Simon W. Young

Drug delivery to the posterior segment of the eye

Delivery of drugs to the posterior eye is challenging, owing to anatomical and physiological constrains of the eye. There is an increasing need for managing rapidly progressing posterior eye diseases, such as age-related macular degeneration, diabetic retinopathy and retinitis pigmentosa. Drug delivery to the posterior segment of the eye is therefore compounded by the increasing number of new therapeutic entities (e.g. oligonucleotides, aptamers and antibodies) and the need for chronic therapy. Currently, the intravitreal route is widely used to deliver therapeutic entities to the retina. However, frequent administration of drugs via this route can lead to retinal detachment, endophthalmitis and increased intraocular pressure. Various controlled delivery systems, such as biodegradable and non-biodegradable implants, liposomes and nanoparticles, have been developed to overcome such adverse effects, with some success. The periocular route is a promising alternative, owing to the large surface area and the relatively high permeability of the sclera. Yet, the blood-retinal barrier and efflux transporters hamper the transport of therapeutic entities to the retina. As such, the efficient delivery of drugs to the posterior eye remains a major challenge facing the pharmaceutical scientist. In this review, we discuss the barriers of the posterior eye drug delivery and the various drug-delivery strategies used to overcome these barriers.

Comparison of functional outcomes of reverse shoulder arthroplasty versus hemiarthroplasty in the primary treatment of acute proximal humerus fracture.

Background:  Treatment of complex proximal humeral fractures remains controversial. In cases where adequate open reduction and internal fixation cannot be achieved, hemiarthroplasty has been the traditional treatment; however, clinical results have been mixed. Reverse shoulder arthroplasty (RSA) has been suggested as an alternative, and this study aimed to compare the functional results of RSA versus hemiarthroplasty in patients with acute proximal humeral fracture.

The SMR reverse shoulder prosthesis in the treatment of cuff-deficient shoulder conditions

BACKGROUND Reverse total shoulder arthroplasty (RSA) is a relatively recent concept that provides further options in the management of cuff-deficient shoulder disorders. While early results utilizing the Delta III prosthesis (DePuy, Warsaw, IN) have been promising, there is limited data in the literature on outcomes utilizing differing prosthetic designs. We report on the outcomes of Reverse total shoulder arthroplasty (RSA) utilizing a previously unreported prosthesis, the SMR Modular Shoulder System (Systema Multiplana Randelli, Lima-LTO, Italy). MATERIAL AND METHODS 49 arthroplasties in 48 patients who underwent Reverse Shoulder Arthroplasty with the SMR prosthesis were available for follow up. There were 10 males and 38 females with a mean age of 78.9 years (55-94) at time of operation. The most common indications were cuff tear arthropathy and osteoarthritis with cuff deficiency (66%), followed by fracture and fracture sequelae (16%). RESULTS At a mean 38 months follow up, 89% of patients rated their outcome as good or excellent. The mean American Shoulder and Elbow Surgeon Score was 70.1 (range 3-100), and the mean Oxford Shoulder Score 22.0 (12-47). The mean active anterior elevation was 122 degrees (range 45-180) and the mean external rotation 14.7 degrees (25-75). Inferior glenoid notching was seen in 24% of patients. There was no radiological evidence of component loosening and no reoperations. CONCLUSION Modern RSA designs give encouraging results in the treatment of cuff deficient shoulder conditions. Our early experience with the SMR RSA shows favourable outcomes and a low rate of complications. LEVEL OF EVIDENCE Level 4 Retrospective case series, no control group.

The Chitranjan S. Ranawat Award : No Difference in 2-year Functional Outcomes Using Kinematic versus Mechanical Alignment in TKA: A Randomized Controlled Clinical Trial.

