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A long-standing challenge is how to formulate proteins and vaccines to retain function during storage and transport and to remove the burdens of cold-chain management. Any solution must be practical to use, with the protein being released or applied using clinically relevant triggers. Advanced biologic therapies are distributed cold, using substantial energy, limiting equitable distribution in low-resource countries and placing responsibility on the user for correct storage and handling. Cold-chain management is the best solution at present for protein transport but requires substantial infrastructure and energy. For example, in research laboratories, a single freezer at -80 °C consumes as much energy per day as a small household1. Of biological (protein or cell) therapies and all vaccines, 75% require cold-chain management; the cost of cold-chain management in clinical trials has increased by about 20% since 2015, reflecting this complexity. Bespoke formulations and excipients are now required, with trehalose2, sucrose or polymers3 widely used, which stabilize proteins by replacing surface water molecules and thereby make denaturation thermodynamically less likely; this has enabled both freeze-dried proteins and frozen proteins. For example, the human papilloma virus vaccine requires aluminium salt adjuvants to function, but these render it unstable against freeze-thaw4, leading to a very complex and expensive supply chain. Other ideas involve ensilication5 and chemical modification of proteins6. In short, protein stabilization is a challenge with no universal solution7,8. Here we designed a stiff hydrogel that stabilizes proteins against thermal denaturation even at 50 °C, and that can, unlike present technologies, deliver pure, excipient-free protein by mechanically releasing it from a syringe. Macromolecules can be loaded at up to 10 wt% without affecting the mechanism of release. This unique stabilization and excipient-free release synergy offers a practical, scalable and versatile solution to enable the low-cost, cold-chain-free and equitable delivery of therapies worldwide.

OBJECTIVE: Evaluate the penetration of hydrogen peroxide (HP) into the pulp chamber, bleaching efficacy (BE) and amount of gel expended during in-office bleaching using an applicator brush tip and conventional tip from different commercial brands.
METHODS: 104 human premolars were randomly distributed into thirteen groups (n = 8) according to the commercial brand: DSP White Clinic 35 % Calcium (DW), Nano White 35 % (NW), Total Blanc One-Step 35 % (TS), Whiteness HP Blue 35 % (WB), Potenza Bianco Pro SS 38 % (PB), Opalescence XTra Boost 40 % (OB), no bleaching (negative control), and application method: applicator brush tip and conventional tip for all groups. Initial HP concentration (%) was determined via titration and pH was measured with digital pH meter. Concentration (µg/mL) of HP into the pulp chamber was measured using UV-Vis spectrophotometry, the BE (ΔE*ab, ΔE00 and ΔWID) was evaluated with a digital spectrophotometer, and the amount of gel expended was evaluated using a precision analytical digital balance. Statistical analysis included two-way ANOVA, Tukey\'s, and Dunnett\'s test. Comparison between HP into the pulp chamber vs BE was performed with Person\'s correlation (α = 0.05).
RESULTS: Brush tip demonstrated a low amount of HP in the pulp chamber compared to the conventional method for all bleaching gels (p < 0.0003), as well as lower amount of gel expended (p < 0.002). The brush tip did not result in a significant difference in BE compared to the conventional (p > 0.05). No correlations were found between both factors (p > 0.05).
CONCLUSIONS: Brush tip showed lower penetration of HP in the pulp chamber and a reduced volume of spent gel when compared to the conventional tip, for all commercial brands.
CONCLUSIONS: Brush tip is recommended for bleaching gels in an attachable syringe due to its ability to reduce the penetration of HP into the pulp chamber and minimize the amount of bleaching gel used.

BACKGROUND: SB11 (Byooviz™; Samsung Bioepis Co., Ltd.) is a ranibizumab (Lucentis®; Genentech, Inc.) biosimilar targeting vascular endothelial growth factor A for the treatment of retinal diseases. The pre-filled syringe (PFS) presentation of SB11 offers an alternative administration method to the vial, with the potential for enhanced safety and efficient syringe preparation. The objective of this study was to assess the ability of healthcare professionals (HCPs) to follow the instructions for use to prepare and administer SB11 PFS intravitreal (IVT) injections to patients with neovascular age-related macular degeneration (nAMD) or macular edema secondary to retinal vein occlusion (RVO).
METHODS: This study was an open-label, single-arm, single-dose clinical study to evaluate the usability of the SB11 PFS in patients with nAMD or macular edema secondary to RVO. Four HCPs prepared and administered 0.5 mg SB11 PFS IVT injections to 34 patients. Product use task completion (12 tasks in total) was assessed by independent observers. Safety was assessed up to 7 days after injection of the investigational product.
RESULTS: A total of 34 patients were enrolled and completed the study. All 12 tasks were successfully completed in 34 (100%) patients without a use-related failure. Most patients (32 patients, 94.1%) experienced no adverse events (AEs), whereas 2 (5.9%) patients experienced three treatment-emergent AEs (TEAEs) which were mild to moderate in severity. There were no severe or serious TEAEs reported during the study.
CONCLUSIONS: This study showed that HCPs were able to successfully prepare and administer the SB11 PFS via IVT injection. No unexpected safety issues were identified. The SB11 PFS is a promising alternative for therapeutic administration of SB11 in patients with retinal disease.
BACKGROUND: ClinicalTrials.gov identifier NCT06176963; EudraCT number 2021-003566-12.

