国外经典慢性病管理模式对我国慢性病管理的启示

随着城镇化加快、生活方式变化及全球人口老龄化,慢性病带来的危害日益严重。慢性病的服务提供是卫生服务系统的难题之一,而慢性病管理模式为其创设了一个新的框架。本文主要介绍慢性病照护模式、慢性病自我管理计划和创新型慢性病照护框架3种国外经典慢性病管理模式,从特点、应用效果、局限性等方面进行比较,发现其核心要素包括多方协同、连续性服务、患者自我管理、循证决策、信息技术支持等。以上经验为我国的慢性病管理工作提供了新思路：建立政府主导、多元协同的管理制度,以家庭医生签约服务为“抓手”提高服务连续性,借力智慧医疗并强化患者赋能等,以期取得更好的慢性病管理效果。     

慢性阻塞性肺疾病的新定义及临床诊疗建议——基于2022年《柳叶刀》文件解读

慢性阻塞性肺疾病(以下简称慢阻肺)是一种常见的慢性气道异质性疾病。近年来,尽管国内外慢阻肺相关研究不断深入,管理日趋完善,但仍有许多难点亟待解决。2022年9月,《柳叶刀》杂志发布《消除慢阻肺之路》,该文件针对慢阻肺的认识、诊断、评估和个体化治疗等方面提出了新理念并提供临床诊疗指导。本文重点对该文件中慢阻肺的分类、诊断标准及诊断建议、慢阻肺的急性加重和迈向消除慢阻肺5个方面进行介绍和解读,以期为我国临床工作者开展慢阻肺相关研究和管理提供一定的参考及启示。     

备孕期高血压的规范管理

近年来由于生活压力的增加,我国越来越多的育龄期男女罹患高血压,因此如何规范管理备孕期高血压已成为当前的焦点。本文从备孕期间血压的监测与评估和降压药的使用两方面分别对育龄期男性和女性备孕期间的血压规范管理进行阐述,强调女性备孕期间的高血压管理应同时考虑母体和胎儿的安全性,选择相对安全的降压药,如甲基多巴、拉贝洛尔、硝苯地平等;男性备孕期间的高血压管理应同时考虑降压药的疗效及其对性功能和精子的影响,推荐奈必洛尔、血管紧张素转换酶抑制剂（ACEI）/血管紧张素Ⅱ受体拮抗剂（ARB）和钙离子通道阻滞剂（CCB）类药物,旨在为临床备孕期高血压的管理提供指导并为未来研究提供参考方向。     

经皮脊柱内镜下可视化置钉在Endo-LIF椎弓根螺钉置钉中的应用价值

研究经皮内镜下可视化置钉在经皮内镜下后路腰椎融合术（End-PLIF）椎弓根螺钉置钉中的应用价值。方法 纳入2020年10月—2021年4月我院有腰椎融合手术指征的腰椎间盘源性腰痛、腰椎管狭窄症伴腰椎不稳、腰椎间盘突出症伴腰椎不稳、腰椎滑脱症（Meyerding分级I、II）患者共50例。50例患者随机分为甲、乙两组,每组25例。甲组的手术方式为经皮内镜下后路腰椎融合术+经皮脊柱内镜下可视化椎弓根螺钉置钉,乙组的手术方式为经皮内镜下后路腰椎融合术+传统X线透视下经皮椎弓根螺钉置钉。比较两组X线透视总次数、导丝置入时间、手术时间、术后住院时间;采用Gertzbein-Robbins标准评价置钉优良率;术前及术后24 h VAS评分和ODI指数、改良Macnab标准及术后并发症的发生率评价疗效。同时对经皮内镜下改进的置钉器械进行3D打印制造并验证其可行性、实用性。通过上述指标观察其医患X线辐射情况、微创性、置钉的优良率及手术效果。结果 全部患者均完成了手术和随访。甲组患者X线透视总次数、手术时间、导丝置入时间,均少于乙组（P＜0.05）,两组术后住院时间比较差异无统计学意义（P＞0.05）。两组术前、术后24 h VAS、ODI比较差异无统计学意义（P＞0.05）,但两组术后24 hVAS、ODI均较术前改善（P＜0.05）。末次随访时,两组患者改良Macnab标准的优良率比较差异无统计学意义（P＞0.05）。甲组经皮内镜置钉优良率优于乙组（P＜0.05）。两组患者术后并发症发生率比较差异无统计学意义（P＞0.05）。结论 经皮内镜下置钉能减少医患X线辐射次数,降低医患辐射暴露风险,且置钉的优良率较高;同时,3D打印的经皮内镜下置钉器械具有可行性和实用性     

