Delivery System Research Articles

Chondroitin sulfate-modified tragacanth gum–gelatin composite nanocapsules loaded with curcumin nanocrystals for the treatment of arthritis

Rheumatoid arthritis (RA) is a chronic autoimmune disease of yet undetermined etiology that is accompanied by significant oxidative stress, inflammatory responses, and damage to joint tissues. In this study, we designed chondroitin sulfate (CS)-modified tragacanth gum–gelatin composite nanocapsules (CS-Cur-TGNCs) loaded with curcumin nanocrystals (Cur-NCs), which rely on the ability of CS to target CD44 to accumulate drugs in inflamed joints. Cur was encapsulated in the form of nanocrystals into tragacanth gum–gelatin composite nanocapsules (TGNCs) by using an inborn microcrystallization method, which produced CS-Cur-TGNCs with a particle size of approximately 80 ± 11.54 nm and a drug loading capacity of 54.18 ± 5.17%. In an in vitro drug release assay, CS-Cur-TGNCs showed MMP-2-responsive properties. During the treatment of RA, CS-Cur-TGNCs significantly inhibited oxidative stress, promoted the polarization of M2-type macrophages to M1-type macrophages, and decreased the expression of inflammatory factors (TNF-α, IL-1β, and IL-6). In addition, it also exerted excellent anti-inflammatory effects, and significantly alleviated the swelling of joints during the treatment of gouty arthritis (GA). Therefore, CS-Cur-TGNCs, as a novel drug delivery system, could lead to new ideas for clinical therapeutic regimens for RA and GA.Graphical

Antibody-displaying extracellular vesicles for targeted cancer therapy.

Extracellular vesicles (EVs) function as natural delivery vectors and mediators of biological signals across tissues. Here, by leveraging these functionalities, we show that EVs decorated with an antibody-binding moiety specific for the fragment crystallizable (Fc) domain can be used as a modular delivery system for targeted cancer therapy. The Fc-EVs can be decorated with different types of immunoglobulin G antibody and thus be targeted to virtually any tissue of interest. Following optimization of the engineered EVs by screening Fc-binding and EV-sorting moieties, we show the targeting of EVs to cancer cells displaying the human epidermal receptor 2 or the programmed-death ligand 1, as well as lower tumour burden and extended survival of mice with subcutaneous melanoma tumours when systemically injected with EVs displaying an antibody for the programmed-death ligand 1 and loaded with the chemotherapeutic doxorubicin. EVs with Fc-binding domains may be adapted to display other Fc-fused proteins, bispecific antibodies and antibody-drug conjugates.

Nanotechnology-Based Strategy for Enhancing Therapeutic Efficacy in Pancreatic Cancer: Receptor-Targeted Drug Delivery by Somatostatin Analog

A novel nanotechnology-based drug delivery system (DDS) targeted at pancreatic cancer cells was developed, characterized, and tested. The system consisted of liposomes as carriers, an anticancer drug (paclitaxel) as a chemotherapeutic agent, and a modified synthetic somatostatin analog, 5-pentacarbonyl-octreotide, a ligand for somatostatin receptor 2 (SSTR2), as a targeting moiety for pancreatic cancer. The cellular internalization, cytotoxicity, and antitumor activity of the DDS were tested in vitro using human pancreatic ductal adenocarcinoma (PDAC) cells with different expressions of the targeted SSTR2 receptors, and in vivo on immunodeficient mice bearing human PDAC xenografts. The targeted drug delivery system containing paclitaxel exhibited significantly enhanced cytotoxicity compared to non-targeted DDS, and this efficacy was directly related to the levels of SSTR2 expression. It was found that octreotide-targeted DDS proved exceptionally effective in suppressing the growth of PDAC tumors. This study underscores the potential of octreotide-targeted liposomal delivery systems to enhance the therapeutic outcomes for PDAC compared with non-targeted liposomal DDS and Paclitaxel-Cremophor® EL, suggesting a promising avenue for future cancer therapy innovations.

Exploring molecular mechanisms, therapeutic strategies, and clinical manifestations of Huntington's disease.

