Hydrogel-Forming Microneedles with Applications in Oral Diseases Management.

Controlled drug delivery in the oral cavity poses challenges such as bacterial contamination, saliva dilution, and inactivation by salivary enzymes upon ingestion. Microneedles offer a location-specific, minimally invasive, and retentive approach. Hydrogel-forming microneedles (HFMs) have emerged for dental diagnostics and therapeutics. HFMs penetrate the stratum corneum, undergo swelling upon contact, secure attachment, and enable sustained transdermal or transmucosal drug delivery. Commonly employed polymers such as polyvinyl alcohol (PVA) and polyvinyl pyrrolidone are crosslinked with tartaric acid or its derivatives while incorporating therapeutic agents. Microneedle patches provide suture-free and painless drug delivery to keratinized or non-keratinized mucosa, facilitating site-specific treatment and patient compliance. This review comprehensively discusses HFMs' applications in dentistry such as local anesthesia, oral ulcer management, periodontal treatment, etc., encompassing animal experiments, clinical trials, and their fundamental impact and limitations, for example, restricted drug carrying capacity and, until now, a low number of dental clinical trial reports. The review explores the advantages and future perspectives of HFMs for oral drug delivery.

Effects of the epiretinal membrane on the outcomes of intravitreal dexamethasone implantation for macular edema secondary to branch retinal vein occlusion / Os efeitos de uma membrana epirretiniana nos resultados da implantação de dexametasona intravítrea para edema macular secundário à oclusão de ramo da veia retiniana

ABSTRACT Purpose: To investigate the effects of epiretinal membrane formation on the clinical outcomes of intravitreal dexamethasone implantation for macular edema secondary to branch retinal vein occlusion. Methods: This retrospective interventional case series includes the treatment of naive patients with macular edema secondary to non-ischemic branch retinal vein occlusion who underwent intravitreal dexamethasone implantation. The patients were divided into two groups as follows: Group 1 (n=25), comprised of patients with macular edema secondary to branch retinal vein occlusion without epiretinal membrane, and Group 2 (n=16), comprised of patients with macular edema secondary to branch retinal vein occlusion with an epiretinal membrane. Corrected visual acuity, central macular thickness, and central macular volume values were measured before and after treatment. The clinical outcomes of the groups were compared. Results: Mean age and male-to-female ratio were similar between the two groups (p>0.05, for both). The baseline and final corrected visual acuity values, central macular thickness, and central macular volumes of the groups were similar (p>0.05, for all). All the parameters were significantly improved after intravitreal dexamethasone implantation treatment (p<0.001, for all). The changes in central macular thickness and volume were also similar (p>0.05, for both). The mean number of intravitreal dexamethasone implantations was 2.1 ± 1.0 (range, 1-4) in Group 1 and 3.0 ± 1.2 (range, 1-5) in Group 2 (p=0.043). Conclusion: Epiretinal membrane formation had no effects on the baseline and final clinical parameters, including corrected visual acuity and central macular thickness and volume. The only parameter affected by the presence of epiretinal membrane formation is the number of intravitreal dexamethasone implantations, a greater number of which is needed for macular edema secondary to branch retinal vein occlusion with an epiretinal membrane.

RESUMO Objetivo: Investigar os efeitos da formação de uma membrana epirretiniana nos resultados clínicos da implantação intravítrea de dexametasona para edema macular secundário à oclusão de um ramo da veia retiniana. Métodos: Esta série retrospectiva de casos intervencionais inclui o tratamento de indivíduos com edema macular secundário à oclusão não isquêmica de um ramo da veia retiniana, sem tratamento prévio e que foram submetidos a implantação intravítrea de dexametasona. Os indivíduos foram divididos em dois grupos: Grupo 1 (n=25), composto por indivíduos com edema macular secundário à oclusão de um ramo da veia retiniana sem a presença de uma membrana epirretiniana, e Grupo 2 (n=16), composto por indivíduos com edema macular secundário à oclusão de um ramo da veia retiniana com a presença de uma membrana epirretiniana. Os valores da acuidade visual corrigida, espessura macular central e volume macular central foram obtidos antes e após o tratamento. Os resultados clínicos dos grupos foram comparados. Resultados: A média de idade e a proporção entre homens e mulheres foram semelhantes nos dois grupos (p>0,05 para ambos os valores). Os valores iniciais e finais da acuidade visual corrigida, espessura macular central e volume macular central foram semelhantes nos dois grupos (p>0,05 para todos os valores). Todos os parâmetros melhoraram significativamente após o tratamento com implante de dexametasona intravítrea (p<0,001 para todos os parâmetros) e as alterações na espessura macular central e no volume macular central também foram semelhantes (p>0,05 para ambos os valores). O número médio de implantações intravítreas de dexametasona foi 2,1 ± 1,0 (faixa de 1-4) no Grupo 1 e 3,0 ± 1,2 (faixa de 1-5) no Grupo 2 (p=0,043). Conclusão: A formação de uma membrana epirretiniana não tem efeitos sobre os parâmetros clínicos iniciais e finais, incluindo a acuidade visual corrigida, a espessura macular central e o volume macular central. O único parâmetro afetado pela formação de uma membrana epirretiniana é o número de implantações intravítreas de dexametasona, sendo necessário um número maior de implantações em casos de edema macular secundário à oclusão de um ramo da veia retiniana com a presença de uma membrana epirretiniana.

