Intermittent theta burst stimulation and functional connectivity in people living with HIV/AIDS who smoke tobacco cigarettes: a preliminary pilot study.

Background: People living with HIV (PLWHA) smoke at three times the rate of the general population and respond poorly to cessation strategies. Previous studies examined repetitive transcranial magnetic stimulation (rTMS) over left dorsolateral prefrontal cortex (L. dlPFC) to reduce craving, but no studies have explored rTMS among PLWHA who smoke. The current pilot study compared the effects of active and sham intermittent theta-burst stimulation (iTBS) on resting state functional connectivity (rsFC), cigarette cue attentional bias, and cigarette craving in PLWHA who smoke. Methods: Eight PLWHA were recruited (single-blind, within-subject design) to receive one session of iTBS (n=8) over the L. dlPFC using neuronavigation and, four weeks later, sham iTBS (n=5). Cigarette craving and attentional bias assessments were completed before and after both iTBS and sham iTBS. rsFC was assessed before iTBS (baseline) and after iTBS and sham iTBS. Results: Compared to sham iTBS, iTBS enhanced rsFC between the L. dlPFC and bilateral medial prefrontal cortex and pons. iTBS also enhanced rsFC between the right insula and right occipital cortex compared to sham iTBS. iTBS also decreased cigarette craving and cigarette cue attentional bias. Conclusion: iTBS could potentially offer a therapeutic option for smoking cessation in PLWHA.

Comparing cigarette-cue attentional bias between people with HIV/AIDS and people with opioid use disorder who smoke.

Background: Special populations like people living with HIV/AIDS (PLWHA) and people with opioid use disorder (OUD) smoke tobacco cigarettes at rates three to four times greater than the general population. Patients with tobacco use disorder exhibit attentional bias (AB) for cigarette cues. Eye tracking can quantify this bias by measuring fixation time (FT) on cigarette and matched neutral cues, to calculate an AB score. Although previous studies have measured this bias in people who smoke without any other comorbid conditions, no study, to our knowledge, has measured or compared this bias in special populations. Methods: We performed exploratory analyses on eye tracking data collected in two separate randomized clinical trials (RCTs) (NCT05049460, NCT05295953). We compared FT and cigarette-cue AB score (measured by subtracting FT on neutral cues from FT on cigarette cues) between PLWHA and people with OUD who smoke, using a visual probe task and Tobii Pro Fusion eye tracker. We used two cigarette cue types, one encompassing people smoking cigarettes and the other consisting of cigarette paraphernalia. We used two cue presentation times, 1000 and 2000 milliseconds (ms). Results: Cues of people smoking cigarettes elicited greater AB than cues of cigarette paraphernalia across both subject groups when cues were presented for 2000 ms, but not 1000 ms. PLWHA who smoke exhibited greater AB for cues of people smoking cigarettes than cigarette paraphernalia when presented for 2000 ms compared to people with OUD who smoke. Conclusion: We use cigarette-cue AB to quantify craving and cigarette consumption in two populations smoking at elevated rates. The addition of social cues potentiates cigarette cue AB, based on cue type and stimulus presentation time. Understanding the neurobiology of this relationship can help design novel smoking cessation treatments that target AB and prevent relapse in these populations with suboptimal response to smoking cessation treatments. Trial registration: Clinical trials that provided the data for post hoc analyses are NCT05049460 and NCT05295953.

Protocol for expression of murine milk using modified human breast pump parts.

Understanding the nutritional and immunomodulatory components of breast milk is crucial to developing novel mechanisms to optimize neonatal health. Here, we present a protocol to express and isolate murine milk in sufficient quantities for further analysis of components and bioactivity. We describe steps for separating dams from pups, administering intraperitoneal anesthetic and oxytocin, and expressing milk using a minimally modified and readily available commercial breast pump parts. For complete details on the use and execution of this protocol, please refer to Meyer et al. (2022).1.

Surfactant protein a attenuates generalized and localized neuroinflammation in neonatal mice.

