Global Efficacy Research Articles

Management of 10 Children With Inflammatory Rosacea With Topical Ivermectin.

Rosacea diagnosis and treatment in children are challenging, due to its rarity and to the lack of approved pharmacological agents for its treatment in this age group. In this case series, response to treatment with once daily applications of ivermectin (IVM) 1% cream for 12 weeks in 10 children affected by mild to severe inflammatory rosacea was evaluated clinically by Investigator Erythema Severity Assessment (IESA), Investigator Global Assessment of Severity (IGA-S), Investigator Global Assessment score of Global Efficacy (IGA-GE), and instrumentally by dermoscopy and Erythema-Directed Digital Photography (EDDP). Clinical improvement was achieved at the end of treatment compared to baseline (IESA: 2.3 vs. 0.5; IGA-S: 2.1 vs. 0.3) and confirmed by IGA-GE (0 = 55%, 1 = 33%, 3 = 11%) and instrumental monitoring (EDDP: 2.7 vs. 0.6). Once daily IVM application may be an effective therapeutic option for children with rosacea.

Dust impact on photovoltaic Modules: Global Data, predictive Models, Emphasis on chemical composition

This study explores the influence of dust on optical properties such as transmittance, absorptance, and emissivity of photovoltaic (PV) modules using over 300 experimental readings from various dust types. These readings were collected during regional storms and ground sources, data encompass different weight levels. Incorporating 690 global datasets and leveraging Artificial Neural Networks (ANN) and Multiple Linear Regression (MLR) in MATLAB, the study integrates key dust chemical components (Si, Fe, Ca, Al) and weight to predict the PV optical properties. This approach enhances models’ predictive accuracy across diverse environmental settings, which in turn enables more accurate forecasting of PV power output and thermal behavior under varying dust conditions, as these optical properties govern the module equations. Additionally, comparative analysis with existing literature shows superior accuracy, achieving Mean Squared Errors (MSEs) of 1.8 and 8.44, surpassing previous benchmarks. Results underscore the global efficacy of our methodologies in revealing dust’s impact on PV module thermal behaviour and efficiency.

Clinical and genomic diversity of Treponema pallidum subspecies pallidum to inform vaccine research: an international, molecular epidemiology study

The increase in syphilis rates worldwide necessitates development of a vaccine with global efficacy. Weaimed to explore Treponema pallidum subspecies pallidum (TPA) molecular epidemiology essential for vaccine research by analysing clinical data and specimens from early syphilis patients using whole-genome sequencing (WGS) and publicly available WGS data. In this multicentre, cross-sectional, molecular epidemiology study, we enrolled patients with primary, secondary, or early latent syphilis from clinics in China, Colombia, Malawi, and the USA between Nov 28, 2019, and May 27, 2022. Participants aged 18years or older with laboratory confirmation of syphilis by direct detection methods or serological testing, or both, were included. Patients were excluded from enrolment if they were unwilling or unable to give informed consent, did not understand the study purpose or nature of their participation, or received antibiotics active against syphilis in the past 30days. TPA detection and WGS were conducted on lesion swabs, skin biopsies, skin scrapings, whole blood, or rabbit-passaged isolates. We compared our WGS data to publicly available genomes and analysed TPA populations to identify mutations associated with lineage and geography. We screened 2802patients and enrolled 233participants, of whom 77 (33%) had primary syphilis, 154 (66%) had secondary syphilis, and two (1%) had early latent syphilis. The median age of participants was 28years (IQR22-35); 154 (66%) participants were cisgender men, 77 (33%) were cisgender women, and two (1%) were transgender women. Of the cisgender men, 66 (43%) identified as gay, bisexual, or other sexuality. Among all participants, 56(24%) had HIV co-infection. WGS data from 113participants showed a predominance of SS14-lineage strains with geographical clustering. Phylogenomic analyses confirmed that Nichols-lineage strains were more genetically diverse than SS14-lineage strains and clustered into more distinct subclades. Differences in single nucleotide variants (SNVs) were evident by TPA lineage and geography. Mapping of highly differentiated SNVs to three-dimensional protein models showed population-specific substitutions, some in outer membrane proteins (OMPs) of interest. Our study substantiates the global diversity of TPA strains. Additional analyses to explore TPA OMP variability within strains is vital for vaccine development and understanding syphilis pathogenesis on a population level. US National Institutes of Health National Institute for Allergy and Infectious Disease, the Bill & Melinda Gates Foundation, Connecticut Children's, and the Czech Republic National Institute of Virology and Bacteriology.

