1.Exploration of Milestone Evaluation System for Core Competencies in Knowledge and Skills of Neurology Residents
Liling DONG ; Dan XU ; Yuze CAO ; Siyuan FAN ; Hang LI ; Yicheng ZHU ; Lixin ZHOU ; Jun NI
Medical Journal of Peking Union Medical College Hospital 2025;16(6):1619-1628
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. Using the Delphi method, the study first constructed an initial framework through literature review, on-site investigation and expert-group discussion. Two rounds of expert consultation were then conducted among specialists in neurology education across China. Indicators were screened and optimized according to the mean score, agreement rate and coefficient of variation (CV), ultimately finalizing the system. The expert response rates in both rounds were 100%. The group authority coefficients were 0.97 and 0.98, with Cronbach's α of 0.90 and 0.88, respectively. The mean scores of all indicators ranged from 3.88 to 5.00, agreement rates from 62.50 % to 100 %, and CVs from 0 to 0.21. The finalized framework comprises one first-level indicator, three second-level indicators and 17 third-level indicators. The milestone evaluation system for core competencies in "knowledge and skills" of neurology residents developed in this study is scientific and reasonable, providing a standardized and scientific assessment tool for the standardized training of neurology residents.
3.Efficacy observation of pelvic floor autologous fascia integrated repair based on membrane anatomy for complete rectal prolapse
Zhibiao MEI ; Yongli CAO ; Bingbing LV ; Siyuan WANG ; Kun TIAN ; Qingli LIU ; Linzi MA ; Yunshuai WANG ; Dong WEI
Chinese Journal of Gastrointestinal Surgery 2025;28(12):1441-1447
Objective:To compare the clinical efficacy of laparoscopic pelvic floor autologous fascia integral repair based on membrane anatomy versus transperineal proctosigmoidectomy (Altemeier procedure) in the treatment of patients with complete rectal prolapse (CRP).Methods:This study employed a retrospective observational cohort design. Clinical data were collected from a total of 55 CRP patients who underwent surgical treatment between January 2018 and July 2023, including 25 patients from Luoyang Central Hospital, affiliated with Zhengzhou University, and 30 patients from the 989th Hospital of the Joint Logistics Support Force & Military Anorectal Surgery Research Institute. All patients undergoing surgery met the following criteria: aged ≥ 18 years, rectal prolapse protruding outside the anus, prolapse length > 5 cm with inability to self-reduce, conforming to the diagnostic criteria for CRP, and being first-time treated patients. Twenty-seven patients who underwent the Altemeier procedure between January 2018 and March 2021 were assigned to the Altemeier group; 28 patients who underwent laparoscopic pelvic floor autologous fascia integral repair based on membrane anatomy between April 2021 and July 2023 were assigned to the integral repair group. The therapeutic efficacy differences between the two groups were analyzed and compared, including the CRP length (DCRP), Wexner Constipation Score, Wexner Fecal Incontinence Score, and Gastrointestinal Quality of Life Index (GIQLI) before surgery and at 6, 12, and 24 months after surgery, as well as postoperative complications and recurrence at 24 months after surgery.Results:There were no statistically significant differences between the two groups in terms of gender distribution, age, preoperative body mass index (BMI), defecation frequency, DCRP, Wexner Constipation Score, Wexner Fecal Incontinence Score, and GIQLI (all P>0.05). All patients completed the surgery. The length of hospital stay and intraoperative blood loss in the integral repair group were significantly less than those in the Altemeier group (both P<0.01). At 6, 12, and 24 months after surgery, the DCRP, Wexner Constipation Score, Wexner Fecal Incontinence Score, and GIQLI in both groups significantly improved compared with the preoperative values (all P<0.001). At 6, 12, and 24 months after surgery, the CRP treatment effect, Wexner Constipation Score, Wexner Fecal Incontinence Score, and GIQLI in the integral repair group were significantly better than those in the Altemeier group (χ2=15.821, P<0.001; χ2=18.238, P<0.001; χ2 = 12.558, P=0.001; and χ2 =22.413, P<0.001, respectively). In the integral repair group, 4 patients (14.3%) developed grade I-III postoperative complications, including 2 cases of urinary retention, 1 case of anastomotic bleeding, and 1 case of anastomotic stenosis. In the Altemeier group, 11 patients (40.7%) developed grade I-III postoperative complications, including 4 cases of urinary retention, 3 cases of anastomotic bleeding, 1 case of anastomotic stenosis, 2 cases of intestinal fistula, and 1 case of fecal incontinence. The difference between the two groups was statistically significant (χ2=4.850, P=0.028). There was no recurrence of CRP in the integral repair group at 24 months after surgery, while 7 cases of CRP recurrence were observed in the Altemeier group at 24 months after surgery. The difference between the two groups was statistically significant (χ2=6.148, P=0.013). Conclusion:The autologous fascia repair technique based on membrane anatomy and the pelvic floor integral theory is superior to the transperineal Altemeier procedure in the treatment of CRP. Furthermore, it is an effective surgical method for CRP.
