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EDITOR-IN-CHIEF 
HYPERLINK "https://www.scitechnol.com/editor-profile/Douglas_Vetter_PHD/"Douglas Vetter, 
Department of Neurobiology and Anatomical Sciences,
HYPERLINK "https://www.scitechnol.com/universities/University_of_Mississippi_Medical_Center/" \o "University of Mississippi Medical Center"University of Mississippi Medical Center, USA
Journal of Traumatic Stress Disorders & Treatment



Attached you will find our original manuscript titled � Frailty syndrome among older patients with posttraumatic stress disorder  written by Parnicka Agnieszka,  Piotrowicz Karolina, Mielimka MichaB, Walczewska Jolanta, Falisz Katarzyna, Skalska Anna, Rutkowski Krzysztof and Grodzicki Tomasz, that we would like to submit for the publication in Journal of Traumatic Stress Disorders & Treatment. Based on data from the cross-sectional study included older participants who were deported to remote regions of the former Soviet Union in their childhood because of political reasons, or who were born in Siberia or Kazakhstan as children of the deportees, we showed that frailty syndrome occurs more often among patients with PTSD than in general population. Our findings suggest that PTSD could be a risk factor for frailty syndrome therefore prevention and treatment of PTSD will be very important. To the best of the authors� knowledge, it is the first research that assessed frailty syndrome in older patients with posttraumatic disorders. 
All authors participated in the study, they have seen and approved the manuscript and have no conflict of interest regarding it. No part of the work has not been published previously in print or electronic format and is not under consideration by another publication or electronic medium.  The munuscript has seven tables and only one figure.
Project was approved by the Bioethics Committee of the Jagiellonian University Medical College (nb: KBET/110/B/2011), all subjects signed informed consent. 



Related paper from the same study:
1. Rutkowski K, DembiDska E, Walczewska J. Effect of trauma onset on personality traits of politically persecuted victims. BMC Psychiatry.2016;16:148.doi:10.1186/s12888-016-0853-2. 
2. Walczewska J, Rutkowski K, Cwynar M, Wizner B, Grodzicki T. Comprehensive geriatric evaluation in former Siberian deportees with posttraumatic stress disorder. Am J Geriatr Psychiatry. 2014;22(8):820-8. doi: 10.1016/j.jagp.2013.01.044. 
3. Walczewska J, Rutkowski K, Wizner B, Cwynar M, Grodzicki T. Stiffness of large arteries and cardiovascular risk in patients with post-traumatic stress disorder. Eur Heart J. 2011;32(6):730-6. doi: 10.1093/eurheartj/ehq354. 
4. Heitzman J, Rutkowski K. Mental disturbances in persons persecuted for political reasons in Poland in the years 1944-1955. Psychiatr Pol. 1997 Mar-Apr;31(2):153-64. Polish. 


We are looking forward to hearing from you soon, 
Yours sincerely, 
Parnicka Agnieszka, MD; 				e-mail: HYPERLINK "mailto:agnieszka.parnicka@interia.pl"agnieszka.parnicka@interia.pl
							Adress:  Zniadeckich 10 Str.
  31-351   Krak�w
  Poland
							Tel: +484248800
							Fax: +484248854

Karolina Piotrowicz, MD, PhD 
Mielimka MichaB, MD, PhD 
Walczewska Jolanta, MD, PhD 
Falisz Katarzyna, MD 
Anna Skalska, MD, PhD 
Prof. Rutkowski Krzysztof, MD, PhD 
Prof. Tomasz Grodzicki, MD, PhD



































Frailty syndrome among older patients with posttraumatic stress disorder.




