Pharmacological Treatment Research Articles

Non-pharmacological Treatment for Nontuberculous Mycobacterial Pulmonary Disease.

Nontuberculous mycobacterial pulmonary disease (NTM-PD) arises from the exposure of susceptible hosts to a diverse group of environmental mycobacteria. The emphasis on non-pharmacological strategies is motivated by widespread presence of nontuberculous mycobacteria (NTM) in various environments and the inconsistent success rates of pharmacological treatments. Modifiable factors contributing to NTM-PD development include impaired airway clearance, low body mass index, gastroesophageal reflux disease, and exposure to NTM habitats. This suggests that lifestyle and environmental modifications could affect disease development and progression. The review highlights several modalities that can modify the risk factors. Airway clearance techniques, informed by the "gel-on-brush" model of the bronchial epithelium, aims at enhancing mucociliary clearance and have potential in alleviating symptoms and potentially improving lung function. The impact of nutritional status is also examined, with a lower body mass index linked to an increased risk and progression of NTM-PD, indicating the importance of targeted nutritional support. Additionally, the theoretical and epidemiological links between gastroesophageal reflux disease and NTM-PD advocates for careful management of reflux episodes. Understanding the risk of NTM transmission through environmental exposure to contaminated water and soil is also crucial. Strategies to mitigate this risk, including effective water management and minimizing soil contact, are presented as vital preventive measures. In conclusion, the review supports the inclusion of non-pharmacological treatments within a comprehensive NTM-PD management strategy, alongside conventional pharmacological therapies. This integrated approach seeks to improve the overall understanding and handling of NTM-PD.

Surgery is associated with better long-term outcomes than pharmacological treatment for obesity: a systematic review and meta-analysis

Obesity is a highly prevalent disease with numerous complications. Both intensive medical treatment with the use of pharmacological drugs and bariatric surgery are current options. The objective of this meta-analysis was to compare, in the long-term, intensive medical treatment and surgery based on twelve parameters related to weight loss, cardiovascular and endocrine changes. A review of the literature was conducted in accordance with the PRISMA guidelines (PROSPERO: CRD42021265637). The literature screening was done from inception to October 2023 through PubMed, EMBASE and Web of Science databases. We included randomized clinical trials that had separate groups for medical treatment and bariatric surgery as an intervention for obesity. The risk of bias was assessed through RoB2. A meta-analysis was performed with measures of heterogeneity and publication bias. Subgroup analysis for each surgery type was performed. Data is presented as forest-plots. Reviewers independently identified 6719 articles and 6 papers with a total 427 patients were included. All studies were randomized controlled trials, three had a follow up of 5 years and two had a follow up of 10 years. Both groups demonstrated statistical significance for most parameters studied. Surgery was superior for weight loss (− 22.05 kg [− 28.86; − 15.23), total cholesterol (− 0.88 [− 1.59; − 0.17]), triglycerides (− 0.70 [− 0.82; − 0.59]), HDL (0.12 [0.02; 0.23]), systolic pressure (− 4.49 [− 7.65; − 1.33]), diastolic pressure (− 2.28 [− 4.25; − 0.31]), Hb glycated (− 0.97 [− 1.31; − 0.62]), HOMA IR (− 2.94; [− 3.52; − 2.35]) and cardiovascular risk (− 0.08; [− 0.10; − 0.05]). Patient in the surgical treatment group had better long term outcomes when compared to the non-surgical group for most clinical parameters.

What are the effects of pharmacological, non-invasive brain stimulation and psychological interventions, and their combination, in the treatment of post-stroke depression? A Cochrane Review summary with commentary.

Post-stroke depression (PSD) is a prevalent condition that can significantly influence the recovery process. To assess the effects of pharmacological, non-invasive brain stimulation and psychological interventions, and their combination on PSD. A summary of the Cochrane Review by Allida et al. (2023), with comments from a rehabilitation perspective. Sixty-one studies with 5831 participants were included in the Cochrane Review. Very low-certainty evidence indicated favorable treatment effects of pharmacological interventions, psychological therapies, and the combination of pharmacological intervention and non-invasive brain stimulation on PSD. Pharmacological intervention has resulted in increased side effects associated with the central nervous system and gastrointestinal system, with very low-certainty evidence. Evidence for the effectiveness of pharmacological, psychological, and combination therapies for the management of PSD is uncertain, as the quality of the evidence has been assessed as very low. Therefore, further studies with improved methods should investigate pharmacological and non-pharmacological interventions for the treatment of depression in stroke survivors.

