To develop a milestone-based evaluation system for the core "knowledge and skills" competency of neurology residents that is tailored to China's medical context, so as to provide precise guidance for their training and assessment.

Objective:To investigate the related factors for unexpected positive intraoperative cultures (UPC) in patients undergoing aseptic hip revision and the long-term prosthesis survival rate in such patients.Methods:A retrospective cases series analysis was conducted in 397 patients who underwent aseptic hip revision surgery at the Department of Orthopaedics, First Affiliated Hospital of Xinjiang Medical University from January 2012 to December 2021. There were 225 females and 172 males with an age ( M(IQR)) of 58(23) years (range:21 to 89 years) and a body mass index (BMI) of 25(6) kg/m 2 (range:15 to 39 kg/m 2). Based on the culture results of intraoperative specimens, patients were divided into culture-positive group (32 cases) and culture-negative group (365 cases). The clinical data were analyzed including gender, age, BMI, preoperative C-reactive protein, preoperative erythrocyte sedimentation rate, American Society of Anesthesiologists(ASA) classification, preoperative urinary bacteria, preoperative hypoproteinemia; comorbidities of diabetes mellitus, anemia, chronic obstructive pulmonary disease, cerebral infarction; history of allergy to antibiotics, smoking, drinking, previous prosthetic dislocation, previous surgical intervention; and time from symptom onset to admission, duration of surgery, etc. A univariate analysis was performed by Mann-Whitney U orχ2 test and the independent risk factors were identified by including the independent variables with P<0.20 in the univariate analysis in a logistic regression analysis of dichotomous variables. The study outcomes were defined as :(1) re-surgical treatment for any reason; (2)symptoms of infection such as sinus and incision seepage; (3) persistent excessive hip pain.The Kaplan-Meier survival curve was plotted using the study outcome of any cause as the endpoint event, and the log-rank test was used to compare the 10-year survival rate of the prosthesis in the culture-negative group with that in the culture-positive group. Results:Univariate analysis showed statistically significant differences between the culture-negative and culture-positive groups when comparing gender, BMI, ASA classification, and preoperative urinary bacterial results ( χ2=2.368, P=0.124; χ2=-1.648, P=0.098; χ2=14.128, P=0.003; and χ2=7.384, P=0.007). Logistic regression analysis showed that male, ASA classification Ⅳ, and positive preoperative urinary bacteria were independent risk factors for the development of UPC during aseptic hip revision( OR=2.35,95% CI:1.08 to 5.36, P=0.040; OR=37.32,95% CI:1.80 to 1 810.63, P=0.030; OR=4.11,95% CI:1.40 to 11.12, P=0.012). The follow-up time of the 397 patients included in this study was 70 (134) months (range:12 to 146 months). The Kaplan-Meier survival curves showed that the 10-year survival rates of the prostheses in the culture-negative and culture-positive groups were 95.7% and 75.0%, respectively. There was no statistically significant difference in the 10-year survival rate comparing the two groups ( P=0.661). Conclusions:UPC is more likely to occur in patients undergoing hip revision due to noninfectious factors in those who are male, have positive preoperative urinary bacteria, and have an ASA classification of Ⅳ. Intraoperative specimen culture results (negative or positive) do not affect 10-year prosthesis survival rate after hip revision.