Anesthetic considerations in patients with implantable devices and chronic pain surgery / Consideraciones anestésicas en pacientes con dispositivos implantables y para cirugía de dolor crónico

Abstract The use of advanced invasive techniques for the control of chronic pain in patients with multiple comorbidities is becoming increasingly common. Neuromodulation offers a new management alternative involving the infusion of one or more drugs into the epidural or intrathecal space through a fully implantable infusion pump. It also involves spinal stimulation, a minimally invasive technique in which electrodes are positioned in the epidural space and connected to a pulse generator that is implanted subcutaneously and generates pulses designed to suppress the noxious stimulus. This article will describe the anesthetic considerations in cases of implantable drug delivery systems, and spinal and peripheral nerve stimulation devices. Additionally, patients with electrical or drug neuromodulation devices may present to anesthetic practice for surgical indications unrelated to their chronic pain pathology. Hence the importance of being familiar with the basic components of these devices, how they work, what drugs they use and the potential associated complications in the perioperative context, in order to ensure proper management and patient safety.

Resumen Cada vez es más común el empleo de técnicas invasivas avanzadas para el control del dolor crónico en paciente con múltiples comorbilidades. La neuro-modulación ofrece una nueva alternativa de manejo, que involucra la infusión de uno o más medicamentos en el espacio epidural o intratecal a través de una bomba de infusión totalmente implantable. También incluye la estimulación espinal, una técnica mínimamente invasiva que consiste en el posicionamiento de electrodos en el espacio epidural, conectados a un generador de pulso que se implanta subcutáneo y genera pulsos que buscan suprimir el estímulo nocivo. En este artículo se hará la descripción de las consideraciones anestésicas que se deben tener con sistemas de liberación de medicamentos implantables, dispositivos de estimulación medular y de nervio periférico. Adicionalmente, pueden aparecer pacientes portadores de dispositivos de neuromodulación eléctrica o medicamentosa que deben recibir anestesia para someterse a cirugía por razones diferentes a su patología de dolor crónico y deben conocerse sus implicaciones anestésicas. Por lo anterior, es importante conocer y estar familiarizados con los componentes básicos de dichos dispositivos: funcionamiento, medicamentos que utilizan y las potenciales complicaciones que se puedan tener con estos en el contexto perioperatorio, para garantizar un manejo adecuado y la seguridad del paciente.

Comparative Efficacy and Safety of Advanced Intravitreal Therapeutic Agents for Noninfectious Uveitis: A Systematic Review and Network Meta-Analysis.

Background: To compare the efficacy and safety of advanced intravitreal therapeutic regimens, including a dexamethasone implant at 350 and 700 µg; a fluocinolone acetonide (FA) implant, 0.2 µg/day, 0.59 and 2.1 mg; intravitreal bevacizumab, 1.25 mg; intravitreal ranibizumab, 0.5 mg; intravitreal triamcinolone acetonide (IVTA), 2 and 4 mg; and standard of care (SOC, systemic therapy) for noninfectious uveitis. Methods: We searched the Cochrane Library database, EMBASE, Medline, clinicaltrials.gov until April 2021 with 13 RCTs (1806 participants) identified and conducted a pairwise and Bayesian network meta-analysis with random effects. Results: No specific regimen showed a statistically significant advantage or disadvantage to another treatment regimen with regard to efficacy. However, the FA implant, 0.59 mg was associated with a higher risk of cataract (RR 4.41, 95% CI 1.51-13.13) and raise in intraocular pressure (IOP) (RR 2.53 95% CI 1.14-6.25) compared with SOC at 24 months. IVTA, 4 mg at 6 months was associated with lower risk of IOP rising compared with FA implant, 0.2 µg/day at 36 months (RR 3.43 95% CI 1.12-11.35). Conclusion: No intravitreal therapeutic regimens showed a significant advantage or disadvantage with regard to efficacy. However, SOC was associated with lower risk of side effects compared with FA implants. IVTA, 4 mg, might be the best choice with lowest risk of IOP rising. Systematic Review Registration: clinicaltrials.gov, identifier CRD42020172953.

