Better evaluation of the contribution of the main diseases, injuries, and risk factors for mortality and life expectancy is crucial for more efficient policy making at the national and subnational levels in Iran. The aim of this study is to assess the effect of emerging causes of mortality on health, specifically COVID-19, which can help policy makers implement preventive measures in similar situations. In this systematic analysis of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023, we present estimates of cause-specific mortality at the national and subnational levels in Iran from 1990 to 2023. New to this iteration of GBD, we present a decomposition analysis of the contribution of specific causes of death to net gain or loss in life expectancy across 31 provinces of Iran. We used an array of data sources including censuses, vital registration, and surveys for national and subnational estimates. The two leading causes of death in Iran were ischaemic heart disease and stroke in both 1990 and 2019. However, in 2020 and 2021, the COVID-19 pandemic displaced the leading causes of death, ranking first with age-standardised mortality rates of 286·2 deaths (95% uncertainty interval 267·9-310·5) per 100 000 in 2020 and 250·0 deaths (233·2-272·5) per 100 000 in 2021. COVID-19 ranked second and tenth in 2022 and 2023, respectively. Life expectancy at birth for both sexes combined declined from 78·0 years (77·7-78·1) in 2019 to 74·3 years (74·0-74·4) in 2020. It steadily recovered to 78·8 years (78·5-79·2) in 2023. COVID-19 was the main cause of loss in life expectancy, by 4·19 years, between 2019 and 2020. There was a net gain of 12·4 years in life expectancy in Iran from 1990 to 2023. The net gain at the national level can be mostly attributed to reduced mortality from ischaemic heart disease (2·61 years), stroke (1·63 years), neonatal disorders (1·26 years), transport injuries (0·88 years), and neoplasms (0·64 years). The decline in mortality rates of major causes continued to 2023 despite the pandemic. An exception was Alzheimer's disease, which showed a 4·0% increase in rate between 2019 and 2023 and led to a net loss of 0·04 years in life expectancy since 1990. Diabetes led to a net loss of 0·09 years since 1990. There were variations between provinces in terms of age-standardised rates and the net change in life expectancy before and after the COVID-19 pandemic. The COVID-19 pandemic disrupted the rising trend of life expectancy in Iran, varying across provinces. Findings show that the health-care infrastructure and policies in Iran were not efficient in controlling the pandemic in 2020 and 2021, mainly due to inadequate vaccination coverage and timeliness, specifically for vulnerable subgroups. Sanctions may have aggravated the effect of COVID-19 on loss in life expectancy of Iranians. Despite the pandemic, the declining trend in age-standardised rates for top causes of mortality has continued to 2023, leading to a full recovery of life expectancy and underscoring the ultimate resilience of Iran's health system. Gates Foundation.
Aim: To evaluate the cost-utility of pulsed field ablation (PFA) compared with radiofrequency ablation (RFA) and cryoablation, respectively, in Chinese patients with paroxysmal atrial fibrillation. Materials & methods: Patients with paroxysmal atrial fibrillation at different levels of atrial arrhythmia burden (<0.1%, 0.1-9.9%, ≥10%) may experience various atrial arrhythmia burden states after undergoing ablation. A decision tree model was developed to simulate this process from a healthcare perspective, where patients could undergo a repeat ablation or experience a nonfatal stroke. Transition probabilities, clinical outcome and quality of life data were obtained from published sources and confirmed by expert physicians. Cost data were estimated from a survey of clinicians at tertiary hospitals, based on actual clinical practices. The uncertainty of results was explored through one-way sensitivity analysis and probabilistic sensitivity analysis by Monte Carlo simulation. The secondary outcome, return on investment, was calculated from hospital administrator perspective, as net revenue divided by total cost of certain ablation type. Results: PFA demonstrated favorable cost-effectiveness compared with both RFA and cryoablation under the three-times China's per capita GDP threshold. When compared with RFA, PFA yielded an incremental 0.016 quality-adjusted life years (QALYs) (0.859 vs 0.842) with an incremental cost-effectiveness ratio of ¥37,000 per QALY gained. This cost-effectiveness was primarily driven by savings of ¥1558 in weighted repeat ablation surgery costs and ¥506 in long-term medication costs for anti-arhythmic and anticoagulants. When compared with cryoablation, PFA resulted in an incremental 0.006 QALYs (0.859 vs 0.852) with an incremental cost-effectiveness ratio of ¥231,167 per QALY gained, mainly attributed to savings of ¥1300 in repeat ablation surgery costs and ¥133 in long-term medication costs. As a secondary outcome, PFA yielded a return on investment of 0.313. Conclusion: PFA was likely to be more cost effective than both radiofrequency ablation and cryoablation in China. The study suggests that PFA represents a high-value intervention that aligns superior clinical outcomes with favorable hospital financial sustainability, supporting its prioritized adoption in the management of atrial fibrillation in China. What is this article about? This article investigates the economic value of a new heart ablation technology called pulsed field ablation (PFA) for treating patients with paroxysmal atrial fibrillation (a common type of irregular heartbeat) in China. We compared the costs and health outcomes of PFA against two established ablation techniques: radiofrequency ablation and cryoablation. The goal was to determine if the new PFA technology provides good value for money for the Chinese healthcare system. What were the results? Over a 1-year period, treatment with PFA was found to be more cost-effective than both traditional methods. Although the initial procedure cost for PFA was slightly higher, patients receiving PFA required fewer repeat procedures, had fewer complications, and incurred lower long-term medication costs. Patients treated with PFA also experienced a very small but meaningful improvement in quality of life. The results were confirmed through analyses that tested how sensitive the findings were to changes in key assumptions, showing that the conclusion is robust. What do the results mean? These results suggest that from a cost–effectiveness perspective, PFA is an economically favorable first-line treatment option for paroxysmal atrial fibrillation in China. Adopting PFA could lead to better outcomes for patients and more efficient use of healthcare resources compared with currently standard thermal ablation techniques.
