Pharmacological Treatment Research Articles

Coordination-Driven Nanomedicine Mitigates One-Lung Ventilation-Induced Lung Injury via Radicals Scavenging and Cell Pyroptosis Inhibition.

One-lung ventilation (OLV) during thoracic surgery often leads to post-operative complications, yet effective pharmacological interventions are lacking. This study reports a baicalin-based metal-coordination nanomedicine with disulfiram (DSF) co-loading to address one-lung ventilation-induced lung injury and reperfusion injury (OLV-LIRI). Baicalin, known for its robust antioxidant properties, suffers from poor water solubility and stability. Leveraging nanotechnology, baicalin's coordination is systematically explored with seven common metal ions, designing iron/copper-mediated binary coordination nanoparticles to overcome these limitations. The self-assembled nanoparticles, primarily formed through metal coordination and π-π stacking forces, encapsulated DSF, ensuring high colloidal stability in diverse physiological matrices. Upon a single-dose administration via endotracheal intubation, the nanoparticles efficiently accumulate in lung tissues and swiftly penetrate the pulmonary mucosa. Intracellularly, baicalin exhibits free radical scavenging activity to suppress inflammation. Concurrently, the release of Cu2+ and DSF enables the in situ generation of CuET, a potent inhibitor of cell pyroptosis. Harnessing these multifaceted mechanisms, the nanoparticles alleviate lung injury symptoms without notable toxic side effects, suggesting a promising preventive strategy for OLV-LIRI.

Adenosine A2AR in viral immune evasion and therapy: unveiling new avenues for treating COVID-19 and AIDS.

Adenosine is a neuro- and immunomodulator that functions via G protein-coupled cell surface receptors. Several microbes, including viruses, use the adenosine signaling pathway to escape from host defense systems. Since the recent research developments in its role in health and disease, adenosine and its signaling pathway have attracted attention for targeting to treat many diseases. The therapeutic role of adenosine has been extensively studied for neurological, cardiovascular, and inflammatory disorders and bacterial pathophysiology, but published data on the role of adenosine in viral infections are lacking. Therefore, the purpose of this review article was to explain in detail the therapeutic role of adenosine signaling against viral infections, particularly COVID-19 and HIV. Several therapeutic approaches targeting A2AR-mediated pathways are in development and have shown encouraging results in decreasing the intensity of inflammatory reaction. The hypoxia-adenosinergic mechanism provides protection from inflammation-mediated tissue injury during COVID-19. A2AR expression increased remarkably in CD39 + and CD8 + T cells harvested from HIV patients in comparison to healthy subjects. A combined in vitro treatment performed by blocking PD-1 and CD39/adenosine signaling produced a synergistic outcome in restoring the CD8 + T cells funstion in HIV patients. We suggest that A2AR is an ideal target for pharmacological interventions against viral infections because it reduces inflammation, prevents disease progression, and ultimately improves patient survival.

Pharmacologic activation of activating transcription factor 6 contributes to neuronal survival after spinal cord injury in mice.

The impact of primary and secondary injuries of spinal cord injury (SCI) results in the demise of numerous neurons, and there is still no efficacious pharmacological intervention for it. Recently, studies have shown that endoplasmic reticulum stress (ERS) plays a pivotal role in recovery of neurological function after spinal cord injury. As a process to cope with intracellular accumulation of misfolded and unfolded proteins which triggers ERS, the unfolded protein response (UPR) plays an important role in maintaining protein homeostasis. And, a recently disclosed small molecule AA147, which selectively activates activating transcription factor 6 (ATF6), has shown promising pharmacological effects in several disease models. Thus, it seems feasible to protect the neurons after spinal cord injury by modulating UPR. In this study, primary neurons were isolated from E17-19 C57BL/6J mouse embryos and we observed that AA147 effectively promoted the survival of neurons and alleviated neuronal apoptosis after oxygen-glucose deprivation/reoxygenation (OGD/R) invitro. This was evident through a decrease in the proportion of PI-positive and TUNEL-positive cells, an increase in BCL-2 expression, and a decrease in the expression of BAX and C-caspase3. In in-vivo experiments, these findings were corroborated by TUNEL staining and immunohistochemistry. It was also found that AA147 enhanced three arms of the unfolded protein response with reduced CHOP expression. Besides, AA147 mitigated the accumulation of ROS in neurons probably by upregulating catalase expression. Furthermore, spinal cord injury models of C57BL/6J mice were established and behavioral experiments revealed that AA147 facilitated the recovery of motor function following SCI. Thus, pharmacologic activation of ATF6 represents a promise therapeutic approach to ameliorate the prognosis of SCI.

