Umbilical Artery Doppler and Adverse Outcomes in Severe Preeclampsia Without Fetal Growth Restriction: A Retrospective Cohort Study.

Background and objective Severe preeclampsia may be managed expectantly before 34 weeks gestation with close surveillance. Utilized in fetal growth restriction (FGR), evidence supports umbilical artery (UA) Doppler preventing neonatal morbidity from hypertensive disease and predicting adverse outcomes in preeclampsia. We evaluated the association of abnormal UA Doppler waveforms with early delivery (before 34 weeks gestation) and adverse maternal-fetal outcomes in patients with early severe preeclampsia without FGR. Methodology This is a retrospective cohort study of singleton pregnancies with International Classification of Diseases (ICD) Ninth or Tenth Revision, defined severe preeclampsia diagnosed before 34 weeks gestation without FGR from January 1, 2018, through January 27, 2023, at a large tertiary care center where S/D ratios were calculated from UA Doppler interrogation of a free loop of cord at least once weekly. This study was approved by the IRB (ID:00002216) and granted a full Health Insurance Portability and Accountability Act (HIPAA) waiver of consent. Exclusion criteria were major congenital anomalies, congenital infection, aneuploidy, leaving against medical advice >24 hours, and patient instability on admission defined as condition(s) precluding expectant management by the American College of Obstetrics and Gynecology. The primary outcome was delivery before 34 weeks gestation. Secondary outcomes were the mode of delivery and maternal/fetal complications. Patient characteristics and outcomes for normal versus abnormal UA Doppler groups were compared with chi-square, t-tests, and Fisher's exact test. Odds ratios and relative risks were calculated to compare outcomes. Results Of 194 patients with severe preeclampsia, 107 met inclusion criteria. Thirty-four patients had abnormal UA Doppler studies. There were no differences in demographic and clinical data between patients with normal and abnormal UA Doppler studies. Patients with abnormal UA Doppler studies were more likely to deliver before 34 weeks (OR=3.91; 95% CI 1.24-12.33) for worsening severe features (OR=3.85; 95% CI 1.42-10.41), and were less likely to deliver vaginally (OR=0.12; 95% CI 0.03-0.54). Abnormal UA Doppler studies were associated with an increased risk of neonatal complications (OR=6.46; 95% CI 1.42-29.42) and respiratory distress syndrome (RDS) (OR=4.75; 95% CI 1.32-17.16). Abnormal UA Doppler subgroups were divided into patients with elevated S/D >95% Acharya (N=22) and absent end-diastolic flow (EDF) (N=10). The elevated S/D group tended to deliver before 34 weeks gestation for worsening severe features (OR=3.71, 95% CI 1.144-12.050) and had a higher risk of neonatal complications (RR 1.404; 95% CI 1.213-1.624). The absent EDF subgroup was more likely to deliver before 34 weeks (RR=1.52; 95% CI 1.29-1.79) for abnormal fetal testing (OR=6.92; 95% CI 1.71-28.08) and undergo primary cesarean delivery (OR=7.23; 95% CI 1.43-36.61). Conclusion Pregnancies with severe preeclampsia without FGR displayed a high incidence of abnormal UA Doppler waveforms associated with loss of clinical stability and adverse fetal outcomes. The groups with more impedance to umbilical artery flow tended to deliver earlier, and as the Doppler shifted from elevated S/D to absent end-diastolic flow, the mode of delivery shifted to cesarean delivery with increased risk of abnormal fetal testing. These results support the utility of UA Doppler surveillance in severe preeclampsia.

Anxiety, OCD, Psychological Flexibility, and Depression: A Replication With Racially Minoritized University Students.

OCD and anxiety are both associated with depression and suicide, but there is a need for comprehensive assessment and screening of depression risk factors within ethnically and racially minoritized college students. In total, 128 university students were surveyed in 2022 in the northeastern United States who all endorsed at least one non-white racial identity. They completed measures of anxiety, depression, OCD symptoms and psychological flexibility. Results supported that anxiety and OCD symptoms were positively associated with high depression, and high psychological flexibility was associated with low depression. Results support continued screening and intervention for anxiety and OCD symptoms to address depression in diverse young adults. Future work should continue to assess the protective effects of targeting psychological flexibility constructs and to assess longitudinal impacts of OCD symptoms and anxiety on depression.

