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1.
Nat Commun ; 14(1): 35, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36627280

RESUMO

Long-acting injectables are considered one of the most promising therapeutic strategies for the treatment of chronic diseases as they can afford improved therapeutic efficacy, safety, and patient compliance. The use of polymer materials in such a drug formulation strategy can offer unparalleled diversity owing to the ability to synthesize materials with a wide range of properties. However, the interplay between multiple parameters, including the physicochemical properties of the drug and polymer, make it very difficult to intuitively predict the performance of these systems. This necessitates the development and characterization of a wide array of formulation candidates through extensive and time-consuming in vitro experimentation. Machine learning is enabling leap-step advances in a number of fields including drug discovery and materials science. The current study takes a critical step towards data-driven drug formulation development with an emphasis on long-acting injectables. Here we show that machine learning algorithms can be used to predict experimental drug release from these advanced drug delivery systems. We also demonstrate that these trained models can be used to guide the design of new long acting injectables. The implementation of the described data-driven approach has the potential to reduce the time and cost associated with drug formulation development.


Assuntos
Sistemas de Liberação de Medicamentos , Polímeros , Humanos , Injeções , Liberação Controlada de Fármacos , Aprendizado de Máquina
2.
Int J Mol Sci ; 24(1)2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36614220

RESUMO

Current literature has indicated that Peyronie's disease (PD) could be initiated by microtrauma and the subsequent inflammation episodes that follow. PD could be sorted into acute or chronic status, and it can differ when selecting the clinical therapeutics. PD would cause pain and penile deformity to diseased men and impair their erectile function. Occasionally, surgical revision of the penis might be needed to correct the penile curvature. We find that there are limited effective options of intra-lesion injections for the PD plaques. By searching the databases and screening the literature with the PRISMA 2020 guideline, we observed that several preclinical studies that applied stem cell therapy in treating PD were fruitful in the acute phase. Although in the chronic phase of PD, erectile parameters were not significantly improved, and therefore, future studies might be better elevated in certain aspects, such as the sites selected for harvesting stem cells or changing the centrifugation forces. In this review, we concluded the contemporary understanding of inflammatory microenvironments in PD, the stem cell therapy in PD, and our perspectives on future studies. We concluded that there may be great potential in stem cell therapy for treating both acute and chronic phases PD.


Assuntos
Induração Peniana , Masculino , Humanos , Induração Peniana/tratamento farmacológico , Pênis , Ereção Peniana , Injeções , Células-Tronco
4.
Int J Mol Sci ; 24(2)2023 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-36675200

RESUMO

In Parkinson's disease, hypercholinism in the striatum occurs, with the consequence of disturbed motor functions. Direct application of Botulinum neurotoxin-A in the striatum of hemi-Parkinsonian rats might be a promising anticholinergic therapeutic option. Here, we aimed to determine the spread of intrastriatally injected BoNT-A in the brain as well as the duration of its action based on the distribution of cleaved SNAP-25. Rats were injected with 1 ng of BoNT-A into the right striatum and the brains were examined at different times up to one year after treatment. In brain sections immunohistochemically stained for BoNT-A, cleaved SNAP-25 area-specific densitometric analyses were performed. Increased immunoreactivity for cleaved SNAP-25 was found in brain regions other than the unilaterally injected striatum. Most cleaved SNAP-25-ir was found in widespread areas ipsilateral to the BoNT-A injection, in some regions, however, immunoreactivity was also measured in the contralateral hemisphere. There was a linear relationship between the distance of a special area from the injected striatum and the time until its maximum averaged immunoreactivity was reached. Moreover, we observed a positive relationship for the area-specific distance from the injected striatum and its maximum immunoreactivity as well as for the connection density with the striatum and its maximum immunoreactivity. The results speak for a bidirectional axonal transport of BoNT-A after its application into the striatum to its widespread connected parts of the brain. Even one year after BoNT-A injection, cleaved SNAP-25 could still be detected.


