Treatment Of Disorders Research Articles

Advancing Research on and Treatment of Dissociative Identity Disorder With People With Lived Experience.

Dissociative identity disorder is a posttraumatic, psychobiological syndrome that develops over time during childhood. Despite empirical evidence supporting the validity of this diagnosis and its relation to trauma, the disorder remains a misunderstood and stigmatized condition. This article highlights expert consensus guidelines and current empirical research on the treatment of dissociative identity disorder. In addition, the authors describe the Lived Experience Advisory Panel (LEAP), which was designed to leverage the expertise of individuals with dissociative identity disorder to combat stigma and improve research, clinical programming, professional education, and public outreach related to the disorder. This article also describes how LEAP members have partnered with other researchers to create new knowledge through participatory action research in order to advance equitable service provision and effect positive change.

Perinatal women in substance use disorder treatment: Interest in partnering with family and friends to support recovery needs.

Perinatal women treated for substance use disorder (SUD) face considerable barriers to recovery that might be ameliorated through activation of community support. This descriptive study evaluated the presence of drug-free family and friends in the social networks of perinatal women treated for SUD. It also assessed the interest of these women to partner with network members to mobilize support across several recovery needs. Social network interviews were conducted with 40 pre- and post-partum women treated at the Center for Addiction and Pregnancy (CAP) in Baltimore, Maryland. These interviews also prompted participants to consider which network members to invite to the program to support recovery efforts. Study participants reported that their personal social networks included 4.4 drug-free adults. An overwhelming majority (80%) of participants reported a willingness to invite at least one person to the CAP program. Participants also endorsed several opportunities for collaboration between the program and community support. These findings suggest that treatment program guided activation of network support offers a testable strategy to help perinatal women reduce barriers to recovery and improve treatment outcomes.

Advances in non-viral mRNA delivery to the spleen.

Developing safe and effective delivery strategies for localizing messenger RNA (mRNA) payloads to the spleen is an important goal in the field of genetic medicine. Accomplishing this goal is challenging due to the instability, size, and charge of mRNA payloads. Here, we provide an analysis of non-viral delivery technologies that have been developed to deliver mRNA payloads to the spleen. Specifically, our review begins by outlining the unique anatomy and potential targets for mRNA delivery within the spleen. Next, we describe approaches in mRNA sequence engineering that can be used to improve mRNA delivery to the spleen. Then, we describe advances in non-viral carrier systems that can package and deliver mRNA payloads to the spleen, highlighting key advances in the literature in lipid nanoparticle (LNP) and polymer nanoparticle (PNP) technology platforms. Finally, we provide commentary and outlook on how splenic mRNA delivery may afford next-generation treatments for autoimmune disorders and cancers. In undertaking this approach, our goal with this review is to both establish a fundamental understanding of drug delivery challenges associated with localizing mRNA payloads to the spleen, while also broadly highlighting the potential to use these genetic medicines to treat disease.

Surgical treatment of intracapsular temporomandibular disorders.

Temporomandibular joint (TMJ) pathologies are prevalent, affecting approximately 40% of the worldwide population, with nearly 80% involving intracapsular disorders. Despite this, standardized treatment protocols are lacking. This study aimed to compare the efficacy of conservative and surgical approaches in managing intracapsular TMJ disorders. Eighty-six patients diagnosed with intracapsular TMJ disorders were included in the study, with 40 males and 46 females, averaging 52.4 ± 4.7 years. Patients were recruited from polyclinics in Beijing, China (n = 36), and Kyiv, Ukraine (n = 50). A comprehensive examination protocol was conducted, including assessment of patient complaints, medical history, jaw mobility measurements, TMJ palpation, and magnetic resonance imaging (MRI) screening. The main outcomes of our study revealed significant improvements in patients undergoing surgical intervention for intracapsular TMJ disorders, particularly in cases of disc displacement. Conservative mouth guard/occlusal splint treatment showed limited effectiveness, primarily improving joint effusion and disc displacement. Surgical intervention led to notable enhancements in various TMJ parameters, with significant improvements observed in joint function and pain reduction. Based on these findings, orthodontic rehabilitation was recommended to ensure long-term efficacy, focusing on optimizing occlusion and restoring TMJ function. These results highlight the importance of tailored treatment approaches for managing intracapsular TMJ disorders, emphasizing the role of surgical intervention coupled with comprehensive rehabilitation strategies. Future research should consider demographic factors and explore innovative examination methods, such as optical systems, to enhance understanding and management of intracapsular TMJ disorders.