BackgroundNeutral mechanical alignment (MA) in total knee arthroplasty (TKA) aims to position femoral and tibial components perpendicular to the mechanical axis of the limb. In contrast, kinematic alignment (KA) attempts to match implant position to the prearthritic anatomy of the individual patient with the aim of improving functional outcome. However, comparative data between the two techniques are lacking.Questions/purposesIn this randomized trial, we asked: (1) Are 2-year patient-reported outcome scores enhanced in patients with KA compared with an MA technique? (2) How does postoperative component alignment differ between the techniques? (3) Is the proportion of patients undergoing reoperation at 2 years different between the techniques?MethodsNinety-nine primary TKAs in 95 patients were randomized to either MA (n = 50) or KA (n = 49) groups. A pilot study of 20 TKAs was performed before this trial using the same patient-specific guides positioning in kinematic alignment. In the KA group, patient-specific cutting blocks were manufactured using individual preoperative MRI data. In the MA group, computer navigation was used to ensure neutral mechanical alignment accuracy. Postoperative alignment was assessed with CT scan, and functional scores (including the Oxford Knee Score, WOMAC, and the Forgotten Joint Score) were assessed preoperatively and at 6 weeks, 6 months, and 1 and 2 years postoperatively. No patients were lost to followup. We set sample size at a minimum of 45 patients per treatment arm based on a 5-point improvement in the mean Oxford Knee Score (OKS; the previously reported minimum clinically significant difference for the OKS in TKA), a pooled SD of 8.3, 80% power, and a two-sided significance level of 5%.ResultsWe observed no difference in 2-year change scores (postoperative minus preoperative score) in KA versus MA patients for the OKS (mean 21, SD 8 versus 20, SD 8, least square means 1.0, 95% confidence interval [CI], −1.4 to 3.4, p = 0.4), WOMAC score (mean 38, SD 18 versus 35, SD 8, least square means 3, 95% CI, −3.2 to 8.9, p = 0.3), or Forgotten Joint score (28 SD 37 versus 28, SD 28, least square means 0.8, 95% CI, −9.1–10.7, p = 0.8). Postoperative hip-knee-ankle axis was not different between groups (mean KA 0.4° varus SD 3.5 versus MA 0.7° varus SD 2.0), but in the KA group, the tibial component was a mean 1.9° more varus than the MA group (95% CI, 0.8°−3.0°, p = 0.003) and the femoral component in 1.6° more valgus (95% CI, −2.5° to −0.7°, p = 0.003). Complication rates were not different between groups.ConclusionsWe found no difference in 2-year patient-reported outcome scores in TKAs implanted using the KA versus an MA technique. The theoretical advantages of improved pain and function that form the basis of the design rationale of KA were not observed in this study. Currently, it is unknown whether the alterations in component alignment seen with KA will compromise long-term survivorship of TKA. In this study, we were unable to demonstrate an advantage to KA in terms of pain or function that would justify this risk.Level of EvidenceLevel I, therapeutic study.

Comparison of functional outcomes of reverse shoulder arthroplasty with those of hemiarthroplasty in the treatment of cuff-tear arthropathy: a matched-pair analysis.

BACKGROUND Rotator cuff-tear arthropathy has traditionally represented a challenge to the shoulder arthroplasty surgeon. The poor results of conventional total shoulder arthroplasty in rotator-cuff-deficient shoulders due to glenoid component loosening have led to hemiarthroplasty being the traditional preferred surgical option. Recently, reverse total shoulder arthroplasty has gained increasing popularity because of a clinical perception of an improved functional outcome, despite the lack of comparative data. The aim of this study was to compare the early functional results of hemiarthroplasty with those of reverse shoulder arthroplasty in the management of cuff-tear arthropathy. METHODS The results of 102 primary hemiarthroplasties for rotator cuff-tear arthropathy were compared with those of 102 reverse shoulder arthroplasties performed for the same diagnosis. Patients were identified from the New Zealand Joint Registry and matched for age, sex, and American Society of Anesthesiologists (ASA) scores. Oxford Shoulder Scores (OSS) collected at six months postoperatively as well as mortality and revision rates were compared between the two groups. RESULTS There were fifty-one men and fifty-one women in each group, with a mean age of 71.6 years in the hemiarthroplasty group and 72.6 years in the reverse shoulder arthroplasty group. The mean OSS at six months was 31.1 in the hemiarthroplasty group and 37.5 in the reverse shoulder arthroplasty group. At the time of follow-up, there were nine revisions in the hemiarthroplasty group and five in the reverse shoulder arthroplasty group. No difference in mortality rate was seen between the two groups. CONCLUSIONS In this unselected population with rotator cuff-tear arthropathy, controlled for age, sex, and ASA score, reverse shoulder arthroplasty resulted in a functional outcome that was superior to that of hemiarthroplasty. Longer-term follow-up is needed to confirm these findings.

