Hot Melt Extruded High-Dose Amorphous Solid Dispersions Containing Lumefantrine and Soluplus.

Over the last 15 years, a small number of paediatric artemisinin-based combination therapy products have been marketed. These included Riamet® and Coartem® dispersible tablets, a combination of artemether and lumefantrine, co-developed by the Medicines for Malaria Venture and Novartis. Disappointingly, patient compliance, requirement for high-fat meal, and sporadic drug dissolution behaviours following administration still result in considerable challenges for these products. The first and foremost barrier that needs addressed for successful delivery of the artemether/lumefantrine combination is the poor solubility of lumefantrine within the gastrointestinal fluids. In this work, amorphous solid dispersions of lumefantrine within Soluplus®-based matrices have been manufactured using hot melt extrusion as a potential formulation strategy to achieve enhanced dissolution and apparent solubility. The drug loading capacity of Soluplus® to accommodate amorphous lumefantrine, whilst ensuring improved in-vitro dissolution performance, was investigated. The extrusion process employed a variety of processing parameters, including various temperature profiles and different production scales. The influence of variation in extrusion conditions upon the physical stability of manufactured amorphous solid dispersions was also examined. This allowed for a greater understanding of the role of extrusion processing conditions on the performance of supersaturated amorphous solid dispersions during dissolution and storage. This may allow for the design and manufacture of drug enabled formulations with lower drug dosing and thus a lower risk of adverse effects.

Comparison of Postoperative Effects between Medial Pivot Prosthesis and Posterior Stabilized Prosthesis.

OBJECTIVE: To compare the postoperative inflammation and pain response between medial pivot (MP) and posterior stabilized (PS) prostheses among total knee arthroplasty (TKA) patients. METHODS: A prospective cohort study was conducted from January 2019 to May 2019 at the Affiliated Hospital of Qingdao University. The study included patients diagnosed with stage III or IV Kellgren-Lawrence knee osteoarthritis (KOA) who had failed conservative treatment, had undergone no previous knee surgeries, had varus substantial deformities (11°-20° deviation), and had received their first unilateral TKA. A total of 109 patients who underwent PS prosthesis TKA and 98 patients who underwent MP prosthesis TKA were continuously enrolled. Inflammation biomarkers, such as leukocyte (white blood cells), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP), together with hemoglobin (Hb), the visual analog pain score (VAS) and range of motion (ROM) were compared between the two groups. The Student t-test was applied to analyze continuous parameters, and the χ2 -test was used for categorical parameters. The linear mixed model was used for the repeated measurement data from the follow-up visits. Multivariate backward logistic and linear regression models were used to determine the factors potentially influencing prostheses and VAS scores. RESULTS: All these enrolled patients were followed up at 2, 4, 7, and 30 days after TKA. There were no significant differences between the PS group and the MP group in body mass index (BMI), gender, laterality, usage of nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids, and drain tube extubation time (P > 0.05). Compared with the PS group, the MP group were older (67.5 years vs 65.4 years), and had a higher mid-vastus approach rate (67.3% vs 26.6%), a shorter tourniquet duration (68.3 ± 10.2 h vs 73.9 ± 11.2 h), a larger prosthetic pad (10.8 ± 1.2 mm vs 10.4 ± 1.2 mm), and a lower drain tube diversion volume (187.6 ± 119.3 mL vs 234.0 ± 155.7 mL). In the linear mixed model, MP prostheses had less CRP and ESR elevation and less Hb decrease than PS prostheses (P for group × time < 0.001). There were no significant differences in the changing trends between MP and PS prostheses by time for VAS scores and ROM. In the multivariate logistic regression model, MP prostheses showed significant differences compared with PS prostheses in treatment approach (odds ratio [OR] = 3.371, 95% confidence interval [CI]: 1.953-7.127; P < 0.001), ultrasound treatment start time (OR = 2.669, 95% CI: 1.385-5.141; P = 0.003), and tourniquet duration (OR = 0.954, 95% CI: 0.925-0.984; P = 0.003). Higher VAS scores on the second day postoperatively were related to high VAS scores preoperatively, use of opioids, high drain tube diversion, long tourniquet duration, and long drain tube extubation (P < 0.05), respectively. CONCLUSION: The MP prostheses showed potential advantages compared with PS prostheses in TKA in inflammatory responses.

