Because it is impractical to test for frailty in all patients attending an HIV clinic we recommend the following patients be assessed for the presence of frailty: patients entering care with a CD4 cell count &lt;200, patients complaining of unintentional weight loss, severe neuropathy or patients who are not compliant with HIV therapy.
<ol>
	<li>Obtain verbal consent of the patient to undergo tests for frailty or "weakness". Consent need not be written since everything that is performed is part of a normal physical examination.</li>
	<li>Perform a Mini-Cog test if the patient appears confused or apathetic.
	<ol>
		<li>Instruct the patient to listen carefully to, and remember 3 unrelated words. The examiner states the three words out loud.</li>
		<li>Instruct the patient to draw the face of a clock, either on a blank sheet of paper or on a sheet with the clock circle already drawn on the page. After the patient puts the numbers on the clock face, ask him or her to draw the hands of the clock to read a specific time.</li>
		<li>Ask the patient to repeat the 3 previously stated words. Give 1 point for each recalled word. Patients recalling none of the three words are classified as cognitively impaired (Score = 0). Patients recalling all three words are classified as cognitively intact (Score = 3) Patients with intermediate word recall of 1-2 words are classified based on the clock draw test (Abnormal = impaired; Normal = intact).</li>
		<li>If the patient fails the Mini-Cog, the clinician should examine further for causes of confusion and/or delirium. Testing for frailty would not be appropriate at this time.</li>
	</ol>
	</li>
	<li>Weigh patient and assess for weight loss. Someone who is frail may have unintentional weight loss of &ge; 10 pounds in the prior year.</li>
	<li>Time a patient's walk for slowness. Someone who is frail has a decreased walking time as defined by a timed 15-foot walk test. The time is adjusted for gender and standing height. Men with a height of &lt;173 cm and women with a height &lt;159 cm who walked 15 feet in &gt;7 sec are considered frail; men &gt;173 cm and women &gt;159 cm who walked 15 feet in &gt;6 sec are considered frail.</li>
	<li>Determine if the patient has weakness. Weakness is established when there is decreased grip strength measured by a dynamometer with the value adjusted for gender and body mass index (BMI). Men with a BMI &lt;24 are considered frail if the grip strength (kg) is &lt;29, for a BMI of 24.1-28, a man is frail if &lt;30, for a BMI &gt;28 a man is frail if &lt;32. For women, a BMI of &lt;23 is considered frail if the grip strength (kg) is &lt;17, a BMI 23.1-26 is considered frail if &lt;17.3, a BMI of 26.1-29 is considered frail if &lt;18, and a BMI &gt;29 is considered frail if &lt;21.</li>
	<li>Determine if the patient has a low physical activity level. This is established by a weighted score of kilocalories expended per week measured by the Minnesota Leisure Time Activity Questionnaire. The questionnaire asks about activities like daily living, sports and hobbies. Frailty is present when males use &lt;383kcal/week, and females &lt;270 kcal/week.12</li>
	<li>Determine if the patient shows evidence of exhaustion. This is self-reported by answering 2 questions from the Center for Epidemiologic Studies Depression Scale.13 The questions asked are: How often in the last week did you feel: (a) that everything I did was an effort?; or (b) I could not get going? Answers were: 0 = less than 1 day, 1 = 1-2 days, 2 = 3-4 days, 3 = most of the time. Answering 2 or 3 to either of these questions is a positive criterion for frailty.14</li>
</ol>