A kinome drug screen identifies multi-TKI synergies and ERBB2 signaling as a therapeutic vulnerability in MYC/TYR subgroup atypical teratoid rhabdoid tumors.

BACKGROUND: Atypical teratoid rhabdoid tumor (ATRT) is a rare, devastating, and largely incurable pediatric brain tumor. Although recent studies have uncovered 3 molecular subgroups of ATRTs with distinct disease patterns, and signaling features, the therapeutic profiles of ATRT subgroups remain incompletely elucidated. METHODS: We examined the effect of 465 kinase inhibitors on a panel of ATRT subgroup-specific cell lines. We then applied multiomics analyses to investigate the underlying molecular mechanism of kinase inhibitor efficacy in ATRT subgroups. RESULTS: We observed that ATRT cell lines are broadly sensitive to inhibitors of the PI3K and MAPK signaling pathways, as well as CDKs, AURKA/B kinases, and polo-like kinase 1. We identified 2 classes of multikinase inhibitors predominantly targeting receptor tyrosine kinases including PDGFR and EGFR/ERBB2 in MYC/TYR ATRT cells. The PDGFRB inhibitor, Dasatinib, synergistically affected MYC/TYR ATRT cell growth when combined with broad-acting PI3K and MAPK pathway inhibitors, including Rapamycin and Trametinib. We observed that MYC/TYR ATRT cells were also distinctly sensitive to various inhibitors of ERBB2 signaling. Transcriptional, H3K27Ac ChIPSeq, ATACSeq, and HiChIP analyses of primary MYC/TYR ATRTs revealed ERBB2 expression, which correlated with differential methylation and activation of a distinct enhancer element by DNA looping. Significantly, we show the brain penetrant EGFR/ERBB2 inhibitor, Afatinib, specifically inhibited in vitro and in vivo growth of MYC/TYR ATRT cells. CONCLUSIONS: Taken together, our studies suggest combined treatments with PDGFR and ERBB2-directed TKIs with inhibitors of the PI3K and MAPK pathways as an important new therapeutic strategy for the MYC/TYR subgroup of ATRTs.

Evaluating the impact of minimum unit pricing (MUP) on alcohol sales after 3 years of implementation in Scotland: A controlled interrupted time-series study.

BACKGROUND AND AIMS: On 1 May 2018, Scotland introduced minimum unit pricing (MUP), a strength-based floor price below which alcohol cannot be sold, throughout all alcoholic beverages. The legislation necessitates an evaluation of its impact across a range of outcomes that will inform whether MUP will continue beyond its sixth year. We measured the impact of MUP on per-adult alcohol sales (as a proxy for consumption) after 3 years of implementation. DESIGN, SETTING AND PARTICIPANTS: Controlled interrupted time-series regression was used to assess the impact of MUP on alcohol sales in Scotland after 3 years of implementation, with England and Wales (EW) being the control group. In adjusted analyses, we included household disposable income, on-trade alcohol sales (in off-trade analyses) and substitution between drink categories (in drink category analyses) as covariates. MEASUREMENTS: Weekly data were assessed on the volume of pure alcohol sold in Scotland and EW between January 2013 and May 2021, expressed as litres of pure alcohol per adult. The impact of MUP on total (on- and off-trade combined), off-trade and on-trade alcohol sales was assessed separately. RESULTS: The introduction of MUP in Scotland was associated with a 3.0% (95% confidence interval = 1.8-4.2%) net reduction in total alcohol sales per adult after adjustment for the best available geographical control, disposable income and substitution. This reflects a 1.1% fall in Scotland in contrast to a 2.4% increase in EW. The reduction in total alcohol sales in Scotland was driven by reduced sales of beer, spirits, cider and perry. The reduction in total sales was due to reductions in sales of alcohol through the off-trade. There was no evidence of any change in on-trade alcohol sales. CONCLUSION: Minimum unit pricing has been effective in reducing population-level alcohol sales in Scotland in the 3 years since implementation.