4.Efficacy observation of pelvic floor autologous fascia integrated repair based on membrane anatomy for complete rectal prolapse
Zhibiao MEI ; Yongli CAO ; Bingbing LV ; Siyuan WANG ; Kun TIAN ; Qingli LIU ; Linzi MA ; Yunshuai WANG ; Dong WEI
Chinese Journal of Gastrointestinal Surgery 2025;28(12):1441-1447
Objective:To compare the clinical efficacy of laparoscopic pelvic floor autologous fascia integral repair based on membrane anatomy versus transperineal proctosigmoidectomy (Altemeier procedure) in the treatment of patients with complete rectal prolapse (CRP).Methods:This study employed a retrospective observational cohort design. Clinical data were collected from a total of 55 CRP patients who underwent surgical treatment between January 2018 and July 2023, including 25 patients from Luoyang Central Hospital, affiliated with Zhengzhou University, and 30 patients from the 989th Hospital of the Joint Logistics Support Force & Military Anorectal Surgery Research Institute. All patients undergoing surgery met the following criteria: aged ≥ 18 years, rectal prolapse protruding outside the anus, prolapse length > 5 cm with inability to self-reduce, conforming to the diagnostic criteria for CRP, and being first-time treated patients. Twenty-seven patients who underwent the Altemeier procedure between January 2018 and March 2021 were assigned to the Altemeier group; 28 patients who underwent laparoscopic pelvic floor autologous fascia integral repair based on membrane anatomy between April 2021 and July 2023 were assigned to the integral repair group. The therapeutic efficacy differences between the two groups were analyzed and compared, including the CRP length (DCRP), Wexner Constipation Score, Wexner Fecal Incontinence Score, and Gastrointestinal Quality of Life Index (GIQLI) before surgery and at 6, 12, and 24 months after surgery, as well as postoperative complications and recurrence at 24 months after surgery.Results:There were no statistically significant differences between the two groups in terms of gender distribution, age, preoperative body mass index (BMI), defecation frequency, DCRP, Wexner Constipation Score, Wexner Fecal Incontinence Score, and GIQLI (all P>0.05). All patients completed the surgery. The length of hospital stay and intraoperative blood loss in the integral repair group were significantly less than those in the Altemeier group (both P<0.01). At 6, 12, and 24 months after surgery, the DCRP, Wexner Constipation Score, Wexner Fecal Incontinence Score, and GIQLI in both groups significantly improved compared with the preoperative values (all P<0.001). At 6, 12, and 24 months after surgery, the CRP treatment effect, Wexner Constipation Score, Wexner Fecal Incontinence Score, and GIQLI in the integral repair group were significantly better than those in the Altemeier group (χ2=15.821, P<0.001; χ2=18.238, P<0.001; χ2 = 12.558, P=0.001; and χ2 =22.413, P<0.001, respectively). In the integral repair group, 4 patients (14.3%) developed grade I-III postoperative complications, including 2 cases of urinary retention, 1 case of anastomotic bleeding, and 1 case of anastomotic stenosis. In the Altemeier group, 11 patients (40.7%) developed grade I-III postoperative complications, including 4 cases of urinary retention, 3 cases of anastomotic bleeding, 1 case of anastomotic stenosis, 2 cases of intestinal fistula, and 1 case of fecal incontinence. The difference between the two groups was statistically significant (χ2=4.850, P=0.028). There was no recurrence of CRP in the integral repair group at 24 months after surgery, while 7 cases of CRP recurrence were observed in the Altemeier group at 24 months after surgery. The difference between the two groups was statistically significant (χ2=6.148, P=0.013). Conclusion:The autologous fascia repair technique based on membrane anatomy and the pelvic floor integral theory is superior to the transperineal Altemeier procedure in the treatment of CRP. Furthermore, it is an effective surgical method for CRP.