Surfactant protein A (SP-A) has important roles in innate immunity and modulation of pulmonary and extrapulmonary inflammation. Given SP-A has been detected in rat and human brain, we sought to determine if SP-A has a role in modulating inflammation in the neonatal mouse brain. Neonatal wildtype (WT) and SP-A-deficient (SP-A-/-) mice were subjected to three models of brain inflammation: systemic sepsis, intraventricular hemorrhage (IVH) and hypoxic-ischemic encephalopathy (HIE). Following each intervention, RNA was isolated from brain tissue and expression of cytokine and SP-A mRNA was determined by real-time quantitative RT-PCR analysis. In the sepsis model, expression of most cytokine mRNAs was significantly increased in brains of WT and SP-A-/- mice with significantly greater expression of all cytokine mRNA levels in SP-A-/- mice compared to WT. In the IVH model, expression of all cytokine mRNAs was significantly increased in WT and SP-A-/- mice and levels of most cytokine mRNAs were significantly increased in SP-A-/- mice compared to WT. In the HIE model, only TNF-α mRNA levels were significantly increased in WT brain tissue while all pro-inflammtory cytokine mRNAs were significantly increased in SP-A-/- mice, and all pro-inflammatory cytokine mRNA levels were significantly higher in SP-A-/- mice compared to WT. SP-A mRNA was not detectable in brain tissue of adult WT mice nor in WT neonates subjected to these models. These results suggest that SP-A-/- neonatal mice subjected to models of neuroinflammation are more susceptible to both generalized and localized neuroinflammation compared to WT mice, thus supporting the hypothesis that SP-A attenuates inflammation in neonatal mouse brain.

Naltrexone-bupropion combinations do not affect cocaine self-administration in humans.

The FDA has not yet approved a pharmacotherapy for cocaine use disorder despite nearly four decades of research. This study determined the initial efficacy, safety, and tolerability of naltrexone-bupropion combinations as a putative pharmacotherapy for cocaine use disorder. Thirty-one (31) non-treatment seeking participants with cocaine use disorder completed a mixed-design human laboratory study. Participants were randomly assigned to the naltrexone conditions (i.e., 0, 50 mg/day; between-subject factor) and maintained on escalating doses of bupropion (i.e., 0, 100, 200, 400 mg/day; within-subject factor) for at least four days prior to the conduct of experimental sessions. Cocaine self-administration (IN, 0, 40, 80 mg) was then determined using a modified progressive ratio and relapse procedure. Subjective and cardiovascular effects were also measured. Cocaine produced prototypical dose-related increases in self-administration, subjective outcomes (e.g., "Like Drug"), and cardiovascular indices (e.g., heart rate, blood pressure) during placebo maintenance. Naltrexone and bupropion alone, or in combination, did not significantly decrease self-administration on either procedure. Low doses of bupropion (i.e., 100 mg) blunted the effects of the cocaine on subjective measures of "Like Drug" and "Stimulated". No unexpected adverse effects were observed with naltrexone and bupropion, alone and combined, in conjunction with cocaine. Together, these results do not support the use of these bupropion-naltrexone combinations for the treatment of cocaine use disorder. Future research should determine if novel drug combinations may decrease cocaine self-administration.

A phase II, multicenter, open-label, randomized trial of pegfilgrastim for patients with alcohol-associated hepatitis.

Background: In trials conducted in India, recombinant granulocyte colony stimulating factor (GCSF) improved survival in alcohol-associated hepatitis (AH). The aim of this trial was to determine the safety and efficacy of pegfilgrastim, a long-acting recombinant GCSF, in patients with AH in the United States. Methods: This prospective, randomized, open label trial conducted between March 2017 and March 2020 randomized patients with a clinical diagnosis of AH and a Maddrey discriminant function score ≥32 to standard of care (SOC) or SOC+pegfilgrastim (0.6 mg subcutaneously) on Day 1 and Day 8 (clinicaltrials.gov NCT02776059). SOC was 28 days of either pentoxifylline or prednisolone, as determined by the patient's primary physician. The second injection of pegfilgrastim was not administered if the white blood cell count exceeded 30,000/mm3 on Day 8. Primary outcome was survival at Day 90. Secondary outcomes included the incidence of acute kidney injury (AKI), hepatorenal syndrome (HRS), hepatic encephalopathy, or infections. Findings: The study was terminated early due to COVID19 pandemic. Eighteen patients were randomized to SOC and 16 to SOC+pegfilgrastim. All patients received prednisolone as SOC. Nine patients failed to receive a second dose of pegfilgrastin due to WBC > 30,000/mm3 on Day 8. Survival at 90 days was similar in both groups (SOC: 0.83 [95% confidence interval [CI]: 0.57-0.94] vs. pegfilgrastim: 0.73 [95% CI: 0.44-0.89]; p > 0.05; CI for difference: -0.18-0.38). The incidences of AKI, HRS, hepatic encephalopathy, and infections were similar in both treatment arms and there were no serious adverse events attributed to pegfilgrastim. Interpretation: This phase II trial found no survival benefit at 90 days among subjects with AH who received pegfilgrastim+prednisolone compared with subjects receiving prednisolone alone. Funding: was provided by the United States National Institutes of Health and National Institute on Alcohol Abuse and Alcoholism U01-AA021886 and U01-AA021884.