Dopamine D1 receptor in medial prefrontal cortex mediates the effects of TAAR1 activation on chronic stress-induced cognitive and social deficits.

Trace amine-associated receptor 1 (TAAR1) is an intracellular expressed G-protein-coupled receptor that is widely expressed in major dopaminergic areas and plays a crucial role in modulation of central dopaminergic neurotransmission and function. Pharmacological studies have clarified the roles of dopamine D1 receptor (D1R) in the medial prefrontal cortex (mPFC) in cognitive function and social behaviors, and chronic stress can inhibit D1R expression due to its susceptibility. Recently, we identified TAAR1 in the mPFC as a potential target for treating chronic stress-induced cognitive and social dysfunction, but whether D1R is involved in mediating the effects of TAAR1 agonist remains unclear. Combined genomics and transcriptomic studies revealed downregulation of D1R in the mPFC of TAAR1-/- mice. Molecular dynamics simulation showed that hydrogen bond, salt bridge, and Pi-Pi stacking interactions were formed between TAAR1 and D1R indicating a stable TAAR1-D1R complex structure. Using pharmacological interventions, we found that D1R antagonist disrupted therapeutic effect of TAAR1 partial agonist RO5263397 on stress-related cognitive and social dysfunction. Knockout TAAR1 in D1-type dopamine receptor-expressing neurons reproduced adverse effects of chronic stress, and TAAR1 conditional knockout in the mPFC led to similar deficits, along with downregulation of D1R expression, all of these effects were ameliorated by viral overexpression of D1R in the mPFC, suggesting the functional interaction between TAAR1 and D1R. Collectively, our data elucidate the possible molecular mechanism that D1R in the mPFC mediates the effects of TAAR1 activation on chronic stress-induced cognitive and social deficits.

Advances in Gut Microbiota-Targeted Therapeutics for Metabolic Syndrome

Previous investigations have illuminated the significant association between the gut microbiome and a broad spectrum of health conditions, including obesity, diabetes, cardiovascular diseases, and psychiatric disorders. Evidence from certain studies suggests that dysbiosis of the gut microbiota may play a role in the etiology of obesity and diabetes. Moreover, it is acknowledged that dietary habits, pharmacological interventions, psychological stress, and other exogenous factors can substantially influence the gut microbial composition. For instance, a diet rich in fiber has been demonstrated to increase the population of beneficial bacteria, whereas the consumption of antibiotics can reduce these advantageous microbial communities. In light of the established correlation between the gut microbiome and various pathologies, strategically altering the gut microbial profile represents an emerging therapeutic approach. This can be accomplished through the administration of probiotics or prebiotics, which aim to refine the gut microbiota and, consequently, mitigate the manifestations of associated diseases. The present manuscript evaluates the recent literature on the relationship between gut microbiota and metabolic syndrome published over the past three years and anticipates future directions in this evolving field.

Unravelling pituitary tumours in medically treated patients with acromegaly: the impact of systematic MRI reassessment.

In acromegaly, the primary tumor is usually found during magnetic resonance imaging (MRI) of the pituitary gland. A remnant tumor after surgery is, however, harder to depict. When a tumor is missed, the remaining option is usually lifelong pharmacological treatment. To identify tumors by reassessment of all available MRI scans in pharmacologically treated patients, operated or not, and to compare our results with the routine MRI reports. Adult patients diagnosed with acromegaly and managed at a tertiary care center between 2005 and 2021 and currently on pharmacological treatment were included. MRI scans were evaluated in a standardized manner and classified independently by a radiologist and an endocrinologist into "certain," "suspected," or "no tumor." In case of disagreement, consensus was achieved with a senior neuroradiologist. The results were compared using the clinical radiologists' routine MRI reports. We identified certain and suspected tumors in 29/74 and 36/74 patients, respectively. No tumor was identified in nine patients. In five of these, no MRI contrast agent was given. Discrepancy between our results and the routine MRI reports was found in 31/74 patients (P = 0.01). In 22 patients, the routine reports described no tumor while we identified certain tumors in 2/22 patients and suspected tumors in 13/22 patients. In most patients with pharmacologically treated acromegaly, we identified a certain or suspected pituitary tumor. These findings were more frequent compared to the routine MRI reports. Based on our results, patients will be considered for a change in long-term treatment modality.