The use of prolonged-release melatonin in circadian medicine: a systematic review.

Melatonin, a hormone produced by the pineal gland, regulates the sleep-wake cycle and is effective in restoring biological rhythms. Prolonged-release melatonin (PRM) is designed to mimic the natural physiological pattern of melatonin release. In circadian medicine, PRM can be used to treat sleep and circadian rhythm disorders, as well as numerous organic diseases associated with sleep disorders. This systematic review analyzed 62 studies and adhered to the PRISMA guidelines, examining the effectiveness of PRM in organic pathologies and mental disorders. The main evidence concerns primary insomnia in subjects over the age of 55, showing significant improvements in sleep quality. In neurodevelopmental disorders, there is evidence of a positive impact on sleep quality and quality of life for patients and their caregivers. PRM shows efficacy in the treatment of sleep disorders in mood disorders, schizophrenia, and neurocognitive disorders, but requires further confirmation. The additional use of PRM is supported for the withdrawal of chronic benzodiazepine therapies. The tolerability and safety of PRM are excellent, with ample evidence supporting the absence of tolerance and dependence. Overall, PRM in circadian medicine is an effective chronopharmaceutical for restoring the sleep-wake rhythm in patients with insomnia disorder. This efficacy may also extend to sleep disorders associated with mood, neurodevelopmental and neurocognitive disorders, suggesting a further potential role in insomnia associated with various organic diseases.

Social communication and restricted, repetitive behavior as assessed with a diagnostic tool for autism (ADOS-2) in women with anorexia nervosa.

In anorexia nervosa (AN), the traits of autism spectrum disorder (ASD) are associated with poor outcomes. However, the subtle nature of these characteristics remains poorly understood. We investigated the in-depth patterns of ASD traits using Autism Diagnostic Observation Schedule-Second Edition (ADOS-2) in women with AN. Of 28 women with ICD-10 AN, 16 (age 19-30 years) participated in the ADOS-2, a video-recorded, semistructured diagnostic assessment for social communication and interaction and restricted, repetitive behaviors and interests related to ASD. None of the participants had previously been diagnosed with ASD. Other measurements included the Eating Disorder Examination Questionnaire and the Wechsler Abbreviated Scale of Intelligence-IV. Five individuals (18% of all, 31% of those assessed) scored above the cutoff for autism in ADOS-2. They had challenges in social communication and interaction, manifesting as sustained difficulties in social relationships and deficits in conversation skills. Few described being frequently misunderstood by others, including in the eating disorder treatment settings. Three individuals showed prominent restricted and repetitive behaviors such as ritual seeking, eating-related routines, sensory sensitivity related to food texture and selective eating, and intense interest in specific topics. The mean duration of AN in women above the cutoff was twice as long compared with those below (12.3 vs. 6.2 years). The ASD-related characteristics and behavior appear to contribute to the manifestation and duration of AN in a subgroup of women. Among these women, the traits of ASD appear to be mixed with eating disorder symptoms, which should be taken into account in the treatment.

Pharmacologic profile of ITI-333: a novel molecule for treatment of substance use disorders.