Impact of Surfactant Protein-A on Immunomodulatory Properties of Murine and Human Breast Milk.

OBJECTIVES: Human milk reduces the incidence of necrotizing enterocolitis (NEC). Prior studies have demonstrated that exogenous surfactant protein-A (SP-A) modulates intestinal inflammation, reduces NEC-like pathology in SP-A-deficient (SPAKO) pups, and may contribute to breast milk's immunomodulatory potential. We hypothesize that SP-A is present in milk and impacts inflammatory responses in the terminal ileum of neonatal mice. METHODS: Human milk was collected at postpartum days 1-3 and 28. Mouse milk was collected at postpartum days 1-10. SP-A was detected in milk through immunoprecipitation and western blot analysis. The impact of murine wild-type (WT) milk on SPAKO pup ileum was evaluated in a model of intestinal inflammation via cross-rearing experiments. Terminal ileum was evaluated for inflammatory cytokine and toll-like receptor 4 (TLR4) mRNA expression via quantitative real-time RT-PCR. RESULTS: SP-A was detected in human milk and wild type (WT) mouse milk, but not in SPAKO mouse milk. Expression of TLR4, interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α was decreased in SPAKO pups reared with WT dams compared to SPAKO pups reared with SPAKO dams, with a peak effect at day of life 14. When inflammation was induced using a lipopolysaccharide-induced model of inflammation, expression of TLR4, IL-1ß, IL-6, CXCL-1, and TNF-α was significantly lower in SPAKO pups reared with WT dams compared to SPAKO pups reared with SPAKO dams. CONCLUSIONS: SP-A is present in human and murine milk and plays a role in lowering inflammation in murine pup terminal ileum. Both baseline inflammation and induced inflammatory responses are reduced via exposure to SP-A in milk with the effect amplified in inflammatory conditions.

Influence of pregabalin maintenance on cannabis effects and related behaviors in daily cannabis users.

No medications are approved for cannabis use disorder (CUD), though a small clinical trial demonstrated that the voltage-dependent calcium channel (VDCC) ligand gabapentin reduced cannabis use in treatment seekers. VDCCs are modulated by cannabinoid (CB) ligands, and there are shared effects between CB agonists and VDCC ligands. This overlapping neuropharmacology and the initial clinical results supported the evaluation of pregabalin, a "next-generation" VDCC ligand, as a CUD medication. Two separate placebo-controlled, double-blind, counterbalanced, within-subjects human laboratory studies tested placebo and 300 (N = 2 females, 11 males; Experiment [EXP] 1) or 450 (N = 3 females, 11 males; EXP 2) mg/day pregabalin in cannabis users who were not seeking treatment or trying to reduce/quit their cannabis use. The protocol consisted of two outpatient maintenance phases (11 days in EXP 1 and 15 days in EXP 2) that concluded with four experimental sessions within each phase. During experimental sessions, maintenance continued, and participants completed two 2-day blocks of sampling and self-administration sessions to determine the reinforcing effects of smoked cannabis (0% and 5.9% delta9-tetrahydrocannabinol [THC]), as well as subjective, attentional bias, performance, and physiological responses. In addition, naturalistic cannabis use, side effects, sleep quality, craving, and other self-reported substance use were measured during pregabalin maintenance. Cannabis was self-administered and produced prototypical effects, but pregabalin generally did not impact the effects of cannabis or alter naturalistic use. These human laboratory results in cannabis users not trying to reduce/quit their use do not support the efficacy of pregabalin as a stand-alone pharmacotherapy for CUD. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Cytotoxic Lactalbumin-Oleic Acid Complexes in the Human Milk Diet of Preterm Infants.