Profile of etodolac: Pharmacokinetic evaluation in special populations

The pharmacokinetics of etodolac, a new nonsteroidal anti-inflammatory drug, were compared in normal subjects, in patients with renal and hepatic disease, and in elderly patients. In 28 normal subjects, orally administered etodolac was rapidly absorbed. By 1.2 hours after ingestion of a 200 mg dose, the maximum serum concentration (C_max) averaged 15.9 g/ml, with more than 99% of the drug bound to serum protein. Clearance was primarily hepatic. The mean half-life (t_1/2) was 6 to 7 hours. There were no apparent differences in C_max, the time at which C_max occurred (t_max), area under the serum concentration/time curve (AUC_0–24), or t_1/2 between groups of young men (n=20), elderly men (n=24), and elderly men with osteoarthritis (n=20), after a single dose of etodolac or after 7 days of subchronic administration. Moreover there was no evidence of accumulation. There also were no differences in C_max, t_max, AUC_0–24 or t_1/2 between groups of normal subjects (n=10) and patients with mild-to-moderate renal impairment (n=10). Patients with end-stage renal disease who were receiving chronic hemodialysis had the same mean serum concentration of free drug as normal subjects, even though mean serum levels of protein-bound etodolac were slightly lower than those in the normal subjects. The only significant (p<0.05) difference between patients with stable hepatic cirrhosis and normal, age-matched subjects was a slightly shorter t_max in the cirrhotic subjects (1.1 vs. 1.4 hours). These findings suggest that no alteration of etodolac dosage would be necessary in these high-risk groups.Die pharmakokinetischen Parameter von Etodolac, einem neuen, nichtsteroidalen entzündungshemmenden Therapeutikum, wurden an gesunden Probanden, an Patienten mit Leber- und Nierenleiden und an Älteren Patienten untersucht. Orale Etodolac Gaben wurden von den 28 gesunden Probanden schnell resorbiert. Nach einer einmaligen Dosis von 200 mg betrug nach 1,2 Stunden die durchschnittliche maximum Serumkonzentration (C_max) 15,9 g/ml, wobei mehr als 99% des Medikaments an das Serumprotein gebunden war. Clearance erfolgte hauptsÄchlich über die Niere. Die mittlere Eliminationshalbwertszeit (t_1/2) variierte zwischen 6 und 7 Stunden. In Bezug auf C_max, dem Zeitpunkt an dem C_max auftrat (t_max), FlÄche unter der Serumkonzentrationskurve (AUC_0–24) und t_1/2 wurden keine offensichtliche Unterschiede festgestellt zwischen der Gruppe junger MÄnnern (n=20), Älterer MÄnner (n=24) und Älteren MÄnnern mit Osteoarthritis (n=20) nach einer einmaligen Etodolac-Gabe oder nach 7 tÄgiger subchronischer Dosierung. Es bestanden auch keine Anzeichen einer Kumulation. ZusÄtzlich wurden auch keine Unterschiede in C_max, t_max, AUC_0–24 und t_1/2 zwischen der Gruppe gesunder Probanden (n=10) und der Patientengruppe mit leichten bis mÄigen NierenfunktionsschÄden (n=10) beobachtet. Im mittleren Serumspiegel des nicht gebundenen Medikaments in Patienten im Endstadium der Nierenerkrankung, die mit Langzeitdialyse behandelt wurden, konnte kein Unterschied im Vergleich zu gesunden Probanden festgestellt werden, obwohl der mittlere Serumspiegel für proteingebundenes Etodolac in den Patienten etwas niedriger lag als in gesunden Probanden. Der einzige signifikante Unterschied (p<0.05) zwischen Patienten mit stabilisierter Leberzirrhose und gleichaltrigen Probanden war eine etwas kürzere t_max in den Zirrhosepatienten (1,1 versus 1,4 Stunden). Diese Ergebnisse beweisen, dakeine Notwendigkeit vorliegt, die Etodolac-Dosierung für diese Risikogruppen zu modifizieren.Se comparó la farmacocinética de etodolac, un fármaco antiinflamatorio no esteroide nuevo, en sujetos normales y en pacientes con enfermedad renal y hepática y en pacientes ancianos. Etodolac administrado por vía oral a 28 sujetos normales fue rápidamente absorbido. A las 1,2 horas siguientes a la administración de una dosis de 200 mg, la concentración sérica máxima (C_max) alcanzó un promedio de 15,9 g/ml, con más del 99% del fármaco unido a la proteína sérica. La eliminación fue principalmente hepática. La vida media (t_1/2) fue 6–7 horas. No se observaron diferencias en C_max, en el tiempo en el cual se produjo C_max, en el área bajo la curva de concentración sérica/tiempo (ABC_0–24) ni en t_1/2 entre los grupos de hombres jóvenes (n=20), de hombres ancianos (n=24) y de hombres ancianos con osteoartritis (n=20), después de la administración de una dosis Única o después de 7 días de administración subcrónica de etodolac. Además, no hubo evidencia de