[A comparative research on the treatment of ankle fracture with dislocation between emergency surgery and selective surgery].

OBJECTIVE: To investigate the differences between emergency surgery and selective surgery treatment of ankle fractures with dislocation. METHODS: In the study, 40 patients with ankle fracture and dislocation were treated and followed up from May 2013 to May 2014, and all the data were collected and analyzed. The subjects involved 29 male patients and 11 female patients. The patients were randomly separated into two groups, and the patients in group A were given surgical intervention within 6 hours after injury, while those in group B were initially given close reduction and given selective operation when the soft tissue condition got better. Group A contained 13 male patients and 7 female patients with average age of 37.10; Group B consisted of 15 male and 5 female, with average age of 37.85. RESULTS: The Baird-Jackson score was applied for assessment of the patients' outcomes. According to the score, the outcomes were classified into excellent, good, fair, and poor. In group A (emergency group), the outcomes were 13 (65.0%), 4 (20.0%), 3 (15.0%), and 0, respectively. In group B (selective group), they were 11 (55.0%), 7 (35.0%), 2 (10.0%), and 0, respectively. The numbers of the patients from excellent to poor were 24 (55.0%), 11 (27.5%), 5 (12.5%), and 0, respectively. CONCLUSION: There is no significant difference in postoperative function between the two groups, however, early surgical intervention can benefit in accomplishing anatomical reduction much easier and shortening the time of hospitalization, which is cost-saving for the patients.

Printed three-dimensional anatomic templates for virtual preoperative planning before reconstruction of old pelvic injuries: initial results.

BACKGROUND: Old pelvis fractures are among the most challenging fractures to treat because of their complex anatomy, difficult-to-access surgical sites, and the relatively low incidence of such cases. Proper evaluation and surgical planning are necessary to achieve the pelvic ring symmetry and stable fixation of the fracture. The goal of this study was to assess the use of three-dimensional (3D) printing techniques for surgical management of old pelvic fractures. METHODS: First, 16 dried human cadaveric pelvises were used to confirm the anatomical accuracy of the 3D models printed based on radiographic data. Next, nine clinical cases between January 2009 and April 2013 were used to evaluate the surgical reconstruction based on the 3D printed models. The pelvic injuries were all type C, and the average time from injury to reconstruction was 11 weeks (range: 8-17 weeks). The workflow consisted of: (1) Printing patient-specific bone models based on preoperative computed tomography (CT) scans, (2) virtual fracture reduction using the printed 3D anatomic template, (3) virtual fracture fixation using Kirschner wires, and (4) preoperatively measuring the osteotomy and implant position relative to landmarks using the virtually defined deformation. These models aided communication between surgical team members during the procedure. This technique was validated by comparing the preoperative planning to the intraoperative procedure. RESULTS: The accuracy of the 3D printed models was within specification. Production of a model from standard CT DICOM data took 7 hours (range: 6-9 hours). Preoperative planning using the 3D printed models was feasible in all cases. Good correlation was found between the preoperative planning and postoperative follow-up X-ray in all nine cases. The patients were followed for 3-29 months (median: 5 months). The fracture healing time was 9-17 weeks (mean: 10 weeks). No delayed incision healing, wound infection, or nonunions occurred. The results were excellent in two cases, good in five, and poor in two based on the Majeed score. CONCLUSIONS: The 3D printing planning technique for pelvic surgery was successfully integrated into a clinical workflow to improve patient-specific preoperative planning by providing a visual and haptic model of the injury and allowing patient-specific adaptation of each osteosynthesis implant to the virtually reduced pelvis.