Medium-term mortality after hip fractures and COVID-19: A prospective multi-centre UK study.

PURPOSE: The COVID-19 pandemic has caused 1.4 million deaths globally and is associated with a 3-4 times increase in 30-day mortality after a fragility hip fracture with concurrent COVID-19 infection. Typically, death from COVID-19 infection occurs between 15 and 22 days after the onset of symptoms, but this period can extend up to 8 weeks. This study aimed to assess the impact of concurrent COVID-19 infection on 120-day mortality after a fragility hip fracture. METHODS: A multi-centre prospective study across 10 hospitals treating 8% of the annual burden of hip fractures in England between 1st March and 30th April, 2020 was performed. Patients whose surgical treatment was payable through the National Health Service Best Practice Tariff mechanism for "fragility hip fractures" were included in the study. Patients' 120-day mortality was assessed relative to their peri-operative COVID-19 status. Statistical analysis was performed using SPSS version 27. RESULTS: A total of 746 patients were included in this study, of which 87 (11.7%) were COVID-19 positive. Mortality rates at 30- and 120-day were significantly higher for COVID-19 positive patients relative to COVID-19 negative patients (p < 0.001). However, mortality rates between 31 and 120-day were not significantly different (p = 0.107), 16.1% and 9.4% respectively for COVID-19 positive and negative patients, odds ratio 1.855 (95% CI 0.865-3.978). CONCLUSION: Hip fracture patients with concurrent COVID-19 infection, provided that they are alive at day-31 after injury, have no significant difference in 120-day mortality. Despite the growing awareness and concern of "long-COVID" and its widespread prevalence, this does not appear to increase medium-term mortality rates after a hip fracture.

Evaluating gender bias in an eating disorder risk assessment questionnaire for athletes.

Due to stigma, eating disorders are under-researched, underdiagnosed and undertreated among men. This is particularly pertinent among athletes, as athletic goals are a major risk factor for disordered eating in men. This gender stereotype may be reinforced by eating disorder risk assessment tools that better reflect female symptoms. We examine an eating disorder risk assessment questionnaire in a population of athletes to assess both (1) gender bias in individual items and (2) gender differences on a cognitive and behavioral subscale, identified through a factor analysis. Controlling for eating disorder risk, we found that female gender significantly predicted high risk scores on four items; male gender significantly predicted high risk scores on four other items. We also found that women were more likely to score above the median on a cognitive subscale than men with the same level of eating disorder risk, while men were more likely to score above the median on a behavioral subscale. These results may be applied practically to allow eating disorder risk assessment tools to better capture eating disorder risk independent of gender. These methods may be applied to other questionnaires and other social identities, to expand the scope of eating disorder research and treatment.

Validation of the Hip Arthroscopy Module of the VirtaMed Virtual Reality Arthroscopy Trainer.

OBJECTIVE: To assess the face, content and construct validity of a virtual reality hip arthroscopy simulator (Arthros™, VirtaMed AG, Schlieren, Switzerland). DESIGN: Participants were divided into Expert and Novice groups depending on whether or not they had assisted with or performed more than 50 hip arthroscopy procedures. Participants were given a standardized introduction and shown a video on how to use the simulator. To familiarise themselves with the equipment, they were then given a 5-minute diagnostic task to complete. Participants then performed a therapeutic task. On completion, the simulator produced a summary of performance metrics for the following domains: Operation Time, Safety, Economy, Detailed Visualization and Overall Score. Participants completed a 7-point Likert-scale questionnaire to assess the face and content validity of the simulator. SETTING: University lab or exhibition stand at an orthopaedic conference. PARTICIPANTS: Clinicians from a hospital orthopaedic department and attendees at a UK orthopaedic conference with varying levels of experience in hip arthroscopy surgery. RESULTS: Twenty-two participants were recruited. Six were classified as Expert and 16 as Novice. Statistically significant differences were found between the Expert and Novice groups for Overall Score (p=0.001), Safety (p=0.002) and Economy (p=0.033), but not Detailed Visualization (p=0.097). Questionnaire responses were positive for all items related to face and content validity. CONCLUSION: This study suggests that training on the ArthroS™ VR hip arthroscopy simulator has construct, face and content validity. It expands the evidence base for VR simulator training and is the first study to evaluate this hip arthroscopy module.

Validation of the Anterior Cruciate Ligament (ACL) Module of the VirtaMed Virtual Reality Arthroscopy Trainer.