Assuntos
Corpo Estriado , Doença de Parkinson , Ratos , Animais , Neostriado , Injeções , Tempo
5.
J Manag Care Spec Pharm ; 29(2): 139-150, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36705280

RESUMO

BACKGROUND: The process used to prefer certain products across drug classes for diabetes is generally focused on comparative effectiveness and cost. However, payers rarely tie patient preference for treatment attributes to formulary management resulting in a misalignment of value defined by providers, payers, and patients. OBJECTIVES: To explore patients' willingness to pay (WTP) for the predetermined high-value and low-value type 2 diabetes mellitus (T2DM) treatments within a health plan. METHODS: A cross-sectional discrete choice experiment (DCE) survey was used to determine patient preference for the benefit, risk, and cost attributes of T2DM treatments. A comprehensive literature review of patient preference studies in diabetes and a review of guidelines and medical literature identified study attributes. Patients and diabetes experts were interviewed and instructed to identify, prioritize, and comment on which attributes of diabetes treatments were most important to T2DM patients. The patients enrolled in a health plan were asked to respond to the survey. A multinomial logit model was developed to determine the relative importance and the patient's WTP of each attribute. The patients' relative values based on WTPs for T2DM treatments were calculated and compared with the treatments by a health plan. RESULTS: A total of 7 attributes were selected to develop a web-based DCE questionnaire survey. The responses from a total of 58 patients were analyzed. Almost half (48.3%) of the respondents took oral medications and injections for T2DM. The most prevalent side effects due to diabetes medications were gastrointestinal (43.1%), followed by weight gain (39.7%) and nausea (32.8%). Patients were willing to pay more for treatments with proven cardiovascular benefit and for the risk reduction of hospitalization from heart failure. On the other hand, they would pay less for treatments with higher gastrointestinal side effects. Patients were willing to pay the most for sodium-glucose cotransporter 2 inhibitor and glucagon-like peptide 1 receptor agonist agents and the least for dipeptidyl peptidase-4 inhibitors and thiazolidinediones. CONCLUSIONS: This study provides information to better align patient, provider, and payer preferences in both benefit design and value-based formulary strategy for diabetes treatments. A preferred placement of treatments with cardiovascular benefits and lower adverse gastrointestinal side effects may lead to increased adherence to medications and improved clinical outcomes at a lower overall cost to both patients and their health plan. DISCLOSURES: This study was supported by a grant from the PhRMA Foundation.


Assuntos
Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Estudos Transversais , Comportamento de Escolha , Administração Oral , Injeções , Inquéritos e Questionários
6.
Langmuir ; 39(4): 1529-1537, 2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36683534

RESUMO

Injectable hydrogels with strong mechanical properties have significant potential for biomedical applications, including the development of electronic skin, intelligent medical robots, as well as tissue engineering. In this study, we report on an injectable hydrogel with notable tensile strength and adhesion properties, achieved through cross-linking thiol-terminated four-arm poly (ethylene glycol) using silver-doped nano-hydroxyapatite, modified with dopamine. Subsequently, the hydrogel was injected in vivo through the perivascular interstitial space of rats. The hydrogel wrapped around the damaged abdominal aortic adventitia, which greatly increases the stress strength of the arterial adventitia. We found that the hydrogel was characterized by excellent biocompatibility, and it induced little immune response over a span of 21 days post-implantation. This simple and minimally invasive vascular protection strategy appears promising for the treatment of vascular diseases, such as abdominal aortic aneurysm (AAA).


