Criterion Validity of Protective Behavioral Strategies for Alcohol Consumption among College Students: Comparison across Two Measures.

BACKGROUND: Protective behavioral strategies (PBS), or behaviors used to reduce harm associated with alcohol use, are often associated with lower levels of alcohol consumption, lower engagement in high-risk drinking behaviors, and fewer alcohol-related consequences. Although the majority of studies have found significant associations between higher PBS use and lower consumption or consequences, some studies have found nonsignificant or even positive associations. One explanatory hypothesis is that the mixed findings are due to differential content in PBS measures. OBJECTIVES: The current study examined the criterion validity of two widely-used PBS measures, the PBSS and the SQ. In a multi-institution online study assessing alcohol outcomes, college drinkers were randomly assigned to complete one PBS measure. Both measures had the same response options to standardize assessment and focus on content. RESULTS: Findings suggest both measures of PBS are consistently predictive of alcohol outcomes among college drinkers, across multiple subpopulations (i.e., strength of association was not moderated by sex, race, or drinking level). CONCLUSIONS/IMPORTANCE: Some PBS subscales were more impactful than others, suggesting researchers may want to choose which PBS scale to use based on outcomes of interest, or after determining if alternatives to drinking is an important facet of PBS for the research questions being examined. Moreover, the differential findings for subscales suggest that prevention and intervention programs incorporating PBS should focus on strategies that avoid high-risk scenarios (e.g., avoiding shots or drinking games), rather than general strategies of self-pacing.

Axonal excitability changes in children with spinal muscular atrophy treated with nusinersen.

Spinal muscular atrophy (SMA) is associated with developmental disruption of motor axons in ventral roots of the spinal cord alongside motor axon degeneration. The pathogenesis of peripheral axonal change during development is pertinent to understand treatment response. Nerve excitability techniques, stimulating the median motor nerve at the wrist, were utilised to investigate axonal change during neurodevelopment in 24 children with SMA, compared with 71 age-matched controls. Longitudinal axonal response to nusinersen treatment in 18 children was also investigated. Significant differences in axonal development were noted in the youngest children with SMA, signified by reduced compound muscle action potential (CMAP) (P = 0.030), higher axonal threshold (P = 0.016), rheobase (minimal current amplitude of infinite duration, required to generate an action potential) (P = 0.012) and greater changes in depolarising and hyperpolarising threshold electrotonus. Subexcitability increased in all children with SMA, compared to controls. With treatment, nerve excitability changes were observed prominently in young children, with increases in CMAP, reduction in axonal threshold, fanning-in of threshold electrotonus, increase in resting current-threshold slope and reduction in subexcitability. Whilst motor axons continue to mature in SMA, developmental delays in passive and active membrane properties occur especially in early childhood. Concurrently, motor axons actively undergo degeneration. Nusinersen restores the developmental trajectory of motor axons reducing degeneration, especially in children with early treatment initiation. Our findings move the field forward in understanding the developmental aspect of childhood-onset motor neurone diseases and changes in axonal function associated with disease modification. KEY POINTS: Pathomechanisms in spinal muscular atrophy involve concurrent neurodevelopmental and neurodegenerative processes. The greatest delays in maturation of the passive and active properties of the peripheral motor axon are seen in early childhood. Nusinersen facilitates developmental recovery of the motor axon whilst also reducing neurodegeneration. Axonal dysfunction is reversed with SMN repletion particularly when intervention occurs early in development.

Oral digoxin effects on exercise performance, K+ regulation and skeletal muscle Na+ ,K+ -ATPase in healthy humans.

