Pharmacological Factors Research Articles

B-071 Unraveling Histamine Intolerance: Exploring DAO Quantity, Elimination Ratios and Cofactor Influences

Abstract Background Non-allergic reactions to food, often triggered by biogenic amines like histamine, result in symptoms such as headache, rhinitis, respiratory issues, digestive complaints, and eczema. The symptomatic overlap between histamine intolerance (HIT) and allergies may contribute to potential underdiagnosis. Limited data impedes precise incidence determination, but estimates suggest 1-3% of the population is affected, with increasing cases anticipated as knowledge and diagnostic tools for HIT advance. Despite histamine's physiological importance, elevated levels pose health risks. HIT arises when ingested or internally released histamine surpasses rapid breakdown capacity. Studies link HIT to DAO deficiency and/or impaired DAO activity, often in subgroups with genetic, pathological, or pharmacological factors. DAO cofactor deficiencies like copper, zinc, vitamin C or vitamin B6 may exacerbate DAO impairment. The trial aimed to explore the relationship of histamine elimination, DAO quantity, and essential cofactors for DAO activity. Methods Serum samples from 40 patients underwent analysis for DAO quantity and histamine elimination ratio using Immundiagnostik AG test kits. ELISA quantification employed a sandwich technique with polyclonal antibodies against recombinant DAO. Low DAO levels (< 3 U/ml) indicated histamine intolerance, moderate levels (3 - 10 U/ml) suggested probability, and high levels (< 10 U/ml) initially ruled out intolerance. Histamine elimination efficiency was assessed by comparing spiked sample levels at 0 and 24 hours after incubation, gauging histamine breakdown mechanisms without directly measuring enzyme quantity. Histamine elimination > 40% indicated unlikely intolerance, 25 - 40% (moderate) suggested probability, and < 25% (poor) indicated likelihood. Additionally, vitamin B6 influence was explored using Immundiagnostik AG's microbiological ID-VIT Test system, spiking samples with DAO for supplementation. Six samples with varying B6 levels underwent investigation. Results The investigation revealed that DAO quantity and histamine elimination highlight the enzyme's pivotal role. Distinctions emerged in histamine intolerance classification, with more than 25% of the population showing reduced elimination in samples with moderate DAO levels (3-10 U/mL), and more than 10% showing reduced elimination in samples with high DAO levels (>10 U/mL), suggesting potential DAO inhibition contributing to impaired histamine breakdown. Analyses based on functional vitamin B6 levels demonstrated varying responses to DAO supplementation. Samples with high functional B6 levels (>20 µg/l) showed a 20% increase in elimination with DAO supplementation of 3 U/mL. In contrast, samples with lower B6 levels (<7 µg/l) exhibited minimal to no additional elimination, despite supplemental DAO at 6 U/mL. These findings underscore the nuanced interplay among DAO levels, histamine elimination, and the influence of vitamin B6, providing insights into factors impacting histamine metabolism across diverse patient profiles. Conclusions The data unveil a high potential for differential diagnosis, particularly in the realm of moderate to high DAO quantity, where the dependence on DAO inhibition yields a different classification of HIT probability. Analyzing DAO cofactors, such as vitamin B6, emerges as a valuable complementary tool for the diagnosis and treatment of HIT. These findings underscore the importance of considering DAO levels, their inhibition, and cofactors in a comprehensive approach to enhance the accuracy of HIT assessment and guide effective therapeutic interventions.

