超声引导下髂腰肌平面阻滞用于人工髋关节置换术后镇痛效果及对运动功能的影响

目的 探讨超声引导下髂腰肌平面阻滞用于人工髋关节置换术后镇痛的效果及对运动功能的影响。
方法 选择择期全麻下行人工髋关节置换术患者60例,男34例,女26例,年龄31～80岁,ASA Ⅰ—Ⅲ级。采用随机数字表法将患者分为两组：髂腰肌平面阻滞组（I组）和股神经阻滞组（F组）,每组30例。I组在超声引导下行髂腰肌平面阻滞,注射0.5%罗哌卡因10 ml;F组在超声引导下行股神经阻滞,注射0.5%罗哌卡因10 ml。两组均行股外侧皮神经阻滞,注射0.5%罗哌卡因5 ml。随后两组均行全麻。术后若患者VAS疼痛评分≥4分,静脉注射地佐辛5 mg。记录入PACU即刻及术后2、4、6、24、48 h静息和活动时VAS疼痛评分和股四头肌徒手肌力（MMT）分级。记录术后首次下床时间、补救镇痛情况和患者满意情况。记录恶心呕吐、头晕、神经损伤、血管损伤及穿刺部位感染的发生情况。
结果 与F组比较,I组入PACU即刻及术后2、4、6、24 h MMT分级明显升高（P＜0.05）,首次下床时间明显缩短（P＜0.05）。两组入PACU即刻及术后2、4、6、24、48 h静息和活动时VAS疼痛评分差异无统计学意义。两组补救镇痛率、患者满意率、术后48 h MMT分级差异无统计学意义。两组恶心呕吐、头晕的发生情况差异无统计学意义。两组无一例发生穿刺相关并发症。
结论 超声引导下髂腰肌平面阻滞为人工髋关节置换术患者提供良好的术后镇痛效果的同时保留患者运动能力,安全性较好,能够促进患者术后早期康复。     

超声引导下颈浅丛或颈中间丛神经阻滞联合肌间沟臂丛神经阻滞在锁骨骨折手术中的比较

目的 比较超声引导下颈浅丛联合肌间沟臂丛神经阻滞与颈中间丛联合肌间沟臂丛神经阻滞在锁骨骨折内固定术中的应用效果。
方法 选择择期拟行单侧锁骨骨折内固定术的患者60例,男36例,女24例,年龄18～64岁,BMI≤30 kg/m²,ASA Ⅰ或Ⅱ级。采用随机数字表法分为两组：颈浅丛神经阻滞组（S组）和颈中间丛神经阻滞组（M组）,每组30例。两组均先行超声引导下肌间沟臂丛神经阻滞,给予患侧0.4%罗哌卡因15 ml,S组行超声引导下颈浅丛神经阻滞,给予患侧0.4%罗哌卡因10 ml;M组行超声引导下颈中间丛阻滞,给予患侧0.4%罗哌卡因10 ml。记录颈浅丛和颈中间丛神经阻滞操作时间、麻醉起效时间。记录神经阻滞效果满意例数。记录术后1、2、4、6、12、24 h的VAS疼痛评分。记录局麻药物中毒、声音嘶哑、术后恶心呕吐等不良反应的发生情况。
结果 M组阻滞操作时间和麻醉起效时间明显短于S组（P<0.05）。两组神经阻滞效果满意率均为100%。M组术后1、2、4、6 h的VAS疼痛评分明显低于S组（P<0.05）。两组均无局麻药物中毒、声音嘶哑等不良反应发生,两组术后恶心呕吐发生率差异无统计学意义。
结论 超声引导下颈浅丛联合肌间沟臂丛神经阻滞与颈中间丛联合肌间沟臂丛神经阻滞均可为锁骨骨折内固定术提供安全有效的麻醉效果,但颈中间丛阻滞操作时间及起效时间更短、术后早期镇痛效果更优。     

