Anterior-segment optical coherence tomography of filtering blebs in the early postoperative period of ab externo SIBS microshunt implantation with mitomycin C: Morphological analysis and correlation with intraocular pressure reduction.

PURPOSE: To analyse the morphological evolution of filtering blebs with anterior-segment OCT (AS-OCT) and its correlation with intraocular pressure after ab externo SIBS microshunt implantation with mitomycin C (MMC) during a 3-month follow-up period. METHODS: Twenty-eight filtering blebs of 28 patients with open-angle glaucoma were measured horizontally and vertically in the sub-Tenon space with AS-OCT after ab externo SIBS microshunt implantation with MMC. The intraocular pressure (IOP) was monitored simultaneously at each visit. Maturation of and morphological changes in the blebs and correlations with the IOP were recorded. RESULTS: The average median preoperative IOP of 20.7 (range, 12-30) mmHg decreased to 8.5 (range, 4-17), 8.9 (range, 5-17), 10.4 (range, 8-16) and 10.9 (range, 9-15) mmHg at 24 hr, 1 week, 1 month and 3 months, respectively (p < 0.001). A multiform morphology on AS-OCT prevailed at all time points, with a 3.5% rate of a uniform bleb morphology at the first week. The horizontal and vertical diameters of the blebs increased from baseline to the third month. The horizontal expansion (406 ± 127 µm on day 7, p = 0.04, 712 ± 211 µm on day 30, p = 0.02 and 952 ± 218 µm on day 90, p < 0.001) was greater than the vertical expansion (16 ± 18 µm, p = 0.3 on day 1, 63 ± 27 µm, p = 0.02 on day 30 and 137 ± 34 µm, p < 0.001 on day 90) without correlation with the IOP (r = -0.3, p = 0.2). CONCLUSION: Anterior-segment OCT (AS-OCT) of the filtering blebs formed after ab externo SIBS microshunt implantation showed progressive horizontal and vertical expansion of the blebs in the sub-Tenon space, with a significant peak at the first month not significantly correlated with the decrease in the IOP.

Phase 3, Randomized, 20-Month Study of the Efficacy and Safety of Bimatoprost Implant in Patients with Open-Angle Glaucoma and Ocular Hypertension (ARTEMIS 2).

OBJECTIVE: To evaluate the intraocular pressure (IOP)-lowering efficacy and safety of 10 and 15 µg bimatoprost implant in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT). METHODS: This randomized, 20-month, multicenter, masked, parallel-group, phase 3 trial enrolled 528 patients with OAG or OHT and an open iridocorneal angle inferiorly in the study eye. Study eyes were administered 10 or 15 µg bimatoprost implant on day 1, week 16, and week 32, or twice-daily topical timolol maleate 0.5%. Primary endpoints were IOP and IOP change from baseline through week 12. Safety measures included treatment-emergent adverse events (TEAEs) and corneal endothelial cell density (CECD). RESULTS: Both 10 and 15 µg bimatoprost implant met the primary endpoint of noninferiority to timolol in IOP lowering through 12 weeks. Mean IOP reductions from baseline ranged from 6.2-7.4, 6.5-7.8, and 6.1-6.7 mmHg through week 12 in the 10 µg implant, 15 µg implant, and timolol groups, respectively. IOP lowering was similar after the second and third implant administrations. Probabilities of requiring no IOP-lowering treatment for 1 year after the third administration were 77.5% (10 µg implant) and 79.0% (15 µg implant). The most common TEAE was conjunctival hyperemia, typically temporally associated with the administration procedure. Corneal TEAEs of interest (primarily corneal endothelial cell loss, corneal edema, and corneal touch) were more frequent with the 15 than the 10 µg implant and generally were reported after repeated administrations. Loss in mean CECD from baseline to month 20 was ~ 5% in 10 µg implant-treated eyes and ~ 1% in topical timolol-treated eyes. Visual field progression (change in the mean deviation from baseline) was reduced in the 10 µg implant group compared with the timolol group. CONCLUSIONS: The results corroborated the previous phase 3 study of the bimatoprost implant. The bimatoprost implant met the primary endpoint and effectively lowered IOP. The majority of patients required no additional treatment for 12 months after the third administration. The benefit-risk assessment favored the 10 over the 15 µg implant. Studies evaluating other administration regimens with reduced risk of corneal events are ongoing. The bimatoprost implant has the potential to improve adherence and reduce treatment burden in glaucoma. CLINICALTRIALS. GOV IDENTIFIER: NCT02250651.