Frozen storage is necessary to preserve expressed human milk for critically ill and very preterm infants. Milk pasteurization is essential for donor milk given to this special population. Due to these storage and processing conditions, subtle changes occur in milk nutrients. These changes may have clinical implications. Potentially, bioactive complexes of unknown significance could be found in human milk given to preterm infants. One such complex, a cytotoxic α-lactalbumin-oleic acid complex named "HAMLET," (Human Alpha-Lactalbumin Made Lethal to Tumor cells) is a folding variant of alpha-lactalbumin that is bound to oleic acid. This complex, isolated from human milk casein, has specific toxicity to both carcinogenic cell lines and immature non-transformed cells. Both HAMLET and free oleic acid trigger similar apoptotic mechanisms in tissue and stimulate inflammation via the NF-κB and MAPK p38 signaling pathways. This protein-lipid complex could potentially trigger various inflammatory pathways with unknown consequences, especially in immature intestinal tissues. The very preterm population is dependent on human milk as a medicinal and broadly bioactive nutriment. Therefore, HAMLET's possible presence and bioactive role in milk should be addressed in neonatal research. Through a pediatric lens, HAMLET's discovery, formation and bioactive benefits will be reviewed.

A primate-specific RNA-binding protein (RBMXL3) is involved in glucocorticoid regulation of human pulmonary surfactant protein B (SP-B) mRNA stability.

The ability of pulmonary surfactant to reduce alveolar surface tension requires adequate levels of surfactant protein B (SP-B). Dexamethasone (DEX) increases human SP-B expression, in part, through increased SP-B mRNA stability. A 30-nt-long hairpin element (RBE) in the 3'-untranslated region of human SP-B mRNA mediates both DEX-induced and intrinsic mRNA stabilities, but the mechanism is unknown. Proteomic analysis of RBE-interacting proteins identified a primate-specific protein, RNA-binding motif X-linked-like-3 (RBMXL3). siRNA directed against RBMXL3 reduces DEX-induced SP-B mRNA expression in human bronchoalveolar cells. Human SP-B mRNA stability, measured by our dual cistronic plasmid assay, is unaffected by DEX in mouse lung epithelial cells lacking RBMXL3, but DEX increases human SP-B mRNA stability when RBMXL3 is expressed and requires the RBE. In the absence of DEX, RBE interacts with cellular proteins, reducing intrinsic SP-B mRNA stability in human and mouse lung epithelial cells. RBMXL3 specifically binds the RBE in vitro, whereas RNA immunoprecipitation and affinity chromatography analyses indicate that binding is enhanced in the presence of DEX. These results describe a model where intrinsic stability of human SP-B mRNA is reduced through binding of cellular mRNA decay factors to RBE, which is then relieved through DEX-enhanced binding of primate-specific RBMXL3.

Surfactant protein A reduces TLR4 and inflammatory cytokine mRNA levels in neonatal mouse ileum.

Levels of intestinal toll-like receptor 4 (TLR4) impact inflammation in the neonatal gastrointestinal tract. While surfactant protein A (SP-A) is known to regulate TLR4 in the lung, it also reduces intestinal damage, TLR4 and inflammation in an experimental model of necrotizing enterocolitis (NEC) in neonatal rats. We hypothesized that SP-A-deficient (SP-A-/-) mice have increased ileal TLR4 and inflammatory cytokine levels compared to wild type mice, impacting intestinal physiology. We found that ileal TLR4 and proinflammatory cytokine levels were significantly higher in infant SP-A-/- mice compared to wild type mice. Gavage of neonatal SP-A-/- mice with purified SP-A reduced ileal TLR4 protein levels. SP-A reduced expression of TLR4 and proinflammatory cytokines in normal human intestinal epithelial cells (FHs74int), suggesting a direct effect. However, incubation of gastrointestinal cell lines with proteasome inhibitors did not abrogate the effect of SP-A on TLR4 protein levels, suggesting that proteasomal degradation is not involved. In a mouse model of experimental NEC, SP-A-/- mice were more susceptible to intestinal stress resembling NEC, while gavage with SP-A significantly decreased ileal damage, TLR4 and proinflammatory cytokine mRNA levels. Our data suggests that SP-A has an extrapulmonary role in the intestinal health of neonatal mice by modulating TLR4 and proinflammatory cytokines mRNA expression in intestinal epithelium.