Assuntos
Túnica Adventícia , Hidrogéis , Ratos , Animais , Hidrogéis/farmacologia , Injeções , Polietilenoglicóis/toxicidade , Engenharia Tecidual
7.
Toxins (Basel) ; 15(1)2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36668880

RESUMO

DaxibotulinumtoxinA for Injection (DAXI) is a novel botulinum toxin type A product containing daxibotulinumtoxinA with a stabilizing excipient peptide (RTP004). DAXI immunogenicity was assessed in three phase 3 glabellar line studies (two placebo-controlled, single-dose studies and an open-label repeat-dose safety study). Binding antibodies to daxibotulinumtoxinA and RTP004 were detected by validated ELISAs. Samples positive for daxibotulinumtoxinA-binding antibodies were evaluated further for titer and neutralizing antibodies by mouse protection assay. Overall, 2786 subjects received DAXI and 2823 subjects were exposed to RTP004 as DAXI (n = 2786) or placebo (n = 37). Treatment-related anti-daxibotulinumtoxinA binding antibodies were detected in 21 of 2737 evaluable subjects (0.8%). No subject developed neutralizing antibodies. Treatment-related anti-RTP004 binding antibodies were detected in 35 (1.3%) of 2772 evaluable subjects. Binding antibodies were generally transient, of low titer (<1:200), and no subject had binding antibodies to both daxibotulinumtoxinA and RTP004. All subjects with treatment-induced binding antibodies to daxibotulinumtoxinA or RTP004 achieved none or mild glabellar line severity at Week 4 following each DAXI cycle, indicating no impact on DAXI efficacy. No subjects with binding antibodies to daxibotulinumtoxinA or RTP004 reported immune-related adverse events. This evaluation of anti-drug antibody formation with DAXI shows low rates of antibody formation to both daxibotulinumtoxinA and RTP004.


Assuntos
Toxinas Botulínicas Tipo A , Fármacos Neuromusculares , Envelhecimento da Pele , Animais , Camundongos , Toxinas Botulínicas Tipo A/uso terapêutico , Injeções , Anticorpos Neutralizantes , Fármacos Neuromusculares/uso terapêutico , Resultado do Tratamento , Método Duplo-Cego
8.
Schizophr Res ; 251: 74-81, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36587541

RESUMO

OBJECTIVES: Weight gain remains a major problem in young people with psychosis treated with antipsychotic medication. Aripiprazole is now available in monthly long-acting injection (LAI) and daily oral tablet formulation, but information is lacking about differences in weight gain between the two formulations. We monitored for up to 24 months the weight changes associated with oral or LAI-administered aripiprazole and in a group who not prescribed any antipsychotic medication. METHODS: Participants included 109 young people with early psychosis (n = 30 Oral, 41 LAI, 38 Nil antipsychotic) with a treatment completion median time of 15 months. Weight (kilogram) and body mass index (BMI) were recorded at 3 monthly intervals. Multilevel modelling analyses assessed the contribution of time and group on weight change. RESULTS: Participants taking nil antipsychotics did not gain weight over time, while the two aripiprazole groups gained a combined average of 7.1 kg (SD = 5.0) or 1.9 BMI (SD = 0.4). An examination of formulation effects showed a significantly greater rate of change over time in the Oral group with a weight increase of approximately 11.0 kg (SD = 8.2) or 3.5 BMI (SD = 0.7, compared to the LAI group with a gain of 3.7 kg (SD = 2.1) or 0.8 BMI (SD = 0.1) in the LAI group. These differences could not be explained by demographic or clinical characteristics, medication dosage, or baseline weight. CONCLUSIONS: While aripiprazole is generally considered relatively benign in terms of weight, it still poses a significant risk especially for people with early psychosis. However the current study suggests that the risk may be lower in those treated with LAI than with Oral formulation, consolidating the clinical utility of LAI.


Assuntos
Antipsicóticos , Transtornos Psicóticos , Esquizofrenia , Humanos , Adolescente , Aripiprazol/uso terapêutico , Antipsicóticos/uso terapêutico , Esquizofrenia/tratamento farmacológico , Transtornos Psicóticos/tratamento farmacológico , Injeções , Preparações de Ação Retardada/uso terapêutico
10.
A A Pract ; 17(1): e01644, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36602918

RESUMO

The parasternal block is an ultrasound-guided interfascial plane block that provides anesthesia of the medial quadrants of the breast. The original approach provided injections in the fascial plane between the pectoral major and external intercostal muscles. We observed that this technique might limit an adequate diffusion of the injectate due to the anatomical convexity of the ribs, which might hinder fascial hydrodissection. We suggest a modified approach by positioning the tip of the needle on the rib dome to reduce the local anesthetic volume and obtain a more homogeneous and longitudinal spread into the target fascial compartment.


