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Ophthalmology Mar 2018
Topics: Anti-Inflammatory Agents; Drug Implants; Humans; Immunosuppressive Agents; Treatment Outcome; Uveitis
PubMed: 29458826
DOI: 10.1016/j.ophtha.2017.09.033 -
Scientific Reports Jul 2022The aim of the present study was to describe foveal eversion patterns in diabetic macular edema (DME) and to assess their relationship with the course of the disease and...
The aim of the present study was to describe foveal eversion patterns in diabetic macular edema (DME) and to assess their relationship with the course of the disease and the outcome. The study was designed as prospective, observational, with two years of follow-up. DME patients were divided in two groups, one treated by combined anti-VEGF injections and dexamethasone (DEX) implants, and the other treated by fluocinolone acetonide (FAc) implant with additional anti-VEGF retreatments if needed. Main outcome measures were foveal eversion prevalence, foveal eversion patterns, best-corrected visual acuity (BCVA), central macular thickness (CMT), structural OCT metrics, number of intravitreal injections. One hundred and forty-six eyes (146 patients; 80 males; mean age 67 ± 8 years) affected by already treated DME, with 84 eyes treated with anti-VEGF/DEX treatments (mean of 10 ± 3 injections) and 62 treated with FAc implant. Looking at the treatments administered before the inclusion into the study, 84 eyes (58%) were treated with anti-VEGF injections, whereas 62 eyes (42%) underwent a combination of anti-VEGF and corticosteroids implants. DME eyes showed statistically significant improvements of LogMAR BCVA and CMT over the 2-year follow-up. Foveal eversion was found in 83 eyes (57%), categorized as follows: Pattern 1a (16;19%); Pattern 1b (22;27%) and Pattern 2 (45;54%). BCVA improvement was detected in all the subgroups, excepting for Pattern 2, which showed also significantly worse structural OCT parameters. Pattern 1b and Pattern 2 were characterized by significantly higher prevalence of persistent DME (64% and 89% of cases, respectively). Foveal eversion patterns were correlated with progressively worse DME outcome. Foveal eversion may be associated to the loss of foveal homeostasis, with consequent poor response to intravitreal treatments and worse DME outcome.
Topics: Aged; Angiogenesis Inhibitors; Dexamethasone; Diabetes Mellitus; Diabetic Retinopathy; Drug Implants; Fovea Centralis; Glucocorticoids; Humans; Intravitreal Injections; Macular Edema; Male; Middle Aged; Prospective Studies; Retrospective Studies; Visual Acuity
PubMed: 35907954
DOI: 10.1038/s41598-022-17555-8 -
Drugs Nov 2021To 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... (Randomized Controlled Trial)
Randomized Controlled Trial
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.
Topics: Adult; Aged; Aged, 80 and over; Antihypertensive Agents; Bimatoprost; Dose-Response Relationship, Drug; Double-Blind Method; Drug Implants; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Timolol; Young Adult
PubMed: 34724172
DOI: 10.1007/s40265-021-01624-9 -
International Journal of Surgery... 2012
Topics: Anti-Bacterial Agents; Bacterial Infections; Collagen; Drug Implants; Gentamicins; Humans; Surgical Wound Infection
PubMed: 22659312
DOI: 10.1016/j.ijsu.2012.05.019 -
Sexual and Reproductive Health Matters Dec 2023A new public policy was instituted in Argentina for free distribution of subdermal contraceptive implants to women aged 15-24 years old in the public healthcare system....