<ol>
	<li>Ianas, V., Berg, E., Mohler, M. J., Wendel, C., Klotz, S. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Antiretroviral+therapy+protects+against+frailty+in+HIV-1+infection.">Antiretroviral therapy protects against frailty in HIV-1 infection.</a> J. Int. Assoc. Physicians AIDS Care. , (2012).</li><li>Fried, L. P., Tangen, C. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Frailty+in+older+adults:+evidence+for+a+phenotype.">Frailty in older adults: evidence for a phenotype.</a> J. Gerontol. A. Biol. Sci. Med. Sci. 56 (3), M146-M156 (2001).</li><li>Effros, R. B., Fletcher, C. V., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Aging+and+infectious+diseases:+workshop+on+HIV+infection+and+aging:+what+is+known+and+future+research+directions.">Aging and infectious diseases: workshop on HIV infection and aging: what is known and future research directions.</a> Clin. Infect. Dis. 47 (4), 542-553 (2008).</li><li>Desquilbet, L., Jacobson, L. P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=HIV-1+infection+is+associated+with+an+earlier+occurrence+of+a+phenotype+related+to+frailty.">HIV-1 infection is associated with an earlier occurrence of a phenotype related to frailty.</a> J. Gerontol. A. Biol. Sci. Med. Sci. 62 (11), 1279-1286 (2007).</li><li>Desquilbet, L., Margolick, J. B., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Relationship+between+a+frailty-related+phenotype+and+progressive+deterioration+of+the+immune+system+in+HIV-infected+men.">Relationship between a frailty-related phenotype and progressive deterioration of the immune system in HIV-infected men.</a> J. Acquir. Immune Defic. Syndr. 50 (3), 299-306 (2009).</li><li>Onen, N. F., Agbebi, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Frailty+among+HIV-infected+persons+in+an+urban+outpatient+care+setting.">Frailty among HIV-infected persons in an urban outpatient care setting.</a> J. Infect. 59 (5), 346-352 (2009).</li><li>Terzian, A. S., Holman, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Factors+associated+with+preclinical+disability+and+frailty+among+HIV-infected+and+HIV-uninfected+women+in+the+era+of+cART.">Factors associated with preclinical disability and frailty among HIV-infected and HIV-uninfected women in the era of cART.</a> J. Womens Health (Larchmt). 18 (12), 1965-1974 (2009).</li><li>Ahmed, N., Mandel, R., Fain, M. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Frailty:+an+emerging+geriatric+syndrome.">Frailty: an emerging geriatric syndrome.</a> Am. J. Med. 120 (9), 748-753 (2007).</li><li>Bergman, H., Ferrucci, L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Frailty:+an+emerging+research+and+clinical+paradigm--issues+and+controversies.">Frailty: an emerging research and clinical paradigm--issues and controversies.</a> J. Gerontol. A. Biol. Sci. Med. Sci. 62 (7), 731-737 (2007).</li><li>Bandeen-Roche, K., Xue, Q. L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Phenotype+of+frailty:+characterization+in+the+women's+health+and+aging+studies.">Phenotype of frailty: characterization in the women's health and aging studies.</a> J. Gerontol. A. Biol. Sci. Med. Sci. 61 (3), 262-266 (2006).</li><li>Wilson, J. F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Frailty--and+its+dangerous+effects--might+be+preventable.">Frailty--and its dangerous effects--might be preventable.</a> Ann. Intern. Med. 141 (6), 489-492 (2004).</li><li>Martin, C. P., Fain, M. J., Klotz, S. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+older+HIV-positive+adult:+a+critical+review+of+the+medical+literature.">The older HIV-positive adult: a critical review of the medical literature.</a> Am. J. Med. 121 (12), 1032-1037 (2008).</li><li>Taylor, H. L., Jacobs, D. R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+questionnaire+for+the+assessment+of+leisure+time+physical+activities.">A questionnaire for the assessment of leisure time physical activities.</a> J. Chronic Dis. 31 (12), 741-755 (1978).</li><li>Radloff, L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+CES-D+Scale:+A+self-report+depression+scale+for+research+in+the+general+population.">The CES-D Scale: A self-report depression scale for research in the general population.</a> Applied Psychological Measurement. 1 (3), 385-401 (1977).</li></ol>

No conflicts of interest declared.

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 &lt;200 cells/&mu;l) 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 &lt;50 years had significantly fewer co-morbidities than the frail population &gt;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.