P079 Denosumab treatment for bone marrow oedema - a case series

Abstract Background/Aims This is a case series of patients treated with a single dose of denosumab to improve bone marrow oedema. Bone marrow oedema can cause significant pain and functional limitations. On MRI imaging, bone marrow oedema is identified as T1 hypointensities and T2 hyperintensities. Denosumab is a human monoclonal antibody that inhibits osteoclast bone absorption via binding to the cytokine RANKL [receptor activator of nuclear factor kappa-B ligand]. The exact aetiology of bone marrow oedema is unknown. It typically occurs in those aged between 40 to 60 years old. Studies have described therapeutic improvement with antiresorptive medications. Bone marrow oedema will generally resolve if left untreated. However, pharmacological treatments can curtail the clinical course. Methods This case series has emerged from Chelsea and Westminster hospital. Data was collected over a five year period for seven patients with bone marrow oedema [demonstrated on MRI] that were treated with denosumab. Six of the seven patients had a spontaneous insufficiency fracture associated with the bone marrow oedema on imaging. In our case series, two of the patients had bone marrow oedema in their hips and five in their knees. Denosumab was administered as a single 60mg subcutaneous injection. Response to treatment was ascertained by repeat MRI scan 2-4 months after denosumab treatment as well as patient reported outcomes. Results The average age of the patients was 56.4 years [age range 48-68 years]. Five of the patients [71%] reported improved symptoms at the affected site. Four patients [57%] had complete resolution of their bone marrow oedema on imaging with a further patient [14%] having an improved radiological appearance. Visual analogue scale [VAS] scores improved by 50%, although this data was only collected for some of the patients. No side-effects or complications were noted from the treatment. One of the patients who did not improve with denosumab treatment went on to have a total hip replacement due to complete loss of joint space. It is noteworthy that following further investigations, five of the seven patients were diagnosed with osteopenia on dual-energy x-ray absorptiometry [DEXA] scan, one had osteoporosis [and was subsequently commenced on alendronic acid] and one did not attend for their DEXA scan. Conclusion This series demonstrates that denosumab is an effective treatment for bone marrow oedema. Denosumab given as a single dose can be considered a safe treatment; there is not the risk of rebound worsening of bone density on treatment cessation that can be seen with prolonged treatment. Denosumab should be offered to patients who are symptomatic from bone marrow oedema to allow for quicker symptom relief and radiological improvement. Our findings are similar to that of a slightly larger case series of fourteen patients by Rolvien et al. published in 2017. Disclosure M. Galloway: None. A. Jacobs: None. M. Ismajli: None.

NBR1-dependent autophagy activation protects against environmental cadmium-evoked placental trophoblast senescence

Cadmium (Cd), a well-established developmental toxicant, accumulates in the placentae and disrupts its structure and function. Population study found adverse pregnancy outcomes caused by environmental Cd exposure associated with cell senescence. However, the role of autophagy activation in Cd-induced placental cell senescence and its reciprocal mechanisms are unknown. In this study, we employed animal experiments, cell culture, and case-control study to investigate the above mentioned. We have demonstrated that exposure to Cd during gestation induces placental senescence and activates autophagy. Pharmacological and genetic interventions further exacerbated placental senescence induced by Cd through the suppression of autophagy. Conversely, activation of autophagy ameliorated Cd-induced placental senescence. Knockdown of NBR1 exacerbated senescence in human placental trophoblast cells. Further investigations revealed that NBR1 facilitated the degradation of p21 via LC3B. Our case-control study has demonstrated a positive correlation between placental senescence and autophagy activation in all-cause fetal growth restriction (FGR). These findings offer a novel perspective for mitigating placental aging and placental-origin developmental diseases induced by environmental toxicants.