Dermatological care of gender-diverse patients in Australia.

In recent years, there has been an increasing recognition of the unique healthcare needs of gender-diverse patients in Australia. With the continuous growth of referrals to gender health services, there is an increased demand for specialised dermatological care. There is still a significant knowledge gap and a lack of guidelines specifically tailored to this patient group. In this article, we will provide a brief overview of the journey of Transgender and Gender Diverse (TGD) individuals as they embark on psychological and pharmacologic treatment for gender dysphoria in Australia. We endeavour to contribute to the existing body of knowledge by examining the evidence surrounding the treatment of skin, hair and nail issues for TGD patients. This article will outline how dermatologists can assist in the care of the gender-diverse patient. Although puberty blockade (stage 1 treatments) has minimal dermatological impact, gender-affirming pharmacotherapy (stage 2 treatments) can lead to many dermatological issues including acne, patterned hair loss (PHL) and dermatitis. The dermatologist may also play a role in stage 3 treatments which include surgical or procedural interventions for gender affirmation.

Predicting disease recurrence in patients with endometriosis: an observational study

BackgroundDespite surgical and pharmacological interventions, endometriosis can recur. Reliable information regarding risk of recurrence following a first diagnosis is scant. The aim of this study was to examine clinical and survey data in the setting of disease recurrence to identify predictors of risk of endometriosis recurrence.MethodsThis observational study reviewed data from 794 patients having surgery for pelvic pain or endometriosis. Patients were stratified into two analytic groups based on self-reported or surgically confirmed recurrent endometriosis. Statistical analyses included univariate, followed by multivariate logistic regression to identify risk factors of recurrence, with least absolute shrinkage and selection operator (Lasso) regularisation. Risk-calibrated Supersparse Linear Integer Models (RiskSLIM) and survival analyses (with Lasso) were undertaken to identify predictive features of recurrence.ResultsSeveral significant features were repeatedly identified in association with recurrence, including adhesions, high rASRM score, deep disease, bowel lesions, adenomyosis, emergency room attendance for pelvic pain, younger age at menarche, higher gravidity, high blood pressure and older age. In the surgically confirmed group, with a score of 5, the RiskSLIM method was able to predict the risk of recurrence (compared to a single diagnosis) at 95.3% and included adenomyosis and adhesions in the model. Survival analysis further highlighted bowel lesions, adhesions and adenomyosis.ConclusionsFollowing an initial diagnosis of endometriosis, clinical decision-making regarding disease management should take into consideration the presence of bowel lesions, adhesions and adenomyosis, which increase the risk of endometriosis recurrence.

Audiovestibular outcomes in adult patients with cogan syndrome: a systematic review.

To determine factors associated with steroid responsiveness and efficacy of biologic disease-modifying anti-rheumatic (DMARD) use in patients with Cogan Syndrome (CS). A systematic search of Cochrane Library, PubMed, CINAHL, and Scopus was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Any study describing audiometric or vestibular data and pharmacologic treatment in patients with CS was included. Due to limited literature, only case reports/case series were included. Seventy case reports or case series studies comprising 79 individual cases of CS were included. A difference in vestibular symptoms with a higher prevalence in the steroid-resistant group than the steroid-responsive group was found (79.5% vs 57.9%, p = 0.04). Eighteen (60.0%) patients treated only with oral steroids had no audiological improvement, while twelve (n = 12; 85.7%) patients treated with biologic DMARD showed audiological improvement. The steroid-responsive group had an overall better response to DMARDs than the steroid-resistant group (62.1% vs 45.0%; 100.0% vs 77.8%). Our study synthesized the available literature to better characterize steroid resistance in patients with Cogan syndrome and treatment outcomes. Vestibular symptoms were noted to be more prevalent in patients who were eventually labeled as steroid resistant. There were higher rates of audiological improvement in patients given biologic DMARDs rather than conventional DMARDs or steroids only. Further studies are needed to characterize each individual vestibular symptom and investigate the utility and timing of biologic DMARDs in managing patients with Cogan syndrome.