The Centers for Disease Control projects that more than half of HIV-1 infected individuals in the United States will be over the age 50 by the year 2015. The increasing life expectancy of HIV-1 infected patients has resulted in an unexpected increase in aging-related co-morbidities, placing HIV-positive elders at increased risk of morbidity and mortality. One important example of this is with the newly described syndrome of frailty, which may play an important role in accelerated aging of HIV-1 infected adults.3-7
Frailty has been defined in the aged as a biologic syndrome of decreased reserve and resistance to stressors, resulting from the cumulative decline of physiologic systems and often progresses in a step-wise functional decline over time. The clinical importance of frailty is that the syndrome is considered a high-risk state, predictive of adverse health outcomes such as decreased function and mobility, hospitalization and death.8 Numerous studies in the last 10 years have tried to assess frailty in different populations. Fried et al. studied frailty in men and women older than 65 years of age who were enrolled in a cardiovascular study.2 Their definition of frailty was validated in a study of aging women.9 Modifications of their definition have been used in other studies including HIV-1 infected individuals.4-7 Fried et al. described a frail phenotype that even in the absence of disabilities or co-morbidities showed that 7% of population older than 65 years of age are frail whereas, 20-26% older than 80 years of age were frail.2 Frailty can be a primary finding, but also a secondary diagnosis as a result of an acute event or co-morbidity like malignancy, atherosclerosis, infection (HIV), or depression.10 Additionally, other factors likely contribute to frailty in HIV patients, for example, intravenous drug abuse, indigence and mental illness.
Frailty has been found in HIV-1 infected patients at younger ages than non-HIV infected patients.4 Older HIV-1 infected individuals frequently present with more severe HIV disease and have a shorter survival time than younger individuals, often because they are not diagnosed until very late in the disease process.11 Another reason may be that older patients have more co-morbid diseases interacting with HIV-1. Older HIV-1 infected individuals have been described as frailer than age-matched control individuals without HIV-1 infection.4
Clinical measurement of frailty in HIV-1 infected patients is important as frailty may be reversible in its early stages (e.g. interventions to reverse deconditioning, protein-energy malnutrition, depression, vitamin D deficiency and other frailty related conditions) before depleted reserves reach a critical threshold leading to irreversible vulnerability and functional decline.

measuring frailty in hiv-infected individuals. identification of frail patients is the first step to amelioration and reversal of frailty

A simple, validated protocol consisting of a battery of tests is available to identify elderly patients with frailty syndrome. This syndrome of decreased reserve and resistance to stressors increases in incidence with increasing age. In the elderly, frailty may pursue a step-wise loss of function from non-frail to pre-frail to frail. We studied frailty in HIV-infected patients and found that ~20% are frail using the Fried phenotype using stringent criteria developed for the elderly1,2. In HIV infection the syndrome occurs at a younger age.
HIV patients were checked for 1) unintentional weight loss; 2) slowness as determined by walking speed; 3) weakness as measured by a grip dynamometer; 4) exhaustion by responses to a depression scale; and 5) low physical activity was determined by assessing kilocalories expended in a week's time. Pre-frailty was present with any two of five criteria and frailty was present if any three of the five criteria were abnormal.
The tests take approximately 10-15 min to complete and they can be performed by medical assistants during routine clinic visits. Test results are scored by referring to standard tables. Understanding which of the five components contribute to frailty in an individual patient can allow the clinician to address relevant underlying problems, many of which are not evident in routine HIV clinic visits.