A phase III randomized controlled clinical trial evaluating the efficacy and safety of naftifine 2% cream versus terbinafine 1% cream in patients with superficial fungal infection of the skin

Background: Dermatophytosis is the prevailing fungal infection, typically addressed through topical, systemic antifungal medications, or a combination of both. Naftifine hydrochloride, belonging to the allylamine group, is a topical antifungal, exhibiting fungicidal properties alongside antibacterial and anti-inflammatory effects. This study evaluated the efficacy and safety of naftifine hydrochloride 2% w/w in 268 patients with dermatophytosis versus terbinafine hydrochloride 1% w/w. Methods: The drugs were applied daily for two weeks, with the primary endpoint being a clinical cure at the end of the treatment. Secondary endpoints included mycological cure, composite cure, global efficacy assessment, and post-treatment relapse. Results: In both groups, most patients experienced both clinical and mycological cures, with composite cures observed in 94.07% of the test group and 87.97% of the reference group. The global assessment of efficacy was 3.59 in the test group and 3.48 in the reference group, showing no notable difference between the two groups. All adverse events in both groups were mild and resolved within four days. Overall tolerability was comparable between the study groups. Conclusions: The study concluded that topical naftifine was effective and safe in patients with dermatophytosis and its efficacy and safety were found comparable to topical terbinafine.

Efficacy and Safety of Amorolfine Lotion 0.25% w/v Compared to Amorolfine Cream 0.25% w/w in Patients With Superficial Fungal Infections of the Skin: A Multi-center, Randomized, Open-Label, Active-Controlled, Non-inferiority Phase III Clinical Trial.

Dermatophytosis, a major cause of superficial fungal infections, requires topical and systemic antifungals. Amorolfine, a morpholine derivative, is a new topical antifungal available in cream and lotion formulations. To evaluate the efficacy and safety of amorolfine lotion 0.25% compared to amorolfine cream 0.25% in patients with dermatophytosis. A multi-center randomized, two-arm, active-controlled, parallel, non-inferiority phase III clinical trial involving 284 dermatophytosis patients was conducted, with the test arm using amorolfine lotion and the reference arm using amorolfine cream. The study drugs were applied once daily in the evening for four weeks and patients were followed up for another two weeks. The primary endpoint was clinical cure, while secondary endpoints included mycological cure, composite cure, global efficacy assessment, and post-treatment relapse. Safety and tolerability were assessed. Amongst the enrolled patients, 69.9% and 68.1% of patients had tinea corporis, while 30.1% and 31.9% had tinea cruris. The majority of patients in both groups (99.3% test and 97% reference) achieved a clinical cure at the end of treatment. Mycological cure was achieved by 98.6% and 96.3% respectively. A composite cure was achieved by 98.6% in the test arm versus 96.3% in the reference arm. A total of two AEs were reported in two (1.4%) patients in the test group and three AEs were reported in three (2.1%) patients in the reference group, all of the AEs were mild and resolved within three days without supportive medication. No severe adverse effects were reported in any of the study subjects. Amorolfine lotion 0.25% w/v showed a non-inferior clinical, mycological, and composite cure in dermatophytosis patients, was well-tolerated, and had a similar safety profile to amorolfine cream 0.25% w/w.

SECUREMEDS: BLOCKCHAIN PROTECTION FOR DRUG CHANNELS

The World Health Organisation (WHO) highlights the global threat of medicine counterfeiting, particularly in low- and middle-income countries where 10% of drugs may be counterfeit or of inferior quality, hence creating serious health hazards to the general public. Because there are shortages of necessary medications during illness outbreaks, this problem gets worse. Fighting this issue requires increased public awareness campaigns, improved pharmaceutical accessibility, and international cooperation Our goal is to create a strong framework for monitoring pharmaceuticals at every stage of the supply chain—manufacturers, distributors, retailers, and government agencies such as the FDA. A tamper-proof and easily traceable supply chain can be ensured by implementing blockchain technology and using transparent contractual arrangements. Furthermore, cutting-edge techniques like smart contracts made possible by Ganache and Ethereum improve supply chain integrity. Verification codes are sent via email to strengthen authentication processes and provide an additional degree of protection. Moreover, batch number hashing is secured by SHA encryption, guaranteeing complete protection during the distribution process. Global pharmaceutical safety and efficacy are guaranteed by this all-encompassing strategy.. . Keywords— Pharmaceutical Supply Chain Counterfeit Medications Blockchain Technology FDA (Food and Drug Administration).