Huntington's disease (HD) is a paradigm of a genetic neurodegenerative disorder characterized by the expansion of CAG repeats in the HTT gene. This extensive review investigates the molecular complexities of HD by highlighting the pathogenic mechanisms initiated by the mutant huntingtin protein. Adverse outcomes of HD include mitochondrial dysfunction, compromised protein clearance, and disruption of intracellular signaling, consequently contributing to the gradual deterioration of neurons. Numerous therapeutic strategies, particularly precision medicine, are currently used for HD management. Antisense oligonucleotides, such as Tominersen, play a leading role in targeting and modulating the expression of mutant huntingtin. Despite the promise of these therapies, challenges persist, particularly in improving delivery systems and the necessity for long-term safety assessments. Considering the future landscape, the review delineates promising directions for HD research and treatment. Innovations such as Clustered regularly interspaced short palindromic repeats associated system therapies (CRISPR)-based genome editing and emerging neuroprotective approaches present unprecedented opportunities for intervention. Collaborative interdisciplinary endeavors and a more insightful understanding of HD pathogenesis are on the verge of reshaping the therapeutic landscape. As we navigate the intricate landscape of HD, this review serves as a guide for unraveling the intricacies of this disease and progressing toward transformative treatments.

Erythrocyte membrane-camouflaged mesoporous silica composite nanoparticles for loading and controlled release of the hepatoprotective agent silibinin: A-synthesis and physicochemical characterization.

Milk thistle has long been used in the treatment of liver and biliary disorders. In the present study, to make a long-acting delivery system for silibinin (SBN, a major active constituent of milk thistle seeds with antioxidant and hepatoprotective function), mesoporous silica composite nanoparticles (NC) were synthesized and coated with RBC membrane. A modified Stöber method was used for NC synthesis, which was then characterized using FE-SEM, DLS, TEM, FTIR, and EDAX techniques. A suitable lysis buffer was used to prepare RBC-ghost, and sonication was used to coat SBN-loaded NC (SBN-NC). The RBC-ghost coated SBN-NC (SBN-NC-RBCG) was evaluated by SDS-PAGE, Bradford, TEM, EDAX, and DLS methods. SBN release was then compared for the SBN-NC and SBN-NC-RBCG samples. the RBC membrane proteins were recovered from the coating of SBN-NC-RBCG, and SBN release was sustained over 24h when compared with the SBN-NC. Overall, through prolonging circulation in the bloodstream and evading the immune system, the developed system can improve SBN bioavailability in liver inflammation and fibrosis conditions that need further research.

Antiepileptic drug-loaded and multifunctional iron oxide@silica@gelatin nanoparticles for acid-triggered drug delivery

The current study developed an innovative design for the production of smart multifunctional core-double shell superparamagnetic nanoparticles (NPs) with a focus on the development of a pH-responsive drug delivery system tailored for the controlled release of Phenytoin, accompanied by real-time monitoring capabilities. In this regard, the ultra-small superparamagnetic iron oxide@silica NPs (IO@Si MNPs) were synthesized and then coated with a layer of gelatin containing Phenytoin as an antiepileptic drug. The precise saturation magnetization value for the resultant NPs was established at 26 emu g-1. The polymeric shell showed a pH-sensitive behavior with the capacity to regulate the release of encapsulated drug under neutral pH conditions, simultaneously, releasing more amount of the drug in a simulated tumorous-epileptic acidic condition. The NPs showed an average size of 41.04 nm, which is in the desired size range facilitating entry through the blood–brain barrier. The values of drug loading and encapsulation efficiency were determined to be 2.01 and 10.05%, respectively. Moreover, kinetic studies revealed a Fickian diffusion process of Phenytoin release, and diffusional exponent values based on the Korsmeyer-Peppas equation were achieved at pH 7.4 and pH 6.3. The synthesized NPs did not show any cytotoxicity. Consequently, this new design offers a faster release of PHT at the site of a tumor in response to a change in pH, which is essential to prevent epileptic attacks.

Emerging Medications and Strategies in Acute Pain Management: Evolving Role of Novel Sodium and Calcium Channel Blockers, Peptide-Based Pharmacologic Drugs, and Non-Medicinal Methods.