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 &lt; 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 &lt;200 cells/mm3 were associated with 9-fold increased odds of frailty relative to patients with a CD4 count &gt;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 &lt; 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
<table border="1">
	<tbody>
		<tr>
			<td>&nbsp;</td>
			<td>&nbsp;</td>
			<td>Frail, N=19 (19%)</td>
			<td>Non-Frail, N=81 (81%)</td>
		</tr>
		<tr>
			<td>Sex</td>
			<td>Male</td>
			<td>14 (74%)</td>
			<td>60 (74%)</td>
		</tr>
		<tr>
			<td>&nbsp;</td>
			<td>Female</td>
			<td>5 (26%)</td>
			<td>21 (26%)</td>
		</tr>
		<tr>
			<td>Age</td>
			<td>&lt;50</td>
			<td>12 (63%)</td>
			<td>46 (57%)</td>
		</tr>
		<tr>
			<td>&nbsp;</td>
			<td>&gt;=50</td>
			<td>7 (37%)</td>
			<td>35 (43%)</td>
		</tr>
		<tr>
			<td>Comorbidity</td>
			<td>Dyslipidemia</td>
			<td>6 (32%)</td>
			<td>25 (31%)</td>
		</tr>
		<tr>
			<td>&nbsp;</td>
			<td>Psychiatric</td>
			<td>4 (21%)</td>
			<td>29 (36%)</td>
		</tr>
		<tr>
			<td>&nbsp;</td>
			<td>Neuropathy</td>
			<td>8 (42%)</td>
			<td>15 (19%)</td>
		</tr>
		<tr>
			<td>&nbsp;</td>
			<td>Hypertension</td>
			<td>2 (11%)</td>
			<td>17 (21%)</td>
		</tr>
		<tr>
			<td>&nbsp;</td>
			<td>Hepatitis C</td>
			<td>6 (32%)</td>
			<td>12 (15%)</td>
		</tr>
		<tr>
			<td>&nbsp;</td>
			<td>Diabetes mellitus</td>
			<td>3 (16%)</td>
			<td>6 (7%)</td>
		</tr>
		<tr>
			<td>&nbsp;</td>
			<td>Coronary artery disease</td>
			<td>1 (1%)</td>
			<td>5 (6%)</td>
		</tr>
	</tbody>
</table>
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.
<table border="1">
	<tbody>
		<tr>
			<td>CD4 Cell Count (cells/&mu;l)</td>
			<td>&lt;50 Years of Age, N (%)</td>
			<td>&gt;=50 Years of Age, N (%)</td>
		</tr>
		<tr>
			<td>&lt;200</td>
			<td>7</td>
			<td>3</td>
		</tr>
		<tr>
			<td>200-350</td>
			<td>4</td>
			<td>1</td>
		</tr>
		<tr>
			<td>&gt;350</td>
			<td>1</td>
			<td>3</td>
		</tr>
		<tr>
			<td>&Rho;-value</td>
			<td>0.028</td>
			<td>0.021</td>
		</tr>
	</tbody>
</table>
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.
<table border="1">
	<tbody>
		<tr>
			<td>Patient</td>
			<td>Initial CD4 Cell Count (cells/&mu;l)</td>
			<td>Initial Viral Load (RNA copies/&mu;l)</td>
			<td>Retest CD4 Cell Count (cells/&mu;l)</td>
			<td>Retest Viral Load (RNA copies/&mu;l)</td>
			<td>Comorbidity</td>
			<td>Outcome</td>
		</tr>
		<tr>
			<td>1</td>
			<td>26</td>
			<td>2 million</td>
			<td>N/A</td>
			<td>N/A</td>
			<td>hepatitis C, alcoholism</td>
			<td>Dead; refused ART</td>
		</tr>
		<tr>
			<td>2</td>
			<td>3</td>
			<td>52,000</td>
			<td>1</td>
			<td>82,000</td>
			<td>coccidioido-mycosis</td>
			<td>Dead; stopped ART</td>
		</tr>
		<tr>
			<td>3</td>
			<td>12</td>
			<td>12,000</td>
			<td>36</td>
			<td>&lt;48</td>
			<td>none</td>
			<td>Not frail</td>
		</tr>
		<tr>
			<td>4</td>
			<td>169</td>
			<td>&lt;48</td>
			<td>991</td>
			<td>&lt;48</td>
			<td>blindness, peripheral neuropathy, pulmonary embolism</td>
			<td>Not frail</td>
		</tr>
		<tr>
			<td>5</td>
			<td>141</td>
			<td>1,000</td>
			<td>54</td>
			<td>&lt;48</td>
			<td>lymphoma, peripheral neuropathy</td>
			<td>Not frail</td>
		</tr>
		<tr>
			<td>6</td>
			<td>151</td>
			<td>&lt;48</td>
			<td>393</td>
			<td>&lt;48</td>
			<td>coccidioido-mycosis, deep venous thrombosis</td>
			<td>Not frail</td>
		</tr>
		<tr>
			<td>7</td>
			<td>106</td>
			<td>44,620</td>
			<td>229</td>
			<td>&lt;48</td>
			<td>hepatitis C, chronic obstructive lung disease</td>
			<td>Frail</td>
		</tr>
	</tbody>
</table>
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.
<img alt="Figure 1" src="/files/ftp_upload/50537/50537fig1.jpg" /> 
 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 &lt; 0.05).

Watch this Scientific Journal Video about Measuring Frailty in HIV-infected Individuals. Identification of Frail Patients is the First Step to Amelioration and Reversal of Frailty at JoVE.com

Measuring Frailty in HIV-infected Individuals. Identification of Frail Patients is the First Step to Amelioration and Reversal of Frailty

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.

A simple, validated protocol consisting of a battery of tests is available to identify elderly patients with frailty syndrome. This syndrome of decreased ...

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16.2K Views.  University of Arizona. 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 stat...

