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Amrita Journal of Medicine


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Original Article

Clinical Profile and Treatment of Primary Myelofi-brosis - An Observational Study from a Tertiary Care Centre in Kerala, South India

Lipid Profile in Executive Health Checkup Patients in a Tertiary Health Care Center in KeralaHigh Burden of Cardiovascular Diseases in Kerala:

High Time to Reorient the Primary Health Care System

Comparision of APACHE 2 vs SOFA Scores in Predicting Mortality Among Patients in ICU

Neeraj Sidharthan, Mariam Varsha Joseph, Sharon Ann Georgy, Priyanka S, Devayani Santhu, Meenu Vijayan, Raghuveer Prabhu, Govind Vijayakumar, Remya Sudevan

Ayesha Taniya P H, Niranjana Rajesh, Anu Sasidharan

DayanaAntony, Nisha Bhavani

Rakesh P S

Editorial Board

CONTENTS

Rema pai, Pillai MGK, Mohanakkannan S

25 Need of Routine Upper GI Endoscopy in Renal Transplant Workup Patients in a Resource Limit-ed Setting- A Cross Sectional Study from Kerala, South IndiaVijay Anand Viswanathen, Remya Sudevan, Govind Vijayakumar

31

Clinical Features and Treatment Outcomes in Axial Spondyloarthritis Patients in India: A Single Center Retrospective AnalysisAnuj Singhal, Sudhir K Joshi, Rahul Tyag

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Child Sexual Abuse – The Current Scenario

41

36 Age Influence on Clinical Profile and Outcome of Stroke – A Hospital based Cohort Study from a Comprehensive Stroke Care Centre in Kerala, South India Vivek Nambiar, Jisha S Das, Jeslyn Mary Philip, Delcey Rachel Vargheese, Ashly Alexander Fernandez, Uma devi P, Dhanya T S, Remya Sudevan, Manu Raj, Amrutha Ajai, Georgeena Pulickal

A Case of Non Bacterial Thrombotic Endocarditis in ElderlyAswin Rajeev, George Paul, Priya Vijayakumar

Case Report

43 Phenytoin Toxicity in an Adolescent with EpilepsyFollowing Self Harm – Is Early Detection of Depression Imperative?

Kotchuthressia Mathew, Kesavankutty Nayar, Sree- kumar, Dinesh Narayanan

Vol. 14, NO: 1Jan - Mar 2018, Page 1 - 44

Review Article

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Editorial BoardAdvisers

Dr. Prem Nair Dr. Vishal Marwaha

Editorial Board Chairman

Dr. D M Vasudevan

Chief Editor

Dr. Harish Kumar

Editorial Board Members

Dr. Beena K v

Dr. Vijayakumar K

Dr. Sundaram K R

Dr. P G Nair

Dr. Manuraj R

Dr. Unnikrishnan Menon

Dr. Meenakshi Dhar

Dr. Debanand Dutta

Dr. Hisham Ahammed

Dr. Venkitachalom

Dr. Rakesh P S

Dr. Anupama R

Dr. Sandeep Sreedhar

Dr. Gireesh Kumar

Publicity Officer

Mrs. Gita Rajagopal

Design & Artwork

Sivaprasad

Copyright Although every possible care has been taken to avoid any mistake and this publication is being sold on condi-tion and understanding that the information it contains are merely for guidance and reference and must not be taken as having the complete authority. The Institution and The Editors do not owe any responsibility for any action taken on the basis of this publication. The copy rights on the material and its contents vests exclusively with the publisher. Nobody can reproduce or copy the prints in any manner.

Amrita Journal of Medicine Vol. 14, NO: 1Jan - Mar 2018, Page 1 - 44

Site Link: http//www.amritahospital.org/amrita_journal

2


Child Sexual Abuse – The Current ScenarioAyesha Taniya P H*, Niranjana Rajesh*, Anu Sasidharan*

ABSTRACTChild Sexual Abuse (CSA) is prevalent all over the world. The dynamics of CSA is very different from Adult Sexual Abuse and there-fore cannot be considered in the same way. It is said that 90% of the perpetrators of CSA are known to the child. The ravages of CSA are deep seated and lifelong. Victims of CSA are much more prone to major depression, anxiety disorder, suicidal ideation, suicide attempt, alcohol dependence, illicit drug dependence, post traumatic stress disorder (PTSD) symptoms, decreased self-esteem, and decreased life satisfaction. The prevalence of CSA in India is 52.94% of boys and 47.06% of girls. In 2012, ‘The Protection of Chil-dren from Sexual Offences Act (POCSO Act) 2012’ was passed. This protects children and criminalizes sexual assault, harassment and pornography involving a child. In spite of POCSO, there is still a lot to be done to protect children from CSA.