Objective:To investigate the diagnostic efficacy of intraoperative direct sonication in periprosthetic joint infection (PJI).Methods:This is a retrospective case series study. The clinical data of 490 patients with PJI or aseptic prosthesis loosening after hip or knee arthroplasty admitted to the Department of Orthopaedics, First Affiliated Hospital of Xinjiang Medical University from January 2018 to December 2023 were retrospectively analyzed. There were 209 male cases, 281 female cases, aged ( M(IQR)) 63 (19) years (range: 15 to 89 years). There were 328 cases of PJI (123 cases of traditional sonication, 205 cases of intraoperative direct sonication, and 204 cases had simultaneous intraoperative synovial fluid), and 162 patients of aseptic loosening (89 cases of traditional sonication, 73 cases of intraoperative direct sonication, and 96 cases had simultaneous intraoperative synovial fluid). The method of traditional sonication: the prosthesis components were placed in a sterile container, vortexed for 30 seconds, then placed in an ultrasound bath to sonication (frequency:(40±2) kHz, power density:(0.22±0.04) W/cm2) for 5 minutes, vortexed again for 30 seconds, and the resulting sonicate fluid was extracted for culture. The method of intraoperative direct sonication: during the operation, the surgical area, the prosthesis and the tissues around the prosthesis which were placed in a sterile container were respectively subjected to sonication for 5 minutes using a portable handheld ultrasonic cell disruptor device (frequency: 25 kHz, power density:(0.22±0.04) W/cm2), and the fluids before and after sonication were extracted for culture. The method of intraoperative synovial fluid: during the operation, the joint capsule was incised, and the synovial fluid was extracted under direct vision for culture. The sensitivity, specificity, positive and negative predictive values, Youden index, the effect of preoperative antimicrobial agents on culture results, and culture duration for different culture methods. Receiver operating characteristic (ROC) curves were plotted, and the diagnostic efficacy of these methods for PJI was compared using the χ2 test, the Wilcoxon signed-rank test, and other appropriate statistical methods. Results:The sensitivity of intraoperative direct sonication was significantly higher than that of intraoperative synovial fluid culture (89.8%(184/205) vs.56.9%(116/204), χ2=44.457, P<0.01) and traditional sonication (89.8%(184/205) vs.66.7%(82/123), χ2=121.588, P<0.01). However, its specificity was lower compared to intraoperative synovial fluid (87.5%(64/73) vs. 99.0%(95/96), χ2=9.491, P=0.002). The culture duration for intraoperative direct sonication was shorter than for intraoperative synovial fluid 87.0 (41.8) hours vs. 112.5 (78.5) hours, Z=-5.121, P<0.01) and traditional sonication (87.0 (41.8) hours vs. 119.0 (67.5) hours, Z=-7.119, P<0.01). Gram-positive bacteria (predominantly Staphylococcus aureus and Staphylococcus epidermidis) were the most common isolates across all three culture methods. Furthermore, intraoperative direct sonication was more likely to detect polymicrobial infections compared to traditional sonication (38.6% vs. 2.4%, χ2=37.223, P<0.01) and intraoperative synovial fluid (38.6% vs. 0.9%, χ2=55.527, P<0.01). The ROC curve revealed that the area under the curve of intraoperative direct sonication,intraoperative synovial fluid culture and traditional sonication were 0.886 (95% CI:0.843 to 0.930), 0.779 (95% CI:0.743 to 0.815) and 0.788 (95% CI: 0.736 to 0.839). Conclusions:Compared with intraoperative synovial fluid and traditional sonication, intraoperative direct sonication has excellent sensitivity, the shortest appropriate culture duration for pathogenic bacteria, and it is more likely to diagnose PJI patients with polymicrobial infections, having better diagnostic efficacy in the diagnosis of PJI.

Objective:To evaluate the effects of low-frequency ultrasound on antibiotic susceptibility and biofilm formation of methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli (E. coli).Methods:After MRSA and E. coli were treated with low-frequency ultrasound with different parameters, they were divided into a group with different ultrasound durations and a group with different ultrasound powers. With the power parameter set at 100%, the former was divided into 5 subgroups: control, 1.0 min, 2.5 min, 5.0 min, and 10.0 min subgroups. The bacteria were sonicated for 0, 1.0, 2.5, 5.0, 10.0 min, respectively. The group with different ultrasound powers was also divided into 5 subgroups: control, 25% power, 50% power, 75% power, and 100% power subgroups. The bacteria were treated with ultrasonic powers of 0, 25%, 50%, 75%, and 100% for 5.0 min. The MRSA and E. coli corresponded to antibiotic susceptibility testing using vancomycin and meropenem. The number of bacteria surviving was assessed by colony counts. Confocal microscopy was used to observe the changes in biofilms co-cultured with 1/2 