5.Discussion on the Scientific Connotation of Fortifying Spleen, Resolving Phlegm and Dispelling Stasis in the Treatment of Coronary Heart Disease under the Guidance of Dysfunctional High-Density Lipoprotein
Lianqun JIA ; Qige WANG ; Guoyuan SUI ; Nan SONG ; Huimin CAO ; Liang KONG ; Meijun LV ; Yuan CAO ; Ning YU ; Siyuan DING ; Guanlin YANG
Journal of Traditional Chinese Medicine 2024;65(2):128-133
The key pathogenesis of coronary heart disease (CHD) is spleen deficiency and phlegm stasis, and dysfunctional high-density lipoprotein (dys-HDL) may be the biological basis for the occurrence of CHD due to spleen deficiency and phlegm stasis. Considering the biological properties and effects of high-density lipoprotein (HDL), it is believed that the structure and components of HDL are abnormal in the state of spleen deficiency which led to dys-HDL; and dys-HDL contributes to the formation of atherosclerotic plaques through two major pathways, namely, mediating the dysfunction of endothelial cells and mediating the foaminess of macrophages and smooth muscle cells, thus triggering the development of CHD. It is also believed that dys-HDL is a microcosmic manifestation and a pathological product of spleen deficiency, and spleen deficiency makes foundation for the production of dys-HDL; dys-HDL is also an important biological basis for the phlegm-stasis interactions in CHD. The method of fortifying spleen, resolving phlegm, and dispelling stasis, is proposed as an important principle in the treatment of CHD by traditional Chinese medicine, which can achieve the therapeutic purpose by affecting the changes in the structure and components of dys-HDL, thus revealing the scientific connotation of this method, and providing ideas for the diagnosis and treatment of CHD by traditional Chinese medicine.
6.The 504th case: Multiple lymph node enlargement, renal insufficiency, blindness, and white matter lesions of the brain
Chong WEI ; Zhe ZHUANG ; Yunlong LI ; Xiaoxiao SHI ; Yubing WEN ; Wei CAO ; Siyuan FAN ; Xiao ZHANG ; Yan ZHANG ; Wei ZHANG ; Daobin ZHOU
Chinese Journal of Internal Medicine 2024;63(3):316-320
A 65-year-old male patient was admitted for recurrent lymph node enlargement for 5 years and elevated creatinine for 6 months. This patient was diagnosed with angioimmunoblastic T-cell lymphoma 5 years ago and underwent multiple lines of anti-tumor therapy, including cytotoxic chemotherapy; epigenetic modifying drugs such as chidamide and azacitidine; the immunomodulator lenalidomide; and targeted therapy such as rituximab, a CD20-targeting antibody, and brentuximab vedotin, which targets CD30. Although the tumor was considered stable, multiple virus activation (including BK virus, JC virus, and cytomegalovirus) accompanied by the corresponding organ damage (polyomavirus nephropathy, cytomegalovirus retinitis, and progressive multifocal leukoencephalopathy) occurred during anti-tumor treatment. Anti-tumor therapy was suspended and ganciclovir was used. The serum viral load decreased and organ functions were stabilized. The purpose of this report was to raise clinicians′ awareness of opportunistic virus reactivation during anti-tumor treatment.
