HPTN 083-02: factors influencing adherence to injectable PrEP and retention in an injectable PrEP study.

INTRODUCTION: HPTN 083 demonstrated the superiority of long-acting cabotegravir (CAB-LA) versus daily oral emtricitabine/tenofovir disoproxil fumarate (TDF/FTC) as pre-exposure prophylaxis (PrEP) among cisgender men and transgender women who have sex with men (MSM/TGW). HPTN 083 provided the first opportunity to understand experiences with injectable PrEP in a clinical trial. METHODS: Participants from two US sites (Chicago, IL and Atlanta, GA) and one international site (Rio de Janeiro, Brazil) were purposively sampled for individual qualitative interviews (N = 40), between November 2019 and March 2020, to explore trial experiences, barriers to adherence and other factors that may have impacted study implementation or outcomes. The blinded phase ended early due to efficacy; this analysis includes interviews conducted prior to unblinding with three groups defined by adherence (i.e. injection visit attendance): adherent (n = 27), non-adherent (n = 12) and early discontinuers (n = 1). Data were organized using NVivo software and analysed using content analysis. RESULTS: Participants (mean age: 27) were primarily cisgender MSM (90%) and Black/African American (60%). Reasons for trial enrolment and PrEP use included a preference for using HIV prevention medication versus treatment in the event of HIV acquisition; the ability to enhance health via study-related education and services; access to a novel, convenient HIV prevention product at no cost; and contributing to MSM/TGW communities through research. Participants contrasted positive experiences with study staff with their routine clinical care, and emphasized increased scheduling flexibility, thorough communication, non-judgemental counselling and open, affirming environments (e.g. compassion, less stigma) as adherence facilitators. Injection experiences were positive overall; some described early injection-related anxiety, which abated with time and when given some measure of control (e.g. pre-injection countdown), and minimal injection site discomfort. Some concerns and misperceptions about injectable PrEP were reported. Barriers to adherence, across all adherence categories, included structural factors (e.g. financial constraints, travel) and competing demands (e.g. work schedules). CONCLUSIONS: Respondents viewed injectable PrEP trial participation as a positive experience and a means of enhancing wellbeing. Study site flexibility and affirming clinic environments, inclusive of non-judgemental counselling, were key facilitators of adherence. To support injection persistence, interventions that address structural barriers and promote flexible means of injection delivery may be most effective.

Injectable Hydrogels for Nervous Tissue Repair-A Brief Review.

The repair of nervous tissue is a critical research field in tissue engineering because of the degenerative process in the injured nervous system. In this review, we summarize the progress of injectable hydrogels using in vitro and in vivo studies for the regeneration and repair of nervous tissue. Traditional treatments have not been favorable for patients, as they are invasive and inefficient; therefore, injectable hydrogels are promising for the treatment of damaged tissue. This review will contribute to a better understanding of injectable hydrogels as potential scaffolds and drug delivery system for neural tissue engineering applications.

Preference for long-acting injectable for ART and PrEP among people with and without HIV: a cross-sectional study in Argentina.

Background: Little is known about the preferences for antiretroviral therapy (ART) administration methods, such as oral daily pills or long-acting injectable (LAI) options, as well as preferences for pre-exposure prophylaxis (PrEP) administration methods among people without HIV in Latin America. Objectives: This study aimed to assess the preferences for ART administration methods among people with HIV and PrEP methods among those without HIV, as well as to examine the correlations and reasons for these preferences. Design: We conducted a cross-sectional web-based questionnaire between April and July 2021, using social media accounts of a HIV non-governmental organization. The questionnaire was open to all adults living in Argentina, irrespective of their sexual orientation or gender identity. Methods: The questionnaire included questions on substance use, depression, chronic treatment, previous experiences with injectable medication, and HIV status. Those with HIV answered questions about ART adherence and their preferences for ART methods, while those without HIV were asked about condom use, awareness of PrEP, and their preferences for PrEP methods. Results: Out of 1676 respondents, 804 had HIV, and 872 did not. Among those with HIV, 91.5% expressed a high preference for LAI-ART, with significantly higher preferences among participants with higher educational levels, cisgender gay, bisexual, and queer men, younger individuals, and those with prior injectable medication experience. Among those without HIV, 68% preferred LAI-PrEP, and this preference was positively associated with previous positive experiences with injectable medication. Conclusion: The strong preference for LAI-ART suggests the potential for improved adherence and well-being among people with HIV. Additionally, the preference for LAI-PrEP among those without HIV emphasizes the importance of considering this option for HIV prevention strategies. This study highlights the need to offer diverse methods for ART and prevention to accommodate different preferences and improve health care outcomes in Latin America.