Keywords: Child Sexual Abuse (CSA), Perpetrators, POCSO Act, PTSD, Psychological effects, UNICEF, WHO

Corresponding Author: Anu Sasidharan

INTRODUCTION Child Sexual Abuse (CSA) is prevalent all over the world, and has many long term deleterious effects on a child. The World Health Organisation (WHO) has defined CSA as “the involvement of a child in sexual activity that he or she does not fully comprehend, is unable to give in-formed consent to, or for which the child is not develop-mentally prepared and cannot give consent, or that vi-olates the laws or social taboos of society”. Child sexual abuse is evidenced by this activity between a child and an adult or another child who by age or development is in a relationship of responsibility, trust or power, the activity being intended to gratify or satisfy the needs of the other person. This may include but is not limited to the exploitative use of a child to be engaged: in any un-lawful sexual activities; in prostitution or other unlawful sexual practices and in pornographic performance and materials1. While sexual abuse in adults and children seem com-parable in theory, the dynamics of the two are very different. In CSA, the perpetrators use manipulation, threats and promises of love to gain the child’s trust and hide the abuse. CSA often occurs over weeks, months and sometimes years. The perpetrators “groom” the child, and the intensity of the abuse gradually increases over a period of time. This as opposed to sexual abuse in adults, is usually an isolated event, with involvement of force1.

*Dept. of Forensic Medicine & Toxicology, AIMS, Amrita Vishwa Vidyapeetham, Kochi, India.

Prevalence of CSA In The World

REVIEW


The WHO concluded in 2002 that 150 million girls and 73 million boys have experienced sexual violence be-fore the age of 18.2 In 2016, The WHO claimed that 1 in 5 women and 1 in 13 men report having been sexually abused as a child. The National Criminal Justice Refer-ence Service reported that 1 in 15 US adults reported to have had forced intercourse at least once in their life-

time4. According to a 2009 meta-analysis which studied prevalence over 22 countries - 7.9% of men and 19.7% of women globally experienced sexual abuse prior to the age of 18.4• The highest prevalence rate of child sexual abuse

was found in Africa (34.4%),4 followed by Ameri-ca and Asia which had prevalence rates between 10.1% and 23.9%. Europe showed the lowest preva-lence rate with 9.2%2.

• South Africa has the highest prevalence rates for both men (60.9%) and women (43.7%)4.

• For women, seven countries reported prevalence rates above 20%: Australia (37.8%), Costa Rica (32.2%), Tanzania (31.0%), Israel (30.7%), Sweden (28.1%), United States (25.3%) and Switzerland (24.2%)4.

• Whereas for men, Jordan presented with the sec-ond highest prevalence for sexual abuse with 27%4.

Another study which assessed the prevalence in 24 countries found that prevalence of CSA varied from 0-69% in girls and 0-47% for boys. In this, 9% of girls and 3% of boys have undergone forced intercourse. More-over, 15% of girls and 7% of boys have suffered mixed sexual abuse5. The Centres for Disease Control and the US Depart-ment of Justice conducted a study in the US and report-ed prevalence of being forced to have sex at some point of time in their lives as 11% and 4% of the high-school girls and boys, respectively4. A review of studies from 21 high- and middle-income nations showed that 7- 36% of females and 3- 29% of males reported being victims of sexual abuse during their childhood6. Few investigators conducted a study in Brazil in 2009. It was found that 5.6% of girls and 1.6% of boys were sexually abused. 60% of these incidents took place when the victims were younger than 12 years old. It was also found that boys were to be abused at younger ages in comparison to girls. CSA is accountable for about 1% of the global

3

Amrita Journal of MedicineChild Sexual Abuse – The Current Scenario

Prevalance of CSA in India Nineteen percent of the world’s children live in India. According to the 2001 Census, some 440 million people in the country today are aged below eighteen years and constitute 42 percent of India’s total population i.e., four out of every ten persons. With growing concerns about the child rapes and institutional abuse, the Ministry of Women and Child Development conducted a study in India about the prevalence of child abuse in the coun-try. The study, based on a well-designed methodology, covered 13 states (two states from each of the six geo-graphic zones in the country) including states with the highest through to the lowest crime rates incidence of offences against children.6 Out of 12,447 child respondents, 52.94% of boys and 47.06% of girls were found to be sexually abused. From these, 21% reported being subjected to severe forms of sexual abuse. This means that across the country - every second child was being subjected to other forms of sex-ual abuse and every fifth child was facing severe forms of sexual abuse. For these reported cases of CSA, major-ity of the perpetrators were6:

Uncles or Neighbours (31%)Friends/ Classmates (29%)Cousins (10%)Employers (9%)

Remaining 21% children reported sexual assault by others that included strangers, persons they were faint-ly acquainted with, teachers, care givers, etc. When one looked within the evidence groups, the highest per-centages of children reporting sexual assault were6:Working children (8.70%)Children in institutional care (7.08%)Street children (6.53%)

Assam, Andhra Pradesh, Bihar and Delhi reported the highest incidence of sexual abuse of both boys and girls and Goa reported the lowest prevalence amongst boys and girls. Majority of children subjected to sexual as-sault kept quiet (72.1%) and did not report the matter

to anyone. Among those who reported, the majority of children shared the incident with their parents followed by brother and sister (6.7%). Only 3.4% children report-ed the matter to police6. The prevalence of CSA in Kerala was found to be 55.04% in boys and 44.96% in girls. Out of these 21.22% of boys and 13.84% of girls experienced severe forms of sexual abuse. This shows that the prevalence of CSA in Kerala is at par with the national statistics. This seems surprising as Kerala has the highest literacy rate in the country, and so one would assume that the prevalence of CSA might be lower6.