Legal analysis of the merits of electronic transferable records: toward cross-border trade digitalization

Purpose The basis for this study on electronic transferable records (ETRs) in the context of digitalizing cross-border trade is established in this chapter. It illustrates how the growing trend toward paperless trade and technological improvements is changing trade operations. This chapter focuses on the need to look into ETRs because of their capacity to influence business transactions while navigating complex legal issues. The specific goals of the study are outlined, including a review of the advantages, legality, difficulties and best practices of ETRs. This study aims to shed light on the possible advantages and disadvantages of ETRs, the legal framework that controls their use and the best practices for their efficient implementation. This study also seeks to provide informative recommendations for businesses and people that are considering using ETRs. Design/methodology/approach This study explores the evolving world of ETRs and their crucial function in international trade. Multidimensional technique is used to examine the transformative potential of ETRs from a variety of research angles. The research design is based on a comprehensive evaluation of the literature that includes a wide range of reliable sources, including academic papers, business reports and legal documents. The comprehensive retrieval of essential material is ensured through keyword searches in renowned academic databases and industry resources. The qualitative synthesis of secondary sources further enhances this methodology and allows for a complex examination of the implications of ETRs. The case study analysis provides practical information on the benefits, hazards and practical applications of ETRs. Multifaceted aspects are uncovered via a thematic approach and qualitative investigation, including potential advantages, hazards, implementation plans and regulatory frameworks. Findings ETRs offer a range of potential advantages for cross-border trade, encompassing augmented efficiency, reduced costs and heightened security. Nonetheless, their implementation also presents legal challenges and risks, spanning security and privacy concerns, legal ambiguities and technical complexities. Consequently, it is crucial for individuals and businesses to meticulously assess and mitigate these risks through the integration of robust security protocols, staying informed about legal developments and adhering to pertinent regulatory stipulations. In spite of these hurdles, the trajectory of ETR adoption is anticipated to remain on an upward trajectory, driven by increasing recognition of their potential benefits and the concurrent evolution of legal frameworks and technical standards. Research limitations/implications Research limitations included the following: lack of adoption of ETRs internationally; and legal diversity and different legal systems results in different consideration of the ETRs. It makes reaching a unified ETR system more difficult. Practical implications It is necessary to develop clear policies and procedures and establish well-defined policies and procedures governing ETR use. These should encompass security guidelines, data protection measures and adherence to legal mandates. Regular review and updates are imperative. Stay current on legal developments: In light of the continuously evolving legal and regulatory landscape pertaining to ETRs, businesses and individuals must stay abreast of pertinent changes and seek professional counsel when necessary. Collaborate with partners and stakeholders: To ensure harmonization and standardization in ETR deployment, active collaboration with partners, regulators and industry associations is vital. Social implications Enhance awareness and education: Investment in awareness and educational initiatives is crucial. Decision-makers should organize training programs, workshops and seminars to enhance understanding of ETRs’ potential benefits in cross-border trade among stakeholders. Socially, the use of ETR can achieve several political advantages for the society. It minimizes risks of corruption through enhancing tracing and auditing abilities for relevant authorities making it more difficult to engage in corrupt practices. That can promote integrity within government and public procurement system. Originality/value The development of standardized technical frameworks and interoperable platforms for ETRs could enhance their seamless integration into existing trade systems. Additionally, investigating the integration of emerging technologies like blockchain, IoT and AI into ETR ecosystems could unlock innovative solutions to security, authenticity and data management concerns. This study examines how ETRs can radically alter how trade is conducted on a global scale. This paper examines ETRs’ role in improving cross-border trade digitization by examining their advantages, legal difficulties and implementation techniques. The conclusions will aid firms, decision-makers and attorneys in navigating the constantly changing world of trade agreements. The study’s ultimate goal is to offer takeaways that support effective, secure and legally compliant integration of ETRs, ensuring that they operate as a catalyst for improved global trade efficacy and efficiency.