Injectable Composite Resin Technique: An Alternative for Anterior Esthetic Restorations - Case Report / Técnica de Resina Compuesta Inyectable: Una Alternativa para Restauraciones Estéticas Anteriores - Reporte de Caso

This article aims to describe a clinical case of the use of the injectable restorative technique with composite resin in a patient with an esthetic complaint in the anterior teeth. Producing direct restorations in anterior teeth when performed with composite resin demands a long clinical time. Results often depend on the operator's ability to reproduce proper form, function, and esthetics. Lately, the versatility of composite resins has increased. As this material evolved, new techniques were introduced to simplify the restorative process and save time. The restorative technique with injectable fluid composite resin, in addition to delivering faster and with a certain ease, is capable of increasing the predictability of treatment results. However, it is known that flowable resins have lower wear resistance and color stability compared to conventional resins. Thus, a version of this material with a higher filler content in its composition was introduced to the market, to improve wear resistance and gloss retention. Long-term studies evaluating the use of low-viscosity resins are needed. The injectable technique can accurately reproduce the morphology obtained in the wax-up of the case, generating a satisfactory esthetic and functional result. Despite simplifying the fabrication of restorations when compared to the conventional technique, it is still necessary for the operator to have some experience and aptitude. The clinical time for the production of restorations has been considerably reduced. The material showed good flow, shine, and polish in the immediate result. However, the finishing and polishing of the restorations required a longer clinical period than usual and in the short- term follow-up, flaws in the gingival margins and a new finishing and polishing procedure were necessary. Therefore, the technique described in this article can be considered a restorative alternative, but it is still not able to replace the tradit ional method of making previous esthetic restorations.

Este artículo tiene como objetivo describir un caso clínico del uso de la técnica restauradora inyectable con resina compuesta en un paciente con una queja estética en los dientes anteriores. Producir restauraciones directas en dientes anteriores cuando se realizan con resina compuesta demanda un largo tiempo clínico. Los resultados a menudo dependen de la capacidad del operador para reproducir la forma, la función y la estética adecuadas. Últimamente, la versatilidad de las resinas compuestas ha aumentado. A medida que este material evolucionó, se introdujeron nuevas técnicas para simplificar el proceso de restauración y ahorrar tiempo. La técnica restauradora con resina compuesta fluida inyectable, además de una entrega más rápida y segura, es capaz de aumentar la previsibilidad de los resultados del tratamiento. Sin embargo, se sabe que las resinas fluidas tienen menor resistencia al desgaste y estabilidad del color en comparación con las resinas convencionales. Así, se introdujo en el mercado una versión de este material con un mayor contenido de relleno en su composición, con el objetivo de mejorar la resistencia al desgaste y la retención del brillo. Se necesitan estudios a largo plazo que evalúen el uso de resinas de baja viscosidad. La técnica inyectable es capaz de reproducir fielmente la morfología obtenida en el encerado del caso, generando un resultado estético y funcional satisfactorio. A pesar de simplificar la fabricación de restauraciones en comparación con la técnica convencional, todavía es necesario que el operador tenga cierta experiencia y aptitud. El tiempo clínico para la producción de restauraciones se ha reducido considerablemente. El material mostró buena fluidez, brillo y pulido en el resultado inmediato. Sin embargo, el acabado y pulido de las restauraciones requirió de un período de tiempo clínico más largo de lo habitual y en el seguimiento a corto plazo, fueron necesarios defectos en los márgenes gingivales y un nuevo procedimiento de acabado y pulido. Por lo tanto, la técnica descrita en este artículo puede considerarse una alternativa restauradora, pero aún no es capaz de reemplazar el método tradicional de realizar restauraciones estéticas previas.

A novel porous hydrogel based on hybrid gelation for injectable and tough scaffold implantation and tissue engineering applications.

Although there have been many advances in injectable hydrogels as scaffolds for tissue engineering or as payload-containing vehicles, the lack of adequate microporosity for the desired cell behavior, tissue integration, and successful tissue generation remains an important drawback. Herein, we describe an effective porous injectable system that allowsin vivoformation of pores through conventional syringe injection at room temperature. This system is based on the differential melting profiles of photocrosslinkable salmon gelatin and physically crosslinked porogens of porcine gelatin (PG), in which PG porogens are solid beads, while salmon methacrylamide gelatin remains liquid during the injection procedure. After injection and photocrosslinking, the porogens were degraded in response to the physiological temperature, enabling the generation of a homogeneous porous structure within the hydrogel. The resultant porogen-containing formulations exhibited controlled gelation kinetics within a broad temperature window (18.5 ± 0.5-28.8 ± 0.8 °C), low viscosity (133 ± 1.4-188 ± 16 cP), low force requirements for injectability (17 ± 0.3-39 ± 1 N), robust mechanical properties after photo-crosslinking (100.9 ± 3.4-332 ± 13.2 kPa), and favorable cytocompatibility (>70% cell viability). Remarkably,in vivosubcutaneous injection demonstrated the suitability of the system with appropriate viscosity and swift crosslinking to generate porous hydrogels. The resulting injected porous constructs showed favorable biocompatibility and facilitated cell infiltration for desirable potential tissue remodeling. Finally, the porogen-containing formulations exhibited favorable handling, easy deposition, and good shape fidelity when used as bioinks in 3D bioprinting technology. This injectable porous system serves as a platform for various biomedical applications, thereby inspiring future advances in cell therapy and tissue engineering.