We investigated whether digoxin lowered muscle Na+ ,K+ -ATPase (NKA), impaired muscle performance and exacerbated exercise K+ disturbances. Ten healthy adults ingested digoxin (0.25 mg; DIG) or placebo (CON) for 14 days and performed quadriceps strength and fatiguability, finger flexion (FF, 105%peak-workrate , 3 × 1 min, fourth bout to fatigue) and leg cycling (LC, 10 min at 33% V O 2 peak ${\rm{V}}_{{{\rm{O}}}_{\rm{2}}{\rm{peak}}}$ and 67% V O 2 peak ${\rm{V}}_{{{\rm{O}}}_{\rm{2}}{\rm{peak}}}$ , 90% V O 2 peak ${\rm{V}}_{{{\rm{O}}}_{\rm{2}}{\rm{peak}}}$ to fatigue) trials using a double-blind, crossover, randomised, counter-balanced design. Arterial (a) and antecubital venous (v) blood was sampled (FF, LC) and muscle biopsied (LC, rest, 67% V O 2 peak ${\rm{V}}_{{{\rm{O}}}_{\rm{2}}{\rm{peak}}}$ , fatigue, 3 h after exercise). In DIG, in resting muscle, [3 H]-ouabain binding site content (OB-Fab ) was unchanged; however, bound-digoxin removal with Digibind revealed total ouabain binding (OB+Fab ) increased (8.2%, P = 0.047), indicating 7.6% NKA-digoxin occupancy. Quadriceps muscle strength declined in DIG (-4.3%, P = 0.010) but fatiguability was unchanged. During LC, in DIG (main effects), time to fatigue and [K+ ]a were unchanged, whilst [K+ ]v was lower (P = 0.042) and [K+ ]a-v greater (P = 0.004) than in CON; with exercise (main effects), muscle OB-Fab was increased at 67% V O 2 peak ${\rm{V}}_{{{\rm{O}}}_{\rm{2}}{\rm{peak}}}$ (per wet-weight, P = 0.005; per protein P = 0.001) and at fatigue (per protein, P = 0.003), whilst [K+ ]a , [K+ ]v and [K+ ]a-v were each increased at fatigue (P = 0.001). During FF, in DIG (main effects), time to fatigue, [K+ ]a , [K+ ]v and [K+ ]a-v were unchanged; with exercise (main effects), plasma [K+ ]a , [K+ ]v , [K+ ]a-v and muscle K+ efflux were all increased at fatigue (P = 0.001). Thus, muscle strength declined, but functional muscle NKA content was preserved during DIG, despite elevated plasma digoxin and muscle NKA-digoxin occupancy, with K+ disturbances and fatiguability unchanged. KEY POINTS: The Na+ ,K+ -ATPase (NKA) is vital in regulating skeletal muscle extracellular potassium concentration ([K+ ]), excitability and plasma [K+ ] and thereby also in modulating fatigue during intense contractions. NKA is inhibited by digoxin, which in cardiac patients lowers muscle functional NKA content ([3 H]-ouabain binding) and exacerbates K+ disturbances during exercise. In healthy adults, we found that digoxin at clinical levels surprisingly did not reduce functional muscle NKA content, whilst digoxin removal by Digibind antibody revealed an ∼8% increased muscle total NKA content. Accordingly, digoxin did not exacerbate arterial plasma [K+ ] disturbances or worsen fatigue during intense exercise, although quadriceps muscle strength was reduced. Thus, digoxin treatment in healthy participants elevated serum digoxin, but muscle functional NKA content was preserved, whilst K+ disturbances and fatigue with intense exercise were unchanged. This resilience to digoxin NKA inhibition is consistent with the importance of NKA in preserving K+ regulation and muscle function.

Attitude toward heavy drinking as a key longitudinal predictor of alcohol consumption and problems.

BACKGROUND: Little research has considered the importance of a person's attitude toward heavy drinking when evaluated against other well-known predictors of alcohol use and related harm including drinking motives and drinker identity. The current study aimed to evaluate whether one's favorable attitude toward heavy drinking is a unique predictor of prospectively assessed drinking-related outcomes when considered against descriptive and injunctive norms, drinking intentions, drinking motives, and drinker identity. METHODS: Participants in the current study comprised mandated students (n = 374; 54% male) who violated a campus alcohol policy and received a brief intervention (eCHECKUP TO GO). Analyses included the use of negative binomial regression to examine baseline predictors- attitude toward heavy drinking, perceived descriptive and injunctive norms, drinking intentions, drinking motives, and drinker identity-of prospective alcohol use outcomes and alcohol-related problems 1 month later. RESULTS: We found that one's attitude toward heavy drinking remains a significant predictor of binge frequency, peak drinking, and alcohol-related problems when accounting for norms, intentions, motives, and identity. CONCLUSIONS: This study has important theoretical and intervention implications. Indeed, the finding that one's attitude toward heavy drinking remains a significant predictor of alcohol-related outcomes when intentions are included in the model has implications within the theory of planned behavior. Furthermore, attitude toward heavy drinking has predictive utility when considered against descriptive and injunctive norms, drinking motives, and drinker identity. These findings contribute to a growing literature suggesting that attitudes could be an important intervention target when the goal is to change drinking behavior.