Parnicka Agnieszka �, Piotrowicz Karolina�, Mielimka MichaB�, Walczewska Jolanta�,Falisz Katarzyna�, Skalska Anna�, Rutkowski Krzysztof� , Grodzicki Tomasz�

�Department of Internal Medicine and Gerontology, Jagiellonian University Medical College, 31-531Krakow, 10 Zniadeckich Str., Poland,
�Department of Psychotherapy, Jagiellonian University Medical College, Krak�w, Poland







Agnieszka Parnicka, MD email address:  HYPERLINK "mailto:agnieszka.parnicka@interia.pl" agnieszka.parnicka@interia.pl
Karolina Piotrowicz MD, PhD email address:  HYPERLINK "mailto:zona3@interia.pl" zona3@interia.pl
Walczewska Jolanta, MD, PhD email address: jolawalcz@op.pl
Falisz Katarzyna, MD email address: kasia.falisz@gmail.com
Anna Skalska, MD, PhD email address: anskal@su.krakow.pl
MichaB Mielimka, MD, PhD, email address:  HYPERLINK "mailto:michal.mielimaka@gmail.com" michal.mielimaka@gmail.com
Prof. Tomasz Grodzicki, MD, PhD email address: tomekg@su.krakow.pl
Prof.  Krzysztof Rutkowski, MD, PhD email address: mzrutkow@cyf-kr.edu.pl


Key words: PTSD, frailty, grip strength, TUG, older adults, Posttraumatic Stress Disorder, 




Words: 4632


Correspondence to:
Agnieszka Parnicka
Department of Internal Medicine and Gerontology
Jagiellonian University Medical College
31-351 Krakow, Zniadeckich 10 Str.
email address: agnieszka.parnicka@interia.pl














Abstract:

Introduction:
Aim: to assess frailty syndrome in elderly people with posttraumatic stress disorder (PTSD). 

Materials and Methods:
The study included people e"60 years old with PTSD. The Patients from the study group were deported during the World War II or born on in exile in the Soviet Union. PTSD was diagnosed according to the criteria of Diagnosis and Statistical Manual of Mental Disorders (DSM-IV). To assess frailty three scales were used: Canadian Study of Health and Aging Clinical Frailty Scale (CSHA-CFS), Cardiovascular Health Survey frailty definition (CSH) and the Identification of Seniors At Risk (ISAR) screening tool.

Results: 
The study group consisted of 59 patients (52.5% males) whose mean age was 71.1�6.8 years
With the Fried�s criteria 61% of the patients were pre-frail, 23.7% were frail, almost half of the respondents reported exhaustion, 25.4% weight loss, and 18.6% low activity level; 64.4% presented weakness and 10.2% slow walking speed. According to the CSHA CFS 32.2% of all respondents were mildly frail, 8.5%-moderately frail, 1.7%-severely frail and only 1.7%-was very fit. According to the ISAR tool there was 83.1% at risk and 61.0% of the group, according to the threshold of two and three points, respectively. There was a significant correlation between the results of the Timed Up and Go test and ISAR (r=0.45, p<0.05) and between the results of grip strength and ISAR (r=0.41, p<0.05). 

Conclusions:
Frailty syndrome occurs more often among patients with PTSD than in general population. There was a relationship between ISAR and muscle strength and mobility.

Keywords: 
PTSD, frailty, grip strength, TUG, elderly, older adults


Introduction
Frailty (FS) is a geriatric syndrome of loss of reserves that gives rise to vulnerability (1). FS is associated with poor prognosis, falls, adverse outcomes, disability and loss off independence (1-6). The prevalence of frailty in people older than 65 years ranging from 7% to 16.3% and increases with age (4-6). A standardized definition and diagnostic criteria has not been established yet (2), there have been a lot of concepts of frailty definition in the literature, the most known is the �phenotyp mode� by L. Fried and �cumulative deficit model-Frailty Index�by Rockwood (2,7,8). Only few definitions of FS have been directly compared with each other so far (7,9). Frailty is a result of overlapping of age related changes, unfavorable lifestyle and the presence of chronic conditions. It is a potentially reversible syndrome. Many geriatric interventions have been developed to improve clinical outcomes for frail adults (7). The most important is the comprehensive geriatric assessment with nutritional interventions and exercise programs (6). 
Posttraumatic stress disorder (PTSD) is defined as a severe psychological and physical response or the result of exposure to a stressful event that the person perceives as highly traumatic (10). PTSD patients have been shown to present significantly higher prevalence of a variety of diseases and multimorbidity with cardiovascular diseases, including hypertension and coronary artery disease (11). Posttraumatic stress disorder is associated with self-reported mental and functional impairment (12). The spread of PTSD in the general population is estimated at 1% (11). The prevalence of PTSD in populations particularly exposed to stressors increases to 30-80% (13). PTSD just as frailty syndrome very often co-occurs with other diseases and syndromes, for example with chronic heart diseases, arterial hypertension, chronic arthritis (11).
The aim of our study was to assess frailty syndrome in the elderly people with PTSD. There has been no data about this problem in PTSD patients in the literature yet.