Inflammation is associated with metabolic alterations that can lead to the release of volatile organic compounds (VOCs) reflecting cellular biochemical activity. Profiling these volatile metabolites may provide insight into cellular responses to inflammatory stimuli, although their characterization in skin-derived cells remains limited. In this exploratory proof-of-concept study, we investigated the volatile metabolite profiles of human skin fibroblasts exposed to different inflammatory stimuli. Fibroblast cell lines were stimulated with polyinosinic:polycytidylic acid (Poly I:C), tumor necrosis factor-alpha (TNF-α), and lipopolysaccharide (LPS) to model viral-, cytokine-, and bacterial-associated stress conditions. Headspace solid-phase microextraction coupled with comprehensive two-dimensional gas chromatography and time-of-flight mass spectrometry (HS-SPME-GC×GC-TOFMS) was applied to analyze volatile metabolites released from the cell cultures, enabling exploratory profiling of the fibroblast volatilome. A data-processing workflow including pairwise comparisons between experimental groups and statistical filtering was implemented to identify volatile features associated with the different conditions. Several VOCs were tentatively identified, mainly belonging to alcohol, ester, and hydrocarbon classes, and showed differential abundance patterns between stimulated and control samples. Multivariate analysis indicated a separation between stimulated and non-stimulated groups, suggesting stimulus-associated differences in the volatile profiles of fibroblast cultures. While these observations may reflect metabolic responses occurring under inflammatory stimulation, the chemical identity and biochemical origins of several detected features remain to be confirmed. All in all, this study demonstrates the feasibility of applying HS-SPME-GC×GC-TOFMS-based volatilome profiling to investigate stimulus-associated changes in fibroblast cultures. The detected VOC patterns should therefore be considered preliminary observations requiring further chemical characterization and independent validation. Future studies including larger sample numbers, complementary biological verification of the inflammatory response, and more physiologically relevant experimental models will be necessary to further assess the robustness and potential relevance of these volatile signatures in the context of inflammatory processes.
The efficacy and adverse reactions of Maren Runchang Pills among patients of different genders remain unclear. This study aims to analyze the efficacy and safety differences of Maren Runchang Pills in patients of different genders, providing a basis for the implementation of gender-precise treatment in clinical practice. Gender-stratified analysis was adopted to include constipation-predominant irritable bowel syndrome (IBS-C) patients who met the syndrome of intestinal heat and accumulation. The efficacy and safety of Maren Runchang Pills were evaluated after 4 weeks of treatment. The main evaluation indicators include the complete spontaneous bowel movement response rates, visual analogue scale scores for abdominal pain and distension, traditional Chinese medicine syndrome scores, irritable bowel syndrome-symptom severity scale/irritable bowel syndrome-quality of life scale scores, and safety indicators. A total of 126 patients were included, among whom 101 were female and 25 were male. After 4 weeks of treatment, the proportion of female patients with a complete spontaneous bowel movement response rate of ≥75% was significantly higher than that of male patients (71.29% vs 48%, P = .0270), and the improvement in abdominal distension visual analogue scale score was also significantly better in females (decrease of 2.78 points vs 1.84 points, P = .0199). However, the total score of traditional Chinese medicine syndromes in male patients was higher than that in female patients (7.08 points vs 5.09 points, P = .0341). There were no statistically significant differences in the scores of the irritable bowel syndrome-symptom severity scale, irritable bowel syndrome-quality of life scale and safety indicators between the 2 groups. Maren Runchang Pills can effectively alleviate the constipation symptoms of patients with IBS-C, and the therapeutic effect is even better in female patients. The research results support considering gender factors in the clinical treatment of IBS-C to achieve individualized and precise intervention.