OBJECTIVE: To assess the newly developed anterior cruciate ligament (ACL) module of a VR arthroscopy trainer for content, construct and face validity. DESIGN: Participants were divided into expert and novice groups based on their experience with ACL arthroscopy. Participants were given a standardized introduction, shown a video on how to use the simulator, and performed a 5-minute partial meniscectomy task, to familiarise them with the equipment. Participants then undertook an ACL reconstruction task. On completion, the simulator produced a summary of performance metrics for the following domains: Operation Time, ACL Reconstruction, Safety, Economy, Detailed Visualization and Total Score. A 7-point Likert scale questionnaire was used to assess the face and content validity of the simulator. PARTICIPANTS: Twenty one participants from a hospital orthopaedic department were recruited. Five were classified as expert, 16 as novice. RESULTS: An independent Mann-Whitney U test showed no significant differences between experts and novices for any of the domains. Questionnaire responses regarding hand-eye coordination, camera navigation training, diagnostic training, tunnel preparation and overall training capacity were scored as either 'good' or 'excellent' by more than 70% of the participants. All responses regarding the 'graft insertion task' scored low. CONCLUSION: The current iteration of the VR knee ArthroS™ simulator (VirtaMed AG, Zurich, Switzerland) is promising, but requires further development of the ACL procedure, in particular the graft insertion task, before it can be considered as part of training curricula.

A Clinical Audit of Orthopaedic Operation Note Documentation and Digitalization of the Operative Note Template: A Quality Improvement Project.

Background Good communication between a surgical team and other colleagues is vital, and the medium of communication is often the operative note. It is essential to ensure continuity of care between the operating team and other colleagues; also, it provides a medicolegal record of patient care. It checks all the four main domains of good surgical practice guidelines set by the Royal College of Surgeons (RCS) of England. The aims of this project were to evaluate the quality of operation notes against the set parameters by the RCS and to improve quality of the operative notes using information technology (IT) service software update to provide operative note digitalization. Methods This was a retrospective and prospective closed-loop audit, in which the operative notes were analysed for the Trauma and Orthopaedics speciality. Three separate cycles of audits were completed. In the the first cycle, data were collected retrospectively from all the operative notes, from June 1, 2020, to June 15, 2020; then, data were collected prospectively after making interventions to establish digitalization of the operative notes. The second cycle was completed from February 14 to 21, 2021, and from March 1 to 7, 2021. The third cycle was completed from August 1 to 31, 2021. All data were collected in Excel using a checklist that evaluated 34 parameters. These parameters were based on the recommendations of RCS Good Surgical Practice guidelines. All trauma and orthopaedic patients were included regardless of the type of procedure. There were no exclusion criteria in place. Results An overall increase from 9.5% to 66.7% in typed operative notes was achieved with the introduction of the templated operative note documentation service. There was a 40% reduction in the use of handwritten operative notes. Concerns regarding legibility were reduced in view of the digitalization of the operative notes. The first cycle of the audit, in terms of the parameters yielded, found that the operative notes were missing 10 important parameters, independent of the author grade; these were recorded in less than 10% of the operative notes. The second cycle, in terms of the parameters yielded, found that the operative notes were missing four important parameters, independent of the author grade; these were recorded in less than 10% of the operative notes. The third cycle of the audit, in terms of the parameters yielded, found that the operative notes were missing three important parameters. Specific documentation for 12 different parameters improved over the course of the three Plan-Do-Study-Act (PDSA) cycles. Conclusion Royal College of Surgeons guidelines and integration with IT services significantly improved the quality and legibility of operative notes that were being documented in the trauma and orthopaedics department. Structured document standards and good integration with a computer-based IT service help prompt surgeons to document in a better and easy way, thereby leading to improved clinical documentation.

Postpartum Length of Stay and Hospital Readmission Before and During the Coronavirus Disease 2019 (COVID-19) Pandemic.

