高通量透析对尿毒症血液透析患者不宁腿综合征的疗效

目的 观察高通量透析对尿毒症血液透析患者不宁腿综合征(RLS)的临床疗效.方法 尿毒症维持性血液透析患者45例,随机分为观察组和对照组,分别接受高通量透析和低通量透析,每周3次,每次4 h,观察6个月.疗程前后测定血清尿素氮(BUN),血清肌酐(CRE),β<'2>-微球蛋白(β<,2>-MG),甲状旁腺激索(iPTH)等指标变化,并用国际不宁腿综合征委员会(IRLSSG)制的调查问卷,评估RLS的严重程度.结果 两组BUN、CRE下降率比较差异无统计学意义(P>0.05),观察组β<,2>-MP、iPTH下降率高于对照组(P<0.05),治疗后观察组iPTH下降明显,与对照组比较差异有统计学意义(P<0.05).治疗后两组RLS评分均有下降,观察组较对照组更为明显(P<0.05).结论 高通量透析在保证尿毒症小分子毒素充分清除的基础上,加强了中大分子毒素的清除,可明显改善尿毒症维持性血液透析患者RLS.     

不安腿综合征的发生及对尿毒症隐性结核血液透析患者生活、睡眠质量的影响

目的探讨不安腿综合征(RLS)发病因素及对尿毒症隐性结核血液透析患者生活、睡眠质量的影响。方法采用匹兹堡睡眠质量指数(PSQI)以及简明健康状况调查量表(SF-36)对患者睡眠质量以及生活质量进行调查,分析RLS发病情况及其可能的影响因素,并比较RLS与非RLS患者生活质量、睡眠质量。结果经单因素、多因素Logistic回归分析显示,β2-微球蛋白、透析龄及甲状旁腺激素为影响尿毒症隐性结核血液透析患者RLS发生的独立危险因素;RLS组患者SF-36生理功能评分显著低于非RLS组(P0.05);RLS组患者主观睡眠质量、睡眠持续性、习惯睡眠效率以及日间功能障碍PSQI评分显著高于非RLS患者(P0.05)。结论尿毒症隐性结核维持性血液透析患者RLS患病率较高。     

血液灌流对老年血液透析患者不安腿综合征和睡眠质量的影响

目的 了解老年维持性血液透析(maintenance hemodialysis,MHD)患者不安腿综合征(restless legs syndrome,RLS)的患病率、危险因素及其对睡眠质量的影响,观察血液灌流改善对老年血液透析患者不安腿症状和睡眠质量的有效性和安全性.方法 以118例因慢性肾衰竭进行MHD治疗的老年患者为研究对象.不安腿综合征的诊断采用国际不安腿综合征研究小组制定的诊断标准量表,以匹兹堡睡眠质量指数(Pittsburgh sleep quality index,PSQI)进行睡眠质量评估.对伴有RLS老年MHD患者进行血液灌流治疗,疗程3个月,观察治疗前后患者RLS症状和PSQJ评分情况及不良反应.收集患者的临床和生化资料,进行t检验或x2检验,部分指标间进行相关分析和Logistic回归分析. 结果 (1)118例老年血液透析患者中,并存RLS者31例,患病率为26.3%,其中男性11例,女性20例;(2)RLS组患者透析龄(t=2.332,P=0.021)、性别比(女/男)(X2=15.343,P=0.000)、血磷(t=4.784,P=0.000)、β2-微球蛋白(t=13.124,P-0.000)和甲状旁腺激素水平(t=10.900,P=0.000)明显高于非RLS组,差异均有统计学意义.而在年龄(t=0.341,P=0.734)、干体质量(t=0.008,P=0.994)、透析器膜材料(X2=1.055,P=0.304)、血肌酐(t=0.051,P=0.960)、血尿素(t=0.899,P=0.370)、血红蛋白(t=0.912,P=0.364)、红细胞压积(t=0.601,P=0.549)、血钙(t=0.192,P=0.124)、铁蛋白(t=0.200,P=0.842)、转铁蛋白饱和度(t=1.094,P=0.276)等生化指标方面,两组差异均无统计学意义;Logistic回归分析结果 显示,血甲状旁腺激素和血β2-微球蛋白是老年MHD患者并发RLS的独立危险因素;(3)RLS组PSQI明显高于非RLS组,分别为10.7±2.7和4.9±2.5(t=10.948,P=0.000);睡眠差主要表现在主观睡眠质量、睡眠时间、习惯睡眠效应、日间功能等方面,且RLS严重程度与PSQI总分呈正相关(r=0.839,P<0.05);(4)经血液灌流治疗后,RLS患者血磷,血甲状旁腺激素、血β2-微球蛋白、RLS和PSQI评分均明显下降,与治疗前比较,差异有统计学意义;(5)患者在治疗过程中牛命体征平稳,无不良反应发生. 结论 老年MHD患者RLS的患病率较高,且普遍存在睡眠质量差等问题;血甲状旁腺激素和β2-微球蛋白是老年MHD患者并发RLS的独立危险因素,血液灌流能改善老年MHD患者的RLS和睡眠质量,且安全性好.     