Factors affecting uptake of the levonorgestrel-releasing intrauterine device: A mixed-method study of social franchise clients in Nigeria.

BACKGROUND: Despite the positive characteristics of the levonorgestrel-releasing intrauterine device (IUD)-a long-acting, highly effective contraceptive with important non-contraceptive attributes-the method has not been widely available in low- and middle-income countries. This study of hormonal IUD, copper IUD, implant and injectable users in Nigeria compares their characteristics, reasons for method choice, and experiences obtaining their method. METHODS: We conducted a phone survey with 888 women who received a hormonal IUD, copper IUD, contraceptive implant or injectable from 40 social franchise clinics across 18 states in Nigeria. We analyzed survey data descriptively by method and assessed factors associated with hormonal IUD use through multivariate logistic regression models. Follow-up in-depth interviews conducted with 32 women were analyzed thematically. RESULTS: There were few differences by method used in the socio-demographic profiles and contraceptive history of participants. Among users choosing a long-acting, reversible method, the top reasons for method choice included perceptions that the method was "right for my body," long duration, recommended by provider, recommended by friends/family, few or manageable side effects, and high effectiveness. Among hormonal IUD users, 17% mentioned reduced bleeding (inclusive of lighter, shorter, or no period), and 16% mentioned treatment of heavy or painful periods. Qualitative data supported these findings. Among survey respondents, between 25% and 33% said they would have chosen no method if the method they received had not been available. Both quantitative and qualitative data indicated that partner support can affect contraceptive use, with in-depth interviews revealing that women typically needed partner permission to use contraception, but men were less influential in method choice. CONCLUSIONS: Expanding access to the hormonal IUD as part of a full method mix provides an opportunity to expand contraceptive choice for women in Nigeria. Findings are timely as the government is poised to introduce the method on a wider scale.

Clinical characteristics and treatment patterns with histrelin acetate subcutaneous implants vs. leuprolide injections in children with precocious puberty: a real-world study using a US claims database.

OBJECTIVES: Gonadotropin-releasing hormone analogs are the treatment of choice for central precocious puberty (CPP). This study characterizes patients treated with histrelin implant or leuprolide injection. METHODS: A US claims database was used to identify patients aged ≤20 years with ≥1 histrelin or leuprolide claim (index treatment) between April 2010 and November 2017 and continuous enrollment ≥3 months before and ≥12 months after the index treatment date. RESULTS: Overall, 4,217 patients (histrelin, n=1,001; leuprolide, n=3,216) were identified. The percentage of patients with CPP diagnosis was greater in the histrelin (96.5%) vs. leuprolide (68.8%; p<0.0001) cohort. In patients with CPP (histrelin, n=966; leuprolide, n=2,214), mean age at treatment initiation was similar for histrelin (9.0 ± 2.0 years) and leuprolide (9.1 ± 2.3 years), with >50% of patients aged 6-9 years. Mean treatment duration was significantly longer for histrelin (26.7 ± 14.8 months) vs. leuprolide (14.1 ± 12.1 months; p<0.0001), and was longer in younger patient groups. More patients switched from leuprolide to histrelin (12.3%) than vice versa (3.6%; p<0.0001). Median annual total treatment costs were slightly lower for the histrelin cohort ($23,071 [interquartile range, $16,833-$31,050]) than the leuprolide cohort ($27,021 [interquartile range, $18,314-$34,995]; p<0.0001). CONCLUSIONS: Patients with CPP treated with histrelin had a longer duration of treatment, lower rates of index treatment discontinuation, and lower annual treatment costs vs. those treated with leuprolide.

Accelerated in vitro release testing method for a long-acting peptide-PLGA formulation.