Anatomy, molecular structures, and hyaluronic acid - Gelatin injectable hydrogels as a therapeutic alternative for hyaline cartilage recovery: A review.

Cartilage damage caused by trauma or osteoarthritis is a common joint disease that can increase the social and economic burden in society. Due to its avascular characteristics, the poor migration ability of chondrocytes, and a low number of progenitor cells, the self-healing ability of cartilage defects has been significantly limited. Hydrogels have been developed into one of the most suitable biomaterials for the regeneration of cartilage because of its characteristics such as high-water absorption, biodegradation, porosity, and biocompatibility similar to natural extracellular matrix. Therefore, the present review article presents a conceptual framework that summarizes the anatomical, molecular structure and biochemical properties of hyaline cartilage located in long bones: articular cartilage and growth plate. Moreover, the importance of preparation and application of hyaluronic acid - gelatin hydrogels for cartilage tissue engineering are included. Hydrogels possess benefits of stimulating the production of Agc1, Col2α1-IIa, and SOX9, molecules important for the synthesis and composition of the extracellular matrix of cartilage. Accordingly, they are believed to be promising biomaterials of therapeutic alternatives to treat cartilage damage.

Long-Acting Injectable Cabotegravir for HIV Preexposure Prophylaxis Among Sexual and Gender Minorities: Protocol for an Implementation Study.

BACKGROUND: Long-acting injectable cabotegravir (CAB-LA) for preexposure prophylaxis (PrEP) has proven efficacious in randomized controlled trials. Further research is critical to evaluate its effectiveness in real-world settings and identify effective implementation approaches, especially among young sexual and gender minorities (SGMs). OBJECTIVE: ImPrEP CAB Brasil is an implementation study aiming to generate critical evidence on the feasibility, acceptability, and effectiveness of incorporating CAB-LA into the existing public health oral PrEP services in 6 Brazilian cities. It will also evaluate a mobile health (mHealth) education and decision support tool, digital injection appointment reminders, and the facilitators of and barriers to integrating CAB-LA into the existing services. METHODS: This type-2 hybrid implementation-effectiveness study includes formative work, qualitative assessments, and clinical steps 1 to 4. For formative work, we will use participatory design methods to develop an initial CAB-LA implementation package and process mapping at each site to facilitate optimal client flow. SGMs aged 18 to 30 years arriving at a study clinic interested in PrEP (naive) will be invited for step 1. Individuals who tested HIV negative will receive mHealth intervention and standard of care (SOC) counseling or SOC for PrEP choice (oral or CAB-LA). Participants interested in CAB-LA will be invited for step 2, and those with undetectable HIV viral load will receive same-day CAB-LA injection and will be randomized to receive digital appointment reminders or SOC. Clinical appointments and CAB-LA injection are scheduled after 1 month and every 2 months thereafter (25-month follow-up). Participants will be invited to a 1-year follow-up to step 3 if they decide to change to oral PrEP or discontinue CAB-LA and to step 4 if diagnosed with HIV during the study. Outcomes of interest include PrEP acceptability, choice, effectiveness, implementation, and feasibility. HIV incidence in the CAB-LA cohort (n=1200) will be compared with that in a similar oral PrEP cohort from the public health system. The effectiveness of the mHealth and digital interventions will be assessed using interrupted time series analysis and logistic mixed models, respectively. RESULTS: During the third and fourth quarters of 2022, we obtained regulatory approvals; programmed data entry and management systems; trained sites; and performed community consultancy and formative work. Study enrollment is programmed for the second quarter of 2023. CONCLUSIONS: ImPrEP CAB Brasil is the first study to evaluate CAB-LA PrEP implementation in Latin America, one of the regions where PrEP scale-up is most needed. This study will be fundamental to designing programmatic strategies for implementing and scaling up feasible, equitable, cost-effective, sustainable, and comprehensive alternatives for PrEP programs. It will also contribute to maximizing the impact of a public health approach to reducing HIV incidence among SGMs in Brazil and other countries in the Global South. TRIAL REGISTRATION: Clinicaltrials.gov NCT05515770; https://clinicaltrials.gov/ct2/show/NCT05515770. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/44961.

Preferences for pre-exposure prophylaxis (PrEP) among sexual and gender minorities: a discrete choice experiment in Brazil.