Perpetrators and Other Associated Factors of CSA It is said that 9 out of 10 perpetrators of CSA are known to the child, with only 10% of strangers accounting as perpetrators of CSA. Approximately 30% of victims of CSA are sexually abused by family members. The young-er the victim, the more likely it is that the abuser is a fam-ily member. Of those molested under the age of6, 50% of perpetrators were family members. About 60% of the victims are abused by people their family trusts12. It is also seen that the younger the child is, the more likely it is that the offender is a juvenile. Forty three per-centage of perpetrators of CSA (where victims were be-low 6 years) happen to be juveniles13. Most incidents of CSA occur in residences, typically that of the victim or perpetrator – 84% for children un-der age 12, and 71% for children aged 12 to 1713. Though all children are at risk of sexual abuse, children living with step parents, single parents, single parents with a boyfriend/girlfriend and foster children seem to have a higher risk of being sexually abused. Children in low socioeconomic status households, rural area also are seen to have a higher risk14. The low incidence of CSA seen in boys may be due to not reporting it from fear of “looking weak” (if the offender was a female) or being viewed as homosexu-al (if offender was a male)3. Age is also a factor, where children seem to most vulnerable at ages 7-13. It is also found that children who are victims of other crimes have a higher risk of being sexually abused15.

Sequelae of CSA The ravages of abuse are deep seated and often life-long. The evidence suggests that sexual abuse is an im-portant problem with serious long-term effects. Abuse is unique in the way it damages children because it leaves the survivor with shame, intimacy issues, or even low self esteem as a result of their experience that could haunt them for well into their adulthood. Child Sexual Abuse is associated with substantial increased risk of subsequent psychopathology. Although a wide variety of psychological sequelae have been documented in sexually abused children re-ferred for evaluation or treatment, there appears to be considerable variability in the severity of the symptoms,

burden of disease, but it is likely to be a risk factor for several other conditions like alcohol consumption, ille-gal drug usage, development of mental disorders, and spread of sexually transmitted diseases, which when pooled, are accountable for over 20% of the global bur-den7. Similarly in China a study concluded that 33% of the participants were victims of CSA.8 Another study done in Boston concluded that the burden of CSA was 26.7% and 16.7% in girls and boys, respectively.9 In Mexico, one research work reported a prevalence of 18.7% of CSA (58% in girls and 42% in boys). Physical abuse was involved in 75% of the cases10. In Croatia, 10.8% of the children reported as having faced some form of CSA during childhood11.

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Detecting Sexual Abuse in Children

and we remain ignorant of these sequelae in the abused children who never enter the mental health system16. A study in the United States shows that those who experience Child Sexual Abuse are more likely to be diagnosed with mental disorders, have suicide-related problems and are at increased likelihood for experienc-ing adult victimization17. Meanwhile, a study done in New Zealand concludes that the extent of exposure to Child Sexual Abuse was associated with increased rates of: major depression, anxiety disorder, suicidal ideation, suicide attempt, alcohol dependence, and illicit drug dependence. In addition, at age of 30 years Child Sexual Abuse was as-sociated with higher rates of post traumatic stress dis-order (PTSD) symptoms, decreased self-esteem, and decreased life satisfaction. Childhood sexual abuse was also associated with decreased age of onset of sexual activity, increased number of sexual partners, increased medical contacts for physical health problems and wel-fare dependence18. An article showing a study aimed at comparing the socio-demographic, abuse-related, and clinical features of female adolescents who were sexually abused by different perpetrators, and identifying the factors asso-ciated with suicidal and non-suicidal self-injury (NSSI) concluded that Major Depressive Disorder was the most common psychiatric diagnosis, which was present in 44.9% of the cases. Among all the victims, 25.6% had at-tempted suicide, 52% had suicidal ideation, and 23.6% had NSSI during the post-abuse period19.

In a prospective investigation the results supported the notion that childhood sexual abuse may be a risk factor for early and risky sexual activity and teenage motherhood. Sexually abused participants have report-ed: being significantly younger at the age of voluntary intercourse, less birth control efficacy, were younger at the birth of their first child, and were more likely to be teen mothers than were comparison participants19.

Abuse in childhood could interfere with the develop-ment of the child; affect regulation and interpersonal relatedness, which would impact on the individual’s awareness of danger and ability to respond to threat-ening situations, hence leading to an increased risk of re-victimization. Secrecy and stigmas associated with Child Sexual Abuse may lead to reluctance to seek men-tal health treatment, and increased risk of experiencing mental health impairment including suicide attempts.

Since there are no behavioural signs or symptoms that clearly indicate the presence of sexual abuse, physicians must examine and observe children with a high degree of suspicion. The child’s disclosure is the most important part of detecting sexual abuse. Children must be interviewed, preferably alone, using open ended questions like “Has

anyone ever touched you in a way that made you un-comfortable or in a way that you didn’t like?” It is im-portant to keep a neutral tone, and to not ask leading questions20. There are certain behaviours that are more suggestive of sexual abuse like sexualized behaviour. This can vary depending on the developmental stage of the child. In very young children it can be compulsive masturbation, preoccupation with the sexual parts of others or per-forming developmentally inappropriate sexual acts. In older children it can mean promiscuous behaviour or unusually sexualized way of dressing or acting20. Another common set of behaviours are “post traumat-ic” symptoms. These include high levels of anxiety, fear-fulness of certain places or people. Other behaviours are depression, aggressiveness, eat-ing disorders, self harm/ self abuse, school problems of sudden onset, suicidal tendencies, and substance abuse20.

