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1.
Healthcare (Basel) ; 11(17)2023 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-37685445

RESUMO

Digital health interventions have shown promise in improving patient outcomes and experiences in various healthcare settings. However, their effectiveness in the context of cardiac surgery remains uncertain. This systematic review aims to evaluate the existing evidence on the use of digital health interventions for patients undergoing cardiac surgery. A comprehensive search of PubMed MEDLINE, Elsevier EMBASE, Elsevier Scopus databases, and ClinicalTrials.gov was conducted to identify relevant studies published up to the present. Studies that examined the effects of digital health interventions, including mobile applications and web-based interventions, on perioperative care and patient outcomes in cardiac surgery were included. The data were extracted and synthesized to provide a comprehensive overview of the findings. The search yielded 15 studies composed of 4041 patients, analyzing the feasibility and implementation of mobile or internet applications for patients undergoing cardiac surgery. The studies included the use of mobile applications (ManageMySurgery, SeamlessMD, mHeart, Telediaglog, ExSed, Soulage Tavie, Heart Health application, and Mayo Clinic Health Connection) and web-based interventions (Heartnet and Active Heart). The findings indicated that these digital health interventions were associated with improved patient engagement, satisfaction, and reduced healthcare utilization. Patients reported finding the interventions helpful in their recovery process, and there was evidence of enhanced symptom monitoring and timely intervention. The completion rates of modules varied depending on the phase of care, with higher engagement observed during the acute phase. Interest in using digital health applications was expressed by patients, regardless of age, gender, or complexity of the cardiac defect. The results demonstrated that web-based interventions resulted in improvements in mental health, quality of life, and eHealth literacy. This systematic review highlights the potential benefits of digital health interventions in the context of cardiac surgery. Further research, including randomized controlled trials, is needed to establish the effectiveness, feasibility, and generalizability of digital health interventions in cardiac surgery.

2.
Neuromodulation ; 26(7): 1450-1458, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36872148

RESUMO

OBJECTIVE: High-frequency spinal cord stimulation (HF-SCS) is a treatment option for postsurgical persistent spinal pain syndrome (type 2 PSPS). We aimed to determine the health care costs associated with this therapy in a nationwide cohort. MATERIALS AND METHODS: IBM Marketscan® Research Databases were used to identify patients who underwent HF-SCS implantation from 2016 to 2019. Inclusion criteria included prior spine surgery or diagnoses of PSPS or postlaminectomy pain syndrome any time within the two years before implantation. Inpatient and outpatient service costs, medication costs, and out-of-pocket costs were collected six months before implantation (baseline) and one, three, and six months after implantation. The six-month explant rate was calculated. Costs were compared between baseline and six months after implant via Wilcoxon sign rank test. RESULTS: In total, 332 patients were included. At baseline, patients incurred median total costs of $15,393 (Q1: $9,266, Q3: $26,216), whereas the postimplant median total costs excluding device acquisition were $727 (Q1: $309, Q3: $1,765) at one month, $2,840 (Q1: $1,170, Q3: $6,026) at three months, and $6,380 (Q1: $2,805, Q3: $12,637) at six months. The average total cost was reduced from $21,410 (SD $21,230) from baseline to $14,312 (SD $25,687) at six months after implant for an average reduction of $7,237 (95% CI = $3212-$10,777, p < 0.001). The median device acquisition costs were $42,937 (Q1: $30,102, Q3: $65,880). The explant rate within six months was 3.4% (8/234). CONCLUSIONS: HF-SCS for PSPS was associated with significant decreases in total health care costs and offsets acquisition costs within 2.4 years. With the rising incidence of PSPS, it will be critical to use clinically effective and cost-efficient therapies for treatment.


