Biofilm-associated infections remain difficult to treat because the extracellular polymeric substance matrix, charge-selective transport, microenvironmental gradients, and persister formation together limit effective drug exposure and reduce the antimicrobial efficacy. Traditional Chinese Medicine-derived bioactives provide structurally diverse small-molecule payloads with promising antibiofilm potential, but their therapeutic utility is often constrained by poor aqueous solubility, chemical instability, rapid clearance, and insufficient local retention at the infected sites. This Review surveys recent advances in drug delivery-enabled antibiofilm therapeutics based on TCM-derived bioactives, with emphasis on how delivery design addresses distinct biofilm-associated barriers. Representative payload liabilities are first discussed to clarify why formulation design is central to improving performance. Major delivery platforms, including nanoparticles, hydrogels, and microneedle-assisted systems, are then compared by using shared pharmaceutics criteria such as loading strategy, release behavior, penetration, retention, and model relevance. In addition, photodynamic, photothermal, and sonodynamic approaches are examined as combination strategies that can augment delivery-enabled biofilm control. Rather than cataloging natural products or delivery systems, this Review focuses on the relationship among biofilm barriers, payload properties, delivery design, and preclinical evaluation. Current challenges related to model relevance, quality consistency, safety, manufacturability, and further development are also discussed. Overall, this Review aims to provide a practical framework for the rational design of antibiofilm therapeutics based on TCM-derived bioactives.
Breast cancer-related fatigue is a persistent and subjective sense of tiredness caused by either the cancer itself or its treatments. This fatigue is disproportionate to recent physical activity and significantly interferes with daily life. The exact pathogenesis of Breast cancer-related fatigue remains unclear. Breast cancer cells induce metabolic abnormalities through reprogramming. This disruption in metabolic balance-particularly in various systems-may contribute to Breast cancer-related fatigue by compromising the body's overall metabolic homeostasis, all while supporting the biosynthetic demands of cancer cell proliferation. Current pharmacological treatments for cancer-related fatigue have demonstrated limited and inconsistent efficacy. These treatments are often hindered by a narrow drug target profile, high rates of adverse effects, and the complex mechanisms underlying fatigue, particularly those related to metabolic changes. Traditional Chinese medicine, with its multi-target modulation and lower toxicity, holds significant potential as long-term adjunctive or alternative treatments for Breast cancer-related fatigue. This article reviews the current understanding of the metabolic causes of Breast cancer-related fatigue and explores the role of traditional Chinese medicine interventions, offering new insights into potential targeted therapies for this condition.
The integration of artificial intelligence (AI) into pharmaceutical care represents a paradigm shift in healthcare delivery, offering unprecedented opportunities to revolutionize medication management, accelerate drug development, and enhance patient outcomes. This comprehensive review synthesized evidence from global literature (2021-2025) examining AI applications across drug discovery and development, clinical trials optimization, medication therapy management, and pharmacy operations. The AI demonstrated prediction accuracies of 86-98% in drug discovery, 80% improvement in clinical trial recruitment efficiency, and 32.7% increase in medication adherence over standard care. The global AI drug discovery market, valued at $1.5 billion (2023), is projected to reach $11.8 billion by 2030, reflecting substantial industry investment. However, implementation challenges persist including data quality concerns (30% accuracy in some datasets), regulatory compliance issues, and algorithmic bias (8-12% performance variations across demographics). Successful implementation requires coordinated efforts across technological development, regulatory frameworks, healthcare professional training, and continuous validation protocols addressing technical, organizational, and ethical dimensions simultaneously.