This review critically examines the integration of nanocarriers into oral tablet formulations, focusing on compaction strategies, excipient selection, and the impact of nanosystem properties on manufacturability, drug release, and biopharmaceutical performance. A comprehensive literature search was conducted in PubMed and Web of Science to identify peer-reviewed publications reporting oral tablet formulations based on nanocarriers, including polymeric nanoparticles, liposomes, mesoporous silica nanoparticles (MSNs), dendrimers, and hybrid or lipid-based nanosystems. Relevant data on formulation strategies, compression methods, excipients, in vitro and in vivo performance, and critical quality attributes were extracted and analyzed. After removing duplicates and assessing relevance, 40 studies were selected for in-depth review. Polymeric nanoparticles consistently enhanced controlled release, with chitosan, polylactide acid, and casein-based systems enabling mucoadhesion or delayed dissolution. Silica-based nanocarriers, particularly MSNs, enhanced powder flow and tablet hardness when used within an optimal concentration range, whereas higher loadings negatively affected compressibility. Lipid nanoparticles and self-emulsifying systems facilitated immediate or sustained release while improving drug solubility. Freeze-drying, spray drying, and 3D printing were pivotal for stabilizing sensitive carriers. Hybrid systems, including metal-organic frameworks and chitosomes, provided tailored release and pharmacokinetic enhancement. Challenges included aggregation, poor flow, mechanical fragility, and regulatory limitations, though advances in excipient engineering, smart coatings, and manufacturing technologies are mitigating these barriers. Nanocarrier-based tablets are a promising frontier for improving oral drug delivery, offering controlled release, enhanced bioavailability, and potential for multifunctionality. While nanocrystal-based products dominate the market, newer nanosystems show increasing promise. Future directions include personalized therapies, oral delivery of biologics, and integration of multifunctional nanocarriers enabled by emerging technologies such as 3D printing and stimuli-responsive coatings.
To explore barriers and enablers to the implementation of the Global Initiative for Asthma (GINA) recommendations in Jordan, building on prior quantitative survey findings. We aimed to examine healthcare professionals' experiences, perceptions and contextual challenges in translating guideline awareness into practice. Qualitative descriptive study using semi-structured interviews. Analysis was inductive thematic, guided by the Consolidated Criteria for Reporting Qualitative Research (COREQ). Healthcare services in Jordan, including public hospitals, private hospitals, outpatient clinics and community pharmacies, spanning both urban and semi-urban areas. 28 healthcare professionals were purposively sampled to capture diverse roles, sectors and levels of experience. The sample included physicians (general practitioners and pulmonologists), pharmacists (community and hospital), nurses and Doctor of Pharmacy (PharmD) graduates. Eligibility required direct involvement in the management and counselling of adult patients with asthma within the preceding 12 months. Perceptions of and experiences with implementing GINA recommendations in clinical practice, focusing on provider-level, system-level and patient-level barriers and enablers. Eight interrelated themes were identified. A consistent 'know-do gap' emerged, whereby clinicians were aware of guidelines but reverted to habitual practice due to insufficient training, scepticism or lack of support systems. Limited diagnostic capacity, particularly the absence of spirometry in public settings, led to symptom-based management. Pharmacotherapy decisions were shaped by patient demand, entrenched short-acting β₂-agonist use and affordability concerns. Inhaler technique counselling and written action plans were infrequently provided, largely due to workload and unclear interprofessional roles. Patients' beliefs (eg, steroid fears, avoidance of inhalers during Ramadan, low health literacy) further impeded adherence. Despite these barriers, participants proposed pragmatic solutions, including concise locally adapted tools, structured Continuing Medical Education (CME), digital decision support, pharmacy-based inhaler technique clinics and public awareness campaigns. Asthma care in Jordan reflects a gap between GINA awareness and consistent application, driven by resource, organisational and cultural barriers. Improving outcomes will require system-level investment in diagnostic infrastructure, sustainable access to controller medications, interprofessional care models and culturally tailored patient education. These findings highlight the need for a coordinated national strategy to strengthen guideline implementation and provide a basis for developing policy and practice interventions across similar middle-income settings.