minimum inhibitory concentration (MIC) antibiotics after sonication.Results:The E. coli enhanced its susceptibility to meropenem after 5.0 min of high-power sonication while the susceptibility of MRSA to vancomycin was unaffected. The number of E. coli decreased significantly with increasing ultrasound time and power: the numbers of E. coli in the 1.0 min, 2.5 min, 5.0 min, and 10.0 min subgroups [(51.00±18.73), (30.00±9.17), (5.33±4.04), and (0.23±0.03)×10 4 CFU/mL] were significantly smaller than that in the control subgroup [(120.00±7.81)×10 4 CFU/mL], and the numbers of E. coli in the 25%, 50%, 75%, and 100% subgroups [(25.00±3.00), (8.00±2.65), (5.00±2.00), and (5.33±4.04)×10 4 CFU/mL] were significantly smaller than that in the control subgroup [(120.00±7.81)×10 4 CFU/mL] ( P<0.05). However, the number of MRSA was not significantly affected. After treatment with ultrasound combined with 1/2 MIC meropenem, the ratio of live/dead biofilm areas of E. coli decreased significantly with increasing ultrasound time and power: the proportions of E. coli in the 1.0 min, 2.5 min, 5.0 min and 10.0 min subgroups (66.10%±1.78%, 50.84%±7.99%, 60.98%±2.23%, and 29.20%±16.49%) were significantly smaller than those in the control subgroup (93.73%±0.44%), and the proportions of E. coli in the 25%, 50%, 75%, and 100% subgroups (75.23%±2.21%, 65.10%±1.25%, 57.34%±11.21%, and 60.98%±2.23%) were significantly smaller than that in the control subgroup (93.73%±0.44%) ( P<0.05). However, the MRSA live/dead biofilm area ratio was not significantly affected by the treatment with ultrasound combined with 1/2 MIC vancomycin. Conclusions:Low frequency ultrasound can effectively inhibit the growth of E. coli and significantly enhance its sensitivity to antibiotics, and its combination with antibiotics can inhibit the formation of bacterial biofilm. However, low frequency ultrasound or its combination with antibiotics has no significant effect on MRSA.

Objective:To evaluate the effects of low-frequency ultrasound on antibiotic susceptibility and biofilm formation of methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli (E. coli).Methods:After MRSA and E. coli were treated with low-frequency ultrasound with different parameters, they were divided into a group with different ultrasound durations and a group with different ultrasound powers. With the power parameter set at 100%, the former was divided into 5 subgroups: control, 1.0 min, 2.5 min, 5.0 min, and 10.0 min subgroups. The bacteria were sonicated for 0, 1.0, 2.5, 5.0, 10.0 min, respectively. The group with different ultrasound powers was also divided into 5 subgroups: control, 25% power, 50% power, 75% power, and 100% power subgroups. The bacteria were treated with ultrasonic powers of 0, 25%, 50%, 75%, and 100% for 5.0 min. The MRSA and E. coli corresponded to antibiotic susceptibility testing using vancomycin and meropenem. The number of bacteria surviving was assessed by colony counts. Confocal microscopy was used to observe the changes in biofilms co-cultured with 1/2 minimum inhibitory concentration (MIC) antibiotics after sonication.Results:The E. coli enhanced its susceptibility to meropenem after 5.0 min of high-power sonication while the susceptibility of MRSA to vancomycin was unaffected. The number of E. coli decreased significantly with increasing ultrasound time and power: the numbers of E. coli in the 1.0 min, 2.5 min, 5.0 min, and 10.0 min subgroups [(51.00±18.73), (30.00±9.17), (5.33±4.04), and (0.23±0.03)×10 4 CFU/mL] were significantly smaller than that in the control subgroup [(120.00±7.81)×10 4 CFU/mL], and the numbers of E. coli in the 25%, 50%, 75%, and 100% subgroups [(25.00±3.00), (8.00±2.65), (5.00±2.00), and (5.33±4.04)×10 4 CFU/mL] were significantly smaller than that in the control subgroup [(120.00±7.81)×10 4 CFU/mL] ( P<0.05). However, the number of MRSA was not significantly affected. After treatment with ultrasound combined with 1/2 MIC meropenem, the ratio of live/dead biofilm areas of E. coli decreased significantly with increasing ultrasound time and power: the proportions of E. coli in the 1.0 min, 2.5 min, 5.0 min and 10.0 min subgroups (66.10%±1.78%, 50.84%±7.99%, 60.98%±2.23%, and 29.20%±16.49%) were significantly smaller than those in the control subgroup (93.73%±0.44%), and the proportions of E. coli in the 25%, 50%, 75%, and 100% subgroups (75.23%±2.21%, 65.10%±1.25%, 57.34%±11.21%, and 60.98%±2.23%) were significantly smaller than that in the control subgroup (93.73%±0.44%) ( P<0.05). However, the MRSA live/dead biofilm area ratio was not significantly affected by the treatment with ultrasound combined with 1/2 MIC vancomycin. Conclusions:Low frequency ultrasound can effectively inhibit the growth of E. coli and significantly enhance its sensitivity to antibiotics, and its combination with antibiotics can inhibit the formation of bacterial biofilm. However, low frequency ultrasound or its combination with antibiotics has no significant effect on MRSA.