Poly (lactic-co-glycolic acid) (PLGA), a biocompatible and biodegradable polymer, is one of the most commonly used vehicles for controlled-release (CR) implantable dosage forms. Drug molecules formulated in such CR vehicles are released slowly over an extended period of time - often months to years - posing challenges for batch release and quality control testing. Thus, reliable and reproducible accelerated testing methods are required to bridge this gap during early formulation development. This work describes the development of an accelerated in vitro release testing method to predict the real-time in vitro release of a synthetic peptide from a 6-month CR PLGA implant formulation. While accelerated methods have been previously reported for PLGA-based formulations, this work describes a unique case of an aggregation-prone peptide, which required careful attention to the impact of different conditions on both release kinetics and peptide stability. This method describes a suitable combination of release conditions that could help in understanding the release profiles of such peptides prone to aggregation. Parameters including pH, buffer species, temperature, and addition of organic co-solvents and surfactants were evaluated separately and in combination for their ability to achieve complete peptide release within 2 weeks while accurately recapitulating release rate, profile and peptide stability. The accelerated release method that gave the best agreement with real-time release was a mixed media of co-solvent (5% tetrahydrofuran), surfactant (5% TritonX-100) and elevated temperature (50 °C) in a neutral buffer (PBS pH 7.4). This optimized accelerated release method achieved complete release of the peptide load within 14-21 days compared to 3- to 6-months of real-time release and could discriminate critical differences in release behavior between different CR formulations to guide formulation and process development.

Real-life medium term follow-up data for intravitreal dexamethasone implant in retinal vein occlusion.

Macular edema (ME) is the most frequent vision threatening consequence after retinal vein occlusion (RVO). In this study, we evaluate the effect of dexamethasone intravitreal implants (DII, Ozurdex) in a real-life cohort of 99 patients with ME due to RVO. All patients who received DII for ME following RVO between 2011 and 2016 at the University Eye Hospital Freiburg, Germany and who had fully accessible electronic medical records were eligible for this study. Most of the patients included in this study were not treatment-naïve: 61 eyes had received prior anti-VEGF drugs, 6 eyes had received intravitreal corticosteroids (triamcinolone) and 15 had been treated with both; 17 eyes were treatment-naïve. Mean follow-up was 312 ± 310 days. Mean visual acuity (VA) was maintained throughout the observation period (mean VA at baseline: 66.7 ± 23.5 letters; at last observation 64.9 ± 28.3). Central retinal thickness (CRT) decreased from 526 ± 179 µm at baseline to 431 ± 199 µm. Mean intraocular pressure (IOP) increased from 14.4 ± 3.1 mmHg at baseline to 17.1 ± 6.3 mmHg. Cataract surgery was performed in 22% of phakic eyes. DII was used as second-line treatment in the majority of cases in this cohort. The fact that mean VA remained unchanged while mean CRT decreased illustrates that morphologic improvement does not always translate into functional gain. Mean IOP was maintained within normal limits and cataract formation was as expected in this age group.

Biosensitive and antibacterial coatings on metallic material for medical applications.

Metallic materials are commonly used for load-bearing implants and as internal fixation devices. It is customary to use austenitic stainless steel, especially surgical grade type 316L SS as temporary and Ti alloys as permanent implants. However, long-term, poor bonding with bone, corrosion, and release of metal ions, such as chromium and nickel occur. These ions are powerful allergens and carcinogens and their uncontrolled leaching may be avoided by surface coatings. Therefore, bioactive glasses (BGs) became a vital biomedical material, which can form a biologically active phase of hydroxycarbonate apatite on their surface when in contact with physiological fluids. To reduce the high coefficient of friction and the brittle nature of BGs, polymers are normally incorporated to avoid the high-temperature sintering/densification of ceramic-only coatings. For medical application, electrophoretic deposition (EPD) is now used for polymer (organic) and ceramic (inorganic) components at room temperature due to its simplicity, control of coating thickness and uniformity, low cost of equipment, ability to coat substrates of intricate shape and to supply thick films in composite form, high purity of deposits as well as no phase transformation during coating. Although extensive research has been conducted on polymer/inorganic composite coatings, only some studies have reported multifunctional properties, such as biological antibacterial activity, enhanced cell adhesion, controlled drug release ability, and mechanical properties. This review will focus on biodegradable coatings, including zien, chitosan, gelatin, cellulose loaded with antibacterial drugs/metallic ions/natural herbs on biostable substrates (PEEK/PMMA/PCL/PLLA layers), which have the potential of multifunctional coating for metallic implants.

