Therapeutic Relationships in Applied Behavior Analysis: Current Status and Future Directions.

For behavior analytic practitioners, skills related to building a therapeutic alliance (e.g., empathic statements, reflective listening, affirmations) may be as important as knowledge of and skills in implementation of the science of behavior analysis. We surveyed 277 board certified behavior analysts (BCBAs) to learn more about their training, use of these skills, and their perceptions of how their skills might have changed over years of practicing. The findings suggest that behavior analysts may benefit from explicit training in skills required to establish and maintain therapeutic relationships with parents of children with autism. In this article we review recent research in this area and suggest directions for training of behavior analysts. Further, motivational interviewing is introduced as an evidence-based clinical approach that encompasses many of the skills required to build a therapeutic alliance.

Non-viral in vivo cytidine base editing in hepatocytes using focused ultrasound targeted microbubbles.

CRISPR-Cas9-based genome editing technologies, such as base editing, have the potential for clinical translation, but delivering nucleic acids into target cells in vivo is a major obstacle. Viral vectors are widely used but come with safety concerns, while current non-viral methods are limited by low transfection efficiency. Here we describe a new method to deliver CRISPR-Cas9 base editing vectors to the mouse liver using focused ultrasound targeted microbubble destruction (FUTMD). We demonstrate, using the example of cytosine base editing of the Pde3b gene, that FUTMD-mediated delivery of cytosine base editing vectors can introduce stop codons (up to ∼2.5% on-target editing) in mouse liver cells in vivo. However, base editing specificity is less than one might hope with these DNA constructs. Our findings suggest that FUTMD-based gene editing tools can be rapidly and transiently deployed to specific organs and sites, providing a powerful platform for the development of non-viral genome editing therapies. Non-viral delivery also reveals greater off-target base exchange in vivo than in vitro.

Behavioral Parent Training via Telehealth for Autistic Children: Further Exploration of Feasibility During the COVID-19 Pandemic.

Objectives: Many autistic children exhibit challenging and disruptive behaviors that can present challenges for both children and their families by interfering with acquisition of adaptive skills and affecting family and peer relationships. Behavioral parent training (BPT) is an evidence-based approach to reducing autistic children's disruptive behavior, but many families face a number of barriers to accessing BPT, such as availability of BPT in their community, and transportation and scheduling challenges. Therefore, we sought to explore the feasibility and promise of effectiveness of adapting an established BPT program to a telehealth format during the COVID-19 pandemic. Methods: A feasibility trial of BPT via telehealth was conducted with fourteen parents of autistic children. Results: Parents and clinicians were able to implement BPT via telehealth with a high degree of fidelity, and parents rated both BPT and the telehealth format favorably. The program also showed promise of effectiveness in reducing autistic children's disruptive behavior, improving their adaptive skills, as well as reducing parents' stress, and improving parents' sense of parenting competence. Conclusions: The findings replicate and extend findings from previous studies, further demonstrating the promise of telehealth as a viable alternative format for delivering BPT. We also explore implications for future research, including the opportunity for more thorough evaluation of the effectiveness of BPT via telehealth.

Effect of Prearrival Orders on Time to Antibiotics for Immunocompromised Oncology Patients Presenting to the Emergency Department With Fever.

OBJECTIVE: Pediatric cancer patients with fever are at risk for invasive bacterial infection. The administration of antibiotics to these patients within the first hour of evaluation is viewed as a quality of care metric with potential to improve outcome. We sought to evaluate the impact of prearrival patient orders on the timeliness of antibiotic administration for this patient population presenting to the emergency department (ED) because of fever. METHODS: A single-site pediatric ED intervention study was performed. Four hundred thirty-nine consecutively referred febrile immunocompromised pediatric oncology patients were included in the study. The intervention used structured monthly messages sent to oncology and emergency medicine providers highlighting specific roles in prehospital communication and in ED-based care emphasizing the use of standardized, prearrival order (PAO) sets. Primary outcome measures were time to antibiotic administration (TTA) and the proportions of patients receiving PAO placement and antibiotics within 60 minutes of ED arrival. Results were analyzed for the preintervention (September 2016-July 2017), intervention (August 2017-February 2018), and postintervention (March-December 2018) periods. RESULTS: Improvements occurred across the study periods in the proportion of patients with PAO placement (preintervention, 68%; intervention, 82%; postintervention, 87%; P = 0.001) as well as in the percentages of patients receiving antibiotics in less than 60 minutes (preintervention, 73%; intervention, 84%; postintervention, 85%; P = 0.02). Median TTA decreased from 48 to 40 minutes ( P = 0.018). Linear regression with TTA as a dependent variable revealed that PAO placement predicted a shorter TTA, decreasing by more than 15 minutes ( B = -15.90; [95% confidence interval, -20.03--11.78]; P < 0.001). CONCLUSIONS: Standardizing elements of prehospital communication and ED-based care using PAO sets resulted in significant improvements in time to antibiotics and in the proportion of febrile immunocompromised oncology patients receiving antibiotics within 60 minutes of ED arrival.