Exploring the cessation efficacy and harm reduction potential of heated tobacco and nicotine pouch products in smokers and smokeless tobacco users: study protocol of a 6-month randomized controlled switching trial

Background: Despite decades of research on pharmacological and behavioural smoking cessation treatments, current quit aids are of limited success. The introduction of new, combustion-free nicotine and tobacco products extended the tool kit for people who smoke to switch away from their risky habit. We performed a systematic review including 120 studies resulting in several recommendations for a robust study design to determine the cessation efficacy of a new nicotine or tobacco product. Consequently, we prepared this study protocol to assess the cessation efficacy of heated tobacco products (HTPs) and nicotine pouches (NPs). Methods: 250 subjects (125 exclusive smokers and 125 exclusive smokeless tobacco (SLT) users) will be recruited and offered a choice of HTPs in case of smokers and a choice of NPs in case of SLT users in order to switch. Subjects will undergo four visits (baseline, 1, 3, and 6 months) to collect biospecimens and for physical examinations. Use behaviour and questionnaires will be monitored on a regular basis by means of a smartphone-app. We describe a sensitive and specific compliance monitoring using suitable biomarkers of exposure. The sample size of 250 subjects and duration of 6 months will allow the quit rates to be assessed with sufficient statistical power. Finally, the choice between different products shall reflect the individuals’ preferences. Conclusions: This protocol can be applied generically, providing a robust determination of a products’ cessation efficacy. Trial Registration: The trial will be registered in the International Clinical Trials Registry Platform.

Baccharoides anthelmintica (L.) Moench: A Review on Ethnomedicinal, Phytochemical, Pharmacological and Toxicological Profile.

Baccharoides anthelmintica (L.) Moench is a popular medicinal plant with a long history of use in several traditional remedies to cure a variety of diseases including; its effect on the central nervous system, gastrointestinal tract, metabolism, kidneys, gynecology, skin diseases, and general health. The present review aims to provide the latest, organized information on toxicological, pharmacological, phytochemical, and ethnomedicinal applications of Baccharoides anthelmintica. For this; several well-known searchable websites (search engines) like; Web of Science, Google Scholar, Scopus-Elsevier, Taylor & Francis, Springer, and DOAJ, were used to empirically investigate the knowledge of this useful medicinal plant. Based on previous studies, the pharmacological action of B. anthelmintica is due to various secondary metabolites including alkaloids, terpenoids, lignans, steroids, and other phytoconstituents. Hence, the present study recorded 225 phytochemicals obtained from different parts of the plant, where the steroids and derivatives (48), terpenes and sesquiterpenes (46), flavonoids and derivatives (41), fatty acids and derivatives (40), phenolic acids (12), triterpenes (11), chalcones (06), diterpenes (01) and miscellaneous (20) were reported. The present review also covered the pharmacological importance, including antioxidant, antimicrobial, antiparasitic, antidiabetic, hypolipidemic action, liver disease, anticancer potential, anti-HIV, antiosteoporotic action, antitoxic action, skin disorder, wound healing and immunomodulatory activity, systemic infection, and treatment of neurodegenerative diseases etc. The review concluded that B. anthelmintica has several pharmacological activities, which were due to the presence of secondary metabolites present in it, and thus indicates the importance of medicinal value of this plant. Hence, B. anthelmintica may be a good source for developing a lead molecule in the process of new drug discovery and development. More study is required to determine the pharmacokinetics, mechanism of action, long-term toxicology testing, safe dosage, and possible interactions with other herbs/drugs.

P119 The effectiveness of drug-induced immunosuppression using biologics and Janus-kinase inhibitors in improving fatigue in adults with rheumatoid arthritis: a systematic review of randomised controlled trials