Background: Men who have sex with men (MSM) and transgender women (TGW) are disproportionally affected by HIV infection in Latin America. This study aims to assess pre-exposure prophylaxis (PrEP) preferences among sexual and gender minorities (SGM) and identify attributes and levels that are related to PrEP uptake and adherence, both crucial for PrEP success. Methods: We conducted a discrete choice experiment (DCE) among SGM from all Brazilian regions (September-December/2020). The survey was administered face-to-face (five Brazilian capitals) and online (entire country). We used a D-efficient zero-prior blocked experimental design to select 60 paired-profile DCE choice tasks. Findings: The total sample size was 3924 (90.5% MSM; 7.2% TGW and 2.3% non-binary or gender diverse persons). In random-effects logit models, highest levels of protection and "no side effects" were the most important attribute levels. For "presentation", injectable and implant were preferred over oral. Participants were willing to accept a 4.1% protection reduction to receive injectable PrEP or a 4.2% reduction if PrEP were taken monthly. The largest class in the latent class models was defined predominantly by the preference for the highest HIV protection level (p < 0.005). Respondents in this class also preferred no side effects, injectable and implant presentations. Interpretation: Higher HIV protection, no side effects, and presentation, whether injectable or implant, were the most important attributes in PrEP preferences. Protection against HIV was the most important attribute. PrEP programs should make available technologies such as long-acting presentations that could reunite the most desired attributes, thus maximizing acceptability and user-appropriateness. Funding: Unitaid.

Effects of injectable and intravaginal progesterone on ewes' reproductive performance at breeding season beginning.

Progesterone (P4) is a steroid hormone that has a regulatory role in the female reproductive system. Studies on the effects of injectable progesterone on ewes are scarce, mainly related to their reproductive responses in the breeding season. This study aimed to compare reproductive performance and serum P4 concentration using injectable or intravaginal P4 in ewes. Two hundred and forty and eight Santa Inês x Dorper ewes (BW; 52.67 ± 11.76 kg; mean ± SE), body condition score (BCS; 2.5 ± 0.8; scale of 1-5), were distributed in four treatments: (i) Control: without administration of P4; (ii) CIDR: intravaginal implantation of 330 mg of P4 for 7 days; (iii) 1P4: 15 mg of P4 intramuscular (IM); and (iv) 2P4I: 30 mg of P4 IM. The first 18 days of breeding season were considered the synchronization period. Except for ewes in the control group, all other ewes received 263 µg IM of cloprostenol sodium for lysis of eventual CL at 24 h before the P4 treatment. After the synchronization period, all ewes were kept together with males for extra 28 days in the breeding season. At the beginning of breeding season, 90% of the ewes had serum P4 concentration less than 1 ng/mL. The estrus rate was greater (P < 0.01) in ewes on the CIDR treatment, with similar estrus rate among the other treatments. The P4 implant was able to keep blood P4 concentration greater than 1 ng/mL in ewes that received an implant of P4 during the 7 days. After implant removal, there was a great increase in the estrus manifestation on ewes in the CIDR treatment, leading to an increase in pregnancy rate at the beginning of breeding season. The current study demonstrated that ewes that received an intramuscular injection of 15 or 30 mg of P4 had similar reproductive performance than ewes that did not receive any P4 intramuscular injection. However, when ewes were implanted with P4 (CIDR), these animals had an increase in estrus manifestation, leading to greater pregnancy earlier during the breeding season.

Delusional Jealousy: How Can Treatment be Improved? A Case Report / Delirio celotípico: ¿cómo se puede mejorar el tratamiento? Un reporte de caso

RESUMEN Introducción: Aunque el delirio celotípico represente solo cerca del 10% de los trastornos delirantes, se asocia un riesgo de violencia grave y suicidio. Con este caso clínico se pretende explorar las dificultades en el tratamento farmacológico del trastorno de delirio celotípico y resumir los hallazgos más recientes en el tratamiento de esta enfermedad. Métodos: Reporte de caso. Presentación del caso: Un varón de 76 anos tuvo un ingreso involuntario en el departamento de psiquiatría debido a amenazas de agresión física a su esposa en el contexto de ideas irreductibles de su infidelidad. Inicialmente se observó una mejoría de los síntomas con risperidona y su formulación inyectable de acción prolongada, pero la aparición de efectos secundarios hipotensivos requirió la prescripción off-label de palmitato de paliperidona 50 mg/ml. Conclusiones: Pocos estudios, principalmente reportes de casos, abordan el tratamiento específico del delirio celotípico. Dadas las consecuencias negativas para los pacientes y sus cónyuges, se necesita una mejor evidencia científica para el tratamiento de esta enfermedad.

ABSTRACT Introduction: Although delusional jealousy accounts for merely 10% of delusional disorders, it is associated to risk of serious violence and suicide. With this clinical case, we intend to explore the difficulties in the pharmacological approach of delusional jealousy disorder and to summarise the most recent findings in the treatment of this condition. Methods: Case report. Case presentation: A 76-year-old man involuntarily admitted to a psychiatric ward due to threats of physical aggression to his wife in the context of irreducible ideas of her infidelity. Initially, we observed an improvement of symptomatology with risperidone and its long-acting injectable formulation, but the emergence of hypotensive side effects required the off-label use of paliperidone palmitate 50 mg/ml. Conclusions: Few studies, mainly case reports, look at the specific treatment of delusional jealousy. Given the negative consequences for patients and for their spouses, better scientific evidence to treat this condition is needed.

