high blood pressure and dyslipidemia.     

Prevention of atherosclerosis

Primary prevention instituted early in life offers the most promising opportunity to affect morbidity and mortality of atherosclerosis. This conclusion is inevitable because of the sudden catastrophic nature of the first event in many patients and the demonstration of advanced pathologic changes in those who are symptomatic. There is little evidence that advanced lesions regress.A prerequisite to the achievement of the goal of primary prevention is the training of “preventive cardiologists” dedicated to accumulating new data and utilizing information now available for the design and implementation of such programs in the young. A scientific approach to primary prevention requires documentation of the basic mechanism of the cause and progression of plaque formation. This information is not presently available. However, it is now possible to identify children at high risk of premature development of complication of the disease utilizing known risk factors and their tendency to familial aggregation. A plan for identification and management of such children is outlined. As new data become available one can anticipate changes in methods of detection and management with a view toward improving results in primary prevention.     

The Israel Society for the Prevention of Alcoholism

This paper describes the profile of the Israel Society for the Prevention of Alcoholism (ISPA), which is a nation-wide, public, non-profit association. It portrays various aspects of ISPA treatment and rehabilitation facilities-the residential treatment center, the rehabilitative hostel and the 'warm home' for homeless alcoholics. It depicts ISPA prevention activities, prevention materials and its usage of the media, and deals with ISPA involvement in policy issues. The paper also addresses the research reality of ISPA and its scientific journal, and refers to the society's structure and its future.     

Performance and Limitations of Administrative Data in the Identification of AKI

Background and objectives

Billing codes are frequently used to identify AKI events in epidemiologic research. The goals of this study were to validate billing code–identified AKI against the current AKI consensus definition and to ascertain whether sensitivity and specificity vary by patient characteristic or over time.

Design, setting, participants, & measurements

The study population included 10,056 Atherosclerosis Risk in Communities study participants hospitalized between 1996 and 2008. Billing code–identified AKI was compared with the 2012 Kidney Disease Improving Global Outcomes (KDIGO) creatinine-based criteria (AKI_cr) and an approximation of the 2012 KDIGO creatinine- and urine output–based criteria (AKI_{cr_uop}) in a subset with available outpatient data. Sensitivity and specificity of billing code–identified AKI were evaluated over time and according to patient age, race, sex, diabetes status, and CKD status in 546 charts selected for review, with estimates adjusted for sampling technique.

Results

A total of 34,179 hospitalizations were identified; 1353 had a billing code for AKI. The sensitivity of billing code–identified AKI was 17.2% (95% confidence interval [95% CI], 13.2% to 21.2%) compared with AKI_cr (n=1970 hospitalizations) and 11.7% (95% CI, 8.8% to 14.5%) compared with AKI_{cr_uop} (n=1839 hospitalizations). Specificity was >98% in both cases. Sensitivity was significantly higher in the more recent time period (2002–2008) and among participants aged 65 years and older. Billing code–identified AKI captured a more severe spectrum of disease than did AKI_cr and AKI_{cr_uop}, with a larger proportion of patients with stage 3 AKI (34.9%, 19.7%, and 11.5%, respectively) and higher in-hospital mortality (41.2%, 18.7%, and 12.8%, respectively).

Conclusions

The use of billing codes to identify AKI has low sensitivity compared with the current KDIGO consensus definition, especially when the urine output criterion is included, and results in the identification of a more severe phenotype. Epidemiologic studies using billing codes may benefit from a high specificity, but the variation in sensitivity may result in bias, particularly when trends over time are the outcome of interest.     

Stochastic nanoroughness modulates neuron–astrocyte interactions and function via mechanosensing cation channels