Materials and methods: 
The study population consisted of the patients followed up at the Clinic for Former Victims of Political Persecution affiliated at the Department of Psychotherapy, Jagiellonian University Medical College. The data has been collected from September 2012 to August 2014. The study group included out-patients with PTSD e" 60 years, who had been deported or born in exile in the former Soviet Union during the World War II. Project was approved by the Bioethics Committee of the Jagiellonian University Medical College (nb: KBET/110/B/2011), all subjects signed informed consent.
Medical, psychiatric and psychological examinations were performed in all patients.
Clinical assessment included: obtaining medical history using a standardized questionnaire, a physical examination, weight and height measurements. Medical history comprised data on deportation, included a place and duration of deportation, history of acute and chronic illnesses, injuries, number of drugs, tobacco use and geriatric assessment focused on investigation of the geriatric syndromes and deficits. The clinical assessment was made by the medical doctors trained in geriatrics.
The formal psychological and psychiatric examination was performed. Posttraumatic stress disorder was diagnosed according to the criteria of Diagnosis and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV) (Table 1), the severity of symptoms was also assessed using Global Assessment of Functioning (GAF Axis V DSM). 
According DSM-IV mild PTSD was diagnosed when a participant obtained from 6 to 21 points, moderate from 22 to 36 points, and severe if a score was greater than 36 points (10). 
Frailty syndrome was evaluated using three scales: the Canadian Study of Health and Aging Clinical Frailty Scale (CSHA-CFS, Table 2), the Cardiovascular Health Survey frailty definition (CHS, Table 3) and the Identification of Seniors At Risk (ISAR) screening tool (9, 14,15,16,17).
Unintentional weight loss was self-reported and considered as positive if the participant reported loss of weight more than 5% during the last 12 months. Feeling of exhaustion was checked with two questions of the Center of Epidemiological Study Center Scale (CES-D): �Have you felt that you had to make an effort to do you customary tasks?� or �Were you unable to proceed when doing your things?�.
The �time up and go� (TUG) for a distance of 3 meters was used to assess patients� mobility. Slowness was defined as TUG result over 20 sec.
Hand grip strength (kg) was measured using the manual dynamometer (model SH5001, Saehan) three-times, on a dominant hand with 30 seconds intervals. The best result was considered. The results were presented in kilograms and adjusted for gender and a body mass index (BMI).
To identify those seniors who were vulnerable to some complications of hospitalization, we used a simple scoring system designed for geriatric screening of elderly people (ISAR tool). The tool is mostly useful to identify frail seniors in inpatients hospital care (14). The ISAR tool is comprised of 6 �yes-no� questions: if the respondent needed help on a regular basis, needed more help than usual to take care of himself during the past 6 months, had been hospitalized in the past 6 months, had sight problems, had serious problems with memory, was taking more than three medications per day (15,16). For the purpose of the analysis, 2 and 3-point cut-off values of ISAR tool were used (18).
Statistical analyses have been done with Statistica package [StatSoft, Inc. version 10]. Continuous variables were presented as mean (SD) and median (Q1, Q3) values and compared with U Mann- Whitney test; Pearson chi-squared test (�2) was used for categorical data. We analyzed the results in the subgroups of age (median age) and gender. Nonparametric statistics were used to assess the correlations between the FS results.



Results:
The study group included 59 patients (52.5 % men); mean (�SD) age: 71.1�6.8 years (min.-max.: 60-88 years), median (Q1, Q3):71 (66,75). All persons have been diagnosed with PTSD according to the DSM-IV criteria; 16.9% of the former deportees had mild PTSD; 49,2% of them was classified as moderate and 33.9% as severe PTSD. There was no significant difference in age and PTSD severity with regard to sex.