OBJECTIVE: To compare postpartum hospitalization length of stay (LOS) and hospital readmission among obstetric patients before (March 2017-February 2020; prepandemic) and during the coronavirus disease 2019 (COVID-19) pandemic (March 2020-February 2021). METHODS: We conducted a retrospective cohort study, using Epic Systems' Cosmos research platform, of obstetric patients who delivered between March 1, 2017, and February 28, 2021, at 20-44 weeks of gestation and were discharged within 7 days of delivery. The primary outcome was short postpartum hospitalization LOS (less than two midnights for vaginal births and less than three midnights for cesarean births) and secondary outcome was hospital readmission within 6 weeks of postpartum hospitalization discharge. Analyses compared outcomes before and during the pandemic using standardized differences and Bayesian logistic mixed-effects models, among all births and stratified by mode of delivery. RESULTS: Of the 994,268 obstetric patients in the study cohort, 742,113 (74.6%) delivered prepandemic and 252,155 (25.4%) delivered during the COVID-19 pandemic. During the COVID-19 pandemic, the percentage of short postpartum hospitalizations increased among all births (28.7-44.5%), vaginal births (25.4-39.5%), and cesarean births (35.3-55.1%), which was consistent with the adjusted analysis (all births: adjusted odds ratio [aOR] 2.35, 99% credible interval 2.32-2.39; vaginal births: aOR 2.14, 99% credible interval 2.11-2.18; cesarean births aOR 2.90, 99% credible interval 2.83-2.98). Although short postpartum hospitalizations were more common during the COVID-19 pandemic, there was no change in readmission in the unadjusted (1.4% vs 1.6%, standardized difference=0.009) or adjusted (aOR 1.02, 99% credible interval 0.97-1.08) analyses for all births or when stratified by mode of delivery. CONCLUSION: Short postpartum hospitalization LOS was significantly more common during the COVID-19 pandemic for obstetric patients with no change in hospital readmissions within 6 weeks of postpartum hospitalization discharge. The COVID-19 pandemic created a natural experiment, suggesting shorter postpartum hospitalization may be reasonable for patients who are self-identified or health care professional-identified as appropriate for discharge.

Birth Hospital Length of Stay and Rehospitalization During COVID-19.

OBJECTIVES: To determine if birth hospitalization length of stay (LOS) and infant rehospitalization changed during the coronavirus disease 2019 (COVID-19) era among healthy, term infants. METHODS: Retrospective cohort study using Epic's Cosmos data from 35 health systems of term infants discharged ≤5 days of birth. Short birth hospitalization LOS (vaginal birth <2 midnights; cesarean birth <3 midnights) and, secondarily, infant rehospitalization ≤7 days after birth hospitalization discharge were compared between the COVID-19 (March 1 to August 31, 2020) and prepandemic eras (March 1 to August 31, 2017, 2018, 2019). Mixed-effects models were used to estimate adjusted odds ratios (aORs) comparing the eras. RESULTS: Among 202 385 infants (57 110 from the COVID-19 era), short birth hospitalization LOS increased from 28.5% to 43.0% for all births (vaginal: 25.6% to 39.3%, cesarean: 40.1% to 61.0%) during the pandemic and persisted after multivariable adjustment (all: aOR 2.30, 95% confidence interval [CI] 2.25-2.36; vaginal: aOR 2.12, 95% CI 2.06-2.18; cesarean: aOR 3.01, 95% CI 2.87-3.15). Despite shorter LOS, infant rehospitalizations decreased slightly during the pandemic (1.2% to 1.1%); results were similar in adjusted analysis (all: aOR 0.83, 95% CI 0.76-0.92; vaginal: aOR 0.82, 95% CI 0.74-0.91; cesarean: aOR 0.87, 95% CI 0.69-1.10). There was no change in the proportion of rehospitalization diagnoses between eras. CONCLUSIONS: Short infant LOS was 51% more common in the COVID-19 era, yet infant rehospitalization within a week did not increase. This natural experiment suggests shorter birth hospitalization LOS among family- and clinician-selected, healthy term infants may be safe with respect to infant rehospitalization, although examination of additional outcomes is needed.

Coronavirus Disease 2019 (COVID-19) Pandemic and Pregnancy Outcomes in a U.S. Population.