足踝手术后连续腓肠肌平面阻滞的镇痛效果

目的：探索连续腓肠肌平面阻滞镇痛用于足踝部手术患者术后镇痛效果。
方法：选择全麻下行足踝部择期手术患者42例,男19例,女23例,年龄18～64岁,BMI 18～28 kg/m²,ASAⅠ—Ⅲ级。将患者随机分为两组：连续腓肠肌平面阻滞镇痛组（CN组）和患者自控静脉镇痛（PCIA）组（I组）,每组21例。CN组术毕行连续腓肠肌平面阻滞镇痛,配方为0.125%罗哌卡因300 ml,背景剂量为3 ml/h,单次给药剂量为 8 ml,锁定时间为25 min。I组术毕使用羟考酮PCIA,配方为羟考酮30 mg、托烷司琼6 mg加生理盐水至150 ml,输注速度0.5 ml/h,单次追加剂量5 ml。观察两组术后0～16、16～24、24～48、0～48 h时段静息和活动时NRS评分曲线下面积（AUC）,1、8、16、24、32、48 h静息和活动时NRS评分,CN组术后胫神经和腓总神经运动功能恢复时间、羟考酮滴定量、术后48 h内补救镇痛药物的吗啡当量累计使用量、补救镇痛次数、补救镇痛率、首次下床活动时间、术后恶心呕吐的发生情况和患者满意度评分。
结果：与I组比较,CN组0～16、16～24、24～48、0～48 h静息和活动时NRS评分AUC明显降低（P<0.01）,术后1、8、16、24、32、48 h NRS评分明显降低（P<0.01）,CN组16 h有10例（50%）患者腓总神经运动功能恢复,24 h有17例（85%）患者腓总神经运动功能恢复,32～48 h所有患者腓总神经运动功能恢复,48 h内所有患者胫神经运动功能正常。与I组比较,CN组吗啡当量累计使用量和补救镇痛次数明显减少（P<0.01）,补救镇痛率明显降低（P<0.01）,患者满意度评分明显升高（P<0.01）。两组羟考酮滴定量、首次下床活动时间,恶心呕吐发生率差异无统计学意义。
结论：超声引导下连续腓肠肌平面阻滞可以实现胫神经运动和感觉阻滞分离,可在足踝手术后提供良好且持续的镇痛效果。     

超声引导下经弓状韧带上或前路腰方肌阻滞在腹腔镜全子宫切除术中的比较

目的 探讨超声引导下经弓状韧带上入路或前路腰方肌阻滞（QLB）在腹腔镜全子宫切除术中的镇痛效果。
方法 择期行腹腔镜全子宫切除术的患者38例,年龄18～64岁,BMI 16～29 kg/m²,ASA Ⅰ或Ⅱ级。随机分为经前路QLB组（C组）和经弓状韧带上QLB组（E组）,每组19例。麻醉诱导前在超声引导下C组行双侧前路QLB,E组行弓状韧带上QLB,每侧给予0.3%罗哌卡因20 ml。记录术后住院时间、阻滞操作时间、阻滞后起效时间,测定阻滞后5、10、20、30 min的阻滞平面和术中瑞芬太尼和麻黄碱用量。记录术后2、6、12、24、48 h的VAS疼痛评分和补救镇痛,局麻药中毒、血肿、严重低血压、内脏损伤、肌力下降等神经阻滞并发症和恶心呕吐等不良反应。
结果 两组术后住院时间、阻滞操作时间差异无统计学意义。E组阻滞起效时间明显短于C组（P<0.05）。阻滞后5、10、20、30 min E组阻滞平面节段数量明显多于C组（P<0.05）。术后2、6、12 h E组静息和活动时VAS疼痛评分明显低于C组（P＜0.05）。两组均无补救镇痛,术中瑞芬太尼、麻黄碱用量,局麻药中毒、血肿、严重低血压、内脏损伤、肌力下降等神经阻滞并发症和恶心呕吐等不良反应差异无统计学意义。
结论 在腹腔镜全子宫切除术中经弓状韧带上腰方肌阻滞较传统前路腰方肌阻滞起效更快,阻滞平面更广,术后12 h镇痛效果更好。     