Prognostic Factors of Falls in Hospitalized Adults and Elderly: An Epidemiological and Clinical Analysis

BackgroundFalls are known to cause injuries ranging from minor to severe, resulting in local or systemic lesions. Addressing prognostic factors associated with falls is crucial for preventing this adverse event through the implementation of patient care protocols. This study aimed to explore the epidemiological, clinical, and pharmacological prognostic factors influencing falls in adult and elderly patients, assessing the timing and impact of these factors using survival curve analysis. MethodsA retrospective observational cohort study included 176 hospitalized patients experiencing falls, categorized into adults (<60 years) and elderly (≥60 years). Binomial tests and logistic regression assessed variable associations, while Kaplan-Meier curves and Cox proportional hazards models analyzed survival. ResultsOverall, 25.9% of adults and 33.3% of the elderly experienced some form of injury (minor or moderate). Patients were alone during the fall in 77.6% of cases for those under 60, compared to 50% for those 60 and older (p<0.001). Falls from own height were the most common, occurring in 46.6% of patients under 60 years and 66.7% of elderly patients (p=0.011). Among adults under 60, factors such as past alcohol history (p=0.0276), falling alone (p=0.0002), benzodiazepine use (p=0.0001), antiarrhythmic/antihypertensive medication (p=0.0005), and antipsychotics (p=0.0001) were significantly associated with falls. In the elderly, significant factors included falling from one's own height (p=0.0112), muscle weakness (p=0.0183), gait disorders (p=0.0443), vasodilators (p=0.0107), antihistamines (p=0.0003), and hypoglycemic agents (p=0.0041). Survival curve analysis indicated women under 60 had a worse prognosis for falls compared to elderly women (p=0.038). For the elderly, opioid use (p=0.045) and muscle weakness (p=0.037) represented poor prognostic factors compared to adults under 60. In Cox regression, only female sex in patients under 60 showed a higher risk (HR=1.47) compared to women over 60 (p=0.0014). Although not significant in multivariate analysis, muscle weakness (p=0.066) and opioid use (p=0.0545) had proportional hazards of 1.37 and 1.12, respectively. ConclusionFemale sex indicated poorer prognosis in <60s, while opioids and muscle weakness were concerning for the elderly. These findings emphasize the need for tailored care protocols to stratify patient fall risk and prognosis during hospitalization and develop effective preventive strategies in healthcare.

The role of lifestyle physical activity in preventing multiple sclerosis

Multiple sclerosis (MS) is a devastating neurodegenerative disorder that affects more than three million people worldwide. Among the environmental, lifestyle, dietary, comorbid, and pharmacological factors investigated as possible modifiable protective or risk factors for MS, physical activity (PA) seems to play a valuable role in its prevention. Currently, there is no comprehensive review article on the preventive effects of PA in MS. This narrative review aimed to evaluate the most recent and extensive pooled analysis and evidence and to explore the influence of lifestyle PA on primary and secondary prevention in MS. Literature articles were searched through several databases, including PubMed, Cochrane Library, Embase, and Web of Science, from 1985 to March 2024. The review focused on lifestyle PA, defined as the daily accumulation of at least 30 min of self-selected activities. This includes all leisure, occupational, or household activities that are at least moderate to vigorous in intensity and may be planned or unplanned activities that are part of everyday life. The most valuable and representative reports on primary and secondary prevention in MS have been selected. Lifestyle PA, practised at moderate and high intensity, plays a protective role in reducing the risk of developing MS and delaying the onset of disability in persons with MS. Future studies are required to identify specific types of PA that are particularly recommended for patients with MS.

Exploring the Interconnection between Metabolic Dysfunction and Gut Microbiome Dysbiosis in Osteoarthritis: A Narrative Review.

Osteoarthritis (OA) is a prevalent joint disorder and the most common form of arthritis, affecting approximately 500 million people worldwide, or about 7% of the global population. Its pathogenesis involves a complex interplay between metabolic dysfunction and gut microbiome (GM) alterations. This review explores the relationship between metabolic disorders-such as obesity, diabetes, and dyslipidemia-and OA, highlighting their shared risk factors, including aging, sedentary lifestyle, and dietary habits. We further explore the role of GM dysbiosis in OA, elucidating how systemic inflammation, oxidative stress, and immune dysregulation driven by metabolic dysfunction and altered microbial metabolites contribute to OA progression. Additionally, the concept of "leaky gut syndrome" is discussed, illustrating how compromised gut barrier function exacerbates systemic and local joint inflammation. Therapeutic strategies targeting metabolic dysfunction and GM composition, including lifestyle interventions, pharmacological and non-pharmacological factors, and microbiota-targeted therapies, are reviewed for their potential to mitigate OA progression. Future research directions emphasize the importance of identifying novel biomarkers for OA risk and treatment response, adopting personalized treatment approaches, and integrating multiomics data to enhance our understanding of the metabolic-GM-OA connection and advance precision medicine in OA management.