Functional outcome of femoral peri prosthetic fracture and revision hip arthroplasty: A matched‐pair study from the New Zealand Registry

Background and purpose The number of periprosthetic fractures following total hip arthroplasty (THA) is increasing. There is, however, limited data on the functional outcome following these injuries. We analyzed functional outcome for revision THA following periprosthetic fracture, and compared this to the outcome of elective revision THA performed for aseptic loosening. Methods 232 patients undergoing revision THA for femoral fracture were identified from the New Zealand National Registry. Functional outcome was measured using the Oxford 12 hip score (OHS). A reference group of 232 patients undergoing elective revision THA was selected and matched for age and sex. Results Outcome was worse following revision THA for periprosthetic fracture than in reference patients (mean OHS: 29 vs. 24, p = 0.006). A higher 6‐month mortality rate was seen in periprosthetic fracture patients (7.3% vs. 0.9%, p < 0.001), along with a higher likelihood of re‐revision (7.3% vs. 2.6%, p = 0.06). Interpretation This large comparative series of periprosthetic fractures following THA shows that patients with periprosthetic fracture have poorer functional outcome and higher death rates than patients undergoing revision THA for aseptic loosening.

The impact of patient and surgical factors on the rate of infection after primary total knee arthroplasty : an analysis of 64 566 joints from the New Zealand Joint Registry.

AIMS The aim of this study was to identify risk factors for prosthetic joint infection (PJI) following total knee arthroplasty (TKA). PATIENTS AND METHODS The New Zealand Joint Registry database was analysed, using revision surgery for PJI at six and 12 months after surgery as primary outcome measures. Statistical associations between revision for infection, with common and definable surgical and patient factors were tested. RESULTS A total of 64 566 primary TKAs have been recorded on the registry between 1999 and 2012 with minimum follow-up of 12 months. Multivariate analysis showed statistically significant associations with revision for PJI between male gender (odds ratio (OR) 1.85, 95% confidence interval (CI) 1.24 to 2.74), previous surgery (osteotomy (OR 2.45 95% CI 1.2 to 5.03), ligament reconstruction (OR 1.85, 95% CI 0.68 to 5.00)), the use of laminar flow (OR 1.6, 95% CI 1.04 to 2.47) and the use of antibiotic-laden cement (OR 1.93, 95% CI 1.19 to 3.13). There was a trend towards significance (p = 0.052) with the use of surgical helmet systems at six months (OR 1.53, 95% CI 1.00 to 2.34). CONCLUSION These findings show that patient factors remain the most important in terms of predicting early PJI following TKA. Furthermore, we found no evidence that modern surgical helmet systems reduce the risk of PJI and laminar flow systems may actually increase risk in TKA. The use of this registry data assists the estimation of the risk of PJI for individual patients, which is important for both informed consent and the interpretation of infection rates at different institutions. TAKE HOME MESSAGE Infection rates in TKA are related to both individual patient and surgical factors, and some modern methods of reducing infection may actually increase infection risk.

Foot pumps without graduated compression stockings for prevention of deep-vein thrombosis in total joint replacement: efficacy, safety and patient compliance