Disparities in Liver Transplantation for Nonalcoholic Steatohepatitis in Women.

BACKGROUND: Nonalcoholic steatohepatitis (NASH) is the fastest-growing indication for liver transplantation (LT). Sex disparities among patients with cirrhosis on the LT waitlist are well known. We wanted to understand these disparities further in women with end-stage liver disease patients listed for NASH cirrhosis in a contemporary cohort. METHODS: We used data from the Scientific Registry of Transplant Recipients to assess sex racial, and ethnic differences in NASH patients listed for LT. Adults transplanted from August 1997 to June 2021 were included. Inferential statistics were used to evaluate differences with univariate and multivariate comparisons, including competitive risk analysis. RESULTS: During the study time period, we evaluated 12 844 LT for NASH cirrhosis. Women were transplanted at a lower rate (46.5% versus 53.5%; P  < 0.001) and higher model for end-stage liver disease (MELD) (23.8 versus 22.6; P < 0.001) than men. Non-White women were transplanted at a higher MELD (26.1 versus 23.1; P  < 0.001) than White women and non-White male patients (26.1 versus 24.8; P  < 0.001). Graft and patient survivals were significantly different ( P  < 0.001) between non-White women and White women and men (White and non-White). CONCLUSIONS: Evaluation of LT candidates in the United States demonstrates women with NASH cirrhosis have a higher MELD than men at LT. Additional disparities exist among non-White women with NASH as they have higher MELD and creatinine at LT compared with White women. After LT, non-White women have worse graft and patient survival compared with men or White women. These data indicate that non-White women with NASH are the most vulnerable on the LT waitlist.

Acetylation of homogalacturonan and rhamnogalacturonan-I is catalyzed by a suite of trichome birefringence-like proteins.

Plant cell wall polysaccharides, including xylan, mannan, xyloglucan, and pectins, are often acetylated and members of the domain of unknown function 231 (DUF231)/trichome birefringence-like (TBL) family have been shown to be O-acetyltransferases mediating the acetylation of xylan, mannan, and xyloglucan. However, little is known about the O-acetyltransferases responsible for pectin acetylation. In this report, we biochemically characterized a suite of Arabidopsis DUF231/TBL proteins for their roles in pectin acetylation. We generated 24 TBL recombinant proteins in mammalian cells and demonstrated that 10 of them were able to transfer acetyl groups from acetyl-CoA onto the pectins homogalacturonan (HG) or rhamnogalacturonan-I (RG-I), and thus were named pectin O-acetyltransferase 1 to 10 (POAT1 to 10). It was found that POAT2,4,9,10 specifically acetylated HG and POAT5,6 acetylated RG-I, whereas POAT1,3,7,8 could act on both HG and RG-I. The acetylation of HG and RG-I by POATs was further corroborated by hydrolysis with pectin acetylesterases and by nuclear magnetic resonance spectroscopy. In addition, mutations of the conserved GDS and DXXH motifs in POAT3 and POAT8 were shown to lead to a loss of their ability to acetylate HG and RG-I. Furthermore, simultaneous RNA interference downregulation of POAT1,3,6,7,8 resulted in reduced cell expansion, impaired plant growth, and decreased pectin acetylation. Together, our findings indicate that these POATs are pectin O-acetyltransferases involved in acetylation of the pectin polysaccharides HG and RG-I.

Perceived stress and pain interference in acute rehabilitation following spinal cord injury: Resilience as a moderator.

PURPOSE/OBJECTIVE: Higher levels of resilience is associated with improved pain outcomes in chronic pain and other neurological populations, but the role of resilience in pain following spinal cord injury (SCI) remains unclear. This study examined resilience as a moderator in the relationship between perceived stress and both pain intensity and interference during acute rehabilitation for SCI. RESEARCH METHOD/DESIGN: Individuals admitted to inpatient rehabilitation acutely following SCI (N = 57) completed measures of perceived stress, resilience, pain intensity, and interference. The Johnson-Neyman procedure was used to examine significance of conditional relationships that emerged. RESULTS: Resilience was found to moderate the relationship between perceived stress and pain interference, but not pain intensity, during inpatient rehabilitation. CONCLUSIONS/IMPLICATIONS: When resilience is low, perceived stress has a more profound and adverse impact on pain interference during inpatient rehabilitation, suggesting therapeutic strategies that build components of resilience are needed during acute rehabilitation following SCI. The relationship between stress, resilience, and pain may differ postinpatient rehabilitation for SCI and warrants further investigation. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Pain interference, pain type, and quality of life among adults with spina bifida.