A Comparison of Focused and Unfocused Ultrasound for Microbubble-Mediated Gene Delivery.

We compared focused and unfocused ultrasound-targeted microbubble destruction (UTMD) for delivery of reporter plasmids to the liver and heart in mice. Optimal hepatic expression was seen with double-depth targeting at 5 and 13 mm in vivo, incorporating a low pulse repetition frequency and short pulse duration. Reporter expression was similar, but the transfection patterns were distinct, with intense foci of transfection using focused UTMD (F-UTMD). We then compared both approaches for cardiac delivery and found 10-fold stronger levels of reporter expression for F-UTMD and observed small areas of intense luciferase expression in the left ventricle. Non-linear contrast imaging of the liver before and after insonation also showed a substantially greater change in signal intensity for F-UTMD, suggesting distinct cavitation mechanisms for both approaches. Overall, similar levels of hepatic transgene expression were observed, but cardiac-directed F-UTMD was substantially more effective. Focused ultrasound presents a new frontier in UTMD-directed gene therapy.

Thinking Small to Think Big: Modular Approach for Autism Programming in Schools (MAAPS).

To date there are no evidence-based comprehensive interventions for use in school settings. There are numerous barriers to delivery of high-quality interventions in schools that have limited the transfer of research-based interventions to school settings. Modular Approach to Autism Programing for Schools (MAAPS) is a framework for implementation of evidence-based interventions in school settings that is designed to address these barriers. The development and initial evaluation of MAAPS was conducted using an implementation-science framework and results indicate that MAAPS is aligned with needs and resources available in schools, that it had excellent social validity, and that there is good evidence that MAAPS is effective for addressing core and associated features of autism in educational settings.

Humanistic medicine in anaesthesiology: development and assessment of a curriculum in humanism for postgraduate anaesthesiology trainees.

BACKGROUND: An unintended consequence of medical technologies is loss of personal interactions and humanism between patients and their healthcare providers, leading to depersonalisation of medicine. As humanism is not integrated as part of formal postgraduate anaesthesiology education curricula, our goal was to design, introduce, and evaluate a comprehensive humanism curriculum into anaesthesiology training. METHODS: Subject-matter experts developed and delivered the humanism curriculum, which included interactive workshops, simulation sessions, formal feedback, and patient immersion experience. The effectiveness of the programme was evaluated using pre- and post-curriculum assessments in first-year postgraduate trainee doctors (residents). RESULTS: The anaesthesiology residents reported high satisfaction scores. Pre-/post-Jefferson Scale of Patient Perceptions of Physician Empathy showed an increase in empathy ratings with a median improvement of 12 points (range; P=0.013). After training, patients rated the residents as more empathetic (31 [4] vs 22 [5]; P<0.001; 95% confidence interval [CI]: 7-12) and professional (47 [3] vs 35 [8]; P<0.001; 95% CI: 9-16). Patient overall satisfaction with their anaesthesia provider improved after training (51 [6] vs 37 [10]; P<0.001; 95% CI: 10-18). Patients rated their anxiety lower in the post-training period compared with pretraining (1.8 [2.3] vs 3.6 [1.6]; P=0.001; 95% CI: 0.8-2.9). Patient-reported pain scores decreased after training (2.3 [2.5] vs 3.8 [2.1]; P=0.010; 95% CI: 0.4-2.8). CONCLUSIONS: Implementation of a humanism curriculum during postgraduate anaesthesiology training was well accepted, and can result in increased physician empathy and professionalism. This may improve patient pain, anxiety, and overall satisfaction with perioperative care.

Protein kinase C binding protein 1 inhibits hypoxia-inducible factor-1 in the heart.