OBJECTIVE: To examine whether the coronavirus disease 2019 (COVID-19) pandemic altered risk of adverse pregnancy-related outcomes and whether there were differences by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection status among pregnant women. METHODS: In this retrospective cohort study using Epic's Cosmos research platform, women who delivered during the pandemic (March-December 2020) were compared with those who delivered prepandemic (matched months 2017-2019). Within the pandemic epoch, those who tested positive for SARS-CoV-2 infection were compared with those with negative test results or no SARS-CoV-2 diagnosis. Comparisons were performed using standardized differences, with a value greater than 0.1 indicating meaningful differences between groups. RESULTS: Among 838,489 women (225,225 who delivered during the pandemic), baseline characteristics were similar between epochs. There were no significant differences in adverse pregnancy outcomes between epochs (standardized difference<0.10). In the pandemic epoch, 108,067 (48.0%) women had SARS-CoV-2 testing available; of those, 7,432 (6.9%) had positive test results. Compared with women classified as negative for SARS-CoV-2 infection, those who tested positive for SARS-CoV-2 infection were less likely to be non-Hispanic White or Asian or to reside in the Midwest and more likely to be Hispanic, have public insurance, be obese, and reside in the South or in high social vulnerability ZIP codes. There were no significant differences in the frequency of preterm birth (8.5% vs 7.6%, standardized difference=0.032), stillbirth (0.4% vs 0.4%, standardized difference=-0.002), small for gestational age (6.4% vs 6.5%, standardized difference=-0.002), large for gestational age (7.7% vs 7.7%, standardized difference=-0.001), hypertensive disorders of pregnancy (16.3% vs 15.8%, standardized difference=0.014), placental abruption (0.5% vs 0.4%, standardized difference=0.007), cesarean birth (31.2% vs 29.4%, standardized difference=0.039), or postpartum hemorrhage (3.4% vs 3.1%, standardized difference=0.019) between those who tested positive for SARS-CoV-2 infection and those classified as testing negative. CONCLUSION: In a geographically diverse U.S. cohort, the frequency of adverse pregnancy-related outcomes did not differ between those delivering before compared with during the pandemic, nor between those classified as positive compared with negative for SARS-CoV-2 infection during pregnancy.

Modelling and understanding powder flow properties and compactability of selected active pharmaceutical ingredients, excipients and physical mixtures from critical material properties.

The development of solid dosage forms and manufacturing processes are governed by complex physical properties of the powder and the type of pharmaceutical unit operation the manufacturing processes employs. Suitable powder flow properties and compactability are crucial bulk level properties for tablet manufacturing by direct compression. It is also generally agreed that small scale powder flow measurements can be useful to predict large scale production failure. In this study, predictive multilinear regression models were effectively developed from critical material properties to estimate static powder flow parameters from particle size distribution data for a single component and for binary systems. A multilinear regression model, which was successfully developed for ibuprofen, also efficiently predicted the powder flow properties for a range of batches of two other active pharmaceutical ingredients processed by the same manufacturing route. The particle size distribution also affected the compactability of ibuprofen, and the scope of this work will be extended to the development of predictive multivariate models for compactability, in a similar manner to the approach successfully applied to flow properties.

Mitigating unwanted amorphisation: A screening method for the selection of suitable excipients.

Co-processing an active pharmaceutical ingredient (API) with a low Tg excipient has been previously reported to be an effective strategy for preventing drug amorphisation on milling. This technique relies on the ability of the excipient to form a molecular dispersion with the amorphous API during the milling process. The presence of the excipient within the amorphous phase induces a reduction of the Tg. Hence, the molecular dispersion becomes less stable than the amorphous API alone and recrystallises upon milling. The objective of this study was to develop a screening method for the selection of suitable excipients to prevent amorphisation, based on two criteria: the Tg of the excipient and the solubility of the excipient in the amorphous API. The ability of the excipients to induce Tg reduction was first assessed by measuring the Tg of the amorphous composite by thermal analysis and comparing it with that of the pure API (griseofulvin). A predicted ability for mitigation of amorphisation upon milling was then deduced from these observations for each excipient and assessed against experimental results. The same excipients were then studied with regard to their expected solubility in another amorphous API (budesonide) by Hildebrand solubility parameter calculations in order to evaluate their capacity to form an amorphous composite with the drug. The predicted effects of the excipients on comilling were compared with the amorphous content of the processed API. The screening method as applied to both APIs showed good agreement with the experimental results and were shown to be efficient for the selection of the most appropriate excipient. This approach revealed that the two key parameters involved are the Tg of the excipient and the ability of the API to form an amorphous molecular dispersion with the excipients. This work confirms and completes our previously published results on the mitigation of the amorphisation by comilling with low Tg excipients and constitutes the first report of the use of a polymeric additive for this purpose.

Emerging Nanonisation Technologies: Tailoring Crystalline Versus Amorphous Nanomaterials.