Medications are urgently needed to treat symptoms of drug withdrawal and mitigate dysphoria and psychiatric comorbidities that drive opioid abuse and relapse. ITI-333 is a novel molecule in development for treatment of substance use disorders, psychiatric comorbidities, and pain. Characterize the preclinical profile of ITI-333 using pharmacological, behavioral, and physiological assays. Cell-based assays were used to measure receptor binding and intrinsic efficacy of ITI-333; animal models were employed to assess effects on opioid reinstatement, precipitated oxycodone withdrawal, and drug abuse liability. In vitro, ITI-333 is a potent 5-HT2A receptor antagonist (Ki = 8nM) and a biased, partial agonist atμ-opioid (MOP) receptors (Ki = 11nM; lacking β-arrestin agonism) with lesser antagonist activity at adrenergic α1A (Ki = 28nM) and dopamine D1 (Ki = 50nM) receptors. In vivo, ITI-333 blocks 5-HT2A receptor-mediated head twitch and MOP receptor-mediated effects on motor hyperactivity in mice. ITI-333 alone is a naloxone-sensitive analgesic (mice) which suppresses somatic signs of naloxone-precipitated oxycodone withdrawal (mice) and heroin cue-induced reinstatement responding without apparent tolerance or physical dependence after chronic dosing (rats). ITI-333 did not acutely impair gastrointestinal or pulmonary function (rats) and was not intravenously self-administered by heroin-maintained rats or rhesus monkeys. ITI-333 acts as a potent 5-HT2A receptor antagonist, as well a biased MOP receptor partial agonist with low intrinsic efficacy. ITI-333 mitigates opioid withdrawal/reinstatement, supporting its potential utility as a treatment for OUD.

Targeting pentamidine towards CD44-overexpressing cells using hyaluronated lipid-polymer hybrid nanoparticles.

Biodegradable nanocarriers possess enormous potential for use as drug delivery systems that can accomplish controlled and targeted drug release, and a wide range of nanosystems have been reported for the treatment and/or diagnosis of various diseases and disorders. Of the various nanocarriers currently available, liposomes and polymer nanoparticles have been extensively studied and some formulations have already reached the market. However, a combination of properties to create a single hybrid system can give these carriers significant advantages, such as improvement in encapsulation efficacy, higher stability, and active targeting towards specific cells or tissues, over lipid or polymer-based platforms. To this aim, this work presents the formulation of poly(lactic-co-glycolic) acid (PLGA) nanoparticles in the presence of a hyaluronic acid (HA)-phospholipid conjugate (HA-DPPE), which was used to anchor HA onto the nanoparticle surface and therefore create an actively targeted hybrid nanosystem. Furthermore, ionic interactions have been proposed for drug encapsulation, leading us to select the free base form of pentamidine (PTM-B) as the model drug. We herein report the preparation of hybrid nanocarriers that were loaded via ion-pairing between the negatively charged PLGA and HA and the positively charged PTM-B, demonstrating an improved loading capacity compared to PLGA-based nanoparticles. The nanocarriers displayed a size of below 150nm, a negative zeta potential of -35mV, a core-shell internal arrangement and high encapsulation efficiency (90%). Finally, the ability to be taken up and exert preferential and receptor-mediated cytotoxicity on cancer cells that overexpress the HA specific receptor (CD44) has been evaluated. Competition assays supported the hypothesis that PLGA/HA-DPPE nanoparticles deliver their cargo within cells in a CD44-dependent manner.

Levels of engagement among office-based opioid treatment (OBOT) patients with concurrent methamphetamine use.

Recent increases in methamphetamine use among people seeking treatment for opioid use disorder (OUD) has created significant demand for effective approaches to support this clinical population. This study assessed the extent to which office-based opioid treatment (OBOT) patients, who were diagnosed with methamphetamine use disorder (MUD), engaged with providers. A retrospective analysis was conducted of adult patients (n = 470) seeking treatment for OUD who attended at least one visit between March 2020 and March 2023 at a rural regional OBOT provider. Approximately one quarter (28.7%) of patients were diagnosed with MUD in addition to receiving an OUD diagnosis. Bivariate methods and multivariate negative binomial regression models were estimated to examine the associations between clinical measures and the numbers of office visits, peer visits, and telehealth visits. Regression results indicated patients who met criteria for MUD in addition to OUD attended a higher rate of peer visits (incidence rate ratio [IRR] = 2.63, p = .036) when compared to patients who did not meet criteria for MUD. In contrast, patients with MUD and OUD diagnoses displayed significantly lower (IRR = 0.68, p < .001) engagement rates through fewer office visits relative to those who did not meet MUD criteria. Patients seeking treatment for OUD who meet criteria for MUD are more likely to engage through peer support specialists rather than office visits. This study demonstrates the ways patients who meet criteria for OUD and MUD engage with providers to receive treatment.