Comparison of the efficacy of conbercept and intravitreal dexamethasone implant Ozurdex in the treatment of diabetic macular edema / 中华实验眼科杂志

Objective:To compare the efficacy and safety of intravitreal injection of anti-vascular endothelial growth factor drug conbercept and intravitreal dexamethasone implant Ozurdex in the treatment of diabetic macular edema (DME).Methods:A randomized controlled clinical study was performed.Thirty-six DME patients (36 eyes) were enrolled in Weifang Eye Hospital from March 2018 to June 2019.The patients were randomized into Ozurdex group and conbercept group via a random number table, with 18 eyes in each group.Patients received Ozurdex injection once, which was maintained for 6 months, or conbercept injection once a month for 3 times according to grouping.Before and after treatment, the best corrected visual acuity (BCVA) was examined with the International Standard Visual acuity chart and converted to logarithm of minimal angle resolution unit.The intraocular pressure (IOP) was measured using a non-contact tonometer.The central retinal thickness (CRT) was detected by optical coherence tomography (OCT).This study followed the Declaration of Helsinki and was approved by the Ethics Committee of Weifang Eye Hospital.Results:All patients were followed up for 6 months.In Ozurdex group, the BCVA pre-injection and at 1 month, 3, 4, 6 months after the first injection was 0.59±0.22, 0.53±0.20, 0.41±0.16, 0.38±0.19 and 0.56±0.19, respectively.The BCVA at 1 month, 3 and 4 months after the first injection were better than that before injection, and the differences were statistically significant (all at P<0.05).In conbercept group, the BCVA pre-injection and at 1 month, 3, 4, 6 months after the first injection were 0.60±0.23, 0.51±0.17, 0.29±0.13, 0.56±0.18 and 0.60±0.18, respectively.The BCVA at 1 month and 3 months after the first injection were better than that before injection, showing statistically significant differences (all at P<0.05).The CRT at 1 month, 3 and 4 months after the first injection were significantly lower than that before treatment in both the two groups (all at P<0.05).The CRT pre-injection was (498.61±77.14)μm in Ozurdex group, which was significantly higher than (462.17±48.74)μm at 6 months after the first injection ( P<0.05).No significant difference in CRT was found between pre-injection and 6 months after the first injection in conbercept group ( P>0.05).The incidence of high IOP in Ozurdex group was 33.3%(6/18), which was higher than 5.56%(1/18) in conbercept group, with a significant difference ( χ2=4.433, P=0.035).No adverse effects such as aggravation of cataract, lens injury, endophthalmitis, vitreous hemorrhage and retinal detachment was found during the follow-up. Conclusions:For DME, both conbercept and Ozurdex can improve BCVA and reduce CRT.Ozurdex shows durable efficacy and needs fewer injections than conbercept, but conbercept has less effect on IOP and is safer than Ozurdex.

Drug Release Kinetics from Nondegradable Hydrophobic Polymers Can Be Modulated and Predicted by the Glass Transition Temperature.

Controlling drug release kinetics within a desired therapeutic window is the central task when designing polymeric drug delivery systems. Complex polymer chemistries have often been explored to control water penetration, polymer degradation rate, or the mesh network size of delivery systems. Here, a simple parameter for controlling the release rate and duration of nondegradable hydrophobic polymers is discovered. A systematic study involving 59 polymers and multiple drugs demonstrates that the glass transition temperature, Tg , is a critical factor that dictates drug release kinetics from nondegradable hydrophobic polymers. Drug release rate exhibits a unique and simple linear correlation of (T - Tg )0.5 despite variability of polymer structure and type. An empirical model established based on the special correlation can accurately simulate and predict drug release kinetics from polymers saving substantial time typically required to test long-acting drug delivery systems.

Unintentional injection of a dexamethasone implant into the crystalline lens: a case report / Injeção não intencional de implante de dexametasona no cristalino: relato de caso, acompanhamento e desfecho

ABSTRACT The intravitreal dexamethasone implant is a sustained-release anti-inflammatory drug system that releases 0.7 mg of dexamethasone into the vitreous cavity. The following case report describes a rare complication: accidental injection of the dexamethasone implant into the crystalline lens. A 73-year-old woman was diagnosed with central retina vein occlusion and cystoid macular edema. Initial tSreatment included three monthly intravitreal doses of anti-vascular endothelial growth factor treatment, which was not successful. Treatment was then modified to an intravitreal dexamethasone implant. Ten weeks later, the implant was observed in the posterior cortex of the crystalline lens. Because no improvement had occurred, the patient underwent phacoemulsification surgery, during which part of the lens migrated into the vitreous cavity. Therefore, 23-gauge pars plana complete vitrectomy was performed with trans-surgical administration of intravitreal aflibercept. Crystalline lens injury due to an intravitreal dexamethasone implant is a rare complication and typically results from the injection procedure. Immediate surgical or conservative approaches should be considered on an individual basis.

RESUMO O implante intravítreo de dexametasona é um sistema anti-inflamatório de liberação sustentada que libera 0,7 mg de dexametasona na cavidade vítrea. O relato de caso a seguir descreve uma complicação rara: injeção acidental do implante de Dexametasona no cristalino. Uma mulher de 73 anos foi diagnosticada com oclusão da veia central da retina e edema macular cistóide. O tratamento inicial incluiu três doses intravítreas mensais de tratamento com fator de crescimento endothelial anti-vascular, que não tiveram sucesso. O tratamento foi então mudado para um implante intravítreo de dexametasona. Dez semanas depois, o implante foi observado no córtex posterior do cristalino. Como não houve melhora, a paciente foi submetida à cirurgia de facoemulsificação, durante a qual parte do cristalino migrou para a cavidade vítrea. Portanto, foi realizada vitrectomia completa via pars plana 23-gauge com administração de aflibercepte intravítreo durante a cirurgia. Lesões no cristalino devido a implantes intravítreos de dexametasona são uma complicação rara e geralmente resulta do procedimento de injeção. Abordagens cirúrgicas ou conservadoras imediatas devem ser consideradas caso a caso.