Surfactant Protein A and Microbiome Composition in Patients With Atraumatic Intraoral Lesions.

Oral ulcers are lesions that occur due to disruption of epithelial integrity of the mucosa of the oral cavity. Intraoral ulcers are often associated with pain, redness, symptoms of discomfort, and blood hemorrhage. The etiology for many oral ulcers is local trauma, systemic health conditions, or medication; for other ulcers the cause is less clear. This pilot study aims to evaluate the salivary components and microbiome in patients with atraumatic pre-ulcerous and ulcerous oral lesions compared to control individuals, while considering three common risk factors for atraumatic ulcers, smoking, stress, and gender. This study uses matched age, sex, and ethnicity samples from healthy otherwise and oral lesion patients to investigate the changes in salivary surfactant protein A (SP-A) and examines the prevalence and diversity of the salivary oral microflora. The goal is to determine if there are factors in saliva that have the potential to be used as biomarkers for risk of developing atraumatic oral ulcers. Our data show that the average level of SP-A is significantly reduced in female smokers compared to non-smoker healthy females. The average level of SP-A in female oral lesion patients is reduced compared to controls. The microbiome composition is significantly affected by smoking and the level of SP-A. Comparing the control participants and oral lesion patients, there are 16 species of bacteria that are significantly different, and all of these bacteria are significantly affected by smoking and SP-A. LEfSe analysis identified five bacteria that may represent potential biomarkers. This preliminary study demonstrates the potential of the oral microbiome to act as a biomarker for oral ulcer risk and infers potential mechanistic links between risk factors and alterations in innate immune mechanisms such as SP-A levels.

Topiramate-phentermine combinations reduce cocaine self-administration in humans.

RATIONALE: Cocaine use disorder is an unrelenting public health concern. Despite nearly four decades of research, an FDA approved medication is not yet available. OBJECTIVES: The objective of this human laboratory study was to demonstrate the initial efficacy, safety and tolerability of topiramate-phentermine combinations for cocaine use disorder. METHODS: Thirty-one (31) participants with cocaine use disorder completed this mixed-model inpatient laboratory study. Participants were maintained on topiramate (0 [N = 11], 50 [N = 9] or 100 [N = 11] mg/day). Each topiramate group was concurrently maintained on phentermine (0, 15, 30 mg). Drug self-administration, subjective responses and cardiovascular effects following acute doses of intranasal cocaine (0, 40, 80 mg) were determined during separate experimental sessions after at least seven (7) days of maintenance on each condition. RESULTS: The three groups of participants were well matched demographically and generally did not differ significantly in their responses to a range of doses of intranasal cocaine (0, 10, 20, 40, 80 mg) during a medical safety session. Maintenance on topiramate and phentermine alone significantly decreased cocaine self-administration although these effects were modest in magnitude. Combining topiramate and phentermine robustly decreased cocaine self-administration. Topiramate and phentermine were well tolerated alone and combined, as well as in conjunction with cocaine. CONCLUSIONS: The results of the present study support advancing topiramate-phentermine combinations as a putative pharmacotherapeutic for cocaine use disorder.

An internal amino-terminal FLAG-tag octapeptide alters oligomerization of expressed surfactant protein-A.