7.Mechanism of HMGB1 in scarring after glaucoma drainage valve implantation
Siyuan LIU ; Fan CAO ; Jingjing DING ; Chuanxi WANG ; Biqing DING ; Kun LIANG ; Zhengxuan JIANG ; Ning BAO
International Eye Science 2024;24(1):18-23
AIM: To explore the dynamic expression of high mobility group box 1(HMGB1)in scar tissues after glaucoma drainage valve implantation, and to further reveal the role and possible mechanism of HMGB1 in scarring after glaucoma surgery.METHODS: A total of 60 New Zealand white rabbits were randomly divided into control group(n=20), model group(n=20, silicone implantation under conjunctival sac)and model with drug administration group(n=20, silicone implantation under conjunctival sac combined with 5-fluorouracil injection). The conjunctival tissues were collected at 4 and 8 wk after surgery. HE staining and Masson staining were used to detect the proliferation and distribution of fibroblasts and collagen fibers in conjunctival tissues. Immunohistochemistry was utilized to detect the distribution and changes of HMGB1, transforming growth factor(TGF)-β1, Smad3 and α-smooth muscle actin(SMA)in conjunctival tissues. RT-PCR and Western blot were adopted to detect the mRNA and protein expression of HMGB1, TGF-β1, Smad3 and α-SMA in conjunctival tissues.RESULTS: HE staining and Masson staining showed that the proliferation of inflammatory cells, fibroblasts and collagen fibers in the model group was significantly higher than that in the control group at both 4 and 8 wk. Meanwhile, the proliferation of fibroblasts and collagen fibers in the model with drug administration group was significantly lower than that in the model group. Immunohistochemical staining showed that the expression of HMGB1, TGF-β1, Smad3 and α-SMA protein was observed in the conjunctival tissues of the model group both 4 and 8 wk, with brown and significantly deeper staining of the model group at 8 wk. Meanwhile, the positive staining in the model with drug administration group at both 4 and 8 wk was significantly lower than that in the model group. There was positive correlations between the number of fibroblasts stained with HE and the expression of HMGB1 in the conjunctival tissue of the model group at both 4 and 8 wk(r=0.602, 0.703, all P<0.05). RT-PCR and Western blot revealed that the mRNA and protein expression levels of HMGB1, TGF-β1, Smad3 and α-SMA in the model group were significantly higher than those in the control group at both 4 and 8 wk(all P<0.05). Meanwhile, the mRNA and protein expression levels of HMGB1, TGF-β1, Smad3 and α-SMA in the model with drug administration group were significantly lower than those in the model group(all P<0.05). There was positive correlations between mRNA expressions of HMGB1 and TGF-β1, Smad3 in the model group and the model with drug administration group(all P<0.05).CONCLUSION: The expression of HMGB1 increased at a time-dependent manner after glaucoma valve implantation. HMGB1 acts an indispensable role in the initiation and progression of scar formation after glaucoma surgery, which may be involved in the regulation of TGF-β/Smad signaling pathway.
8.Application and progress of optogenetic technique in neural circuits in depression
Shaowei LI ; Sheng WEI ; Jiehui LI ; Siyuan LIU ; Yalin CAO ; Haijun WANG
Chinese Journal of Neuromedicine 2024;23(5):520-525
Optogenetic technique is a cellular activity regulation technology that combines optics and genetics, which can specifically regulate the relevant brain regions and neural circuits in depressive animal models, thereby slowing down or aggravating depression-like behaviors in experimental animals. Optogenetic technique combined with neuroimmunoassay, behavioral detection and brain imaging techniques can provide technical support for elucidating the pathogenesis of depression, developing new antidepressants and diagnosis and treatment methods. In this paper, the application of optogenetic technique in the ventral tegmental area, nucleus accumbens, prefrontal cortex, hippocampus, dorsal raphe nucleus and other brain regions closely related to depression is reviewed to provide ideas and directions for study of neural circuits of depression.