Atopic dermatitis (AD) is a chronic inflammatory skin disease often exacerbated by psychological stress, yet the underlying mechanisms remain unclear. Wushe Zhiyang Pills (WZP), an oral Chinese patent medicine, is clinically used for dermatological conditions, but its efficacy and mechanisms in stress-aggravated AD have not been defined. This study aims to evaluate the protective effects of WZP against AD under stress conditions, elucidate its molecular mechanisms, and identify its bioactive compounds. A murine AD model was established using repeated DNCB application, with or without chronic restraint stress to simulate psychological stress exposure. AD-like phenotypic severity, immune dysfunction, and inflammatory responses were comprehensively assessed. Targeted oxylipin lipidomics was performed to profile lipid mediator alterations, while molecular docking, molecular dynamics simulations, and cellular thermal shift assays (CETSA) were employed to identify and validate the direct target and active components of WZP. WZP treatment significantly ameliorated AD-like symptoms, restored the Th1/Th2 immune balance, reduced mast cell infiltration and cutaneous inflammatory cytokine expression, and lowered serum IgE levels. Notably, psychological stress exacerbated AD by upregulating ALOX15 expression and disrupting the cutaneous oxylipin profile, with marked elevations in pro-inflammatory mediators such as 15-HETE. WZP effectively reversed these stress-induced oxylipin derangements. Mechanistically, cimifugin, a bioactive component of WZP, was identified as a direct inhibitor of ALOX15, binding stably to the enzyme and suppressing its activity, thereby restoring oxylipin homeostasis. WZP alleviates stress-aggravated AD by inhibiting ALOX15-mediated oxylipin disruption, with cimifugin as a key active component. This reveals a novel "Stress-ALOX15-oxylipin-inflammation" axis and supports WZP as a promising therapy for stress-associated AD.
The genus Volkameria, belonging to the family Lamiaceae, comprises flowering plants with a pantropical distribution and a rich diversity of traditional applications and phytochemical compositions. Currently, 13 species are classified under this genus, which were previously categorized under different genera. This review aims to summarize the most up-to-date botanical descriptions, geographical distributions, ethnobotanical uses, phytochemistry, and pharmacological activities of Volkameria plants. Various databases and search engines, such as PubMed, Science Direct, Google Scholar, Sci-finder, Research Gate, online floras, and other published/unpublished resources, were consulted to compile this article. Volkameria species have been extensively used in traditional medicinal practices across different cultures to treat conditions such as fever, malaria, edema, cough, skin diseases, ulcers, inflammation, and rheumatism. Among the 13 accepted species, only four have been phytochemically investigated, with significant research focused on Volkameria inermis. Nearly 145 phytochemicals belonging to various classes, including flavonoids, diterpenoids, triterpenoids, steroids, and phenolic/lignan/iridoid/megastigmane glycosides, have been isolated and reported. Notably, flavonoids, diterpenoids, and triterpenoids have shown significant biological activities. V. glabra, and V. inermis have been studied for their pharmacological properties, such as antioxidant, anti-inflammatory, antimicrobial (including antibacterial, antiviral, antifungal, antimalarial, neuroprotective, anti-motor tics, insecticidal, and antifeedant effects. However, the remaining species require further investigation. Comprehensive studies, including preclinical and clinical trials, are essential to validate the efficacy and safety of these plants for medicinal use.
[Formula: see text] Dr. Tayade earned a Doctor of Veterinary Medicine, Masters, and PhD in Immunology from the Indian Veterinary Research Institute. He then completed a postdoctoral fellowship at the University of Guelph. He joined Queen's University in 2009 as an Assistant Professor and is currently working as a Vice Dean, and the Director of MD PhD Program in the Faculty of Health Sciences. The central theme of Dr. Tayade's research focusses on how immune dysfunction contributes to endometriosis pathophysiology, and identifying immune-based markers for diagnostic and therapeutic interventions. Dr. Tayade has published over 100 peer-reviewed articles in journals such as JCI Insight, Journal of Immunology, American Journal of Pathology, American Journal of Obstetrics and Gynecology, and Trends in Molecular Medicine. He has received competitive funding from the Canadian Institutes of Health Research (CIHR), the Natural Sciences and Engineering Research Council of Canada (NSERC), and the Endometriosis Foundation of America; and industrial funding from Bayer, Aurinia Pharmaceutical, and AbbVie. For his outstanding contributions to research, Dr. Tayade has received numerous special recognitions. In 2012, he won both the Early Researcher Award from the Ministry of Research and Innovation, as well as the Christian J Herr Award for Outstanding Contributions in Reproductive Immunology from the American Society for Reproductive Immunology. In 2014, he earned the Mihran and Mary Basmajian Award for Research Excellence from the Queen's Faculty of Health Sciences.