RTMS as a Next Step in Antidepressant Nonresponders: A Randomized Comparison With Current Antidepressant Treatment Approaches.

Although repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for depression, little is known about the comparative effectiveness of rTMS and other treatment options, such as antidepressants. In this multicenter randomized controlled trial, rTMS was compared with the next pharmacological treatment step in patients with treatment-resistant depression. Patients with unipolar nonpsychotic depression (N=89) with an inadequate response to at least two treatment trials were randomized to treatment with rTMS or to a switch of antidepressants, both in combination with psychotherapy. Treatment duration was 8 weeks and consisted of either 25 high-frequency rTMS sessions to the left dorsolateral prefrontal cortex or a switch of antidepressant medication following the Dutch treatment algorithm. The primary outcome was change in depression severity based on the Hamilton Depression Rating Scale (HAM-D). Secondary outcomes were response and remission rates as well as change in symptom dimensions (anhedonia, anxiety, sleep, rumination, and cognitive reactivity). Finally, expectations regarding treatment were assessed. rTMS resulted in a significantly larger reduction in depressive symptoms than medication, which was also reflected in higher response (37.5% vs. 14.6%) and remission (27.1% vs. 4.9%) rates. A larger decrease in symptoms of anxiety and anhedonia was observed after rTMS compared with a switch in antidepressants, and no difference from the medication group was seen for symptom reductions in rumination, cognitive reactivity, and sleep disorders. Expectations regarding treatment correlated with changes in HAM-D scores. In a sample of patients with moderately treatment-resistant depression, rTMS was more effective in reducing depressive symptoms than a switch of antidepressant medication. In addition, the findings suggest that the choice of treatment may be guided by specific symptom dimensions.

Role of Microglial Mitophagy in Alleviating Postoperative Cognitive Dysfunction: a Mechanistic Study.

Postoperative cognitive dysfunction (POCD), a common complication following anesthesia and surgery, is influenced by hippocampal neuroinflammation and microglial activation. Mitophagy, a process regulating inflammatory responses by limiting the accumulation of damaged mitochondria, plays a significant role. This study aimed to determine whether regulating microglial mitophagy and the cGAS-STING pathway could alleviate cognitive decline after surgery. Exploratory laparotomy was performed to establish a POCD model using mice. Western blotting, immunofluorescence staining, transmission electron microscopy, and mt-Keima assays were used to examine microglial mitophagy and the cGAS-STING pathway. Quantitative polymerase chain reaction (qPCR) was used to detect inflammatory mediators and cytosolic mitochondrial DNA (mtDNA) levels in BV2 cells. Exploratory laparotomy triggered mitophagy and enhanced the cGAS-STING pathway in mice hippocampi. Pharmacological treatment reduced microglial activation, neuroinflammation, and cognitive impairment after surgery. Mitophagy suppressed the cGAS-STING pathway in mice hippocampi. In vitro, microglia-induced inflammation was mediated by mitophagy and the cGAS-STING pathway. Small interfering RNA (siRNA) of PINK1 hindered mitophagy activation and facilitated the cytosolic release of mtDNA, resulting in the initiation of the cGAS-STING pathway and innate immune response. Microglial mitophagy inhibited inflammatory responses via the mtDNA-cGAS-STING pathway inducing microglial mitophagy and inhibiting the mtDNA-cGAS-STING pathway may be an effective therapeutic approach for patients with POCD.

Combination of low doses of mirtazapine plus venlafaxine produces antidepressant-like effects in rats, without affecting male or female sexual behavior.