Objective:To investigate the related factors for unexpected positive intraoperative cultures (UPC) in patients undergoing aseptic hip revision and the long-term prosthesis survival rate in such patients.Methods:A retrospective cases series analysis was conducted in 397 patients who underwent aseptic hip revision surgery at the Department of Orthopaedics, First Affiliated Hospital of Xinjiang Medical University from January 2012 to December 2021. There were 225 females and 172 males with an age ( M(IQR)) of 58(23) years (range:21 to 89 years) and a body mass index (BMI) of 25(6) kg/m 2 (range:15 to 39 kg/m 2). Based on the culture results of intraoperative specimens, patients were divided into culture-positive group (32 cases) and culture-negative group (365 cases). The clinical data were analyzed including gender, age, BMI, preoperative C-reactive protein, preoperative erythrocyte sedimentation rate, American Society of Anesthesiologists(ASA) classification, preoperative urinary bacteria, preoperative hypoproteinemia; comorbidities of diabetes mellitus, anemia, chronic obstructive pulmonary disease, cerebral infarction; history of allergy to antibiotics, smoking, drinking, previous prosthetic dislocation, previous surgical intervention; and time from symptom onset to admission, duration of surgery, etc. A univariate analysis was performed by Mann-Whitney U orχ2 test and the independent risk factors were identified by including the independent variables with P<0.20 in the univariate analysis in a logistic regression analysis of dichotomous variables. The study outcomes were defined as :(1) re-surgical treatment for any reason; (2)symptoms of infection such as sinus and incision seepage; (3) persistent excessive hip pain.The Kaplan-Meier survival curve was plotted using the study outcome of any cause as the endpoint event, and the log-rank test was used to compare the 10-year survival rate of the prosthesis in the culture-negative group with that in the culture-positive group. Results:Univariate analysis showed statistically significant differences between the culture-negative and culture-positive groups when comparing gender, BMI, ASA classification, and preoperative urinary bacterial results ( χ2=2.368, P=0.124; χ2=-1.648, P=0.098; χ2=14.128, P=0.003; and χ2=7.384, P=0.007). Logistic regression analysis showed that male, ASA classification Ⅳ, and positive preoperative urinary bacteria were independent risk factors for the development of UPC during aseptic hip revision( OR=2.35,95% CI:1.08 to 5.36, P=0.040; OR=37.32,95% CI:1.80 to 1 810.63, P=0.030; OR=4.11,95% CI:1.40 to 11.12, P=0.012). The follow-up time of the 397 patients included in this study was 70 (134) months (range:12 to 146 months). The Kaplan-Meier survival curves showed that the 10-year survival rates of the prostheses in the culture-negative and culture-positive groups were 95.7% and 75.0%, respectively. There was no statistically significant difference in the 10-year survival rate comparing the two groups ( P=0.661). Conclusions:UPC is more likely to occur in patients undergoing hip revision due to noninfectious factors in those who are male, have positive preoperative urinary bacteria, and have an ASA classification of Ⅳ. Intraoperative specimen culture results (negative or positive) do not affect 10-year prosthesis survival rate after hip revision.