Chronic wounds remain a major global health challenge, characterized by persistent inflammation, biofilm formation, oxidative stress, and impaired angiogenesis. Despite extensive research on biopolymers and phytochemicals for wound management, an integrated framework that combines agro-derived excipients with nanomedicine-based delivery systems is still limited. This review introduces a hybrid carrier strategy combining chitosan and sago-derived sodium starch glycolate (SSG) for the nanoformulation of α-mangostin (α-MG) in chronic wound therapy. The concept integrates biomaterials science and phytopharmaceutical delivery to address both biological and formulation-related challenges. A structured literature search was conducted using Scopus, PubMed, and Google Scholar to identify peer-reviewed studies on chitosan-based dressings, SSG functional properties, and α-MG nanoformulations. The findings were critically synthesized to evaluate physicochemical characteristics, biological activities, and translational considerations. Chitosan provides hemostatic, antibiofilm, and immunomodulatory properties due to its cationic nature, while sago-derived SSG functions as a swelling matrix that regulates hydration and maintains moisture balance. Incorporation of α-MG, known for its antibacterial and antioxidant activity but limited by poor solubility, enables a biphasic delivery profile with an initial antimicrobial effect followed by sustained anti-inflammatory activity. Preclinical evidence indicates improved wound closure, reduced infection risk, and enhanced tissue regeneration. Chitosan-SSG hybrid systems represent a promising and sustainable platform for α-MG delivery in wound care. This review highlights their synergistic potential and outlines future directions for translational development in chronic wound management.
Obesity and related metabolic disorders, including metabolic dysfunction-associated fatty liver disease, dyslipidemia, and type 2 diabetes, are pressing global health concerns. Traditional Chinese medicine, specifically modified Lingguizhugan decoction (MLGZGD), has shown promise for managing these conditions. MLGZGD contains bioactive compounds that may modulate lipid metabolism and gut microbiota, suggesting potential therapeutic benefits for obesity and associated metabolic disorders. However, the underlying mechanisms remain largely unknown. This study investigated the therapeutic effects of MLGZGD on obesity and lipid metabolism. Specifically, we sought to examine how MLGZGD influences gut microbiota, modulates lipid metabolism, and contributes to improved metabolic health using a multi-omics approach. This study identified the active compounds in MLGZGD using UPLC-Q-TOF-MS/MS. The mice were divided into four groups (n = 8 per group) and received different treatments: model, positive control (atorvastatin 2.6 mg kg-1), low-dose MLGZGD (7 g kg-1), or high-dose MLGZGD (14 g kg-1). The effects of MLGZGD on the gut microbiota and lipid metabolism were evaluated using 16S rRNA sequencing and lipidomic analysis, and correlations between the two were explored. In normal mice, MLGZGD significantly altered the gut microbiota composition, increasing the abundance of beneficial genera such as Akkermansia and Dubosiella, while reducing the abundance of Enterorhabdus. In high-fat diet-induced obese mice, MLGZGD restored the disrupted gut microbiota, notably reducing the Firmicutes/Bacteroidetes ratio, improving Akkermansia levels, and increasing Clostridiales abundance. Lipidomic analysis showed that MLGZGD significantly improved triglyceride and phosphatidylcholine metabolism, with a notable correlation between Akkermansia and Clostridiales abundance and the lipid profile. MLGZGD effectively ameliorates obesity and lipid metabolism-related disorders by reshaping the gut microbiota and modulating lipid metabolism. These findings support the therapeutic potential of MLGZGD in treating obesity and related metabolic disorders, with modulation of gut microbiota and lipid metabolism as key mechanisms.