BACKGROUND: In Mexico and around the world, water in dental units, including triple syringes, comes from municipal chlorinated water mains. The microbial contamination of dental unit water systems constitutes a risk factor for opportunistic infections.
OBJECTIVE: The present work aimed to identify the bacteria present in the triple-syringe water lines of dental units at a dental school of a public university in Mexico, with a hypothesis that opportunistic bacteria of importance to human health would be found.
METHODS: A cross-sectional study was carried-out. A total of 100 samples of triple-syringe tubing from dental units operated by a dental school of a public university in Mexico were analyzed before and after their use in dental practice. Bacterial biofilm was cultured and isolated from the tubing, using standard microbiological methods, and then the species present were identified through 16S rRNA gene sequencing. The characterization of the biofilm was performed by means of scanning electron microscopy (SEM).
RESULTS: Bacterial growth was observed in 20% of the non-disinfected and 10% of the disinfected samples, with 11 strains isolated. Six genera and 11 bacterial species were genetically identified. Coagulasenegative staphylococci (CoNS), considered opportunistic human pathogens, were among the most critical microorganisms. Scanning electron microscopy revealed a thick polymeric matrix with multiple bacterial aggregates.
CONCLUSIONS: Opportunistic bacteria from human skin and mucous membranes were detected. Under normal conditions, these bacteria are incapable of causing disease, but are potentially harmful to immunosuppressed patients.

Evidence of harm reduction interventions\' morbidity and mortality benefits is abundant and of high quality, so there are good reasons for regional and national groups to advocate for more widespread distribution of legally regulated \"drug paraphernalia,\" including needles, syringes, and fentanyl test strips. But lack of consistency among states\' laws means that patients\' interstate travel can subject them to being charged with possession of illegal items. This commentary on a case offers guidance to clinicians looking to help patients understand legal risks of interstate travel with supplies that are prescribed or recommended to reduce harms of their drug use and explores the ethical responsibilities of physicians in jurisdictions that legally prohibit these harm reduction interventions.

UNASSIGNED: This study compared the pharmacokinetics (PK), immunogenicity, and safety of candidate tocilizumab biosimilar, CT-P47, administered via auto-injector (CT-P47 AI) or pre-filled syringe (CT-P47 PFS), in healthy Asian adults.
UNASSIGNED: In this phase I, multicenter, open-label study, participants were randomized 1:1 to receive a single 162 mg/0.9 mL dose of CT-P47 via AI or PFS. Primary endpoints were area under the concentration - time curve from time zero to infinity (AUC0-inf) and maximum serum concentration (Cmax). PK equivalence was determined if 90% confidence intervals (CIs) for the ratios of geometric least-squares means (gLSMs) were within the predefined 80-125% equivalence margin. Secondary PK parameters, immunogenicity, and safety outcomes were also assessed.
UNASSIGNED: Of 314 participants randomized (155 CT-P47 AI; 159 CT-P47 PFS), 310 received the study drug (153 CT-P47 AI; 157 CT-P47 PFS). Primary and secondary PK results, immunogenicity and safety were similar between groups. Ninety percent CIs for the ratio of gLSMs were within the predefined equivalence margin for AUC0-inf (85.87-102.94) and Cmax (82.98-98.16).
UNASSIGNED: PK equivalence between CT-P47 AI and CT-P47 PFS was demonstrated in healthy Asian adults, with comparable immunogenicity and safety between the two devices.
UNASSIGNED: ClinicalTrials.gov: NCT05617183.
Tocilizumab is a biologic medicine used to treat inflammatory diseases, such as rheumatoid arthritis. A biosimilar is a drug that is an almost identical copy of an approved original (‘reference’) biologic medicine; it has identical efficacy and safety to the original medicine but is typically less expensive. CT‑P47 is in development as a possible tocilizumab biosimilar.Some patients prefer injections using an auto-injector (AI) rather than a pre-filled syringe (PFS), for reasons including ease of use and convenience. With an AI, medicine is delivered automatically by firmly pressing the device against the skin, whereas, with a PFS, a needle is inserted into the skin and medicine delivered by depressing the plunger. The injection of CT‑P47 using a PFS has shown comparable pharmacokinetics (i.e., the uptake, metabolism and excretion of the drug by the body) and safety to tocilizumab. Therefore, if the pharmacokinetics and safety of CT‑P47 administered via AI and PFS were shown to be similar, this might expand the choice of administration devices available to patients.In this study, 310 healthy adults received a single injection of CT‑P47 via AI or PFS. Blood samples were taken over 43 days to analyze pharmacokinetics. The uptake, metabolism and elimination of CT‑P47 by the body was similar when administered by each device, suggesting that CT‑P47 can be administered by either AI or PFS.