acumulación. Tampoco se registraron diferencias en C_max, t_max, ABC_0–24 o t_1/2 entre los grupos de sujetos normales (n=10) y los pacientes con insuficiencia renal leve a moderada (n=10). Los pacientes con nefropatía terminal que estaban recibiendo hemodiálisis crónica tuvieron las mismas concentraciones séricas medias de fármaco libre que los sujetos normales, a pesar de que las concentraciones séricas medias de etodolac unido a proteina fueron levemente inferiores que en los sujetos normales. La Única diferencia significativa (p<0,05) entre los pacientes con cirrosis hepática estable y los sujetos normales de edad similar fue t_max ligeramente inferior en los sujetos cirróticos (1,1 vs 1,4 horas). Estos hallazgos sugieren que no es necesario modificar la dosis de etodolac para su uso en estos grupos de alto riesgo.La pharmacocinétique de l'étodolac, un anti-inflammatoire non stéroÏdien, a été comparé chez des sujets normaux et des patients présentant des affections rénales et hépatiques, et chez des malades âgés. Chez 28 sujets normaux, la résorption d'étodolac administré par voie orale a été rapide. Dès 1,2 heure suivant l'absorption d'une dose de 200 mg, la moyenne des concentration sériques maximales (C_max) était de 15,9 g/ml, plus de 99% pour cent du médicament étant liés aux protéines sériques. La clairance se fait surtout par voie hépatique. La demivie moyenne (t_1/2) était de 6 à 7 heures. Il n'y avait aucune différence apparente en ce qui concerne C_max, le temps d'apparition de C_max (t_max), l'aire sous la courbe concentration sérique/temps (AUC_0–24) ni t_1/2 entre les groupes d'hommes jeunes (n=20), d'hommes âgés (n=24), et d'hommes âgés atteints d'arthrose (n=20) à la suite d'une dose unique d'étodolac ou après 7 jours d'administration subchronique. De plus, aucune accumulation n'a été constatée. D'autre part, aucune différence de C_max, t_max, AUC_0–24 ni t_1/2 n'a été notée entre les groupes de sujets normaux (n=10) et de malades présentent des altérations rénales légères ou modérées (n=10). Les malades en insuffisance rénale terminale soumis à l'hémodialyse chronique ont présenté une concentration sérique moyenne de médicament libre analogue à celle des sujets normaux, mais la moyenne des taux sériques d'étodolac lié aux protéines était légèrement inférieure à celle observée chez les sujets normaux. La seule différence significative (p<0.05) entre les malades présentant une cirrhose hépatique stable et des sujets normaux appariés quant à l'âge était représentée par un t_max légèrement plus court chez les cirrhotiques (1,1 contre 1,4 heure). Ces données permettent de penser qu'aucune modification posologique de l'étodolac ne serait nécessaire pour ces groupes à haut risque.La farmacocinetica dell'etodolac, un nuovo farmaco anti-infiammatorio non steroidale è stata messa a confronto in gruppi normali, in pazienti affetti da malattia rénale ed epatica ed in pazienti anziani. In 28 soggetti normali l'etodolac somministrato oralmente è stato rapidamente assorbito. Dopo 1.2 ore dall'ingestione di una dose di 200 mg la massima concentrazione di siero (Cmax) presentava un valore medio di 15,9 mg/ml, con più del 99% del farmaco legato alla proteina del siero. La clearance era soprattutto a livello epatico. L'emivita media (t1/2) era di 6–7 ore. Non vi sono state evidenti differenze medie nei valori di concentrazione massima (Cmax), tempo (Tmax) al quale si aveva la Cmax, nella curva dell'area sotto concentrazione di siero/tempo (AUCo-24) oppure nel valore dell'emivita media (t1/2) tra gruppi di uomini giovani (n=20), uomini anziani (n=24) e anziani con osteoartrite (n=20), dopo una dose singola di etodolac o dopo 7 giorni di somministrazione subcronica. Inoltre non vi sono stati segni di accumulo. Per di più non vi sono state differenze nei valori di Cmax, tmax, AUCo-24 o t1/2 tra gruppi di soggetti normali (n=10) e pazienti con alterazioni renali da leggere a moderate (n=10). I pazienti con malattia renale all'ultimo stadio che ricevevano emodialisi cronica presentavano la stessa concentrazione media di siero di farmaco libero dei soggetti normali, anche se i livelli medi di siero di etodolac legato alle proteine erano leggermente inferiori a quelli di soggetti normali. L'unica differenza significativa (p<0.05) tra pazienti con cirrosi epatica stabile e soggetti normali della stessa età era nei tmax leggermente più brevi nei soggetti cirrotici (1.1. contro 1.4 ore). Questi risultati suggeriscono che nessuna alterazione del dosaggio di etodolac sarebbe necessaria in questi gruppi ad alto rischio.     