利多卡因复合氢吗啡酮神经阻滞在全关节镜下踝关节手术中的应用

目的 探讨利多卡因复合氢吗啡酮神经阻滞在全关节镜下踝关节手术中的应用效果。
方法 选择行全关节镜下踝关节手术患者100例,男61例,女39例,年龄18～64岁,BMI 18.5~25.0 kg/m²,ASA Ⅰ或Ⅱ级。采用随机数字表法将患者分为两组：2%利多卡因+氢吗啡酮组（LH组）和0.5%罗哌卡因组（R组）,每组50例。两组均采用隐神经联合腘窝坐骨神经阻滞,LH组药物配方为氢吗啡酮2 ml（2 mg）+2%利多卡因20 ml共计22 ml,R组为0.5%罗哌卡因22 ml。记录神经感觉阻滞起效时间、持续时间、术后神经运动阻滞恢复情况、术后不良反应发生情况及患者满意情况。
结果 与R组比较,LH组神经感觉阻滞起效时间明显缩短,持续时间明显缩短（P<0.05）。与R组比较,LH组术后2、4、6 h胫神经、腓总神经运动恢复速度明显,患者术后满意度明显升高（P<0.05）。两组镇痛不全、局部血肿、恶心呕吐不良反应的发生率差异无统计学意义。
结论 与0.5%罗哌卡因比较,2%利多卡因复合氢吗啡酮用于隐神经联合坐骨神经阻滞用于全关节镜下踝关节手术,镇痛起效时间缩短,对术后肌力影响更小。     

超声引导下腹横筋膜平面阻滞与腹横肌平面阻滞在剖宫产术后镇痛中的效果比较

目的 比较超声引导下腹横筋膜平面(TFP)阻滞与腹横肌平面(TAP)阻滞在剖宫产术后镇痛中的效果。
方法 择期蛛网膜下腔阻滞下行剖宫产术产妇60例,年龄20～35岁,体重50～75 kg,ASA Ⅰ或Ⅱ级,采用随机数字表法分为两组：腹横筋膜平面阻滞组（TFP组）和腹横肌平面阻滞组（TAP组）,每组29例。术毕TFP组行超声引导下双侧腹横筋膜平面阻滞,TAP组行超声引导下双侧腹横肌平面阻滞,两组均每侧注射0.375%罗哌卡因1.25 mg/kg。术后均行曲马多PCIA,若VAS疼痛评分≥4分,肌肉注射曲马多100 mg行补救镇痛。记录术后6、12、24、36、48 h PCIA中曲马多累积用量;记录术后48 h内曲马多补救镇痛情况;记录镇痛期间恶心呕吐、局麻药中毒、呼吸抑制、穿刺部位血肿、穿刺部位感染、腹膜刺穿造成腹腔内注射等不良反应的发生情况。
结果 与TAP组比较,TFP组术后6、12、24、36、48 h PCIA中曲马多累积用量明显减少 （P＜0.05）,术后48 h内曲马多补救镇痛率明显降低 （P＜0.05）。两组镇痛期间恶心呕吐发生率差异统计学意义。两组均无其他不良反应发生。
结论 与超声引导下腹横肌平面阻滞比较,腹横筋膜平面阻滞可减少剖宫产术后阿片类药物用量,镇痛效果更佳。     

0.5%罗哌卡因用于超声引导下腹股沟韧带上髂筋膜间隙阻滞的半数有效容量

目的 测定0.5%罗哌卡因用于患者超声引导下腹股沟韧带上髂筋膜间隙阻滞（S-FICB）的半数有效容量（EV₅₀）。
方法 选择2021年3月至2022年4月骨科择期行股骨与膝关节手术的患者28例，男19例，女9例，年龄18～64岁，BMI 18～28 kg/m ²，ASAⅠ或Ⅱ级，术前行超声引导下S-FICB，局麻药为0.5%罗哌卡因。阻滞30 min后分别测定股外侧皮神经、股神经、闭孔神经支配区皮肤感觉，三者痛觉均消失定义为阻滞成功，否则为阻滞失败。局麻药初始容量设为25 ml，容量梯度为5 ml，若阻滞成功则下一例患者容量减少5 ml，若阻滞失败则下一例患者容量增加5 ml，直至出现7个容量拐点后完成研究。采用概率回归法计算罗哌卡因EV₅₀和95%可信区间（CI）。记录患者穿刺部位血肿、穿刺针误入血管、局麻药中毒、恶心呕吐等并发症情况。
结果 本研究共阻滞成功15例（54%），罗哌卡因用于非老年患者超声引导下髂筋膜间隙阻滞EV₅₀为15.47 ml（95%CI 12.64～18.94 ml）。所有患者在阻滞后均未出现穿刺部位血肿、穿刺针误入血管、局麻药中毒和恶心呕吐等并发症。
结论 0.5%罗哌卡因用于非老年患者超声引导下髂筋膜间隙阻滞 EV₅₀为15.47 ml（95%CI 12.64～18.94 ml）。     