Oral administration of Lactobacillus delbrueckii subsp. lactis LDL557 attenuates airway inflammation and changes the gut microbiota in a Der p-sensitized mouse model of allergic asthma.

Atopic dermatitis (AD) is a chronic inflammatory skin disorder affecting up to 20% of children in developed countries. Although probiotics have shown promise as adjuvant treatments for AD, their mechanisms are not well understood. Building upon our previous studies, we investigated whether Lactobacillus gasseri and its moonlighting glyceraldehyde 3-phosphate dehydrogenase (GAPDH), namely LGp40, could be beneficial in AD management. In AD mouse models (SKH and C57BL/6J mice) with ovalbumin (OVA) and Dermatophagoides pteronyssinus (Der p) allergens, aligning with the "outside-in" and "inside-out" hypotheses, we administered L. gasseri orally and LGp40 intraperitoneally to investigate their protective effects. The evaluation involved measuring physiological, pathological, and immune function parameters. To delve deeper into the detailed mechanism of LGp40 protection in AD, additional assays were conducted using human skin keratinocytes (HaCaT) and monocytes (THP1) cell lines. L. gasseri and LGp40 enhanced skin barrier function and increased skin moisture retention. They also led to reduced infiltration of Langerhans cells in the dermis and mitigated skewed Th2 and Th17 immune responses. Moreover, LGp40 inhibited allergen-induced keratinocyte apoptosis through the blockade of the caspase-3 cascade and reduced the NLR family pyrin domain containing 3 (NLRP3) inflammasome in macrophages. These inhibitions were achieved through the activation of the peroxisome proliferator-activated receptor gamma (PPARγ) pathway. The results of this study provide a novel insight into the mechanism of action of probiotics in the prevention and treatment for allergic disorders through the moonlighting GAPDH protein.

The reflections of health service providers on implementing contingency management for methamphetamine use disorder in Australia.

Contingency management (CM) is the most effective treatment for reducing methamphetamine use. We sought to understand why CM has not been taken up to manage methamphetamine use disorder in Australia. Six focus groups (4-8 participants per group) were conducted with health workers from agencies in Australia that provided drug-related health care to people who use methamphetamine. These agencies had no previous experience delivering CM for substance use. The potential acceptability and feasibility of implementing CM in their services were discussed. Participants felt that it would be beneficial to have an evidence-based treatment for methamphetamine use disorder. This sentiment was offset by concerns that CM conflicted with a client-centred harm-reduction approach and that it dictated the goal of treatment as abstinence. It was also perceived as potentially coercive and seen to reify the power imbalance in the therapeutic relationship and therefore potentially reinforce stigma. There was also concern about the public's perception and the political acceptability of CM, who would fund CM, and the inequity of providing incentives only to clients with a methamphetamine use disorder. Some concerns could be ameliorated if the goals and structure of CM could be tailored to a client's needs. Many healthcare workers were keen to offer CM as an effective treatment option for people with methamphetamine use disorder, but CM would need to be sufficiently flexible to allow it to be tailored to client needs and implemented in a way that did not adversely impact the therapeutic relationship.

Sacral neuromodulation in children and adolescents with defecation disorders.