Assuntos
Síndrome Pós-Laminectomia , Estimulação da Medula Espinal , Humanos , Custos de Cuidados de Saúde , Síndrome Pós-Laminectomia/terapia , Coluna Vertebral , Dor Pós-Operatória , Medula Espinal , Resultado do Tratamento
3.
Neuromodulation ; 26(1): 115-123, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35871122

RESUMO

INTRODUCTION: Chronic refractory low back pain (CRLBP) is a diagnosis characterized by chronic low back pain in patients who are poor candidates for surgery and fail conservative management. High-frequency spinal cord stimulation (HF-SCS) is a new advance in neuromodulation that may be effective in treating these patients. However, the cost burden of this therapy is yet undetermined. MATERIALS AND METHODS: IBM MarketScan® (IBM, Armonk, NY) data bases were used to retrospectively identify patients with HF-SCS implantation between 2016 and 2019 in the United States. Those with low back pain diagnosis without history of surgery were included in the cohort. Cost data, including inpatient and outpatient service, medication, and out-of-pocket costs, were collected at six months before HF-SCS implantation and one, three, and six months after implantation. The explant rate within six months was evaluated. RESULTS: A total of 119 patients met the inclusion criteria. Most patients were female (73.1%) and owned commercial insurance (83.2%). Common comorbidities included inflammatory arthritis (22.7%), depression (26.1%), hypertension (44.5%), and obesity (26.1%). In the six months before HF-SCS implantation, patients incurred median total costs of $15,766 (first quartile [Q1]: $8,847; third quartile [Q3]: $24,947), whereas the postimplant median total cost excluding device acquisition was $398 (Q1: $145, Q3: $1,272) at one month, $2,569 (Q1: $823, Q3: $5,266) at three months, and $5,840 (Q1: $2,160; Q3: $14,607) at six months. The average reduction in total cost was $6,914 (95% CI: $588, $12,458, p < 0.001). The median total acquisition cost was $43,586 (Q1: $29,506, Q3: $69,426), with most coming from outpatient services. Of 88 patients with six-month continuous enrollment, two (2.3%) had device explant. CONCLUSIONS: We present an analysis using large claims data bases of the cost of HF-SCS for treating CRLBP and show that it may be associated with a significant decrease in total health care costs, offsetting device acquisition costs in 27 months. As advances in neuromodulation expand therapy options for patients, it will be important to understand their financial implications.


Assuntos
Dor Crônica , Dor Lombar , Estimulação da Medula Espinal , Humanos , Feminino , Masculino , Dor Lombar/terapia , Estudos Retrospectivos , Aceitação pelo Paciente de Cuidados de Saúde , Custos de Cuidados de Saúde , Dor Crônica/terapia , Resultado do Tratamento , Medula Espinal
4.
Transl Stroke Res ; 14(3): 347-356, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-35881231

RESUMO

Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating neurological condition. Endovascular coiling or surgical clipping have equivocal success rates, but relatively little is known regarding the health economics and complications of these procedures at the population level. We aimed to analyze the complication profiles and healthcare resource utilization (HRCU) associated with the treatment of aSAH in the USA. We performed a retrospective analysis utilizing the IBM MarketScan database between 2008 and 2015. Primary outcomes included economic analysis stratified by post-operative complication; determination of the effect of several factors on total cost by multivariable regression; and analysis of the incidence, timing, and associated HCRU of aSAH-related post-operative complications. Of the 2374 patients meeting inclusion criteria for economic analysis, 1783 (75.1%) patients had at least one of the ten complications. The most common complications included hydrocephalus (43.8%), transient cerebral ischemia (including vasospasm) (30.6%), ischemic stroke (29.1%), syndrome of inappropriate antidiuretic hormone (SIADH)/hyposmolarity/hyponatremia (22.1%), and seizures (14.9%). Patients who experienced complications had higher median 90-day total costs [$161,127 (Q1 to Q3, $101,411 to $257,662)] than those who did not [$97,376 (Q1 to Q3, $55,692 to $147,447)]. Length of stay was longest for those with pulmonary embolism and pneumonia (27 days) and shortest for those with SIADH/hyposmolarity/hyponatremia (16 days). Brain compression/herniation had the highest mortality rate (19.5%). In total, 14.6% of all patients experienced a readmission within 30 days. In conclusion, patients with aSAH have high post-operative complication rates and costs. Development of novel interventions to reduce complications and improve outcomes is crucial.