Family, healthcare professional, and societal preferences for the treatment of infantile spinal muscular atrophy: A discrete choice experiment.

AIM: To understand the factors that most influence decision-making in the treatment of infantile spinal muscular atrophy (SMA). METHOD: A discrete choice experiment was conducted among parents of people with SMA (parents), healthcare professionals (HCPs), and members of the Australian general population (GenPop). Respondents were asked to accept/reject treatment for an infant newly diagnosed with SMA in eight hypothetical scenarios, characterized by different combinations of the attributes of the treatment offered. The results were analyzed using probability analysis. RESULTS: Completed responses were provided from 1113 individuals (1024 GenPop, 21 parents, 68 HCPs). Respondents were more likely to accept treatments that improved functioning and mobility. Treatments with higher costs, invasive delivery, and risks of adverse events were accepted less often. Cost most affected treatment choices by HCPs and GenPop, while change in mobility and mode of administration were most influential for parents. INTERPRETATION: These results highlight the importance of understanding value for money and clinical impact in affecting treatment choice, which are crucial for effective planning of healthcare and the successful implementation of treatment programmes for SMA. What this paper adds Spinal muscular atrophy (SMA) treatments with a higher chance of improving functioning and mobility are preferred by the general population, parents, and healthcare professionals. Treatments with higher costs, invasive delivery, and risk of adverse events are less preferred. Willingness to pay for SMA treatments increases with impact on functioning.

Values of College Students Mandated to an Alcohol Intervention: A Qualitative Examination.

Background: Personal values motivate action and have been shown to influence behavioral choices. Objectives: The purpose of this qualitative study was to identify which values are important to college student drinkers and what underlying principles and motivations support those values. A sample of 198 students who received a university mandate to complete an alcohol education intervention following a campus alcohol policy violation wrote essays regarding their values. These essays were categorized and thematically analyzed by the research team. Results: The majority of values fell under the category of Relationships, followed by Morality, Future Orientation, Wellness, and Benevolence. Conclusions: Most students placed a high value on their commitment to others, which may provide insight into effective and novel ways in which health messages could be communicated to college students. Additionally, findings show a relative lack of future-oriented values, particularly among the heavy-drinking students. Because future orientation is associated with engaging in less risky health behaviors, results suggest it may be beneficial to cultivate goal setting tasks early in college student education to enhance the efficacy of health promotion messages.

Opportunities for reducing college drinking: The roles of drinking attitudes and blackout experience.

BACKGROUND: As many as 35% of college students report having been drunk in the past month, and greater alcohol use and alcohol-related problems are associated with a positive attitude toward heavy drinking. One serious consequence of heavy drinking is alcohol-induced blackout. When they occur, alcohol-induced blackouts present a unique opportunity to increase motivation to change drinking. However, it is unclear under what conditions an alcohol-related heavy drinking attitude and experiencing a blackout represent an opportunity to change and how experiencing a blackout(s) influences an individual's motivation to reduce drinking and actual behavior. METHODS: This study tested the interplay between one's positive attitude toward heavy drinking and experiencing a blackout in the past year in predicting motivation to reduce drinking (Study 1) and its impact on drinking over time (Study 2). Data were derived from complementary datasets collected at two universities (Study 1 n = 703, mean age = 20.63 years, 44% male, 52% White; Study 2 n = 568, mean age = 19.18 years, 72% male, 84% White). Drinking behavior was measured using a modified Daily Drinking Questionnaire, the Drinking Norms Rating Form, the Alcohol Use Disorders Identification Test (AUDIT), and estimated peak blood alcohol concentration (BAC). Regression analyses were conducted to determine whether a blackout would moderate the association between attitude and motivation to reduce drinking (Study 1) and drinking over time (Study 2). RESULTS: Results revealed a significant interaction between attitude and blackout, such that individuals who experience a blackout (vs. those who do not) and positively evaluate heavy drinking evidenced lower motivation to reduce drinking (Study 1) and higher levels of estimated peak BAC (Study 2). CONCLUSIONS: Drinkers with a negative attitude toward heavy drinking who have experienced a blackout have the strongest motivation to reduce drinking and the greatest reductions in peak drinking behavior over time. These effects are over and above that related to the level of alcohol consumed. For young adults who do not positively endorse heavy drinking, blackouts may present a "moment of opportunity" for intervention.