Protocolo diagnóstico de la hiperprolactinemia

Hyperprolactinemia is a common cause for assessment in clinical endocrinology practice. It can have several causes, including prolactinoma, the most common functioning pituitary tumor. In order to reach an accurate differential diagnosis, it is essential to take a detailed medical history to rule out possible physiological or pathological causes. Non-tumoral hyperprolactinemia of pathological origin is usually associated with pharmacological factors as the predominant cause. Typical clinical symptoms include galactorrhea and manifestations resulting from hypogonadism induced by excess prolactin. The clinical presentation may vary according to gender, age, and underlying cause. The necessary additional tests, including magnetic resonance imaging, should be performed based on the medical history.

Allelic frequencies of polymorphism c.521T>C (rs4149056) favor preemptive SLCO1B1 genotyping in Armenia.

Statins represent an important pharmacological factor for the prevention of cardiovascular diseases but may also cause severe cases of myotoxicity. Numerous studies have described the association of the SLCO1B1 gene variant c.521C with statin-induced myopathy across different populations. This study aimed at evaluating the usefulness of preemptive SLCO1B1 genotyping in Armenia. A total of 202 Armenian patients referred to the Center of Medical Genetics and Primary Health Care in Yerevan for upper respiratory tract infection between January and May 2022 were included in this study. Genotyping for SLCO1B1 c.521T>C (rs4149056) was performed using a commercially available real-time PCR assay (RealFast™). In total, 3/202 (1.5 %) samples were C/C homozygotes and 52/202 (25.7 %) were T/C heterozygotes, associated with a high and increased risk for statin-induced myopathy, respectively. The SLCO1B1 c.521C allelic frequency was 14.4 %. The observed allele frequency of 14.4 % for thec.521C variant is slightly lower than frequencies reportedfrom Europe, but relatively high compared to Asianpopulations, suggesting that preemptive SLCO1B1 genotyping could be a useful approach for the reduction of statin-induced adverse effects in Armenia.

Pain perception enhancement in consecutive second-eye phacoemulsification cataract surgeries under topical anesthesia.

Cataract is the main cause of visual impairment and blindness worldwide while the only effective cure for cataract is still surgery. Consecutive phacoemulsification under topical anesthesia has been the routine procedure for cataract surgery. However, patients often grumbled that they felt more painful during the second-eye surgery compared to the first-eye surgery. The intraoperative pain experience has negative influence on satisfaction and willingness for second-eye cataract surgery of patients with bilateral cataracts. Intraoperative ocular pain is a complicated process induced by the nociceptors activation in the peripheral nervous system. Immunological, neuropsychological, and pharmacological factors work together in the enhancement of intraoperative pain. Accumulating published literatures have focused on the pain enhancement during the second-eye phacoemulsification surgeries. In this review, we searched PubMed database for articles associated with pain perception differences between consecutive cataract surgeries published up to Feb. 1, 2024. We summarized the recent research progress in mechanisms and interventions for pain perception enhancement in consecutive second-eye phacoemulsification cataract surgeries. This review aimed to provide novel insights into strategies for improving patients' intraoperative experience in second-eye cataract surgeries.

The Frequency of Risk Factors for Cleft Lip and Palate in Mexico: A Systematic Review.