The role of cGMP-signalling and calcium-signalling in photoreceptor cell death: perspectives for therapy development.

The second messengers, cGMP and Ca2+, have both been implicated in retinal degeneration; however, it is still unclear which of the two is most relevant for photoreceptor cell death. This problem is exacerbated by the close connections and crosstalk between cGMP-signalling and calcium (Ca2+)-signalling in photoreceptors. In this review, we summarize key aspects of cGMP-signalling and Ca2+-signalling relevant for hereditary photoreceptor degeneration. The topics covered include cGMP-signalling targets, the role of Ca2+ permeable channels, relation to energy metabolism, calpain-type proteases, and how the related metabolic processes may trigger and execute photoreceptor cell death. A focus is then put on cGMP-dependent mechanisms and how exceedingly high photoreceptor cGMP levels set in motion cascades of Ca2+-dependent and independent processes that eventually bring about photoreceptor cell death. Finally, an outlook is given into mutation-independent therapeutic approaches that exploit specific features of cGMP-signalling. Such approaches might be combined with suitable drug delivery systems for translation into clinical applications.

Unilateral intravitreal dexamethasone implant for the treatment of cystoid macular edema in intermediate uveitis / Implante unilateral de dexametasona intravítrea para tratamento de edema macular cistoide na uveíte intermediária

ABSTRACT This report aims to describe the effectiveness of a unilateral intravitreal dexamethasone implant (Ozurdex®) used for the treatment of cystoid macular edema in a patient with recurrent intermediate uveitis. Bearing in mind the adverse effects of the prolonged use of systemic corticosteroids, the objective here was to provide a less damaging form of intervention, and also to demonstrate the safety of the dexamethasone implant for patients who fail to respond to conventional treatment. In the present case, there was bilateral improvement in retinal anatomy and function with use of the unilateral intravitreal dexamethasone implant (Ozurdex®).

RESUMO Neste estudo, o objetivo foi descrever, a partir de um relato de caso, a eficácia do uso de implante de dexametasona intravítrea (Ozurdex®) unilateral, para o tratamento de edema macular cistoide, em um paciente com quadro de uveíte intermediária recorrente, visando uma terapêutica menos lesiva, diante dos efeitos colaterais do uso prolongado de corticoesteroides sistêmicos, demonstrando também a segurança desse tratamento alternativo para aqueles pacientes que se apresentam refratários a terapêutica tradicional. No caso relatado, vale ressaltar a melhora bilateral da anatomia e função retiniana com o implante unilateral de dexametasona intravítrea (Ozurdex®).

Electrosprayed minocycline hydrochloride-loaded microsphere/SAIB hybrid depot for periodontitis treatment.

Minocycline hydrochloride (MINO) has been one of the most frequently used antibiotics in the treatment of periodontitis due to its antibacterial activity and osteogenesis effects; however, high levels of MINO administered during the treatment halt the formation of new bone. Therefore, the purpose of the present study was to prepare a MINO-microsphere/sucrose acetate isobutyrate (SAIB) hybrid depot to reduce the burst release of MINO and ensure antibacterial and osteogenesis effects of MINO in the treatment of periodontitis. Uniform microspheres, approximately 5 µm size, with a slightly rough surface and different MINO loading (10, 12, and 14%) were prepared, and the microspheres were added into SAIB, after which the burst release significantly decreased from 66.18 to 2.92%, from 71.82 to 3.82%, and from 73.35 to 4.45%, respectively, and the release from all the MINO-microspheres/SAIB hybrid depots lasted for 77 days. In addition, cytotoxicity test showed that the MINO-microsphere with 12% drug loading promoted the proliferation of osteoblasts the most and was subsequently used in vivo experiments. Moreover, in the model of ligatured-induced periodontitis in SD rats, the MINO-microsphere/SAIB hybrid depot not only significantly increased the alveolar bone height and bone volume but also reduced the inflammation of the periodontal tissue. Additionally, it also inhibited the expression of the receptor activator of nuclear factor-kappa B ligand (RANKL) and promoted the expression of osteoprotegerin (OPG).. These results indicated that the MINO-microsphere/SAIB hybrid depot might be promising in the treatment of periodontitis.

Difference in the efficacy of intravitreal dexamethasone implant before and after silicone oil removal: A case report.

