A meta-analysis of Nd:YAG capsulotomy rates for two hydrophobic intraocular lens materials.

PURPOSE: The purpose of this study is to estimate and compare neodymium-doped yttrium aluminum garnet (Nd:YAG) capsulotomy rates for AcrySof ® and Clareon® intraocular lens (IOL) materials using historical data from the medical literature and Alcon-sponsored clinical studies. METHODS: Clinical trials that involved the implantation of AcrySof or Clareon monofocal IOLs in subjects with cataract or presbyopia were extracted from the literature and a company repository of clinical studies. The study duration, number of eyes, and cumulative percent of Nd:YAGs for posterior capsule opacification were extracted. Bayesian random effects meta-analyses were conducted to estimate and compare outcomes for the 2 different IOL materials. RESULTS: A Bayesian random effects, meta-analysis was performed that combined a literature review of published AcrySof Nd:YAG posterior capsulotomy rates and Nd:YAG rates observed in Alcon-sponsored clinical studies of AcrySof and Clareon. Sixteen Alcon studies contained Nd:YAG data suitable for meta-analysis. Three of these Alcon studies contained results for the Clareon material (2 one-year studies, and 1 three-year study). The literature review included 50 papers from 1998 to 2015. In combination, 30,891 eyes were available for analysis and 2040 Nd:YAG procedures were reported in studies with a follow-up duration ranging in length from 4 months to 10 years. The overall probability of performing a Nd:YAG capsulotomy within a year of implant for AcrySof was 1.44% (1.11% to 1.83%) and 0.62% (0.21% to 1.38%) for Clareon. There was small improvement in the probability of Nd:YAG within a year of implant for Clareon lenses of about 0.82% with a 95% credible interval of (0.07% to 1.36%) at 1 year. Results were similar for incidence rates per 100 surgeries in a year: 0.62 (0.21 to 1.40) for Clareon, 1.46 (1.12 to 1.87) for AcrySof, and the difference was 0.84 (0.07 to 1.39) favoring Clareon. At 3 years, the overall probability of performing a Nd:YAG capsulotomy for AcrySof was 4.19% (3.24% to 5.30%) compared with only 1.82% (0.63% to 4.02%) for Clareon. CONCLUSION: A meta-analysis of Clareon multi-piece and single-piece clinical data predicts that the cumulative Clareon Nd:YAG probability will be ≤ AcrySof by 2.37% (0.18% to 3.91%) at 3 years. The results indicate that Clareon is likely to perform as well as, and possibly better than, AcrySof in terms of Nd:YAG capsulotomy rates.

Improved healing efficacy in canine ulnar segmental defects with increasing recombinant human bone morphogenetic protein-2/allograft ratios.

OBJECTIVES: A validated canine critical-sized segmental defect model was used to compare efficacy of volumetric ratios of recombinant human bone morphogenetic protein-2 (rhBMP-2)/absorbable collagen sponge (ACS) with cancellous allograft bone or biphasic calcium phosphate ceramic granules using radiographic, biomechanical, and histologic analyses. METHODS: Eighteen mixed-breed hounds received bilateral critical-sized ulnar segmental defects. The six treatment groups included 1:5, 1:2, and 1:1 volumetric ratios of rhBMP-2/ACS to cancellous allograft chips; a 1:1 volumetric ratio of rhBMP-2/ACS to biphasic calcium phosphate ceramic granules; iliac crest autograft alone; and cancellous allograft chips alone (n = 6 ulna per group). Animals were euthanized at 12 weeks and analyzed by radiography, torsion testing, and histology. RESULTS: rhBMP-2/ACS groups demonstrated higher radiographic union than autograft or allograft at 12 weeks. Both treatment groups receiving a 1:1 ratio demonstrated union rates of 100% (12/12 ulna) compared with 17% (1/6) and 0% (0/6) for autograft and allograft, respectively. Torsion testing to failure demonstrated significant increases in maximum torque for all rhBMP-2 groups compared with autograft, but no differences between the rhBMP-2 groups. Ulnae treated with the 1:1 volume ratio of rhBMP-2/ACS to ceramic had the highest histologic union grades followed by 1:1 and 1:2 volume ratios of rhBMP-2/ACS to allograft. CONCLUSIONS: In this study, efficacy of the treatment correlated with the ratio of rhBMP-2/ACS to allograft. As volume of rhBMP-2/ACS decreased below a 1:1 volume ratio, the overall efficacy decreased, thus indicating a potential limit to extending rhBMP-2/ACS past a 1:1 volumetric ratio in large segmental defects. Furthermore, ceramic was found to be a successful replacement for cancellous allograft bone at a 1:1 volumetric ratio. Clinical application using graft expanders or bone void fillers with rhBMP-2 should be used carefully and requires further investigation.

Bactericidal activity of antimicrobial coated polyurethane sleeves for external fixation pins.