9.Outcomes and care practices of extremely preterm infants at 22-25 weeks′ gestation age from the Chinese Neonatal Network
Siyuan JIANG ; Chuanzhong YANG ; Xiuying TIAN ; Dongmei CHEN ; Zuming YANG ; Jingyun SHI ; Falin XU ; Yan MO ; Xinyue GU ; K. Shoo LEE ; Wenhao ZHOU ; Yun CAO
Chinese Journal of Pediatrics 2024;62(1):22-28
Objective:To describe the current status and trends in the outcomes and care practices of extremely preterm infants at 22-25 weeks′ gestation age from the Chinese Neonatal Network (CHNN) from 2019 to 2021.Methods:This cross-sectional study used data from the CHNN cohort of very preterm infants. All 963 extremely preterm infants with gestational age between 22-25 weeks who were admitted to neonatal intensive care units (NICU) of the CHNN from 2019 to 2021 were included. Infants admitted after 24 hours of life or transferred to non-CHNN hospitals were excluded. Perinatal care practices, survival rates, incidences of major morbidities, and NICU treatments were described according to different gestational age groups and admission years. Comparison among gestational age groups was conducted using χ2 and Kruskal-Wallis tests. Trends by year were evaluated by Cochran-Armitage and Jonckheere-Terpstra tests for trend. Results:Of the 963 extremely preterm infants enrolled, 588 extremely preterm infants (61.1%) were male. The gestational age was 25.0 (24.4, 25.6) weeks, with 29 extremely preterm infants (3.0%), 88 extremely preterm infants (9.1%), 264 extremely preterm infants (27.4%), and 582 extremely preterm infants (60.4%) at 22, 23, 24, and 25 weeks of gestation age, respectively. The birth weight was 770 (680, 840) g. From 2019 to 2021, the number of extremely preterm infants increased each year (285, 312, and 366 extremely preterm infants, respectively). Antenatal steroids and magnesium sulfate were administered to 67.7% (615/908) and 51.1% (453/886) mothers of extremely preterm infants. In the delivery room, 20.8% (200/963) and 69.5% (669/963) extremely preterm infants received noninvasive positive end-expiratory pressure support and endotracheal intubation. Delayed cord clamping and cord milking were performed in 19.0% (149/784) and 30.4% (241/794) extremely preterm infants. From 2019 to 2021, there were significant increases in the usage of antenatal steroids, antenatal magnesium sulfate, and delivery room noninvasive positive-end expiratory pressure support (all P<0.05). Overall, 349 extremely preterm infants (36.2%) did not receive complete care, 392 extremely preterm infants (40.7%) received complete care and survived to discharge, and 222 extremely preterm infants (23.1%) received complete care but died in hospital. The survival rates for extremely preterm infants at 22, 23, 24 and 25 weeks of gestation age were 10.3% (3/29), 23.9% (21/88), 33.0% (87/264) and 48.3% (281/582), respectively. From 2019 to 2021, there were no statistically significant trends in complete care, survival, and mortality rates (all P>0.05). Only 11.5% (45/392) extremely preterm infants survived without major morbidities. Moderate to severe bronchopulmonary dysplasia (67.3% (264/392)) and severe retinopathy of prematurity (61.5% (241/392)) were the most common morbidities among survivors. The incidences of severe intraventricular hemorrhage or periventricular leukomalacia, necrotizing enterocolitis, and sepsis were 15.3% (60/392), 5.9% (23/392) and 19.1% (75/392), respectively. Overall, 83.7% (328/392) survivors received invasive ventilation during hospitalization, with a duration of 22 (10, 42) days. The hospital stay for survivors was 97 (86, 116) days. Conclusions:With the increasing number of extremely preterm infants at 22-25 weeks′ gestation admitted to CHNN NICU, the survival rate remained low, especially the rate of survival without major morbidities. Further quality improvement initiatives are needed to facilitate the implementation of evidence-based care practices.
10.Status of delivery room continuous positive airway pressure in very preterm infants in China
Chun CHEN ; Dan DANG ; Xinyue GU ; Juan DU ; Lee Shoo K. ; Lizhong DU ; Yun CAO ; Wenhao ZHOU ; Siyuan JIANG ; Chuanzhong YANG ; Jianguo ZHOU
Chinese Journal of Perinatal Medicine 2024;27(12):1007-1014