Video: Measuring Frailty in HIV-infected Individuals. Identification of Frail Patients is the First Step to Amelioration and Reversal of Frailty

Manual Muscle Testing:  A Method of Measuring Extremity Muscle Strength Applied to Critically Ill Patients

Survivors of acute respiratory distress syndrome (ARDS) and other causes of critical illness often have generalized weakness, reduced exercise tolerance, and persistent nerve and muscle impairments after hospital discharge.1-6 Using an explicit protocol with a structured approach to training and quality assurance of research staff, manual muscle testing (MMT) is a highly reliable method for assessing strength, using a standardized clinical examination, for patients following ARDS, and can be completed with mechanically ventilated patients who can tolerate sitting upright in bed and are able to follow two-step commands. 7, 8 
This video demonstrates a protocol for MMT, which has been taught to &ge;43 research staff who have performed &gt;800 assessments on &gt;280 ARDS survivors. Modifications for the bedridden patient are included. Each muscle is tested with specific techniques for positioning, stabilization, resistance, and palpation for each score of the 6-point ordinal Medical Research Council scale.7,9-11 Three upper and three lower extremity muscles are graded in this protocol: shoulder abduction, elbow flexion, wrist extension, hip flexion, knee extension, and ankle dorsiflexion. These muscles were chosen based on the standard approach for evaluating patients for ICU-acquired weakness used in prior publications. 1,2.

Survivors of acute respiratory distress syndrome (ARDS) and critical illness frequently develop long-lasting muscle weakness. Manual muscle testing (MMT) is a standardized clinical examination commonly used to measure strength of peripheral skeletal muscle groups. This video demonstrates MMT using the 6-point Medical Research Council scale.

Survivors of acute respiratory distress syndrome (ARDS) and other causes of critical illness often have generalized weakness, reduced exercise tolerance, ...

Sequencing of Bacterial Microflora in Peripheral Blood: our Experience with HIV-infected Patients

The healthy gastrointestinal tract is physiologically colonized by a large variety of commensal microbes that influence the development 
	of the humoral and cellular mucosal immune system1,2. 
 Microbiota is shielded from the immune system via a strong mucosal barrier. Infections and antibiotics are known to alter both the normal 
	gastrointestinal tract barrier and the composition of resident bacteria, which may result in possible immune abnormalities3.
HIV causes a breach in the gastrointestinal barrier with progressive failure of mucosal immunity and leakage into the systemic circulation of bacterial bioproducts, such as lipopolysaccharide and 
	bacterial DNA fragments, which contribute to systemic immune activation4-7. Microbial translocation is implicated in HIV/AIDS immunopathogenesis and response to therapy 4,8.
We aimed to characterise the composition of bacteria translocating in peripheral blood of HIV-infected patients. To pursue our aim we set up a PCR reaction for the panbacteric 16S ribosomial gene 
	followed by a sequencing analysis.
Briefly, whole blood from both HIV-infected and healthy subjects is used. Given that healthy individuals present normal intestinal homeostasis no translocation of microflora is expected in 
	these patients. Following whole blood collection by venipuncture and plasma separation, DNA is extracted from plasma and used to perform a broad range PCR reaction for the panbacteric 
	16S ribosomial gene9. Following PCR product purification, cloning and sequencing analyses are performed.

Our experiment will show how to perform a sequencing analysis of bacterial species translocating in peripheral blood of HIV positive patients.

The healthy gastrointestinal tract is physiologically colonized by a large variety of commensal microbes that influence the development 
	of the humoral ...

The Measurement and Treatment of Suppression in Amblyopia

Amblyopia, a developmental disorder of the visual cortex, is one of the leading causes of visual dysfunction in the working age population. Current estimates put the prevalence of amblyopia at approximately 1-3%1-3, the majority of cases being monocular2. Amblyopia is most frequently caused by ocular misalignment (strabismus), blur induced by unequal refractive error (anisometropia), and in some cases by form deprivation.
Although amblyopia is initially caused by abnormal visual input in infancy, once established, the visual deficit often remains when normal visual input has been restored using surgery and/or refractive correction. This is because amblyopia is the result of abnormal visual cortex development rather than a problem with the amblyopic eye itself4,5 . Amblyopia is characterized by both monocular and binocular deficits6,7 which include impaired visual acuity and poor or absent stereopsis respectively. The visual dysfunction in amblyopia is often associated with a strong suppression of the inputs from the amblyopic eye under binocular viewing conditions8. Recent work has indicated that suppression may play a central role in both the monocular and binocular deficits associated with amblyopia9,10 .
Current clinical tests for suppression tend to verify the presence or absence of suppression rather than giving a quantitative measurement of the degree of suppression. Here we describe a technique for measuring amblyopic suppression with a compact, portable device11,12 . The device consists of a laptop computer connected to a pair of virtual reality goggles. The novelty of the technique lies in the way we present visual stimuli to measure suppression. Stimuli are shown to the amblyopic eye at high contrast while the contrast of the stimuli shown to the non-amblyopic eye are varied. Patients perform a simple signal/noise task that allows for a precise measurement of the strength of excitatory binocular interactions. The contrast offset at which neither eye has a performance advantage is a measure of the "balance point" and is a direct measure of suppression. This technique has been validated psychophysically both in control13,14 and patient6,9,11 populations.
In addition to measuring suppression this technique also forms the basis of a novel form of treatment to decrease suppression over time and improve binocular and often monocular function in adult patients with amblyopia12,15,16 . This new treatment approach can be deployed either on the goggle system described above or on a specially modified iPod touch device15.