AIMS: Hypoxia-inducible factor-1 alpha (HIF-1α) is a key transcription factor responsible for the induction of genes that facilitate adaptation to hypoxia. To study HIF-1 signalling in the heart, we developed a mouse model in which an oxygen-stable form of HIF-1α can be inducibly expressed in cardiac myocytes, under the regulation of tetracycline. METHODS AND RESULTS: Remarkably, expression of the transgene in mice generated two distinct phenotypes. One was the expected expression of HIF-regulated transcripts and associated changes in cardiac angiogenesis and contractility. The other was an unresponsive phenotype with much less expression of typical HIF-response genes and substantial expression of a zinc-finger protein, Protein Kinase C Binding Protein 1 (PRKCBP1). We have demonstrated that this second phenotype is due to an insertion of a fragment of DNA upstream of the PRKCBP1 gene that contains two additional canonical HIF binding sites and leads to substantial HIF binding, assessed by chromatin immunoprecipitation, and transcriptional activation. This insertion is found only in the FVB strain of mice that contributed the αMHC-tet binding protein transgene to these biallelic mice. In HEK293 cells transfected with oxygen-stable HIF-1α and PRKCBP1, we demonstrated inhibition of HIF-1 activity by a luciferase reporter assay. Using mouse primary cells and cell lines, we show that transfection with oxygen-stable HIF-1α and PRKCBP1 reduced expression of direct HIF-1 gene targets and that knockdown of PRKCBP1 removes that negative inhibition. Consistent with previous reports suggesting that PRKCBP1 modulates the chromatin landscape, we found that HL-1 cells transfected with oxygen-stable HIF-1α and PRKCBP1 have reduced global 5-methyl cytosine compared to HIF-1 alone. CONCLUSION: We show genetic, transcriptional, biochemical, and physiological evidence that PRKCBP1 inhibits HIF activity. Identification of a new oxygen-dependent and previously unsuspected regulator of HIF may provide a target for new therapeutic approaches to ischaemic heart disease.

Casting a Wider Net: an Analysis of Scholarly Contributions of Behavior Analysis Graduate Program Faculty.

As interest in careers in behavior analysis has grown, there has been a concomitant increase in the number of training programs providing coursework in behavior analysis. There is a growing need for indices of quality of these programs, with some authors recently suggesting that faculty research productivity might serve as one indicator of program quality. We continue this conversation, taking a broad view of faculty scholarly contributions by conducting a search of all articles authored by instructors in graduate-level Behavior Analyst Certification Board verified course sequences (VCSs) and published from 2000 to 2015 in peer-reviewed journals indexed by the PsycINFO database. The resulting list includes 8,906 publication records in 715 journals, authored by 1,232 instructors from 224 programs. Our analysis suggests that graduate-level VCS instructors have published in a broad array of journals and topic areas. We discuss implications of these data for prospective students' evaluations of program quality and fit.

Advances in School-Based Interventions for Students With Autism Spectrum Disorder: Introduction to the Special Issue.

As the diagnosis of autism spectrum disorder has increased, so too has research on interventions to address core and associated features of autism. Although many methodologically rigorous studies on interventions have been reported, their relevance to educators is somewaht unclear. For example, only about 32% of evidence-based strategies identifed in these reviews were conducted in k-12 settings. Current literature also is limited in that, although many studies show that interventions can improve the communication and social interaction skills of individuals with autism, most of this work has been conducted with pre-school children; questions remain about the generality of these findings to school-aged children. Further, there are relatively few studies demonstrating effective interventions for restricted and repetitive behavior and much of this work was conducted in clinical settings. There is a need for studies documenting effective interventions that are feasible in school settings. The purpose of this special issue is two-fold. First, to highlight the need for school-based research with students with autism and second to highlight recent work delineating intervention strategies found to be effective in school settings.

Revised Ion/Substrate Coupling Stoichiometry of GABA Transporters.

The purpose of this review is to highlight recent evidence in support of a 3 Na+: 1 Cl-: 1 GABA coupling stoichiometry for plasma membrane GABA transporters (SLC6A1 , SLC6A11 , SLC6A12 , SLC6A13 ) and how the revised stoichiometry impacts our understanding of the contribution of GABA transporters to GABA homeostasis in synaptic and extrasynaptic regions in the brain under physiological and pathophysiological states. Recently, our laboratory probed the GABA transporter stoichiometry by analyzing the results of six independent measurements, which included the shifts in the thermodynamic transporter reversal potential caused by changes in the extracellular Na+, Cl-, and GABA concentrations, as well as the ratio of charge flux to substrate flux for Na+, Cl-, and GABA under voltage-clamp conditions. The shifts in the transporter reversal potential for a tenfold change in the external concentration of Na+, Cl-, and GABA were 84 ± 4, 30 ± 1, and 29 ± 1 mV, respectively. Charge flux to substrate flux ratios were 0.7 ± 0.1 charges/Na+, 2.0 ± 0.2 charges/Cl-, and 2.1 ± 0.1 charges/GABA. We then compared these experimental results with the predictions of 150 different transporter stoichiometry models, which included 1-5 Na+, 0-5 Cl-, and 1-5 GABA per transport cycle. Only the 3 Na+: 1 Cl-: 1 GABA stoichiometry model correctly predicts the results of all six experimental measurements. Using the revised 3 Na+: 1 Cl-: 1 GABA stoichiometry, we propose that the GABA transporters mediate GABA uptake under most physiological conditions. Transporter-mediated GABA release likely takes place under pathophysiological or extreme physiological conditions.