RATIONALE: An intravitreal dexamethasone (IV-DEX) implant is safe and effective for the treatment of macular edemas; however, the efficacy of IV-DEX implants in silicone oil (SO)-filled eyes remains controversial. There is no previous study comparing an IV-DEX implant in the same eye with and without intravitreal SO. PATIENT CONCERNS: A 72-year-old man with proliferative diabetic retinopathy, macular edema, and rhegmatogenous retinal detachment, treated with pars plana vitrectomy with SO tamponade had refractory macular edema. DIAGNOSIS: Refractory macular edema. INTERVENTION: Subtenon triamcinolone injection, intravitreal anti-vascular endothelial growth factor injection, and IV-DEX implantation were performed; this was followed by intravitreal SO removal combined with IV-DEX implantation. OUTCOMES: The macular edema did not decrease significantly with posterior subtenon triamcinolone injection, intravitreal anti-vascular endothelial growth factor injection, and IV-DEX implantation; however, the edema was relieved after SO removal and a new IV-DEX implantation. LESSONS: IV-DEX implant may be less efficacious in the treatment of macular edema in an SO-filled eye than that in a normal vitreous cavity.

A rodent model of human dose-equivalent progestin-only implantable contraception.

BACKGROUND: Long-acting, reversible contraceptives (LARC; progestin only) are an increasingly common hormonal contraceptive choice in reproductive aged women looking to suppress ovarian function and menstrual cyclicity. The overall objective was to develop and validate a rodent model of implanted etonogestrel (ENG) LARC, at body size equivalent doses to the average dose received by women during each of the first 3 years of ENG subdermal rod LARC use. METHODS: Intact, virgin, female Sprague-Dawley rats (16-wk-old) were randomized to 1 of 4 groups (n = 8/group) of ENG LARC (high-0.30µg/d, medium-0.17µg/d, low-0.09µg/d, placebo-0.00µg/d) via a slow-release pellet implanted subcutaneously. Animals were monitored for 21 days before and 29 days following pellet implantation using vaginal smears, ultrasound biomicroscopy (UBM), saphenous blood draws, food consumption, and body weights. Data were analyzed by chi-square, non-parametric, univariate, and repeated measures 2-way ANOVA. RESULTS: Prior to pellet implantation there was no difference in time spent in estrus cycle phases among the treatment groups (p > 0.30). Following pellet implantation there was a dose-dependent impact on the time spent in diestrus and estrus (p < 0.05), with the high dose group spending more days in diestrus and fewer days in estrus. Prior to pellet insertion there was not an association between treatment group and estrus cycle classification (p = 0.57) but following pellet implantation there was a dose-dependent association with cycle classification (p < 0.02). Measurements from the UBM (ovarian volume, follicle count, corpora lutea count) indicate an alteration of ovarian function following pellet implantation. CONCLUSION: Assessment of estrus cyclicity indicated a dose-response relationship in the shift to a larger number of acyclic rats and longer in duration spent in the diestrus phase. Therefore, each dose in this model mimics some of the changes observed in the ovaries of women using ENG LARC and provides an opportunity for investigating the impacts on non-reproductive tissues in the future.

Evolution of drug-eluting biomedical implants for sustained drug delivery.

In the field of drug delivery, the most commonly used treatments have traditionally been systemically delivered using oral or intravenous administration. The problems associated with this type of delivery is that the drug concentration is controlled by first pass metabolism, and therefore may not always remain within the therapeutic window. Implantable drug delivery systems (IDDSs) are an excellent alternative to traditional delivery because they offer the ability to precisely control the drug release, deliver drugs locally to the target tissue, and avoid the toxic side effects often experienced with systemic administration. Since the creation of the first FDA-approved IDDS in 1990, there has been a surge in research devoted to fabricating and testing novel IDDS formulations. The versatility of these systems is evident when looking at the various biomedical applications that utilize IDDSs. This review provides an overview of the history of IDDSs, with examples of the different types of IDDS formulations, as well as looking at current and future biomedical applications for such systems. Though there are still obstacles that need to be overcome, ever-emerging new technologies are making the manufacturing of IDDSs a rewarding therapeutic endeavor with potential for further improvements.

Breast Cancer Risk with Progestin Subdermal Implants: A Challenge in Patients Counseling.