Dexamethasone intravitreal implant in the crystalline lens: a case report / Implante intravítreo de dexametasona nas lentes do cristalino: um relato de caso

ABSTRACT This report describes the therapeutic effects and outcomes of an accidental injection of an intralenticular sustained-release dexamethasone implant (Ozurdex®) in three patients with diabetic macular edema. All three patients underwent accidental injections of sustained-release intravitreal dexamethasone implants into the crystalline lens by the same surgeon. After the accidental injection of Ozurdex® into the crystalline lens, a remarkable reduction in the macular edema and an improvement in visual acuity were observed, suggesting that a positive outcome can be achieved without immediate surgery.

RESUMO Este estudo descreve os efeitos terapêuticos e os resultados de uma injeção acidental de implante intralenticular de dexametasona de liberação sustentada (Ozurdex®) em três pacientes com edema macular diabético. Todos os três pacientes foram submetidos a injeções acidentais de implantes intravítreos de dexametasona de liberação sustentada na lente do cristalino pelo mesmo cirurgião. Após a injeção acidental de Ozurdex® na lente do cristalino, observou-se uma redução notável no edema macular e uma melhora na acuidade visual, sugerindo que um resultado positivo pode ser alcançado sem cirurgia imediata.

Optical biometry-based axial length alterations after intravitreal dexamethasone implant / Alterações do comprimento axial com base na biometria óptica após o implante de dexametasona intravítrea

ABSTRACT Purpose: To investigate changes in axial length after intravitreal dexamethasone implantation in patients with macular edema. Methods: We performed a prospective comparative study of 46 patients with unilateral macular edema, due to diabetic retinopathy, retinal vein occlusion, and non-infectious uveitis, who underwent dexamethasone implantation. The fellow eyes of the patients were considered the control group. The central macular thickness was measured by spectral-domain optical coherence tomography, and axial length was measured by IOLMaster 700 optical coherence biometry. We compared axial length and central macular thickness values within the groups. Results: In the study group, the baseline central macular thickness was 460.19 ± 128.64 mm, significantly decreasing to 324.00 ± 79.84 mm after dexamethasone implantation (p=0.000). No significant change in central macular thickness measurements was seen in the control group (p=0.244). In the study group, the baseline axial length was 23.16 ± 0.68 mm, significantly increasing to 23.22 ± 0.65 mm after dexamethasone implantation (p=0.039). However, the control group exhibited no significant change in axial length (p=0.123). Conclusions: In addition to significantly reducing central macular thickness measurements, intravitreal dexamethasone implantation also significantly changes optical biometry-based axial length measurements.

RESUMO Objetivo: Investigar alterações no comprimento axial após implante de dexametasona intravítrea em pacientes com edema macular. Métodos: Foi realizado um estudo prospectivo e comparativo de 46 pacientes com edema macular unilateral, devido à retinopatia diabética, oclusão da veia retiniana e uveíte não infecciosa, que foram submetidos ao implante de dexametasona. Os olhos contralateral de cada paciente foram considerados o grupo controle. A espessura macular central foi medida por tomografia de coerência óptica de domínio espectral, e o comprimento axial foi medido por meio de biometria de coerência óptica de domínio espectral e o comprimento axial foi medido pela biometria de coerência óptica com IOLMaster 700. Comparamos o comprimento axial e os valores da espessura macular central dentro dos grupos. Resultados: No grupo de estudo, a espessura macular basal foi de 460,19 ± 128,64 mm, diminuindo significativamente para 324,00 ± 79,84 mm após o implante de dexametasona (p=0,000). Nenhuma mudança significativa nas medidas da espessura macular central foi observada no grupo controle (p=0,244). No grupo de estudo, o comprimento axial basal foi de 23,16 ± 0,68 mm, aumentando significativamente para 23,22 ± 0,65 mm após o implante de dexametasona (p=0,039). No entanto, o grupo controle não apresentou alteração significativa no comprimento axial (p=0,123). Conclusões: Além de reduzir significativamente as medidas da espessura macular central, o implante de dexametasona intravítrea também altera significativamente as medidas de comprimento axial baseadas na biometria óptica.

[Analysis of the Cochrane Review: Cortisteroid Implants for Chronic Non-Infectious Uveitis. Cochrane Database Syst Rev. 2016;2:CD010469]. / Análise da Revisão Cochrane: Implantes de Corticóides na Uveíte Não-Infecciosa Crónica. Cochrane Database Syst Rev. 2016;2:CD010469.