The overall pharmaceutical market is changing. A more personalised medicine approach is replacing the concept of blockbuster drugs and the "one size fits all" model. The two main forces that fuel the growth of nano-enabled drug technologies are the low aqueous solubility of new chemical entities and the pharmaceutical market itself, as the development of novel drug delivery systems can extend the drug patent lifetime. Classical solubilisation techniques, such as salt formation and the use of cyclodextrins can only be applied to drugs with ionisable groups or specific molecular weight ranges in order to fit in the cavity of the cyclodextrin. However, drug nanonisation, or particle size reduction into the nanosize range, is a versatile technique that can be applied to a wide range of pharmaceutical compounds. Nano-drugs exhibit higher surface area per unit of volume, which leads to faster dissolution kinetics and hence potentially improved bioavailability. Marketed nano-drugs are mostly crystalline due to the improved physical stability afforded by the crystalline state whereas amorphous nano-drugs have been largely neglected in spite of generating higher saturation solubility compared to their crystalline counterparts. Due to the vast potential in the global pharmaceutical market, many technologies have been licensed to produce nano-drugs. Among them, the most successful by far is Nanocrystal(®); Technology based on wet milling methods. In this review, the main methods to generate and characterise nano-drugs are covered and also, the biopharmaceutical characteristics of the marketed nano-drugs are discussed.

Outcome of combined autologous chondrocyte implantation and anterior cruciate ligament reconstruction.

BACKGROUND: Instability of the knee joint, after anterior cruciate ligament (ACL) injury, is contraindication to osteochondral defect repair. This prospective study is to investigate the role of combined autologous chondrocyte implantation (ACI) with ACL reconstruction. MATERIALS AND METHODS: Three independent groups of patients with previous ACL injuries undergoing ACI were identified and prospectively followed up. The first group had ACI in combination with ACL reconstruction (combined group); the 2(nd) group consisted of individuals who had an ACI procedure having had a previously successful ACL reconstruction (ACL first group); and the third group included patients who had an ACI procedure to a clinically stable knee with documented nonreconstructed ACL disruption (No ACL group). Their outcomes were assessed using the modified cincinnati rating system, the Bentley functional (BF) rating system (BF) and a visual analog scale (VAS). RESULTS: At a mean followup of 64.24 months for the ACL first group, 63 months for combined group and 78.33 months for the No ACL group; 60% of ACL first patients, 72.73% of combined group and 83.33% of the No ACL group felt their outcome was better following surgery. There was no significant difference demonstrated in BF and VAS between the combined and ACL first groups. Results revealed a significant affect of osteochondral defect size on outcome measures. CONCLUSION: The study confirms that ACI in combination with ACL reconstruction is a viable option with similar outcomes as those patients who have had the procedures staged.

Effectiveness of a tailored neck training program on neck strength, movement, and fatigue in under-19 male rugby players: a randomized controlled pilot study.

PURPOSE: To investigate the effect of a tailored neck muscle conditioning program on neck muscle strength, neck muscle fatigue, and range of neck movement in 16-18-year-old male rugby players. MATERIALS AND METHODS: Thirty-four male rugby players were divided into forward and back playing positions and randomized within these groups. Seventeen players were randomly assigned to each group. The test group was given a tailored 6-week exercise regime based on their baseline measurements to be performed three times a week in addition to their normal training and playing. The control group trained and played as normal. The outcome measures used were cervical spine range of movement, neck strength, and neck muscle fatigability. RESULTS: There were no clinically relevant statistically significant differences between the two groups. Trends identified between the two groups suggest that a tailored neck exercise program increases neck strength, particularly neck extension, and increases resistance to fatigue, as well as influencing right- and left-sided neck muscle balance. A reduction in range of movement was also demonstrated in the test group. There was a great deal of variability in range of movement and strength within this age group. No previously undiagnosed neck conditions were detected, and there were no adverse events reported. CONCLUSION: This study has shown that neck strength, range of movement, and susceptibility of the neck muscles to fatigue can be influenced using a focused neck training regime. It forms an important basis for a larger, multicenter study to ensure the neck is given due attention in rugby training and receives the same focus of conditioning as other parts of the body.

Nasotemporal asymmetry of retinopathy of prematurity.