In this study, sorafenib (an established anticancer drug) and curcumin (a polyphenolic compound), both with numerous challenges like solubility, permeation, bioavailability, and dose-dependent toxicity, were co‑loaded in a microemulsion-based hydrogel for breast cancer management by the topical route. Based on the solubility studies, Capmul MCM was selected as the oil, and the surfactant mixture was selected as Labrasol and Tween‑80. A total of three pseudoternary phase diagrams were explored to select the optimum composition. Out of three studied compositions, the selected one exhibited a globule size of 100.7 ± 6.83 nm with a polydispersity index value of 0.239, zeta potential of -8.14 ± 1.61 mV, and pH of 5.7 ± 0.2. The developed Carbopol-based hydrogel offered shear‑thinning rheology with appreciable spreadability, higher drug content, and skin-compatible pH. MCF‑7 cell-based cytotoxicity studies not only established the substantial decrease in the IC₅₀ values for both sorafenib and curcumin when co‑delivered but also offered a combination index < 1, indicating synergism. Rodent skin permeation studies offered a higher release flux and drug retention for both the drugs vis-à-vis the conventional gel, and the dermatokinetics proved the skin delivery potential of the developed system with elevated Cmax, permeation rates, and AUC, and also slower elimination for sorafenib. The studies established the synergism of both drugs and provided a proof of concept for enhanced topical delivery with substantial in vitro anticancer effect that can be further explored in the in vivo models.
To examine the association between prenatal exposure to benzodiazepines or Z-hypnotics and a spectrum of psychiatric disorders in children. Population based cohort study with sibling controlled analysis. National Health Information Database of South Korea, 2009-23. All liveborn children between 2010 and 2022 were followed until 2023. Pregnancies exposed to benzodiazepines or Z-hypnotics were compared with unexposed pregnancies and with pregnancies in women with previous use of these drugs (past users). Overall and 12 specific psychiatric disorders in offspring. Propensity score overlap weighting was applied to balance covariates, and hazard ratios with 95% confidence intervals were estimated using Cox proportional hazards models. Sibling controlled analyses were conducted to account for shared familial factors. Among 3 809 949 liveborn children, 94 482 (2.5%) were exposed to benzodiazepines or Z-hypnotics during pregnancy, 3 715 467 were unexposed, and 147 307 were born to past users. During the follow-up period, a total of 10 060, 311 997, and 15 645 events occurred in the exposed, unexposed, and past user groups, respectively. Prenatal exposure was associated with a higher risk of psychiatric disorders compared with unexposed pregnancies and past users; however, this association was attenuated in the sibling controlled analysis (hazard ratio 0.99, 95% confidence interval 0.94 to 1.04). No increased risk was observed for individual psychiatric disorders. In subgroup analyses, modestly elevated hazard ratios were observed for exposure during the second half of pregnancy (sibling controlled hazard ratios: 1.27 (0.95 to 1.71) for benzodiazepine; 1.81 (0.57 to 5.74) for Z-hypnotic), during both the first and second half of pregnancy (sibling controlled hazard ratios: 1.35 (0.93 to 1.96) for benzodiazepine; 1.44 (0.93 to 2.21) for Z-hypnotic), and for 30 or more days of Z-hypnotic exposure (sibling controlled hazard ratio 1.31, 0.96 to 1.78), although the confidence intervals in sibling analyses were wide and included the null. In this large population based cohort, prenatal exposure to benzodiazepines or Z-hypnotics was not associated with an increased risk of psychiatric disorders in offspring after familial factors were accounted for. However, given the modest elevations in point estimates observed in certain subgroups-particularly with benzodiazepine and Z-hypnotic exposure during the latter half of pregnancy, as well as with exposure in both early and late pregnancy, and with longer durations of Z-hypnotic use-the potential for a slightly increased risk in these specific contexts could not be ruled out.
Oligometastatic cancer is characterised by a low volume of metastases to a small number of anatomical sites. However, evaluating the impact of metastases-directed therapies (MDTs) on overall survival or quality of life is often challenging. Current clinical trials use a wide range of primary endpoints that might not be validated or suited to MDT. To address this issue, we did a systematic review of international trial registries, alongside a Delphi consensus process involving 30 experts and five patient representatives. The aim was to identify preferred primary endpoints for MDT trials in oligometastatic disease, regardless of tumour type. Overall survival and progression-free survival were the most frequently used endpoints across the 121 comparative trials reviewed. Over four Delphi consensus rounds, overall survival had the highest level of agreement, although its limitations as a sole endpoint were emphasised. In addition to the widely used progression-free survival endpoint, polymetastatic progression-free survival and start-or-switch of systemic therapy-free survival also reached consensus, particularly for trials integrating systemic therapies. Both polymetastatic progression-free survival and systemic therapy-free survival permit repeat MDT without classifying it as treatment failure. Patient representatives highlighted the importance of time-to-deterioration of quality of life. This consensus supports overall survival as a primary endpoint and, in addition to progression-free survival, recommends polymetastatic progression-free survival and systemic therapy-free survival, especially in combination with systemic therapies. Adopting these endpoints will make MDT trials more relevant, comparable, and patient-centred, thereby empowering future clinical and policy decisions.