The present investigation evaluated integration of novel medication technology to enhance treatment options, while improving patient outcomes in acute pain management. In this regard, we focused on determining the role of development and utilization of cutting-edge pharmaceutical advancements, such as targeted drug delivery systems, as well as non-pharmacologic interventions in addressing acute pain states. Further research in this area is warranted related to the need for increased patient comfort and reduced adverse effects. Recent innovations and techniques are discussed including pharmacologic drugs targeting sodium and calcium channels, peptide-based pharmacologic drugs, and non-medicinal methods of alleviating pain such as soothing music or virtual reality. The present investigation included review of current literature on the application of these innovative technologies, analyzing mechanisms of action, pharmacokinetics, and clinical effectiveness. Our study also investigated the potential benefits in terms of pain relief, reduced side effects, and improved patient adherence. The research critically examines the challenges and considerations associated with implementing these technologies in acute pain management, considering factors like cost, accessibility, and regulatory aspects. Additionally, case studies and clinical trials are highlighted which demonstrate practical implications of these novel medication technologies in real-world scenarios. The findings aim to provide healthcare professionals with a comprehensive understanding of the evolving landscape in acute pain management while guiding future research and clinical practices toward optimizing their use in enhancing patient care.

Vaping Behavior and Intention to Quit among Undergraduate Students in a Hispanic-Serving University.

The surge in electronic nicotine delivery systems (ENDS) usage, particularly among young adults, poses significant public health concerns. This study aimed to identify predictors of e-cigarette use, quit attempts, and frequency among undergraduate students in a Hispanic-serving university in Texas. A cross-sectional study was conducted between August 1 and October 26, 2023, recruiting undergraduate students through the Sona system, an online experiment management platform. Participants completed an online survey that covered demographics, educational status, vaping status, initiation age, reasons for first and current e-cigarette use, frequency of past usage, intentions to quit, and quit attempt frequency. Statistical analysis included descriptive statistics, multinomial logistic regression, and multivariable linear regression. Among 316 participants, 33.9% reported current e-cigarette use. Junior and senior students, as well as prior tobacco users, were more likely to be current vapers. Prior vaping experience was more prevalent among Hispanic individuals and those with a history of tobacco use. Notably, 74.3% of current users attempted to quit in the past year, with a higher frequency of quit attempts among females, Hispanic students, and those with vaping acquaintances. However, the vaping behavior and quit attempt patterns were similar across other categories. This study highlights how various factors influence e-cigarette use among college students. It suggests that prevention and quitting programs should consider the specific needs of different groups. Future studies will continue to look at different student groups to find the most effective ways to help them quit vaping.

Wearable Sensors for Physiological Condition and Activity Monitoring

Rapid technological advancements have transformed the healthcare sector from traditional diagnosis and treatment to personalized health management. Biofluids such as teardrops, sweat, interstitial fluids, and exhaled breath condensate offer a rich source of metabolites that can be linked to the physiological status of an individual. More importantly, these biofluids contain biomarkers similar to those in the blood. Therefore, developing sensors for the noninvasive determination of biofluid‐based metabolites can overcome traditionally invasive and laborious blood‐test‐based diagnostics. In this context, wearable devices offer real‐time and continuous physiological conditions and activity monitoring. The first‐generation wearables included wristwatches capable of tracking heart rate variations, breathing rate, body temperature, stress responses, and sleeping patterns. However, wearable sensors that can accurately measure the metabolites are needed to achieve real‐time analysis of biomarkers. In this review, recent progresses in wearable sensors utilized to monitor metabolites in teardrops, breath condensate, sweat, and interstitial fluids are thoroughly analyzed. More importantly, how metabolites can be selectively detected, quantified, and monitored in real‐time is discussed. Furthermore, the review includes a discussion on the utility of, multifunctional sensors that combine metabolite sensing, human activity monitoring, and on‐demand drug delivery system for theranostic applications.