Pharmacological treatments for depression are not always effective and produce unwanted side effects. Male and female sexual dysfunction is one of these side effects, which can lead to treatment withdrawal. Combination of two antidepressants with different mechanisms of action, like mirtazapine (MTZ) and venlafaxine (VLF) have been shown to be effective for treatment-resistant depression in humans. Combination of low doses of these drugs may still exert antidepressant-like effects without altering sexual behavior. To investigate the potential antidepressant-like effect of the chronic administration of low doses of MTZ plus VLF combined, as well as its impact on male and female sexual behavior in rats. The antidepressant-like effect of a 14-day treatment with combinations of MTZ plus VLF (0/0, 2.5/3.75 or 5/7.5mg/kg) was assessed in young adult male and female rats in the forced swim test (FST). The 5/7.5mg/kg MTZ/VLF combination was also tested in the chronic mild stress (CMS) test, in both males and females treated for 21days. The sexual effects of this last treatment were assessed in sexually experienced males and in gonadally-intact females during proestrus. The 5/7.5mg/kg MTZ/VLF combination produced an antidepressant-like effect in the FST and reversed the CMS-induced anhedonia in both male and female rats. This combination did not alter male sexual behavior, female proceptive and receptive behaviors or the regularity of the estrous cycle. The combination of low doses of MTZ and VLF might be a promising therapeutic alternative to treat depression without affecting the sexual response.

Compassionate use of esketamine intranasal in patients with severe major depressive disorder resistant to the treatment.

Treatment-resistant depression (TRD) is defined as the failure of at least two antidepressants in adequate doses and timing during a major depressive episode. Esketamine intranasal (ESK-IN) has been approved by the Food and Drug Administration and the European Medicines Agency for the treatment of TRD in combination with other antidepressants. To assess the effectiveness and tolerability of a sample of TRD patients who received treatment with ESK-IN as part of the compassionate use program. A retrospective, observational study was carried out on patients with a diagnosis of TRD enrolled in the early access program of ESK-IN in nine centers. Effectiveness was assessed with the Montgomery-Asberg depression rating scale (MADRS) at four time points: baseline, 28, 90, and 180 days of treatment. The sample included 71 patients (70% women) with a mean baseline MADRS score of 38.27 ± 5.9 and total or partial work disability rates of 85%. ESK-IN treatment was associated with a statistically and clinically significant reduction in the severity of depressive symptoms at all time points assessed. The presence of side effects was common but the majority were mild in severity and resolved after the observation period. Those patients who received psychotherapy in combination with ESK-IN showed a significantly lower MADRS score at 90 and 180 days than those patients who did not undergo psychotherapy. ESK-IN has proven to be effective and safe in a clinical sample of patients with severe TRD. To optimize clinical outcomes, the pharmacological treatment for TRD should always be integrated into a comprehensive therapeutic plan that encompasses strategies such as psychotherapy, social support, and family interventions.

Estimation of the Clinical, Economic, and Social Burden of Stage IV Non-Small Cell Lung Cancer in Mexico.

Lung cancer continues to be the leading cause of death among cancer patients worldwide. This study aimed to estimate the clinical, economic, and social burdens of stage IV non-small cell lung cancer (NSCLC) in private and public healthcare centers in Mexico, utilizing real-world evidence. The study population included patients >18 years of age diagnosed with stage IV NSCLC who received cancer treatment at the Centro Médico Nacional Siglo XXI (IMSS), the Centro Médico Nacional "20 de Noviembre" (ISSSTE), the Mexican Institute of Respiratory Diseases (INER), and the Medical Center ABC (American British Cowdray) from 1 January 2019 to 31 December 2020. The analysis included evaluation of epidemiological data, treatment regimens, and clinical outcomes, and emphasized pharmacological and non-pharmacological treatments, including detailed follow-up investigations, as part of comprehensive clinical management. Additionally, the study assessed the social burden through variables such as working-age absenteeism and presenteeism and caregiver productivity loss, as well as economic burden, considering both clinical and social components, with costs adjusted to 2022 Mexican pesos (MXN) values. A total of 188 patients with metastatic NSCLC were studied. The main type of NSCLC tumor found in the sample was adenocarcinoma (81%). Treatment regimens included pharmacological treatments (78%), non-pharmacological treatments (25%), and palliative care (24%). Complications were present in 73% of the cohort, while 60% presented adverse events. Clinical management costs of up to MXN1,001,579 per patient in the public sector and MXN2,140,604 in the private sector were reported. It was estimated that working-age patients lose 84-335 days yearly due to absenteeism and presenteeism, while caregivers report a productivity loss equivalent to 13-30 days due to the management of NSCLC patients. These indirect costs of NSCLC contribute to the social burden. A working-age patient with stage IV disease is associated with an average indirect cost of MXN49,731-178,287 in public institutions, while in private institutions, the cost elevates to MXN438,103. This study highlights the substantial clinical, economic, and social burdens of stage IV NSCLC in Mexico, revealing significant disparities between public and private healthcare sectors. It underscores the urgent need for standardized practices and equitable care across all systems.