Extracellular soluble signals are known to play a critical role in maintaining neuronal function and homeostasis in the CNS. However, the CNS is also composed of extracellular matrix macromolecules and glia support cells, and the contribution of the physical attributes of these components in maintenance and regulation of neuronal function is not well understood. Because these components possess well-defined topography, we theorize a role for topography in neuronal development and we demonstrate that survival and function of hippocampal neurons and differentiation of telencephalic neural stem cells is modulated by nanoroughness. At roughnesses corresponding to that of healthy astrocytes, hippocampal neurons dissociated and survived independent from astrocytes and showed superior functional traits (increased polarity and calcium flux). Furthermore, telencephalic neural stem cells differentiated into neurons even under exogenous signals that favor astrocytic differentiation. The decoupling of neurons from astrocytes seemed to be triggered by changes to astrocyte apical-surface topography in response to nanoroughness. Blocking signaling through mechanosensing cation channels using GsMTx4 negated the ability of neurons to sense the nanoroughness and promoted decoupling of neurons from astrocytes, thus providing direct evidence for the role of nanotopography in neuron–astrocyte interactions. We extrapolate the role of topography to neurodegenerative conditions and show that regions of amyloid plaque buildup in brain tissue of Alzheimer’s patients are accompanied by detrimental changes in tissue roughness. These findings suggest a role for astrocyte and ECM-induced topographical changes in neuronal pathologies and provide new insights for developing therapeutic targets and engineering of neural biomaterials.Cellular homeostasis in the brain tissue is believed to be regulated primarily by a complex spatiotemporal signaling environment involving soluble neurotrophic factors (1, 2). These factors, including neurotrophins such as brain-derived neurotrophic factor, the TGF-β family including bone morphogenetic proteins (BMPs), and the IL-6 superfamily including ciliary neurotrophic factor (CNTF), regulate survival, steer progenitor fate decision, and critically affect the development of the nervous system as well as the homeostasis of the adult CNS (3–6). However, developmental processes such as axon pathfinding, synapse formation, nervous system patterning, neuronal plasticity, and degeneration fail to be explained solely on the basis of soluble factors. There is increasing evidence that physical variables such as the stiffness of a cellular environment influence cell development (7–12). However, the cells of the brain tissue reside in a soft environment that is rich in polysaccharides (13, 14). In the context of neuronal development and neurophysiology, astrocytes have an established role in maintaining neuronal function. They form a vast network that provides the physical and biochemical matrix over which neurons thrive and function (15, 16). The plasticity found in the brain can be attributed in part to the morphological changes that occur in astrocyte processes that can not only alter the geometry of the neuronal environment but also induce dynamic changes in astrocyte–neuron interactions affecting neurotransmission, signal gradients, and the relationship between synapses (15). Interestingly, the changes to the physical aspects of a neuronal environment can originate from changes to morphology of support cells such as astrocytes and also changes to ECM structure and properties. Cells and ECM polysaccharides play an important role in growth, differentiation, and migration of neural precursors, as well as in repair and plasticity in the central nervous system (17, 18). However, in addition to a biological function, cells and macromolecules provide a physically defined environment (19, 20), and we postulate a significant role for topography in neural development. Studies to date have focused on the effects of microscale topography, deterministic roughness, and substrate chemistry on neurite outgrowth and neuronal function (7, 21–23). However, the influence of ECM-like nanotopography on neuronal development and fate is a realm that has not been investigated thus far. Therefore, in this work we specifically focus on the impact of stochastic nanoroughness as would be provided by neighboring cells and ECM molecules on neuronal cell interactions, function, and differentiation.     

A vaccine directed to B cells and produced by cell-free protein synthesis generates potent antilymphoma immunity

Clinical studies of idiotype (Id) vaccination in patients with lymphoma have established a correlation between the induced anti-Id antibody responses and favorable clinical outcomes. To streamline the production of an Id vaccine, we engineered a small diabody (Db) molecule containing both a B-cell-targeting moiety (anti-CD19) and a lymphoma Id. This molecule (αCD19-Id) was designed to penetrate lymph nodes and bind to noncognate B cells to form an antigen presentation array. Indeed, the αCD19-Id molecule accumulated on B cells in vivo after s.c. administration. These noncognate B cells, decorated with the diabody, could then stimulate the more rare Id-specific B cells. Peptide epitopes present in the diabody linker augmented the response by activating CD4(+) helper T cells. Consequently, the αCD19-Id molecule induced a robust Id-specific antibody response and protected animals from tumor challenge. Such diabodies are produced in a cell-free protein expression system within hours of amplification of the specific Ig genes from the B-cell tumor. This customized product can now be available to vaccinate patients before they receive other, potentially immunosuppressive, therapies.     

Detecting intraannual dietary variability in wild mountain gorillas by stable isotope analysis of feces

We use stable isotope ratios in feces of wild mountain gorillas (Gorilla beringei) to test the hypothesis that diet shifts within a single year, as measured by dry mass intake, can be recovered. Isotopic separation of staple foods indicates that intraannual changes in the isotopic composition of feces reflect shifts in diet. Fruits are isotopically distinct compared with other staple foods, and peaks in fecal δ¹³C values are interpreted as periods of increased fruit feeding. Bayesian mixing model results demonstrate that, although the timing of these diet shifts match observational data, the modeled increase in proportional fruit feeding does not capture the full shift. Variation in the isotopic and nutritional composition of gorilla foods is largely independent, highlighting the difficulty for estimating nutritional intake with stable isotopes. Our results demonstrate the potential value of fecal sampling for quantifying short-term, intraindividual dietary variability in primates and other animals with high temporal resolution even when the diet is composed of C₃ plants.     

A point-by-point response to recent arguments against the use of statins in primary prevention: this statement is endorsed by the American Society for Preventive Cardiology

Recently, a debate over the merits of statin therapy in primary prevention was published in the Wall Street Journal. The statin opponent claimed that statins should only be used in secondary prevention and never in any primary-prevention patients at risk for cardiovascular events. In this evidence-based rebuttal to those claims, we review the evidence supporting the efficacy of statin therapy in primary prevention. Cardiovascular risk is a continuum in which those at an elevated risk of events stand to benefit from early initiation of therapy. Statins should not be reserved until after a patient suffers the catastrophic consequences of atherosclerosis. Contrary to the assertions of the statin opponent, this principle has been demonstrated through reductions in heart attacks, strokes, and mortality in numerous randomized controlled primary-prevention statin trials. Furthermore, data show that once a patient tolerates the initial treatment period, the few side effects that subsequently emerge are largely reversible. Accordingly, every major guidelines committee endorses statin use in secondary prevention and selectively in primary prevention for those with risk factors. The foundation for prevention remains increased physical activity, better dietary habits, and smoking cessation. However, prevention of heart attacks, strokes, and death from cardiovascular disease does not have to be all or none-all statin or all lifestyle. In selected at-risk individuals, the combination of pharmacotherapy and lifestyle changes is more effective than either alone. Future investigation in prevention should focus on improving our ability to identify these at-risk individuals.