Synthesis of novel stimuli-responsive hydrogels based on polyurethane

This article describes the study of a thermo-responsive hybrid systems based on polyurethane (PU) modified with sensitive acrylamide derivates. The hybrid systems were synthesized using PU and two acrylamide derivatives (N-isopropylacrylamide (NIPA) and N-isopropylmethacrylamide (NIPMA)) in different proportions. The systems were characterized using infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and dynamic light scattering (DLS). Water-uptake capacity and sedimentation rate were also determined. The results showed that the hybrids with 30% acrylamide derivate (AD) showed a T50 of approximately 360 °C indicating that thermal degradation decreased with the addition of NIPA and NIPMA. Additionally, the incorporation of AD increases the glass transition temperature from −34 to −22 °C when 30% AD was used. The hybrids with 30% AD showed a variation in the diameters (above 60%) when the temperature was decreased from 50 to 22 °C. These changes were attributed to the hydrophilic → hydrophobic transition that occurs when measuring below and above the low critical solution temperature (LCST) of the polymer. Furthermore, the extra methyl group in the structure of NIPMA makes the collapse less pronounced than in NIPA, decreasing the relative diameter change by 10%. Sedimentation tests showed that the addition of the hybrid hydrogels in the sand increased the time of decantation by 60%. So, the combination of two thermo-responsive polymers to alter the hydrophilic/hydrophobic balance allows these polymers to modify their conformation at a specific temperature and could be potentially useful as self-suspending support agents or drug delivery systems.

Drug release profile of a novel exenatide long-term drug delivery system (OKV-119) administered to cats

Beneficial weight-loss properties of glucagon-like peptide-1 receptor agonists (GLP-1RA) in obese people, with corresponding improvements in cardiometabolic risk factors, are well established. OKV-119 is an investigational drug delivery system that is being developed for the long-term delivery of the GLP-1RA exenatide to feline patients. The purpose of this study was to evaluate the drug release characteristics of subcutaneous OKV-119 implants configured to release exenatide for 84 days. Following a 7-day acclimation period, five purpose-bred cats were implanted with OKV-119 protypes and observed for a 112-day study period. Food intake, weekly plasma exenatide concentrations and body weight were measured. Exenatide plasma concentrations were detected at the first measured timepoint (Day 7) and maintained above baseline for over 84 Days. Over the first 28 days, reduced caloric intake and a reduction in body weight were observed in four of five cats. In these cats, a body weight reduction of at least 5% was maintained throughout the 112-day study period. This study demonstrates that a single OKV-119 implant can deliver the GLP-1RA exenatide for a months long duration. Results suggest that exposure to exenatide plasma concentrations ranging from 1.5 ng/ml to 4 ng/ml are sufficient for inducing weight loss in cats.

Pluronic-Based Nanoparticles for Delivery of Doxorubicin to the Tumor Microenvironment by Binding to Macrophages.

The active targeting drug delivery system based on special types of endogenous cells such as macrophages has emerged as a promising strategy for tumor therapy, owing to its tumor homing property and biocompatibility. In this work, the active tumor-targeting drug delivery system carrying doxorubicin-loaded nanoparticles (DOX@MPF127-MCP-1, DMPM) on macrophage (RAW264.7) surfaces via the mediation of interaction with the CCR2/MCP-1 axis was exploited. Initially, the amphiphilic block copolymer Pluronic F127 (PF127) was carboxylated to MPF127 at the hydroxyl terminus. Subsequently, MPF127 was modified with MCP-1 peptide to prepare MPF127-MCP-1 (MPM). The DOX was wrapped in MPM to form DMPM nanomicelles (approximately 100 nm) during the self-assembly process of MPM. The DMPM spontaneously bound to macrophages (RAW264.7), which resulted in the construction of an actively targeting delivery system (macrophage-DMPM, MA-DMPM) in vitro and in vivo. The DOX in MA-DMPM was released in the acidic tumor microenvironment (TME) in a pH-responsive manner to increase DOX accumulation and enhance the tumor treatment effect. The ratio of MA-DMPM homing reached 220% in vitro compared with the control group, indicating that the MA-DMPM was excellently capable of tumor-targeting delivery. In in vivo experiments, nonsmall cell lung cancer cell (NCI-H1299) tumor models were established. The results of the fluorescence imaging system (IVIS) showed that MA-DMPM demonstrated tremendous tumor-targeting ability in vivo. The antitumor effects of MA-DMPM in vivo indicated that the proportion of tumor cell apoptosis in the DMPM-treated group was 63.33%. The findings of the tumor-bearing mouse experiment proved that MA-DMPM significantly suppressed tumor cell growth, which confirmed its immense potential and promising applications in tumor therapy.