Amblyopia is a developmental disorder of the visual cortex that is often accompanied by strong suppression of one eye. We present a new technique for measuring and treating interocular suppression in patients with amblyopia that can be deployed using virtual reality goggles or a portable iPod Touch device.

Amblyopia, a developmental disorder of the visual cortex, is one of the leading causes of visual dysfunction in the working age population. Current ...

Collecting Saliva and Measuring Salivary Cortisol and Alpha-amylase in Frail Community Residing Older Adults via Family Caregivers

Salivary measures have emerged in bio-behavioral research that are easy-to-collect, minimally invasive, and relatively inexpensive biologic markers of stress. This article we present the steps for collection and analysis of two salivary assays in research with frail, community residing older adults-salivary cortisol and salivary alpha amylase. The field of salivary bioscience is rapidly advancing and the purpose of this presentation is to provide an update on the developments for investigators interested in integrating these measures into research on aging. Strategies are presented for instructing family caregivers in collecting saliva in the home, and for conducting laboratory analyses of salivary analytes that have demonstrated feasibility, high compliance, and yield quality specimens. The protocol for sample collection includes: (1) consistent use of collection materials; (2) standardized methods that promote adherence and minimize subject burden; and (3) procedures for controlling certain confounding agents. We also provide strategies for laboratory analyses include: (1) saliva handling and processing; (2) salivary cortisol and salivary alpha amylase assay procedures; and (3) analytic considerations.

We demonstrate: (1) procedures for collection of salivary samples in cognitive impaired older adults by family caregivers in the home setting, (2) procedures for measuring stress activity via salivary cortisol and alpha amylase, and (3) representative profiles. Protocols that allow researchers to study stress-linked processes advance our understanding of biological sensitivity and susceptibility.

Salivary measures have emerged in bio-behavioral research  that are easy-to-collect, minimally invasive, and relatively inexpensive  biologic markers of ...

Heterotopic Renal Autotransplantation in a Porcine Model: A Step-by-Step Protocol

Kidney transplantation is the treatment of choice for patients suffering from end-stage renal disease. It offers better life expectancy and higher quality of life when compared to dialysis. Although the last few decades have seen major improvements in patient outcomes following kidney transplantation, the increasing shortage of available organs represents a severe problem worldwide. To expand the donor pool, marginal kidney grafts recovered from extended criteria donors (ECD) or donated after circulatory death (DCD) are now accepted for transplantation. To further improve the postoperative outcome of these marginal grafts, research must focus on new therapeutic approaches such as alternative preservation techniques, immunomodulation, gene transfer, and stem cell administration.
Experimental studies in animal models are the final step before newly developed techniques can be translated into clinical practice. Porcine kidney transplantation is an excellent model of human transplantation and allows investigation of novel approaches. The major advantage of the porcine model is its anatomical and physiological similarity to the human body, which facilitates the rapid translation of new findings to clinical trials. This article offers a surgical step-by-step protocol for an autotransplantation model and highlights key factors to ensure experimental success. Adequate pre- and postoperative housing, attentive anesthesia, and consistent surgical techniques result in favorable postoperative outcomes. Resection of the contralateral native kidney provides the opportunity to assess post-transplant graft function. The placement of venous and urinary catheters and the use of metabolic cages allow further detailed evaluation. For long-term follow-up studies and investigation of alternative graft preservation techniques, autotransplantation models are superior to allotransplantation models, as they avoid the confounding bias posed by rejection and immunosuppressive medication.

Porcine models of organ transplantation provide an important platform to study mechanisms of organ preservation. This article describes a heterotopic porcine renal autotransplantation model, which allows investigating new approaches to improve the outcome of transplantation using marginal kidney grafts.