Multi-strategy augmented Harris Hawks optimization for feature selection

Abstract In the context of increasing data scale, contemporary optimization algorithms struggle with cost and complexity in addressing the feature selection (FS) problem. This paper introduces a Harris hawks optimization (HHO) variant, enhanced with a multi-strategy augmentation (CXSHHO), for FS. The CXSHHO incorporates a communication and collaboration strategy (CC) into the baseline HHO, facilitating better information exchange among individuals, thereby expediting algorithmic convergence. Additionally, a directional crossover (DX) component refines the algorithm's ability to thoroughly explore the feature space. Furthermore, the soft-rime strategy (SR) broadens population diversity, enabling stochastic exploration of an extensive decision space and reducing the risk of local optima entrapment. The CXSHHO's global optimization efficacy is demonstrated through experiments on 30 functions from CEC2017, where it outperforms 15 established algorithms. Moreover, the paper presents a novel FS method based on CXSHHO, validated across 18 varied datasets from UCI. The results confirm CXSHHO's effectiveness in identifying subsets of features conducive to classification tasks.

Discovering peptides and computational investigations of a multiepitope vaccine target Mycobacterium tuberculosis

Mycobacterium tuberculosis (MTB) is the causative agent of tuberculosis (TB), a prevalent airborne infectious disease. Despite the availability of the Bacille Calmette-Guerin vaccine, its global efficacy remains modest, and tuberculosis persists as a significant global public health threat. Addressing this challenge and advancing towards the End MTB Strategy, we developed a multiepitope vaccine (MEV) based on immunoinformatics and computational approaches. Immunoinformatics screening of MBT protein identified immune-dominant epitopes based on Major Histocompatibility Complex (MHC) allele binding, immunogenicity, antigenicity, allergenicity, toxicity, and cytokine inducibility. Selected epitopes were integrated into an MEV construct with adjuvant and linkers, forming a fully immunogenic vaccine candidate. Comprehensive analyses encompassed the evaluation of immunological and physicochemical properties, determination of tertiary structure, molecular docking with Toll-Like Receptors (TLR), molecular dynamics (MD) simulations for all atoms, and immune simulations. Our MEV comprises 534 amino acids, featuring 6 cytotoxic T lymphocyte, 8 helper T lymphocyte, and 7 linear B lymphocyte epitopes, demonstrating high antigenicity and stability. Notably, molecular docking studies and triplicate MD simulations revealed enhanced interactions and stability of MEV with the TLR4 complex compared to TLR2. In addition, the immune simulation indicated the capacity to effectively induce elevated levels of antibodies and cytokines, emphasizing the vaccine's robust immunogenic response. This study presents a promising MEV against TB, exhibiting favorable immunological and physicochemical attributes. The findings provide theoretical support for TB vaccine development. Our study aligns with the global initiative of the End MTB Strategy, emphasizing its potential impact on addressing persistent challenges in TB control.

A129 OUTCOMES FOLLOWING ENDOSCOPIC SUBMUCOSAL DISSECTION OF SUPERFICIAL GASTROINTESTINAL TRACT NEOPLASTIC LESIONS FROM A TERTIARY-CARE ACADEMIC CENTRE