Physical Findings in Victims of Child Sexual Abuse It is now well acknowledged that, unlike physical abuse, very few cases sexual abuse can be diagnosed on physical examination alone. Summaries from nearly two dozen studies show that 50% of sexually abused girls and 53% of sexually abused boys appear entirely normal on physical examination. Nonetheless, it is recommend-ed that all children of suspected sexual abuse must be fully examined20. Most patients have normal and nonspecific findings on examination. These findings include the following:21

1. Hymenal tags, bumps or mounds2. Labial adhesions3. Clefts or notches in the anterior half (between the

9- and 3-o’clock position) of the hymen4. Vaginal discharge5. Erythema of the genitalia or anus6. Perianal skin tags7. Anal fissures8. Anal dilatation with stool in the ampulla.9. Sexually transmitted infections in children.

Physical findings that are concerning but not diagnostic of sexual abuse include the following: 1. Notches or clefts in the posterior half of the hymen

extending nearly to the vaginal floor2. Condylomata acuminata in a child older than two

years who gives no history of sexual contact3. Immediate, marked anal dilatation4. Anal scarring.

Physical findings that are diagnostic of penetrating trau-ma include: 1. Acute laceration or ecchymosis of the hymen2. Absence of hymenal tissue in the posterior half

5


REFERENCES

Legal Status of CSA in India Until 2012, the only sexual offences against children recognised by the law were covered in three sections of the Indian Penal Code (IPC). These provisions in law were not specific to children. The only crimes registered were rape (sexual intercourse without consent—section 376 IPC), outraging modesty of a woman (unspecified acts—section 354 IPC) and unnatural acts defined as “carnal intercourse against the order of nature with any man, woman or animal” (anal sex, homosexuality or bes-tiality—section 377 IPC). This meant that other forms of sexual assault were not applicable to any of these laws, leaving children vulner-able to sexual abuse without being able to be reported or to take action against the perpetrators. Increased concern and awareness of the despair of chil-dren and prevalence of CSA in the country by the pub-lic and social media may account for the Government of India passing a special law called, ‘The Protection of Children from Sexual Offences Act (POCSO Act) 2012’. This Act criminalises sexual assault, sexual harassment, and pornography involving a child (less than 18 years of age) and mandates the setting up of Special Courts to expedite trials of these offences. This is the first time that an Act has listed aspects of touch as well as non touch behaviour (eg: photographing a child in an ob-scene manner) under the ambit of sexual offences. For more heinous offences of Penetrative Sexual Assault, Aggravated Penetrative Sexual Assault, Sexual Assault and Aggravated Sexual Assault, the burden of proof is shifted on to the accused. The act further incorporates child friendly procedures for reporting of offences, recording of evidence, investi-gation and trial of offences. Even the attempt to commit an offence and abetment of the offence has also been made liable for punishment under the act22.

RECOMENDATIONS AND CONCLUSION Sex has always been a taboo topic in India. This is usually where the problem begins. Most children don’t know that they’re being abused because sexual abuse has not been spoken about at home, and the few chil-dren who do know about it don’t feel free enough to tell anyone. Most of the time, when children do tell an adult about their abuse, they’re made to keep quiet about it because of the social stigma and the shame that is as-sociated with sexual abuse, which ends up affecting the victim. This has to stop if we ever want to overcome this problem. Awareness and knowledge have always been key to bringing about change. As Child Sexual Abuse has major impact on the psychological, physical and re-productive health of individuals, it is the responsibility

of the medical community to take a more active role in detecting, treating and preventing child sexual abuse.

• Parents must be counselled and taught the signs to look out for and to detect probable sexual abuse in children by medical professionals from the very beginning.

• There should be regular workshops for teachers on how to detect and deal with a sexually abused child by professionals specialized in the field.

• There should be regular classes by a trained pro-fessional on good touch and bad touch and body ownership in schools.

• Physicians must be alert, and must interview the child, preferably alone, about sexual abuse.

• It has also been suggested that all children seen in emergency rooms should be given a brief examina-tion to screen for sexual abuse. In one study, the re-cords of 26,000 children seen in the emergency de-partment of a teaching hospital over an 18-month period were analyzed. Three hundred of those pa-tients were identified by medical staff as victims of sexual abuse23.

• All schools must have a trained counsellor, who is well equipped to detect and deal with victims of sexual abuse.

• During the school health programme, physicians must carefully bring up the subject and ask the child for history of sexual abuse.

• More research must be done about child sexual abuse.

Child Sexual Abuse – The Current Scenario

1. World Health Organisation Guidelines. [Online] 2017 [cited 2017 Jul 2]. Available from: URL: http://www.who.int/violence_inju-ry_prevention/resources/publications/en/guidelines_chap7.pdf

2. Geneva: World Health Organization; Child maltreatment. [On-line] 2017 [cited 2017 Jul 2] Available from: URL: http://www.who.int/topics/child_abuse/en/

3. Geneva: World Health Organization; Child maltreatment. [On-line] 2018 [cited 2018 January 20] Available from: URL: http://www.who.int/mediacentre/factsheets/fs150/en/

4. Wihbey J. Global prevalence of child sexual abuse. Journalist Resource. [Online] 2017 [cited 2017 Jul 2] Available from: URL: https://journalistsresource.org/studies/government/crimi-nal-justice/global-prevalence-child-sexual-abuse

5. Barth J, Bermetz L, Heim E, Trelle S, Tonia T. The current preva-lence of child sexual abuse worldwide: a systematic review and meta-analysis. Int. J. Public Health. 2012; 58(3): 469-83.