Digital transformation is increasingly shaping how the Medical Affairs (MA) function generates insights, engages stakeholders, and demonstrates value within the pharmaceutical industry. This article examines how MA professionals can navigate and lead the digital revolution reshaping healthcare delivery and stakeholder engagement. Digital maturity progresses from basic channel activation through tactical integration to advanced personalisation enabled by artificial intelligence (AI). Central to this transformation is the convergence of omnichannel engagement with real-world evidence generation, creating unprecedented opportunities to deliver personalised, scientifically rigorous interactions that enhance patient outcomes and healthcare professional (HCP) satisfaction. AI applications are creating new opportunities for MA to generate insights, communicate evidence, and measure impact across the healthcare ecosystem, enabling predictive analytics and intelligent content delivery at scale. Digital transformation is less likely to be effective when implemented through organisational silos. Important enablers include cross-functional collaboration, robust governance for responsible AI deployment, co-creation with external partners including HCPs and patient advocacy groups, and shared technology infrastructure that supports coordinated engagement. Best practices for digital communication strategies, fostering innovation cultures, and demonstrating measurable value are explored. As healthcare's digital evolution accelerates, MA has an important role in ensuring that digital tools are applied in ways that remain scientifically rigorous, ethically governed, and aligned with stakeholder needs. By treating digital as an enabler of high-quality scientific exchange rather than an end in itself, MA can support more relevant engagement and strengthen the translation of evidence into practice.
The United States overdose crisis is driven in large part by an increasingly unpredictable and contaminated drug supply, including fentanyl and its analogs and emerging adulterants such as xylazine and nitazenes. Drug checking interventions such as fentanyl test strips and Fourier Transform Infrared Spectroscopy are essential for harm reduction, yet they also highlight a central policy failure: they place the burden of safety on people who use drugs (PWUD) and frontline programs after drugs have already entered an unregulated market. We argue for a more pragmatic upstream public health response, authorizing pilots of a safer, regulated drug supply ("safer supply"), broadly defined as legal and regulated access to psychoactive substances or close pharmaceutical alternatives intended to reduce reliance on the unregulated drug market. International experience, particularly models in Switzerland, Canada, and the United Kingdom, demonstrates feasibility and suggests potential benefits, including improved health and social stability, reduced reliance on unregulated supply, and reduced acute care utilization in some settings. For the United States context, we propose a portfolio approach: near-term, healthcare-based pilots leveraging existing controlled-substance infrastructure (eg, opioid treatment programs, clinics, pharmacies, and tech-enabled dispensing) while preserving space for community-governed models with legal protections and longer-horizon, state-regulated pathways. We address predictable concerns (secondary sharing, youth initiation, community impact, mixed population-level findings) and outline guardrails and evaluation strategies that are PWUD-led, nonpunitive, and methodologically rigorous. We conclude with concrete policy actions to authorize pilots, establish legal protections, fund independent evaluation, and scale models that demonstrably reduce harm while integrating with harm reduction and treatment services.
Vitamin D plays a crucial role in maintaining bone health, regulating the immune system and enhancing metabolic function. Although supplementation is recommended for individuals with confirmed deficiency, the increasing trend of empirical prescribing and self-medication has raised concerns about inappropriate use, particularly in low- and middle-income countries like Pakistan. This study aimed to explore perceptions, attitudes and practices regarding the prescription of vitamin D supplementation among healthcare professionals and self-medicating patients in Pakistan, with a specific focus on identifying factors contributing to non-evidence-based prescribing and unregulated consumption. A qualitative, exploratory design was adopted to investigate the study objectives. In-depth, semistructured interviews were conducted with 20 doctors from five medical specialities and 17 patients who reported using vitamin D supplements. Participants were recruited from healthcare settings in Lahore using a purposive sampling approach. Thematic analysis was used to identify key patterns in prescribing and self-use behaviour. Four themes emerged from the doctor interviews: empirical prescribing without diagnostic testing, the influence of pharmaceutical marketing, the perceived harmlessness of vitamin D and the absence of standardised guidelines. From patients, themes included self-medication and over-the-counter access, belief in vitamin D as a general wellness booster, long-term unmonitored use and lack of awareness about dosing and risks. Neither group was aware of the potential toxicity and follow-up testing was done rarely. The study's findings highlight a widespread perception of availability, potentially inappropriate and unregulated use of vitamin D, underscoring the need for nationwide action through education, regulation and public awareness. Coordinated efforts by health organisations, clinicians and pharmacists can promote safer supplementation practices and help prevent long-term adverse health effects.