Objective:To investigate the diagnostic efficacy of intraoperative direct sonication in periprosthetic joint infection (PJI).Methods:This is a retrospective case series study. The clinical data of 490 patients with PJI or aseptic prosthesis loosening after hip or knee arthroplasty admitted to the Department of Orthopaedics, First Affiliated Hospital of Xinjiang Medical University from January 2018 to December 2023 were retrospectively analyzed. There were 209 male cases, 281 female cases, aged ( M(IQR)) 63 (19) years (range: 15 to 89 years). There were 328 cases of PJI (123 cases of traditional sonication, 205 cases of intraoperative direct sonication, and 204 cases had simultaneous intraoperative synovial fluid), and 162 patients of aseptic loosening (89 cases of traditional sonication, 73 cases of intraoperative direct sonication, and 96 cases had simultaneous intraoperative synovial fluid). The method of traditional sonication: the prosthesis components were placed in a sterile container, vortexed for 30 seconds, then placed in an ultrasound bath to sonication (frequency:(40±2) kHz, power density:(0.22±0.04) W/cm2) for 5 minutes, vortexed again for 30 seconds, and the resulting sonicate fluid was extracted for culture. The method of intraoperative direct sonication: during the operation, the surgical area, the prosthesis and the tissues around the prosthesis which were placed in a sterile container were respectively subjected to sonication for 5 minutes using a portable handheld ultrasonic cell disruptor device (frequency: 25 kHz, power density:(0.22±0.04) W/cm2), and the fluids before and after sonication were extracted for culture. The method of intraoperative synovial fluid: during the operation, the joint capsule was incised, and the synovial fluid was extracted under direct vision for culture. The sensitivity, specificity, positive and negative predictive values, Youden index, the effect of preoperative antimicrobial agents on culture results, and culture duration for different culture methods. Receiver operating characteristic (ROC) curves were plotted, and the diagnostic efficacy of these methods for PJI was compared using the χ2 test, the Wilcoxon signed-rank test, and other appropriate statistical methods. Results:The sensitivity of intraoperative direct sonication was significantly higher than that of intraoperative synovial fluid culture (89.8%(184/205) vs.56.9%(116/204), χ2=44.457, P<0.01) and traditional sonication (89.8%(184/205) vs.66.7%(82/123), χ2=121.588, P<0.01). However, its specificity was lower compared to intraoperative synovial fluid (87.5%(64/73) vs. 99.0%(95/96), χ2=9.491, P=0.002). The culture duration for intraoperative direct sonication was shorter than for intraoperative synovial fluid 87.0 (41.8) hours vs. 112.5 (78.5) hours, Z=-5.121, P<0.01) and traditional sonication (87.0 (41.8) hours vs. 119.0 (67.5) hours, Z=-7.119, P<0.01). Gram-positive bacteria (predominantly Staphylococcus aureus and Staphylococcus epidermidis) were the most common isolates across all three culture methods. Furthermore, intraoperative direct sonication was more likely to detect polymicrobial infections compared to traditional sonication (38.6% vs. 2.4%, χ2=37.223, P<0.01) and intraoperative synovial fluid (38.6% vs. 0.9%, χ2=55.527, P<0.01). The ROC curve revealed that the area under the curve of intraoperative direct sonication,intraoperative synovial fluid culture and traditional sonication were 0.886 (95% CI:0.843 to 0.930), 0.779 (95% CI:0.743 to 0.815) and 0.788 (95% CI: 0.736 to 0.839). Conclusions:Compared with intraoperative synovial fluid and traditional sonication, intraoperative direct sonication has excellent sensitivity, the shortest appropriate culture duration for pathogenic bacteria, and it is more likely to diagnose PJI patients with polymicrobial infections, having better diagnostic efficacy in the diagnosis of PJI.

Currently， there are many difficulties in formulating recommendations of traditional Chinese medicine （TCM） clinical practice guidelines. This paper analyzed and summarized the unique or prominent difficult issues in the formulation of recommendations faced by TCM guidelines， such as experts' professional background and experience bringing about the preferance from the academic emotion， inconsistency between different academic schools making it difficult to reach consensus， lack of guiding principles of the decision weight of different dimensions for recommendations. Therefore， methodological suggestions have been put forward， including organizing parallel TCM and western medicine consensus group， improving the method of combining TCM and western medicine paradigm， attaching great importance to the evidence-based governance of academic schools， and promoting the research on different dimensions for recommendation formulation， which may provide a methodological reference for the guideline development.