超声引导下横突-胸膜中点阻滞与胸椎旁神经阻滞用于单孔胸腔镜手术后镇痛效果的比较

目的 比较超声引导下横突-胸膜中点阻滞(MTPB)与胸椎旁神经阻滞(TPVB)用于单孔胸腔镜手术术后镇痛的效果。
方法 选择择期行单孔胸腔镜手术患者80例,男36例,女44例,年龄18～65岁,BMI 19～28 kg/m²,ASA Ⅰ―Ⅲ级。采用随机数字表法分为MTPB组（M组）和TPVB组（P组）,每组40例。手术结束后M组行超声引导下MTPB,P组行TPVB,两组均注射0.5%罗哌卡因15 ml。两组患者术后均采用PCIA。记录神经阻滞操作时间、穿刺深度,记录术后2、6、12、24、48 h安静和咳嗽时VAS疼痛评分,记录镇痛泵首次按压时间、总按压次数、舒芬太尼使用量和补救镇痛例数,记录穿刺相关并发症、镇痛不良反应发生情况。
结果 与P组比较,M组神经阻滞操作时间明显缩短（P<0.05）,进针深度明显变浅（P<0.05）。术后2、6、12、24、48 h两组安静和咳嗽时VAS疼痛评分差异无统计学意义。两组患者术后镇痛泵首次按压时间、总按压次数、舒芬太尼用量和补救镇痛率差异无统计学意义。两组患者术后恶心、呕吐等不良反应差异无统计学意义。
结论 MTPB或TPVB联合术后PCIA应用于单孔胸腔镜手术患者,术后均可取得良好的镇痛效果,但MTPB操作简单、安全,可作为单孔胸腔镜手术患者术后镇痛方案的选择。     

神经阻滞预防性镇痛对髋部骨折患者围术期镇痛影响的Meta分析

目的 系统评价神经阻滞预防性镇痛对髋部骨折患者围术期镇痛效果及安全性的影响。
方法 检索Cochrane、Pubmed、Embase、万方、维普、中国知网，收集髋部骨折后使用神经阻滞对患者行创伤后早期疼痛管理的随机对照试验（RCT），检索时间为建库至2023年3月。根据Cochrane指导手册独立筛选文献、提取资料并评价纳入研究的偏倚风险，采用RevMan 5.3软件进行Meta分析。
结果 共纳入13篇RCT，共计患者1 241例，神经阻滞组603例，对照组638例。与对照组比较，神经阻滞（或给药）后24 h运动时VAS疼痛评分明显降低（MD=-2.16分，95%CI -4.04～-0.28分，P＜0.05），恶心呕吐发生率明显降低（OR=0.33，95%CI 0.20～0.52，P＜0.05）。两组补救镇痛率、神经阻滞（或给药）后30 min内HR和MAP差异无统计学意义。
结论 神经阻滞预防性镇痛可降低髋部骨折患者神经阻滞后VAS疼痛评分和恶心呕吐发生率，但对补救镇痛率、神经阻滞后30 min内HR和MAP无明显影响。     

星状神经节阻滞对腹腔镜全子宫切除术患者术后睡眠质量和恶心呕吐的影响

目的 观察超声引导下右侧星状神经节阻滞（SGB）对腹腔镜全子宫切除术患者术后睡眠质量和恶心呕吐（PONV）的影响。
方法 选择择期行腹腔镜全子宫切除术患者98例,年龄42～74岁,BMI 19～25 kg/m ²,ASAⅠ或Ⅱ级。采用随机数字表法分为两组：全身麻醉联合SGB组（S组）和全身麻醉组（GA组）,每组49例。S组于麻醉诱导前在超声引导下行右侧SGB,注入 0.2%罗哌卡因5 ml,GA组不行SGB。两组采用相同的全身麻醉方法和麻醉药物。记录术前1 d、手术当日、术后1 d的匹兹堡睡眠质量指数（PSQI）。记录术后24 h PONV分级和止吐药补救情况。记录术后24 h活动时VAS疼痛评分、镇痛药补救情况、术后首次下床活动时间和术后住院时间。记录局麻药中毒、全脊髓麻醉、气胸、臂丛神经阻滞等SGB相关并发症发生情况。
结果 与GA组比较,S组手术当日、术后1 d PSQI评分、POSD发生率明显降低（P＜0.05）,PONV 0级、1级发生率明显升高,PONV 2级、3级、4级发生率、止吐药补救率明显降低（P＜0.05）,术后24 h活动时VAS疼痛评分明显降低（P＜0.05）,术后首次下床活动时间明显缩短（P＜0.05）。两组补救镇痛情况、术后住院时间差异无统计学意义。S组无一例出现局麻药中毒、全脊髓麻醉、气胸、臂丛神经阻滞等SGB相关并发症。
结论 右侧星状神经节阻滞可有效改善腹腔镜全子宫切除术患者的术后睡眠质量,降低术后恶心呕吐的发生率及严重程度,减轻术后疼痛。     