The 5-year survival rate of early-stage hepatocellular carcinoma (HCC) patients remains only 60%, largely due to the inability to achieve ultra-early detection and safe, minimally invasive intervention of its premalignant precursor-high-grade dysplastic nodules (HGDN). Current clinical practice faces an unresolved dilemma: conventional imaging has limited sensitivity for HGDN, no standardized minimally invasive intervention exists, and no integrated platform enables synchronous detection, boundary localization and on-demand intervention, despite HGDN 80.8% 5-year HCC progression rate. To address these core challenges, we developed a multifunctional dual-hairpin DNA polydopamine nano-system (H/R@PDA-GC) targeting miRNA-224, a biomarker consistently upregulated during HGDN malignant transformation.This system enables specific detection of miRNA-224 with an ultra-low limit of detection (LOD) of 0.068 pM. Clinically, there is a 3-5-year natural history window from HGDN formation to clinically diagnosable early HCC; thus, this system provides a potential technical tool for the ultra-early warning of HCC at the precancerous stage. It simultaneously activates near-infrared fluorescence for targeted imaging of HGDN to precisely delineate lesion boundaries, and leverages its efficient photothermal conversion capability to achieve effective ablation of HGDN in validated murine models. Both cellular and animal studies confirmed its good in vitro and short-term in vivo biocompatibility, significant anti-inflammatory and antioxidant effects, and therapeutic efficacy, addressing the dual clinical needs of ultra-early detection and safe intervention of premalignant lesions. Consequently, H/R@PDA-GC provides an integrated theranostic strategy, which has potential clinical value for reducing the risk of HCC progression, and lays a foundation for ultra-early intervention of HCC precancerous lesions.Clinical trial number. Not applicable.
Antibiotics are among the most concerning pharmaceutical contaminants released from municipal sewage treatment plants (STPs), occurring both in treated effluents and in dewatered biosolids. This study examines key analytical challenges during the determination of ten antibiotics in sewage wastes using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Furthermore, results of their distribution in dewatered biosolids from different STPs are presented. Fluoroquinolones were identified as the most problematic compounds due to sorption on glassware, strong interaction with sample matrix, and signal suppression effects during LC-MS/MS analysis. Optimized extraction, based on sonication of freeze-dried samples with a buffered acetonitrile-water solution (pH 4.4, 1:1), yielded average recoveries between 74% and 108%, with moderate variability across sludge types. During simultaneous quantification of multiclass antibiotics, fluoroquinolones exhibited moderate to high signal attenuation depending on the matrix. For this group of compounds, signal suppression could be mitigated by fractionating extracts using mixed-mode (reversed phase and cation exchange) sorbents. Combined with isotopically labelled surrogate standards, solvent based calibration enabled accurate quantification of all targeted compounds, achieving limits of quantification below 5 ng g⁻¹. Azithromycin, clarithromycin, norfloxacin, ciprofloxacin and ofloxacin were ubiquitous in dewatered biosolids, with median concentrations ranging from 7 ng g-1 (clarithromycin) to 1761 ng g-1 (ofloxacin). A mass balance assessment of emissions through treated wastewater and biosolids highlighted azithromycin, ciprofloxacin, norfloxacin, and ofloxacin as the priority antibiotics for monitoring in final dewatered solid waste streams (biosolids) from STPs.
IntroductionFinancial toxicity (FT) is more prevalent among rural-dwelling cancer survivors who also face greater cancer care-related travel burdens. We sought to examine how FT and travel burdens may pose dual burdens for cancer survivors, and assess their effects on care experiences and subsequent cost-coping strategies.MethodsRapid qualitative analysis of semi-structured interviews with rural-dwelling cancer survivors who screened positive for FT per the COmprehensive Score for financial Toxicity (COST) measure. Our analysis was structured around three inductive themes: rural-dwelling patients' experiences of cancer treatment while navigating FT, patient perceptions of travel burdens undertaken in the course of accessing cancer care, and perceived implications of both FT and travel burdens for care on HRQoL.ResultsThe (n = 12) participants in our study were mostly women, with a median age of 60.1. The median COST score was 9.5, indicating a high degree of FT, and the median round-trip travel distance was 25.6 miles. Participants reported cost-coping strategies to reduce travel-associated costs, such as "stacking" appointments to reduce travel costs and taking advantage of non-medical assistance offered by health systems' financial assistance programs (e.g., gas cards). Participants also reported shared burdens with caregivers who also shouldered costs.ConclusionsEstimates of travel distances to cancer care likely understate travel burdens, because they do not capture the frequency of appointments and their associated indirect and opportunity costs for cancer survivors experiencing FT. Financial assistance for cancer survivors should be responsive to the dual and cumulative financial and travel burdens of cancer care. Rural-dwelling cancer survivors are more likely to experience Financial Toxicity (FT) in tandem with greater cancer care-related travel burdens. This qualitative study sought to examine how FT and travel burdens may pose dual burdens for cancer survivors, and assess their effects on care experiences and subsequent cost-coping strategies. We conducted semi-structured interviews with (n = 12) participants sampled from the Lessening the Impact of Financial Toxicity (LIFT) study, an intervention that screened for FT and provided site-based financial navigation services and supports. Interview participants were mostly women, with a median age of 60.1. The median COmprehensive Score for financial Toxicity (COST) score was 9.5, indicating a high degree of FT, and the median round-trip travel distance was 25.6 miles. Participants reported cost-coping strategies to reduce travel-associated costs, such as “stacking” appointments to reduce travel costs and taking advantage of non-medical assistance offered health systems’ financial assistance programs (e.g., gas cards). Participants also reported shared burdens with caregivers who also shouldered costs. Concomitant caregivers- or cancer survivors who were also caregivers- were especially in need to supports to mitigate the dual burdens of cancer care-related FT and travel burdens.