Recovery and assessment of leukocytes from LR Express filters.

Leukocytes, or white blood cells, are used for a variety of investigational purposes and they offer advantages over laboratory-adapted cell lines. Leukocytes that are typically discarded by blood banks during the collection of red blood cells, platelets, and plasma can often be obtained for research use. However, the available leukocytes are frequently contained within a blood filtration device, such as the Terumo LR Express (TLRE) filter. In this study, procedures were evaluated for the ability to elute viable leukocytes from TLRE filters. The recovered leukocytes were assessed for composition, growth, and functionality. The large majority (>70%) of leukocytes were eluted with a single reverse-elution procedure and the recovered cells contained representative populations of the major leukocyte subsets. Purified T cells exhibited diverse T cell receptor repertoires, characteristic growth upon mitogen stimulation, and CD4+ T cells were able to support HIV-1 propagation. Purified monocytes were able to be differentiated into phenotypically characteristic populations of macrophages and dendritic cells. Overall, TLRE filters offer an attractive source of primary human cells for research and possibly clinical purposes.

Updated feasibility and reproducibility results of multi-institutional study of noninvasive breast tumor bed boost.

PURPOSE: To report updated feasibility and reproducibility results for high-dose-rate noninvasive breast brachytherapy (NIBB) for tumor bed boost with whole breast radiation therapy (WBRT) in the setting of expanded patient and treatment facility number. METHODS AND MATERIALS: Fifteen independent community-based and academic centers reported 518 early-stage breast cancer patients from July 2007 to February 2015 on a privacy-encrypted online data registry. All patients' treatment included lumpectomy followed by combination of WBRT and NIBB. NIBB was completed with commercially available (AccuBoost, Billerica, MA) mammography-based system using high-dose-rate 192Ir emissions along orthogonal axes. Harvard scale was used to grade cosmesis. RESULTS: Total patient cohort had median followup of 12 months (1-75 months) with subset of 268 having available cosmesis. Greater than 2- and 3-year followup was 29% and 14%, respectively. Entire cohort had 97.4% excellent/good (E/G) breast cosmesis and freedom from recurrence of 97.6% at the final followup. WBRT timing with respect to NIBB delivery demonstrated no statistically significant difference in E/G cosmesis. Achieved E/G cosmesis rate was also not statistically significant (χ2p-value = 0.86) between academic and community institutions with 97.8% vs. 96.6%. CONCLUSIONS: NIBB represents an alternative method for delivery of breast tumor cavity boost that has shown feasibility in a diverse group of both academic and community-based practices with reproducible early cosmesis and tumor control results. Recommendations are updated noting ideal timing of boost delivery likely to be before or early during WBRT given equal cosmesis and less documented treatment discomfort.

Ethnopharmacological survey about medicinal plants utilized by herbalists and traditional practitioner healers for treatments of diarrhea in the West Bank/Palestine.