Kidney transplantation is the treatment of choice for patients suffering from end-stage renal disease. It offers better life expectancy and higher quality ...

A Step by Step Protocol for Subretinal Surgery in Rabbits

Age related macular degeneration (AMD), retinitis pigmentosa, and other RPE related diseases are the most common causes for irreversible loss of vision in adults in industrially developed countries. RPE transplantation appears to be a promising therapy, as it may replace dysfunctional RPE, restore its function, and thereby vision.
Here we describe a method for transplanting a cultured RPE monolayer on a scaffold into the subretinal space (SRS) of rabbits. After vitrectomy xenotransplants were delivered into the SRS using a custom made shooter consisting of a 20-gauge metallic nozzle with a polytetrafluoroethylene (PTFE) coated plunger. The current technique evolved in over 150 rabbit surgeries over 6 years. Post-operative follow-up can be obtained using non-invasive and repetitive in vivo imaging such as spectral domain optical coherence tomography (SD-OCT) followed by perfusion-fixed histology.
The method has well-defined steps for easy learning and high success rate. Rabbits are considered a large eye animal model useful in preclinical studies for clinical translation. In this context rabbits are a cost-efficient and perhaps convenient alternative to other large eye animal models.

Retinal pigment epithelium (RPE) replacement strategies and gene-based therapy are considered for several retinal degenerative conditions. For clinical translation, large eye animal models are required to study surgical techniques applicable in patients. Here we present a rabbit model for subretinal surgery geared towards RPE transplantation, which is versatile and cost-efficient.

Age related macular degeneration (AMD), retinitis pigmentosa, and other RPE related diseases are the most common causes for irreversible loss of vision in ...

Exergaming in Older People Living with HIV Improves Balance, Mobility and Ameliorates Some Aspects of Frailty

Approximately 1.2 million people in the United States live with HIV infection. Medical advancements have increased the life expectancy and this cohort is aging. HIV-positive individuals have a high incidence of frailty (~20%) characterized by depression and sedentary behavior. Exercise would be healthy, but due to the frail status of many HIV-positive individuals, conventional exercise is too taxing. The aim of this study was to evaluate the effectiveness and acceptability of a novel game-based training program (exergame) in ameliorating some aspects of frailty in HIV-infected individuals. Ten older people living with HIV were enrolled in an exergame intervention. Patients performed balance exercises such as weight shifting, ankle reaching, and obstacle crossing. Real-time visual/audio lower-extremity joint motion feedback was provided using wearable sensors to assist feedback and encourage subjects to accurately execute each exercise task. Patients trained twice a week for 45 min for 6 weeks. Changes in balance, gait, psychosocial parameters and quality of life parameters were assessed at the beginning, midterm and at conclusion of the training program. Ten patients completed the study and their results analyzed. The mean age was 57.2 &#177; 9.2 years. The participants showed a significant reduction in center of mass sway (78.2%, p = .045) during the semi-tandem balance stance with eyes closed and showed a significant increase in gait speed during a dual task motor-cognitive assessment (9.3%, p = .048) with an increase in stride velocity of over 0.1 m/sec. A significant reduction in reported pain occurred (43.5%, p = .041). Preliminary results of this exergame intervention show promise in improving balance and mobility while requiring older people living with HIV to be more active. The exergame can be continued at home and may have long term as well as short-term benefits for ameliorating frailty associated with HIV infection.

Persons infected with HIV are often frail, depressed and live a sedentary lifestyle for which conventional exercise is too taxing. Here, we present an exercise protocol that ameliorates aspects of frailty in HIV-infected persons. An exergame integrating cognitive control was developed using biosensors that measured balance, weight-shifting and obstacle crossing.

Approximately 1.2 million people in the United States live with HIV infection. Medical advancements have increased the life expectancy and this cohort is ...