INTRODUCTION: Individuals with spina bifida (SB) experience nociceptive and neuropathic pain, and women with SB report more pain. However, the relationship between pain type and gender on pain interference and quality of life (QoL) among individuals with SB is less understood. OBJECTIVE: To assess relationships among pain interference, pain quality, participation-related QoL, and gender among adults with SB. DESIGN: Fifty-one adults with SB completed a self-report survey assessing SB characteristics, pain severity, pain type, pain interference, and QoL. SETTING: Hospital outpatient adult SB clinic. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Measures of nociceptive pain quality, neuropathic pain quality, participation-related QoL, as well as pain interference with general activities, mood, and sleep were selected a priori as study measures. RESULTS: Fifty-eight percent (N = 30) reported pain and more women than men reported pain (69% vs. 38%, p = .003). Higher general pain interference was associated with lower QoL (r = 0.444, p = .042), but not mood or sleep pain interference (both p's ≥ .451). There was no statistically significant difference in pain interference between genders (p = .138). Nociceptive pain was more common. Levels of nociceptive pain were positively associated with general pain interference, sleep pain interference, and mood pain inference. Neither pain type was associated with QoL (both p's > .082). CONCLUSIONS: The results from this study reveal key differences/similarities among four interrelated factors: pain, pain interference, QoL, and gender. Pertinent information gathered on pain type and QoL, like increased prevalence of nociceptive pain, can be utilized to formulate proactive and effective treatment plans for individuals with SB that may benefit their sleep pain interference and mood pain interference.

Cortical Mechanisms Underlying Immersive Interactive Virtual Walking Treatment for Amelioration of Neuropathic Pain after Spinal Cord Injury: Findings from a Preliminary Investigation of Thalamic Inhibitory Function.

BACKGROUND: Neuropathic pain following spinal cord injury (SCI) affects approximately 60% of individuals with SCI. Effective pharmacological and non-pharmacological treatments remain elusive. We recently demonstrated that our immersive virtual reality walking intervention (VRWalk) may be effective for SCI NP. Additionally, we found that SCI NP may result from a decrease in thalamic γ-aminobutyric-acid (GABA), which disturbs central sensorimotor processing. OBJECTIVE: While we identified GABAergic changes associated with SCI NP, a critical outstanding question is whether a decrease in SCI NP generated by our VRWalk intervention causes GABA content to rise. METHOD: A subset of participants (n = 7) of our VRWalk trial underwent magnetic resonance spectroscopy pre- and post-VRWalk intervention to determine if the decrease in SCI NP is associated with an increase in thalamic GABA. RESULTS: The findings revealed a significant increase in thalamic GABA content from pre- to post-VRWalk treatment. CONCLUSION: While the current findings are preliminary and should be interpreted with caution, pre- to post-VRWalk reductions in SCI NP may be mediated by pre- to post-treatment increases in thalamic GABA by targeting and normalizing maladaptive sensorimotor cortex reorganization. Understanding the underlying mechanisms of pain recovery can serve to validate the efficacy of home-based VR walking treatment as a means of managing pain following SCI. Neuromodulatory interventions aimed at increasing thalamic inhibitory function may provide more effective pain relief than currently available treatments.

Non-Lung Solid Organ Transplantation From SARS-CoV-2-Positive Donors to Uninfected Recipients.