维持性血液透析患者周围血管疾病发生情况及相关因素分析

目的 探究维持性血液透析患者周围血管疾病(PAD)的发病情况及相关危险因素.方法 回顾性研究275例我院肾脏病血液净化中心2010 ～ 2012年维持性血液透析患者的临床资料,据踝-肱指数(ABI)将其分为周围动脉疾病(PAD)组和非周围动脉疾病(非PAD)组,比较两组的相关指标水平,并对可能影响PAD发生的相关危险因素进行Logistic回归分析.结果 275例患者中PAD 97例(PAD组),患病率35.3％,PAD组中年龄、糖尿病患病率、心脑血管事件史、收缩压、超敏-C反应蛋白(hs-CRP)、β2微球蛋白(β2-mg)、同型半胱氨酸(Hcy)、可溶性细胞黏附分子-1(sICAM-1)、可溶性血管分子-1水平(sVCAM-1)均明显高于非PAD组,白蛋白及维生素D水平均明显低于非PAD组,两组比较,P均＜0.05;多因素Logistic回归分析显示,年龄、糖尿病、hs-CRP、β2-mg、Hcy、sVCAM-1、sICAM-1、维生素D是PAD的危险因素.结论 维持性血液透析患者PAD发病率高,除传统危险因素外,sICAM-1、sVCAM-1及维生素D亦是PAD发病的危险因素.     

老年人群血清β2微球蛋白水平与脑微出血的相关性分析

目的 探讨老年人群血清β₂微球蛋白水平与脑微出血(CMB)的相关性。方法 回顾性分析2020年1月至2022年11月我院神经内科收治的慢性病老年患者636例,所有患者于入院第2天采集静脉血检测血清β₂微球蛋白水平,并行头颅磁共振磁敏感加权成像扫描,根据患者磁敏感加权成像有无CMB分为CMB组82例和无CMB组554例。采用二元logistic回归分析CMB的独立危险因素。结果 二元logistic回归结果显示,通过不同模型调整混杂因素后,血清β₂微球蛋白水平是老年患者CMB发生的独立危险因素(模型1:β=0.179,OR=1.196,95%CI:1.017～1.407,P=0.031;模型2:β=0.215,OR=1.240,95%CI:1.048～1.468,P=0.012)。ROC曲线结果显示,血清β₂微球蛋白水平诊断CMB的最佳截断值为1.805 mg/L,敏感性为70.7%,特异性为52.5%。曲线下面积为0.657(95%CI:0.595～0.719,P<0.01)。结论 老年人群血...     

维持性血液透析患者睡眠质量影响因素分析

目的：分析影响维持性血液透析（ MHD）患者睡眠质量的相关因素。方法选择MHD患者109例,根据匹兹堡睡眠质量指数问卷（ PSQI）评分将患者分为睡眠质量较差组（ PSQI评分＞5分）57例、睡眠质量较好组（ PSQI评分≤5分）52例。收集并比较两组的一般资料（包括性别、年龄、透析龄、透析时间等）、实验室检查资料（包括血尿素氮、肌酐、白蛋白、血红蛋白、钙磷、β2微球蛋白、全段甲状旁腺激素等）。采用Logistic回归分析上述指标与患者睡眠质量的关系。结果相关分析显示,年龄、透析时间是影响MHD患者睡眠质量的危险因素（ OR分别为1．047、1．261,95％CI分别为1．014～1．081、1．016～1．564,P均＜0．05）。结论年龄、透析时间与MHD患者的睡眠质量有相关性。     