Contextual factors associated with high-intensity drinking events among young adults: A qualitative inquiry.

BACKGROUND: Much of the prior research addressing risky drinking among young adults has focused on heavy episodic drinking (4+/5+ drinks in a single sitting for females/males). However, 1 in 3 young adults engaged in past-year high-intensity drinking (HID, 8+/10+ drinks in a single sitting for females/males). Consuming such large amounts of alcohol is associated with serious acute consequences (e.g., severe injury, overdose) and the development of alcohol use disorder. This qualitative study aimed to gain an in-depth understanding of contextual influences on HID from drinkers' perspectives. METHODS: We conducted individual interviews of 28 young adults (57% female, aged 20 to 25 years old) who engage in HID to assess the role of context in the prediction of HID (relative to non-HID events). Two authors coded each interview following a structured codebook and thematic analysis was used to analyze the qualitative data. RESULTS: Based on identified themes, factors that may increase HID likelihood include being in larger groups or in social contexts where others are drinking heavily, having close relationships with others who are present, on special occasions, when feeling safe, being comfortable in a given situation, and experiencing intense affective states (especially positive ones). Noted deterrents for HID included friends' extreme intoxication, perceptions that heavy drinking is less acceptable in certain contexts (i.e., at work, family events) or among others present, cost/financial constraints, next-day responsibilities, and needing to drive. CONCLUSIONS: Young adults identified a number of social and psychological factors that they perceived influenced their likelihood of engaging in HID. However, they also generated a number of factors that constrained this style of drinking. Understanding the contexts in which HID is most likely to occur will inform interventions that aim to reduce this high-risk behavior.

Partner Type and Young Women's Sexual Behavior: A Qualitative Inquiry.

The incidence of sexually transmitted infections (STIs) has increased over recent years, particularly among young women. Partner type is believed to influence women's STI risk. However, researchers often restrict partner type to "casual" versus "committed," labels that can mask risk variability. Therefore, in this study, we identified and explored a range of sexual partner types in order to understand how young women's perceived risk and condom use intentions vary by partner type. Data were obtained during six focus groups of young women (N =25) who were recruited from a community reproductive healthcare clinic. Women described a range of monogamous and non-monogamous partner types that were distinguished based on partner regularity (i.e., whether the sexual partnership was ongoing) and personal relationship (i.e., degree of involvement outside of the sexual relationship). Women's perceived STI risk was higher and condom use intentions stronger with new partners, particularly unfamiliar partners (i.e., "one-night stand," "fuck boy"). Women identified potential harm from condom negotiation with all but the "friends with benefits" partners. However, the nature of this harm differed by partner type. Clinicians and researchers should consider how to support women in advocating for safer sexual behaviors across these partner types by understanding how partner regularity, degree of personal relationship, and emotional attachment differentially impact couples' condom use decisions.

A Test of the Theory of Planned Behavior in the Prediction of Alcohol-Induced Blackout Intention and Frequency.