Cleft lip and palate is an anomaly that affects both women and men. It is considered to be among the most frequent congenital abnormalities and is related to modifications in chromosomal DNA and multiple genetic alterations. This anomaly can also be associated with various environmental factors, such as tobacco and alcohol consumption, medication use, and exposure to different environmental and industrial toxic substances. The objective of this study was to document the frequency of risk factors related to cleft lip and palate through a systematic review of Mexican studies. In this systematic review, a bibliographic search was conducted following PRISMA guidelines in the databases Scielo, ScienceDirect, PubMed, and EBSCO. Keywords related to cleft lip and palate, epidemiology, and risk factors were used. In all, 3 independent reviewers (J.A.S.L., S.L.V., and N.M.F.) selected and evaluated a total of 17 articles included in this analysis, achieving a coefficient of κ = 0.84. The analysis revealed that the highest frequency of conducted studies was in the State of Mexico. The most common risk factors identified were environmental, pharmacological, consumption habits, and gynecological factors. Identifying the main risk factors for cleft lip and palate in the Mexican population will enable the implementation of preventive measures aimed at reducing exposure to these factors. Additionally, early intervention can improve the quality of life for individuals affected by this condition.

Memory impairments in temporal lobe epilepsy

Temporal lobe epilepsy is known to present with various cognitive impairments, among which memory deficits are frequently reported by patients. Memory deficits can be classified into two types: classical hippocampal amnesia, which is characterized by abnormalities detected in neuropsychological assessments, and atypical memory deficits, such as accelerated long-term amnesia and autobiographical memory impairment, which cannot be identified using standard testing methods. These deficits are believed to arise from a complex interplay among structural brain abnormalities, interictal epileptic discharges, pharmacological factors, and psychological states. While fundamental treatments are limited, there are opportunities for interventions such as environmental adjustments and rehabilitation. This review article aims to provide a comprehensive overview of the types, underlying pathophysiology, and intervention methods for memory disorders observed in patients with temporal lobe epilepsy.

Low Minimum Inhibitory Concentration of an Antibiotic Does Not Necessarily Imply a Better Antibiotic: Other Clinical and Pharmacological Factors Need Consideration for Antibiotic Selection

Low Minimum Inhibitory Concentration of an Antibiotic Does Not Necessarily Imply a Better Antibiotic: Other Clinical and Pharmacological Factors Need Consideration for Antibiotic Selection

Psychological impact of life events in systemic lupus erythematosus patients - Differences between flares and remission.

Stress has been linked to worsening symptoms and increased disease activity in patients with Systemic lupus erythematosus (SLE). Life-events are individual stress points, and there is conflicting evidence regarding their role in SLE activity and disease perception. Adult SLE patients were recruited for the study. Clinical and laboratory features of SLE were recorded, and previous diagnosis of anxiety or depression were retrieved from patients' electronic charts. Flares were defined by the Systemic Lupus Erythematosus Disease Activity (SLEDAI) flare Index, and flares during the previous year were documented. During a routine visit, they completed validated Portuguese translations of the 10-item Perceived Stress Scale (PSS-10), Hospital Anxiety and Depression Scale (HADS) and Life Experience Survey (LES) for the previous year. A total of 47 female SLE patients were recruited. Ten patients (21.3%) had experienced recent flares. Patients with recent flares reported fewer life events, with lower positive, negative, and total weightings sums compared to those without recent flares. Although 42.2% of patients perceived pathological levels of stress in the previous month, 48.9% had anxiety symptoms, and 34% were at high risk for an anxiety disorder, these psychometric measures did not differ significantly between the recent flare and no-flare groups. There is a high prevalence of pathological levels of stress among SLE patients. SLE patients with recent flares report less psychological impact from life events, both positive and negative, independent of other psychological or pharmacological factors.