6. Kacker L, Varadan S, Kumar P. Study on Child Abuse: India. [On-line] [cited 2017 Jul 2]. 2007. Ministry of Women and Child devel-opment, Government of India. Available from: URL: https://www.childlineindia.org.in/pdf/MWCD-Child-Abuse-Report.pdf

7. Bassani D., Palazzo L., Béria J., Gigante L., Figueiredo A., Aerts D., Raymann B. Child sexual abuse in southern Brazil and associat-ed factors: a population-based study.BMC Public Health. 2009; 133(9).

8. Song Yi., Ji C., Agardh A. Sexual coercion and health-risk behav-iors among urban Chinese high school students. Glob Health

3. Healed hymenal transection or complete cleft4. Deep anal laceration5. pregnancy without a history of consensual inter-

course

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Child Sexual Abuse. J Child Sex Abus. 1994; 4(2): 31-53.

16. Sanders, B, Becker-Lausen E. The measurement of psychological maltreatment: Early data on the child abuse and trauma scale. Child Abuse Negl. 1995; 19(3): 315-23

17. Fergusson, David M., Geraldine FH McLeod, and L. John Hor-wood. “Childhood sexual abuse and adult developmental out-comes: Findings from a 30-year longitudinal study in New Zea-land.” Child Abuse Negl. 2013; 37(9): 664-74.

18. Unlu G, Cakaloz B. Effects of perpetrator identity on suicidality and nonsuicidal self-injury in sexually victimized female adoles-cents. Neuropsychiatr Dis Treat. 2016; 12:1489–97.

19. Noll J. G, Trickett P.K., Putnam F.W. A prospective investigation of the Impact of childhood sexual abuse on the development of sexuality. J Consult Clin Psychol. 2003; 71(3): 575–86.

20. Finkelhor D. (1999). Child sexual abuse. Challenges facing child protection and mental health professionals, In: Ullmann E., Hil-weg W. (eds.) Childhood and Trauma: Separation, Abuse, War. Aldershot: Ashgate Publishing; 1999. p.101–16

21. Bowen K, Aldous MB. Medical Evaluation of Sexual Abuse in Children Without Disclosed or Witnessed Abuse. Arch Pediatr Adolesc Med. 1999;153(11):1160–1164. doi:10.1001/archpe-di.153.11.1160

22. Bajpai A. Child Sexual Abuse and Law [Online]. [cited 2017 Jul 14]. Available from: URL: http://www.childlineindia.org.in/Child-Sexual-Abuse-and-Law.htm

23. Kerns DL, Terman DL, Larson CS. The role of physicians in report-ing and evaluating child sexual abuse cases. The Future of Chil-dren. 1994 Jul 1:119-34.

Action. 2014; 7(10).

9. Chiu G., Lutfey K. , Litman H., Link C. , Hall S. , McKinlay J. Preva-lence and Overlap of Childhood and Adult Physical, Sexual, and Emotional Abuse: A Descriptive Analysis of Results from the Bos-ton Area Community Health (BACH) Survey. Violence Vict. 2013; 28(3):381-402.

10. Pineda-Lucatero A., Trujillo-Hernández B., Millán-Guerrero R., Vásquez C. Prevalence of childhood sexual abuse among Mexi-can adolescents. Child Care Health Dev. 2009; 35(2):184-9.

11. Ajdukovic M., Susac N., Rajter M. Gender and age differences in prevalence and incidence of child sexual abuse in Croatia. Croat Med J. 2013; 54(5):469-79.

12. Finkelhor, D, Shattuck A. Characteristics of Crimes against Ju-veniles. Durham, NH: Crimes against Children Research Center, University of New Hampshire. [Online] 2012 [cited 2017 Jul 5]. Available from: URL: http://citeseerx.ist.psu.edu/viewdoc/down-load?doi=10.1.1.361.4579&rep=rep1&type=pdf

13. Snyder, H. N. Sexual Assault of Young Children as Reported to Law Enforcement: Victim, Incident, and Offender Characteristics. U.S. Department of Justice, Office of Justice Programs, Bureau of Justice. [Online] 2000 [cited 2017 Jul 5]. Available from: URL: https://www.bjs.gov/content/pub/pdf/saycrle.pdf

14. Sedlak, A.J et al. Fourth National Incidence Study of Child Abuse and Neglect (NIS–4): Report to Congress. U.S. Department of Health and Human Services. [Online] 2010 [cited 2017 Jul 5]. Available from: URL: https://www.acf.hhs.gov/sites/default/files/opre/nis4_report_congress_full_pdf_jan2010.pdf

15. Finkelhor, D. Current Information on the Scope and Nature of

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High Burden of Cardiovascular Diseases in Kerala: High Time to Reorient the Primary Health Care System

Rakesh P S*

Kerala, a state in southern India, with a population of 33.4 million, has made impressive improvements in its people’s conditions of living. Despite having a low per capita income, Kerala’s indicators of health and social development—such as the human devel-opment index (0.84), life expectancy at birth (75 years), infant mortality rate (06/1000 live births), sex ratio (1084 females to 1000 males), and female literacy rates (92.07%)—are comparable to those of many developed countries1,2. These faster demographic transitions in the state have been attributed to be the results of a political environment that emphasized rights, a policy thrust that ensured rights in education and health and a reasonably strong primary health care system with good infrastructure of primary health centers.