Aloe-emodin (AE), as an anthraquinone active component in traditional Chinese medicine, exhibits multiple pharmacological activities, yet its mechanism of hepatotoxicity remains unclear. The purpose of this study was to systematically investigate the molecular mechanism of AE-induced hepatotoxicity, with a specific focus on hepatic protein adduction. AE was incubated with murine hepatic protein solution, followed by enzymatic digestion and liquid chromatography-tandem mass spectrometry analysis to detect l-cysteine covalent adducts. For in vivo study, mice were administered AE, and the formation of hepatic protein adduction was monitored over time and across different doses. Additionally, buthionine sulfoximine was used as a pretreatment to assess the role of glutathione in the adduction process. Cell experiments were also performed to evaluate the relationship between protein adduct formation and cytotoxicity. AE-cysteine covalent adducts A1 and A2 were identified both in vitro and in livers of AE-treated mice. In vivo study confirmed dose-dependent formation of AE-cysteine adducts (A1/A2) in mouse liver, peaking at 30 min. Depleting glutathione elevated A1 and A2 levels by 40.43% and 27.93% in vivo, indicating the protective role of glutathione through competitively conjugating with AE, thereby reducing its covalent modification of hepatic proteins. Cytotoxicity of AE is positively correlated with its concentration, which reveals the critical role of adduct formation in initiating dosage-dependent cytotoxicity. This study demonstrates that hepatotoxicity of AE is directly associated with the formation of covalent adducts targeting l-cysteine residues, providing a critical theoretical foundation for safety evaluation and clinical application of AE-containing herbs.
To categorize preexisting fundus findings in a large group of healthy young adult cynomolgus macaques [nonhuman primates (NHPs)] and to compare them to similar conditions in young human retinas. During the past 30 years, more than 20,000 young purpose-bred cynomolgus macaques were screened prior to enrollment in nonclinical pharmaceutical development studies at a single contract research organization. The fundus findings were documented by clinical examinations, various retinal imaging modalities, and/or visual electrophysiological testing. Sheen from the internal limiting membrane (ILM) was common in these young adult NHPs as it is in young humans. Infrequent in both NHPs and humans were cilioretinal arteries. Small patches of retinal pigment epithelial (RPE) depigmentation were common, for which there is no human correlate. Likewise, there is no exact human correlate for foveal drusen-like spots in the young NHPs. Also common in NHPs but uncommon in humans were remnants of the fetal vasculature. Conditions rare in both NHPs and humans included myelinated nerve fiber layer, astrocytic hamartoma, coloboma, and congenital hypertrophy of the RPE. Notable rare abnormal findings included a white dot condition, a large macular tumor, and idiopathic optic atrophy, all of which were of unknown etiology. Preexisting abnormalities, when taken together, are common in NHPs and can occasionally complicate the assessment of toxicity from test articles subsequently administered, impacting the clinical development of test articles. As such, it is critical that NHPs be prescreened and, ideally, the fundus appearance be documented with fundus imaging when enrolled in preclinical studies.
This patent describes heterocyclic carboxamindes as new, highly effective α2C-Adrenergic receptor (α2C-AR) antagonists, suitable for treating α2C-ARs-associated disorders. It offers detailed information on the heterocyclic carboxamindes, pharmaceutical formulations, and their applications in managing α2C-ARs-related conditions.