Non-infectious uveitis is a heterogeneous collection of inflammatory eye diseases and is one of the most important causes of blindness among active adults in developed countries. Inflammation control is crucial in the prevention of ocular structural and functional damage. Regarding acute inflammatory control, corticosteroids are the mainstay of treatment. Several types of intra-ocular corticosteroids have been used with the aim of enhanced efficacy compared to their topical or peri-ocular administration, while minimizing its adverse effects associated with the systemic administration. The purpose of this Cochrane review was to synthetize the available evidence regarding the efficacy and safety of corticosteroid implants in comparison with standard treatment. Due to the heterogeneity in the design of the studies and outcome measures assessed, authors could not conclude that implants are superior to traditional systemic therapy in Non-infectious uveitis. The safety analysis suggested increased risks of post-implant surgery for cataract and high intraocular pressure compared with standard-of-care therapy.

A uveíte não infecciosa inclui várias patologias com elevada morbilidade, sendo uma das causas mais importantes de cegueira na população activa de países desenvolvidos. O controlo da inflamação é essencial na prevenção do dano estrutural e funcional às estruturas oculares. Sendo os corticóides fármacos de primeira linha no controlo agudo da inflamação, têm sido usadas formulações intra-oculares destes fármacos, com o objectivo de aumentar a eficácia face ao uso tópico ou periocular e de induzir menos efeitos adversos secundários comparativamente ao uso sistémico. O objectivo desta revisão Cochrane foi sintetizar a evidência existente sobre a eficácia e segurança de implantes de corticóides intravítreos, em comparação com a terapêutica convencional. Devido à heterogeneidade no desenho e medidas de eficácia utilizadas, os autores não conseguiram demonstrar superioridade dos implantes intravítreos de corticóides em comparação com a terapêutica convencional, na uveíte não infecciosa. A análise de segurança sugere que estes possam aumentar a probabilidade de necessidade de cirurgia de catarata e de elevação da pressão intraocular, em comparação com a terapêutica standard.

Safety, Quality, and Acceptability of Contraceptive Subdermal Implant Provision by Community Health Extension Workers Versus Nurses and Midwives in Nigeria: Protocol for a Quasi-Experimental, Noninferiority Study.

BACKGROUND: As part of its Family Planning 2020 commitment, the Nigerian government is aiming for a contraceptive prevalence rate of 36% by 2018, and in 2014, approved a policy to allow community health extension workers (CHEWs), in addition to doctors, nurses, and midwives, to provide contraceptive subdermal implants. There is a lack of rigorous evidence on the safety of long-acting reversible contraceptive provision, such as implants, among lower cadres of health providers. OBJECTIVE: This study aimed to compare implant provision by CHEWs versus nurses and midwives up to 14 days post insertion. METHODS: The quasi-experimental, noninferiority study will take place in public sector facilities in Kaduna and Ondo States. In each state, we will select 60 facilities, and from these, we will select a total of 30 nurses and midwives and 30 CHEWs to participate. Selected providers will be trained to provide implant services. Once trained, providers will recruit a minimum of 8125 women aged between 18 and 49 years who request and are eligible for an implant, following comprehensive family planning counseling. During implant insertion, providers will record data about the process and any adverse events, and 14 days post insertion, providers will ask 4410 clients about adverse events arising from the implant. Supervisors will observe 792 implant insertions to assess service provision quality and ask clients about their satisfaction with the procedure. We will conclude noninferiority if the CI for the difference in the proportion of adverse events between CHEWs and nurses and midwives on the day of insertion or 14 days post insertion lies to the right of -2%. RESULTS: In September and October 2015, we trained 60 CHEWs and a total of 60 nurses and midwives from 12 local government areas (LGAs) in Kaduna and 23 LGAs in Ondo. Recruitment took place between November 2015 and December 2016. Data analysis is being finalized, and results are expected in March 2018. CONCLUSIONS: The strength of this study is having a standard care (nurse and midwife provision) group with which CHEW provision can be compared. The intervention builds on existing training and supervision procedures, which increases the sustainability and scalability of CHEW implant provision. Important limitations include the lack of randomization due to nurses and midwives in Nigeria working in separate types of health care facilities compared with CHEWs, and that providers self-assess their own practices. It is unfeasible to observe all procedures independently, and observation may change practice. Although providers will be trained to conduct implant removals, the study time will be too short to reach the sample size required to make noninferiority comparisons for removals. TRIAL REGISTRATION: ClinicalTrials.gov NCT03088722; https://clinicaltrials.gov/ct2/show/NCT03088722 (Archived by WebCite at http://www.webcitation.org/6xIHImWvu).

Advances in the delivery of buprenorphine for opioid dependence.