Intestinal microvillous atrophy in a patient with Down syndrome and aganglionic megacolon

Intestinal microvillous disorders are an uncommon cause of severe diarrhea, with very poor prognosis. The authors report the case of a female infant with Down syndrome, aganglionic megacolon, severe diarrhea, and jejunal biopsy with ultrastructural changes consistent with microvillous atrophy. The patient condition improved after a colostomy performed in the setting of the treatment of Hirschprung disease.     

Effects of chemical mediators of anaphylaxis on ciliary function

We assessed the effects of selected chemical mediators of anaphylaxis on CBF in vitro. Ciliated epithelial cells were obtained from the trachea of conscious sheep with a cytology brush and suspended in a perfusion chamber containing KH. Ciliary activity was viewed microscopically and recorded on videotape for subsequent slow-motion analysis of CBF. Prostaglandin E1 (10(-8) M to 10(-6) M), prostaglandin E2 (10(-10) M to 10(-6) M), and leukotriene-C4 (10(-8) M) increased CBF between 7% and 33%. Histamine caused ciliostimulation only at the relatively high concentrations above 10(-5) M (7% increase in CBF), whereas prostaglandin F2 alpha (10(-10) M and 10(-6) M) was without effect. In no preparation was ciliary discoordination observed. These findings indicate that several chemical mediators of anaphylaxis stimulate CBF and that the previously described impairment of mucociliary transport in stable allergic asthma or antigen-induced bronchoconstriction is probably not caused by a primary alteration of ciliary function.     