Assuntos
Bloqueio Nervoso , Humanos , Bloqueio Nervoso/métodos , Anestésicos Locais , Ultrassonografia , Anestesia Local , Injeções
11.
Dermatol Surg ; 49(1): 60-65, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36533798

RESUMO

BACKGROUND: Simultaneous treatment of moderate-to-severe upper facial lines is reflective of real-world clinical practice. OBJECTIVE: To evaluate the efficacy and safety of daxibotulinumtoxinA-lanm for injection (DAXI) for simultaneous treatment of glabellar, forehead, and lateral canthal (LC) lines. METHODS: In this open-label, single-arm Phase 2 study, patients (48 enrolled, 94% completed, follow-up 24-36 weeks) received DAXI 40U (glabellar), 32U (forehead), and 48U (LC) lines. Key efficacy endpoints: percentages of patients achieving none/mild wrinkle severity (investigator-rated) for each upper facial line scale at Week 4. RESULTS: At Week 4, most patients achieved none/mild wrinkle severity (investigator-rated): glabellar (96%), forehead (96%), and LC (92%). Median times to loss of none/mild response (investigator- and patient-rated) among all patients were: 24.6 (glabellar), 20.9 (forehead), and 24.9 (LC) weeks; and 25.0, 24.0, and 28.1 weeks, respectively, among Week-4 responders. At Week 4, most patients reported improvements (Global Aesthetic Improvement Scale: 96%-98%) and high satisfaction rates (85%-98%). Five patients experienced treatment-related adverse events: injection-site erythema (3 patients/7 events), facial discomfort (2 patients/2 events), and headache (1 patient/1 event). No patients experienced eyebrow or eyelid ptosis. CONCLUSION: Simultaneous treatment of upper facial lines with DAXI was well tolerated and demonstrated high response rates, extended duration, and high patient satisfaction. CLINICAL TRIAL REGISTRY: https://clinicaltrials.gov/ct2/show/NCT04259086.


Assuntos
Toxinas Botulínicas Tipo A , Fármacos Neuromusculares , Envelhecimento da Pele , Humanos , Testa , Face , Injeções , Resultado do Tratamento , Método Duplo-Cego
12.
Phys Med Rehabil Clin N Am ; 34(1): 275-283, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36410887

RESUMO

The injection of biologic products for musculoskeletal pathologies is an emerging and promising field; however, dubious and unsafe uses for these products are often marketed. The Food and Drug Administration (FDA) has determined the need for varying degrees of regulation for these products for safety and efficacy. These regulations are frequently updated and federally enforced. As the regulatory landscape changes, clinicians using biologic products must stay informed to remain within the purview of the FDA. This article describes the current regulations of the most common products: platelet-rich plasma, bone marrow aspirate concentrate, adipose-derived products, and birth tissue products.


Assuntos
Produtos Biológicos , Plasma Rico em Plaquetas , Humanos , Injeções
13.
Phys Med Rehabil Clin N Am ; 34(1): 285-290, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36410888

RESUMO

There is a pressing need for the standardization of orthobiologics, considering the cellular components, concentrations, and methods of injections may vary wildly, currently without significant standards of care. There is a growing body of evidence that these factors matter significantly for patient outcomes, so it is imperative that orthobiologic constituents are measured and standardized. Cell counts may be performed for platelet-rich plasma and bone marrow aspirate-based injections, whereas adipose should have standardized processing techniques as cellular quantification is more difficult.