ETHNOPHARMACOLOGICAL RELEVANCE: Folk herbal medicine knowledge and its utilization by aboriginal cultures are not only useful for conservation of cultural traditions and biodiversity, but also useful for community healthcare and drug discovery in the present and in the future. AIM OF THE STUDY: Using a semi-structured questionnaire, an ethnopharmacological survey of medicinal plants used for treatment of diarrhea in the West Bank/Palestine was investigated. RESULTS: Information about fifty medicinal plants used for treatment of diarrhea, including the names of plants, parts used, mode and methods of preparation was obtained from 100 traditional healers and herbalists. This research is the first scientific work in the Middle East to collect data about plants used by traditional healers for treatments of diarrhea and their evidence based effects against this disease. The fidelity levels were 97% for Salvia fruticosa, Teucrium polium and Musa paradisiaca, 95% for Camellia sinensis and Aegle marmelos, 79% for Oryza sativa and Solanum tuberosum, 77% for Quercus boissieri, 66% for Psidium guajava, 56% for Anthemis palestina, 54% for Solanum nigrum and 52% for Juglans regia while the highest use and choice values were for S. fruticosa, T. polium and M. paradisiaca as well as the factor of informant's consensus for medicinal plants used for treatment of diarrhea was 0.505.The leaves were the most commonly used parts, followed by fruits, roots and rhizomes, while decoctions and infusions are the preferred methods of preparation. CONCLUSIONS: The Palestinian traditional medicine is rich with herbal remedies for treatment of diarrhea in comparison with other countries, but most of these herbal remedies lack standard in-vitro and in-vivo evaluations to establish their antidiarrheal effects. Therefore, the information obtained can serve as a basis for further phytochemical and pharmacological studies to determine their efficacy and safety which might contribute to a better integration of Palestinian traditional medicine into the national health system in the future.

Effects of a video feedback parent training program during child welfare visitation.

Behavioral parent training programs have documented efficacy for improving behaviors among parents and their children and are frequently used by child welfare agencies to prevent removal of a child from the parental home or to facilitate reunification. Although an ideal time for parent training might be during supervised visits where parents may practice skills with their children under the guidance and support of a therapist or caseworker, this is not typically the case. Most often, parents within the child welfare system receive parent training in small groups without their children present, and to date, few studies have examined effects of behavioral parent training interventions during supervised visitation. In this study, concurrent multiple baseline across behaviors design was used to examine effects of a behavioral parent training program, Filming Interactions to Nurture Development (FIND), on parental skill acquisition with four mothers who had lost custody of their children but were being considered for reunification. Children emitted little or no problem behaviors during baseline or intervention, so parenting behavior was the primary dependent variable. Results obtained across participants documented a clear functional relation between implementation of the FIND intervention and increases in developmentally supportive parenting behaviors. Results of social validity and contextual fit measures suggest the intervention was perceived by mothers to be positive, feasible, and appropriate within the child welfare context. Practical and conceptual implications, limitations of this study, and directions for future research are discussed.

Prevalence and Predictors of Unhealthy Weight Gain in Pregnancy.

IMPORTANCE: Weight gain during pregnancy affects obesity risk in offspring. OBJECTIVE: To assess weight gain among UW Health prenatal patients and to identify predictors of unhealthy gestational weight gain. METHODS: Retrospective cohort study of women delivering at UW Health during 2007-2012. Data are from the UW eHealth Public Health Information Exchange (PHINEX) project. The proportion of women with excess and insufficient (ie, unhealthy) gestational weight gain was computed based on 2009 Institute of Medicine guidelines. Multivariable logistic regression was used to identify risk factors associated with excess and insufficient gestational weight gain. RESULTS: Gestational weight gain of 7,385 women was analyzed. Fewer than 30% of prenatal patients gained weight in accordance with Institute of Medicine guidelines. Over 50% of women gained excess weight and 20% gained insufficient weight during pregnancy. Pre-pregnancy weight and smoking status predicted excess weight gain. Maternal age, race/ethnicity, smoking status, and having Medicaid insurance predicted insufficient weight gain. CONCLUSIONS AND RELEVANCE: Unhealthy weight gain during pregnancy is the norm for Wisconsin women. Clinical and community interventions that promote healthy weight gain during pregnancy will not only improve the health of mothers, but also will reduce the risk of obesity in the next generation.

Epigenetics of drought-induced trans-generational plasticity: consequences for range limit development.

Genetic variation gives plants the potential to adapt to stressful environments that often exist beyond their geographic range limits. However, various genetic, physiological or developmental constraints might prevent the process of adaptation. Alternatively, environmentally induced epigenetic changes might sustain populations for several generations in stressful areas across range boundaries, but previous work on Boechera stricta, an upland mustard closely related to Arabidopsis, documented a drought-induced trans-generational plastic trade-off that could contribute to range limit development. Offspring of parents who were drought treated had higher drought tolerance, but lower levels of glucosinolate toxins. Both drought tolerance and defence are thought to be needed to expand the range to lower elevations. Here, we used methylation-sensitive amplified fragment length polymorphisms to determine whether environmentally induced DNA methylation and thus epigenetics could be a mechanism involved in the observed trans-generational plastic trade-off. We compared 110 offspring from the same self-fertilizing lineages whose parents were exposed to experimental drought stress treatments in the laboratory. Using three primer combinations, 643 polymorphic epi-loci were detected. Discriminant function analysis (DFA) on the amount of methylation detected resulted in significant combinations of epi-loci that distinguished the parent drought treatments in the offspring. Principal component (PC) and univariate association analyses also detected the significant differences, even after controlling for lineage, planting flat, developmental differences and multiple testing. Univariate tests also indicated significant associations between the amount of methylation and drought tolerance or glucosinolate toxin concentration. One epi-locus that was implicated in DFA, PC and univariate association analysis may be directly involved in the trade-off because increased methylation at this site on the genome decreased drought tolerance, but increased glucosinolate concentration.