Cardiovascular Health Survey frailty definition:

The prevalence of FS, diagnosed according to the CHS-frailty definition was 23.7% (recognized in 32.1% women versus in 16.1% of men; p=0.15). 61.0% of patients was in pre-frail stage (57.2% of women and 64.5% of men; p=0.56), whereas only 15.3% (10.7% of women versus 19.4% of men; p=0.36) were non-frail. The women had higher (although not significant) frequencies of weakness (71.4 % versus 58.1%; p=0.28), of low physical activity (28.6% versus 9.7%; p=0.06) and of slow walking speed (14.3 % versus 6.5%; p=0.32). Exhaustion was declared by 48.4% of men and 50.0% of women (p=0.9). An unintentional weight loss was observed in 22.6% of men and in 28.6% of women (p=0.6).
The distribution of the frequency of frailty syndrome based on the Cardiovascular Health Survey frailty definition (CHS), in the whole group and with regard to age (median value) was shown in the table 4.  















Canadian Study of Health and Aging Clinical Frailty Scale definition:

The frequency of mild frailty, according CSHA-CFS, among the elderly outpatients with PTSD was 32.2% (42.9% of women versus 22.6% of men; p= 0.1), of moderate FS 8.5% (7.1% of women versus 9.7% of men; p=0.73), of severe frailty was 1.7% (3.2% of man versus none woman; p=0.34), only 1.7% of them was robust (3.2 % of men versus none woman; p=0.34). The distribution of the results of the Canadian Study of Health and Aging Clinical Frailty Scale in the whole group and with regard to the age was shown in Figure 1.  

 In the whole group, there was no significant correlation between the results of CSHA-CFS and the severity of PTSD (table 5 and table 6).



 The Identification of Seniors At Risk

The third scale diagnosing frailty syndrome was the Identification of Seniors At Risk (ISAR) screening tool. At risk (frail) was 83.1% and 61.0% of the group, according to the threshold of two and three ISAR points, respectively. Frail (threshold e"2 points) were 92.9% of women and 74.2% of men (p=0.06). Among those aged 60-71 years 66.7% of patients with PTSD were frail, in those aged 72-88 years 100% of patients were frail with threshold e"2 (p=0.001).  
Using (threshold e"3 points) frailty was recognized in 75.0% of women and 48.4% of men (p=0.04). Among those aged 60-71 40.0% of patients with PTSD were frail, in those aged 72-88  82.8 % of patients were frail with threshold e"3 (p=0.001).  
Median (Q1, Q3) value of the ISAR tool for the whole group was 3 points (2-5), min-max: 0-6 points, for women: 4 (2.5-5.0), min-max: 1-6 points; for men: 2 (1-4), min-max: 0-6 points (p=0.03). The value of the ISAR tool among those aged 60-71 was 2 (1,4), min-max: 0-6 points and on those aged 72-88: 4(3,5), min-max: 2-6 points (p<0.001).
The results of the assessment with the ISAR tool were presented in table 7.
The severity of PTSD did not correlate with frailty according to ISAR tool. 
In the whole group, there was a significant correlation between the results of the Timed Up and Go test and ISAR (r=0.41, p<0.05) and correlation between the results of hand grip strength and ISAR ( r=-0.40, p<0.05).
     	