Abstract Background Endoscopic submucosal dissection (ESD) is an advanced luminal resection technique for dysplastic and early cancerous gastrointestinal (GI) tract neoplasms. By removing lesions en bloc, this method provides more accurate histopathologic evaluation of resection margins in comparison to endoscopic mucosal resection (EMR). Superior curative resection and lower recurrence rates over EMR have been shown in addition to the benefit of reduced morbidity and mortality compared to surgery. While ESD has become well-established in Asia and Europe, its adoption in North America – and in particular Canada – has been slowed by multiple technical and economic factors including a scarcity of infrastructure, institutional support, and standardized training. Additionally, reproduced Canadian data corroborating its known global efficacy is currently lacking. Aims Our aim was to evaluate clinical and technical outcomes in patients who underwent ESD of superficial GI tract neoplasms at a tertiary-care academic centre. Methods We conducted a retrospective single-centre cohort study at The Centre for Advanced Therapeutic Endoscopy & Endoscopic Oncology, St. Michael’s Hospital, Toronto, Canada. Consecutive adults (age ampersand:003E 18) who underwent ESD of any superficial GI tract neoplasm from October 2017 to December 2022 were included in the study. Primary outcomes were rates of en bloc, complete (R0), and curative resections. Secondary outcomes were rates of recurrence and adverse events. Data was collected through electronic chart review. Results ESD was performed in a total of 308 lesions with a mean size of 2.5 cm (range, 1-7 cm). Gastric ESD was the most common (n=130), followed by esophageal (n=91), rectal (n=62), and colonic (n=22). Three patients underwent duodenal ESD. En bloc, R0, and curative resection rates were 89.2%, 84.7%, and 71.8%, respectively. 64.3% of lesions were cancerous on pathology (n=198), of which 48 had at least submucosal invasion. Rates of delayed bleeding and deep mural injury (DMI) requiring surgical intervention were 3.9% and 1.3%, respectively. Overall recurrence at the first surveillance endoscopy (SE1) was 3.6%. Conclusions En bloc, R0, and curative resection rates reported from this largest single-centre Canadian ESD cohort are comparable to existing North American data. Low rates of early recurrence and an adequate safety profile have been demonstrated with this emerging oncologic method of resection. Additional investigation is warranted to optimize lesion selection and determine long-term clinical outcomes to further establish this technique in the management of superficial GI tract neoplasms. Table I. Procedural characteristics, outcomes, and adverse events for patients who underwent ESD of superficial GI tract neoplasms. Funding Agencies None

Recombinant porcine factor VIII in patients with congenital haemophilia A with inhibitors undergoing surgery: Phase 3, single-arm, open-label study.

Recombinant porcine factor VIII (rpFVIII; susoctocog alfa) is predicted to provide functional FVIII activity in patients with congenital haemophilia A with inhibitors (CHAWI). To evaluate the efficacy and safety of rpFVIII in patients with CHAWI undergoing invasive procedures. This phase 3, multicentre, single-arm, open-label study (NCT02895945) enrolled males aged 12-75 years with severe/moderately severe CHAWI who required surgical/invasive procedures. Patients received a loading dose of rpFVIII 1-2h before surgery. The primary outcome was the proportion of all procedures with a 'good' or 'excellent' response (treatment success) on the global haemostatic efficacy assessment score. Of the eight dosed patients, five completed the study. Six of seven surgeries (85.7%; 95% confidence interval, 42.1-99.6) achieved treatment success; five were rated 'excellent', one was rated 'good'. Seven surgery-related bleeding episodes occurred in three patients during the study, with none requiring additional surgical intervention. Overall, six of eight patients experienced 17 treatment-emergent adverse events. Three patients developed de novo inhibitors to rpFVIII. Five patients reported anamnestic reactions, three to both human (h) FVIII (i.e., alloantibodies to exogenous FVIII detected with anti-hFVIII assays) and rpFVIII, and two to hFVIII only. Four serious adverse events were considered related to rpFVIII (three anti-rpFVIII antibody positive; one anamnestic reaction to hFVIII and rpFVIII). Good haemostasis was achieved with rpFVIII during the immediate perioperative period. The study was terminated early because the study sponsor and health authorities determined that the risk of anamnestic reactions outweighs the benefits in this study population.

Implementation Of Balance Score Card To Improve Employee Performance At PT Gaya Makmur Tractors