An uncommon orthogeriatric syndrome: a case of Ogilvie’s syndrome

Acute colonic pseudo-obstruction (ACPO), also known as Ogilvie’s syndrome, is an uncommon postoperative complication of major orthopedic surgery that is characterized by massive colonic dilatation and the potential for substantial morbidity and mortality. Most patients who had Ogilvie’s syndrome had risk factors that could be identified preoperatively, such as immobility, elevated comorbidity, and polypharmacy, prefiguring the frail elderly patient. In modern terms, it is considered a typical orthogeriatric syndrome. In these kinds of patients, we need to be vigilant for its development and judicious in the use of epidural anesthesia. We present an ACPO case in an elderly frail patient with a hip fracture, and we review the available literature to outline clinical characteristics and outcomes. Our patient presented numerous risk factors for developing the syndrome in the preoperative period: nonautonomy in basic and daily living activities, polypharmacotherapy, spinal trauma, and hyposodiemia. In this patient, epidural anesthesia was an additional risk factor. The purpose of this case report is to emphasize the presence of this rare syndrome (1.5% of orthogeriatric patients) in orthogeriatric departments and to identify not only pharmacological, traumatic, and electrolytic risk factors but also those that can be identified even through geriatric evaluation to avoid the use of anesthesiologic techniques and drugs that may have an impact on the prognosis of these patients.

A mechanistic analysis of metformin's biphasic effects on lifespan and healthspan in C. elegans: Elixir in youth, poison in elder

Aging, a complex biological process influenced by genetic, environmental, and pharmacological factors, presents a significant challenge in understanding its underlying mechanisms. In this study, we explored the divergent impacts of metformin treatment on the lifespan and healthspan of young and old C. elegans, demonstrating a intriguing “elixir in youth, poison in elder” phenomenon. By scrutinizing the gene expression changes in response to metformin in young (day 1 of adulthood) and old (days 8) groups, we identified nhr-57 and C46G7.1 as potential modulators of age-specific responses. Notably, nhr-57 and C46G7.1 exhibit contrasting regulation patterns, being up-regulated in young worms but down-regulated in old counterparts following metformin treatment. Functional studies employing knockdown approaches targeting nhr-57, a gene under the control of hif-1 with a documented protective function against pore-forming toxins in C. elegans, and C46G7.1, unveiled their critical roles in modulating lifespan and healthspan, as well as in mediating the biphasic effects of metformin. Furthermore, deletion of hif-1 retarded the influence of metformin, implicating the involvement of hif-1/nhr-57 in age-specific drug responses. These findings underscored the necessity of deciphering the mechanisms governing age-related susceptibility to pharmacological agents to tailor interventions for promoting successful aging.

Retrospective Observational Analysis of Tocilizumab Outcomes in COVID-19 Patients at a Tertiary Care Hospital

Background: Tocilizumab (TCZ), a monoclonal antibody against interleukin-6 (IL-6), was recommended for treatment of Covid-19 patients with a risk of cytokine storm but showed variable effect on outcome. The aim was to assess the association of outcome following tocilizumab administration with various physiological, pathological and pharmacological factor in Covid- 19 patients Methods: Retrospective observational study from June 2020 to July 2020. All indoor Covid positive patients who received tocilizumab were included and relevant information was captured in the case record form. Data was analyzed to the study association of various physiological factors, comorbidities, severity of disease, laboratory parameters and co-administered drugs with the outcome following tocilizumab administration. Results: Total 25 patients received tocilizumab during study period. Older age group (p=0.001), high NEWS score, hypertension (OR: 3.62; p=0.05) and hydroxychloroquine(HCQ) administration (OP=6.66; p=0.009) showed significant association with a worst outcome. Hypertension and hydroxychloroquine usage was analyzed after adjustment with NEWS score using MH adjusted analysis, which revealed a trend of worst outcome in HCQ recipients but the association was not significant with hypertension. High pre-treatment IL-6 (death 570.11+498.76; discharge110.31+ 49.68; p: 0.0011); high post-treatment ferritin level (death 1756.5+ 1622.03; discharge 711.71+ 421.23; p: 0.019) as well as post-tocilizumab rise in ferritin level was associated with worst outcome (p= 0.029). Conclusion: Participants having higher cytokine level/or high NEWS score were unlikely to benefit from tocilizumab. Increased in ferritin level even after tocilizumab appeared to be an indicator of failure of treatment.