Due to ideal stability, ease of preparation and high cost efficiency, nanozymes have been adopted as the substitutes of natural enzymes in homogeneous catalysis. However, the application of nanozymes was restricted caused by unsatisfactory emulsifying ability in heterogeneous catalysis. Albeit some asymmetric structures on Janus nanozymes are proposed for biphasic catalysis, the precise tuning of their amphiphilicity poses significant challenges especially through one-step self-assembly protocols. Herein, a facile controlled self-assemble protocol is developed to circumvent the utilization of the monophasic sphere as the beginner of Janus nanostructures. Pineapple-like Janus supports can be acquired by the simultaneous polymerization of resorcinol-formaldehyde resins and mesoporous SiO2 nanoparticles. Through the subtle alteration of dual precursors, the accurate tuning of asymmetric proportion allows for the tailorable amphiphilicity of Janus supports. By efficiently anchoring active Ce moieties onto Janus supports, asymmetric Ce@Janus nanozyme possesses superior kinematic locomotion and improved emulsion stabilization ability for dramatically boosting biphasic catalysis. Compared with monophasic nanozymes, Ce@Janus nanozyme with increased active sites and enhanced substrate affinity facilitates the biphasic chemiluminescent enhancement for the precise supervision of fentanyl with the detection limit of 0.47 pg·mL-1, by utilizing CDP-Star chemiluminescent reaction as a mode biphasic system. Moreover, the universality of the Janus support for biphasic nanozymes is demonstrated by the successful loading of a series of active metal sites including Pt, Cu, and Au for pressure sensing, colorimetric assay and photothermal analysis. The principle-of-proof work opens an avenue for the facile regulation of amphiphilic asymmetric nanozymes, which contributes to the intriguing biphasic catalysis efficiency for trace analysis.
Despite limited evidence supporting the long-term effectiveness of opioid therapy and existing recommendations on multi-disciplinary treatment, patients with chronic non-cancer pain (CNCP) continue to receive opioids. In Sweden, most prescription renewals for CNCP are issued by general practitioners (GPs). To explore GPs' experiences with and understanding of opioid prescribing for CNCP and their views on multi-disciplinary collaboration. Semi-structured interviews were conducted with GPs and one GP-trainee in Region Uppsala, Sweden (February-June 2022). Topics included long-term opioid treatment (LTOT), opioid tapering, prescription renewal and multi-disciplinary collaboration. The interviews were recorded, transcribed and thematically analyzed. Twelve participants including one GP trainee with a mean experience of 13 years were involved. Two main themes were developed. (1) To endure the ethical conflicts of opioid prescribing practices, where the GPs negotiated ethical conflicts arising in the intersection between patient needs, personal values and clinical guidelines regarding LTOT. (2) The last resort, where the GP's role was conceptualized through the lens of systemic healthcare structures, perceived patient demands, expectations from fellow healthcare providers and the internal expectations held by themselves. GPs experienced moral distress prescribing opioids and reinforced stigma toward patients with CNCP and LTOT. These dynamics hinder treatment reassessment and biopsychosocial evidence-based care. Perceived expectations of GPs as the 'last resort' may perpetuate opioid use and impede collaborative care with the patient and multi-disciplinary teams. Opioid prescribing involves significant ethical dilemmas for general practitioners (GPs).General practitioners face challenges balancing opioid risks with patient expectations and work load.Tapering long-term opioid therapy (LTOT) is regarded as a time-intensive process and is often deprioritized.The identity of the GP as a comprehensive healer is challenged within the context of chronic non-cancer pain (CNCP) and opioid prescribing.General practitioners infrequently utilize multi-disciplinary approaches for the care of patients with CNCP and LTOT.