To evaluate a company's success, performance evaluations must be conducted using acceptable performance assessment criteria. Performance appraisal also plays a vital role because it seeks to encourage employees to achieve efficiency and effectiveness in a company. Performance assessments help multinationals evaluate global human resource efficacy for optimization and improvement. It can be said that the Balanced Scorecard can help companies communicate the company's business strategy and as a company goal to achieve the vision and mission. Assessment of performance measurement through the balanced scorecard is an important factor in the company. Apart from being used to assess a company's success, performance measurement can also be used as a basis for determining a company's reward system, for example, to determine employee salary levels and appropriate rewards. Management can assess previous times using business efficiency data as the instrument. Traditional performance assessment, which primarily takes the financial sector into account, is currently what is most frequently utilized in businesses. Measuring performance with this system causes the company's orientation to only short-term profits and tends to ignore the long-term survival of the company. Performance measurements that focus on the financial sector are unable to estimate the performance of the company's intangible assets and intellectual assets (human resources). Additionally, this method of assessing achievement is less capable of entirely driving the organization on a better path and pays less consideration to the external sector and its history. Data analysis was carried out descriptively qualitatively. Using a deductive approach, the conclusion is reached by moving from the general to the specific, particularly those that are connected to the research issue, namely Smart Performance from an Islamic Human Resource Management Perspective. According to the findings, PT Gaya Makmur Tractors was urged to prepare for the worldwide marketplace by changes in performance activities. The key to competition in the global market is total quality which includes emphasis on product quality, cost or price quality, service quality, timely delivery quality, and other satisfactions that continue to develop to provide continuous satisfaction to customers. A crucial element of the business is performance measurement or assessment. Apart from being used to assess a company's success, performance measurement can also be used as a basis for determining a company's reward system, for example, to determine employee salary levels and appropriate rewards. Management can also use company performance measurements as a tool to evaluate the previous period

Treponema pallidum genetic diversity and its implications for targeted vaccine development: A cross-sectional study of early syphilis cases in Southwestern Colombia.

Venereal syphilis, caused by the spirochete Treponema pallidum subsp. pallidum (TPA), is surging worldwide, underscoring the need for a vaccine with global efficacy. Vaccine development requires an understanding of syphilis epidemiology and clinical presentation as well as genomic characterization of TPA strains circulating within at-risk populations. The aim of this study was to describe the clinical, demographic, and molecular features of early syphilis cases in Cali, Colombia. We conducted a cross-sectional study to identify individuals with early syphilis (ES) in Cali, Colombia through a city-wide network of public health centers, private sector HIV clinics and laboratory databases from public health institutions. Whole blood (WB), skin biopsies (SB), and genital and oral lesion swabs were obtained for measurement of treponemal burdens by polA quantitative polymerase chain reaction (qPCR) and for whole-genome sequencing (WGS). Among 1,966 individuals screened, 128 participants met enrollment criteria: 112 (87%) with secondary (SS), 15 (12%) with primary (PS) and one with early latent syphilis; 66/128 (52%) self-reported as heterosexual, while 48 (38%) were men who have sex with men (MSM). Genital ulcer swabs had the highest polA copy numbers (67 copies/μl) by qPCR with a positivity rate (PR) of 73%, while SS lesions had 42 polA copies/μl with PR of 62%. WB polA positivity was more frequent in SS than PS (42% vs 7%, respectively; p = 0.009). Isolation of TPA from WB by rabbit infectivity testing (RIT) was achieved in 5 (56%) of 9 ES WB samples tested. WGS from 33 Cali patient samples, along with 10 other genomic sequences from South America (9 from Peru, 1 from Argentina) used as comparators, confirmed that SS14 was the predominant clade, and that half of all samples had mutations associated with macrolide (i.e., azithromycin) resistance. Variability in the outer membrane protein (OMP) and vaccine candidate BamA (TP0326) was mapped onto the protein's predicted structure from AlphaFold. Despite the presence of mutations in several extracellular loops (ECLs), ECL4, an immunodominant loop and proven opsonic target, was highly conserved in this group of Colombian and South American TPA isolates. This study offers new insights into the sociodemographic and clinical features of venereal syphilis in a highly endemic area of Colombia and illustrates how genomic sequencing of regionally prevalent TPA strains can inform vaccine development.

Assessment of the Effect of Rehmannia glutinosa Leaf Extract in Maintaining Skin Health: A Proof-of-Concept, Double-Blind, Randomized, Placebo-Controlled Clinical Trial.