(082) DELAYED ORGASM CAN RESULT FROM LUMBOSACRAL DISC DISEASE DISRUPTING GENITAL SENSORY TRANSMISSION IN THE CAUDA EQUINA: A REVIEW

Abstract Introduction Delayed orgasm may be considered an unwanted, atypically long latency during most genital/sexual activity despite sexual stimulation, causing significant distress to the individual and/or partner, persisting for at least 6 months. Delayed orgasm is reported to affect 6.9% of women. It is associated with negative effects on sexual function, sexual satisfaction, and relationship satisfaction. Pharmacologic, endocrinologic, and neurobiological pathophysiological factors have been identified as possible etiologies of delayed orgasm, but an under-researched etiology is lumbosacral disc disease, specifically lumbosacral annular tear-induced sacral radiculopathy. The pelvic, pudendal, and sciatic nerves all merge at the S2-4 foramina where they coalesce to form the S2-4 nerve roots. These sacral spinal nerve roots (S2-4) ascend to the first synapse in the conus medullaris. During their ascent, they can be irritated mechanically by impingement/compression or chemically by exposure to the extruded nucleus pulposus from lumbosacral annular tears, and thereby disrupt genital sensory transmission with resultant delayed orgasm. The new evidence that delayed orgasm can be successfully treated by endoscopic spine surgery supports the association of delayed orgasm with sacral radiculopathy. There is still a paucity of research regarding delayed orgasm from lumbosacral disc disease. Objective To review the existing literature concerning the contribution of lumbosacral disc disease to delayed orgasm. Methods A literature search on delayed orgasm, its impacts and possible etiologies was performed. The following keywords were searched on Pubmed individually and in combination, related to the association between delayed orgasm and lumbosacral disc disease: delayed orgasm, delayed ejaculation, sexual dysfunction, anorgasmia, and persistent genital arousal disorder. Current definitions were compiled, and overall epidemiology, anatomy, and biopsychosocial factors of delayed orgasm were explored. Results There are a number of publications (n = 19) demonstrating the development of sexual dysfunction after damage to the sacral spinal nerve roots. Furthermore, several studies (n = 4) and case reports (n = 1) have demonstrated that treating lumbosacral disc disease reduces sexual dysfunction including improvement in delayed or reduced ejaculation. While delayed ejaculation encompasses the experience of delayed orgasm for some individuals, the literature fails to address delayed orgasm comprehensively in relation to lumbosacral disc disease, and thus fails to address treatment of lumbosacral disc disease and subsequent resolution of delayed orgasm. People with vulvas are particularly underrepresented in the literature studying the connection between lumbosacral disc disease and delayed orgasm. Conclusions While lumbosacral disc disease has many side effects that may impede daily function, sexual side effects can further detract from one’s personal life and relationship satisfaction. Thus, improving clinician awareness of sexual side effects, particularly delayed orgasm, can help improve treatment for individuals especially as they age. Further research is needed to strengthen the understanding of the effect of sacral radiculopathy on delayed orgasm as well as other sexual dysfunctions. Disclosure No.

Prevalence and factors associated with viral non-suppression in people living with HIV receiving antiretroviral therapy in sub-Saharan Africa: A systematic review and meta-analysis.