Abstract Background/Aims Fatigue is a prominent and debilitating symptom. Many clinicians indicate that they may not assess fatigue frequently because there are no guidelines for fatigue treatment; thus, they feel unskilled to appropriately manage it. Previous evidence from a 2016 Cochrane review supported the use of biologics for fatigue among people with rheumatoid arthritis (RA). As of yet, this evidence has not been incorporated into management guidelines. Further, it is outdated and lacks data on newer drugs such as biosimilars and Janus-Kinase inhibitors (JAKis). We aimed to update the evidence on the effectiveness of biologics and JAKis for RA-fatigue, with a view to informing future guidelines. Methods Five electronic databases (Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL and PubMed) were systematically searched, from 2014 to present, for randomised controlled trials (RCTs) evaluating pharmacological interventions in adults with RA. Two reviewers contributed to the screening and analysis of the included papers, and any dispute was resolved through a comprehensive discussion. One reviewer then extracted the data and assessed methodological quality using the Cochrane Risk of Bias Tool. The effectiveness of treatments was determined by extracting change from baseline (CFB) data and/or the proportion achieving the minimal clinically important difference (MCID) in fatigue. Where only CFB data were provided, reviewers compared absolute change values against the relevant MCID to evaluate intervention superiority. Owing to data heterogeneity, a narrative synthesis approach was undertaken. Results A total of 43 RCTs and post hoc analyses were included. No eligible studies were found regarding biosimilars. Drug classes investigated included JAKis (n = 27), interleukin-6 inhibitors (n = 9), anti-CD-20 monoclonal antibody (n = 1), selective so-stimulation modulators (n = 2) and TNF inhibitors (n = 4). Of these studies, four were inactive placebo comparator studies, 33 were active placebo comparator studies (i.e. csDMARDs), and six were head-to-head comparator studies. Studies had a low to unclear risk of bias, perhaps due to the high number of post hoc analyses (n = 28, 65%). In total, 37 studies (86%) determined an advantage to using biologics/JAKis; five (12%) determined that treatment with biologics/JAKis was not superior to csDMARDs. The final study showed no meaningful improvement in fatigue from treatment or control. Conclusion Most studies showed that biologics/JAKis hold the potential for fatigue management. However, fatigue reporting was poor, and few studies focussed on fatigue as a primary outcome in post hoc analyses. Therefore, it is not clear whether these treatments may, in fact, be more effective in certain subgroups of patients, for example, those for whom fatigue is a significant problem. Accordingly, the development of treatment guidelines involving these therapies is currently unlikely. We propose that future clinical trials designating fatigue as a primary endpoint will be crucial to improving the establishment of guidelines to support fatigue management. Disclosure H.J. Ghadanfari: None. J.H. Humphreys: None. K.L. Druce: None.

The pharmacoepigenetic paradigm in cancer treatment.

Epigenetic modifications, characterized by changes in gene expression without altering the DNA sequence, play a crucial role in the development and progression of cancer by significantly influencing gene activity and cellular function. This insight has led to the development of a novel class of therapeutic agents, known as epigenetic drugs. These drugs, including histone deacetylase inhibitors, histone acetyltransferase inhibitors, histone methyltransferase inhibitors, and DNA methyltransferase inhibitors, aim to modulate gene expression to curb cancer growth by uniquely altering the epigenetic landscape of cancer cells. Ongoing research and clinical trials are rigorously evaluating the efficacy of these drugs, particularly their ability to improve therapeutic outcomes when used in combination with other treatments. Such combination therapies may more effectively target cancer and potentially overcome the challenge of drug resistance, a significant hurdle in cancer therapy. Additionally, the importance of nutrition, inflammation control, and circadian rhythm regulation in modulating drug responses has been increasingly recognized, highlighting their role as critical modifiers of the epigenetic landscape and thereby influencing the effectiveness of pharmacological interventions and patient outcomes. Epigenetic drugs represent a paradigm shift in cancer treatment, offering targeted therapies that promise a more precise approach to treating a wide spectrum of tumors, potentially with fewer side effects compared to traditional chemotherapy. This progress marks a step towards more personalized and precise interventions, leveraging the unique epigenetic profiles of individual tumors to optimize treatment strategies.