Corresponding Author: Rakesh P S

Burden of Cardiovascular Disease in Kerala

*Dept. of Public Health, AIMS, Amrita Vishwa Vidyapeetham, Kochi, India.

REVIEW


ABSTRACT

However, Kerala which seems to have entered into the fourth stage of the epidemiological transition is now facing a huge threat due to alarmingly rising trends of Non communicable diseases (NCD). Cardiovascu-lar diseases (CVDs) have become the leading cause of mortality in Kerala contributing to as much as 40% of all deaths while the proportion of deaths due to infectious diseases was 5% and due to maternal and perinatal conditions was less than 1%3. There are no representa-tive surveillance data on the prevalence of CVD and the secular trends of CVD mortality in the state. However, a well conducted cohort study has shown that the age adjusted death rate due to cardiovascular diseases in the state is 490 and 234 per 100,000 for men and wom-en respectively every year, which is far higher than the figures for many industrialised countries3. In Kerala, 60% of Ischemic Heart Disease (IHD) deaths in men and 40% of IHD deaths in women occurs before the age of 654. A multi-centric study in the state has shown that the age-adjusted prevalence of definite IHD is 3.5%, thrice as high as the figures two decades ago5,6.

Determinants of CVD in Kerala Multi-centric studies done in India by different agen-cies have shown that the prevalence of CVD risk factors are markedly high in Kerala as compared to the other states in the country7,8. Kerala has high prevalence of most known risk factors of CVD like tobacco smok-ing: men- 39.7%, women-0.4%, overweight (BMI> 25.0 kg/m ): men- 23.9%, women- 37.5%, unhealthy diet (< five servings of fruits and vegetables/day): men-42.9%, women-50.9%, diabetes (fasting blood sugar > 126 mg/dl or on 3 medication): men-14.3%, women-17.8%, hy-percholesterolaemia (total cholesterol >200 mg/dl):

men-51.4%, women-61.5% and hypertension (JNC VII): men-33.9%, women- 31.6%7.

There was not much urban-rural differences in the prevalence of IHD in the state5. A rise in the prevalence of CVD in the state has been attributed to changes in lifestyle and dietary practices in the state which in turn has been attributed to the rapid urbanisation that hap-pened in last two decades. Table 1 summarises the find-ings of major studies in CVD epidemiology done in the state and Figure 1 shows the prevalence of risk factors of cardiovascular diseases in Kerala in comparison with India and Sri Lanka. High prevalence and rising trends of the risk factors indicates that the CVD burden would continue to rise in Kerala in the coming years.

Current policies and programs for CVD prevention Recognising the problem, State Government has initi-ated own program in 2007 for combating NCDs- first of its kind in the country. The program aimed at early diag-nosis and treatment of NCDs particularly Diabetes and Hypertension where multi- purpose health workers do screening at community and refer them for treatment and follow up care to the medical doctors at primary health centre. Medicines were provided free of cost at the Primary Health Centre. However, a recent evalua-tion of the NCD control program in the state highlight-ed that the program did not focus much on primodial and primary prevention interventions. NCD control pro-gram has now been also operating through National Program for the Prevention and Control of Cancer, Di-abetes, Cardiovascular Diseases, and Stroke by Govern-ment of India which focuses on screening for risk fac-tors, health promotion, and health education advocacy at various settings10. Government of Kerala is commit-ted to attain Sustainable Development Goals and has formulated strategies for the same. Key targets for NCD control include a 30% reduction in premature mortality

8


Study sample

1253 adults in Trivandrum

Prevalence of Definitive Coronary Artery Disease was 1.4%, Obesity 5.5%, Diabetes 4%, Smoking 21.5%, Hypertension 17.9%

Year

Kutty VR et al6

Cross sectional

1993

Description of study

Major Findings of the studyAuthors

161942 people from 7 villages in Trivandrum

Prevalence of Definitive Coronary Artery Disease was 1.4%, Obesity 5.5%, Diabetes 4%, Smoking 21.5%, Hypertension 17.9% Age-standardized cardiovascular disease (CVD) death rates were 490 for men and 231 for women per 100 000 person years

PROLIFE3 Cohort study.4272 deaths recorded in 5 years

2002-2007

251015-64 yearsTrivandrum

Over a seven year period, several NCD risk fac-tors have increased in the study cohort. There were significant increases in weight (mean change +5.0 kg, 95% CI 4.2 to 5.8), Physical inactivity (OR 2.0, 95% CI 1.3 to 3.0), obesity (OR 2.2, 95% CI 1.7 to 2.8), and central obesity (OR 1.9, 95% CI 1.5 to 2.3) increased.

Satishet al 1

Followed upsameindividualsafter 7 years.

2003 And2010

7449 individ-uals between 15-64 years

Tobacco (21.9%), Alcohol (11.1%), low fruit and vegetable intake (39.7%), physical inactiv-ity (6.8%), overweight (24.9%), hypertension (28.8%), Diabetes Mellitus (14.8%), Hypercho-lesterolemia (54.1%)

Thankappanet al6et al 1

Part of ICMR Multicentre survey

2007

5000 house-holds from the state

Obesity (43%) prevalence highest in Kerala as compared to other states. Fruits consumption less than 5 servings-87%, Low physical activi-ty-76% and Hypertension-24%

IDSP Risk factor survey7

Survey Con-ducted in 7 states

2007-2008

741 000 urban and 185 000 rural people Trivandrum

Adjusted annual incidence rates for Cerebro-vascular disease per 100 000 was 135 (95% CI123 to 146) for total, 135 (122–148) for ur-ban, and 138 (112–164) for rural populations.

