Sixty treatment-seeking individuals with methamphetamine (MA) dependence entered a randomized, placebo-controlled, double-blind clinical trial of oral dextroamphetamine (d-AMP) as a replacement therapy for MA dependence. The subjects took 60 mg sustained-release d-AMP for 8 weeks, during which time they received eight 50-min sessions of individual psychotherapy. Adverse events and urine toxicology for MA were assessed two times a week. There were no serious adverse events. Urine samples containing <1,000 ng/ml of MA were classified as negative for MA. The MA-negative scores in the d-AMP group (3.1 ± SD 4.6) were no higher than those in the placebo group (3.3 ± SD 5.3; P > 0.05). However, withdrawal and craving scores were significantly lower in the d-AMP group (P < 0.05 for both). Although subjects taking d-AMP did not reduce their use of MA, the significant reductions observed in withdrawal and craving scores in this group support the need for further exploration of d-AMP as a pharmacologic intervention for MA dependence, possibly at higher doses.

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Acute malnutrition accounts for an immense disease burden and is implicated as a key, underlying cause of child mortality in low resource settings. Child wasting, defined as weight-for-length more than 2 standard deviations below international standards, is a leading indicator to measure the Sustainable Development Goal target to end malnutrition by 2030. Prevailing methods to measure wasting rely on cross-sectional surveys that are unable to measure onset, recovery, and persistence - key features of wasting epidemiology that could inform preventive interventions and disease burden estimates. Here, we show through an analysis of 18 longitudinal cohorts that child wasting is a highly dynamic process of incident onset and recovery, and that peak incidence is between birth and 3 months - far earlier than peak prevalence at 12-15 months. By age 24 months the proportion of children who had ever experienced a wasting episode (33%) was more than 5-fold higher than prevalence (6%), suggesting that the wasting burden is likely far higher than cross-sectional surveys suggest. Seasonally driven changes in population mean weight-for-length were large (>0.5 z in some cohorts) and were synchronous with rainfall across diverse settings, creating potential for seasonally targeted interventions. Our results motivate a new focus on extending preventive interventions for child wasting to pregnant and lactating mothers, and for preventive and therapeutic interventions to include children below age 6 months in addition to current targets of ages 6-59 months.

Globally 149 million children under five are estimated to be stunted (length more than 2 standard deviations below international growth standards). Stunting, a form of linear growth failure, increases risk of illness, impaired cognitive development, and mortality. Global stunting estimates rely on cross-sectional surveys, which cannot provide direct information about the timing of onset or persistence of growth failure- a key consideration for defining critical windows to deliver preventive interventions. We performed the largest pooled analysis of longitudinal studies in low- and middle-income countries to date (n=31 cohorts, 62,993 children, ages 0-24 months), allowing us to identify the typical age of linear growth failure onset and to investigate recurrent faltering in early life. The highest incidence of stunting onset occurred from birth to age 3 months. From 0 to 15 months, less than 5% of children per month reversed their stunting status, and among those who did, stunting relapse was common. Early timing and low reversal rates emphasize the importance of preventive intervention delivery within the prenatal and early postnatal phases coupled with continued delivery of postnatal interventions through the first 1000 days of life.

Child growth failure is associated with a higher risk of illness and mortality, which contributed to the United Nations Sustainable Development Goal 2.2 to end malnutrition by 2030. Current prenatal and postnatal interventions, such as nutritional supplementation, have been insufficient to eliminate growth failure in low resource settings -motivating a search for key age windows and population subgroups in which to focus future preventive efforts. Quantifying the effect of early growth failure on severe outcomes is important to assess burden and longer-term impacts on the child. Here we show through an analysis of 35 longitudinal cohorts (108,336 children) that maternal and child characteristics at birth accounted for the largest attributable differences in growth. Yet, postnatal growth failure was larger than differences at birth, and characteristics of the child's household environment were additional determinants of growth failure after age 6 months. Children who experienced early ponderal or linear growth failure were at much higher risk of persistent growth failure and were 2.0 to 4.8 times more likely to die by age 24 months. High attributable risk from prenatal causes, and severe consequences for children who experienced early growth failure, support a focus on pre-conception and pregnancy as key opportunities for new preventive interventions. Our results suggest that broad improvements in wellbeing will be necessary to eliminate growth failure in low resource settings, but that screening based on weight could help identify children at highest risk of death before age 24 months.

Objective While several studies have found an association between excessive gestational weight gain and obesity later in life, to the best of our knowledge, no studies have explored the role of gestational weight gain events across the life course. Design and Methods We describe how the prevalence of mid-life obesity (BMI≥30 at age 40 or 41) among women varies by life course patterns of gestational weight gain (using 2009 IOM guidelines) in the USA’s National Longitudinal Survey of Youth 1979 cohort. Results Among women who reported 1–3 births before age 40, the prevalence of mid-life obesity increased with a rising number of excessive gestational weight gain events: from none (23.4%, n=875), to one (37.6%, n=707), to two (46.8%, n=427), and to three (54.6%, n=108), p<0.00005 for trend. Obesity prevalence was similar for the same number of excessive gestational weight gain events, regardless of parity. No clear pattern emerged for the sequencing of excessive gestational weight gain event(s) and later obesity. Conclusions In our descriptive exploratory study, excessive gestational weight gain events appear to be associated with increased prevalence of obesity for parous women, suggesting the importance of preventive interventions regardless of timing of pregnancy-related weight changes over the life course.

The drug 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy", "molly") is a widely used illicit drug and experimental adjunct to psychotherapy. MDMA has unusual, poorly understood socioemotional effects, including feelings of interpersonal closeness and sociability. To better understand these effects, we conducted a small (n=12) within-subjects double-blind placebo controlled study of the effects of 1.5 mg/kg oral MDMA on social emotions and autobiographical disclosure in a controlled setting. MDMA displayed both sedative- and stimulant-like effects, including increased self-report anxiety. At the same time, MDMA positively altered evaluation of the self (i.e. increasing feelings of authenticity) while decreasing concerns about negative evaluation by others (i.e. decreasing social anxiety). Consistent with these feelings, MDMA increased how comfortable participants felt describing emotional memories. Overall, MDMA produced a prosocial syndrome that seemed to facilitate emotional disclosure and that appears consistent with the suggestion that it represents a novel pharmacological class.

RationaleSalvinorin A (SA) is a highly selective kappa opioid receptor agonist and the putative psychoactive compound in Salvia divinorum (SD), an increasingly abused hallucinogenic plant.ObjectivesThe objectives of this study were to characterize the physiological and subjective effects of SA versus placebo and measure drug and metabolite levels.MethodsSublingual SA doses up to 4 mg were administered in dimethyl sulfoxide/polyethylene glycol 400 solution to eight SD-experienced subjects using a placebo-controlled ascending-dose design.ResultsNo dose of SA produced significantly greater physiological or subjective effects than placebo. Furthermore, effects did not resemble reported “typical” effects of smoked SD. SA was detectable in plasma and urine, but was, in most cases, below the reliable limit of quantification (0.5 ng/mL).ConclusionsOur results suggest that the sublingual bioavailability of SA is low. Higher doses, alternate formulations, or alternate routes of administration will be necessary to study the effects of SA in humans.