BACKGROUND: This study examined the theory of planned behavior (TPB) as an explanatory model for alcohol-induced blackouts among college students. Blackouts are periods of time wherein individuals continue to function and engage in their social environment but do not remember it as a result of consuming large quantities of alcohol. Social cognitive factors posited within TPB, such as perceived norms and personal attitudes toward alcohol consumption, are reliable predictors of alcohol use and related problems. However, research to date has not examined these theoretical antecedents as predictors of alcohol-induced blackout. METHODS: College students with a history of blackout (N = 384) completed a baseline survey, and a subsample (N = 120) completed a 1-month follow-up survey. Negative binomial mediation models were used to evaluate intentions to blackout as a mediator of the norms, attitudes, and self-efficacy to avoid blackout-blackout frequency association at baseline and 1-month follow-up. RESULTS: Norms, attitudes, and self-efficacy to avoid blackout all significantly predicted blackout intentions at baseline, which in turn predicted more frequent blackouts both at baseline and at 1-month follow-up. Notably, blackout attitudes demonstrated both direct and indirect associations with blackout frequency. CONCLUSIONS: Prospective analyses provided partial support for the TPB, with only attitudes and intentions demonstrating prospective associations with actual blackout frequency. Given the particularly strong association between blackout attitudes and frequency of blackouts, attitudes may represent an important and novel target for prevention and intervention efforts.

A Brief Clinic-Based Intervention to Reduce Alcohol Misuse and Sexual Risk Behavior in Young Women: Results from an Exploratory Clinical Trial.

This exploratory trial determined the feasibility, acceptability, and preliminary efficacy of a brief intervention (BI), supplemented with text messaging and a curated Web site, on alcohol use and sexual risk behavior among young women. Young women seeking care at a reproductive health clinic were screened for alcohol misuse and sexual risk behavior. Those who screened positive and who agreed to participate (N = 48; M = 22.67 years) were randomized to either (a) a brief in-person session during which personalized feedback regarding alcohol use and sexual risk taking was provided and discussed, or (b) a control condition. Feasibility was assessed by recruitment and retention rates. Acceptability was assessed with participant ratings of their intervention. Efficacy was measured using self-reported alcohol use and sexual behavior at baseline and during a 3-month follow-up. We supplemented the quantitative data with qualitative data from semi-structured interviews. Feasibility data indicated that 64% of eligible women agreed to participate, 74% of eligible women were enrolled, and 86% of enrolled women were retained through follow-up. Acceptability data showed that women who received the BI reported strong satisfaction with their intervention (M = 4.65 vs. 3.98 on a five-point scale) and also reported that text messaging was helpful (M = 4.73 on a seven-point scale) and acceptable (M = 5.27 on a seven-point scale). Qualitative data provided additional support for BI feasibility and acceptability. Efficacy data showed that women in both conditions reduced alcohol use and sexual risk behavior over time; women who received the BI reduced their maximum daily alcohol intake more than controls (BI from 7.68 to 4.82 standard drinks vs. control from 6.48 to 5.65; Wald χ2 = 4.93, p < .05). Women in the BI reported fewer occasions of condomless sex (median = 2.50) than controls (median = 5.00) at the follow-up, but this difference was not statistically significant (OR = 0.61, 95% CI [0.32, 1.15]). A brief intervention, supplemented with text messaging and a Web site, that targeted alcohol use and sexual behavior was feasible and acceptable to young women and led to lower levels of alcohol misuse and sexual risk behavior.

Location-Specific Social Norms and Personal Approval of Alcohol Use are Associated with Drinking Behaviors in College Students.

Background: Prior research on risky alcohol use points to drinking norms as predictors of drinking behavior. Most research to date has only explored global (versus context-specific) drinking norms as they relate to general drinking behavior. To better understand risky drinking behavior in students, how norms may vary across drinking environments should be considered. Objectives: We sought to explore differences in drinking norms (descriptive and injunctive), personal approval, and alcohol use across specific drinking locations and how these location-specific predictors combine to best predict alcohol consumption in home/dorm locations, bars, and parties. Methods: College student drinkers (N = 115, 76% female) participated in an anonymous online cross-sectional survey in 2015-2016 assessing personal and perceived drinking experiences and attitudes across various locations. Results: Alcohol use, descriptive norms of alcohol use, and injunctive norms of alcohol use (but not personal approval) varied across location. In addition, location-specific descriptive norms were associated with alcohol use in each drinking location, whereas location specific personal approval was associated with alcohol use only at home/dorm and bar locations. Furthermore, descriptive norms and personal approval of drinking in a given location predicted alcohol use in that same location, while norms or approval for other locations did not. Conclusion/Importance: Results highlight the importance of specificity of perceived drinking norms and personal approval for predicting location-specific alcohol use. These findings have implications for interventions, which may benefit from discussions of students' preferred drinking locations and providing location-specific normative feedback.