A double-blind, placebo-controlled, randomized, proof-of-concept trial aimed to evaluate the efficacy and safety of VerbasnolTM [Rehmannia glutinosa Libosch leaf-based extract (RGLE)] in females, with moderate to severe acne vulgaris. Twenty-two females aged 18 to 35 years having moderate to severe acne with Global Acne Grading System (GAGS) scores of 19 to 38 were included in the study and were randomized in a 1:1 ratio to receive either one capsule (100 mg/day) of RGLE or placebo orally after breakfast for 56 days. The primary outcome was a change in acne severity measured by the GAGS compared to the placebo on day 56. The secondary outcomes were changes in the number of inflammatory acne lesions, facial sebum secretion, quality of life, local pain and itching, skin wrinkle severity, and other skin characteristics, including radiance, luminosity, smoothness, texture, firmness, and hydration. Additionally, the percentage of responders and global tolerability and efficacy were evaluated. The mean GAGS score was reduced by 21.72% and 14.20% on day 28 in RGLE (n=10) and placebo groups (n=12), respectively, which further reduced in both groups on day 56. The RGLE group reported better improvement in other skin characteristics on day 56. No safety or tolerability concerns were reported for the extract. RGLE reduced acne and improved the skin quality in females compared to placebo as early as 28 days of supplementation. RGLE supplementation at a dose of 100 mg/day has provided a clinically relevant decrease in acne severity and improved the skin hydration and quality of life of the participants with acne after 56 days of dose administration.

Real-World Efficacy and Safety of Plasma-Derived Von Willebrand Factor-Containing Factor VIII Concentrates in Patients With Von Willebrand Disease in Italy.

Plasma-derived von Willebrand factor-containing factor VIII concentrates (pd-VWF/FVIII-C) are the mainstay of treatment in von Willebrand disease (VWD). Real-world data on efficacy and safety of these pd-VWF/FVIII-C are required. To retrospectively evaluate the efficacy and safety of pd-VWF/FVIII-C (Fanhdi® and Alphanate®, Grifols) in clinical practice in Italy. A multicentric, observational, retrospective study at 10 Italian centers was conducted. Eligible patients diagnosed with inherited VWD (ISTH criteria) were treated with either Fanhdi® or Alphanate® for bleeding episodes, prevention of surgical bleeding and secondary long-term prophylaxis (SLTP) according to clinical practice with medical records collected from January 2007 to December 2019. Efficacy/safety of pd-VWF/FVIII-C was assessed according to FDA-agreed objective criteria following regulatory procedures. Fifty-seven patients (M/F: 21/36) were enrolled in the study with the following VWD types: VWD1 (n = 29, 52%), VWD2A (n = 10, 18%), VWD2B (n = 7, 12%), VWD2M (n = 2, 4%), VWD2N (n = 1, 2%), VWD2 unclassified (n = 1, 2%), and VWD3 (n = 7, 12%). These pd-VWF/FVIII-C were used to manage 58 bleeding episodes (n = 24 patients), 100 surgeries (n = 47 patients), and 7 SLTP (n = 6 patients). Global clinical efficacy with these pd-VWF/FVIII-C was reported to be excellent/good in 85% of bleeding episodes, 98% of surgeries, and 100% of SLTP. As far as safety, no adverse-drug-related episodes, immunogenic or thrombotic events were reported. This study confirmed that Fanhdi® and Alphanate® were effective and safe in the management of bleeding episodes, the prevention of bleeding during surgeries and for SLTP in Italian patients with inherited VWD.

Prevalence, Risk Factors, and Management of Cluster headache; A systematic Review

Cluster headache (CH) is intricately linked to diverse risk factors, spanning hereditary, environmental, and lifestyle elements. This systematic study, guided by PRISMA guidelines, delves into the prevalence, risk factors, and management of CH. Examining English-language articles from 2010 to 2023 via PubMed/Medline, Scopus, and Embase, our findings reveal a significant association between cluster headaches and factors including family history, smoking, alcohol consumption, male predominance, and head trauma. Notably, a reevaluation of sex discrimination in familial cases is warranted, given the observed female predominance in familial history and CH association studies. Reviewing 739 studies, 7 met inclusion criteria, predominantly utilizing surveys and national database analyses (n=7). Improving our grasp of diagnosis and treatment holds promise for future evaluation and management. Our conclusion underscores global variability in CH prevalence, urging more rigorous population-based surveys. The substantial and persistent burdens associated with CH, from suicidality to economic stress, underscore the need for comprehensive research and intervention. CH transcends the label of a mere \"trigeminal autonomic headache,\" showcasing a diverse spectrum of attack and bout characteristics across countries and ethnicities. Despite the global efficacy of current diagnostic criteria, CH emerges as a dynamic illness, demonstrating progression or regression over time. This underscores the necessity for further research in comprehending its trajectory.