Fagopyrum acutatum is used in Chinese medicine for its heat-clearing, detoxifying and pus-expelling properties, particularly for respiratory diseases. However, the effect of Fagopyrum acutatum on inflammation induced by influenza A virus (IAV) remains unclear. This study aimed to assess how Fagopyrum acutatum extract (FAE) affected the inflammation underlying mechanisms of IAV in vitro and in vivo. The pharmacodynamic components in FAE were identified using ultrahigh-performance-liquid-chromatography (UPLC)-Q-Exactive mass spectrometry (MS). The mechanism of FAE was predicted through RNA sequencing (RNA-seq) analysis and confirmed via reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot. The protective effects of FAE on lung injury and systemic inflammation were evaluated based on survival rate, lung index, histopathological alterations in lung tissues, lung cytokine levels, leukocyte counts in peripheral blood and serum inflammatory factor levels. There were 103 compounds (mainly carbohydrates and organic acids) identified in FAE. FAE reversed the IAV-induced expression of RIG-I, MDA5, TLR3, IP-10, IL-6, IL-8, IL-1β, TNF-α, and MCP-1 in A549 cells, and reduced NF-κB P65 and IKBα phosphorylation. In vivo, FAE improved survival rates, decreased lung index and alleviated pathological changes in lung tissue caused by IAV. Expression of MCP-1, TNF-α, IL-6, IP-10 in lung tissues of mice with influenza pneumonia decreased by FAE. In addition, FAE significantly improved H1N1-induced leukocyte alterations and serum cytokine levels. FAE effectively alleviates IAV-stimulated inflammation and lung damage via NF-κB signaling pathway.
Ovarian stimulation is an essential step during in vitro fertilisation (IVF) and intra-cytoplasmic sperm injection (ICSI), needed to produce multiple follicles for follicle aspiration. The strategy of stimulating the ovaries with gonadotropins is well established and can be performed using different types of gonadotropins. This review update brings together all randomised studies that compare recombinant follicle stimulating hormone (rFSH) with urinary gonadotropins and other recombinant rFSH (including rFSH from a human cell line) and biosimilars. To compare the effectiveness and safety of recombinant follicle-stimulating hormone (rFSH) with the three main types of urinary gonadotropins, rFSH derived from a human cell line (follitropin delta) and rFSH biosimilars for ovarian stimulation in women undergoing IVF or ICSI treatment cycles. We carried out an extensive search on 31 March 2025, according to Cochrane guidelines. The databases searched included: the Cochrane Gynaecology and Fertility Specialised Register of controlled trials, CENTRAL, MEDLINE and Embase. We also searched trials registries, reference lists and contacted experts in the field for additional studies. We included all randomised controlled trials reporting data comparing clinical outcomes of women undergoing IVF/ICSI cycles and using rFSH in comparison with human menopausal gonadotropin (HMG) or highly purified HMG (HP-HMG), purified urinary follicle-stimulating hormone (FSH-P), highly purified urinary FSH (FSH-HP), follitropin delta, and rFSH biosimilars for ovarian hyperstimulation. We used the Trustworthiness in RAndomised Controlled Trials (TRACT) checklist to assess trustworthiness and excluded potentially problematic studies from the analyses. We implemented the core outcome set for infertility. Our main outcomes were live birth, ovarian hyperstimulation syndrome (OHSS) (both critical outcomes) and clinical pregnancy. We