2型糖尿病患者脉压与血管病变的相关性研究

目的:研究2型糖尿病(DM)患者脉压(PP)大小与其血管病变的相关性.方法:以145例2型DM患者为研究对象,根据PP水平分为A组[PP<60 mmHg(1 mmHg=0.133 kPa)],B组(PP≥60 mmHg).比较2组患者冠状动脉病变积分、血β2-微球蛋白、尿β2-微球蛋白的差异.结果:2组患者相比:B组冠状动脉病变积分、血β2-微球蛋白、尿β2-微球蛋白显著高于A组(P<0.01).logistic逐步回归分析发现PP是冠状动脉病变积分、血β2-微球蛋白、尿β2-微球蛋白的独立危险因素.结论:PP是预测2型DM患者血管病变严重程度的参考指标.     

非小细胞肺癌合并静脉血栓栓塞症危险因素研究

目的 探讨非小细胞肺癌(NSCLC)患者发生静脉血栓栓塞症(VTE)的危险因素.方法 回顾性分析2005年1月至2016年1月新疆医科大学第一附属医院收治的57例NSCLC合并VTE患者的资料,选取同期在我院确诊为NSCLC的患者105例,用二元logistic回归分析NSCLC患者并发VTE的可能危险因素.结果 二元logistic回归多因素分析显示,化疗(OR =5.91,95％CI:1.47～10.76)、白细胞＞11×109/L(OR=7.54,95％ CI:1.69～13.25)、白蛋白＜35 g/L(OR =5.25,95％ CI:1.89～12.42)、D-二聚体＞500 μg/L(OR=25.16,95％ CI:7.87～80.41)与NSCLC患者发生VTE存在显著的相关关系.结论 化疗、白细胞＞1i×109/L、白蛋白＜35 g/L、D-二聚体＞500 μg/L是NSCLC患者并发VTE的独立危险因素.     

老年维持性血液透析患者死亡原因分析

目的 探讨老年维持性血液透析患者死亡原因及导致其死亡的主要危险因素. 方法 对2010年6月在我科血液透析中心进行维持性血液透析治疗3个月以上、有完整基本资料登记、年龄≥60岁老年患者105例临床资料进行回顾性分析,观察至2013年6月30日. 结果 105例患者中位年龄69岁,中位透析龄27个月.截止2013年6月30日死亡33例,主要死因为心血管疾病11例(33.3％)、肺部感染7例(21.2％)及脑血管疾病5例(15.2％).死亡组患者年龄、合并心血管疾病比例及外周血管钙化评分明显高于非死亡组,死亡组合并高血压比例、血浆白蛋白水平明显低于非死亡组.COX回归分析结果显示,校正年龄、体质指数、尿素清除指数及钙化评分等因素后,合并心血管疾病(HR=2.143,95％CI:1.010～4.613,P=0.049)、不合并高血压(HR=0.293,95％CI:0.097～0.889,P=0.03)及低血浆白蛋白(HR=0.838,95％CI:0.748～0.904,P=0.002)是老年维持性血液透析患者死亡的主要危险因素. 结论 心脑血管疾病及肺部感染是老年患者死亡的主要原因,营养不良及心血管系统并发症是患者死亡的主要危险因素.     

尿pH值与慢性肾脏疾病患者对比剂肾病的关系

目的 探讨尿pH值与慢性肾脏疾病（chronic kidney disease,CKD）患者经皮冠状动脉介入（percutaneous coronary intervention,PCI）治疗或冠状动脉造影术（coronary angiography,CAG）后对比剂肾病（contrast-induced nephropathy,CIN）的相关性.方法 回顾性分析2009年9月至2012年8月在广东省人民医院行择期PCI治疗或CAG的CKD患者453例的临床资料.按术前尿pH值水平将患者分为2组：尿pH值≥6组（n=254例）,尿pH值＜6组（n=199例）.比较两组之间的基线资料、CIN发病率、院内病死率及血液透析率.采用单因素Logistic 回归分析筛选CIN的危险因素,采用多因素Logistic回归分析尿pH值＜6与CIN的关系.结果 共52例患者（11.5％）发生CIN;尿pH值≥6组,尿pH值＜6组CIN的发病率分别5.5％ （14/254）、19.1％（38/199）,两组比较差异有统计学意义（P＜0.001）;院内病死率分别为0和1.5％ （3/199）,两组比较差异无统计学意义（P=0.050）;血液透析率分别为0.4％（1/254）和1.5％（3/199）,两组比较差异无统计学意义（P=0.209）.单因素Logistic回归分析显示,尿pH值＜6与CIN的发病率相关（OR =4.406,95％CI：2.124-7.708,P＜0.001）;多因素Logistic回归分析提示,尿pH值＜6是CIN的独立危险因素（OR =3.267,95％CI：1.674-6.374,P=0.001）.结论 CKD患者术前尿pH值＜6与择期PCI或CAG术后CIN相关,尿pH值＜6增加发生CIN的风险.     