BACKGROUND: There is a paucity of evidence on the risk of donor-recipient transmission of the SARS-CoV-2 in solid organ transplant recipients. Initial impressions suggest non-lung solid organs may be safely transplanted from SARS-CoV-2-positive donors without risk of viral transmission. METHODS: We reviewed clinical results of transplants in which SARS-CoV-2-negative recipients received non-lung solid organs from SARS-CoV-2-positive donors at a single transplant center. No prisoners were used in this study, and participants were neither coerced nor paid. The manuscript was created in compliance with the Helsinki Congress and the Declaration of Istanbul. RESULTS: Between June 2021 and January 2023, we transplanted 26 solid organs, including 13 kidneys, 8 livers, 3 hearts, and 1 simultaneous heart and kidney, from 23 SARS-CoV-2-positive donors into 25 SARS-CoV-2 negative recipients. Two of the recipients had a positive SARS-CoV-2 real-time polymerase chain reaction after transplantation, but otherwise, patients had no SARS-CoV-2-related complications, and all patients to date are alive with excellent allograft function. CONCLUSION: Transplantation of non-lung solid organs from SARS-CoV-2-positive donors into uninfected recipients can be safely performed without adverse effects from SARS-CoV-2.

A pilot study of experiencing racial microaggressions, obsessive-compulsive symptoms, and the role of psychological flexibility.

BACKGROUND: Experiencing racial microaggressions has clear effects on physical and psychological health, including obsessive-compulsive disorder symptoms (OCS). More research is needed to examine this link. Psychological flexibility is an important process to examine in this work. AIMS: This study aimed to examine if, while controlling for depression and anxiety, experiences of microaggressions and psychological flexibility helped explain OCD symptoms within a university-affiliated sample (undergraduate, graduate and law students). This was a pilot exploration of the relationships across themes. METHOD: Initial baseline data from a longitudinal study of psychological flexibility, OCD symptoms, depression, anxiety and experience of microaggressions was utilized. Correlations and regressions were utilized to examine which OCD symptom dimensions were associated with experiencing racial microaggressions in addition to anxiety and depression, and the added role of psychological flexibility was examined. RESULTS: OCD symptoms, experiences of microaggressions and psychological flexibility were correlated. Experiences of racial microaggressions explained responsibility for harm and contamination OCD symptoms above and beyond psychological distress. Exploratory results support the relevance of psychological flexibility. CONCLUSION: Results support other work that experiences of racial microaggressions help explain OCS and they add some support for psychological flexibility as a relevant risk or protective factor for mental health in marginalized populations. These topics should be studied longitudinally with continued consideration of all OCD themes, larger sample sizes, intersecting identities, clinical samples, and continued exploration of psychological flexibility and mindfulness and values-based treatments.

Educational stakeholders' attitudes and knowledge about nonsuicidal self-injury among university students: A cross-national study.

Nonsuicidal self-injury (NSSI) is a commonly occurring, yet historically poorly understood, mental health concern among post-secondary students. The present study sought to identify the current knowledge needs of university stakeholders to inform training efforts around effective NSSI response and student support on university campuses.Participants were 1,762 university students, staff, and student-staff (77% female) from seven universities in Canada, the USA, New Zealand, and Australia.Participants completed an online survey about their attitudes and knowledge of both general mental health and NSSI.University stakeholders reported significantly greater stigma toward NSSI than mental illness in general. Student-staff reported greater perceived knowledge and comfort, and demonstrated greater knowledge of NSSI, than students and staff.Findings underscore the need for additional training and resources to reduce stigma and increase knowledge about NSSI on university campuses internationally.

The Negative Effect of Social Discrimination on Pain Tolerance and the Moderating Role of Pain Catastrophizing.

This study examined the negative impact of social discrimination on the time to pain tolerance during experimentally induced cold pressor pain among healthy individuals. It was hypothesized that the degree to which one catastrophized about pain would exacerbate the negative impact of a history discriminatory experiences on pain tolerance, and that this interaction would be different between individuals of a racial and ethnic minority and non-Hispanic white individuals (thus testing catastrophizing as a moderated moderator). Higher levels of discrimination were positively related to catastrophic thinking about pain, and there was a significant negative relationship between the level of experienced discrimination and time to pain tolerance. Pain catastrophizing emerged as a significant moderator in that when pain catastrophizing levels were high, there was no association between social discrimination and pain tolerance. A history of social discrimination was significantly associated with reduced pain tolerance at low and moderate levels of pain catastrophizing. Racial minority status did not significantly alter this moderating relationship. Implications for the importance of assessing sociocultural variables, such as experiencing social discrimination in the clinical assessment of the individual with pain are outlined.