Zero knowledge and high interest in the use of long-acting injectable pre-exposure prophylaxis (PrEP) among adolescent men who have sex with men and transgender women in two capital cities in Brazil.

BACKGROUND: Adolescent men who have sex with men (aMSM) and transgender women (aTGW) are affected disproportionately by human immunodeficiency virus (HIV) infection. Although new methods of pre-exposure prophylaxis (PrEP), such as long-acting injectable (LAI-PrEP), have been approved by the Food and Drug Administration, their acceptability among aMSM/aTGW is not well known. METHODS: Forty-eight semi-structured interviews were conducted to assess the knowledge and interest in LAI-PrEP among aMSM/aTGW enrolled in a daily oral PrEP cohort from two capital cities of Brazil since 2019. RESULTS: Previous knowledge of LAI-PrEP remains scarce, but the high interest regarding its use has been reported. Interest in the use of LAI-PrEP is associated with eliminating the burden of daily responsibility or the risk of missing the necessary medications, lowering the costs of this method, increasing confidentiality, and decreasing the frequency of visiting PrEP clinics. The reported barriers to uptake included fear of injection, doubts on its effectiveness, side effects, and greater dependence on a health provider. CONCLUSIONS: There is an urgent need to strengthen the preventive strategies against HIV infection among the youth, enhance their knowledge and those of healthcare providers, and offer safe and new options.

Biopredictive tools for the development of injectable drug products.

INTRODUCTION: Biopredictive release tests are commonly used in the evaluation of oral medicines. They support decision-making in formulation development and allow predictions of the expected in-vivo performances. So far, there is limited experience in the application of these methodologies to injectable drug products. AREAS COVERED: Parenteral drug products cover a variety of dosage forms and administration sites, including subcutaneous, intramuscular, and intravenous injections. In this area, developing biopredictive and biorelevant methodologies often confronts us with unique challenges and knowledge gaps. Here, we provide a formulation-centric approach and explain the key considerations and workflow when designing biopredictive assays. Also, we outline the key role of computational methods in achieving clinical relevance and put all considerations into context using liposomal nanomedicines as an example. EXPERT OPINION: Biopredictive tools are the need of the hour to exploit the tremendous opportunities of injectable drug products. A growing number of biopharmaceuticals such as peptides, proteins, and nucleic acids require different strategies and a better understanding of the influences on drug absorption. Here, our design strategy must maintain the balance between robustness and complexity required for effective formulation development.

Involuntary Administration of Long-Acting Injectable Antipsychotics for Competency Restoration.

In implementing the decisions in the landmark case Sell v. United States, jurisdictions have adopted mechanisms for the involuntary medication of defendants to restore competency to stand trial. These procedures attempt to balance the liberty and privacy rights of the accused against the government's responsibility to ensure timely prosecution and fair trial. The question of which medications are most appropriate for this goal, however, remains open. This article reviews the legal status of the administration of long-acting injectable (LAI) antipsychotics for sustained competency restoration. We explore case law and discuss the theoretical and empirical benefits and drawbacks to this practice, considering recent technological advancements in LAI development. Some courts have regarded LAI use pursuant to Sell as equivalent or superior to immediate-acting medications, whereas others have regarded LAIs as either more intrusive or medically riskier. We conclude that the use of LAIs may be carefully integrated into treatment plans to restore and maintain trial competency amid competing interests.

Acceptability of the contraceptive Sayana® Press when injected every four months: Results from a twelve-month trial in Brazil, Chile and the Dominican Republic.

OBJECTIVE: We assessed the acceptability of subcutaneous depot-medroxyprogesterone acetate 104 mg (Sayana® Press) when injected every 4 months for 12 months. STUDY DESIGN: We assessed acceptability using questionnaires within a clinical trial to evaluate contraceptive effectiveness of Sayana® Press when the reinjection interval was extended from 3 to 4 months. We enrolled 750 women aged 18 to 35 years and at risk of pregnancy at 3 centers in Brazil, Chile, and the Dominican Republic who agreed to use Sayana® Press every 4 months for 12 months. Acceptability outcomes included responses to questions about perception of bleeding patterns and side effects, likes, and dislikes about the regimen. We descriptively compared outcomes across study centers and between those who completed the study and those who discontinued early. RESULTS: Across the 3 centers, participants differed in age, marital status, years of schooling, and race. At the final visit, 90% reported being satisfied with Sayana® Press and 75% reported preferring to use this contraceptive every 4 months. The most common reasons women liked using Sayana® Press were for its duration of effectiveness, followed by amenorrhea. The most common dislike, when a reason was identified, was its effect on uterine bleeding, including amenorrhea reported by some participants. We also observed center-level differences in the proportion of women who liked amenorrhea. CONCLUSIONS: Satisfaction with Sayana® Press injected every 4 months was high across the 3 demographically diverse Latin-American centers. However, participants had varied feelings towards contraceptive-induced amenorrhea. IMPLICATIONS: We found that Sayana® Press when injected every 4 months was highly acceptable among women in 3 Latin American settings despite differences in their feelings toward contraceptive-induced amenorrhea. Our results suggest that there will be interest in using this method every 4 months if introduced into these settings.