Exploring the Relationship between Adherence to Therapy, Treatment Acceptability, and Clinical Outcomes in Adults with Attention-Deficit/Hyperactivity Disorder: Results from the COMPAS Multicenter Randomized Controlled Trial

Introduction: Cognitive behavioral therapy and dialectical behavior therapy (DBT) can be effective in treating adults with ADHD, and patients generally consider these interventions useful. While adherence, as measured by attendance at sessions, is mostly sufficient, adherence to therapy skills has not been assessed. Furthermore, the relationship between patient evaluation of therapy effectiveness, treatment adherence, and clinical outcomes is understudied. Objective: This study aimed to examine treatment acceptability and adherence in relation to treatment outcomes in a large randomized controlled trial comparing a DBT-based intervention with a nonspecific active comparison, combined with methylphenidate or placebo. Method: A total of 433 adult patients with ADHD were randomized. Participants reported how effective they found the therapy, and adherence was measured by attendance at therapy sessions and by self-reports. Descriptive, between-groups, and linear mixed model analyses were conducted. Results: Participants rated psychotherapy as moderately effective, attended 78.40–94.37% of sessions, and used skills regularly. The best-accepted skills were sports and mindfulness. Groups receiving placebo and/or nonspecific clinical management rated their health condition and the medication effectiveness significantly worse than the psychotherapy and methylphenidate groups. Improvements in clinical outcomes were significantly associated with treatment acceptability. Subjective (self-reported) adherence to psychotherapy was significantly associated with improvements in ADHD symptoms, clinical global efficacy and response to treatment. Discussion: These results further support the acceptability of DBT for adult ADHD and suggest the need to address adherence to treatment to maximize clinical improvements. Results may be limited by the retrospective assessment of treatment acceptability and adherence using an ad hoc instrument.

Global efficacy and clinical application of androgen receptor inhibitors in metastatic prostate cancer.

Global efficacy and clinical application of androgen receptor inhibitors in metastatic prostate cancer.

Impacts of energy saving measures on IEQ, task performance and COVID-19 contagion risk in public buildings: analysis of a case-study in Bozen-Bolzano, Italy

The recent 2022 energy crisis has pushed several Italian public administrations to adopt solutions to reduce energy demand for space heating in public buildings. Reduction of HVAC system operation time, decrease of heating setpoint and changes to ventilation schedules are some examples of typically implemented measures. However, some of them are in direct competition with those adopted so far to limit the risk of COVID-19 contagion, such as higher ventilation rates. Furthermore, limited operation time and lower setpoints can lead to suboptimal thermal comfort conditions for workers in public buildings, with subsequent decrease of their task performances. In this framework, to assess the global efficacy of the most recent energy saving policies in public buildings, this research focuses not only on the quantification of energy savings but also on the analysis of increased COVID-19 contagion risk, as well as performance loss due to suboptimal building operation conditions. To investigate the impact of new building operation policies for energy savings, an intermediate storey of a public office building in Bolzano, Italy, was selected as a case-study.

Pharmacokinetics, Tolerability, and Safety of Glecaprevir/Pibrentasvir Co-formulated Bilayer Tablet Following Repeated Administration in Healthy Chinese Adults.

Glecaprevir (GLE)/pibrentasvir (PIB) is an all-oral, interferon- and ribavirin-free, pan-genotypic fixed-dose combination regimen approved for the treatment of all major genotypes of hepatitis C virus (HCV) infection in many countries worldwide. To support clinical development in China, an open-label, single-center phase 1 study was conducted to evaluate the pharmacokinetics, safety, and tolerability of GLE/PIB in healthy Chinese adults in Mainland China. Eighteen participants received 3 tablets of coformulated GLE/PIB 100/40mg once daily (QD) for 7 days. Following GLE/PIB 300mg/120mg administration, GLE and PIB reached maximum concentration in 4-5 hours with a terminal elimination half-life of 5.9 and 25 hours, respectively. Both GLE and PIB reached steady state by day 5, with no-to-minimal accumulation (≤17% higher). GLE/PIB exposures in healthy Chinese participants were similar to historical observations across phase 1 studies in healthy Western participants. GLE/PIB was safe and well-tolerated, with most adverse events being mild. These pharmacokinetics and safety data, together with existing global efficacy and safety data in healthy and HCV-infected Western participants, support the use of GLE/PIB 300mg/120mg QD in adult Chinese patients with chronic HCV infection.