Even if understanding of neuronal enteropathies, such as Hirschsprung's disease and functional constipation, has been improved, specialized therapies are still missing. Sacral neuromodulation (SNM) has been established in the treatment of defecation disorders in adults. The aim of the study was to investigate effects of SNM in children and adolescents with refractory symptoms of chronic constipation. A two-centered, prospective trial has been conducted between 2019 and 2022. SNM was applied continuously at individually set stimulation intensity. Evaluation of clinical outcomes was conducted at 3, 6, and 12 months after surgery based on the developed questionnaires and quality of life analysis (KINDLR). Primary outcome was assessed based on predefined variables of fecal incontinence and defecation frequency. Fifteen patients enrolled in the study and underwent SNM (median age 8.0 years (range 4-17 years)): eight patients were diagnosed with Hirschsprung's disease (53%). Improvement of defecation frequency was seen in 8/15 participants (53%) and an improvement of fecal incontinence in 9/12 patients (75%). We observed stable outcome after 1 year of treatment. Surgical revision was necessary in one patient after electrode breakage. Urinary incontinence was observed as singular side effect of treatment in two patients (13%), which was manageable with the reduction of stimulation intensity. SNM shows promising clinical results in children and adolescents presenting with chronic constipation refractory to conservative therapy. Indications for patients with enteral neuropathies deserve further confirmation.

Individual Trajectories of Specialist Substance Use Disorder and Mental Health Treatment Utilization Among Young Adults With Substance Use Problems: A Cohort Study

Objective The aim of the study was to identify groups of young adults with distinct longitudinal patterns of use of treatment for substance use disorders and mental health (MH) problems and to investigate potential explanatory factors for different patterns of treatment use over time, including sociodemographic factors. Methods The sample consisted of 447 young adults aged 16–29 years who entered long-term residential substance use disorder treatment facilities in Norway from 2011 to 2016. In this study, we obtained data collected by the Norwegian Patient Registry and Statistics Norway. These data were linked with the electronic health record data of the substance use disorder treatment facilities from which the participants were recruited. Growth mixture modeling was performed. The identified groups were further compared using analysis of variance or χ 2 test. Results Four groups of participants for total treatment use, substance use disorder treatment use, and MH treatment use were identified. Most participants from the overall sample were classified as members of a group characterized by a low and stable pattern of treatment use over time. A group with a high and stable pattern of treatment use was identified in total and MH treatment use. The proportion of participants with higher levels of substance use disorder treatment use at the end of the study period than at the beginning was larger (35%) than in the case of MH treatment use (14.2%). Younger age was associated with a decreasing pattern of MH treatment use and with an increasing pattern of substance use disorder treatment use over time. There were larger proportions of female participants in groups with a stable high use of MH treatment and in groups with an initially increasing trend of substance use disorder treatment use. Findings revealed that most participants across the identified groups were recipients of welfare benefits, had low educational attainment, and were not working. Conclusions Results demonstrated significant variation in trajectories of treatment use among young adults with substance use disorder. Differences in treatment use could indicate differences in symptom severity and complexity. In this study, treatment use was associated with socioeconomic factors, sex, and age. Integrative approaches, including interagency and interdisciplinary collaboration, will often be necessary to sufficiently address the multidimensionality of substance use disorder.

Trauma exposure across the lifespan among individuals engaged in treatment with medication for opioid use disorder: differences by gender, PTSD status, and chronic pain

BackgroundThere is little study of lifetime trauma exposure among individuals engaged in medication treatment for opioid use disorder (MOUD). A multisite study provided the opportunity to examine the prevalence of lifetime trauma and differences by gender, PTSD status, and chronic pain.MethodsA cross-sectional study examined baseline data from participants (N = 303) enrolled in a randomized controlled trial of a mind–body intervention as an adjunct to MOUD. All participants were stabilized on MOUD. Measures included the Trauma Life Events Questionnaire (TLEQ), the Brief Pain Inventory (BPI), and the Posttraumatic Stress Disorder Checklist (PCL-5). Analyses involved descriptive statistics, independent sample t-tests, and linear and logistic regression.ResultsParticipants were self-identified as women (n = 157), men (n = 144), and non-binary (n = 2). Fifty-seven percent (n = 172) self-reported chronic pain, and 41% (n = 124) scored above the screening cut-off for PTSD. Women reported significantly more intimate partner violence (85%) vs 73%) and adult sexual assault (57% vs 13%), while men reported more physical assault (81% vs 61%) and witnessing trauma (66% vs 48%). Men and women experienced substantial childhood physical abuse, witnessed intimate partner violence as children, and reported an equivalent exposure to accidents as adults. The number of traumatic events predicted PTSD symptom severity and PTSD diagnostic status. Participants with chronic pain, compared to those without chronic pain, had significantly more traumatic events in childhood (85% vs 75%).ConclusionThe study found a high prevalence of lifetime trauma among people in MOUD. Results highlight the need for comprehensive assessment and mental health services to address trauma among those in MOUD treatment.Trial registrationNCT04082637.