Hospitalisation provides an opportunity to deprescribe (withdraw inappropriate medications), however, safe and effective deprescribing relies on good communication between relevant stakeholders. The aim of this study was to explore the perspectives of Australian hospital and community pharmacists on communicating information about deprescribing at transitions of care and their role in the deprescribing process. A diverse group of hospital and community pharmacists was purposively recruited. Data were collected via individual semi-structured interviews and focus groups that were audio-recorded and transcribed verbatim using NVivo. Each transcript was thematically analysed using an inductive coding approach, performed by two independent coders. Thirty-two pharmacists were recruited between June and August 2023. Seventeen participants worked in hospitals, 10 in community pharmacies, and five across both settings. Four themes with 12 subthemes were identified, pertaining to (i) how pharmacists communicate about deprescribing on hospital discharge, (ii) how pharmacists collaborate with other healthcare professionals and patients to optimise deprescribing, (iii) how the role of the pharmacist in deprescribing at transitions of care can be optimised, and (iv) how pharmacists feel about their current and future role in deprescribing. Challenges in communicating deprescribing recommendations and ensuring continuity of care when patients transition between care settings were identified. Development of new tools (e.g., templates and guidance on how and what should be communicated) and processes to support communication at the transition of care from hospital to the community are needed to support deprescribing activities.
Aceclofenac (ACF) is a commonly used non-steroidal anti-inflammatory drugs (NSAID) for numerous inflammatory conditions; however, its therapeutic potential is limited due to suboptimal solubility. Pharmaceutical cocrystals have demonstrated favorable and sustainable results in improving the physicochemical and biopharmaceutical characteristics of poorly soluble drugs. To enhance the solubility, dissolution rate, and bioavailability of ACF, we aimed to prepare cocrystals of this biopharmaceutics classification system (BCS) class II drug with a coformer including nicotinamide (NCT), using hot melt extrusion (HME) and liquid-assisted grinding (LAG) methods. ACF-NCT cocrystals synthesized using these methods were characterized using various methods and were further assessed for in vitro anti-osteoporotic and in vivo anti-arthritic activities. The results indicate that both LAG and HME cocrystals demonstrated significant improvement in solubility and dissolution profile compared to pure ACF. However, among these two methods, HME offered more advantages, including better solubility and dissolution profile, than the LAG method. The cocrystals achieved a remarkable 6.15-fold increase in solubility and ⁓3-fold enhancement in dissolution over pure ACF. The relative bioavailability of ACF-NCT HME cocrystal was 249.98% of pure ACF, indicating an improvement in oral bioavailability. The in vivo anti-arthritic activity also demonstrated significant improvement when compared to pure ACF. ACF-nicotinamide cocrystals prepared by hot melt extrusion achieved remarkable gains in solubility, bioavailability, and therapeutic efficacy, providing a promising strategy to overcome ACF's clinical limitations.
COVID-19 mRNA vaccines have been reported to reduce severe COVID-19 outcomes in high-risk populations. In Japan, booster vaccinations up to the seventh dose are publicly funded; however, evidence regarding the safety and potential benefits of repeated booster doses in younger adults remains limited. This exploratory observational study aimed to describe age-specific patterns of all-cause mortality according to the number of COVID-19 vaccine doses using municipal administrative registry data. Municipal registry data obtained through information disclosure requests from Hamamatsu City (2021-2024) and Matsudo City (2021-2025) were analyzed. The dataset included age group or year of birth (5-year increments), sex, date of residence, COVID-19 vaccination records (date and lot number), and date of death. Individuals aged 20-89 years were categorized into three age groups (20-49, 50-64, and 65-89 years). All-cause mortality rates were calculated per 100,000 person-years according to the number of vaccine doses. Exploratory comparisons between dose groups were conducted using Poisson tests. Because the registry dataset lacked information on comorbidities, healthcare utilization, socioeconomic status, and cause of death, multivariable adjustment and causal inference were not feasible. Age-specific differences in all-cause mortality rates were observed across vaccine dose groups. Among individuals aged 65-89 years, higher numbers of vaccine doses were associated with lower all-cause mortality rates. In contrast, among those aged 20-49 years, all-cause mortality rates were higher among individuals who had received ≥5 doses than among those who had received fewer doses. Among individuals aged 50-64 years, the all-cause mortality rate was higher among those who had received six doses than among those who had received 1, 3, or 4 doses. This exploratory analysis identified age-specific differences in all-cause mortality across COVID-19 vaccine dose groups. However, the dataset available so far lacked important clinical covariates and information on causes of death, limiting causal interpretation. These findings highlight the need for constructing in Japan nationally linked datasets that allow adjustment for comorbidities, healthcare utilization, and other potential confounders.