E053 The use of online platforms in the treatment of chronic musculoskeletal disease

Abstract Background/Aims Persistent pain is a common feature of rheumatic diseases, and has a significant impact on the emotional, physical and social wellbeing of individuals. Despite pharmacological treatment for inflammatory arthritis, such as rheumatoid arthritis (RA), 10-20% have features suggestive of co-existing centralised pain. These patients have worse pain, mood and sleep despite DMARD therapy. Similar to fibromyalgia (FM), non-pharmacological treatments are likely to be useful for this problem. Evidence supports cognitive behavioural therapy (CBT) and acceptance and commitment therapy (ACT) for the management of chronic musculoskeletal pain. Unfortunately, access to services is poor for many people. This has driven the development of online treatment programmes and apps. The current study explores willingness of patients with rheumatic diseases to use online platforms in this context. Methods An observational cohort study of patients with a clinical diagnosis of either RA or FM were recruited from NHS outpatient clinics. Data collection was via the online platform Redcap. Analysis compared demographic and clinical features of those with past use of online platforms or apps for health purposes using Student’s t-test and chi squared tests. A similar comparison was conducted for future use of online platforms or apps. Results Of 343 patients 177(52%) FM, 166(48%) RA), 264 (77%) were female with mean (SD) age 48 (13.6). Past use of online platforms is summarised in Table 1. Significantly more patients with FM (70%) would be willing to try an online platform in future, compared to those with RA (30%). Those with future interest are more likely to be younger (mean age 46), have lower mood (mean PHQ-9 13), worse sleep (mean ISI 14.6) and less pain (mean VAS 6.6) compared to those who would not (mean age 60, PHQ-9 12, ISI 12.6 and VAS 7.0 respectively). Conclusion Those with FM are more likely to engage with online platforms or apps for health purposes than those with RA. In this analysis, users were more likely to be younger and experience more severe anxiety and depression but further work is needed to evaluate the contributing factors which will be essential when optimising the impact of online healthcare initiatives. Disclosure A.J.W. Wall: None. E. Kelleher: None. V. Wanigasekera: None. A. Irani (nee Soni): None.

Plasma IGFBP-3 and IGFBP-5 levels are decreased during acute manic episodes in bipolar disorder patients.

Introduction: Bipolar disorder (BD) is a recurrent and disabling psychiatric disorder related to low-grade peripheral inflammation and altered levels of the members of the insulin-like growth factor (IGF) family. The aim of this study was to evaluate the plasma levels of IGF-2, insulin-like growth factor-binding protein 1 (IGFBP-1), IGFBP-3, IGFBP-5, IGFBP-7, and inflammatory markers such as tumor necrosis factor α (TNF-α), monocyte chemoattractant protein 1 (MCP-1), and macrophage inflammatory protein 1β (MIP-1β). Methods: We used the Young Mania Rating Scale (YMRS) to determine the severity of the symptomatology, while proteins were measured by enzyme-linked immunosorbent assay (ELISA). We included 20 patients with BD who suffered a manic episode and 20 controls. Some BD patients (n = 10) were evaluated after a period (17 ± 8days) of pharmacological treatment. Results: No statistical difference was found in IGF-2, IGFBP-1, IGFBP-7, TNF-α, and MIP-1β levels. However, IGFBP-3 and IGFBP-5 levels were found to be statistically decreased in BD patients. Conversely, the MCP-1 level was significantly increased in BD patients, but their levels were normalized after treatment. Intriguingly, only IGFBP-1 levels were significantly decreased after treatment. No significant correlation was found between the YMRS and any of the proteins studied either before or after treatment or between IGF proteins and inflammatory markers. Discussion: To some extent, IGFBP-3 and IGFBP-5 might be further explored as potential indicators of treatment responsiveness or diagnosis biomarkers in BD.

Wellens Syndrome the Previous Room to A Large Previous Myocardial Infarction. Report of A Case.

Wellens syndrome or also called anterior descending T wave syndrome, described for the first time in 1982 by Wellens and Zwaan, as a subtype of high-risk unstable angina that progresses to myocardial infarction in the anterior face, which can be massive and fatal; Documentation of this pattern on the ECG would be essential to initiate pharmacological treatment and priority referral to the hemodynamics room; A case of a 74-year-old male patient is described who begins symptoms in the early morning with typical chest pain and adrenergic discharge that progressively disappears. The patient is sent to a High Specialty Medical Center for Catheterization, which correlates injury in a rare anatomical site of the middle segment of the anterior descending artery. Knowledge of Wellens Syndrome in the emergency room is of utmost importance to reduce morbidity in patients and avoid its consequences, as well as the importance of primary referral for cardiac catheterization.

Spatiotemporal transmission of SARS-CoV-2 lineages during 2020-2021 in Pernambuco-Brazil.