A new public policy was instituted in Argentina for free distribution of subdermal contraceptive implants to women aged 15-24 years old in the public healthcare system. The objective of this study is to determine the extent to which this population adhered to the implant, as well as predictors of continuation. The retrospective cohort study was based on a telephone survey of a random sample of 1101 Ministry of Health-registered implant users concerning the continuation of use, satisfaction with the method and side-effects, and reasons for removal. Descriptive statistics and multivariate regression analysis were used to explore the association between adherence and having received contraceptive counselling, satisfaction, and side effects. We found high levels of adherence (87%) and satisfaction (94%). Common reported side effects were amenorrhoea or infrequent bleeding, perceived weight gain, increased menstrual bleeding and headaches. Multivariate regression analysis indicates that, among adolescents, having received contraceptive counselling increased comfort, while frequent bleeding at six months hindered trust. Participants who had a history of a prior delivery or who had themselves primarily chosen the method were less likely to request the removal of the implant. Our results support the public policy of free implant distribution in the public health sector. This is a sustainable public policy that contributes to equity and access to effective contraception. It is appropriate for adolescents and young women and will also reduce unintended pregnancies. Our results suggest that counselling patients is key prior to insertion of the implant, as it improves acceptability and continuation.
Topics: Pregnancy; Humans; Female; Adolescent; Young Adult; Adult; Levonorgestrel; Contraceptive Agents, Female; Retrospective Studies; Argentina; Drug Implants
PubMed: 37042700
DOI: 10.1080/26410397.2023.2189507 -
Transactions of the American Clinical... 2017The Johns Hopkins Hunterian Neurosurgical Laboratory at the Johns Hopkins University School of Medicine was created in 1904 by Harvey Cushing and William Halsted and has... (Review)
Review
The Johns Hopkins Hunterian Neurosurgical Laboratory at the Johns Hopkins University School of Medicine was created in 1904 by Harvey Cushing and William Halsted and has had a long history of fostering surgical training, encouraging basis science research, and facilitating translational application. Over the past 30 years, the laboratory has addressed the paucity of brain tumor therapies. Pre-clinical work from the laboratory led to the development of carmustine wafers with initial US Food and Drug Administration (FDA) approval in 1996. Combining carmustine wafers, radiation, and temozolomide led to a significant increase in the median survival of patients with glioblastoma. The laboratory has also developed microchips and immunotherapy to further extend survival in this heretofore underserved population. These achievements were made possible by the dedication, commitment, and creativity of more than 300 trainees of the Hunterian Neurosurgical Laboratory. The laboratory demonstrates the beneficial influence of research experience as well its substantial impact on the field of biomedical research.
Topics: Antineoplastic Agents; Baltimore; Biomedical Research; Brain Neoplasms; Drug Implants; Education, Medical; History, 20th Century; Humans; Neurosurgery; Schools, Medical; Women
PubMed: 28790487
DOI: No ID Found -
Women's Health (London, England) Sep 2013Obesity is a major public health concern affecting an increasing proportion of reproductive-aged women. Avoiding unintended pregnancy is of major importance, given the... (Review)
Review
Obesity is a major public health concern affecting an increasing proportion of reproductive-aged women. Avoiding unintended pregnancy is of major importance, given the increased risks associated with pregnancy, but obesity may affect the efficacy of hormonal contraceptives by altering how these drugs are absorbed, distributed, metabolized or eliminated. Limited data suggest that long-acting, reversible contraceptives maintain excellent efficacy in obese women. Some studies demonstrating altered pharmacokinetic parameters and increased failure rates with combined oral contraceptives, the contraceptive patch and emergency contraceptive pills suggest decreased efficacy of these methods. It is unclear whether bariatric surgery affects hormonal contraceptive efficacy. Obese women should be offered the full range of contraceptive options, with counseling that balances the risks and benefits of each method, including the risk of unintended pregnancy.
Topics: Bariatric Surgery; Body Mass Index; Contraceptive Agents, Female; Contraceptive Devices, Female; Contraceptives, Oral, Hormonal; Contraceptives, Postcoital; Counseling; Drug Implants; Estrogens; Female; Humans; Intrauterine Devices; Obesity; Pregnancy; Pregnancy, Unplanned; Progestins; Women's Health
PubMed: 24007251
DOI: 10.2217/whe.13.41 -
Pharmaceutical Research Apr 2020Sexual transmission of HIV has been clinically proven to be preventable with a once-daily oral tablet; however, missed doses dramatically increase the risk of HIV...