Basal Cell Carcinoma: Comprehensive Review with Emphasis on Scar Tissue Manifestation and Post-Vaccination Incidence

Basal cell carcinoma (BCC) arising within scar tissue is a rare but clinically significant phenomenon. This comprehensive review aims to provide a succinct overview of the current state of knowledge regarding the etiological factors, pathogenesis, clinical presentation, and management of BCC. This study constitutes a literature review pertaining to BCC, with a particular emphasis on BCC developing within scar tissue. It also provides a clinical case presentation of a patient who had developed BCC in a BCG post-vaccination scar and a review of analogous findings available in the existing literature. Despite the fact that an array of mechanisms play a role in injury-related BCC growth, the main mechanism remains ambiguous and yet to be elucidated. The review also includes a detailed description of the various therapeutic options available for BCC, ranging from surgical interventions to novel pharmacological treatments. By examining these intersections, the review seeks to elucidate the potential mechanisms, identify risk factors, and suggest considerations for clinical practice. The findings underscore the importance of vigilant dermatological assessment in patients with scar tissue and those recently vaccinated, aiming to improve early detection and optimize management strategies for BCC.

Evidence based treatment for lupus nephritis: present perspectives and challenges

Systemic lupus erythematosus (SLE) is a complex autoimmune disease known for its high heterogeneity among individuals, which affects various organs including the kidneys. Lupus nephritis (LN) is a frequent and life-threatening manifestation of the disease, with up to 50% of patients developing kidney involvement. Classification of renal involvement in lupus is based on specific histopathological findings, guiding therapeutical decisions. Immunosuppressive therapy, particularly glucocorticoids combined with cyclophosphamide or mycophenolate mofetil, has been the mainstay of treatment for many years, while rates of complete remission have not changed dramatically. Despite advancements in therapy, in an important proportion of patients LN leads to end-stage kidney disease (ESKD). Emerging therapies including belimumab, voclosporin, and obinutuzumab offer promising results in improving renal outcomes, especially in refractory or relapsing disease. Maintenance therapy is crucial to prevent disease flares and preserve renal function. Supportive measures including lifestyle modifications and non-immunosuppressive pharmacological interventions are nowadays also essential in managing LN. This review emphasizes recent advances of therapy and challenges regarding treatment optimization with strategies to improve long-term outcomes.

Subjective risk factors of severe pain at discharge from the emergency department.

To examine the risk factors for severe pain upon discharge from the emergency department, assuming appropriate pharmacological treatment of pain, in order to improve pain relief in emergency departments and reduce the risk of potential chronic pain. An analytic study was conducted utilizing data from a multicenter randomized controlled trial to evaluate patients' experiences upon admission and discharge from the emergency department (ED). Severe pain was defined by a score of six on a numerical rating scale of zero to ten. Stress and negative emotions (including anger, fear, sadness, and regret) were evaluated using numerical rating scales, respectively ranging from 0 to 10 and 1 to 5. The risk factors of severe pain at discharge (SPD) from ED were calculated using logistic regression considering patient characteristics evaluated at their admission to the ED. From the 1240 patients analyzed, 22.2% had SPD from the ED. Each increase of one point in the intensity of acute pain and anger was significantly associated with a higher risk of SPD from ED. In addition, woman, negative self-perceived health, and age under 65years, are other significant factors associated with SPD from the ED. In addition to acute pain on admission, this study highlights new factors to consider when managing pain in emergency care, such as anger, and self-perceived health. Addressing these aspects can help reduce the likelihood of developing SPD from the ED, which in turn could potentially lead to the onset of chronic pain in future. SOFTER IV Project clinical identification number: NCT04916678.