Utilização do método alternativo in vitro em substituição ao método in vivo na detecção de pirogênio para produtos injetáveis

Pyrogens are substances capable of inducing mild reactions such as fever or severe systemic reactions that can lead to death. Injectable products need to be free of pyrogens when released by the quality control of the pharmaceutical industries, to meet good manufacturing practices. Currently there are 3 types of tests for pyrogen detection, the Monocyte Activation Test, the Bacterial Endotoxin Test and the Pyrogen Test in Rabbits, which is widely used in the release of injectable products. However, the pyrogen test in rabbits requires the use of many animals and cannot be used in certain substances such as anti-inflammatory drugs. The alternative method of bacterial endotoxin testing is not able to detect other pyrogens such as products of the metabolism of fungi, viruses and gram-positive bacteria. The Monocytes Activation Test is an alternative method that covers a wide range of pyrogens, can be used on a large scale for the release of injectable products and is more sensitive because it uses human blood as substrate. This study aimed to evaluate the applicability of the use of the monocytes activation test in place of the pyrogen test in rabbits used in biological quality control in the release of batches of injectable products produced by the Butantan Institute.

Pirogênios são substâncias capazes de induzir reações leves como febre ou reações sistêmicas severas que podem levar à morte. Os produtos injetáveis necessitam ser livres de pirogênios quando da sua liberação pelo controle de qualidade das indústrias farmacêuticas, para atender as Boas Práticas de Fabricação. Atualmente existem 3 tipos de testes para detecção de pirogênio, o teste de Ativação de Monócitos, o Teste de Endotoxina Bacteriana e o Teste de Pirogênio em Coelhos, sendo esse amplamente empregado na liberação dos produtos injetáveis. Porém, o teste de pirogênio em coelhos é um teste que demanda a utilização de muitos animais e não pode ser usado em determinadas substâncias como antinflamatórios. O método alternativo de teste de endotoxina bacteriana não é capaz de detectar outros pirogênios como os produtos do metabolismo de fungos, vírus e bactérias gram-positivas. Já o teste de Ativação de Monócitos é um método alternativo que abrange uma ampla gama de pirogênios, pode ser usado em grande escala para liberação dos produtos injetáveis e é mais sensível, pois utiliza como substrato sangue humano. Este trabalho teve como objetivo avaliar a aplicabilidade da utilização do teste de ativação de monócitos em substituição ao teste de pirogênio em coelhos empregado no Controle Qualidade Biológico na liberação dos lotes dos produtos injetáveis produzidos pelo Instituto Butantan.

Resynchronization of follicular wave using long-acting injectable progesterone or estradiol benzoate at 14 days post-timed AI in Bos taurus x Bos indicus beef heifers.

We compared pregnancy rates in beef heifers resynchronized 14 days after the first timed-artificial insemination (TAI) using a P4 intravaginal device associated with either long-acting injectable progesterone (iP4) or estradiol benzoate (EB). Braford and Brangus heifers were submitted to a TAI (D0). On D14, all animals were given a P4 intravaginal device and were randomly divided into two groups, EB (1 mg; n = 339); or iP4 (75 mg; n = 338). On D22, P4 devices were removed, and non-pregnant (NP) heifers were identified by assessing morphological luteolysis with Doppler ultrasonography. The NP heifers had the dominant follicle diameter measured and were submitted to a second TAI on D24. Dominant follicle diameter (mm) on D22 in NP heifers did not differ (P > 0.05) between EB (9.77 ± 0.25) and iP4 (9.92 ± 0.22) groups. No difference was observed between EB and iP4 groups for pregnancy rate on D22 (56.3% vs. 60.1%, respectively), and D40 post-first TAI (49.6% vs. 53.3%, respectively). The rate of potential pregnancy losses from D22 to D40 did not differ between EB (12%, 23/191) and iP4 (11.3%, 23/203) groups. The resynchronization pregnancy rate in the EB group (45.9%, 68/148) was greater (P<0.05) than the iP4 group (31.8%, 43/135). In conclusion, treatment with either 1 mg EB or 75 mg iP4 in combination with P4 device at 14 days after TAI are equally safe for the ongoing pregnancy. The EB treatment can improve the reproductive efficiency, as it resulted in greater resynchronization pregnancy rates than iP4 treatment in beef heifers resynchronized 14 days after TAI.