PURPOSE
Sexual transmission of HIV has been clinically proven to be preventable with a once-daily oral tablet; however, missed doses dramatically increase the risk of HIV infection. Long-acting subcutaneous implants do not allow the user to miss a dose. A desirable long-acting drug-eluting implant can deliver a constant amount of drug, adjust the delivered dose, and be readily manufactured. We present a long-acting, subcutaneous implant design composed of tenofovir alafenamide hemifumarate (TAF) pellets loaded in a sealed polyether urethane tube for the prevention of HIV transmission.
METHODS
Implants were prepared with pressed drug pellets and extruded polyurethane tubing. In vitro release rate of implants using different pellet formulations, rate-controlling membranes, and geometries were measured.
RESULTS
Tenofovir alafenamide release appeared to be governed by a pseudo-steady state and followed a mass transport model of release from a cylindrical drug reservoir. Implant seal integrity was tested and confirmed using mechanical testing. The inclusion of sodium chloride in the pellet increased the release rate and reduced initial lag. The release was sustained for 100 days.
CONCLUSIONS
The release rate of tenofovir alafenamide mechanistically varied with geometry and rate controlling membrane composition. The polyether urethane implant presented herein is modular and tunable to adjust the release rate and duration of the TAF release.
Topics: Anti-HIV Agents; Drug Compounding; Drug Delivery Systems; Drug Implants; Drug Liberation; Equipment Design; Humans; Injections, Subcutaneous; Models, Theoretical; Tenofovir
PubMed: 32296951
DOI: 10.1007/s11095-020-2777-2 -
Pflugers Archiv : European Journal of... Sep 2021The second messengers, cGMP and Ca, have both been implicated in retinal degeneration; however, it is still unclear which of the two is most relevant for photoreceptor... (Review)
Review
The second messengers, cGMP and Ca, 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 (Ca)-signalling in photoreceptors. In this review, we summarize key aspects of cGMP-signalling and Ca-signalling relevant for hereditary photoreceptor degeneration. The topics covered include cGMP-signalling targets, the role of Ca 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 Ca-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.
Topics: Animals; Calcium Signaling; Cell Death; Cyclic GMP; Drug Delivery Systems; Drug Implants; Humans; Nanoparticles; Photoreceptor Cells; Retinal Degeneration
PubMed: 33864120
DOI: 10.1007/s00424-021-02556-9 -
Postgraduate Medical Journal Jan 2004At present there is much excitement about drug-eluting stents, which hold promise for the treatment of coronary artery disease. This ingenious therapy involves coating... (Review)
Review
At present there is much excitement about drug-eluting stents, which hold promise for the treatment of coronary artery disease. This ingenious therapy involves coating the outside of a standard coronary stent with a thin polymer containing medication that can prevent scarring at the site of coronary intervention. Early trials with sirolimus coated stents showed that they might prevent coronary artery restenosis, but later studies, involving more complex coronary lesions, did not show a complete absence of restenosis. Recent studies have demonstrated the long term cost effectiveness of drug-eluting stents as they have reduced the need for revascularisation procedures. At present there are few data on the safety and effectiveness of stents over follow up periods exceeding two years, and data obtained from animal models of stenting might not be completely applicable to humans. There are concerns that drug-eluting stents might delay, rather than inhibit, restenosis. Also there is concern regarding the inflammation caused by the polymer substrate. This article reviews the present data on drug-eluting stents and their benefits, shortcomings, and concerns.
Topics: Antineoplastic Agents, Phytogenic; Clinical Trials as Topic; Coronary Restenosis; Coronary Stenosis; Cost-Benefit Analysis; Drug Implants; Humans; Paclitaxel; Stents
PubMed: 14760171
DOI: 10.1136/pmj.2003.009431