Evidence for a Revised Ion/Substrate Coupling Stoichiometry of GABA Transporters.

Plasma membrane γ-aminobutyric acid (GABA) transporters (GATs) are electrogenic transport proteins that couple the cotranslocation of Na(+), Cl(-), and GABA across the plasma membrane of neurons and glia. A fundamental property of the transporter that determines its ability to concentrate GABA in cells and, hence, regulate synaptic and extra-synaptic GABA concentrations, is the ion/substrate coupling stoichiometry. Here, we scrutinized the currently accepted 2 Na(+):1 Cl(-):1 GABA stoichiometry because it is inconsistent with the measured net charge translocated per co-substrate (Na(+), Cl(-), and GABA). We expressed GAT1 and GAT3 in Xenopus laevis oocytes and utilized thermodynamic and uptake under voltage-clamp measurements to determine the stoichiometry of the GABA transporters. Voltage-clamped GAT1-expressing oocytes were internally loaded with GABA, and the reversal potential (V rev) of the transporter-mediated current was recorded at different external concentrations of Na(+), Cl(-), or GABA. The shifts in V rev for a tenfold change in the external Na(+), Cl(-), and GABA concentration were 84 ± 4, 30 ± 1, and 29 ± 1 mV, respectively. To determine the net charge translocated per Na(+), Cl(-), and GABA, we measured substrate fluxes under voltage clamp in cells expressing GAT1 or GAT3. Charge flux to substrate flux ratios were 0.7 ± 0.1 charge/Na(+), 2.0 ± 0.2 charges/Cl(-), and 2.1 ± 0.1 charges/GABA. Altogether, our results strongly suggest a 3 Na(+):1 Cl(-):1 GABA coupling stoichiometry for the GABA transporters. The revised stoichiometry has important implications for understanding the contribution of GATs to GABAergic signaling in health and disease.

Intravenous immunoglobulin may be an effective therapy for refractory, active diffuse cutaneous systemic sclerosis.

OBJECTIVE: We sought to retrospectively review a single-center experience using intravenous immunoglobulin (IVIG) for the treatment of refractory, active diffuse cutaneous systemic sclerosis (dcSSc). METHODS: The mean modified Rodnan Skin score (mRSS) at baseline was compared to the mRSS at 6, 12, 18, and 24 months post-IVIG initiation by the paired Student t test. Changes in mRSS at 6 and 12 months were also compared to data from historical controls of 3 large, negative, multicenter, randomized clinical trials of other medications [D-penicillamine (D-pen), recombinant human relaxin (relaxin), and oral bovine type I collagen (collagen)] and to patients treated with mycophenolate mofetil (MMF) alone using the Student t test. RESULTS: Thirty patients were treated with adjunctive IVIG (2 g/kg/mo) for refractory, active dcSSc. The mean baseline mRSS of our cohort was 29.6 ± 7.2, and this significantly decreased to 24.1 ± 9.6 (n = 29, p = 0.0011) at 6 months, 22.5 ± 10.0 (n = 25, p = 0.0001) at 12 months, 20.6 ± 11.8 (n = 23, p = 0.0001) at 18 months, and 15.3 ± 6.4 (n = 15, p < 0.0001) at 24 months. The mean change in mRSS at 6 months was not significantly different in the IVIG group (-5.3 ± 7.9) compared to the relaxin trial (-4.8 ± 6.99, p = 0.74) or MMF group (-3.4 ± 7.4, p = 0.26); however, at 12 months, the mean change in mRSS was significantly better in the IVIG group (-8 ± 8.3) than in the D-pen (-2.47 ± 8.6, p = 0.005) and collagen (-3.4 ± 7.12, p = 0.005) groups, and was comparable to the group of primary MMF responders (-7.1 ± 9, p = 0.67). CONCLUSION: Our observational study suggests that IVIG may be an effective adjunctive therapy for active dcSSc in patients failing other therapies.