Bradycardia with sevoflurane in siblings with Branchio-oto-renal syndrome

Branchio-oto-renal syndrome (BOR, Melnick-Fraser syndrome, MIM#113650) refers to a rare autosomal dominant disorder characterized by branchial cysts or fistulas, hearing loss, external ear malformation, preauricular pits and renal abnormalities. The authors present three episodes of significant bradycardia in two siblings diagnosed with BOR syndrome during the sevoflurane general anesthesia. There is no published experience of anesthesia with this syndrome. Bradycardia occurred variously at induction, maintenance and immediately prior to emergence and required surgical stimulation, atropine, or epinephrine to treat. We seek to raise awareness of the potential for bradycardia during the procedures in patients with this syndrome requiring volatile anesthesia, especially sevoflurane.     

Increases in BMD correlate with improvements in bone microarchitecture with teriparatide treatment in postmenopausal women with osteoporosis.

Increases in BMD are correlated with improvements in 2D and 3D trabecular microarchitecture indices with teriparatide treatment. Therefore, improvements in trabecular bone microarchitecture may be one of the mechanisms to explain how BMD increases improve bone strength during teriparatide treatment. INTRODUCTION: Bone strength is determined by BMD and other elements of bone quality, including bone microarchitecture. Teriparatide treatment increases BMD and improves both cortical and trabecular bone microarchitecture. Increases in lumbar spine (LS) BMD account for approximately 30-41% of the vertebral fracture risk reduction with teriparatide treatment. The relationship between increases in BMD and improvements in cortical and trabecular microarchitecture has not yet been studied. MATERIALS AND METHODS: The relationship between increases in BMD and improvements in cortical and trabecular microarchitecture after teriparatide treatment was assessed using data from a subset of patients who had areal BMD measurements and structural parameters from transiliac bone biopsies in the Fracture Prevention Trial. 2D histomorphometric and 3D microCT parameters were measured at baseline and 12 (n = 21) or 22 (n = 36) mo. LS BMD was assessed at baseline and 12 and 18 mo, and femoral neck (FN) BMD was measured at baseline and 12 mo. Pearson correlation was performed to assess the relationship between actual changes in BMD and actual changes in microarchitectural parameters. RESULTS: Changes in LS BMD at 12 mo were significantly correlated with improvements in trabecular bone structure at 22 mo: 2D bone volume (r = 0.45, p = 0.02), 2D mean wall thickness (r = 0.41, p = 0.03), 3D bone volume (r = 0.48, p = 0.006), 3D trabecular thickness (r = 0.44, p = 0.01), 3D trabecular separation (r = -0.37, p = 0.04), 3D structural model index (r = -0.54, p = 0.001), and 3D connectivity density (r = 0.41, p = 0.02). Changes in LS BMD at 18 mo had similar correlations with improvements in bone structure at 22 mo. Changes in FN BMD at 12 mo were significantly correlated with changes in 2D mean wall thickness (r = 0.56, p = 0.002), 3D bone volume (r = 0.51, p = 0.004), 3D trabecular thickness (r = 0.44, p = 0.01), 3D trabecular separation (r = -0.46, p = 0.01), and 3D structural model index (r = -0.55, p = 0.001). CONCLUSIONS: Increases in BMD are correlated with improvements in trabecular microarchitecture in iliac crest of patients with teriparatide treatment. Therefore, improvements in trabecular bone microarchitecture may be one of the mechanisms to explain how BMD increases improve bone strength during teriparatide treatment.     