Re-Arterialized Rat Partial Liver Transplantation with an in vivo Vessel-Oriented 70% Hepatectomy

Split liver transplantation and living liver donor liver transplantation were developed in the clinic to utilize liver organs in a more efficient manner. To better understand the mechanism behind these surgical procedures, a rat partial liver transplantation (PLTx) model was established for relevant surgical studies. Because of the complexity of the rat PLTx model, a protocol with detailed descriptions is required. An article published previously reported a protocol in which ex vivo hepatectomy was used to achieve 50% rat PLTx. In contrast to this protocol, we introduced a re-arterialized PLTx with an in vivo 70% hepatectomy. An updated vessel-oriented hepatectomy was incorporated into the rat PLTx to refine the microsurgical procedure. The portal veins and hepatic arteries of the left lateral lobe and the median lobe were individually dissected and ligated before removal of the liver parenchyma, thereby decreasing the probability of bleeding in the remnant liver stump. Furthermore, an end-to-side vessel anastomosis between the common hepatic artery and the enlarged proper hepatic artery was introduced to re-arterialize the hepatic artery. By using this end-to-side vessel anastomosis technique, the diameter of the anastomosis was enlarged, thereby decreasing the difficulty of hand suture and maintaining a high rate of anastomotic patency. Moreover, the cuff anastomosis of the infrahepatic vena cava was slightly modified. A section of circumferential liver parenchyma around the vena cava of a recipient was preserved during cuff anastomosis to maintain the three-dimensional shape of the vascular lumen. This section of liver parenchyma was removed after completing the anastomosis. With this modification, the step involving placement of stay sutures was omitted, thereby further shortening the cuff anastomosis time. By using this protocol of rat PLTx, a low liver enzyme level, an intact liver lobular architecture and a high survival rate were achieved after microsurgery.

Re-Arterialized Rat Partial Liver Transplantation with an in vivo Vessel-Oriented 70% Hepatectomy

Here, a protocol involving re-arterialized rat partial liver transplantation is presented. Specifically, 70% liver was resected in vivo by using an updated technique of vessel-oriented hepatectomy. The hepatic artery was reconstructed in an end-to-side manner. The cuff technique was modified to shorten the anastomosis time of the infrahepatic vena cava.

Split liver transplantation and living liver donor liver transplantation were developed in the clinic to utilize liver organs in a more efficient manner. ...

Measurement of Tissue Oxygenation Using Near-Infrared Spectroscopy in Patients Undergoing Hemodialysis

Near-infrared spectroscopy (NIRS) has recently been applied as a tool to measure regional oxygen saturation (rSO2), a marker of tissue oxygenation, in clinical settings including cardiovascular and brain surgery, neonatal monitoring and prehospital medicine. The NIRS monitoring devices are real-time and noninvasive, and have mainly been used for evaluating cerebral oxygenation in critically ill patients during an operation or intensive care. Thus far, the use of NIRS monitoring in patients with chronic kidney disease (CKD) including hemodialysis (HD) has been limited; therefore, we investigated rSO2 values in some organs during HD. We monitored rSO2 values using a NIRS device transmitting near-infrared light at 2 wavelengths of attachment. The HD patients were placed in a supine position, with rSO2 measurement sensors attached to the foreheads, the right hypochondrium and the lower legs to evaluate rSO2 in the brain, liver and lower leg muscles, respectively. NIRS monitoring could be a new approach to clarify changes in organ oxygenation during HD or factors affecting tissue oxygenation in CKD patients. This article describes a protocol to measure tissue oxygenation represented by rSO2 as applied in HD patients.

We present a protocol to measure regional oxygen saturation (rSO2) in hemodialysis (HD) patients by using a near-infrared spectroscopy monitor. The rSO2 value is an index of tissue oxygenation. This noninvasive and real-time monitoring could be useful for confirming changes in organ oxygenation during HD.

Near-infrared spectroscopy (NIRS) has recently been applied as a tool to measure regional oxygen saturation (rSO2), a marker of tissue oxygenation, in ...

The Use of Mixed Reality in Custom-Made Revision Hip Arthroplasty: A First Case Report

The technology of 3D printing and visualization of anatomical structures is rapidly growing in various fields of medicine. A custom-made implant and mixed reality were used to perform complex revision hip arthroplasty in January 2019. The use of mixed reality allowed for a very good visualization of the structures and resulted in precise implant fixation. According to the authors' knowledge, this is the first described case report of the combined use of these two innovations. The diagnosis preceding the qualification for the procedure was the loosening of the left hip's acetabular component. Mixed reality headset and holograms prepared by engineers were used during the surgery. The operation was successful, and it was followed by early verticalization and patient rehabilitation. The team sees opportunities for technology development in joint arthroplasty, trauma, and orthopedic oncology.

A complex revision hip arthroplasty was performed using a custom-made implant and mixed reality technology. According to the authors&#39; knowledge, this is the first report of such procedure described in the literature.

The technology of 3D printing and visualization of anatomical structures is rapidly growing in various fields of medicine. A custom-made implant and mixed ...