Mechanical prophylaxis with foot pumps provides an interesting alternative to chemical agents in the prevention of thromboembolic disease following major orthopaedic surgical procedures. Recent studies have suggested that the simultaneous use of graduated compression stockings (GCS) may hinder the pneumatic compression effect of foot pumps. The hypothesis of this prospective study was that the use of foot pumps without GCS does not affect the efficacy of deep-vein thrombosis (DVT) prophylaxis and improves patient compliance. A total of 846 consecutive patients admitted at a single institution undergoing total hip (THR) or knee replacement (TKR) were included in the study. The A-V Impulse System foot-pump unit (Orthofix Vascular Novamedix, Andover, UK) was used in all patients. Of these 846 patients, 46 discontinued the use of foot pumps, leaving 400 patients who received foot pumps in combination with GCS and 400 patients with foot pumps alone. Eleven patients of the stocking group (2.7%) and nine patients of the no-stocking group (2.3%) developed postoperative symptomatic DVT (p = 0.07). DVT was more frequent in TKR (10/364; 2.7%) than in THR (10/436; 2.3%). Non-fatal pulmonary embolism occurred in four of the 20 patients with symptomatic DVT, two patients each of the stocking and no-stocking groups. The foot-pump discontinuation rate of patients treated with stockings was 7% versus 4% of the patients treated without stockings (p < 0.05). In conclusion, management of patients with foot pumps without GCS does not reduce the efficacy of DVT prophylaxis after THR and TKR and improves patient compliance.RésuméLa prophylaxie des complications thrombo-emboliques par « pompage » pédieux est une alternative au traitement médical en chirurgie orthopédique. Une étude récente a montré que l’utilisation simultanée de bas à compression élastique et de compression pneumatique au niveau du pied peut cacher l’effet de cette dernière technique. L’hypothèse émise pour ce travail prospectif est la suivante, l’utilisation de pompes au niveau des pieds sans bas de contention élastique n’entraîne pas de complications thrombo-emboliques complémentaires. 846 patients ayant bénéficié d’une prothèse totale de hanche et du genou ont été inclus dans cette étude. Le système utilisé a été le AV impluse système foot pump units de Orthofix Vascular Novamedix, Andover. 46 patients ont bénéficié de la pompe en discontinue, 400 patients ont utilisé la pompe en combinaison avec les bas de contention et 400 patients la pompe uniquement.11 patients du groupe contention élastique (2,7%) et 9 patients du groupe sans contention (2,3%) ont présenté en post-opératoire une complication thrombo embolique (p = 0.07). Les complications de type thrombose veineuse profonde sont plus fréquentes dans la prothèse du genou (10 sur 364 ; 2.7%) que dans la prothèse de hanche (10 sur 436 ; 2,3%). 4 embolies pulmonaires n’ayant entraîné aucun décès sont survenues sur un groupe de 20 patients ayant présenté une thrombose veineuse symptomatique, 2 dans le groupe bas de contention et deux dans le groupe sans bas de contention. Le système de pompe, au niveau du pied en discontinue associé à des bas de contention élastiques a été de 7% en comparaison de patients traités sans contention 4% (p < 0.05). En conclusion, l’utilisation d’un système de pompe au niveau du pied sans bas de contention élastique ne réduit pas l’efficacité de la prophylaxie du traitement des complications thrombo-emboliques de la prothèse totale de hanche dans la prothèse totale du genou et améliore le confort des patients.

Periprosthetic femoral fractures after total hip arthroplasty.

Background:  The management of periprosthetic fracture following a total hip arthroplasty is difficult, requiring expertise in both trauma and revision surgery. With rising numbers of patients in the population living with hip prostheses in situ, the frequency of these fractures is increasing, and controversy remains over their ideal management. The objective of this study was to review all periprosthetic fractures at a single institution to identify injury and treatment patterns and their associated clinical outcomes.

Does Computer Assisted Navigation Improve Functional Outcomes and Implant Survivability after Total Knee Arthroplasty

The objective of this study was to determine whether computer assisted navigation in total knee arthroplasty (TKA) improves functional outcomes and implant survivability using data from a large national database. We analysed 9054 primary TKA procedures performed between 2006 and 2012 from the New Zealand National Joint Registry. Functional outcomes were assessed using Oxford Knee Questionnaires at six months and five years. On multivariate analysis, there was no significant difference in mean Oxford Knee Scores between the navigated and non-navigated groups at six months (39.0 vs 38.1, P=0.54) or five years (42.2 vs 42.0, P=0.76). At current follow-up, there was no difference in revision rates between navigated and non-navigated TKA (0.46 vs 0.43 revisions 100 component years, P=0.8).