Pyloroplasty in association with Nissen fundoplication in children with neurologic disorders

Previous studies have suggested that delayed gastric emptying occurs in severely mentally retarded patients with gastroesophageal reflux. Based on this data, pyloroplasty was employed in such patients. A retrospective analysis of 99 consecutive patients who underwent primary fundoplication for GER was performed. Gastric emptying, as measured by successful removal of the nasogastric tube or elevation of the gastrostomy tube, was studied. Children with neurologic disorders had no clinically significant difference in gastric emptying after fundoplication (3.31 days) when compared with neurologically normal patients (2.21 days). When added to Nissen fundoplication, pyloroplasty did not hasten the return of gastrointestinal function in the severely impaired patients (4.91 days). A prospective study employing gastric isotope bolus feedings before and after Nissen fundoplication will determine if pyloroplasty improves gastric emptying when used in conjunction with Nissen fundoplication for patients with severe neurologic disorders.     

Chemotherapy in patients with teratoma with malignant transformation

OBJECTIVE: Germ-cell tumours (GCTs) with a non-GCT malignant component are a unique and rare phenomenon called teratoma with malignant transformation (TMT). The only published series of patients with TMT treated with chemotherapy comprised 10 patients. We report here our experience in treating 14 patients with TMT. PATIENTS AND METHODS: Sarcoma was identified in 10 of 14 patients, with rhabdomyosarcoma ranking first (n=4). Other histological types included adenocarcinoma (n=3) and bronchoalveolar carcinoma (n=1). Immunohistochemistry was performed to help in identifying the malignant non-GCT component. RESULTS: Primary treatment consisted of surgery alone in 4 patients. The remaining 10 patients received first-line cisplatin-based chemotherapy with resection of residual masses (n=5): 4 patients had a complete response and 5 had a partial response. Overall, 9 patients developed a relapse with a median time of 84 mo (range: 6-168). At relapse, 8 patients received a chemotherapy regimen directed to the non-GCT component. Four of these patients achieved a partial response. With a median follow-up of 59 mo (range: 3-180), 4 of 14 patients are alive, including 3 who are disease-free. CONCLUSION: To our knowledge, this is by far the largest reported European series of chemotherapy in TMT. Although TMT has a poor prognosis compared to GCT, its management may be improved by adapted chemotherapy associated with surgical resection of residual masses.     

Bradycardia with sevoflurane induction in patients with trisomy 21

The authors present a series of three paediatric patients with trisomy 21 who developed significant bradycardia during inhalation induction with sevoflurane. All three were undergoing adenotonsillectomy. The possible association of such problems with trisomy 21 and treatment options are reviewed. Although the occurrence of bradycardia in these three patients may have been a random occurrence, given its occurrence in three of five consecutive patients with trisomy 21, a causal relationship may be involved and future observation of these patients appears warranted.     

Atherosclerosis in patients with analgesic nephropathy treated with haemodialysis

SUMMARY: Accelerated atherosclerosis was reported to be associated with chronic analgesic consumption, but most studies were retrospective, and individual findings have almost never been controlled with regard to other atherosclerotic risk factors. Ten haemodialysis patients with analgesic nephropathy (group I) and 19 haemodialysis patients where renal failure was not caused by analgesic nephropathy (group II) were included in the study. All patients were female without diabetes. Using B-mode ultrasonography, we compared intima-media thickness (IMT) in the carotid arteries and plaque occurrence, and their thickness in group I with that in group II. the possible differences in atherosclerotic risk factors in both groups were also investigated. In group I, the average age was 60.2 years, and the average dialysis treatment was 55.7 months. In group II, the average age was 54.6 years, and the average duration of dialysis treatment was 50.4 months. We found no statistically significant difference in the age and duration of dialysis treatment between groups I and II. the IMT values of the carotid arteries (0.97 vs 0.78 mm; P = 0.027) were significantly higher in group I. More patients had plaques in group I (90 vs 57.9%), and the number of plaques ( P = 0.037) and their thickness ( P = 0.043) were significantly higher in this group. There was no statistically significant difference in the atherosclerotic risk factors between groups I and II. the results indicate that patients with analgesic nephropathy treated with haemodialysis showed advanced atherosclerosis compared with other haemodialysis patients, despite no difference being found in the atherosclerotic risk factors between these patients.