Background This study aimed to examine the early experience of nusinersen for spinal muscular atrophy (SMA) from the patient and caregiver perspective. Methods A 54‐item online survey was administered to adult patients and caregivers of pediatric patients diagnosed with SMA. Results Overall, respondents (56 patients and 45 caregivers) were satisfied with nusinersen. Satisfaction was highest on changes in energy, stamina, and motor function and lowest on treatment administration and overall time commitment. Differences were noted for treatment effect sustained over time as reported by adult patients vs caregivers reporting on behalf of pediatric patients. Respondents reported insurance approval as a key barrier to access, particularly among adult patients. Conclusions Despite therapeutic advances, there remain significant unmet needs for SMA. Challenges with administration and barriers to access potentially limit the number of patients treated or delay treatment. Continued efforts are needed to develop more treatment options and to improve access to treatments.

Background Parental support (PS) and parental monitoring (PM) are known protective factors against adolescent substance use (SU). However, little is known about whether PS and PM may affect SU outcomes differently by gender and age. This study examined the relationship between PS and PM and adolescent SU, specifically alcohol and tobacco use, stratified by gender and age group. Methods Middle and high school students (n = 2351, 48.5% Female) completed surveys of self-reported SU, perceived PS and PM, and socioeconomic background. Age group was defined dichotomously as grade 7–8 Middle school and grade 9–10 High school students. PS and PM were each measured using previously validated tools. SU was measured by lifetime and past 30 days cigarette/alcohol use. One-way ANOVA and binary logistic regression models were completed. Odds ratios and means were reported. Results PS and PM were significantly and negatively related to all outcome variables regardless of gender and age group. Mean differences in PS and PM were insignificant between age groups. Between genders, PM scores were significantly higher for girls (14.05) compared to boys (13.48) (p < 0.01). Odds Ratios of all four SU types (for alcohol and tobacco use) increased with higher age group, with ORs ranging from 1.45–2.61 (p < .05). Conclusions PS and PM were protective against SU for all participants, consistent with previous literature. Girls reported greater parental monitoring than boys, irrespective of age-group. While girls experienced higher levels of monitoring, they did not report lower SU than boys. This suggests that monitoring girls more closely than boys appears unnecessary in preventing adolescent SU. Finally, PS was a more significant factor in preventing SU for older adolescents (high school aged group) than for younger adolescents, irrespective of gender suggesting that PS may be more impactful and important as adolescents age. As children mature, particularly from middle school to high school, PS may play a larger role in preventing SU for older adolescents compared to younger ones.

Two neurophysins (NPs) that are thought to be the primary protein forms produced with the hormones vasopressin (VP) and oxytocin (OT) were isolated from 5000 human pituitary glands. In sucrose gradient centrifugation of human neural lobes, each of these NPs had a distribution similar to that of either VP or OT. Such differential localization of 1 human NP (HNP) with VP and the other HNP with OT suggests an association of their biosynthesis, and it is on the basis of this association that 1 NP has been named VP-associated HNP (VP-HNP) and the other OT-associated HNP (OT-HNP). The purified proteins were complexed to bovine thyroglobulin in order to develop specific antisera. RIAs developed with these antisera are effective for each HNP in the range of 5-320 pg. Reference standards in both assays were corrected for protein content using amino acid analysis to obtain absolute protein concentration; this type of correction is recommended for all RIAs that measure proteins. The RIAs were used to measure the concentrations of HNPs in unextracted human plasma. In healthy, sitting, normally hydrated subjects of both sexes, VP-HNP and OT-HNP were, respectively, 73 +/- 5 and 382 +/- 30 pg/ml (mean +/- SEM; n = 20); there was no significant difference between values in males and females, provided the latter were not taking medication. Women on oral contraceptives had elevated (> 3 times normal) levels of OT-HNP but normal levels of VP-HNP. Eleven patients who had the syndrome of inappropriate secretion of antidiuretic hormone had elevated levels of VP-HNP but not necessarily of OT-HNP. Surgery was found to consistently increase plasma VP-HNP but not OT-HNP. In two of six subjects smoking caused a dramatic release of VP-HNP, as indexed by plasma levels which rose to more than 50 times the control values. One patient with lithium-induced nephrogenic diabetes insipidus had elevated plasma concentrations of both NPs. The sensitivity and specificity of the RIAs may make them useful clinically in certain pathological states.

BACKGROUND: Cisplatin-based chemotherapy is the first-line (1L) treatment for eligible patients with locally advanced/metastatic urothelial carcinoma (mUC). However, many patients with mUC are ineligible for cisplatin-based therapy due to age-or disease-related factors. Specific criteria used by practicing physicians to determine cisplatin ineligibility have not been well characterized. OBJECTIVE: To understand US oncologists' perspectives and self-reported treatment preferences related to cisplatinineligible patients with mUC. METHODS: An electronic survey was administered (November-December 2017) to a random sample from a panel of US oncologists who had agreed to participate in periodic surveys. Eligible participants were required to have ≥2 years of clinical experience, have experience treating ≥5 patients with mUC in the past year, and be board certified and/or eligible. In addition to providing demographic information, clinical preferences, and self-reported practices, participants identified and ranked criteria and reasons for determining cisplatin ineligibility. Descriptive statistics were used to analyze all demographics and responses. RESULTS: From the 301 respondents, the most commonly identified clinical factors for cisplatin ineligibility were renal dysfunction (78%) and poor performance status (77%), followed by neuropathy (47%), solitary kidney (43%), hearing loss (43%), advanced age (43%), and cardiovascular dysfunction (41%). Patients were typically deemed ineligible for cisplatin at diagnosis (58%) or on initiation of 1L metastatic therapy (61%). The preferred non-cisplatin 1L treatments were checkpoint inhibitors (75%), followed by carboplatin-based chemotherapy (19%). CONCLUSIONS: This survey of US oncologists provides insights into clinical perspectives on cisplatin ineligibility in the context of the evolving treatment landscape for patients with mUC.

Loneliness is a significant risk factor for substance use, however, impacts of treatments on loneliness are relatively unexplored. Living in a rural location is a greater risk factor for loneliness. This study examined data from a quasi-experimental study in rural Appalachia, comparing the effectiveness of Mindfulness-Based Relapse Prevention (MBRP) versus Treatment as Usual (TAU) among adults receiving MOUD in outpatient therapy. Our objective was to determine whether observed reductions in self-reported craving, anxiety, depression, and increased perceived mindfulness would also improve loneliness reports. Eighty participants (n = 35 MBRP; n = 45 TAU) were included in the analysis from a group-based Comprehensive Opioid Addiction Treatment program. Outcomes tracked included craving, anxiety, depression, mindfulness, and loneliness as measured by the Revised UCLA Loneliness Scale (R-UCLA). A linear mixed model ANOVA determined the significance of the treatments on changes in loneliness scores at baseline, 12 weeks, 24 weeks, and 36 weeks post-recruitment. Both groups reported significantly reduced loneliness over the course of the study (F = 16.07, p < 0.01), however there were no significant differences between groups. Loneliness was also significantly positively (p < 0.01) correlated with anxiety (0.66), depression (0.59), and craving (0.38), and significantly (p < 0.01) inversely correlated (−0.52) with mindfulness. Results suggest that participation in MOUD group-based outpatient therapy has the potential to diminish loneliness and associated poor psychological outcomes. Thus, it is possible that a more targeted intervention for loneliness would further diminish loneliness, which is important as loneliness is linked to risk for relapse.