Discussions:
The purpose of this study was to assess frailty syndrome among older people with posttraumatic stress disorder. Our data demonstrated that frailty was a frequent condition among elderly people with PTSD. When applying the CSH-frailty definition our research revealed that, more than 20% of patients with PTSD were frail and over 60% of the deportees to the former Soviet Union were pre-frail. Using ISAR tools we obtained similar results - more than 80% of the deportees were at risk and considered being frail. The lower prevalence of FS was revealed with the CSHA-FS scale, 32.2%, of the participants were mildly frail, 8.3% moderately and 1.7% severely. The prevalence of FS in general populations is meaningly lower; 6.5% in population of people over 60 years were frail (4) and among people aged 65 and older in pre-frail stage were 44.2% (5). For instance FS according to Fried�s criteria among the community-dwelling people aged between 65-74 in UK study was present in 8.5% of women and 4.1% of men (17).  In another Polish study using Tilburg Frailty Indicator (TFI) 40% of outpatients were frail (19). Prevalence of frailty syndrome among people living in Polish nursing homes was much higher than in the present study, the frequency of severe frailty was even 34.9% (20). 
In our study like in other studies which used CSHA-CFS there was a trend towards a higher frequency of frailty in women (8). And, as in other studies, prevalence of FS increased with age. Gale et al. in the English Longitudinal Study of Ageing examined people aged 60 and over according to the Fried�s criteria and the prevalence rose with increasing age, from 6,5% in those aged 60-69 years to 65% in those aged 90 and over (4).
To identify seniors vulnerable to complications of hospitalization we used a simple scoring system designed for geriatric screening of elderly people (ISAR tool). ISAR seems to be a useful screening tool for frailty and identifies elderly patients at risk of adverse outcome, primarily after an Emergency Department visit (21). The ISAR has a good sensitivity to identify frail older patients in inpatients hospital care as well (14). 
The lack of standardized diagnostic criteria limits the ability for a good comparison of the prevalence of this syndrome.
However, the high prevalence of FS in our study may be associated with the characteristics of the research group. Pathogenesis of FS is probably multifactorial including biological, clinical (for example: multimorbility) and social factors (for example:  social isolation, poverty) (22). Patients with PTSD usually suffer from several diseases including various mental disorders (e.g. depression, dementia) and physical disability (23).  For instance, the veterans with late-life PTSD were at a 45% increased risk for incident CVD, 26% increased risk for incident CHF, and 49% increased risk for incident MI compared with veterans without late-life PTSD (11). In literature, the former deportees had higher prevalence of coronary artery disease, hypertension, obesity, diabetes, asthma, and hearing impairment (23, 24, 25). 
The issue of higher prevalence of cognitive function deficits and depression in patients with PTSD has also been recognized by the Polish researchers (23).
The prevalence of severity of PTSD in our study group was similar to another study,    most of former deportees were at moderate stage of PTSD (23). In our study the severity  of PTSD did not correlate with frailty among the study patients. Our research supports the hypothesis that physical impairment should rather be considered as an additional component of PTSD, as was proposed by a Nazi camp survivors Researcher A. KempiDski (KZ-Syndrom). The relations between the physical and mental components in KZ-Syndrom are complex due to extensive and unobvious interactions between psychological processes and body functions. (26)
Statistic correlation showed a strong association between frailty (assessed according ISAR tool) and muscle strength and mobility. This is consistent with the results of the other studies, grip strength could be useful single marker of frailty (27,28). Decreased grip strength is a predictor of disability, mobility and mortality (28,29).
Byers et a., argued that PTSD in later life is a prominent predictor of disability above and beyond other psychiatric disorder and medical conditions (30). In other study it was found that PTSD in older veterans negatively correlated with physical performance and physical function (31,32). Vietnam-era Veterans with PTSD in average age of 61 years demonstrated diminished functioning and decreased disability (32).
  Other prior studies have provided evidence that depression and PTSD (independent of depression) is associated with functional impairment (33-35) and persistent PTSD is associated with global disability (30).
The early recognition of PTSD seems to be very important. Our study suggested that people with PTSD could be a group at risk also in terms of frailty syndrome. We speculate that potential intervention among elderly with PTSD may be well effective, aimed at lessening the state of frailty and at prevention of disability.
This study has some limitations. First, our study group underrepresented the old-old (75-84 years) and the oldest-old (e"85 years). Secondly, the study group is small, but it s a very specific group and it is very difficult to get a larger number of deportees. Thirdly, we don t have a control group; our results were compared to the data on general population published in literature. 

Conclusions:

Frailty syndrome occurs often among older adults who had been deported as children or born in exile in the former Soviet Union and still have suffered from PTSD. These findings suggest that PTSD could be a risk factor for frailty syndrome therefore prevention and treatment of PTSD will be very important.


Disclosure of interest
The authors declare that they have no conflicts of interest concerning this article.


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Table 1. The diagnosis PTSD was based using DSM-IV criteria:


The presence of A1 (when the person experienced, witnessed, or was confronted 
with an event or events that involved actual or threatened death or injury, or a threat 
to the physical health of oneself or others) 

and A2 criteria (when the person's response involved intense fear, helplessness,              
or horror) is OBLIGATORY to diagnose PTSD. 