Evaluation of a High Intensity Interval Training (HIIT) Program for Military Personnel Receiving Inpatient Treatment for a Substance Use Disorder

This study aimed to evaluate a high intensity interval training (HIIT) program delivered in an inpatient treatment setting serving military personnel. This recreational therapy (RT) program assessed the impact of a single session (60-minute) HIIT program on participant affect and state-anxiety. Using a single-group pretest-posttest design, 58 data sets were collected from participants (N = 20). Results indicated an increase in positive affect (z = -.6.52, p &lt; .001), a decrease in negative affect (z = -2.64, p &lt; .01), and a significant reduction in anxiety, t (57) = 1.99, p = .05 following the intervention. The program also resulted in a significant elevation in heart rate, t (57) = -25.89, p &lt; .001 with most participants reaching moderate to high intensity physical activity levels. On a scale of 1–10, participants rated their likelihood of participating in HIIT post-discharge at 6.28 (SD = 2.43). Additional qualitative data provides valuable insight on the perceived benefits to participants and offers suggestions for future program development and research in this area.

Enhancing Cellular Uptake of Native Proteins through Bio-Orthogonal Conjugation with Chemically Synthesized Cell-Penetrating Peptides

The potential for native proteins to serve as a platform for biocompatible, targeted, and personalized therapeutics in the context of genetic and metabolic disorders is vast. Nevertheless, their clinical application encounters challenges, particularly in overcoming biological barriers and addressing the complexities involved in engineering transmembrane permeability. This study is dedicated to the development of a multifunctional nanoentity in which a model therapeutic protein is covalently linked to a cell-penetrating peptide, NickFect 55, with the objective of enhancing its intracellular delivery. Successful binding of the nanoentity fragments was achieved through the utilization of an intein-mediated protein-trans splicing reaction. Our research demonstrates that the fully assembled nanoentity-containing protein was effectively internalized by the cells, underscoring the potential of this approach in overcoming barriers associated with protein-based therapeutics for the treatment of genetic disorders.

Informing the treatment of social anxiety disorder with computational and neuroimaging data

Informing the treatment of social anxiety disorder with computational and neuroimaging data

Metabolic Status Influences Probiotic Efficacy for Depression—PRO-DEMET Randomized Clinical Trial Results

Probiotics may represent a safe and easy-to-use treatment option for depression or its metabolic comorbidities. However, it is not known whether metabolic features can influence the efficacy of probiotics treatments for depression. This trial involved a parallel-group, prospective, randomized, double-blind, controlled design. In total, 116 participants with depression received a probiotic preparation containing Lactobacillus helveticus Rosell®-52 and Bifidobacterium longum Rosell®-175 or placebo over 60 days. The psychometric data were assessed longitudinally at five time-points. Data for blood pressure, body weight, waist circumference, complete blood count, serum levels of C-reactive protein, cholesterol, triglycerides, and fasting glucose were measured at the beginning of the intervention period. There was no advantage of probiotics usage over placebo in the depression score overall (PRO vs. PLC: F(1.92) = 0.58; p = 0.45). However, we found a higher rate of minimum clinically important differences in patients supplemented with probiotics than those allocated to placebo generally (74.5 vs. 53.5%; X2(1,n = 94) = 4.53; p = 0.03; NNT = 4.03), as well as in the antidepressant-treated subgroup. Moreover, we found that the more advanced the pre-intervention metabolic abnormalities (such as overweight, excessive central adipose tissue, and liver steatosis), the lower the improvements in psychometric scores. A higher baseline stress level was correlated with better improvements. The current probiotic formulations may only be used as complementary treatments for depressive disorders. Metabolic abnormalities may require more complex treatments. ClinicalTrials.gov identifier: NCT04756544.