Opioid use disorders (OUDs) have long been a global problem, but the prevalence rates have increased over 20 years to epidemic proportions in the US, with concomitant increases in morbidity and all-cause mortality, but especially opioid overdose. These increases are in part attributable to a several-fold expansion in the prescription of opioid pain medications over the same time period. Opioid detoxification and psychosocial treatments alone have each not yielded sufficient efficacy for OUD, but µ-opioid receptor agonist, partial agonist, and antagonist medications have demonstrated the greatest overall benefit in OUD treatment. Buprenorphine, a µ-opioid receptor partial agonist, has been used successfully on an international basis for several decades in sublingual tablet and film preparations for the treatment of OUD, but the nature of formulation, which is typically self-administered, renders it susceptible to nonadherence, diversion, and accidental exposure. This article reviews the clinical trial data for novel buprenorphine delivery systems in the form of subcutaneous depot injections, transdermal patches, and subdermal implants for the treatment of OUD and discusses both the clinical efficacy of longer-acting formulations through increasing consistent medication exposure and their potential utility in reducing diversion. These new delivery systems also offer new dosing opportunities for buprenorphine and strategies for dosing intervals in the treatment of OUD.

Migration of contraceptive implant into the left pulmonary arterial system.

An 18-year-old woman had an etonogestrel implant inserted into her left upper arm 2 years earlier for menorrhagia. Her symptoms were not well controlled and she requested the implant to be removed. However, clinicians were unable to locate the implant on her left arm. Computed tomography showed that the implant had migrated to a sub-lobar branch of the left lower lobe pulmonary artery. The long-term effect of leaving an etonogestrel implant in the pulmonary arterial system is unknown. This report adds to the small body of evidence on intravascular migration of a subdermally placed contraceptive implant.

Bio-absorbable antibiotic impregnated beads for the treatment of prosthetic vascular graft infections.

OBJECTIVE: There is limited investigation into the use of bio-absorbable antibiotic beads for the treatment of prosthetic vascular graft infections. Our goal was to investigate the rates of infection eradication, graft preservation, and limb salvage in patients who are not candidates for graft explant or extensive reconstruction. METHODS: A retrospective review of patients implanted with antibiotic impregnated bio-absorbable calcium sulfate beads at a major university center was conducted. RESULTS: Six patients with prosthetic graft infections were treated with bio-absorbable antibiotics beads from 2012-2014. Grafts included an aortobifemoral, an aorto-hepatic/superior mesenteric artery, and four extra-anatomic bypasses. Pathogens included Gram-positive and Gram-negative bacteria. Half of the patients underwent graft explant with reconstruction and half debridement of the original graft, all with antibiotic bead placement around the graft. Mean follow-up was 7.3 ± 8.3 months; all patients had infection resolution, healed wounds, and 100% graft patency, limb salvage, and survival. CONCLUSION: This report details the successful use of bio-absorbable antibiotic beads for the treatment prosthetic vascular graft infections in patients at high risk for graft explant or major vascular reconstruction. At early follow-up, we demonstrate successful infection suppression, graft preservation, and limb salvage with the use of these beads in a subset of vascular patients.

The role of Gliadel wafers in the treatment of newly diagnosed GBM: a meta-analysis.

BACKGROUND: Standard treatment for high-grade glioma (HGG) includes surgery followed by radiotherapy and/or chemotherapy. Insertion of carmustine wafers into the resection cavity as a treatment for malignant glioma is currently a controversial topic among neurosurgeons. Our meta-analysis focused on whether carmustine wafer treatment could significantly benefit the survival of patients with newly diagnosed glioblastoma multiforme (GBM). METHOD: We searched the PubMed and Web of Science databases without any restrictions on language using the keywords "Gliadel wafers", "carmustine wafers", "BCNU wafers", or "interstitial chemotherapy" in newly diagnosed GBM for the period from January 1990 to March 2015. Randomized controlled trials (RCTs) and cohort studies/clinical trials that compared treatments designed with and without carmustine wafers and which reported overall survival or hazard ratio (HR) or survival curves were included in this study. Moreover, the statistical analysis was conducted by the STATA 12.0 software. RESULTS: Six studies including two RCTs and four cohort studies, enrolling a total of 513 patients (223 with and 290 without carmustine wafers), matched the selection criteria. Carmustine wafers showed a strong advantage when pooling all the included studies (HR = 0.63, 95% confidence interval (CI) = 0.49-0.81; P = 0.019). However, the two RCTs did not show a statistical increase in survival in the group with carmustine wafer compared to the group without it (HR = 0.51, 95% CI = 0.18-1.41; P = 0.426), while the cohort studies demonstrated a significant survival increase (HR = 0.59, 95% CI = 0.44-0.79; P < 0.0001). CONCLUSION: Carmustine-impregnated wafers play a significant role in improving survival when used for patients with newly diagnosed GBM. More studies should be designed for newly diagnosed GBM in the future.