Sreedharan et al9

Prospective Study- 541 stroke events in 6 months

2009

25278 Acute Cor-onary Syndrome admissions from 125 hospitals

60% of Acute Coronary Syndrome occurred in patients less than 70 years of age; 22% below 50 years

Mohanan et al4

Prospective data collection during 2007-2009 fromACS Registry

2012

5167 adults,Multi stage cluster random sampling

Prevalence of any IHD was 12.5 %Physical inactivity- 17.5%; overweight or obese- 59 %, abdominal obesity- 57 %, hyperten-sion- 28 %, diabetes- 15 %, high total choles-terol -52 %. No urban-rural difference in CAD prevalence.

Krishnan et al5

Cross sec-tional

2012

Table 1: Summary of major studies done in Kerala state regarding Cardio Vascular Disease burden and its risk factors

9


0.00%

5.00%

10.00%

15.00%

20.00%

25.00%

30.00%

35.00%

40.00%

Raised blood glucose (Aged 25+)-Male

Raised blood glucose (Aged 25+)-Female

Raised blood Pressure(Aged 25+)-Male

Raised blood Pressure(Aged 25+)-Female

Tobacco use(Aged 15+)Female

Tobacco use(Aged 15+)Male

Obesity(Aged 20+)Female

Obesity(Aged 20+)Male

11.10%

14.30%

9.30%

10.80%

17.80%

6.60%

23.10%

33.90%

31%

22.60%

31.60%

26.20%

25%

39.70%

31%

25%

0.40%

31%

1.30%

29.30%

2.60%

2.50%

37.50%

7.30%

Kerala

India

Srilanka

Prev

alen

ce o

f ris

k fa

ctor

s

Fig 1: Prevalence of risk factors of cardiovascular diseases in Kerala in comparison with India and Sri Lanka6,12

CONCLUSION CVD has become an important public health issue in Kerala and is one of the most important causes of mor-tality and morbidity in the State. There is an urgent need to reorient primary health care system in the state for better prevention and management of CVD disease and its risk factors.

fruits and vegetables, workplace wellness programs, standardised and quality assured care, task-shifting and task sharing interventions including involving frontline health workers and nurses for lifestyle counselling, mass education, and to ensure adherence, better use of infor-mation communication technology for CVD prevention, better surveillance and reporting systems for CVDs and risk factors, policies to address social determinants of CVD for control of primodial risk factors and having a life cycle approach for prevention are need of the hour. The capacity for CVD research needs to be built to generate contextualized evidence. Policies and programs that in-fluence CVD need to cover a various sectors beyond the healthcare, including finance, agriculture, urban affairs, education, social justice and the environment. To be successful it requires political stewardship with commu-nity ownerships.

High Burden of Cardiovascular Diseases in Kerala: High Time to Reorient the Primary Health Care System

due to CVD by 2025. Government has imposed 14.5% ‘fat-tax’ on organised fast food outlets and raised taxes on tobacco products. Government is strictly implement-ing legislations like Cigarette and Other Tobacco Prod-ucts Act (COTPA), 2003, which envisages prohibition of smoking in public places; total ban on advertisements, prohibition of tobacco sales around educational institu-tions; and strong pictorial warning labels on all tobacco products.

Future Directions for CVD prevention The high burden of cardiovascular morbidity in the pop-ulation has to be tackled with more vigour. More resourc-es need to be routed for applying the existing evidence base to tackle the CVD epidemic in policies, programs and capacity building. In addition to the strengthening of curative services, priority should be given to strategies for CVD prevention and health promotion. The primary health system is still behind the ‘unfinished agenda’ of the management of communicable diseases, maternal and child health care, and immunization which needs to be reoriented towards preventing cardiovascular diseases. Behaviour change communication and health promotion at schools, providing facilities for sports and physical exercise, subsidising and promoting seasonal

10


REFERENCES1. Government of Kerala. Economic Review 2015. State Planning

Board, Thiruvananthapuram, Kerala, India. March 2016. Available from: http://spb.kerala.gov.in/images/er/er14/index.html#p=1

2. Government of India. National Family Health Survey-4 (NFHS-4) 2015-16. State Fact Sheet. Kerala. Ministry of Health and Family Welfare, GOI. New Delhi 2016. Available from: http://rchiips.org/NFHS/pdf/NFHS4/KL_FactSheet.pdf [accessed on July 12, 2017]

3. Soman CR, Kutty VR, Safraj S, Vijayakumar K, Rajamohanan K, Ajayan K. All-cause mortality and cardiovascular mortality in Kerala state of India: results from a 5-year follow-up of 161,942 rural community dwelling adults. Asia Pac J Public Health. 2011;23:896–903

4. Mohanan PP, Mathew R, Harikrishnan S. Presentation, manage-ment and outcome of 25748 acute coronary syndrome admis-sions in Kerala, India: results from Kerala ACS registry. Eur Heart J 2013;34:121-9