There is a steady global rise in the use of progestin subdermal implants, where use has increased by more than 20 times in the past two decades. BC risk has been reported with the older progestin only methods such as oral pills, injectables, and intrauterine devices, however, little is known about the risk with subdermal implants. In this review, we aim to update clinicians and researchers on the current evidence to support patient counseling and to inform future research directions. The available evidence of the association between the use of progestin subdermal implants and BC risk is discussed. We provide an overview of the potential role of endogenous progesterone in BC development. The chemical structure and molecular targets of synthetic progestins of relevance are summarized together with the preclinical and clinical evidence on their association with BC risk. We review all studies that investigated the action of the specific progestins included in subdermal implants. As well, we discuss the potential effect of the use of subdermal implants in women at increased BC risk, including carriers of BC susceptibility genetic mutations.

Twelve-month Continuation of the Etonogestrel Implant in Adolescents With Polycystic Ovary Syndrome.

STUDY OBJECTIVE: To identify why adolescents with polycystic ovary syndrome (PCOS) chose the etonogestrel (ENG) contraceptive implant, to determine the 12-month continuation rate, and to characterize factors related to discontinuation. DESIGN, SETTING, AND PARTICIPANTS: Retrospective chart review of adolescents seen at a tertiary care children's hospital between July 1, 2008, and August 30, 2019, with PCOS diagnosis confirmed per National Institutes of Health criteria and ≥12-month ENG follow-up. INTERVENTIONS AND MAIN OUTCOME MEASURES: Demographic characteristics, reasons for ENG insertion and removal, and information on other hormonal/contraceptive therapies were collected. Patients were categorized as ENG continuers (use ≥12 months) or discontinuers (removal at <12 months), and groups were compared. RESULTS: A total of 96 patients met inclusion criteria (age 17.7 ± 2.2 years, body mass index 34.8 ± 8 kg/m2). Reasons for ENG were documented in 74% (51% contraception, 32% ease of use, 15% other, 13% estrogen avoidance). In all, 27% had never been sexually active, and 67% had had prior sexual activity. Treatments prior to ENG placement included 74% combined hormonal contraception, 20% medroxyprogesterone acetate withdrawal, and 17% depot medroxyprogesterone. A total of 77% continued ENG at 12 months. The main reasons for discontinuation were bleeding (41%), concern about weight gain (23%), and mood changes (18%). No preimplantation characteristics were independently predictive of continuation, although 100% of patients with type 2 diabetes (n = 11) continued. Patients who sought additional care, including telephone calls (41% vs 12%, P = .006) and clinic visits (64% vs 20%, P < .001) were more likely to discontinue. CONCLUSIONS: The ENG implant was well tolerated in adolescents with PCOS and similar to published 12-month continuation rates.

Initial Leuprolide Acetate Release from Poly(d,l-lactide-co-glycolide) in Situ Forming Implants as Studied by Ultraviolet-Visible Imaging.

The initial drug release from in situ forming implants is affected by factors such as the physicochemical properties of the active pharmaceutical ingredient, the type of the excipients utilized, and the surrounding environment. The feasibility of UV-vis imaging for characterization of the initial behavior of poly(d,l-lactide-co-glycolide) (PLGA)/1-methyl-2-pyrrolidinone (NMP) in situ forming implants was investigated. The in vitro release of leuprolide acetate (LA) and implant formation in real time were monitored using dual-wavelength imaging at 280 and 525 nm, respectively, in matrices based on agarose gel and hyaluronic acid (HA) solution emulating the subcutaneous matrix. Three hours upon injection of the pre-formulation, approximately 15% of the total amount of LA administered was found in the agarose gel, while 5% was released from the implant into the HA solution. Concurrently, more extensive swelling of the implants in the HA solution as compared to implants in the agarose gel was observed. Transport of both LA and the solvent NMP was investigated using UV-vis imaging in a small-scale cell where the geometry of the formulation was controlled, showing a linear correlation between drug release and solvent escape. Light microscopy showed that the microstructures of the resulting implants in agarose gel and HA solution were different, which may be attributed to the different solvent exchange rates. UV imaging was also used to examine the interaction of LA with the release medium by characterizing the diffusion of LA in agarose gel, HA solution, and phosphate buffered saline. The reduced LA diffusivity in HA solution as compared to agarose gel and the LA distribution coefficient in the agarose gel-HA system indicated the presence of interactions between LA and HA. Our findings show that the external environment affects the solvent exchange kinetics for in situ forming implants in vitro, resulting in different types of initial release behavior. UV-vis imaging in combination with biorelevant matrices may offer an interesting approach in the development of in situ forming implant delivery systems.