Modification of Living Diatom, Thalassiosira weissflogii, with a Calcium Precursor through a Calcium Uptake Mechanism: A Next Generation Biomaterial for Advanced Delivery Systems.

The diatom's frustule, characterized by its rugged and porous exterior, exhibits a remarkable biomimetic morphology attributable to its highly ordered pores, extensive surface area, and unique architecture. Despite these advantages, the toxicity and nonbiodegradable nature of silica-based organisms pose a significant challenge when attempting to utilize these organisms as nanotopographically functionalized microparticles in the realm of biomedicine. In this study, we addressed this limitation by modulating the chemical composition of diatom microparticles by modulating the active silica metabolic uptake mechanism while maintaining their intricate three-dimensional architecture through calcium incorporation into living diatoms. Here, the diatom Thalassiosira weissflogii was chemically modified to replace its silica composition with a biodegradable calcium template, while simultaneously preserving the unique three-dimensional (3D) frustule structure with hierarchical patterns of pores and nanoscale architectural features, which was evident by the deposition of calcium as calcium carbonate. Calcium hydroxide is incorporated into the exoskeleton through the active mechanism of calcium uptake via a carbon-concentrating mechanism, without altering the microstructure. Our findings suggest that calcium-modified diatoms hold potential as a nature-inspired delivery system for immunotherapy through antibody-specific binding.

Bioinspired Adaptive Microdrugs Enhance the Chemotherapy of Malignant Glioma: Beyond Their Nanodrugs.

Solid nanoparticle-mediated drug delivery systems are usually confined to nanoscale due to the enhanced permeability and retention (EPR) effect. However, they remain a great challenge for malignant glioma chemotherapy because of poor drug delivery efficiency and insufficient tumor penetration resulting from the blood-brain barrier/blood-brain tumor barrier (BBB/BBTB). Inspired by biological microparticles (e.g., cells) with excellent adaptive deformation, we demonstrate that the adaptive microdrugs (even up to 3.0μm in size) are more efficient than their nanodrugs (less than 200nm in size) to cross BBB/BBTB and penetrate into tumor tissues, achieving highly efficient chemotherapy of malignant glioma. The distinct delivery of the adaptive microdrugs is mainly attributed to the enhanced interfacial binding and endocytosis via adaptive deformation. As expected, the obtained adaptive microdrugs exhibited enhanced accumulation, deep penetration, and cellular internalization into tumor tissues in comparison with nanodrugs, significantly improving the survival rate of glioblastoma mice. We believe that the bioinspired adaptive microdrugs enable them to efficiently cross physiological barriers and deeply penetrate tumor tissues for drug delivery, providing an avenue for the treatment of solid tumors. This article is protected by copyright. All rights reserved.

Inhalable spray-dried porous microparticles containing dehydroandrographolide succinate phospholipid complex capable of improving and prolonging pulmonary anti-inflammatory efficacy in mice.