Pulmonary surfactant protein-A (SP-A) is expressed by lung alveolar and bronchiolar epithelial cells and plays a critical role in innate immunity of the lung. Exposure of the lung to various environmental insults alters SP-A homeostasis. To investigate the cellular mechanisms involved in these alterations, we added the FLAG octapeptide (DYKDDDDK) to the carboxy-terminus (SP-A/C-FLAG) or near the amino-terminus (SP-A/N-FLAG) of mouse SP-A (WT-SP-A) to tag specific pools of protein. We hypothesized that addition of FLAG would have negligible effects on SP-A expression, oligomerization and secretion. Analysis of Chinese hamster ovary cells expressing these proteins indicated that tagged SP-A mRNA could be distinguished from WT-SP-A by northern analysis and RT-PCR using sequence-specific oligonucleotides. Tagged SP-A protein could be differentiated from WT-SP-A by western analysis using antibodies specific for the FLAG epitope. Subcellular fractionation and immunocytochemistry indicated the majority of each protein was present in punctuate (presumably endocytic) vesicles, and all forms of SP-A protein were secreted. These results suggest that a FLAG epitope added to the carboxy-terminus or inserted into the amino-terminus of the mature SP-A protein has little effect on its expression and cellular processing. However, disruptions of the amino-terminal end of SP-A prevents proper oligomerization, suggesting that this region of mature SP-A is critical in proper oligomeric assembly and is not useful for studies intended to define mechanisms underlying SP-A homeostasis.

Acute methylphenidate administration reduces cocaine-cue attentional bias.

Mechanistic research on behavioral processes underlying substance use disorder might help identify novel targets for interventions development. Drug-related attentional bias and response inhibition deficits have received a great deal of consideration in substance use research, broadly, and cocaine use research, specifically. Studies investigating pharmacological mechanisms that may ameliorate, or further impair, these behaviors relevant to cocaine use are relatively lacking. This study evaluated the impact of acute administration of methylphenidate, a dopamine-favoring reuptake inhibitor, on both gaze-related cocaine-cue-attentional bias and cocaine-cue related disruptions in response inhibition among individuals with cocaine use disorder. Participants (N = 12; 33% female) completed a within-subject, outpatient, acute dosing study. Two sessions were completed in which methylphenidate (60 mg) or placebo were administered followed by completion of an attentional bias task using eye-tracking technology and neutral-cue and cocaine-cue response inhibition tasks. Subjective and physiological effects were also recorded. Significant cocaine cue attentional bias and response inhibition failures were observed during placebo administration. Acute methylphenidate administration reduced cocaine-cue attentional bias as measured by cocaine-cue gaze fixations (dz = 1.04; Bayes Factor = 12.37). No statistically significant effects of methylphenidate were observed on response inhibition (Bayes Factors = 0.17-1.04). Methylphenidate produced prototypical subjective and physiological effects. Although the small sample should be considered, these findings indicate acute manipulation of dopaminergic activity reduced cue-related attentional allocation related to cocaine use disorder. Future research evaluating alternative dopaminergic agents and applications within a clinical setting are needed to determine the clinical significance of targeting this neurobehavioral mechanism.

A Survey Study of Self-Rated Patients' Knowledge About AKI in a Post-Discharge AKI Clinic.

BACKGROUND: Survivors of acute kidney injury (AKI) are at risk of adverse outcomes. Post-discharge nephrology care may improve patients' AKI knowledge and prevent post-AKI complications. OBJECTIVE: The purpose of this study was to examine patients' awareness about their AKI diagnosis and self-rated knowledge and severity of AKI before and after their first post-discharge AKI Clinic encounter. DESIGN: We conducted a pre- and post-survey study among AKI survivors who attended a post-discharge AKI Clinic. SETTING: AKI Clinic at the University of Kentucky Medical Center (October 2016 to December 2017). Education about AKI was based on transformative learning theory and provided through printed materials and interdisciplinary interactions between patients/caregivers and nurses, pharmacists, and nephrologists. PATIENTS: A total of 104 patients completed the survey and were included in the analysis. MEASUREMENTS: Three survey questions were administered before and after the first AKI Clinic encounter: Question 1 (yes-no) for awareness, and questions 2 and 3 (Likert scale, 1 = lowest to 5 = highest) for self-rated knowledge and severity of AKI. METHODS: Two mixed-model analysis of variance (ANOVA) was used for between-group (AKI severity) and within-group (pre- and post-encounter) comparisons. Logistic regression was used to examine parameters associated with the within-group change in self-perceived knowledge. RESULTS: Twenty-two out of 104 (21%) patients were not aware of their AKI diagnosis before the clinic encounter. Patients' self-ratings of their AKI knowledge significantly increased after the first AKI Clinic encounter (mean ± SEM: pre-visit = 1.94 ± 0.12 to post-visit = 3.88 ± 0.09, P = .001), even after adjustment for age, gender, Kidney Disease Improving Global Outcomes (KDIGO) severity stage, or poverty level. Patients with AKI stage 3 self-rated their AKI as more severe than patients with AKI stage 1 or 2. LIMITATIONS: Our study population may not be representative of the general AKI survivor population. Administered surveys are subject to response-shift bias. CONCLUSIONS: Patients' self-perceived knowledge about AKI significantly increased following the first post-discharge AKI Clinic encounter that included interdisciplinary education. This is the first survey study examining self-perceived AKI knowledge in AKI survivors. Further examination of AKI literacy in survivors of AKI and its effect on post-AKI outcomes is needed. TRIAL REGISTRATION: Not applicable.