Assuntos
Hiponatremia , Síndrome de Secreção Inadequada de HAD , Hemorragia Subaracnóidea , Humanos , Hemorragia Subaracnóidea/epidemiologia , Hemorragia Subaracnóidea/terapia , Hemorragia Subaracnóidea/complicações , Estudos Retrospectivos , Hiponatremia/complicações , Síndrome de Secreção Inadequada de HAD/complicações , Convulsões , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia
5.
J Diabetes Sci Technol ; : 19322968221128321, 2022 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-36314587

RESUMO

BACKGROUND: Painful diabetic peripheral neuropathy (pDPN) is a debilitating complication of long-term diabetes. High-frequency spinal cord stimulation (HF-SCS) was recently shown to be an effective treatment option, but the associated health care resource utilization (HCRU) on real-world patient populations with pDPN is unknown. METHODS: Using IBM MarketScan databases, we identified patients with HF-SCS implantation between January 2016 and December 2019 who had a diagnosis of diabetes or diabetic neuropathy within two years before implant. Cost data were collected for the six months before HF-SCS implantation (baseline) and for the periods of one, three, and six months post-implantation. The six-month explant rate was calculated. RESULTS: A total of 132 patients met inclusion criteria. The median total cost at baseline was $19 220 and was $1356 at one month post-implant, $4858 at three months post-implant, and $13 305 at six months post-implant. The median baseline out-of-pocket cost was $1477 and was $710 at six months post-implant. The average total cost reduction from baseline to six months post-implant was $5118 (P < .001), or $853 per month. The median device acquisition cost was $35 755. The explant rate within six months was 2.1%. CONCLUSIONS: High-frequency spinal cord stimulation significantly reduces total HCRU in patients with pDPN, and based on the average monthly cost reduction of $853, we estimate that the therapy recoups acquisition costs within 3.5 years. As policy increasingly focuses on value-based care, it will be critical to consider the cost and outcomes of innovative therapies.

6.
Diagn Ther ; 1(1): 25-38, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35782783

RESUMO

The breast is one of the common primary sites of brain metastases (BM). Radiotherapy for BM from breast cancer may include whole brain radiation therapy (WBRT), stereotactic radiosurgery (SRS), and stereotactic radiotherapy (SRT), but a consensus is difficult to reach because of the wide and varied protocols, indications, and outcomes of these interventions. Overall, dissemination of disease, patient functional status, and tumor size are all important factors in the decision of treatment with WBRT or SRS. Thus far, previous studies indicate that WBRT can improve tumor control compared to SRS, but increase side effects, however no randomized trials have compared the efficacy of these therapies in BM from breast cancer. Therapies targeting long non-coding RNAs and transcription factors, such as MALAT1, HOTAIR, lnc-BM, TGL1, and ATF3, have the potential to both prevent metastatic spread and treat BM with improved radiosensitivity. Given the propensity for HER2+ breast cancer to develop BM, the above-mentioned cell lines may represent an important target for future investigations, and the development of everolimus and pyrotinib are equally important.

7.
Clin Spine Surg ; 35(9): E725-E730, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-35858207

RESUMO

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: We aimed to characterize the treatment patterns and the associated costs in patients with cerebrospinal fluid (CSF) leak after spine procedures in the United States. BACKGROUND: CSF leak is a common complication after spinal procedures. However, there is a little data regarding the national patterns of treatment choice and the associated health care resource utilization. METHODS: We utilized the IBM MarketScan Research databases to retrospectively analyze adult US patients diagnosed with CSF leak within 30 days of spine procedures between 2001 and 2018. Treatment prevalence, treatment failure, and health care resource utilization data within 30 days of the CSF leak were collected. A subanalysis was performed on patients who received epidural blood patches (EBP) to better understand health care utilization attributable to this treatment modality. RESULTS: Twenty one thousand four hundred fourteen patients were identified. The most common causes of CSF leak were diagnostic spinal tap (59.2%) and laminectomy/discectomy (18.7%). With regard to treatment prevalence, 40.4% of the patients (n=8651) had conservative medical management, 46.6% (n=9987) received epidural blood patch repair, 9.6% required surgical repair (n=2066), and 3.3% (n=710) had lumbar drain/puncture. Nine hundred sixty-seven (9.7%), 150 (21.1%), and 280 (13.5%) patients failed initial EBP, lumbar drain, and surgery, respectively, and the overall failure rate was 10.9% (n=1397). The median 30-day total cost across all groups was $5,101. Patients who received lumbar drain ($22,341) and surgical repair ($30,199) had higher 30-day median total costs than EBP ($8,140) or conservative management ($17,012). The median 30-day total cost for patients whose EBP failed ($8,179) was substantially greater than those with a successful EBP repair ($3,439). CONCLUSIONS: National treatment patterns and costs for CSF leaks were described. When used in the correct patient cohort, EBP has the lower failure rates and costs than comparable alternatives. EBP may be considered more often in situations where conservative management or lumbar drains are currently being used.