The antihypertensive drug felodipine (FEL) suffers from poor solubility, leading to low bioavailability, and is also known to undergo photodegradation. Co-amorphous formulations represent a promising strategy for simultaneously enhancing the physicochemical properties and stability of drugs. This study aimed to develop and characterize a novel co-amorphous system composed of FEL and puerarin (PUE) to address these challenges. The screened co-amorphous with an FEL:PUE ratio of 1:2 was obtained by solvent rotary evaporation and characterized by powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), Fourier transform infrared (FT-IR), and Raman spectroscopy. The formation of co-amorphous is supported by the typical halo pattern in the PXRD, as well as a single Tg of 51.9 °C. FT-IR and Raman spectroscopy revealed that this co-amorphous supramolecular system was connected by CO···H-O and N-H···OC interactions. The results of the dissolution experiment showed that the dissolution rate of FEL was significantly accelerated after co-amorphization. By measuring the oil-water partition coefficient, increased hydrophilicity of FEL and lipophilicity of PUE in the co-amorphous form were observed. Multiple tests suggested that the co-amorphous material had superior physical stability under accelerated or illumination conditions. Encouragingly, the enhanced in vitro physicochemical properties were effectively converted into the in vivo pharmacokinetic performance with the expedited Cmax, enhanced AUC0-t and AUC0-∞ for both FEL and PUE in co-amorphous. The current contribution not only proves that co-amorphization can improve drug bioavailability but also provides a new idea for combined treatment using traditional Chinese and chemical medicines.
Although research on palliative care in hematological malignancies has increased, research examining quality of death (QOD) and quality of care (QOC) in this population remains limited. This study compared QOD and QOC between patients with hematological malignancies and those with solid tumors. The authors conducted a secondary analysis of a nationwide mortality follow-up survey of bereaved family members in Japan (2017-2018). The study included 3575 decedents with hematological malignancies and 50,592 with solid tumors. Propensity score matching was performed to adjust for demographic and clinical characteristics. QOD and QOC were assessed using the Good Death Inventory (GDI) and the Care Evaluation Scale 2.0 (CES). Bivariate analyses compared the matched groups. Overall, QOD and QOC were comparable between groups. However, among the GDI subdomains, patients with hematological malignancies had slightly lower scores for "good relationships with family" (mean difference, 0.2; 95% confidence interval [CI], 0.03-0.3) and "preparation for death" (mean difference, 0.2; 95% CI, 0.04-0.3). In addition, patients with hematological malignancies were less likely to die in palliative care units than those with solid tumors (mean difference, 3.9%; 95% CI, 0.4%-7.4%). Although overall quality measures were similar, specific QOD domains related to family relationships and preparation for death were slightly lower among patients with hematological malignancies. These findings may reflect limited opportunities for end-of-life discussions due to the unpredictable and rapidly progressive course of hematological malignancies. Enhancing communication about prognosis and goals of care and early integration of palliative care may improve end-of-life experiences.
The objectives of this study were to highlight and evaluate the factors affecting the non-adoption, abandonment of and challenges to scale-up, spread and sustainability of mHealth in Sub-Saharan Africa (SSA) and to assess the appropriateness of the Non-adoption, Abandonment, Scale-up, Spread, and Sustainability (NASSS) Framework in the SSA context. A systematic search of published research was conducted using PubMed and Embase research databases from 2012 to 2025. Peer-reviewed studies from SSA countries, evaluating mHealth interventions, were included in this study. Papers were analysed to identify barriers according to the seven domains of the NASSS Framework, which are (1) condition, (2) technology, (3) value proposition, (4) adopters, (5) organisation(s), (6) wider system, (7) embedding and adaptation over time RESULTS: This study identified 409 barriers across 91 papers. 309 barriers were covered by the seven NASSS Framework domains, while 100 were unaddressed by the framework. The main barriers were associated with domain 2, the technical aspects of the technology (27%). Other prominent barriers related to the wider system (18%), the adopter (11%), the organisation (9%) or condition (8%), with the value proposition (1%) and embedding and adaptation over time (1%), least hindering implementation. Challenges which were unaddressed by the framework (24%) included socioeconomic and infrastructural issues, distinct to lower and middle-income countries (LMIC). This paper highlights the importance of evaluating rudimentary aspects of mHealth and preparing infrastructure before addressing more complex issues during mHealth implementation in SSA. Although the NASSS Framework is applicable to the SSA region, it would benefit from some further development to improve its applicability in LMICs.