Event-Level Correlates of Drinking Events Characterized by Alcohol-Induced Blackouts.

BACKGROUND: Prior research identifies a range of potential predictors of blackouts and suggests that blackouts increase risk for additional negative consequences. However, these studies are based on epidemiological work that allows us to draw conclusions about groups of people but not within-person processes. The present study examined within-person, event-level correlates of blackouts. METHODS: Ninety-six heavy drinking college students (52% female) completed 28 days of daily reports of alcohol use and consequences, including blackouts. Thirty-three participants reported 56 blackouts. Hierarchical linear modeling compared morning reports of drinking events on which participants did versus did not report a blackout, controlling for total drinks at the event. RESULTS: Blackout likelihood increased as a function of total drinks consumed and of crossing thresholds for heavy episodic drinking (4+/5+ drinks for women/men) and high-intensity drinking (8+/10+). Participants reported a higher total number of additional negative consequences on blackout events. Specific consequences that were more likely included embarrassing oneself and hangover. Blackouts were associated with morning ratings of less positive mood and a less favorable drinking event. Motives for drinking and simultaneous use of marijuana were not associated with blackouts. CONCLUSIONS: Event-level findings of this study document that events leading to alcohol-induced memory loss are associated with other adverse experiences relative to drinking events that do not result in blackout, and offer potentially motivational levers for preventive interventions.

Alcohol Use and Sexual Risk Behavior in Young Women: A Qualitative Study.

Alcohol use and sexual behavior co-occur frequently in young women, increasing risk for HIV and other sexually transmitted infections. To inform preventive interventions, we used qualitative methods to better understand how women think about the contribution of alcohol use to sexual risk-taking. Young women (N = 25; M = 22.8 years; 64% White) were recruited from a community-based reproductive health clinic to attend focus groups; a semi-structured agenda was used to investigate both a priori explanatory mechanisms as well as participant-driven explanations for the alcohol-sex association. Women reported that alcohol reduced their social anxiety, helped them to feel outgoing and confident, and lowered inhibitions and other barriers to sexual encounters (consistent with alcohol expectancies). During drinking events, women described being less concerned with risks, less discriminating regarding sexual partners, and less likely to insist on safer sex practices (consistent with alcohol myopia). These empirical findings support previous theory-based guidance for tailoring preventive programs for alcohol use and sexual risk reduction for young women.

Sexual risk behavior and substance use among young, diverse women seeking care at a reproductive health clinic.

BACKGROUND: To describe sexual risk behavior, alcohol (and other substance) use, and perceived health promotion needs among young adult women seeking care from an urban reproductive health care clinic in the Northeastern United States, and to examine if these needs differ by race and ethnicity. METHODS: Women 18-29 years old presenting for a routine medical visit were invited to participate. Of 486 eligible women, 466 (96%) agreed to participate and completed a brief survey on a tablet computer. Most of the sample (53%) identified as non-Hispanic White. One-quarter (25%) identified as Hispanic/Latina. A smaller proportion of women identified as African American (19%). RESULTS: One-third (31%) of women reported a history of sexually transmitted infection (STI), and women reported infrequent condom use with recent sexual partners. Regarding behavioral health needs, nearly three-quarters of women (72%) reported regular alcohol use, approximately one-third had used marijuana (37%) or tobacco (33%) in the last month, and 19% reported clinically significant depressive symptoms in the last two weeks. Women reported moderate-to-strong interest in receiving information about relationships and sexual health; however, the majority were not interested in information about their substance use. Hispanic and African-American women were more likely to report STI history despite reporting fewer sexual partners than non-Hispanic White women. Minority women also reported significantly less alcohol and cigarette use, but more water pipe tobacco use, and reported significantly greater interest in interventions to promote sexual health. Hispanic women also evidenced significantly elevated rates of depressive symptoms, with 26% of Hispanic women reporting a clinically significant level of depressive symptoms. CONCLUSIONS: Reproductive health centers are opportune settings to address a broad range of healthcare needs, including sexual health, substance use, and mental health. These centers engage a diverse group of women, which is important given observed disparities in health outcomes based on race/ethnicity. Young women, particularly racial and ethnic minority women, report the most interest in services addressing sexual and relationship health.