SARS-CoV-2 virus emerged as a new threat to humans and spread around the world, leaving a large death toll. As of January 2023, Brazil is among the countries with the highest number of registered deaths. Nonpharmacological and pharmacological interventions have been heterogeneously implemented in the country, which, associated with large socioeconomic differences between the country regions, has led to distinct virus spread dynamics. Here, we investigate the spatiotemporal dispersion of SARS-CoV-2 lineages in the Pernambuco state (Northeast Brazil) throughout the distinct epidemiological scenarios that unfolded in the first 2 years of the pandemic. We generated a total of 1,389 new SARS-CoV-2 genomes from June 2020 to August 2021. This sampling captured the arrival, communitary transmission, and the circulation of the B1.1, B.1.1.28, and B.1.1.33 lineages; the emergence of the former variant of interest P.2; and the emergence and fast replacement of all previous variants by the more transmissible variant of concern P.1 (Gamma). Based on the incidence and lineage spread pattern, we observed an East-to-West to inner state pattern of transmission, which is in agreement with the transmission of more populous metropolitan areas to medium- and small-size country-side cities in the state. Such transmission patterns may be partially explained by the main routes of traffic across municipalities in the state. Our results highlight that the fine-grained intrastate analysis of lineages and incidence spread can provide actionable insights for planning future nonpharmacological intervention for air-borne transmissible human pathogens.IMPORTANCEDuring the COVID-19 pandemic, Brazil was one of the most affected countries, mainly due its continental-size, socioeconomic differences among regions, and heterogeneous implementation of intervention methods. In order to investigate SARS-CoV-2 dynamics in the state of Pernambuco, we conducted a spatiotemporal dispersion study, covering the period from June 2020 to August 2021, to comprehend the dynamics of viral transmission during the first 2 years of the pandemic. Throughout this study, we were able to track three significant epidemiological waves of transmission caused by B1.1, B.1.1.28, B.1.1.33, P.2, and P.1 lineages. These analyses provided valuable insights into the evolution of the epidemiological landscape, contributing to a deeper understanding of the dynamics of virus transmission during the early years of the pandemic in the state of Pernambuco.

Long-term Healthcare Resource Utilization and Costs among Patients with Myasthenia Gravis: A Swedish Nationwide Population-based Study.

Health care costs and societal impact of myasthenia gravis (MG), a potentially life-threatening rare, chronic neuromuscular disease are sparsely studied. We assessed healthcare resource utilization (HCRU) and associated costs among patients with newly diagnosed (ND) and pre-existing (PE) MG in Sweden. This observational, retrospective cohort study used data from four linkable Swedish nationwide population-based registries. Adult MG patients receiving pharmacological treatment for MG and having ≥ 24-month follow-up during the period 1/1/2010 to 12/31/2017 were included. A total of 1,275 patients were included in the analysis, of which 554 patients were categorized into the ND MG group and 721 into the PE MG group. Mean (±SD) age was 61.3 (±17.4) years and 52.3% were female. In first year post-diagnosis, ND patients had significantly higher utilization of acetylcholinesterase inhibitors (96.0% vs 83.9%), corticosteroids (59.6% vs 45.8%), thymectomy (12.1% vs 0.7%) and plasma exchange (3.8% vs 0.6%); had higher all-cause (70.9% vs 35.8%) and MG-related (62.5% vs 18.4%) hospitalization rates with 11 more hospitalization days (all p<0.01) and an increased risk of hospitalization (odds ratio [95% CI] = 4.4 [3.43, 5.64]) than PE MG. In year 1 post-diagnosis, ND MG patients incurred €7302 (p<0.01) higher total all-cause costs than PE MG, of which 84% were estimated to be MG-related and the majority (86%) were related to inpatient care. These results remained significant also after controlling for baseline demographics and comorbidities (p<0.01). In year 2 post-diagnosis, the all-cause medical costs decreased by ~55% for ND MG from year 1 and were comparable with PE MG. In this population-based study, MG patients required significantly more healthcare resources in year 1 post-diagnosis than PE MG primarily due to more pharmacological treatments, thymectomies and associated hospitalizations. These findings highlight the need to better understand potential factors including disease characteristics associated with increased health resource use and costs and need for more efficacious treatments early in the disease course.