Short- and Long-Term Outcomes for Ethnic Minorities in the United States After Liver Transplantation: Parsing the Hispanic Paradox.

BACKGROUND: Racial and ethnic minorities are disproportionally affected by end-stage liver disease. Unfortunately, disparities in referrals to liver transplantation (LT), organ allocation, and posttransplant outcomes exist in this population. METHODS: We performed a retrospective analysis of patients over the age of 18 years undergoing LT in the United States using the Scientific Registry of Transplant Recipients from 2002 to 2016. We evaluated factors associated with patient and graft outcomes and explored the effect of race and ethnicity along with social variables. RESULTS: During the study time period, 78,999 patients received LT. Of these, 60,102 were non-Hispanic White (NHW), 7988 were African American (AA), and 10,909 were Hispanic. AA had significantly lower patient survival, graft survival, and death-censored graft survival at both 1 and 5 years when compared to NHW. Conversely, at 1 and 5 years, patient survival and graft survival were significantly higher for Hispanics compared to NWH. In addition, AA had significantly lower survival outcomes compared to Hispanics. On multivariate analysis after controlling for race/ethnicity, age, AA race, diagnosis, and deceased donor were independent risk factors for patient death and graft failure. CONCLUSIONS: Despite socioeconomic disadvantages seen among Hispanics, this population appears to have improved short- and long-term survival after LT compared to NHW and AA.

Incorporating merged treatment procedures for children with autism: A case report.

We examined interprofessional collaboration in a pre-service training model which incorporated the merging of three treatments: Occupational Therapy, Speech-Language Pathology, and Applied Behavior Analysis. We examined the effects of changes in the clinician interprofessional skill repertoire on therapeutic outcomes for children with Autism Spectrum Disorder. Three licensed professionals modeled core techniques from their respective professions to establish benchmark standards for skill demonstration in the treatment of children with autism. Treatment phases were implemented sequentially targeting multiple therapist and child behaviors within a multiple-baseline across participants' single case experimental design. Therapist skills improved to show a diverse repertoire of intervention techniques to match supervisor proficiencies. These interprofessional skills were delivered simultaneously in a timely and efficient manner. Assessed outcomes for children with autism included increased frequency of verbalizations, engagement during adult-directed interactions, visual-motor task productivity, and improved postural alignment. The study suggests that integrated training across interprofessional techniques enhanced a diverse repertoire of clinician skills, while systematically demonstrating child improvement on many interprofessional treatment goals.

What Should Dietary Supplement Oversight Look Like in the US?

Most American adults who use dietary supplements (eg, vitamins, minerals, plant and animal extracts, hormones, and amino acids) ingest them orally. The market for these products has grown rapidly and significantly over the last 25 years, but consumer protection regulations have not kept pace. In the United States, supplements' safety is regulated by the US Food and Drug Administration (FDA), but statutory limitations prevent the FDA from effectively regulating these products, exacerbate public health risk, and have generated numerous calls for reform. This article considers key features of reforms likely to strengthen the FDA's capacity to promote safety and consumer protection.

Use of M-M-R II outside of the routinely recommended age range - a systematic literature review.

M-M-R®II (M-M-R II) is routinely used in many countries at 12-15 months with a second dose at 4 to 6 years of age. However, the vaccine may need to be administered at other ages due to delays in the immunization schedule or in certain situations such as outbreaks or international travel. A systematic literature review was conducted to evaluate efficacy, immunogenicity and safety of M-M-R II among 6- to 11-month-olds and persons ≥7 years of age. A search for randomized controlled trials (RCTs) was conducted in 2019 including Medline, Embase and Cochrane CENTRAL. Only one study reported seroconversion rates after one dose in infants at 9 months of age: 87.4% (measles), 92.3% (mumps), and 91.2% (rubella); no safety data were reported. Seven studies reported immunogenicity and safety data for M-M-R II at ≥7 years of age. Seroconversion rates ranged from 96%-100% (measles), 65%-100% (mumps), and 91%-100% (rubella). Rates of selected adverse events ranged from 5.2%-8.7% for fever (≥38°C or ≥38.1°C), 2%-33.3% for injection site reactions, and 0.4% for measles/rubella-like rash (one study). No efficacy studies were found. This literature review identified RCTs with evidence to support that M-M-R II is immunogenic and well tolerated in individuals ≥7 years of age.