Self-Efficacy to Limit Drinking Mediates the Association between Attitudes and Alcohol-Related Outcomes.

Personal attitudes toward alcohol consumption are reliable predictors of alcohol use and related problems, with emerging work suggesting that one's favorable attitude toward limited drinking (i.e., at levels below the threshold for heavy episodic drinking) is a buffer against alcohol use and binge drinking. However, little work has examined the specific mechanism(s) through which one's personal attitude toward limited drinking is associated with alcohol use and related problems. One such mechanism may be an individual's self-efficacy to limit their alcohol use. The current study aimed to evaluate whether self-efficacy to limit one's alcohol use mediates the association between one's personal attitude toward limited drinking and actual alcohol use and related problems over time. Participants were mandated students (n = 568; 28% female) who violated campus alcohol policy and received a brief motivational intervention. Mediation models were used to test (a) self-efficacy to limit one's alcohol use as a traditional mediator of the attitudes-drinking quantity association and (b) self-efficacy and drinking quantity as serial mediators of the attitudes-alcohol-problems link. Favorable attitudes toward limiting drinking at baseline were positively associated with self-efficacy to limit drinking at 1 month, which was associated with a reduction in drinking quantity at 3 months; this, in turn, was associated with a reduction in alcohol-related problems at 5 months. These findings provide a rationale for incorporating attitudes and self-efficacy in the development and refinement of intervention strategies.

Emerging therapies and challenges in spinal muscular atrophy.

Spinal muscular atrophy (SMA) is a hereditary neurodegenerative disease with severity ranging from progressive infantile paralysis and premature death (type I) to limited motor neuron loss and normal life expectancy (type IV). Without disease-modifying therapies, the impact is profound for patients and their families. Improved understanding of the molecular basis of SMA, disease pathogenesis, natural history, and recognition of the impact of standardized care on outcomes has yielded progress toward the development of novel therapeutic strategies and are summarized. Therapeutic strategies in the pipeline are appraised, ranging from SMN1 gene replacement to modulation of SMN2 encoded transcripts, to neuroprotection, to an expanding repertoire of peripheral targets, including muscle. With the advent of preliminary trial data, it can be reasonably anticipated that the SMA treatment landscape will transform significantly. Advancement in presymptomatic diagnosis and screening programs will be critical, with pilot newborn screening studies underway to facilitate preclinical diagnosis. The development of disease-modifying therapies will necessitate monitoring programs to determine the long-term impact, careful evaluation of combined treatments, and further acceleration of improvements in supportive care. In advance of upcoming clinical trial results, we consider the challenges and controversies related to the implementation of novel therapies for all patients and set the scene as the field prepares to enter an era of novel therapies. Ann Neurol 2017;81:355-368.

Nusinersen for SMA: expanded access programme.

BACKGROUND: Spinal muscular atrophy (SMA) is a devastating motor neuron disorder causing progressive muscle weakness and respiratory insufficiency. We present the initial Australian experiences implementing the expanded access programme (EAP) to enable preapproval access to nusinersen, the first disease-modifying therapy, for SMA type 1. METHODS: An Australian multicentre, open-label EAP for nusinersen enrolled patients with infantile-onset SMA type 1 from November 2016 to September 2017. Standard-of-care medical therapy and treatment with intrathecal nusinersen were provided to all patients. Clinical and diagnostic characteristics, molecular genetics, treatment administered, and functional motor outcomes were assessed. RESULTS: A total of 20 patients with SMA type 1 met the inclusion criteria, of whom 16 consented and received nusinersen treatment. Median time to diagnosis from symptom onset was 5.0 months and was correlated with age of onset (r=0.54, P<0.05). Management shifts included proactive nutritional and pulmonary support in all newly diagnosed patients with increased complexity of decision making. Supplemental nutrition with or without nocturnal non-invasive ventilation was implemented during follow-up in new diagnoses with age of onset <3 months and 2 SMN2 copies. CONCLUSIONS: The nusinersen EAP highlights difficulties in achieving early diagnosis and/or prevention, the evolution of optimal clinical care in a time of uncertain prognostication, resource implications and ethical issues in clinical practice for SMA type 1. These challenges are broadly relevant to the realisation of all novel therapeutics in neurological disorders.