Due to the unique physiological barriers within the lungs, there are considerable challenges in developing drug delivery systems enabling prolonged drug exposure to respiratory epithelial cells. Here, we report a PulmoSphere-based dry powder technology that incorporates a drug-phospholipid complex to promote intracellular retention of dehydroandrographolide succinate (DAS) in respiratory epithelial cells following pulmonary delivery. The DAS-phospholipid complex has the ability to self-assemble into nanoparticles. After spray-drying to produce PulmoSphere microparticles loaded with the drug-phospholipid complex, the rehydrated microparticles discharge the phospholipid complex without altering its physicochemical properties. The microparticles containing the DAS-phospholipid complex exhibit remarkable aerodynamic properties with a fine particle fraction of ∼ 60% and a mass median aerodynamic diameter of ∼ 2.3μm. These properties facilitate deposition in the alveolar region. In vitro cell culture and lung tissue explants experiments reveal that the drug-phospholipid complex prolongs intracellular residence time and lung tissue retention due to the slow intracellular disassociation of drug from the complex. Once deposited in the lungs, the DAS-phospholipid complex loaded microparticles increase and extend drug exposure to the lung tissues and the immune cells compared to the free DAS counterpart. The improved drug exposure to airway epithelial cells, but not immune cells, is related to a prolonged duration of pulmonary anti-inflammation at decreased doses in a mouse model of acute lung injury induced by lipopolysaccharide. Overall, the phospholipid complex loaded microparticles present a promising approach for improved treatment of respiratory diseases, e.g. pneumonia and acute respiratory distress syndrome.

Advances in preclinical approaches for intravesical therapy of bladder cancer.

The purpose of this review is to explore new strategies to treat bladder cancer. This article addresses challenges and opportunities in intravesical therapy of bladder cancer. The review examines the latest advances in the development of preclinical approaches for intravesical therapy of bladder cancer. It discusses strategies to improve drug delivery efficiency by using synthesized diverse carriers. Immunotherapy with protein aggregate magnesium-ammonium phospholinoleate-palmitoleate anhydride has been shown to be more effective than intravesical Bacillus Calmette-Guerin. Novel drug delivery systems such the urinary drug-disposing strategy and intravesical nanoparticle formulations improve the drug delivery efficiency while minimizing adverse reactions. Innovative imaging techniques using near-infrared fluorescence probes and multifunctional nano-transformers enable real-time detection and targeted therapy in bladder cancer treatment. Treatment of bladder cancer is clinically challenging. However, recent progress in drug delivery technologies shows promise. Optimizing these technologies helps improve patient outcomes, and facilitates clinical translation of different treatment modalities.

Association between hospital case volume and maternal adverse events in patients with placental abruption: An analysis using a Japanese national inpatient database.

To clarify the relationship between the prognosis of patients with placental abruption (PA) and the healthcare delivery system using data from a large national inpatient database in Japan. Using the Diagnosis Procedure Combination database, we conducted a retrospective cohort study with the data of patients in almost 1000 hospitals with the primary diagnosis of PA who were hospitalized from April 2014 to March 2021. We divided the hospitals into four groups based on the number of deliveries per month. We performed multilevel logistic regression analysis to analyze the relationship between hospital case volume and maternal end-organ injury (MEOI). Altogether, 8222 patients were included for analysis; among whom, 3575 (44%) were transferred by ambulance. MEOI was noted in 977 patients (12%) with no obvious difference by hospital case volume. Ambulance transfer, age, gestational weeks at admission, delivery on the first day of hospitalization, and history of eclampsia were significantly associated with a higher incidence of MEOI, but the hospital case volume was not. Using a Japanese administrative database, our study shows that hospital case volume was not significantly associated with the severity of maternal illness among patients with PA.

Investigating a Calcium Alginate-Xylitol Coating Methodology for Controlled Release Profiles of Multivitamin Tablet as a Model Drug

The drug delivery system promotes the release of the active pharmaceutical ingredient (API) to attain the desired therapeutic effect at the time most needed. Alginate is a natural polymer that is frequently employed in drug delivery systems. Calcium alginate can simply coat as a film type on the surface of a tablet, which might be created to be dissolved more quickly and predictably manners in the gastric fluid to deliver as needed in a patient-friendly system. In this study, the sodium alginate solution was reacted with a predetermined calcium compound and xylitol combination, while the multivitamin tablets’ surface was coated with calcium suppliers such as calcium chloride. Then, the coated tablets were subjected to a dissolution test in a simulated gastric fluid. Our study results showed that the sphere formation was excellent in terms of strength and size in 1.0% sodium alginate with 4% calcium chloride. Average sphere sizes were 0.5 ~ 2.0 mm. Their break force was 3.5 N, And the dissolution was the fastest in the coated tablets with 1% sodium alginate and calcium chloride. The dissolution rate was changed proportionally with calcium concentration. A high feasibility of dissolution rate was positively found. When a high concentration of xylitol was mixed with 4% calcium chloride, the dissolution rate was proportional to the concentration of xylitol. In conclusion, the study demonstrated that the dissolution rate of tablets with API might be controllable with the calcium alginate film coating with xylitol.