Three layer functional model and energy exchange concept of aging process

Relying on a certain degree of abstraction, we can propose that no particular distinction exists between animate or living matter and inanimate matter. While focusing attention on some specifics, the dividing line between the two can be drawn. The most apparent distinction is in the level of structural and functional organization with the dissimilar streams of ‘energy flow’ between the observed entity and the surrounding environment. In essence, living matter is created from inanimate matter which is organized to contain internal intense energy processes and maintain lower intensity energy exchange processes with the environment. Taking internal and external energy processes into account, we contend in this paper that living matter can be referred to as matter of dissipative structure, with this structure assumed to be a common quality of all living creatures and living matter in general. Interruption of internal energy conversion processes and terminating the controlled energy exchange with the environment leads to degeneration of dissipative structure and reduction of the same to inanimate matter, (gas, liquid and/or solid inanimate substances), and ultimately what can be called ‘death.’ This concept of what we call dissipative nature can be extended from living organisms to social groups of animals, to mankind. An analogy based on the organization of matter provides a basis for a functional model of living entities. The models relies on the parallels among the three central structures of any cell (nucleus, cytoplasm and outer membrane) and the human body (central organs, body fluids along with the connective tissues, and external skin integument). This three-part structural organization may be observed almost universally in nature. It can be observed from the atomic structure to the planetary and intergalactic organizations. This similarity is corroborated by the membrane theory applied to living organisms. According to the energy nature of living matter and the proposed functional model, the decreased integrity of a human body's external envelope membrane is a first cause of the structural degradation and aging of the entire organism. The aging process than progresses externally to internally, as in single cell organisms, suggesting that much of the efforts towards the restoration and maintenance of the mechanisms responsible for structural development should be focused accordingly, on the membrane, i.e., the skin. Numerous reports indicate that all parts of the human body, like: bones, blood with blood vessels, muscles, skin, and so on, have some ability for restoration. Therefore, actual revival of not only aging tissue of the human body's membrane, but the entire human body enclosed within, with all internal organs, might be expected. We assess several aging theories within the context of our model and provide suggestions on how to activate the body's own anti-aging mechanisms and increase longevity. This paper presents some analogies and some distinctions that exist between the living dissipative structure matter and inanimate matter, discusses the aging process and proposes certain aging reversal solutions.     

Unusual responses of nocturnal pineal melatonin synthesis and secretion to swimming: Attempts to define mechanisms

Abstract: The effect of swimming at night on rat pineal melatonin synthesis was compared with that of light exposure at night. Rats were forced to swim at 0030 hr (lights out at 2000 hr) and sacrificed by decapitation 15 and 30 min later, immediately after swimming. Other groups of animals were exposed to white light (650μW/cm²) for 15 and 30 min at same time. Swimming caused a rapid and highly significant drop in the melatonin content in the pineal gland; however, the activity of N-acetyltransferase (NAT), the supposed rate limiting enzyme in the melatonin production, was not changed. Despite the drop in pineal melatonin levels, serum concentrations of the indole remained elevated in the rats that swam. In contrast, melatonin levels in the pineal and serum of light exposed rats fell precipitously, accompanied by a significant suppression of NAT activity. Since we anticipated that the strenuous exercise associated with swimming may induce release of artrial natriuretic peptide (ANP) from the heart, which in turn could cause the release of pineal melatonin, in a second study we injected physiological saline intravenously to stretch the cardiac muscle and release ANP. Three milliliters of normal saline was injected during the day into the jugular vein of anesthetized rats that were pretreated with isoproterenol to stimulate pineal melatonin production. Animals were killed 15 min after the saline injection, and pineal NAT activity and pineal melatonin levels were measured. The saline injections caused no alteration in the elevated levels of either NAT or melatonin. These data suggest that the disparity in pineal NAT activity (which was high) and pineal melatonin (which was low), in animals swum at night, may not be caused by ANP which is released during strenuous exercise such as swimming.     