CONTEXTE: Les survivants d'un épisode d'insuffisance rénale aiguë (IRA) risquent de souffrir de pathologies associées. Un suivi en néphrologie après la sortie de l'hôpital pourrait accroître les connaissances des patients sur la maladie et prévenir les complications. OBJECTIF: L'étude était bipartite : i) savoir si les patients connaissaient leur diagnostic; ii) mesurer, par auto-évaluation, les connaissances des patients sur l'IRA et sur sa gravité, avant et après une consultation dans une clinique d'IRA. TYPE D'ÉTUDE: Un sondage mené auprès de survivants d'un épisode d'IRA, avant et après une consultation en clinique d'IRA suivant leur congé de l'hôpital. CADRE: La clinique d'IRA du centre médical de l'université du Kentucky (d'octobre 2016 à décembre 2017). L'information fournie suivait la théorie de l'apprentissage transformationnel et était transmise sous forme de documents imprimés et d'interactions interdisciplinaires entre les patients/fournisseurs de soins et les infirmières, les pharmaciens et les néphrologues. PARTICIPANTS: L'étude porte sur 104 patients ayant complété le sondage. MESURES: Trois questions ont été posées aux patients avant et après une première consultation à la clinique. Une question portait sur leur connaissance du diagnostic (oui -non) et deux autres auto-évaluaient leurs connaissances sur l'IRA et sa gravité (échelle de Likert, de 1 [plus faible] à 5 [plus élevé]). MÉTHODOLOGIE: Deux modèles mixtes d'analyse de variance ont été employés pour établir des comparaisons inter-groupes (gravité de l'IRA) et intra-groupes (pré et post-consultation). Une régression logistique a été utilisée pour analyser les paramètres associés aux changements du niveau auto-évalué des connaissances dans un même groupe. RÉSULTATS: Des 104 patients inclus à l'étude, 22 (21 %) ignoraient leur diagnostic d'IRA avant la consultation. L'auto-évaluation des connaissances a augmenté après la première consultation (moyenne ± SEM : 1,94 ± 0,12 [pré-visite]; 3,88 ± 0,09 [post-visite], p=0,001) et ce, même après les ajustements en regard de l'âge et du sexe du patient, du stade de la maladie selon le KDIGO (Kidney Disease Improving Global Outcomes) ou du niveau de revenus. Les patients atteints d'une IRA de stade 3 ont davantage surévalué la gravité de leur maladie que les patients de stades 1 ou 2. LIMITES: La population étudiée pourrait ne pas être représentative de la population générale des survivants d'un épisode d'IRA. Les sondages sont sujets aux biais liés aux changements de réponses. CONCLUSION: L'auto-évaluation des connaissances a augmenté significativement après une première consultation à la clinique d'IRA lorsque celle-ci incluait de l'information interdisciplinaire. Il s'agit de la première étude portant sur l'auto-évaluation des connaissances de survivants d'un épisode d'IRA. Il est nécessaire d'examiner davantage la littératie de l'IRA chez les survivants de la maladie et ses effets sur les pathologies qui en découlent.

Influence of phendimetrazine maintenance on the reinforcing, subjective, performance, and physiological effects of intranasal cocaine.