Despite advances in HIV treatment, the burden of viral non-suppression (VNS) remains a treatment success concern, particularly in Sub-Saharan African (SSA) countries. We determined the prevalence and factors associated with VNS for people living with HIV (PLHIV) receiving antiretroviral therapy (ART). This review, registered with PROSPERO (CRD42023470234), conducted an extensive search for evidence, focusing on PLHIV living in SSA on ART from the year 2000 to 19th October 2023, across databases including PubMed/MEDLINE, Embase, Web of Science, and Scopus. A total of 2357 articles were screened, from which 32 studies met the criteria for the final analysis, involving 756,620 PLHIV of all ages. The pooled prevalance for VNS was found to be 20.0% (95% CI: 15.43%-25.52%, I2=100%, p-value <0.01) Children and adolescents demonstrated the highest prevalence of VNS (viral load ≥1000 copies/mL) at 27.98% (95% CI: 21.91%-34.97%, I2=94%, p-value <0.01). The study revealed various factors associated with increased odds (risk) of VNS, p-value <0.05. These factors encompassed socio-demographics such as sex, age, education level, and marital status. Additionally, aspects related to HIV care, such as the facility attended, HIV status disclosure and adherence exhibited higher odds of VNS. Suboptimal ART adherence, longer duration on ART, socio-economic factors, lack of family and social support, presence of co-morbidities, advanced WHO HIV clinical stage, ART regimens, lower CD4+ count, abnormal body mass index, history of treatment interruptions, and progression of HIV illness were associated with VNS. Furthermore, behavioural/psychological factors including depression, substance use, negative perceptions towards ART, experiences of abuse, alcohol use, stigma, and certain patterns of sexual behaviour were also identified as factors for VNS. The occurrence of two VNS to every ten PLHIV on ART poses a threat to the progress made towards reaching the third 95% UNAIDS target in SSA. Additionally, these findings highlight the intricate interplay of various factors, encompassing patient characteristics, behavioural patterns, sociocultural influences, and pharmacological factors, all impacting VNS among PLHIV. Recognising its multifaceted nature, we recommend designing and implementing high impact interventions to effectively address VNS in SSA.

Investigating the Relationship Between Cannabis Expectancies and Anxiety, Depression, and Pain Responses After Acute Flower and Edible Cannabis Use.

Objective: Cannabis has been touted for a host of pharmacological and therapeutic effects and users commonly report reduced symptoms of physical and mental health conditions, including anxiety, depression, and chronic pain. While there is existing empirical evidence supporting these effects of cannabis use, little is known about the extent to which these effects result from pharmacological versus expectancy factors. We evaluated the associations between participants' cannabis expectancies and their acute self-reported reactions after using legal market forms of cannabis with varying levels of cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) in three domains: anxiety, depression, and pain. Methods: Fifty-five flower and 101 edible cannabis users were randomly assigned and asked to purchase at a local dispensary one of three products containing varying levels of CBD and THC. Participants completed a baseline assessment where they reported expectancies about general health effects of cannabis use and an experimental mobile laboratory assessment where they administered their assigned products. Edible users also reported their domain-specific expectancies about cannabis use in improving anxiety, depression, and pain. Following administration, participants completed acute indicators of anxiety, depression, and pain operationalized through subjective acute tension, elation, and a single-item measure of pain. Results: Among flower users, more positive expectancies for cannabis to improve general health were correlated with greater reductions in tension at acute post-use. This finding was replicated among edible users. Unlike flower users, more positive expectancies for cannabis to improve general health were also correlated with greater increases in elation and greater reductions in pain among edible users. More positive expectancies for cannabis to improve depression and pain were also correlated with greater increases in elation and greater reductions in pain, respectively, among edible users. Conclusions: Cannabis users' expectancies significantly impacted some of the acute subjective effects of legal market cannabis products. Among both flower and edible users, consistent, significant expectancy effects were found. Results were consistent with prior findings and demonstrate the need to measure and control pre-existing expectancies in future research that involves cannabis administration. Clinical trial registration number: NCT03522103.

MDMA-assisted dialectical behavioral therapy for borderline personality disorder: A qualitative study of mental health clinicians

AbstractIn 2021, the final series of phase 3 clinical trials looking at MDMA-AT for treatment-resistant post-traumatic stress disorder (PTSD) found that 71.2% of 3,4-methylenedioxymethamphetamine (MDMA) full-dose participants no longer met criteria for PTSD. MDMA-assisted therapy is not US Food and Drug Administration (FDA) approved in treating borderline personality disorder (BPD), and while PTSD is quite different from BPD, it is possible that some of the beneficial effects of MDMA-assisted therapy may be applicable in treating BPD. Interviewing two clinicians utilizing dialectical behavioral therapy treatment and two MDMA-assisted therapy clinicians was one way to examine the phenomenology of MDMA-assisted therapy with BPD individuals in a thoughtful manner. An exploratory, qualitative, interview-based study assessed clinicians' perspectives of MDMA-assisted therapy and BPD and increased our understanding of underlying therapeutic mechanisms and processes and the role of pharmacological factors in these treatment modalities, optimizing treatment context, and leading to improved clinical responses and patient recovery. The codes generated unique perspectives of the participants revealing a chronological narrative which included three phases of treatment.