OBJECTIVE: To quantify an apparent nasotemporal asymmetry in the location of retinopathy of prematurity with respect to the optic disc. METHODS: Twenty-four-bit color images were captured using a contact digital fundus camera during routine screening. Semiautomated measurements were undertaken to determine the distance between the optic disc and retinopathy located in the nasal and temporal regions of the retina. RESULTS: Forty-nine image pairs (17 right eye, 32 left eye) were captured from 10 infants during a period of 32 to 40 weeks postmenstrual age. For right eyes, averaged across age, the mean (SD) distance between the optic disc and temporal retinopathy was 426 (26) pixels and that between the optic disc and nasal retinopathy was 330 (26) pixels. Corresponding measurements for the left eye were 428 (30) and 332 (24) pixels. This observed asymmetry was found to be statistically significant in both left and right eyes (Mann-Whitney U test, P<.01). While the distance between the optic disc and retinopathy increased with age by 10 to 17 pixels per week, the extent of the asymmetry did not vary systematically with age. CONCLUSION: The location of retinopathy of prematurity is asymmetric along the horizontal meridian with respect to the optic disc-an observation germane to retinal vascular development, the pathogenesis of retinopathy of prematurity, and current disease classification by circular (symmetric) zones.

Solubility of crystalline organic compounds in high and low molecular weight amorphous matrices above and below the glass transition by zero enthalpy extrapolation.

Pharmaceutical applications which require knowledge of the solubility of a crystalline compound in an amorphous matrix are abundant in the literature. Several methods that allow the determination of such data have been reported, but so far have only been applicable to amorphous polymers above the glass transition of the resulting composites. The current work presents, for the first time, a reliable method for the determination of the solubility of crystalline pharmaceutical compounds in high and low molecular weight amorphous matrices at the glass transition and at room temperature (i.e. below the glass transition temperature), respectively. The solubilities of mannitol and indomethacin in polyvinyl pyrrolidone (PVP) K15 and PVP K25, respectively were measured at different temperatures. Mixtures of undissolved crystalline solute and saturated amorphous phase were obtained by annealing at a given temperature. The solubility at this temperature was then obtained by measuring the melting enthalpy of the crystalline phase, plotting it as a function of composition and extrapolating to zero enthalpy. This new method yielded results in accordance with the predictions reported in the literature. The method was also adapted for the measurement of the solubility of crystalline low molecular weight excipients in amorphous active pharmaceutical ingredients (APIs). The solubility of mannitol, glutaric acid and adipic acid in both indomethacin and sulfadimidine was experimentally determined and successfully compared with the difference between their respective calculated Hildebrand solubility parameters. As expected from the calculations, the dicarboxylic acids exhibited a high solubility in both amorphous indomethacin and sulfadimidine, whereas mannitol was almost insoluble in the same amorphous phases at room temperature. This work constitutes the first report of the methodology for determining an experimentally measured solubility for a low molecular weight crystalline solute in a low molecular weight amorphous matrix.

Autologous chondrocyte implantation in the knee: mid-term to long-term results.

BACKGROUND: From 1998 to 2008, 1000 skeletally mature patients underwent autologous chondrocyte implantation for an osteochondral defect of the knee. We evaluated the functional outcomes in 827 of 869 patients who had undergone autologous chondrocyte implantation with Chondron or periosteum (ACI-C/ACI-P) or matrix-assisted chondrocyte implantation (MACI) and attempted to identify factors that influenced outcome. METHODS: The age of the patient, the size and site of the osteochondral lesion, previous surgery, and the presence of early osteoarthritis were assessed for their influence on outcomes. Each factor was evaluated in a separate Cox proportional hazards model with use of hazard ratios (HRs), with 95% confidence intervals (CIs), describing the likelihood of failure for that particular factor. Outcomes were assessed with use of the modified Cincinnati score, visual analog scale pain score, and Stanmore functional score. RESULTS: The mean duration of follow-up was 6.2 years (range, two to twelve years). The mean age was thirty-four years (range, fourteen to fifty-six years), with 493 males and 334 females. The average size of the defect was 409 mm2 (range, 64 to 2075 mm2). Four hundred and twenty-one procedures (51%) were performed on the medial femoral condyle; 109 (13%), on the lateral femoral condyle; 200 (24%), on the patella; and fifty (6%), on the trochlea. Kaplan-Meier survival analysis revealed that the unadjusted graft survival rate was 78.2% at five years and 50.7% and ten years for the entire cohort. No difference was found between the survival rates of the ACI-C/ACI-P and MACI techniques (HR = 0.948, 95% CI = 0.738 to 1.219, p = 0.678). There was a significant postoperative improvement in the function and pain scores of all three outcome measures (p < 0.002). Survivorship in the group with a previous cartilage regenerative procedure was inferior to that in patients with a previously untreated lesion, with failure five times more likely in the former group (HR = 4.718, standard error [SE] = 0.742, 95% CI = 3.466 to 6.420, p < 0.001). Degenerative change in any compartment had a significant detrimental effect on survivorship, with survivorship worsening as the osteoarthritis grade increased (Grade 1: HR = 2.077, 95% CI = 1.299 to 3.322, p = 0.002; Grade 2: HR = 3.450, 95% CI = 2.646 to 4.498, p < 0.001; and Grade 3: HR = 3.820, 95% CI = 2.185 to 6.677, p < 0.001). CONCLUSIONS: Our study demonstrated an overall graft survival of 78% at five years and 51% beyond ten years following both autologous chondrocyte implantation techniques. Despite study limitations, our results demonstrate that autologous chondrocyte implantation for the treatment of osteochondral defects of the knee can achieve good results. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Reducing mechanical activation-induced amorphisation of salbutamol sulphate by co-processing with selected carboxylic acids.