Airway responses to antigen challenge in allergic rhinitis and allergic asthma

The density dependence of the maximum expiratory flow-volume curve, functional residual capacity (FRC), and specific airway conductance (SGaw) were determined before and during bronchial provocation with ragweed extract in 27 subjects with ragweed hypersensitivity and a history of either bronchial asthma (16 subjects) or allergic rhinitis (11 subjects). Mean baseline SGaw was significantly lower while mean volume of isoflow (Visov) and FrC were significantly higher in subjects with bronchial asthma. During antigen challenge, 10 of 16 subjects with bronchial asthma (63%) and five of 11 subjects with allergic rhinitis (45%) showed a greater than 35% decrease in SGaw ("reactors"): mean relative decreases in SGaw from baseline were 46% and 53%, respectively. The remaining subjects showed a less than 35% decrease in SGaw ("nonreactors") with mean relative decreases of 9% (allergic asthma) and 6% (allergic rhinitis). Mean Visov increased in all subjects with bronchial asthma and in eight of 11 subjects with allergic rhinitis. A significant increase in FRC (6%) was seen only in the "reactors" with bronchial asthma. Following antigen challenge, the beta adrenergic agonist, isoetharine, increased SGaw and decreased Visov. We conclude that in asymptomatic subjects with ragweed hypersensitivity, (1) central and peripheral airway function is more abnormal in subjects with bronchial asthma than in subjects with allergic rhinitis, (2) subjects of both groups show quantitatively and qualitatively comparable airway responses during antigen challenge with a decrease in SGaw or an increase in Visov, possibly representing increase in central and/or peripheral airflow resistance, respectively, (3) Visov may be a more sensitive indicator of airway response to antigen challenge than SGaw, and (4) the bronchodilator effects of a beta adrenergic agonist on antigen-induced bronchospasm are similar in both groups.     

Effects of tryptophan depletion on central and peripheral chemoreflexes in man

Klein (Arch. Gen. Psychiatry 50, 306-317, 1993) suggests that panic attacks are the result of a defective 'suffocation alarm' threshold that presents with carbon dioxide (CO(2)) hypersensitivity, exaggerated ventilatory response and panic in panic disorder (PD) patients. Serotonergic deficiencies enhance this ventilatory response in PD patients, as per 'suffocation alarm' theory predictions, suggesting that serotonin (5-HT) normalizes the ventilatory response. Other research supports a serotonin system-mediated stimulation of ventilation. Knowledge of 5-HT's role on ventilatory output and its neurophysiological sources impacts on the 'suffocation alarm' theory validity and predictive value. We used tryptophan depletion (TRP-) in concert with a modified Read rebreathing test to determine the effect of deficient serotonergic modulation on the central and peripheral chemoreflex threshold and sensitivity of response to CO(2) in 11 healthy men. TRP- did not affect central or peripheral chemoreflex threshold or sensitivity of response to CO(2). However, basal ventilation was significantly elevated during TRP-. In contrast to 'suffocation alarm' theory predictions, decreased 5-HT neurotransmission does not significantly affect the respiratory chemoreflex response to CO(2), impacting on non-chemoreflex drives to breathe. Panic associated respiratory abnormalities may be related to defective 5-HT modulation of non-chemoreflex drives to breathe, unrelated to any respiratory chemoreflex abnormality.     

Spontaneous age-associated amyloidosis in senescence-accelerated mouse (SAM)

Morphological studies on spontaneous systemic amyloidosis were conducted on 222 senescence-accelerated mice (SAM) (P) and on 150 mice in the senescence-resistant series (R).Among the pathologic findings, amyloidosis showed the highest incidence in both SAM (79.7%) and R (32.7%) Although an extensive deposition of amyloid was evident in some aged mice in the R series, a more severe amyloidosis occurred with a higher incidence in the P series. There was a statistical significance between the incidence of amyloidosis and age, in both the P and R series. There were no differences in organ distribution and mode of amyloid deposition between the P and R series or between the sexes. In about 60% of the amyloid-positive cases in the 28 killed SAM and 7 mice in the R series, there were no signs of inflammation or neoplasm.The morphological features in SAM more closely resembled those seen in cases of murine spontaneous senile amyloidosis than the features seen in cases of experimentally induced amyloidosis. This model is expected to be a valuable tool with which to assess the relationship between amyloid deposition and the aging process or senescence, perhaps even cases of human senile amyloidosis.