Prevenção de gestações não planejadas com implante subdérmico em mulheres da Cracolândia, São Paulo / Preventing unplanned pregnancies with subdermal etonogestrel implant in woman living in Cracolândia, São Paulo

Introdução: As drogas ilícitas promovem danos sociais e à saúde. Muitas mulheres que consomem drogas estão em situação de rua, trocam sexo para sua compra e não fazem contracepção adequada. Entre essas mulheres vulneráveis há aumento no risco de doenças sexualmente transmissíveis (DST) e de gestações não planejadas, com consequente aumento de abortos e partos prematuros, além de efeitos sobre o recém-nascido que, na sua maioria, tem como destino viver com parentes ou esperar por adoção em abrigos. A busca pela redução desses danos deve passar pela promoção de ações para uma maior integração social e de prevenção de gestações não planejadas por meio do implante de etonogestrel. Objetivo: Usar o implante subdérmico de etonogestrel para a prevenção de gestação não planejada entre mulheres usuárias de drogas ilícitas e de redução de danos.Método: Foram inseridos 106 implantes de etonogestrel em mulheres da Cracolândia, região central da cidade de São Paulo, onde foram colhidas informações na anamnese geral e específica em 101 usuárias de drogas ilícitas. Nessas foram feitos exames em 54 para diagnóstico de DST e de câncer de colo do útero.Resultado: Entre as mulheres usuárias de drogas que fizeram a inserção do implante 41,6%usam o crack como droga de preferência e 48,5% fazem associação com álcool e 85,2% como tabaco. Em relação à contracepção 36,7% das mulheres não usam qualquer método contraceptivo.Houve aumento na morbidade gestacional, 16,1% delas tiveram aborto e 20,6%filhos prematuros.Conclusão: O implante subdérmico de etonogestrel é indicação precisa para a prevenção de gravidez não planejada entre mulheres usuárias de drogas, reduz o risco de morbidade gestacional e neonatal, além de promover redução no dano social.

Introduction: Illicit drugs promote social and health harm. Many female illicit drug users live on the streets, exchanging sex to buy drugs leaving aside proper contraception methods. This situation facilitates the occurrence of sexually transmitted diseases (STD) and unplanned pregnancies among these women in such vulnerable conditions, causing an increase in abortion and premature birth as well as direct effects on the newborn, which often are abandoned or forced to live with relatives. The efforts to reduce such damages must involve the realization of activities that stimulate greater social inclusion, and prevent unplanned pregnancies through the etonogestrel implant. Objective: Use the subdermal etonogestrel implant to prevent unplanned pregnancy among female illicit drug users as a mean of social inclusion and social damage control. Method: The project applied 106 etonogestrel implants in women living in Cracolândia, central region of São Paulo, where information regarding general and specific history of 101 female drug users was collected. Also, from these 101 users, exams were performed in 54 women in order to diagnose STD and uterine cervix cancer. Result: Among the 106 women who had implant insertion, 41.6% use crack as main drug, in which 48.5% associate the drug with alcohol and 85.2% with tobacco. Regarding contraception methods, 36.7% do not use any kind of contraceptive method. As for pregnancy conditions, an increase in gestational morbidity was stated, where 16.1% had abortion and20.6% had premature deliveries. Conclusion: The etonogestrel subdermal implant is a precise indication to prevent unplanned pregnancy among female drug users, because it reduces the risk of gestational and neonatal morbidity, promoting also a reduction in social damage.

Effects of Intra-Abdominal Implantation of Sustained-Releasing Fluorouracil on Expressions of Survivin, Caspase-3 and CD44V6 in Patients with Colorectal Cancer / 天津医药

Objectives To observe the pre and post-operational changes of the expressions of survivin, caspase-3 and CD44V6 in patients with colorectal cancer after intra-abdominal implantation of sustained releasing fluorouracil. Meth-ods Sixty-four patients with colorectal cancer (Dukes’stage of B and C) were divided into treatment group and control group, 32 patients in each group. The standard radical surgery was performed in two groups of patients. The fluorouracil im-plants were implanted intra-abdominally in treatment group. The peripheral blood levels of surviving and caspase-3 were de-tected by RT-PCR. The level of CD44V6 was detected by flow cytometry in two groups of patients. Results There were no significant differences in levels of survivin, caspase-3 and CD44V6 before surgery between two groups (P>0.05). The level of survivin (0.362 ± 0.183) was significantly lower at 14 days after operation in treatment group than that of control group (0.585±0.207), but the level of caspase-3 (2.001±0.146) was significantly higher than that of control group (1.654±0.111). The levels of CD44V6 were significantly lower in treatment group (1.857±0.535) and control group (3.471±0.496) after opera-tion than those before operation (9.557±1.170 and 9.729±0.943, P＜0.05), and the level of CD44V6 was significantly lower in treatment group than that of control group (P＜0.05). Conclusion The implant for the sustained release of fluorouracil showed a positive impact on micrometastases and prognosis of colorectal cancer, while improved the long-term efficacy of postoperative colorectal cancer.

Implante intravítreo de liberação crônica de dexametasona (Ozurdex®) para o tratamento de edema macular por retinose pigmentar: relato de caso / Intravitreal implantation of Ozurdex® chronic delivery system for management of macular edema related to retinitis pigmentosa: case report

Retinose pigmentar indica um grupo heterogêneo de doenças genéticas oculares raras em que tanto bastonetes quanto cones estão danificados, levando a um prognóstico ruim com eventual perda da visão. Descrevemos o caso de mulher de 22 anos com edema macular recorrente devido à retinose pigmentar. Obteve-se sucesso terapêutico após o tratamento com o implante intravítreo de dexamentasona (Ozurdex®, Allergan,USA).