Objective:To investigate the current status, trends, and differences among institutions in the application of delivery room continuous positive airway pressure (DRCPAP) for very preterm infants treated in the institutions in the Chinese Neonatal Network (CHNN). Also, to explore the impact of DRCPAP on the outcomes of very preterm infants in China.Methods:A retrospective cohort study was conducted. Based on the CHNN very preterm infant cohort, very preterm infants (gestational ages ranging from 25 weeks +0 to 31 weeks +6) born in-hospital and treated in 79 tertiary neonatal intensive care units (NICUs) participating in the CHNN from 2019 to 2021 were included. The usage rates of DRCPAP in different hospitals, as well as gestational ages and years, were described. Data were analyzed using the Chi-square test (or Fisher's exact test) or t-test. A multivariate logistic regression model was established to explore the correlation between DRCPAP and clinical outcomes. Results:(1) A total of 18 048 very preterm infants were included. Among them, 3 666 (20.3%) received DRCPAP, and 14 382 (79.7%) did not. (2) The usage rate of DRCPAP for very preterm infants among different institutions is from 0.0% to 94.5%. Fourteen institutions did not use DRCPAP, and 55 institutions had a usage rate below 30%. The usage rate of DRCPAP in very preterm infants increased annually, from 13.8% (818/5 916) in 2019 to 26.0% (1 583/6 097) in 2021 ( χ2trend=122.00, P<0.001). (3) The DRCPAP group had higher rates of maternal assisted reproductive technology pregnancy, chorioamnionitis, a full course of antenatal corticosteroids, gestational diabetes, fetal distress, antenatal magnesium sulfate use, and cesarean delivery compared to the non-DRCPAP group [20.3% (744/3 665) vs. 17.6% (2 529/14 369), χ2=14.45; 23.0% (695/3 021) vs. 16.4% (1 956/11 926), χ2=72.57; 57.1% (2 090/3 660) vs. 54.3% (7 766/14 302), χ2=9.55; 23.0% (844/3 669) vs. 20.7% (2 969/14 342), χ2=9.77; 8.7% (319/3 666) vs. 7.0% (1 006/14 371), χ2=12.51; 87.1% (3 186/3 657) vs. 82.0% (11 736/14 312), χ2=81.38; 63.5% (2 327/3 664) vs. 60.7% (8 722/14 369), χ2=9.59; all P<0.05]. While the incidence of hypertensive disorders of pregnancy and the proportion of infants not using antenatal corticosteroids were lower in the non-DRCPAP group [17.1% (626/3 660) vs. 22.6% (3 183/14 084), χ2=44.70; 14.2% (520/3 661) vs. 19.7% (2 814/14 284), χ2=57.34; all P<0.05]. The DRCPAP group had lower birth weight and gestational age, higher 1 min and 5 min Apgar scores, and lower neonatal transport stabilization index scores [(1 308±314) g vs. (1 325±315) g, t=2.90; (29.5±1.7) weeks vs. (29.7±1.6) weeks, t=3.96; (7.9±1.8) scores vs. (7.6±1.9) scores, t=-9.80; (9.0±1.1) scores vs. (8.7±1.3) scores, t=-13.01; (11.0±9.4) scores vs. (13.1±9.8) scores, t=11.31; all P<0.05]. The incidence of early-onset sepsis was higher in the DRCPAP group than in the non-DRCPAP group [1.8% (68/3 578) vs. 1.3% (193/14 296), adjusted OR (95% CI): 1.417 (1.028-1.955)], while the rates of tracheal intubation within 72 hours, PS use, invasive mechanical ventilation, mortality, admission hypothermia, grade Ⅲ-Ⅳ intracranial hemorrhage, and stage≥3 ROP were all lower in the DRCPAP group compared to the non-DRCPAP group [22.6% (830/3 666) vs. 36.9% (5 310/14 374), adjusted OR (95% CI): 0.499 (0.448-0.555); 53.1% (1 947/3 666) vs. 58.3% (8 388/14 377), adjusted OR (95% CI): 0.764 (0.697-0.836); 30.1% (1 104/3 662) vs. 43.9% (6 307/14 366), adjusted OR (95% CI): 0.539 (0.487-0.595); 7.4% (274/3 666) vs. 10.6% (1 526/14 342), adjusted OR (95% CI): 0.709 (0.601-0.836); 57.5% (2 103/3 657) vs. 66.5% (9 501/14 287), adjusted OR (95% CI): 0.722 (0.661-0.788); 3.0% (101/3 366) vs. 5.9% (763/12 932)], adjusted OR (95% CI): 0.525 (0.412-0.669); 2.2% (65/2 954) vs. 3.3% (367/11 121), adjusted OR (95% CI): 0.692 (0.505-0.947); all P<0.05]. There were no statistically significant differences between the two groups in the incidence rates of BPD at a corrected gestational age of 36 weeks, patent ductus arteriosus ligation, spontaneous intestinal perforation, and pneumothorax. Conclusions:Domestically, the application of DRCPAP might be related to a decrease in the demand for invasive ventilation, the use of surfactants, and mortality, but it might not reduce the occurrence of bronchopulmonary dysplasia, at a corrected gestational age of 36 weeks. In recent years, the use of DRCPAP in very premature infants in China has increased, but the overall usage rate is still low, and there are significant differences between units, requiring continuous quality improvement.

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