used the Cochrane risk of bias tool (RoB 1) to assess the risk of bias. We combined data using a fixed-effect model to calculate an odds ratio (OR) or mean difference (MD). We summarised the overall certainty of evidence for the main outcomes using GRADE criteria. We included 59 studies (25 new studies) with a total of 18,119 women undergoing fertility treatment. rFSH versus HMG/HP-HMG Live birth is probably lower with rFSH compared to HMG/HP-HMG (OR 0.83, 95% CI 0.73 to 0.95; 15 studies, 4793 participants, moderate-certainty evidence). OHSS is probably higher with rFSH compared to HMG/HP-HMG (OR 1.42, 95% CI 1.12 to 1.80; 37 studies, 9813 participants, moderate-certainty evidence). Clinical pregnancy is probably lower with rFSH compared to HMG/HP-HMG (OR 0.87, 95% CI 0.76 to 0.98; 15 studies, 4839 participants, moderate-certainty evidence). rFSH versus FSH-HP Live birth: there is probably little or no difference in live birth between rFSH and FSH-HP (OR 1.02, 95% CI 0.86 to 1.21; 15 studies, 2956 participants, moderate-certainty evidence) OHSS: there is probably little or no difference in OHSS between rFSH and FSH-HP (OR 1.01, 95% CI 0.67 to 1.53; 18 studies, 3640 participants, moderate-certainty evidence). Clinical pregnancy: there is probably little or no difference in clinical pregnancy between rFSH and FSH-HP (OR 1.00, 95% CI 0.88 to 1.14; 22 studies, 4535 participants, moderate-certainty evidence). rFSH versus follitropin delta Live birth: there is probably little or no difference in live birth between rFSH and follitropin delta (OR 0.88, 95% CI 0.74 to 1.04; 3 studies, 2688 participants, moderate-certainty evidence). OHSS is probably higher with rFSH compared to follitropin delta (OR 1.62, 95% CI 1.18 to 2.23; 4 studies, 2988 participants, moderate-certainty evidence). Clinical pregnancy: there is no difference in clinical pregnancy between rFSH and follitropin delta (OR 0.94, 95% CI 0.80 to 1.11; 3 studies, 2688 participants, high-certainty evidence). rFSH versus biosimilars Live birth is probably higher with rFSH compared to biosimilars (OR 1.29, 95% CI 1.09 to 1.54; 8 studies, 2883 participants, moderate-certainty evidence). OHSS: there may be little or no difference in OHSS between rFSH and biosimilars (OR 0.77, 95% CI 0.57 to 1.06; 8 studies, 2883 participants, low-certainty evidence). Clinical pregnancy was probably higher with rFSH compared to biosimilars (OR 1.35, 95% CI 1.14 to 1.60; 7 studies, 2783 participants, moderate-certainty evidence). The certainty of the evidence ranged from low to moderate for live birth and OHSS, and from moderate to high for clinical pregnancy. The main limitations were risk of bias in the included studies - unclear selection bias and selective reporting, as well as high risk of other bias. Many studies were sponsored by the pharmaceutical industry. Live birth and clinical pregnancies are probably lower with rFSH compared to HMG/HP-HMG, while OHSS is probably higher with rFSH when compared to HMG/HP-HMG. There is probably little to no difference in live birth, clinical pregnancy, or OHSS between rFSH and FSH-HP. When compared with follitropin delta, there is probably little or no difference in live birth or clinical pregnancy, while OHSS is probably higher with rFSH. When compared with biosimilars, live birth and clinical pregnancies are probably higher with rFSH, while there may be little or no difference in OHSS. This Cochrane review had no dedicated funding. Protocol (2005) https://doi.org/10.1002/14651858.CD005354 Review (2011) https://doi.org/10.1002/14651858.CD005354.pub2.
