在感染艾滋病毒的个体的测量弱者。体弱患者的识别是第一步改良与弱者拨回

Summary

Frailty syndrome is commonly seen in the aged and reflects multi-system physiological change. However, with reduced functional reserve and resilience frailty is also known to be common in the HIV infected population. This study outlined an easily administered screening test to identify HIV patients with frailty. When significant components of frailty are identified, clinicians will be able to focus on amelioration of the problem and promote reversion to the pre-frail state.

Abstract

一个简单的，经过验证的协议组成的电池测试可用于识别老年患者虚弱综合征。增加储备下降和抗应激综合征的发病率随着年龄的增加。在老年人中，脆弱性可能采取分步进行的非体弱，体弱，体弱丧失功能。我们研究的脆弱在感染艾滋病毒的患者，并发现，约20％是年老体弱的使用油炸型，采用严格的标准开发的老人^1,2。在艾滋病毒感染综合征的发生有年轻化。

艾滋病患者进行了检查1）无意减肥; 2）步行速度缓慢; 3）的弱点，作为衡量一个握力计; 4）用尽的抑郁量表的反应;和5）低体力活动，通过评估决定千卡的热量消耗在一个星期的时间。预脆弱存在任何两个五标准，脆弱性是存在的，如果任意三个五个标准为异常。

测试大约需要10-15分钟才能完成，他们可以在例行就诊的医疗助理。测试结果得分参照标准表。了解这五个组件有助于在个别病人的脆弱可以使医师能够解决相关的问题，其中有许多是不体现在日常HIV就诊。

Introduction

该中心疾病控制项目，一半以上的HIV-1感染在美国的个人将超过50岁，到2015年。 HIV-1感染的病人的预期寿命增加导致意外增加与老化相关的疾病，发病率和死亡率的风险增加的艾滋病毒呈阳性的长辈。一个重要的例子就是新近被描述的虚弱综合征，这可能会加速老化HIV-1感染的成人中发挥了重要作用^。3-7

弱者已定义的中老年作为生物的储备下降和抗应激综合征，导致生理系统累计跌幅往往进展分步进行的功能随着时间的推移下降。脆弱的临床重要性综合征被认为是一个高风险的状态，预测功能和流动性下降等不良健康结果，hospitalizat离子和死亡。在过去的10年中，许多研究试图评估在不同人群中的脆弱。炒等研究脆弱在男性和女性年龄超过65岁参加在心血管研究它们的定义脆弱女性衰老的研究中得到了验证^。9修改它们的定义已被用于在其他研究中，包括HIV-1感染的个体^。4-7炸等描述残疾或疾病的情况下，即使是在表明，老年人口的7％，比65岁体弱多病体弱的表型，而年纪比20-26％ 80岁体弱^。2弱者可以是一个主要发现，也有辅助诊断为急性事件或合并症，如恶性肿瘤，动脉粥样硬化，感染（HIV），或抑郁症的结果。此外，其他因素可能在艾滋病患者脆弱，例如，静脉吸毒，贫困和精神疾病。

弱者已发现的HIV-1感染的病人更小的年龄比非HIV感染患者⁴旧版HIV-1感染的个体经常出现更严重的HIV疾病并有较短的存活时间比年轻的人，往往因为他们都不能确诊直到很晚才在疾病过程中^。11另一个原因可能是，老年患者有更多的共同病态与HIV-1相互作用的疾病。旧的HIV-1感染的个体被描述为虚弱比年龄匹配控制个人无HIV-1感染。

脆弱的HIV-1感染患者的临床测量非常重要，因为可能是可逆的脆弱性在其早期阶段（ 如干预扭转失调，蛋白质能量营养不良，抑郁症，维生素D缺乏和其他脆弱性相关的条件）储备耗尽之前达到一个临界阈值导致不可逆转的脆弱性和功能下降。