Assuntos
Vazamento de Líquido Cefalorraquidiano , Doença Iatrogênica , Adulto , Humanos , Estados Unidos , Estudos Retrospectivos , Vazamento de Líquido Cefalorraquidiano/cirurgia , Atenção à Saúde , Aceitação pelo Paciente de Cuidados de Saúde , Resultado do Tratamento
8.
Neurosurgery ; 91(2): 272-279, 2022 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-35384918

RESUMO

BACKGROUND: Spinal cord stimulation (SCS) effectively reduces opioid usage in some patients, but preoperatively, there is no objective measure to predict who will most benefit. OBJECTIVE: To predict successful reduction or stabilization of opioid usage after SCS using machine learning models we developed and to assess if deep learning provides a significant benefit over logistic regression (LR). METHODS: We used the IBM MarketScan national databases to identify patients undergoing SCS from 2010 to 2015. Our models predict surgical success as defined by opioid dose stability or reduction 1 year after SCS. We incorporated 30 predictors, primarily regarding medication patterns and comorbidities. Two machine learning algorithms were applied: LR with recursive feature elimination and deep neural networks (DNNs). To compare model performances, we used nested 5-fold cross-validation to calculate area under the receiver operating characteristic curve (AUROC). RESULTS: The final cohort included 7022 patients, of whom 66.9% had successful surgery. Our 5-variable LR performed comparably with the full 30-variable version (AUROC difference <0.01). The DNN and 5-variable LR models demonstrated similar AUROCs of 0.740 (95% CI, 0.727-0.753) and 0.737 (95% CI, 0.728-0.746) ( P = .25), respectively. The simplified model can be accessed at SurgicalML.com . CONCLUSION: We present the first machine learning-based models for predicting reduction or stabilization of opioid usage after SCS. The DNN and 5-variable LR models demonstrated comparable performances, with the latter revealing significant associations with patients' pre-SCS pharmacologic patterns. This simplified, interpretable LR model may augment patient and surgeon decision making regarding SCS.


Assuntos
Estimulação da Medula Espinal , Analgésicos Opioides/uso terapêutico , Redução da Medicação , Humanos , Modelos Logísticos , Aprendizado de Máquina
9.
J Mov Disord ; 15(1): 21-32, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34814237

RESUMO

Parkinson's disease (PD) is a neurodegenerative disorder characterized by both motor and nonmotor symptoms. Although the basal ganglia is traditionally the primary brain region implicated in this disease process, this limited view ignores the roles of the cortex and cerebellum that are networked with the basal ganglia to support motor and cognitive functions. In particular, recent research has highlighted dysfunction in the supplementary motor complex (SMC) in patients with PD. Using the PubMed and Google Scholar search engines, we identified research articles using keywords pertaining to the involvement of the SMC in action sequencing impairments, temporal processing disturbances, and gait impairment in patients with PD. A review of abstracts and full-text articles was used to identify relevant articles. In this review of 63 articles, we focus on the role of the SMC in PD, highlighting anatomical and functional data to create new perspectives in understanding clinical symptoms and, potentially, new therapeutic targets. The SMC has a nuanced role in the pathophysiology of PD, with both hypo- and hyperactivation associated with various symptoms. Further studies using more standardized patient populations and functional tasks are needed to more clearly elucidate the role of this region in the pathophysiology and treatment of PD.