RATIONALE: No pharmacotherapies are approved for cocaine use disorder. Phendimetrazine, a prodrug of the monoamine-releaser phenmetrazine, attenuates the reinforcing effects of cocaine in preclinical models, has minimal abuse potential, and is safe when combined with cocaine. OBJECTIVES: This study determined the influence of phendimetrazine maintenance on the reinforcing effects of cocaine (i.e., choice to self-administer cocaine), along with the subjective, performance, and physiological effects of cocaine. We hypothesized that phendimetrazine would attenuate the reinforcing effects of cocaine. METHODS: Twenty-nine subjects with cocaine use disorder completed this within-subject, inpatient study. The subjects were maintained on placebo and 210 mg phendimetrazine in a counterbalanced order. After at least 7 days of maintenance on the target dose, the subjects completed experimental sessions in which the effects of single doses of 0, 20, 40, and 80 mg of intranasal cocaine were determined. RESULTS: Cocaine functioned as a reinforcer, producing significant dose-related increases in self-administration. Cocaine increased prototypic effects (e.g., ratings of stimulated and blood pressure). Phendimetrazine attenuated ratings on a select set of subjective outcomes (e.g., ratings of talkative/friendly), but failed to reduce the reinforcing effects of cocaine or a majority of positive subjective cocaine effects. Phendimetrazine increased heart rate, indicating a physiologically active dose was tested, but heart rate increases were not clinically significant. CONCLUSIONS: These results indicate that although phendimetrazine can safely be combined with cocaine, it does not attenuate the abuse-related effects of cocaine. It is unlikely, then, that phendimetrazine will be an effective standalone treatment for cocaine use disorder.

Using behavioral economic variables to predict future alcohol use in a crowdsourced sample.

BACKGROUND: Theoretical perspectives at the intersection of behavioral economics and operant theory have resulted in numerous advances for addiction science. Three mechanisms (i.e. behavioral economic demand [consumption-price relationships], delay discounting [reinforcer devaluation with delay], and proportionate alcohol-related reinforcement [relative reinforcement attributable to alcohol]) are proposed to contribute to problematic alcohol use. Limited research has evaluated the unique contribution of these mechanisms for predicting future alcohol consumption. AIM: The purpose of this study was to evaluate the predictive relationship between these mechanisms and self-reported alcohol use frequency, quantity, and severity. METHODS: Participants (n=223) sampled from the crowdsourcing website Amazon Mechanical Turk completed a survey containing behavioral economic measures. Weekly reports of daily alcohol use were then collected for 18 weeks. Unadjusted and adjusted models determined the association between behavioral economic variables and alcohol use. RESULTS/OUTCOMES: Behavioral economic measures were associated with alcohol and soda use at baseline in a stimulus-selective manner (e.g. alcohol demand associated with alcohol, but not soda, variables). Predictive models adjusted for Alcohol Use Disorder Identification Test scores indicated that increased proportionate alcohol-related reinforcement and behavioral economic demand were uniquely and incrementally associated with frequency (e.g. adjusted odds ratio (AOR)=5.54 for proportionate alcohol-related reinforcement, p<0.05) and quantity-severity measures (e.g. AOR=7.58 for alcohol demand intensity, p<0.001), respectively. Test-retest reliability was generally acceptable (rxx=0.42-0.76) with the exception of proportionate alcohol-related reinforcement (rxx=0.29). CONCLUSION/INTERPRETATION: These findings indicate the unique, predictive, and incremental validity of behavioral economic measures for evaluating future alcohol consumption, supporting their continued use in addiction science research.

Attentional bias to cannabis cues in cannabis users but not cocaine users.

Attentional bias to drug cues has been associated with the problematic use of drugs, including cannabis. The cognitive mechanisms underlying this bias are not fully understood. The purpose of this study was to determine whether cannabis-cue attentional bias is associated with disruptions in attentional processing. To this end, a novel cannabis-cue visual probe task that incorporated eye tracking technology and attention-based metrics derived from signal detection theory was administered to seventeen individuals who reported daily/near-daily cannabis use. Seventeen individuals with cocaine use disorder were also enrolled as a clinical-control group. Cannabis and neutral images were briefly presented side-by-side on a computer screen, followed by the appearance of a "go" or "no-go" target upon offset of both images to permit assessment of attention-based performance. Cannabis users exhibited attentional bias to cannabis cues, as measured by fixation time and response time, but not cue-dependent disruptions on subsequent attentional performance. Cocaine users did not display an attentional bias to cannabis cues but did display poorer attentional performance relative to cannabis users. These results indicate that attentional bias to cannabis cues is selective to cannabis use history and not associated with impaired attentional processing.