Factors Associated With Delayed Contraceptive Implant Removal in Ethiopia.

BACKGROUND: In 2009, the Government of Ethiopia initiated the implant scale-up initiative, which expanded contraceptive access by training health extension workers (HEWs) to insert single-rod etonogestrel contraceptive implants (Implanon) at rural health posts. Removals were provided by referrals to higher levels of the health system. However, little was known about whether women were getting their implants removed at the recommended 3-year postinsertion date or what barriers they faced to removal. METHODS: Between June and July 2016, 1,860 Ethiopian women, who had a 1-rod etonogestrel implant inserted by either an HEW or another health care provider between 3 and 6 years prior, were surveyed. We describe the characteristics of the sample and use multivariable logistic regression to predict factors associated with keeping implants inserted beyond 3 years. RESULTS: Women who had received their implants from HEWs were significantly more likely to report keeping them inserted for more than 3 years (adjusted odds ratio=2.50; 95% confidence interval=1.19, 5.24), compared with those who got their implant from another health care provider. Women who reported distance to the facility or transportation as a barrier were also significantly more likely to keep their implant for more than 3 years. Married and educated women were less likely to keep their implants for an extended duration. Among women who had their implant for 3 years or less, women who had had it inserted by an HEW were significantly more likely to report that the provider was unable or refused to provide removal as a barrier. DISCUSSION: Efforts to expand lower level and community-based access to contraceptive implants that do not ensure reliable access to removals at the same level as insertions may lead to women using implants beyond the recommended duration.

Eficacia del implante de dexametasona intravítreo en el manejo del «síndrome de Vogt-Koyanagi-Harada-like» secundario a la inhibición de la vía MAP quinasa / Usefulness of intravitreal dexamethasone implant in the management of «Vogt-Koyanagi-Harada-like syndrome» secondary to map kinase pathway inhibition

Mujer de 58 años, con antecedentes personales de melanoma metastásico en tratamiento con trametinib y dabrafenib, que presentaba disminución de agudeza visual bilateral. En la exploración se podía observar uveítis anterior, vitritis, desprendimiento de retina seroso, vasculitis y edema de disco en ambos ojos; se la diagnosticó de síndrome de Vogt-Koyanagi-Harada-like secundario a inhibición de la vía MAP quinasa. Además de la retirada de los fármacos oncológicos, se pautaron corticoides sistémicos y tópicos, pero este tratamiento consiguió solo una mejoría parcial del cuadro cuando se reintrodujo la terapia biológica; se añadió, por tanto, un implante de dexametasona intravítreo bilateral que consiguió una evolución favorable en su sintomatología y en los hallazgos de las pruebas complementarias. La inflamación intraocular es una complicación descrita tras el tratamiento con trametinib y dabrafenib. Un diagnóstico preciso unido al tratamiento corticoideo, tanto sistémico como intravítreo, nos llevó a obtener óptimos resultados

The case is presented of a 58-year-old woman with a personal history of metastatic melanoma under treatment with trametinib and dabrafenib, as well as a decrease in bilateral visual acuity. On examination, it was observed that she had an anterior uveitis, vitritis, serous retinal detachment, vasculitis and disc oedema in both eyes. She was diagnosed with a Vogt-Koyanagi-Harada-like syndrome secondary to MAP kinase pathway inhibition. In addition to the withdrawal of the oncology drugs, systemic and topical corticosteroids were prescribed, but this treatment only achieved a partial improvement of the disease when biological therapy was re-introduced. Therefore, a bilateral intravitreal dexamethasone implant was added, which led to a favourable progression in her symptomatology, as well as in the findings of complementary tests. Intraocular inflammation is a complication described after treatment with trametinib and dabrafenib. An accurate diagnosis, added to corticosteroid treatment, systemic and intravitreal, led us to obtain optimal results