International cross-cultural development and field testing of the primary care practice questionnaire for the PaRIS survey (PaRIS-PCPQ)

BackgroundThe PaRIS survey, an initiative of the Organisation for Economic Co-operation and Development (OECD), aims to assess health systems performance in delivering primary care by measuring the care experiences and outcomes of people over 45 who used primary care services in the past six months. In addition, linked data from primary care practices are collected to analyse how the organisation of primary care practices and their care processes impact care experiences and outcomes. This article describes the development and validation of the primary care practice questionnaire for the PaRIS survey, the PaRIS-PCPQ.MethodThe PaRIS-PCPQ was developed based on domains of primary care practice and professional characteristics included in the PaRIS conceptual framework. Questionnaire development was conducted in four phases: (1) a multi-step consensus-based development of the source questionnaire, (2) translation of the English source questionnaire into 17 languages, (3) cross-national cognitive testing with primary care professionals in participating countries, and (4) cross-national field-testing.Results70 items were selected from 7 existing questionnaires on primary care characteristics, of which 49 were included in a first draft. Feedback from stakeholders resulted in a modified 34-item version (practice profile, care coordination, chronic care management, patient follow-up, and respondent characteristics) designed to be completed online by medical or non-medical staff working in a primary care practice. Cognitive testing led to changes in the source questionnaire as well as to country specific localisations. The resulting 32-item questionnaire was piloted in an online survey and field test. Data from 540 primary care practices from 17 countries were collected and analysed. Final revision resulted in a 34-item questionnaire.ConclusionsThe cross-national development of a primary care practice questionnaire is challenging due to the differences in care delivery systems. Rigorous translation and cognitive testing as well as stakeholder engagement helped to overcome most challenges. The PaRIS-PCPQ will be used to assess how key characteristics of primary care practices relate to the care experiences and outcomes of people living with chronic conditions. As such, policymakers and care providers will be informed about the performance of primary care from the patient’s perspective.

Improvement in Central Serous Chorioretinopathy Following Multiwavelength Photobiomodulation Treatment - Case Report.

Central serous chorioretinopathy (CSCR) is a condition where fluid build-up accumulates underneath the retina, resulting in retinal pigment epithelium (RPE) detachment and vision loss. Irreversible retinal functional and anatomical changes are possible consequences. Research into novel strategies to aid in recovery are of interest. Photobiomodulation (PBM) uses light wavelengths to improve cellular function and shows positive effects in several conditions including those with edema. This prospective case report details a 39-year-old woman with CSCR. Multiwavelength PBM treatment was initiated with the Valeda® Light Delivery System. A series of treatment included nine sessions delivered over 3-5weeks. Follow-up treatments were conducted. Optical coherence tomography (OCT) imaging and best-corrected visual acuity (BCVA) measures were taken. The patient has been followed for approximately 1year. The patient presented with blurred vision and a BCVA score of 65 letters in the left eye. After 3weeks of observation, the patient's vision had further declined two lines on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart to 55 letters. Fluorescein angiography was performed, confirming CSCR diagnosis, and PBM was initiated. PBM treatment improved BCVA and fluid build-up in the RPE within 1week of treatment (three treatment sessions). Following the full series of treatment (nine PBM treatment sessions), fluid was completely resolved and BCVA scored at 80 letters. The patient had a repeat PBM treatmentseries ~ 6months later and has shown stable vision and no fluid present on OCT scan. The patient was seen again ~ 1year later with continued stable vision and no fluid detection. PBM is a non-invasive treatment option that may provide benefit in CSCR to resolve fluid build-up, macular change, and vision loss. Research into PBM as an immediate treatment option for CSCR, especially those with chronic presentations or those posed to have irreversible damage, is warranted to confirm effectiveness.