Central mechanisms of emesis: A role for GDF15.

Nausea and emesis are ubiquitously reported medical conditions and often present as treatment side effects along with polymorbidities contributing to detrimental life-threatening outcomes, such as poor nutrition, lower quality of life, and unfavorable patient prognosis. Growth differentiation factor 15 (GDF15) is a stress response cytokine secreted by a wide variety of cell types in response to a broad range of stressors. Circulating GDF15 levels are elevated in a range of medical conditions characterized by cachexia and malaise. In recent years, GDF15 has gained scientific and translational prominence with the discovery that its receptor, GDNF family receptor α-like (GFRAL), is expressed exclusively in the hindbrain. GFRAL activation may results in profound anorexia and body weight loss, effects which have attracted interest for the pharmacological treatment of obesity. This review highlights compelling emerging evidence indicating that GDF15 causes anorexia through the induction of nausea, emesis, and food aversions, which encourage a perspective on GDF15 system function in physiology and behavior beyond homeostatic energy regulation contexts. This highlights the potential role of GDF15 in the central mediation of nausea and emesis following a variety of physiological, and pathophysiological conditions such as chemotherapy-induced emesis, hyperemesis gravidarum, and cyclic vomiting syndrome.

Non-Suicidal Self-Injury in Eating and Feeding Disorder Patients: Characteristics and Clinical Implications in a Group of Referred Female Adolescents

Background: Non-suicidal self-injury (NSSI) and Feeding or Eating Disorders (FEDs) often coexist during adolescence with reciprocal influences on their clinical picture. The present study aimed to identify differences and similarities in the clinical presentation of young patients with both conditions compared to those with the two non-comorbid disorders. Methods: We consecutively recruited forty-five female patients aged between 11 and 18 at our third-level hospital and subdivided them into three groups (NSSI: n = 15; FED: n = 15; NSSI + FED: n = 15). Patients underwent a full clinical assessment. Results: Based on our results, the NSSI + FED group was characterized by higher rates of binging/purging behaviors, greater prevalence of Cyclothymic Disorder, and a more severe clinical presentation compared to the non-comorbid groups. Moreover, higher levels of suicidal ideation were found in the NSSI + FED group. Pharmacological treatment patterns also differed, with SSRI being prescribed more frequently to NSSI + FED patients while mood stabilizers were prescribed more frequently to NSSI ones. A Principal Component Analysis identified four main dimensions: “Body Image” impairment was more pronounced in NSSI + FED patients, indicating negative attitudes towards their own body; “Metacognition” deficits were higher in NSSI than FED. Conclusions: The present study underscores distinctive clinical features in patients with comorbid NSSI and FED, emphasizing the urgent need for tailored intervention strategies focusing on specific symptom domains.

The complicated relationship between asthma and swimming

Introduction: Apart from pharmacological treatment, non-pharmacological strategies including physical activity play a significant role in the management of asthma. The aim of this paper is to examine various topics related to swimming and asthma. They include the detailed effect of swimming on asthma control,the potential role of swimming in early childhood asthma development, exercise induced asthma in swimmers as well as the relationship between asthma and cold water swimming. Review methods: This article is based on the literature found in the PubMed Database from the period of 1971-2024 with the use of keywords such as “asthma”, “swimming”, “cold water swimming”, “exercise induced asthma”, “childhood asthma” Description of the state of knowledge: Swimming is a safe form of physical activity for asthma patients.Swimming training enhances aerobic capacity, reduces exercise-induced bronchoconstriction and improves lung function in both pediatric and adult patients. However, there is a concern regarding indoor swimming pools that chlorine can potentially induce airway inflammation. There is research suggesting that early life swimming pool exposure may contribute to the asthma development in atopic children. There is some premise to the thought that cold water swimming may help alleviate asthma symptoms, but it also carries many risks.Swimming is a major cause of exercise induced asthma in professional athletes. Conclusions: Alongside appropriate pharmacological treatment, swimming is a valuable strategy in asthma management in both pediatric and adult asthma patients. The risks of chlorinating pools are still not known to outweigh the benefits of swimming for asthmatics. Further research should be carried out on safety of early swimming in atopic children. Cold water swimming should also be evaluated in terms of safety and potential benefits for asthma patients.