Sequential administration of peripheral nerve blocks andonabotulinumtoxinA for the treatment of chronic migraine andother headache disorders-A retrospective tolerability and safety study.

To determine the tolerability and safety of concurrent peripheral nerve blocks and onabotulinumtoxinA treatment during a single outpatient clinic procedure visit. Procedural interventions are available for the treatment of headache disorders. OnabotulinumtoxinA and peripheral nerve blocks are used as alternatives or in addition to oral therapies to reduce the frequency and intensity of migraine attacks. There is currently a lack of safety data focusing on the sequential administration of local anesthetic via peripheral nerve blocks and onabotulinumtoxinA during a single clinical encounter for the treatment of headache. The primary aim of the study was to determine the safety and tolerability of concurrent peripheral nerve blockade and onabotulinumtoxinA injections during a single outpatient clinic procedure visit. We hypothesized that the dual intervention would be safe and well tolerated by patients with chronic migraine and other headache disorders. A retrospective chart review was performed using clinical data from patients seen by multiple providers over a 16-month timeframe at one outpatient headache clinic. Patients were identified by procedure codes and those receiving peripheral nerve block(s) and onabotulinumtoxinA injections during a single encounter within the study period were eligible for inclusion. Inclusion criteria were (1) patients 18 years and older who were (2) receiving both peripheral nerve blocks and onabotulinumtoxinA injections for the treatment of chronic migraine. Patients were excluded if they were under age 18, received their procedure outside of the clinic (emergency room, inpatient ward), or were receiving sphenopalatine ganglion blocks. Age- and sex-matched patients who received one procedure, either peripheral nerve blocks or onabotulinumtoxinA, were used for control. The primary outcome of this safety study was the number of adverse events that occurred in the dual intervention group compared to the single intervention control arms. Information regarding adverse events was gathered via retrospective chart review. If an adverse event was recorded, it was then graded by the reviewer utilizing the Common Terminology Criteria for Adverse Events ranging from Grade 1 Mild Event to Grade 5 Death. Additionally, it was noted whether the adverse event led to treatment discontinuation. In total, 375 patients were considered eligible for inclusion in the study. After age and sex matching of controls, 131 patients receiving dual intervention were able to be compared to 131 patients receiving onabotulinumtoxinA alone and 104 patients receiving dual intervention were able to be compared to 104 patients receiving peripheral nerve block(s) alone. The primary endpoint analysis showed no significant difference in total adverse events between dual intervention compared to nerve blocks alone or onabotulinumtoxinA alone. The number of adverse events that led to treatment discontinuation approached but did not reach statistical significance for those receiving dual intervention versus onabotulinumtoxinA alone in the number of adverse events that led to treatment termination (4.6%, 6/131 vs. 0.8%, 1/131, p = 0.065); however, the number of patients who discontinued therapy was not significantly different between those groups (2.3%, 3/131 vs. 0.8%, 1/131; p = 0.314; odds ratio 0.3 [0-3.2]; p = 0.338). In this retrospective chart review, there was no significant difference in adverse events or therapy discontinuation between patients receiving sequential peripheral nerve block(s) and onabotulinumtoxinA injections versus those receiving either peripheral nerve block(s) or onabotulinumtoxinA injections alone. As a result, we concluded that the combination procedure is likely safe and well tolerated in routine clinical practice.

Korsakoff Psychosis following involuntary treatment for alcohol use disorder

Korsakoff Psychosis following involuntary treatment for alcohol use disorder