10.
J Clin Neurosci ; 94: 298-304, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34863454

RESUMO

Robotic navigation is a new and rapidly emerging niche within minimally invasive spine surgery. The robotic arms-race began in 2004 and has resulted in no less than four major robotic surgical adjuncts. Current Food and Drug Administration (FDA)-approved applications of robotic navigation are limited to pedicle screw instrumentation, but new indications and experimental applications are rapidly emerging. As with any new technology, robotic navigation must be vetted for clinical efficacy, efficiency, safety, and cost-effectiveness. Given the rapid advancements made on a yearly basis, it is important to make frequent and objective assessments of the available technology. Thus, the authors seek to provide the most up-to-date review of the history, currently available technology, learning curve, novel applications, and cost effectiveness of today's available robotic systems as it relates to spine surgery.


Assuntos
Parafusos Pediculares , Procedimentos Cirúrgicos Robóticos , Robótica , Humanos , Procedimentos Cirúrgicos Minimamente Invasivos , Coluna Vertebral/cirurgia
11.
Neurosurg Focus ; 50(6): E6, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34062497

RESUMO

OBJECTIVE: The use of osteobiologics, engineered materials designed to promote bone healing by enhancing bone growth, is becoming increasingly common for spinal fusion procedures, but the efficacy of some of these products is unclear. The authors performed a retrospective, multi-institutional study to investigate the clinical and radiographic characteristics of patients undergoing single-level anterior cervical discectomy with fusion performed using the osteobiologic agent Osteocel, an allograft mesenchymal stem cell matrix. METHODS: The medical records across 3 medical centers and 12 spine surgeons were retrospectively queried for patients undergoing single-level anterior cervical discectomy and fusion (ACDF) with the use of Osteocel. Pseudarthrosis was determined based on CT or radiographic imaging of the cervical spine. Patients were determined to have radiographic pseudarthrosis if they met any of the following criteria: 1) lack of bridging bone on CT obtained > 300 days postoperatively, 2) evidence of instrumentation failure, or 3) motion across the index level as seen on flexion-extension cervical spine radiographs. Univariate and multivariate analyses were then performed to identify independent preoperative or perioperative predictors of pseudarthrosis in this population. RESULTS: A total of 326 patients met the inclusion criteria; 43 (13.2%) patients met criteria for pseudarthrosis, of whom 15 (34.9%) underwent revision surgery. There were no significant differences between patients with and those without pseudarthrosis, respectively, for patient age (54.1 vs 53.8 years), sex (34.9% vs 47.4% male), race, prior cervical spine surgery (37.2% vs 33.6%), tobacco abuse (16.3% vs 14.5%), chronic kidney disease (2.3% vs 2.8%), and diabetes (18.6% vs 14.5%) (p > 0.05). Presence of osteopenia or osteoporosis (16.3% vs 3.5%) was associated with pseudarthrosis (p < 0.001). Implant type was also significantly associated with pseudarthrosis, with a 16.4% rate of pseudarthrosis for patients with polyetherethereketone (PEEK) implants versus 8.4% for patients with allograft implants (p = 0.04). Average lengths of follow-up were 27.6 and 23.8 months for patients with and those without pseudarthrosis, respectively. Multivariate analysis demonstrated osteopenia or osteoporosis (OR 4.97, 95% CI 1.51-16.4, p < 0.01) and usage of PEEK implant (OR 2.24, 95% CI 1.04-4.83, p = 0.04) as independent predictors of pseudarthrosis. CONCLUSIONS: In patients who underwent single-level ACDF, rates of pseudarthrosis associated with the use of the osteobiologic agent Osteocel are higher than the literature-reported rates associated with the use of alternative osteobiologics. This is especially true when Osteocel is combined with a PEEK implant.


Assuntos
Pseudoartrose , Fusão Vertebral , Aloenxertos , Matriz Óssea , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/cirurgia , Discotomia/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pseudoartrose/etiologia , Pseudoartrose/cirurgia , Estudos Retrospectivos , Fusão Vertebral/efeitos adversos , Resultado do Tratamento
12.
Otol Neurotol ; 41(3): e369-e377, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31923083