Formulation and Characterization of a New Injectable Bone Substitute Composed PVA/Borax/CaCO3 and Demineralized Bone Matrix.

The occurrence of bone-related disorders and diseases has dramatically increased in recent years around the world. Demineralized bone matrix (DBM) has been widely used as a bone implant due to its osteoinduction and bioactivity. However, the use of DBM is limited because it is a particulate material, which makes it difficult to manipulate and implant with precision. In addition, these particles are susceptible to migration to other sites. To address this situation, DBM is commonly incorporated into a variety of carriers. An injectable scaffold has advantages over bone grafts or preformed scaffolds, such as the ability to flow and fill a bone defect. The aim of this research was to develop a DBM carrier with such viscoelastic properties in order to obtain an injectable bone substitute (IBS). The developed DBM carrier consisted of a PVA/glycerol network cross-linked with borax and reinforced with CaCO3 as a pH neutralizer, porosity generator, and source of Ca. The physicochemical properties were determined by an injectability test, FTIR, SEM, and TGA. Porosity, degradation, bioactivity, possible cytotoxic effect, and proliferation in osteoblasts were also determined. The results showed that the developed material has great potential to be used in bone tissue regeneration.

Desarrollo tecnológico e introducción del inyectable succinilcolina 50 mg/mL en el cuadro básico de medicamentos nacional de Cuba / Technological development and introduction of the injectable succinylcholine 50 mg/mL in the basic table of national medicines of Cuba / Desenvolvimento tecnológico e introdução da succinilcolina injetável 50 mg/mL na mesa da medicina básica de Cuba

RESUMEN Introducción: El inyectable succinilcolina 50 mg/mL se utiliza para intubaciones traqueales rápidas. Objetivo: Desarrollar e introducir el inyectable succinilcolina 50 mg/mL en el cuadro básico de medicamentos. Tres variantes de formulación fueron diseñadas: dos con preservantes antimicrobianos y presentación (bulbos 6R y 10R) y una sin preservantes (bulbos 6R). Metodología: Se validaron los métodos empleados para el control de calidad y estabilidad. A los lotes elaborados a escala de laboratorio, piloto e industrial con la fórmula seleccionada se les realizó estudio de estabilidad acelerada y vida útil. Las variantes diseñadas evidenciaron adecuada calidad, la no preservada fue seleccionada para realizar lotes a diferentes escalas. Las técnicas cromatográficas empleadas para la cuantificación de la succinilcolina cumplieron con los criterios de validación establecidos. Resultados: Se demostró el desempeño de las pruebas de esterilidad y ensayo de endotoxinas bacterianas. El producto en estudio de estabilidad indicó un adecuado comportamiento físico, químico y micro-biológico durante el período evaluado. Se comprobó la factibilidad del desarrollo tecnológico, con la fórmula seleccionada para el inyectable succinilcolina 50 mg/mL. Se introdujo el inyectable en el cuadro básico de medicamentos nacional.

SUMMARY Introduction: The injectable succinylcholine 50 mg/mL is used for rapid tracheal intubations. Aim: To develop and introduce the injectable succinylcholine 50 mg/mL into the basic drug table. Three formulation variants were designed: two with antimicrobial and presentation preservatives (6R and 10R bulbs) and one unpreserved (6R bulbs). Methodology: The methods used for quality control and stability were validated. Laboratory, pilot and industrial-scale batches with the selected formula were studied for accelerated stability and service life. The designed variants showed adequate quality, selecting the non-preserved, to make batches at different scales. Chromatographic techniques used for the quantification of succinylcholine met established validation criteria. Results: The performance of sterility tests and bacterial endotoxin testing was demonstrated. The product under stability study indicated adequate physical and chemical behavior during the period evaluated. The feasibility of technological development was verified, with the formula selected for the injectable succinylcholine 50 mg/mL. Injectable was introduced in the national medicines basic table.

RESUMO Introdução: A succinilcolina injetável 50 mg/mL é utilizada para intubações traqueais rápidas. Objetivo: Desenvolver e introduzir a succinilcolina injetável 50 mg/mL na tabela básica de medicamentos. Três variantes de formulação foram projetadas: duas com conservantes antimicrobianos e apresentação (lâmpadas 6R e 10R) e uma sem conservantes (lâmpadas 6R). Metodologia: Foram validados os métodos utilizados para o controle de qualidade e estabilidade. Estudos acelerados de estabilidade e vida de prateleira foram realizados nos lotes produzidos em escala laboratorial, piloto e industrial com a fórmula selecionada. As variantes projetadas apresentaram qualidade adequada, a não preservada foi selecionada para a realização de lotes em diferentes escalas. As técnicas cromatográficas utilizadas para a quantificação da succinilcolina atenderam aos critérios de validação estabelecidos. Resultados: Foi demonstrado o desempenho dos testes de esterilidade e do ensaio de endotoxinas bacterianas. O produto em estudo de estabilidade indicou comportamento físico, químico e microbiológico adequado durante o período avaliado. Foi verificada a viabilidade do desenvolvimento tecnológico, com a fórmula selecionada para a succinilcolina injetável 50 mg/mL. O injetável foi introduzido na tabela nacional de medicamentos básicos.