Fracture nonunion and delayed union

Delayed union and non-union of fractures exist in the pediatric population. Fracture healing requires the synergistic collaboration of mechanical support and robust biological processes to allow endochondral ossification, reestablishment of bone continuity, and subsequent remodeling to strong lamellar bone. Failure of either mechanical stability or biology may manifest as delayed fracture healing. While early recognition of potential metabolic and pharmacologic risk factors may be addressed by pre-emptive treatment using nutritional and vitamin D supplements, definitive treatment of established non-union requires a comprehensive approach. Key Concepts words(1)Delayed unions and non-unions are more common in adult bone but can also occur in pediatric bone(2)Fracture healing requires synergistic collaboration of mechanical support and robust biological processes; treatment of non-unions should address both the biological and mechanical factors(3)Vitamin D is an integral component of calcium absorption and bone health

The Complex Role of Botulinum Toxin in Enhancing Goal Achievement for Post-Stroke Patients.

The rehabilitation medical team is responsible for the therapeutic management of post-stroke patients and, therefore, for the complex therapeutic approach of spasticity. Considering the generous arsenal at our disposal in terms of both pharmacological treatment, through the possibility of administering botulinum toxin to combat spasticity, and in terms of accurate assessment through developed functional scales such as the GAS (Goal Attainment Scale), one of our purposes is to monitor the parameters that influence the achievement of functional goals set by patients together with the medical team in order to render the patients as close as possible to achieving their proposed functional goals, thus enhancing their quality of life. By assessing and establishing statistical and clinical correlations between the GAS and quantifiable parameters related to the affected post-stroke upper limb, namely degree of spasticity, motor control, pain level and evolution of pain under treatment with BoNT-A (abobotulinum toxin A), and patients' overall response to BoNT-A treatment, we aim to quantify the improvement of the therapeutic management of post-stroke patients with spasticity and develop a more personalized and effective approach to their disability and impairment. The analysis concluded that there were two independent predictors of the Achieved GAS-T score (the study's endpoint parameter) motor control at any level of the upper limb and number of prior BoNT-A injections. The number of prior BoNT-A injections was an independent predictor of Achieved GAS-T score improvement but had no significant influence over Baseline GAS-T score. Enhancement in proximal and intermediate motor control showed a GAS score improvement of 3.3 points and a 0.93-point GAS score improvement for wrist motor control progress. From a separate viewpoint, patients with motor deficit on the left side have shown significantly greater improvement in Changed GAS-T scores by 2.5 points compared to patients with deficits on the right side; however, we note as a study limitation the fact that there was no statistical analysis over the dominant cerebral hemisphere of each patient. Improvement in the Achieved GAS-T score means better achievement of patients' goals. Thus, after the BoNT- A intervention, at follow-up evaluation, GAS was found to be directly correlated with improvement in motor control of the affected upper limb. Mobility of the corresponding limb was enhanced by pain decrease during p-ROM (passive range of motion) and by amelioration of spasticity. We conducted an observational, non-randomized clinical study on 52 stroke patients, a representative sample of patients with post-stroke spasticity and disability from our neurological rehabilitation clinic, who have been treated and undergone a specific rehabilitation program in our tertiary diagnostic and treatment medical center, including BoNT-A focal treatment for spasticity in the affected upper limb. The primary objective of the study was to assess the influence of abobotulinum toxin A treatment on the Goal Attainment Scale. Secondary objectives of the study included the assessment of BoNT-A treatment efficacy on spasticity with the MAS (Modified Ashworth Scale), pain with the NRS (Numerical Rating Scale), and joint passive range of motion (p-ROM), identifying demographic, clinical, and pharmacological factors that influence the response to BoNT-A treatment, as well as to conduct a descriptive and exploratory analysis of the studied variables.