Objective:To investigate the clinical outcomes of total knee arthroplasty (TKA) combined with the modified “overlap” technique in the treatment of end-stage knee osteoarthritis with fixed patellar dislocation.Methods:This is a retrospective case series study. Clinical data of 19 patients (22 knees) who underwent TKA combined with the modified “overlap” technique for the treatment of end-stage knee osteoarthritis with permanent patellar dislocation from January 2011 to January 2022 in the Department of Orthopaedics, the First Affiliated Hospital of Xinjiang Medical University were retrospectively analyzed. The cohort included 5 males (6 knees) and 14 females (16 knees), with an age of (60.6±12.2) years (range:33 to 77 years) and a body mass index of (25.4±4.1) kg/m2 (range:20.0 to 33.0 kg/m2). Among them, 11 cases (12 knee) had valgus deformity, with Keblish classification showing mild in 2 cases (2 knees), moderate in 6 cases (6 knees), and severe in 4 cases (4 knees). All cases were treated using a medial parapatellar approach, with lateral retinaculum release combined with the “overlap” technique to restore the patellar trajectory. Knee function was evaluated using the American Knee Society (KSS) Score. Paired sample t tests were used for intergroup comparisons. Results:All patients successfully completed the surgery. Postoperatively, patellar dislocation, knee valgus deformity, flexion contracture deformity, and extensor lag were all corrected. All patients were followed up, with a follow-up duration of (63.8±35.2) months (range:24 to 136 months). One patient experienced periprosthetic infection 2 weeks postoperatively, 1 patient had recurrent patellar dislocation 2 months postoperatively, 1 patient developed knee stiffness 3 months postoperatively and underwent closed manipulation. No other patients exhibited signs of patellar dislocation or subluxation. At the last follow-up, the KSS clinical score improved from (36.4±12.7) points preoperatively to (83.4±6.3) points postoperatively ( t=-15.15, P<0.01), and the KSS functional score improved from (30.7±11.1) points preoperatively to (77.6±8.3) points postoperatively ( t=-14.37, P<0.01). The range of motion of the knee increased from 81.7°±19.6° preoperatively to 107.6°±12.5° postoperatively ( t=-4.85, P<0.01). Conclusion:TKA combined with the modified “overlap” technique is an effective surgical option for the treatment of end-stage knee osteoarthritis with permanent patellar dislocation, demonstrating satisfactory clinical outcomes.

Objective:To investigate the clinical outcomes of total knee arthroplasty (TKA) combined with the modified “overlap” technique in the treatment of end-stage knee osteoarthritis with fixed patellar dislocation.Methods:This is a retrospective case series study. Clinical data of 19 patients (22 knees) who underwent TKA combined with the modified “overlap” technique for the treatment of end-stage knee osteoarthritis with permanent patellar dislocation from January 2011 to January 2022 in the Department of Orthopaedics, the First Affiliated Hospital of Xinjiang Medical University were retrospectively analyzed. The cohort included 5 males (6 knees) and 14 females (16 knees), with an age of (60.6±12.2) years (range:33 to 77 years) and a body mass index of (25.4±4.1) kg/m2 (range:20.0 to 33.0 kg/m2). Among them, 11 cases (12 knee) had valgus deformity, with Keblish classification showing mild in 2 cases (2 knees), moderate in 6 cases (6 knees), and severe in 4 cases (4 knees). All cases were treated using a medial parapatellar approach, with lateral retinaculum release combined with the “overlap” technique to restore the patellar trajectory. Knee function was evaluated using the American Knee Society (KSS) Score. Paired sample t tests were used for intergroup comparisons. Results:All patients successfully completed the surgery. Postoperatively, patellar dislocation, knee valgus deformity, flexion contracture deformity, and extensor lag were all corrected. All patients were followed up, with a follow-up duration of (63.8±35.2) months (range:24 to 136 months). One patient experienced periprosthetic infection 2 weeks postoperatively, 1 patient had recurrent patellar dislocation 2 months postoperatively, 1 patient developed knee stiffness 3 months postoperatively and underwent closed manipulation. No other patients exhibited signs of patellar dislocation or subluxation. At the last follow-up, the KSS clinical score improved from (36.4±12.7) points preoperatively to (83.4±6.3) points postoperatively ( t=-15.15, P<0.01), and the KSS functional score improved from (30.7±11.1) points preoperatively to (77.6±8.3) points postoperatively ( t=-14.37, P<0.01). The range of motion of the knee increased from 81.7°±19.6° preoperatively to 107.6°±12.5° postoperatively ( t=-4.85, P<0.01). Conclusion:TKA combined with the modified “overlap” technique is an effective surgical option for the treatment of end-stage knee osteoarthritis with permanent patellar dislocation, demonstrating satisfactory clinical outcomes.