Melatonin and photoperiodic time measurement: Seasonal breeding in the sheep

Abstract: Well-established circadian physiology supports the view that photoperiodic time measurement utilizes the coincidence between the presence of light and a photosensitive phase of a 'biological clock' to alter reproductive status—the so-called external coincidence model of seasonal breeding. In this review, we examine the mechanism whereby photoperiod interacts with presumed suprachiasmatic nuclei activity to allow endogenous melatonin to normally synchronize reproductive activity to the optimal time of year. The Romney Marsh sheep is particularly explored as an experimental model. It is suggested that the on/off activity of seasonal reproduction may be a robust mechanism able to be predictably manipulated by the judicious use of the light/dark cycle and exogenous melatonin, but firmly based on circadian principles.     

MUTATION FREQUENCY IN NURSES AND PHARMACISTS WORKING WITH CYTOTOXIC DRUGS

Individuals occupationally exposed to cytotoxic drugs may be at risk owing to the effects of these agents on DNA. As an index of DNA damage, in vivo mutations were measured in lymphocytes from 24 oncology nurses or pharmacists and 24 matched controls. Mutation frequency was significantly increased in exposed individuals and appeared to be related to duration of exposure. However, the overall magnitude of the increase was small and its biological significance remains to be determined.     

A single injection of adrenergic agonists enhances pineal melatonin production in Turkish hamsters

Abstract: The purpose of this study was to determine whether the pineal gland of Turkish hamsters (Mesocricetus brandti) responds to adrenergic agonists with an increase in melatonin production, and, if it does, whether the sensitivity of the pineal gland to agonists would differ throughout the dark phase. Adult Turkish hamsters weighing 110–210 g received a subcutaneous injection of isoproterenol (ISO, 1 mg/kg B.W.) or norepinephrine (NE, 1 mg/kg B.W.) at different times of night. Animals exposed to LD 16:8 responded to ISO or NE with increased pineal melatonin content only when injected at dawn, when endogenous melatonin is at basal or near-basal levels. When the 8 hr scotophase was entirely replaced with light, the responsiveness to ISO injections at dawn disappeared. In animals exposed to light from 30 min prior to injection to the time of sacrifice, ISO injections increased pineal melatonin content (P < 0.005, three-way ANOVA), which varied, depending on the specific time of injection (effect of time of night, P < 0.05, three-way ANOVA). These results demonstrate that (1) adrenergic agonists enhance the production of pineal melatonin in Turkish hamsters, (2) this stimulatory effect takes place late, but not early in the 8 hr scotophase, and (3) the adrenergic induction of pineal melatonin production in Turkish hamsters requires priming by darkness during the appropriate circadian phase.     

Immune effector mechanisms in malaria: An update focusing on human immunity

The past decade has witnessed dramatic decreases in malaria‐associated mortality and morbidity around the world. This progress has largely been due to intensified malaria control measures, implementation of rapid diagnostics and establishing a network to anticipate and mitigate antimalarial drug resistance. However, the ultimate tool for malaria prevention is the development and implementation of an effective vaccine. To date, malaria vaccine efforts have focused on determining which of the thousands of antigens expressed by Plasmodium falciparum are instrumental targets of protective immunity. The antigenic variation and antigenic polymorphisms arising in parasite genes under immune selection present a daunting challenge for target antigen selection and prioritization, and is a given caveat when interpreting immune recall responses or results from monovalent vaccine trials. Other immune evasion strategies executed by the parasite highlight the myriad of ways in which it can become a recurrent infection. This review provides an update on immune effector mechanisms in malaria and focuses on our improved ability to interrogate the complexity of human immune system, accelerated by recent methodological advances. Appreciating how the human immune landscape influences the effectiveness and longevity of antimalarial immunity will help explain which conditions are necessary for immune effector mechanisms to prevail.     