B, C, and D criteria include other clinical features of PTSD: 
-the traumatic event is persistently re-experienced (B criterion), 
-persistent avoidance of stimuli associated with the trauma and numbing of general 
 responsiveness (C criterion), 
-persistent symptoms of increased arousal (D criterion).


































Table 2. CSHA-clinical frail scale; score range 1-7.

1. very fit, robust, active, energetic, well motivated and fit, these people commonly exercise regularly and are in the most fit group for their age2. well; without active disease, but less fit than people in category 13. well with treated comorbid disease, disease symptoms are well controlled compared with the category 44. apparently vulnerable, although not frankly dependent, these people commonly complain of being slowed up or have disease symptoms5. mildly frail, with limited dependence on other for instrumental activities of daily living6. moderately frail, help is needed with both instrumental and non-instrumental activities of daily living7. severely frail, completely dependent on others for the activities of daily living, or terminally ill.

































Table 3. Frail-CHS; score range 0-5;  
frail e" 3 criteria present, pre-frail 1 or 2 criteria present .

1.Unintentional weight lossunintentional loss  > 5 % loss of weight              or > 10 pounds during 12 months2.Weakness low hand grip strength  3.SlownessTUG 4.Low physical activityin need of assistance during walking5. Self-reported ExhaustionCES: two questions









































Table 4. Distribution of frailty syndrome  according  CHS-frailty definition:

Non-frail




 
(%)Pre-frail





(%)Frail




 
(%)Weight loss





(%)Low physical activity 



 (%)Weakness





(%)Slow walking 
speed



 (%)Exhaustion




 
(%)
All
(n=59)

15.3

61.0

23.7

 25.4
 
18.6

64.4

10.2
 
49.2
60-71 years (n=30)
 
20

    70

10

16.7

10

63.3

 10

 36.7
72-88 years (n=29)


10.3

51.7

38



 34.5
 
27.6
 
65.5

10.3
 
62.1
p value
0.3
0.15
0.01

0.12
0.0
0.86
0.97
0.05



















Table 5.
 The prevalence of Frailty Syndrome (CSHA-CFS ) in all participants 
according to PTSD severity. 

PTSD
Mild
 (%)PTSD 
Moderate
(%)PTSD
Severe
(%)
p  valueMild frail30.031.035.00.95Moderate frail0.013.85.00.32Severe frail10.00.00.00.83Frail (()40.044.840.00.93







































Table 6. 
The prevalence of Frailty Syndrome (CHS frailty scale) in all participants according to PTSD severity.

PTSD
Mild
 (%)PTSD 
Moderate
(%)PTSD
Severe
(%)
p valueNon-frail10.010.325.00.33Pre-frail50.062.165.00.72Frail40.027.610.00.15






































Table 7.  Baseline and distribution of ISAR tools .

ISAR 1
(respondent needed help on a regular basis)




%
ISAR 2
(needed more help than usual to take care of himself during the past 6 months)

%ISAR 3
(had been hospitalized in the past 6 months)





%ISAR 4
(had sight problems)







%ISAR 5
(had serious problems with memory)




%
ISAR 6
(taking more than three medications per day)




%All  (N=59)39.045.820.378.054.276.3Women46.650.025.089.367.982.1Men32.341.916.167.741.971.0P value0.270.530.400.050.050.3160-71 yrs23.333.320.070.036.756.772-88 yrs55.258.620.786.272.496.6p value0.010.050.950.130.0060.0003PTSD mild30.040.020.070.050.070.0PTSD moderate48.358.627.682.851.772.4PTSD severe30.030.010.075.060.085.0P value0.360.130.320.650.810.52Frailty (2+)
N=4946.955.124.583.763.387.8Non-frailty
N=100.00.00.050.010.020.0P value0.0060.0010.080.020.0020.00000Frailty (3+)
N=3663.975.033.388.969.488.9Non-frailty 
N=230.00.00.060.930.456.5P value0.000000.000000.0020.010.0030.004



Figure 1. The distribution of the results of the Canadian Study of Heath and Aging Clinical Frailty Scale in the whole group and with regard to age. 



























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