Patient subjective experience of treatment with long-acting injectable antipsychotics: a systematic review of qualitative studies / Experiência subjetiva do paciente no tratamento com antipsicóticos injetáveis de ação prolongada: uma revisão sistemática de estudos qualitativos

ABSTRACT Objective: To gain a better understanding of how long-acting injectable antipsychotic (LAI) therapy is perceived by patients. Methods: A search for qualitative studies has been carried out on PubMed, Google Scholar, PsycINFO and PsycArticles, yielding 11 studies suitable for a review of qualitative studies. The reporting approach chosen was meta-ethnography, following the ENTREQ statement recommendations. Key concepts common to the different studies were extrapolated and then analysed in a systematic and comparative way. Results: Some recurrent issues were associated with LAIs, such as fear of coercion, fear of needles and lack of knowledge about depot therapy. These topics are linked to each other and the patients most concerned about the disadvantages of LAIs are those who are less informed about them, or who have experienced coercion and trauma during hospitalisation. On the other hand, patients who had already received LAIs, and those who had a good therapeutic relationship with their healthcare providers expressed satisfaction with this form of treatment and its continuation. Conclusion: Long-acting injectable antipsychotics are a tool in the management of mental disorders, and a viable alternative to oral medication. Patients show curiosity towards this method of administration, but lack of knowledge is a common finding. Shared decision making about the use of LAIs antipsychotics requires that patients receive accurate information and support for their decision regarding medication.

RESUMO Objetivo: Compreender melhor de que forma a terapia com antipsicóticos injetáveis de ação prolongada (IAP) é percebida pelos pacientes. Métodos: Uma pesquisa por estudos qualitativos foi conduzida em PubMed, Google Scholar, PsycINFO e PsyArticles, resultando em 11 estudos adequados para desenvolver uma revisão de estudos qualitativos. A abordagem escolhida foi a metaetnografia, seguindo as recomendações da diretriz ENTREQ. Conceitos-chave comuns aos diferentes estudos foram extrapolados e analisados de forma sistemática e comparativa. Resultados: Alguns problemas recorrentes foram associados aos IAPs, como medo de coerção, medo de agulhas e falta de conhecimento sobre a terapia com medicação depot. Esses tópicos se conectam uns aos outros: os pacientes mais preocupados com as desvantagens dos IAPs são os menos informados a seu respeito ou aqueles que passaram por coação e traumas durante a hospitalização. Por outro lado, os pacientes que já receberam IAPs e aqueles que apresentam boa relação terapêutica com seus prestadores de assistência médica demonstraram satisfação com essa forma de tratamento e sua continuidade. Conclusão: Os antipsicóticos injetáveis de ação prolongada são um instrumento para a gestão de transtornos mentais e uma alternativa viável à medicação oral. Pacientes demonstram curiosidade em relação a esse método de administração, mas a falta de conhecimento é um fator comumente encontrado. A tomada de decisão compartilhada sobre o uso de antipsicóticos IAPs requer que os pacientes recebam informações precisas e apoio em suas decisões em relação à medicação.

Latest Advances in Hydrogel-Based Drug Delivery Systems for Optimization of Metabolic Syndrome Treatment.

BACKGROUND: Drug delivery systems such as hydrogels have become relevant in cardiovascular and metabolic therapies due to their sustained and controlled release properties of drugs, versatile polymer structures, safety, and biodegradability. RESULTS: The literature presented demonstrates that a hydrogel-based controlled release system increases the therapeutic efficacy in different components of the metabolic syndrome. Hypertension has been the most explored component with advances in in vitro and murine models. However, clinical evidence in humans is scarce, and more translational studies are needed. Hydrogel-based systems for diabetes, obesity, and dyslipidemia have been little explored. Observations mainly demonstrated an increase in therapeutic efficacy, in vitro and in vivo, for the use of insulin, leptin, and natural components, such as epigallocatechin gallate. In all cases, the hydrogel systems achieve better plasma levels of the loaded compound, higher bioavailability, and low cytotoxicity compared to conventional systems. Also, the evidence existing suggests that the development of an injectable hydrogel system for controlled release of drugs or therapeutic compounds is presented as an attractive option for MeS treatment, and due to the possibility of sustained pharmacological release, there is no need for repeated doses and a safe administration route. CONCLUSION: The following review aims to evaluate the use of the hydrogel systems in the therapy of diabetes, obesity, hypertension, and dyslipidemia, which are the main components of metabolic syndrome.