This study was conducted to assess the potential of gentamicin coated polyurethane sleeves to inhibit bacterial colonization on external fixation pins and wires. These antimicrobial sleeves have been designed to be fitted over the pins and wires, at the time of surgery, as a prophylactic approach to combat the major complication of external fixation treatment, pin tract infection. Elution testing was conducted to estimate the amount of gentamicin released into the pin tract. These gentamicin concentrations were compared to the gentamicin minimal inhibitory concentration (MIC) level for common pin tract pathogens. Elution testing revealed that the gentamicin coated polyurethane sleeves released significant quantities of the antibiotic for up to 26 weeks. The initial bolus release was characterized by predicted pin tract gentamicin concentrations of >80 microg/ml at the 2 h and 1 day elution time points. These amounts of gentamicin, delivered directly to the pin tract, are far beyond those that could be achieved via oral or intravenous administration. Furthermore, the expected concentration of gentamicin in the pin tract remained above the National Committee for Clinical Laboratory Standards (NCCLS) MIC breakpoint of 4 microg/ml, [Performance standards for antimicrobial susceptibility testing: twelfth informational supplement M100-S12, NCCLS, Wayne, PA, 2002], for at least 20 weeks. Data from the SENTRY antimicrobial surveillance program (1997-2002) established a high level of bactericidal activity for gentamicin, with 83.1% of the common pin tract pathogen isolates found to be susceptible to the antibiotic. The initial burst and subsequent long-term sustained local delivery of effective amounts of gentamicin from the antimicrobial sleeves would be expected to inhibit bacterial colonization on external fixation pins and wires. This inhibition of bacterial colonization should substantially reduce the incidence of pin tract infection, and improve the overall outcome and cost effectiveness of external fixation fracture management.

Silicone gel breast implant failure: evaluation of properties of shells and gels for explanted prostheses and meta-analysis of literature rupture data.

After 30 years of clinical use, the 1992 Food and Drug Administration moratorium on silicone gel breast implants (SGBIs) resulted from a paucity of scientific data concerning their safety. The frequency of rupture and reoperative procedures was not known, nor were reliable data available for changes in the physical properties of shells and the composition of gels that might lead to SGBI failure. For this reason the authors conducted large-cohort meta-analyses of failure data for SGBIs based on numerous literature reports and also investigated systematically shell and gel properties from explanted SGBIs. They report their failure analysis data for more than 9,770 SGBIs (an update of an earlier study of more than 8,000 implants) as well an examination of the properties of shells and gels for 74 explanted SGBIs that ranged in age from 2 to 19 years (mean implanted age, 9.9 years). The explants tested were from several different manufacturers. For the modest-size explant cohort that was tested, 31 of 74 implants (42%) were found to be ruptured (some extensively). Even many intact shells were so weakened that only 51 shells had sufficient strength to enable preparation of samples for testing of mechanical properties and for analysis of composition by solvent extraction. Shells were found to contain 15 to 25% of extractable silicone. Exhaustive extraction of gels showed that they actually contained very little crosslinked silicone--85 to 95% being extractable soluble silicone fluid. Tensile and tear strengths of explanted silicone elastomer shells were lower than unimplanted prostheses and were generally well below reported manufacturers' values. This updated large-cohort failure analysis continues to show that shell rupture is related directly to implant duration (e.g., from analysis of variance statistics, 26% failure at 3.9 years, 47% at 10.3 years, 69% at 17.8 years; < or = 0.001). However, for the relatively small series of explants for which physical property data are reported, no significant correlation was observed between implant duration and the degradation of implant strength. It therefore appears most reasonable to conclude that after early weakening of shells as a result of swelling of the shell elastomer by diffusion of silicone oil from the gel, SGBI failure can occur in a time-dependent manner as a result of continuing implant motion and cyclic stresses that are exacerbated by stress concentration at thin areas, defects, and folds in the shells.

Intratumoral cancer chemotherapy and immunotherapy: opportunities for nonsystemic preoperative drug delivery.

The recent literature documents the growing interest in local intratumoral chemotherapy as well as systemic preoperative chemotherapy with evidence for improved outcomes using these therapeutic modalities. Nevertheless, with few exceptions, the conventional wisdom and standard of care for clinical and surgical oncology remains surgery followed by radiation and/or systemic chemotherapy, as deemed appropriate based on clinical findings. This, in spite of the fact that the toxicity of conventional systemic chemotherapy and immunotherapy affords limited effectiveness and frequently compromises the quality of life for patients. Indeed, with systemic chemotherapy, the oncologist (and the patient) often walks a fine line between attempting tumour remission with prolonged survival and damaging the patient's vital functions to the point of death. In this context, it has probably been obvious for more than 100 years, due in part to the pioneering work of Ehrlich (1878), that targeted or localized drug delivery should be a major goal of chemotherapy. However, there is still only limited clinical use of nonsystemic intratumoral chemotherapy for even those high mortality cancers which are characterized by well defined primary lesions i.e. breast, colorectal, lung, prostate, and skin. There has been a proliferation of intratumoral chemotherapy and immunotherapy research during the past two to three years. It is therefore the objective of this review to focus much more attention upon intratumoral therapeutic concepts which could limit adverse systemic events and which might combine clinically feasible methods for localized preoperative chemotherapy and/or immunotherapy with surgery. Since our review of intratumoral chemoimmunotherapy almost 20 years ago (McLaughlin & Goldberg 1983), there have been few comprehensive reviews of this field; only one of broad scope (Brincker 1993), three devoted specifically to gliomas (Tomita 1991; Walter et al. 1995; Haroun & Brem 2000), one on hepatomas (Venook 2000), one concerning veterinary applications (Theon 1998), and one older review of dermatological applications (Goette 1981). However, none have shed light on practical opportunities for combining intratumoral therapy with subsequent surgical resection. Given the state-of-the-art in clinical and surgical oncology, and the advances that have been made in intratumoral drug delivery, minimally invasive tumour access i.e. fine needle biopsy, new drugs and drug delivery systems, and preoperative chemotherapy, it is timely to present a review of studies which may suggest future opportunities for safer, more effective, and clinically practical non-systemic therapy.