Protocol

因为它是不切实际的测试在所有艾滋病诊所求诊的脆弱，我们建议以下的患者进行评估，脆弱的存在：病人进入CD4细胞计数<200，的抱怨无意减肥的患者，严重神经病变患者或护理谁不符合艾滋病毒治疗。 获得口头同意的病人接受测试体弱或“软肋”。同意需要不能被写入，因为所执行的一切是正常体检的一部分。 执行一个Mini-COG测试，如果病人出现混乱或精神萎靡。 指导病人仔细听，记得3个无关的话。考官说三个字出声来。 指导患者脸上画出一个时钟，无论是在空白的纸张，或已经在页面上画一个表与时钟圈。后病人将数字钟面，问他或h呃绘制时钟的指针读取一个特定的时间。 要求病人重复前面提到的3个字。给1点，每个召回字。没有回顾这3个字的患者归类为认知能力受损（比分= 0）。患者回顾三个字全都被列为认知完整（分数= 3）患者1-2个字的中间字召回分类的基础上的时钟​​拉伸试验（异常=受损，正常=完好）。 如果病人没有微型齿轮，临床医生应进一步研究的困惑和/或谵妄的原因。测试脆弱，不适合在这个时候。 称量减肥的病人和评估。有人谁是体弱≥10磅去年可能有无意减肥。 病人的步行缓慢。有人谁是体弱具有降低行走时所定义的定时15英尺的步行测试。时间调整性别和资格高度。男性高度为173厘米，女性<159厘米> 7秒谁走了15英尺的高度被认为是年老体弱;男性> 173厘米，女性> 159厘米，谁走了15英尺6秒被认为是年老体弱。 确定病人有弱点。缺点是当有调整性别和身体质量指数（BMI）值由测力计测量握力下降。与BMI <24的男性认为是年老体弱，如果握力（公斤）<29，为24.1-28 BMI，一个人年老体弱，如果<30，体重指数> 28 <32，如果一个人体弱。对于女性来说，BMI <23被认为是年老体弱，如果握力（公斤）是17，体重指数23.1-26被认为是年老体弱，如果<17.3，BMI在26.1-29被认为是体弱多病，如果<18和BMI > 29被认为是年老体弱，如果<21。 确定如果病人有低体力活动水平。这是为建立加权得分由明尼苏达休闲添测量消耗的卡路里，每周E活动问卷。问卷询问有关的活动，如日常生活，运动和爱好。弱者是当男性使用<383kcal/week，女性<270千卡/周12 确定如果病人出现枯竭的证据。这是自我报告的流行病学研究中心忧郁量表，回答2个问题。13所提出的问题是：你觉得如何往往在上周：（一），我所做的一切努力;或（b）我不能去吗？答案是：0 =少于1天，1 = 1〜2天，2 = 3-4天，3 =的大部分时间。 2个或3个回答这些问题，是一个积极的标准14脆弱。

Representative Results

One hundred outpatient HIV-1-infected persons were prospectively tested for clinical markers of frailty to include shrinking weight, slowness in walking, decrease in grip strength, low activity, and exhaustion. Eighty-one patients were not frail when studied, 19 patients were frail at the initial assessment (Table 1). The characteristics of the frail and non-frail patients were not significantly different except for a higher rate of hepatitis C and neuropathy in the frail group (p < 0.05). Length of infection with HIV, CD4 count and HIV-1 RNA viral load were also compared. As shown in Table 2 the younger patients had a greater incidence of frailty and this was associated with low CD4 cell counts. CD4 counts <200 cells/mm3 were associated with 9-fold increased odds of frailty relative to patients with a CD4 count >350 cells/mm3 (odds ratio [OR] 9.0, 95% confidence interval [CI] 2.1-44). Seven frail patients were measured 6 months later: 2 died refusing therapy, 4 were no longer frail, and 1 patient remained frail (Table 3). From this data it appears that when patients took prescribed anti-retroviral therapy the CD4 cell counts improved along with an improvement in the general state of health of the patient. Finally, if the incidence of frailty in the study population is compared to the number of years of anti-retroviral therapy taken by the patients, the longer patients took anti-retroviral therapy, the less the incidence of frailty (p < 0.05). This fact supports the early use of anti-retroviral therapy in HIV-infected patients which is the preferred approach in recent HIV treatment guidelines.15 We conclude that frailty is common in HIV outpatients and is associated with low CD4 counts more than with advancing age. Our data suggest that frailty is transient, especially in younger patients who may revert to their prefrail state unlike uninfected elderly individuals in whom a stepwise decline in function may occur. Representative Results from our Previous Study1     Frail, N=19 (19%) Non-Frail, N=81 (81%) Sex Male 14 (74%) 60 (74%)   Female 5 (26%) 21 (26%) Age <50 12 (63%) 46 (57%)   >=50 7 (37%) 35 (43%) Comorbidity Dyslipidemia 6 (32%) 25 (31%)   Psychiatric 4 (21%) 29 (36%)   Neuropathy 8 (42%) 15 (19%)   Hypertension 2 (11%) 17 (21%)   Hepatitis C 6 (32%) 12 (15%)   Diabetes mellitus 3 (16%) 6 (7%)   Coronary artery disease 1 (1%) 5 (6%) Table 1. Clinical characteristics of the HIV study patients. Frail patients were compared to non-frail HIV patients with respect to sex, age and comorbidities. The presence of neuropathy and infection with hepatitis C were significant differences between the frail and non-frail patients. CD4 Cell Count (cells/μl) <50 Years of Age, N (%) >=50 Years of Age, N (%) <200 7 3 200-350 4 1 >350 1 3 Ρ-value 0.028 0.021 Table 2. Frail patients and the relationship of age and CD4 cell count in these patients. The frail patients were significantly younger and with lower CD4 cell counts than non-frail patients. Patient Initial CD4 Cell Count (cells/μl) Initial Viral Load (RNA copies/μl) Retest CD4 Cell Count (cells/μl) Retest Viral Load (RNA copies/μl) Comorbidity Outcome 1 26 2 million N/A N/A hepatitis C, alcoholism Dead; refused ART 2 3 52,000 1 82,000 coccidioido-mycosis Dead; stopped ART 3 12 12,000 36 <48 none Not frail 4 169 <48 991 <48 blindness, peripheral neuropathy, pulmonary embolism Not frail 5 141 1,000 54 <48 lymphoma, peripheral neuropathy Not frail 6 151 <48 393 <48 coccidioido-mycosis, deep venous thrombosis Not frail 7 106 44,620 229 <48 hepatitis C, chronic obstructive lung disease Frail Table 3. Outcomes of 7 frail patients with low CD4 cell counts. These patients all needed anti-retroviral therapy, were prescribed therapy and then retested for frailty 6 months later. Only one patient who took the prescribed anti-retroviral therapy was still frail 6 months later. Figure 1. Relationship between number of years of taking anti-retroviral therapy and the incidence of frailty (89 patients were taking anti-retroviral therapy). The longer patients took anti-retroviral therapy the less the incidence of frailty in that population (p < 0.05).