RESUMO

HYPOTHESIS: Intraoperative electrocochleography (ECochG) can differentiate hair cell and neural dysfunction caused by a vestibular schwannoma (VS) and help define the site of lesion as peripheral or central to the spiral ganglion. BACKGROUND: Hearing loss in patients with a VS can be caused by both sensory (cochlear) and neural dysfunction. METHODS: Round-window ECochG using low and high-frequency tone bursts was performed in 49 subjects with a VS. Responses were analyzed for magnitude, spectrum, and shape of the time waveform. Components examined included the cochlear microphonic, auditory nerve neurophonic, compound action potential (CAP), and summating potential (SP). RESULTS: Variability in the summed response magnitudes across frequency, or "total response" (ECochG-TR), varied from 0.1 to 100 µV. Responses were larger for lower frequencies. Subjective estimates revealed a wide range of neural contributions from the auditory nerve neurophonic to low frequencies and the CAP to high frequencies. Cases with larger CAPs had smaller SPs. The correlation of ECochG-TR, with word recognition score (WRS), was moderate (r = 0.67), as well as the correlation between pure-tone averages and ECochG (r = 0.63). The cochlea remained functional in two cases of sudden sensorineural hearing loss with 0% WRS. CONCLUSION: Reduced ECochG-TR and neural activity in many cases indicates both sensory and neural deficits. Smaller SPs when CAPs are present indicate a neural contribution to the SP. Good cochlear function with 0% WRS, and cases of sudden sensorineural hearing loss with retained cochlear function, indicate retrocochlear effects, typically proximal to the spiral ganglion cells.


Assuntos
Audiometria de Resposta Evocada , Neuroma Acústico , Cóclea , Nervo Coclear , Humanos , Neuroma Acústico/cirurgia , Janela da Cóclea
13.
J Control Release ; 278: 37-48, 2018 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-29604311

RESUMO

Retinol, a derivative of vitamin A, is a ubiquitous compound used to treat acne, reduce wrinkles and protect against conditions like psoriasis and ichthyosis. While retinol is used as the primary active ingredient (AI) in many skin care formulations, its efficacy is often limited by an extreme sensitivity to degrade and toxicity at high concentrations. While microencapsulation is an appealing method to help overcome these issues, few microencapsulation strategies have made a major translational impact due to challenges with complexity, cost, limited protection of the AI and poor control of the release of the AI. We have developed a class of silicone particles that addresses these challenges for the encapsulation, protection and controlled release of retinol and other hydrophobic compounds. The particles are prepared by the sol-gel polymerization of silane monomers, which enables their rapid and facile synthesis at scale while maintaining a narrow size distribution (i.e., CV < 20%). We show that our particles can: (i) encapsulate retinol with high efficiency (>85%), (ii) protect retinol from degradation (yielding a half-life 9× greater than unencapsulated retinol) and (iii) slowly release retinol over several hours (at rates from 0.14 to 0.67 µg cm-2 s-1/2). To demonstrate that the controlled release of retinol from the particles can reduce irritation, we performed a double blind study on human subjects and found that formulations containing our particles were 12-23% less irritating than identical formulations containing Microsponge® particles (an industry standard by Amcol, Inc.). To show that the silicone particles can elicit a favorable biological response, similar to the Microsponge® particles, we applied both formulations to reconstructed human epidermal tissues and found an upregulation of keratin 19 (K19) and a downregulation of K10, indicating that the reduced irritation observed in the human study was not caused by reduced activity. We also found a decrease in the production of interleukin-1α (IL-1α) compared to formulations containing the Microsponge particles, suggesting lower irritation levels and supporting the findings from the human study. Finally, we show that the silicone particles can encapsulate other AIs, including betamethasone, N, N-diethyl-meta-toluamide (DEET), homosalate and ingenol mebutate, establishing these particles as a true platform technology.


Assuntos
Fármacos Dermatológicos/administração & dosagem , Sistemas de Liberação de Medicamentos , Silicones/química , Vitamina A/administração & dosagem , Administração Cutânea , Química Farmacêutica/métodos , Preparações de Ação Retardada , Fármacos Dermatológicos/efeitos adversos , Fármacos Dermatológicos/química , Método Duplo-Cego , Regulação para Baixo/efeitos dos fármacos , Portadores de Fármacos/química , Composição de Medicamentos/métodos , Feminino , Humanos , Queratina-10/genética , Queratina-19/genética , Masculino , Pele/metabolismo , Testes de Irritação da Pele/métodos , Regulação para Cima/efeitos dos fármacos , Vitamina A/efeitos adversos , Vitamina A/química
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