Adverse events related to unapproved stem cell products and other regenerative interventions: recommendations for more robust regulation of the direct-to-consumer marketplace.

Tweetable abstract Adverse events continue to occur in the direct-to-consumer market for unapproved regenerative interventions and the US FDA alone cannot adequately address the problem. Other public health strategies are needed to provide better patient protection.

Immersive interactive virtual walking reduces neuropathic pain in spinal cord injury: findings from a preliminary investigation of feasibility and clinical efficacy.

ABSTRACT: Chronic neuropathic pain (NP) is a common and often debilitating secondary condition for persons with spinal cord injury (SCI) and is minimally responsive to existing pharmacological and nonpharmacological treatments. The current preliminary investigation describes the feasibility and initial comparative efficacy of an interactive virtual reality walking intervention, which is a novel extension of visual feedback/illusory walking therapies shown to reduce SCI NP. Virtual reality walking intervention builds on previous research by, for the first time, allowing individuals with SCI NP to volitionally control virtual gait to interact with a fully immersive virtual environment. The current pilot study compared this interactive, virtual walking intervention to a passive, noninteractive virtual walking condition (analogous to previous illusory walking interventions) in 27 individuals with complete paraplegia (interactive condition, n = 17; passive condition, n = 10; nonrandomized design). The intervention was delivered over 2 weeks in individuals' homes. Participants in the interactive condition endorsed significantly greater reductions in NP intensity and NP-related activity interference preintervention to postintervention. Notable improvements in mood and affect were also observed both within individual sessions and in response to the full intervention. These results, although preliminary, highlight the potentially potent effects of an interactive virtual walking intervention for SCI NP. The current study results require replication in a larger, randomized clinical trial and may form a valuable basis for future inquiry regarding the mechanisms and clinical applications of virtual walking therapies.

Evaluation of the Safety and Immunogenicity of M-M-RII (Combination Measles-mumps-rubella Vaccine): Clinical Trials of Healthy Children and Adults Published Between 2010 and 2019.

BACKGROUND: The safety and immunogenicity of M-M-RII (measles, mumps and rubella virus vaccine live, Merck & Co., Inc., West Point, PA)-the only combined measles, mumps and rubella vaccine licensed for use in the United States-were previously reported in pre- and postlicensure clinical trials conducted from 1988 to 2009. M-M-RII continues to be evaluated as a comparator in clinical trials of other vaccines. Here, we review safety and efficacy data from more recent clinical trials of M-M-RII. METHODS: We performed a systematic literature review of trials using M-M-RII published from 2010 to 2019. RESULTS: In the 15 studies that met the inclusion criteria, a total of 12,032 subjects were vaccinated: 7667 persons received a first dose only, 2137 participated in 2-dose studies (128 received 1 dose and 2009 received both) and 2063 received a single dose of M-M-RII as their second dose. Dose number was not specified for 165 participants, ≥6 years old, in 2 studies in which a single dose of M-M-RII was administered. Similar to previous reports, M-M-RII was well tolerated and immunogenic when administered alone or concomitantly with other routinely recommended vaccinations. The most common adverse events included transient injection site pain and fever. Serious adverse events were extremely rare, with only 4 probable or potential vaccine-related events reported among the 12,032 participating subjects. CONCLUSIONS: In trials published from 2010 to 2019, M-M-RII continued to be safe and immunogenic in all age groups studied. These data, along with the results of earlier trials, indicate that the performance of the vaccine has been consistent across more than 30 years of postlicensure studies.