Different hierarchical reconfigurations in the brain by psilocybin and escitalopram for depression

AbstractEffective interventions for neuropsychiatric disorders may work by rebalancing the brain’s functional hierarchical organization. Here we directly investigated the effects of two different serotonergic pharmacological interventions on functional brain hierarchy in major depressive disorder in a two-arm double-blind phase II randomized controlled trial comparing psilocybin therapy (22 patients) with escitalopram (20 patients). Patients with major depressive disorder received either 2 × 25 mg of oral psilocybin, three weeks apart, plus six weeks of daily placebo (‘psilocybin arm’) or 2 × 1 mg of oral psilocybin, three weeks apart, plus six weeks of daily escitalopram (10–20 mg; ‘escitalopram arm’). Resting-state functional magnetic resonance imaging scans were acquired at baseline and three weeks after the second psilocybin dose (NCT03429075). The brain mechanisms were captured by generative effective connectivity, estimated from whole-brain modeling of resting state for each session and patient. Hierarchy was determined for each of these sessions using measures of directedness and trophic levels on the effective connectivity, which captures cycle structure, stability and percolation. The results showed that the two pharmacological interventions created significantly different hierarchical reconfigurations of whole-brain dynamics with differential, opposite statistical effect responses. Furthermore, the use of machine learning revealed significant differential reorganization of brain hierarchy before and after the two treatments. Machine learning was also able to predict treatment response with an accuracy of 0.85 ± 0.04. Overall, the results demonstrate that psilocybin and escitalopram work in different ways for rebalancing brain dynamics in depression. This suggests the hypothesis that neuropsychiatric disorders could be closely linked to the breakdown in regions orchestrating brain dynamics from the top of the hierarchy.

Burn pain management in a female patient with severe burn injuries in Nepal: a case study and review.

Burn injuries in low-resource settings like Nepal present significant public health challenges, leading to substantial morbidity, mortality and severe pain. This paper assesses burn pain management in Nepal, emphasizing the need for enhanced strategies. A case study of a female patient with severe burn injuries from a rural village in Western Nepal illustrates current challenges. Reviewing studies on burn pain management in Nepal shows limited access to specialized facilities, inadequate palliative care, medication shortages and insufficient healthcare professionals. Pharmacological interventions are impacted by financial constraints and a lack of protocols, while nonpharmacological approaches have not been explored and contextualized for the Nepalese context due to similar financial issues. Comprehensive burn pain management requires addressing resource constraints through collaborative health-aid partnerships.

Comparative effectiveness of interventions for cancer treatment–related cognitive impairment in adult cancer survivors: protocol for a systematic review

BackgroundCancer treatment–related cognitive impairment (CTRCI) can substantially reduce the quality of life of cancer survivors. Many treatments of CTRCI have been evaluated in randomized controlled trials (RCTs), including psychological interventions, pharmacologic interventions, and other therapies. There is a pressing need to establish the benefits and harms of previously studied CTRCI treatments. The proposed systematic review and network meta-analyses will assess the relative efficacy and safety of competing interventions for the management of CTRCI.MethodsIn consultation with the review team, an experienced medical information specialist will draft electronic search strategies for MEDLINE®, Embase, CINAHL, PsycINFO, and the Cochrane Trials Registry. We will seek RCTs of interventions for the treatment of CTRCI in adults with any cancer, except cancers/metastases of the central nervous system. Due to the anticipated high search yields, dual independent screening of citations will be expedited by use of an artificial intelligence/machine learning tool. The co-primary outcomes of interest will be subjective and objective cognitive function. Secondary outcomes of interest will include measures of quality of life, mental and physical health symptoms, adherence to treatment, and harms (overall and treatment-related harms and harms associated with study withdrawal), where feasible, random-effects meta-analyses and network meta-analyses will be pursued. We will address the anticipated high clinical and methodological heterogeneity through meta-regressions, subgroup analyses, and/or sensitivity analyses.DiscussionThe proposed systematic review will deliver a robust comparative evaluation of the efficacy and safety of existing therapies for the management of CTRCI. These findings will inform clinical decisions, identify evidence gaps, and identify promising therapies for future evaluation in RCTs.