The first-in-class diarylquinoline (DARQ) bedaquiline (BDQ) is in the medicines list for drug-resistant tuberculosis. TBAJ-587 is a next-generation DARQ with improved anti-Mycobacterium tuberculosis (Mtb) activity and reduced cardiac repolarization abnormalities. The in vitro efficacy of TBAJ-587 and its main metabolites (M2, M3 and M12) was analyzed under standard (ST) growth conditions and with cholesterol (CHO), or fatty acids (FA) as physiologically relevant alternative carbon sources. Minimal inhibitory concentration (MIC) assays and time-kill assays (TKA) linked to drug measurements in bacterial samples were performed to allow correlation of pharmacodynamics (PD) with actual in vitro pharmacokinetics (PK). The most active compounds, TBAJ-587 and its M3 metabolite, exhibited broth media and concentration dependent efficacy showing a bactericidal effect at ≥5x MIC. Bacterial cultures treated with 1x MIC and 2x MIC of TBAJ-587 resumed growth after 28 days and displayed moderate increased MIC values compared to untreated conditions, which were linked to new variants of BDQ resistance mutations in the atpE, atpB, and Rv0678 genes. This study revealed that TBAJ-587 and its metabolites bind to polystyrene plastic-ware, the most commonly used material in antimicrobial research, being the effective unbound drug concentration dependent on the media composition. PKPD analyses determined that Mtb was killed with lower exposures of TBAJ-587 and M3 than expected in ST and FA broth, suggesting previously underestimated potency in these media. Unlike commonly performed in in vitro PKPD studies that solely rely on nominal drug concentrations, our work precisely relates compound activity to actual effective concentrations that are measured over time directly in Mtb cultures, providing improved longitudinal data to feed in silico models for translational research.
This patent discloses carboxamides as novel somatostatin receptor 4 (SSTR4) agonists, and they are potential treatments for SSTR4-related diseases. It provides details on the synthesis of carboxamides, pharmaceutical compositions, and the uses of such compounds in the treatment of SSTR4-related diseases.
Editorial boards determine the direction and scope of journals. The objective of this study was to assess the gender composition of the editorial boards of four Pakistani Medline-indexed journals using a descriptive cross-sectional study design. Gender composition of the editorial boards of four Pakistani Medline-indexed journals was assessed using a descriptive cross-sectional study design. The publicly available official editorial board pages were accessed and analysed for: Journal of the Pakistan Medical Association (JPMA), Journal of Ayub Medical College (JAMC), Journal of the College of Physicians and Surgeons of Pakistan (JCPSP), and Pakistan Journal of Pharmaceutical Sciences (PJPS). Cumulatively, 163 individuals comprised the editorial boards in these journals, out of which 112 (68.7%) were males. JPMA had the largest editorial team with 59 individuals, and JCPSP had the smallest team with 25 individuals. The most and least gender-diverse editorial teams were reported by JPMA and JAMC, with 22 (37.3%) and 6 (20.7%) women, respectively. Results augur the need for gender-sensitive training programmes to promote gender balance in the editorial boards of the country's medical journals.
Neurodevelopmental disorders are lifelong conditions with onset in early childhood that impair cognitive, social, behavioural and physical functioning. Their consequences extend beyond healthcare, shaping education, social and community services, and family life. Economic evaluations can guide payers by quantifying the value for money of interventions, but standard methods require adaptation for this context. This paper offers practical guidance for pharmacoeconomic evaluations of interventions for children with neurodevelopmental disorders, synthesising methodological literature and applied experience to articulate core challenges, recommend solutions and highlight emerging opportunities. Evaluations must address five inter-related issues: defining and justifying an analytic perspective that captures multi-sectoral costs and benefits; identifying and valuing direct, indirect and intangible costs across health, education and social domains; selecting outcomes sensitive to changes in child functioning and health-related quality of life that can be economically valued; incorporating spillover effects for caregivers and families; and modelling long-term developmental trajectories amid data scarcity and uncertainty. We recommend adopting a societal perspective; applying comprehensive context-appropriate costing; combining generic and condition-specific outcome measures; explicitly including caregiver and family impacts; integrating equity analyses; and using long time horizons supported by robust modelling such as microsimulation or agent-based approaches. Promising directions include capability-based frameworks and digital biomarkers to enable real-world measurement of function and quality of life. Tailored pharmacoeconomic methods are essential for credible policy-relevant evaluations of neurodevelopmental disorder interventions. Transparent reporting and alignment with international standards will improve comparability, support uptake by decision makers, and promote equitable resource allocation for children and families affected by neurodevelopmental disorders.