Assuntos
Plasma Rico em Plaquetas , Humanos , Tecido Adiposo , Injeções , Padrões de Referência
14.
Phys Med Rehabil Clin N Am ; 34(1): 135-163, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36410880

RESUMO

Ligament injuries are common causes of joint pain, dysfunction, and disability resulting in disruption of joint homeostasis. Ligament injuries have historically been treated surgically. The autologous orthobiologic preparation used for treatment can influence the varying results reported. Therefore, to truly understand and compare results of these powerful therapies, reporting standardization, such as harvesting techniques, concentration techniques, quantification of the delivered product (platelets, progenitor cells), formulations (leukocyte content), number of injections performed, activation, injection technique (guided vs unguided), in addition to the post treatment rehabilitation process, are all important and necessary to evaluate and compare efficacy of future studies.


Assuntos
Ligamentos , Humanos , Injeções
15.
Phys Med Rehabil Clin N Am ; 34(1): 105-115, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36410878

RESUMO

Many procedural techniques have been described and used for orthobiologics procedures with little research on the ideal technique. This section outlines the commonly used materials and techniques from start to finish for these procedures. Post-procedure pain is common during and after many of these injections, and local and regional anesthesia during these procedures is discussed. Accuracy and safety of tendon, ligament, cartilage, intra-osseous, and spinal orthobiologic procedures are improved with the utilization of image guidance.


Assuntos
Coluna Vertebral , Humanos , Injeções
19.
J Am Acad Orthop Surg ; 31(3): e135-e147, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36584347

RESUMO

INTRODUCTION: The popularity of platelet-rich plasma (PRP) injections for the treatment of orthopaedic conditions has grown markedly. We sought to better define the trends in the usage of orthopaedic PRP injections across an insured US population over the past decade. METHODS: The PearlDiver M91Ortho commercial administrative claims database was queried for all patients receiving PRP injections for orthopaedic conditions from 2010 through the first quarter of 2020 (Q1.2020). Trends in PRP use, reimbursement charges, demographics, joints injected, and administering physicians were assessed over time and reported as year-over-year (YOY) changes. RESULTS: Over the study period, 14,096 unique patients had 17,759 orthopaedic PRP injections. The number of PRP injections administered had a YOY increase of 7.1% (144 injections/year, 95% confidence interval [CI] = 89 to 199, Ptrend = 0.0009). A YOY increase of 895% was observed in total nonsurgical charges ($683,974/yr, 95% CI 441,504 to 926,444, Ptrend = 0.0009). The median age of PRP recipients increased (YOY change = +0.6 years, 95% CI 0.4 to 0.8, Ptrend = 0.0005). Injections to the elbow (YOY change = -0.8%, 95% CI -0.10% to [-0.06%], Ptrend = 0.005) and foot/ankle (YOY change = -1.0%, 95% CI -1.4% to [-0.06%], Ptrend = 0.002) decreased, whereas hip (YOY change = +0.4%, 95% CI 0.2% to 0.6%, Ptrend = 0.019), knee (YOY change = +0.9%, 95% CI 0.3% to 1.2%, Ptrend = 0.016), and spine (YOY change = +0.2%, 95% CI 0.0% to 0.4%, Ptrend = 0.033) injections increased. PRP injections given by sports medicine orthopaedic surgeons (YOY change = +0.8%, 95% CI 0.6% to 1.2%, Ptrend <0.0001) increased over time, whereas those by general orthopaedic surgeons decreased (YOY change = -0.9, 95% CI -1.2 to [-0.6%], Ptrend = 0.001). CONCLUSION: PRP injections quadrupled in prevalence from 2010 to Q1.2020, with a projected increase in annual usage in this data set of 66% by 2030. As greater evidence-based indications for PRP use are identified, more specialists and insurance providers may consider expanding their involvement in this growing field. LEVEL OF EVIDENCE: III, retrospective cohort study.


Assuntos
Seguro , Doenças Musculoesqueléticas , Osteoartrite do Joelho , Plasma Rico em Plaquetas , Humanos , Lactente , Estudos Retrospectivos , Injeções , Osteoartrite do Joelho/terapia , Doenças Musculoesqueléticas/terapia , Resultado do Tratamento , Injeções Intra-Articulares
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