Distinctions in Alcohol-Induced Memory Impairment: A Mixed Methods Study of En Bloc Versus Fragmentary Blackouts.

BACKGROUND: Blackouts-or memory loss for all or part of a drinking event-are reliable predictors of alcohol-related consequences. Studies suggest a distinction between en bloc (complete memory loss) and fragmentary (off-and-on memory loss) blackouts; however, research has not consistently differentiated between these 2 forms of blackout. This study aimed to validate the distinction between en bloc and fragmentary blackouts among young adults. METHODS: Data were collected using qualitative (Study 1) and quantitative (Study 2) research methods. Participants in both studies were college students with a history of alcohol-induced memory impairment. They were recruited using community advertisement (Study 1, N = 50, 56% female) and Qualtrics survey panels (Study 2, N = 350, 56% female). Study 1 participants engaged in 8 focus groups. Discussions were audio-recorded, transcribed verbatim, and coded using applied thematic analysis. Findings guided assessment of en bloc and fragmentary blackout in Study 2. In Study 2, a separate sample of participants completed an online survey assessing drinking behavior, alcohol-induced memory impairment, and theoretical correlates of en bloc and fragmentary blackouts. RESULTS: Study 1 participants differentiated between en bloc and fragmentary blackouts (which they referred to as "blackouts" and "brownouts," respectively) based on duration and extent of memory loss. They indicated that blackouts occur along a continuum, with en bloc "blackouts" at the extreme. They also stated that the term "blackout drinking" does not always imply memory loss. Study 2 participants reported higher rates of "brownouts" (81%) than "blackouts" (54%). They reported less negative outcome expectancies and attitudes, greater personal approval, higher prevalence estimates, lower self-efficacy, and stronger intentions for "brownouts" than "blackouts" (p < 0.001). Women perceived "blackouts/brownouts" as more prevalent than men and reported lower intentions to experience "blackouts" (p < 0.005). CONCLUSIONS: Young adults are more permissive of fragmentary than en bloc blackout. En bloc blackouts may be a target for future interventions.

Blackouts as a Moderator of Young Adult Veteran Response to Personalized Normative Feedback for Heavy Drinking.

BACKGROUND: Blackouts-or periods of alcohol-induced amnesia for all or part of a drinking event-have been identified as independent predictors of alcohol-related harm that may be used to identify individuals who would benefit from intervention. However, little is known about the prevalence and impact of blackouts among Veterans. This study examined blackouts as a moderator of young adult veteran response to a brief, online personalized normative feedback (PNF) intervention for heavy drinking. METHODS: Veterans scoring ≥3/4 (women/men) on the Alcohol Use Disorders Identification Test completed a baseline and 1-month assessment as part of a larger intervention trial (N = 571; 83% male; age M = 28.9, SD = 3.3). Participants were randomized to alcohol PNF (n = 285) or a video game attention control (n = 286). Hierarchical regression was used to examine the interaction between intervention condition and blackouts on alcohol-related outcomes at 1-month follow-up. RESULTS: At baseline, 26% of participants reported loss of memory for drinking events in the past 30 days. The interaction between condition and blackouts was significant, such that PNF participants who had experienced blackouts at baseline reported greater decreases in drinking quantity at 1 month than those who had not, and only PNF participants who had experienced baseline blackouts reported a decrease in alcohol problems at follow-up. CONCLUSIONS: PNF appears to be particularly effective for individuals who have experienced alcohol-induced blackout, perhaps because blackouts prime them for feedback on their alcohol use. While other negative consequences may also prime individuals for behavior change, blackouts are posited as a particularly useful screening tool because they are prevalent among young adults, have a strong association with alcohol-related harm, and are assessed in widely used clinical measures.