The unintentional generation of amorphous character in crystalline active pharmaceutical ingredients (APIs) is an adverse consequence of mechanical activation during dosage form manufacture. In this study, we assess and compare the ability of low glass transition temperature (Tg) dicarboxylic acids to mitigate amorphisation of a model API, salbutamol sulphate (SS), on both co-milling and co-mixing. SS processed alone, as well as co-milled and co-mixed composites of the API with glutaric acid (GA), adipic acid (AA) and pimelic acid (PA) were characterised by powder X-ray diffraction (pXRD), differential scanning calorimetry (DSC) and dynamic vapour sorption (DVS). Milling and dry mixing of SS both resulted in pXRD amorphous materials. No amorphous content of SS was detected by DVS on co-milling with 50% (w/w) GA, while amorphisation was more than halved, relative to the API milled alone, on co-milling with 50% (w/w) AA and PA, respectively. Co-mixing with each excipient also resulted in a decrease in API amorphicity, although the extent of reduction was considerably less compared to the co-milling experiments. The solubility (Solexcipient) of each excipient in amorphous SS was determined by thermal methods. No further reduction in API amorphisation was achieved on co-mixing with 50% (w/w) excipient, compared to concentrations corresponding to the solubility of each excipient in the amorphous API (SolGA=36%, SolAA=21%, SolPA=22%). PXRD confirmed gradual dissolution over time of GA in amorphous SS on co-mixing. In contrast to co-mixing, co-milling SS at excipient weight fractions above their respective solubilities in the amorphous drug resulted in further reductions in API amorphisation. This is thought to be due to the generation of a molecular dispersion of amorphous API, supersaturated with excipient, thereby leading to a more pronounced composite Tg lowering effect. The results indicate that co-processing with low Tg excipients is an effective strategy at minimising amorphisation of an API on mechanical activation.

Mid-term functional outcome after the internal fixation of distal radius fractures.

BACKGROUND: Distal radius fracture is a common injury with a variety of operative and non-operative management options. There remains debate as to the optimal treatment for a given patient and fracture. Despite the popularity of volar locking plate fixation, there are few large cohort or long term follow up studies to justify this modality. Our aim was to report the functional outcome of a large number of patients at a significant follow up time after fixation of their distal radius with a volar locking plate. METHODS: 180 patients with 183 fractures and a mean age of 62.4 years were followed up retrospectively at a mean of 30 months (Standard deviation=10.4). Functional assessment was performed using the Disabilities of the Arm, Shoulder and Hand (DASH) and modified MAYO wrist scores. Statistical analysis was performed to identify possible variables affecting outcome and radiographs were assessed to determine time to fracture union. RESULTS: The median DASH score was 2.3 and median MAYO score was 90 for the whole group. Overall, 133 patients (74%) had a good or excellent DASH and MAYO score. Statistical analysis showed that no specific variable including gender, age, fracture type, post-operative immobilisation or surgeon grade significantly affected outcome. Complications occurred in 27 patients (15%) and in 11 patients were major (6%). CONCLUSION: This single centre large population series demonstrates good to excellent results in the majority of patients after volar locking plate fixation of the distal radius, with complication rates comparable to other non-operative and operative treatment modalities. On this basis we recommend this mode of fixation for distal radius fractures requiting operative intervention.