Between 2017 and 2021, the Brazilian Unified Health System (BUHS) administered a total of 527,903,302 doses of immunizations. Each immunization results in the presence of a residual volume (RV) due to syringe dead space (DS). The International Organization for Standardization 7886-1 allows a DS of up to 0.07mL in sterile single-use hypodermic syringes with volumes less than 5mL. This study aims to quantify the DS of immunization devices used in Brazil, study the best combinations of needles and syringes to minimize RV, estimate the number of wasted doses from 2017 to 2021, and evaluate the impact on the BUHS. Pneumococcal 10 vaccine with a 25x6mm needle and a regular 1mL syringe exhibited a significantly higher average RV (0.0826mL) and waste rate (14.42%). It was observed that for some intramuscular vaccines, there is less waste when using a 20x5.5mm needle compared to a 25x6mm needle. The use of syringes with plunger stoppers that penetrate the syringe barrel, denoted as low dead space syringes, results in less RV and an estimated difference in the waste rate of approximately 10% compared to the regular syringe. The estimated number of wasted doses from 2017 to 2021 by BUHS is approximately 32 million doses.

UNASSIGNED: The current study compared preparation time, errors, satisfaction, and preference for a prefilled syringe (PFS) versus two RSV vaccines requiring reconstitution (VRR1 and VRR2) in a randomized, single-blinded time and motion study.
UNASSIGNED: Pharmacists, nurses, and pharmacy technicians were randomized to a preparation sequence of the three vaccines. Participants read instructions, then consecutively prepared the three vaccines with a 3-5-min washout period in between. Preparations were video recorded and reviewed by a trained pharmacist for preparation time and errors using predefined, vaccine-specific checklists. Participant demographics, satisfaction with vaccine preparation, and vaccine preference were recorded. Within-subjects analysis of variance was used to compare preparation time. Mixed-effects Poisson and ordered logistic regression models were used to compare the number of preparation errors and satisfaction scores, respectively.
UNASSIGNED: Sixty-three pharmacists (60%), nurses (35%), and pharmacy technicians (5%) participated at four sites in the United States. The least squares mean preparation time per dose for PFS was 141.8 s (95% CI = 156.8-126.7; p <.0001) faster than for VRR1, 103.6 s (95% CI = 118.7-88.5; p <.0001) faster than for VRR2, and 122.7 s (95% CI = 134.2-111.2; p <.0001) faster than the pooled VRRs. Overall satisfaction (combined \"Very\" and \"Extremely\") was 87.3% for PFS, 28.6% for VRR1, and 47.6% for VRR2. Most participants (81.0%) preferred the PFS vaccine.
UNASSIGNED: The study is limited by the inability to completely blind observers. To minimize the effects of order, we utilized a 3-sequence block design; however, the order in which the vaccines were prepared may have affected outcomes. Participants were assessed once, whereas if repeated preparations were performed there may have been trained efficiencies gained for each vaccine.
UNASSIGNED: PFS vaccines can greatly simplify the vaccine preparation process, allowing administrators to prepare almost four times more doses per hour than with vial and syringe systems.

Background/Objectives: Catecholamines are among those agents that are indispensable in modern intensive care medicine. The rapid availability of hygienically impeccable and correctly concentrated injectable solutions, e.g., for syringe pumps, is becoming more and more important. However, little research has been conducted regarding how the use of catecholamines is distributed in different wards and what options can be used to achieve optimal availability. Methods: In a retrospective monocentric study from 2019 to 2022, all continuously applied catecholamines in intensive care units (ICU) and intermediate care units (IMC) were investigated. The focus was on potential optimization by utilizing manufactured ready-to-administer solutions in the context of the economization of patient care. Results: Norepinephrine syringes represented 81% of all syringes administered, appearing to be the most frequently used on all wards. Production by the in-house pharmacy showed both financial advantages and an increase in patient safety compared to syringes produced at the bedside. Discussion: Increasing numbers of critically ill patients coupled with growing staff shortages and an increased awareness of safety requirements are driving the move towards ready-to-use and ready-to-administer solutions in critical care medicine. In-house manufacturing by hospital pharmacies can be a promising option to optimize processes and improve the economics of patient care. Conclusions: Individual calculations of the required catecholamine preparations with regard to possible economic advantages should be carried out in hospitals. In particular, in-house production of ready-to-use and ready-to-administer preparations could significantly increase patient safety and seems to be economically viable.