Economic burden assessment for the management of asthma patients at Mexico's National Institute for Respiratory Diseases

Determinar la carga económica anual del asma, desde una perspectiva institucional y con base en la clasificación recomendada por GINA, en una cohorte retrospectiva de adultos atendidos en el Instituto Nacional de Enfermedades Respiratorias (INER) de México. Estudio observacional, longitudinal y retrospectivo, llevado a cabo a partir de la información recabada de 247 pacientes femeninas con asma. Se estimaron los costos directos anuales: visitas, pruebas de laboratorio, tratamiento farmacológico y de las crisis o exacerbaciones, para determinar la carga anual de la enfermedad desde una perspectiva institucional, y según la clasificación de la Iniciativa Global para el Asma. El costo promedio anual fue de $43,813,92, que aumentó en relación con la necesidad de aumento de dosis de corticoides inhalados y beta-agonistas de acción prolongada. El costo promedio de la consulta médica fue de $2004.57, $982.82 por gestión de crisis y $2645.95 por pruebas de laboratorio. El tratamiento farmacológico representó la principal carga económica, con un costo promedio anual de $38,180.58. Los resultados resaltan una carga económica del asma estimada en un costo anual por paciente de $43,813.92 MXN (DE=93,348.85), en el contexto del tercer nivel de atención en el sistema de salud público mexicano. La gravedad del asma, los tratamientos y los biológicos fueron los principales factores que aumentaron los costos directos de la atención.

Rosacea in Older Adults and Pharmacologic Treatments.

Rosacea is a chronic inflammatory skin condition that is often more severe in older patients. The main clinical features are erythema, telangiectasia, and inflammatory lesions of the face. The pathogenesis of this condition is not fully understood but certainly multifaceted. Immune and inflammatory dysregulation, genetics, neurogenic dysregulation, microbiome dysbiosis, and systemic disease have all been implicated in rosacea pathogenesis. As we better understand the various pathways that lead to rosacea, we acknowledge that the different symptoms may have unique underlying triggers and mechanisms. Aging also impacts rosacea diagnosis and treatment. Older adults have more severe rosacea symptoms while also having more sensitive and fragile skin than younger patients; therefore, rosacea treatments for older patients require a balance between delivering adequate potency while also minimizing skin irritation and other adverse effects. Until recently, rosacea diagnoses were based on concrete subtypes that did not necessarily capture each patient's manifestation of rosacea. There is now an emphasis on more personalized phenotype-based diagnoses and treatments, which allows for more emphasis on treating individual symptoms and accounting for the unique characteristics of older patients. Centrofacial erythema is best treated with brimonidine and oxymetazoline, while phymatous change and telangiectasia are best treated with surgery and laser ablation. Treatment for rosacea papules and pustules ranges from topicals, such as azelaic acid, ivermectin, metronidazole, minocycline, and encapsulated benzoyl peroxide, to systemics, such as doxycycline and isotretinoin. It is important to understand these treatments in relation to adverse effects and drug interactions that may specifically arise in older populations to provide optimal care. As we advance in understanding rosacea's pathogenesis and adopt personalized phenotype-based approaches, optimizing care for older patients becomes crucial. Continued research into novel treatments is essential to address their unique needs.

Premenstrual syndrome: new insights into etiology and review of treatment methods.

Premenstrual syndrome (PMS) is a common disorder affecting women of reproductive age, with an estimated global prevalence of 47.8%, with severe symptoms occurring in 3-8%, significantly affecting daily functioning. GABA conductance and changes in neurosteroid levels, particularly allopregnanolone, are suspected to play a substantial role in the disorder's etiology. In this paper, we provide an overview of recent reports on the etiology and recognized therapeutic approaches, encompassing both pharmacological and non-pharmacological interventions. Our examination includes studies on SSRIs, hormonal agents, neurosteroids, supplementation, and therapeutic roles. We aim to determine the most favorable treatment regimen by comparing medication effects and alternative methods. The treatment of PMS is crucial for enhancing the quality of life for affected women. Medications used in PMS treatment should be individually selected to achieve the best therapeutic effect, considering the clinical situation of the patients.