Retinitis pigmentosa denotes a heterogeneous group of rare genetic diseases in which both rods and cones eye are damaged. It is a disease of poor prognosis. We describe the case of a 22 years old woman successfully treated with intravitreal implant of dexamentasone (OZURDEX®, Allergan, USA) for the treatment of macular edema due to retinitis pigmentosa.

Buprenorphine implants for treatment of opioid dependence: randomized comparison to placebo and sublingual buprenorphine/naloxone.

AIMS: To evaluate the safety and efficacy of buprenorphine implants (BI) versus placebo implants (PI) for the treatment of opioid dependence. A secondary aim compared BI to open-label sublingual buprenorphine/naloxone tablets (BNX). DESIGN: Randomized, double-blind, placebo-controlled trial. Subjects received either four buprenorphine implants (80 mg/implant) (n = 114), four placebo implants (n = 54) or open-label BNX (12-16 mg/day) (n = 119). SETTING: Twenty addiction treatment centers. PARTICIPANTS: Adult out-patients (ages 18-65) with DSM-IV-TR opioid dependence. MEASUREMENTS: The primary efficacy end-point was the percentage of urine samples negative for opioids collected from weeks 1 to 24, examined as a cumulative distribution function (CDF). FINDINGS: The BI CDF was significantly different from placebo (P < 0.0001). Mean [95% confidence interval (CI)] proportions of urines negative for opioids were: BI = 31.2% (25.3, 37.1) and PI = 13.4% (8.3, 18.6). BI subjects had a higher study completion rate relative to placebo (64 versus 26%, P < 0.0001), lower clinician-rated (P < 0.0001) and patient-rated (P < 0.0001) withdrawal, lower patient-ratings of craving (P < 0.0001) and better subjects' (P = 0.031) and clinicians' (P = 0.022) global ratings of improvement. BI also resulted in significantly lower cocaine use (P = 0.0016). Minor implant-site reactions were comparable in the buprenorphine [27.2% (31 of 114)] and placebo groups [25.9% (14 of 54)]. BI were non-inferior to BNX on percentage of urines negative for opioids [mean (95% CI) = 33.5 (27.3, 39.6); 95% CI for the difference of proportions = (-10.7, 6.2)]. CONCLUSIONS: Compared with placebo, buprenorphine implants result in significantly less frequent opioid use and are non-inferior to sublingual buprenorphine/naloxone tablets.

Avaliação da mucosa sinusal do coelho à presença de implante biodegradável / Assessing the maxillary sinus mucosa of rabbits in the presence of biodegradable implants

Pensando em melhorar a qualidade de vida dos pacientes com doenças do humor vítreo, os oftalmologistas começaram a utilizar recentemente implantes biodegradáveis com corticoide. Estes mesmos implantes podem ser uma alternativa no tratamento da RSC e, para isso, realizamos um estudo experimental em seios maxilares de coelhos. OBJETIVO: Avaliar histologicamente a mucosa de seio maxilar de coelhos após a colocação de implante biodegradável de prednisolona. MÉTODO: Dezoito coelhos foram divididos aleatoriamente em dois grupos: Grupo 1: no seio maxilar esquerdo foi inserido um implante biodegradável com prednisolona; Grupo 2: No seio maxilar esquerdo foi inserido um implante biodegradável sem medicação. Os seios maxilares do lado direito serviram como controle. Após 7, 14 e 28 dias foram escolhidos aleatoriamente três coelhos de cada grupo e a resposta tecidual inflamatória foi avaliada. RESULTADOS: Foi encontrada diferença não significativa de inflamação na mucosa, quando comparamos o grupo de coelhos que receberam implantes com e sem medicação com o grupo controle; ou quando comparamos o grupo que recebeu implante com prednisolona com o grupo que recebeu implante sem medicação. CONCLUSÃO: Não foram observados sinais de toxicidade ou inflamação na mucosa do seio maxilar do coelho à presença do implante com ou sem prednisolona.

In an attempt to improve the quality of life of patients with vitreous humor disease, ophthalmologists began offering steroid-eluting biodegradable implants to their patients. These implants can be used as an alternative treatment for CRS and this is why this experimental study was carried out on rabbit maxillary sinuses. OBJECTIVE: This study aims to assess the histology of the mucosa of the maxillary sinuses of rabbits after the placement of a prednisolone-eluting biodegradable implant. METHOD: Eighteen rabbits were randomly divided into two groups: group 1 - subjects had drug-eluting implants placed on their left maxillary sinuses; group 2 - subjects had non-drug-eluting implants placed on their left maxillary sinuses. The right maxillary sinuses served as the controls. After seven, 14, and 28 days three rabbits in each group were randomly picked to have their tissue inflammatory response assessed. RESULTS: Levels of mucosal inflammation were not significantly different between the groups with and without drug-eluting implants and the control group, or when the groups with drug-eluting implants and non-drug-eluting implants were compared. CONCLUSION: Signs of toxicity or mucosal inflammation were not observed in the maxillary sinuses of rabbits given prednisolone-eluting implants or non-drug-eluting implants.