Discussion

Previous studies of HIV and frailty: Two retrospective studies by Desquilbet et al. assessed frailty in a cohort of men who have sex with men from the Multicenter AIDS Cohort Studies (MACS). Both studies used a shortened definition of frailty containing fewer criteria than did our study. The first study compared frailty in HIV-1 infected men in the pre-treatment era to a control group of HIV uninfected men.⁴ There were similar rates of frailty in HIV+ men older than 55 years and HIV- men older than 65 years; frailty was found to occur earlier in HIV-1 infected men. Our study had similar findings of an earlier occurrence of frailty phenotype, but we obtained higher rates of frailty compared with MACS, possibly because our use of the full Fried frailty criteria versus surrogate administrative data, but also because of the different population of patients in our study.

Another study by Desquilbet et al. evaluated CD4 cell count and HIV viral load as predictors of frailty in HIV+ men and found that lower CD4 cell counts and viral loads of more than 50,000 copies of RNA were significantly associated with frailty.⁵ Also the prevalence of frailty declined in the era of ART. Despite differences in measuring frailty and in population characteristics our study concluded like Desquilbet et al. that a low CD4 cell count is significantly associated with frailty and that patients on long-term ART have less likelihood of developing frailty.¹ Premature occurrence of prevalence of frailty, shorter duration of ART, more co-morbidities and lower CD4 count were associated with frailty in both studies, but we did not find a strong association between psychiatric diagnosis and frailty. We found a positive relationship between length of ART and not being frail (Figure 1).

Our findings of frailty in HIV patients: Our initial hypothesis that age was not significantly important when measuring frailty of patients with low CD4 cell counts was confirmed. Frailty is likely more causally related to the inflammatory state and profound immunosuppression found in many patients with low CD4 cell counts. Many of these patients had a history of recently treated opportunistic infections. Because of these observations we propose that an active diagnosis of AIDS (CD4 cell count <200 cells/μl) is a significant co-morbidity itself and significantly predisposes patients to being frail. All of our frail patients had at least one co-morbidity besides HIV itself. Our frail patients <50 years had significantly fewer co-morbidities than the frail population >50 years, though in comparison, the younger people had a lower CD4 cell count.

Our other hypothesis was that frailty may be temporary in younger patients with low CD4 cell counts and may revert when CD4 cell counts improve. We were limited by the low number of patients and this hypothesis could not be proven, but it was a likelyexplanation for the small number of patients in which reversal was demonstrated (Table 1). Longer antiretroviral treatment was found to be protective for frailty (Figure 1). This fact on its own would support the recommendations of starting ART at higher CD4 counts and continuing ART without any treatment breaks. We believe that the main reason by which length of ART treatment was shown to be protective for frailty is that patients on long term treatment are more likely to have better control of co-morbidities as well as HIV and less likely to be frail.

In conclusion we have observed an association between low CD4-cell counts and frailty, which is not affected by age, viral load or the presence of co-morbidities. Effective treatment with ART plays a protective role against frailty, reinforcing the importance of effective ART. Early implementation of ART in the care of HIV patients may protect against frailty. Though not tested in our study, future research should address other interventions known to reverse frailty in the aged including treating deconditioning, protein-energy malnutrition, depression, and vitamin D deficiency.