Secondary aortoduodenal fistula

Aorto-duodenal fistulae （ADF） are the most frequent aorto-enteric fistulae （80%）, presenting with upper gastrointestinal bleeding. We report the first case of a man with a secondary aorto-duodenal fistula presenting with a history of persistent occlusive syndrome. A 59-year old man who underwent an aortic-bi-femoral bypass 5 years ago, presented with dyspepsia and biliary vomiting. Computed tomography scan showed in the third duodenal segment the presence of inflammatory tissue with air bubbles between the duodenum and prosthesis, adherent to the duodenum. The patient was submitted to surgery, during which the prosthesis was detached from the duodenum, the intestine failed to close and a gastro-jejunal anastomosis was performed. The post-operative course was simple, secondary ADF was a complication （0.3%-2%） of aortic surgery. Mechanical erosion of the prosthetic material into the bowel was due to the lack of interposed retroperitoneal tissue or the excessive pulsation of redundantly placed grafts or septic procedures. The third or fourth duodenal segment was most frequently involved. Diagnosis of ADF was difficult. Surgical treatment is always recommended by explorative laparotomy. ADF must be suspected whenever a patient with aortic prosthesis has digestive bleeding or unexplained obstructive syndrome. Rarely the clinical picture of ADF is subtle presenting as an obstructive syndrome and in these cases the principal goal is to effectively relieve the mechanical bowel obstruction.     

Serological survey of HIV and syphilis in pregnant women in Madagascar

Objectives Peripartal transmission of human immunodeficiency virus (HIV) and Treponema pallidum, the causative agent of syphilis, leads to severe consequences for newborns. Preventive measures require awareness of the maternal infection. Although HIV and syphilis testing in Madagascar could be theoretically carried out within the framework of the national pregnancy follow‐up scheme, the required test kits are rarely available at peripheral health centres. In this study, we screened blood samples of pregnant Madagascan women for HIV and syphilis seroprevalence to estimate the demand for systemic screening in pregnancy. Methods Retrospective anonymous serological analysis for HIV and syphilis was performed in plasma samples from 1232 pregnant women that were taken between May and July 2010 in Ambositra, Ifanadiana, Manakara, Mananjary, Moramanga and Tsiroanomandidy (Madagascar) during pregnancy follow‐up. Screening was based on Treponema pallidum haemagglutination tests for syphilis and rapid tests for HIV, with confirmation of positive screening results on line assays. Results Out of 1232 pregnant women, none were seropositive for HIV and 37 (3%) were seropositive for Treponema pallidum. Conclusions Our findings are in line with previous studies that describe considerable syphilis prevalence in the rural Madagascan population. The results suggest a need for screening to prevent peripartal Treponema pallidum transmission, while HIV is still rare. If they are known, Treponema pallidum infections can be easily, safely and inexpensively treated even in pregnancy to reduce the risk of transmission.     

Married to M. tuberculosis: risk of infection and disease in spouses of smear-positive tuberculosis patients

Objectives To quantify the risk of infection and disease in spouses of tuberculosis patients and the extent to which intervention could reduce the risk in this highly exposed group. Methods We compared HIV prevalence, TB prevalence and incidence and tuberculin skin test (TST) results in spouses of TB patients and community controls. HIV‐positive spouses were offered isoniazid preventive therapy (IPT), and TST was repeated at 6, 12 and 24 months. Results We recruited 148 spouses of smear‐positive patients ascertained prospectively and 3% had active TB. We identified 203 spouses of previously diagnosed smear‐positive patients, 11 had already had TB, and the rate of TB was 2.4 per 100 person years(py) over 2 years (95% CI 1.15–5.09). 116 were found alive and recruited. HIV prevalence was 37% and 39% in the prospective and retrospective spouse groups and 17% in controls. TST was ≥10 mm in 80% of HIV negative and in 57% of HIV‐positive spouses ascertained retrospectively; 74% HIV negative and 62% HIV‐positive spouses ascertained prospectively, and 48% HIV negative and 26% HIV‐positive community controls. Of 54 HIV‐positive spouses, 18 completed 6‐month IPT. At 2 year follow‐up, 87% of surviving spouses had TST ≥10 mm and the rate of TB was 1.1 per 100 py (95% CI 0.34–3.29). Conclusions Spouses are a high‐risk group who should be screened for HIV and active TB. TST prevalence was already high by the time the spouses were approached but further infections were seen to occur. Uptake and adherence to IPT was disappointing, lessening the impact of short‐duration therapy.