5. Krishnan MN, Zacharia G, Venugopal K. Prevalence of coronary artery disease and coronary risk factors in Kerala, south India-a community based cross sectional study. BMC cardiovasc disord. 2016;16:12

6. Kutty VR, Balakrishnan KG, Jayasree AK, Thomas J. Prevalence of coronary heart disease in the rural population of Thiruvanantha-puram district, Kerala, India. Int J Cardiol. 1993;39:59–70

7. Thankappan KR, Shah B, Mathur P, Sarma PS, Srinivas G, Mini GK,

Daivadanam M, Soman B, Vasan RS. Risk factor profile for chron-ic non-communicable diseases: results of a community-based study in Kerala, India. Indian J Med Res. 2010;131:53–63

8. Government of India. Integrated Disease Surveillance Project NCD Risk Factor Survey Fact Sheet - India Phase – I. IDSP 2007. New Delhi. Available from: http://www.icmr.nic.in/final/ID-SP-NCD%20Reports/Summary.pdf

9. Sridharan SE, Unnikrishnan JP, Sukumaran S, Sylaja PN, Nayak SD, Sarma PS, Radhakrishnan K. Incidence, types, risk factors, and outcome of stroke in a developing country: the Trivandrum Stroke Registry. Stroke. 2009;40:1212–8

10. Government of India. National Programme for Prevention and Control of Cancer, Diabetes, Cardiovascular Diseases and Stroke (NPCDCS). New Delhi. Available from: http://www.nrhmhp.gov.in/sites/default/files/files/NCD_Guidelines.pdf [accessed on July 13, 2017].

11. Satish T, Kannan S, Sharma SP, Razum O, Sauzet O, Thankappan KR.Seven-year longitudinal change in risk factors for non-com-municable diseases in rural Kerala, India: The WHO STEPS ap-proach . PLoS ONE 12(6): e0178949.https://doi.org/10.1371/journal. pone.0178949

12. World Health Organisation. Country statistics and global health estimates by WHO and UN Partners. Global Health Observatory (GHO) data. Available from: http://www.who.int/gho/countries/en/ [accessed on July 10, 2017]

11


Clinical Features and Treatment Outcomes in Axial Spondyloarthritis Patients in India: A Single Center

Retrospective Analysis Cdr Anuj Singhal*, Sudhir K Joshi**, Vivek Hande***, Rahul Tyagi****

ABSTRACTBackground and aim: Axial spondyloarthritis (ASpA) is a chronic inflammatory disease routinely treated with nonsteroidal anti-in-flammatory drugs (NSAIDs). Patients unresponsive to NSAIDs are treated with tumor necrosis factor (TNF-α) inhibitors. The aim of this study is to report clinical features and treatment outcomes in Indian ASpA patients.

Methods: A non-interventional, retrospective analysis of medical records of ASpA patients, obtained from a single center, between January 2014 and 30th June 2016 was performed. All patients (n=130) were initially treated with NSAIDs, and patients who had uveitis received sulfasalazine (SSZ, n=40) therapy. Treatment for patients unresponsive to NSAIDs (n=31) was modified to include anti-TNF-α biologics, etanercept (n=13) or infliximab (n=17). Changes in disease activity, in response to treatment, were assessed by recording Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score (AS-DAS) scores at 0, 6, and 12 months.

Results: Overall, BASDAI scores steadily decreased from 3.2 at baseline to 2.8 and 2.5 at 6 and 12 months, respectively, after treatment (ANOVA, p<0.0001). Similarly, overall ASDAS ESR decreased from 2.7 at baseline to 2.4 and 2.2 after treatment (ANOVA, p<0.0001).

Conclusion: Results of this study show that disease activity in axial spondyloarthritis patients reduces, from baseline to 12 months, in response to treatment.

Keywords: ASpA, disease activity, NSAIDs, anti-tumor necrosis inhibitors, biologics

Corresponding Author: Vivek Hande

INTRODUCTION Spondyloarthritis (SpA) is a set of autoimmune inflam-matory diseases which have shared clinical and genetic characteristics1. Axial spondyloarthritis (ASpA) refers to chronic inflammation involving axial skeleton compo-nents such as the sacroiliac joints and the spine. Non-ra-diographic ASpA without radiographic sacroiliitis and ankylosing spondylitis (AS) or radiographic ASpA are considered to be 2 stages of ASpA1. Axial spondyloar-thritis is linked to HLA-B27 antigen (74%-89%) and is more prevalent in men. The diagnostic features of ASpA include lower back pain, heel pain (enthesitis), dac-tylitis, uveitis (30%-40%), inflammatory bowel disease (5%-10%), hip involvement (24%-36%), psoriasis (10%), asymmetrical arthritis, positive response to NSAIDs, el-evated ESR or C-reactive protein level2. Structural dam-age occurs as a result of bone destruction and abnormal bone formation2. The molecular mechanisms involved in ASpA pathogenesis include abnormal function of anti-gen-presenting cells, abnormal HLA-B27, and increased production of chemokines and cytokines such as tumor necrosis factor-alpha (TNF-α) and interleukin-17 (IL-17)2. Taurog et al. provide an algorithm for diagnosing ASpA in patients who present with the most common spondy-loarthritis symptom lower back pain2. The Assessment of SpondyloArthritis International Society (ASAS) estab-

*Dept. of Rheumatology, **Dept. of Cardiology, ***Dept. of Medicine, ****Dept. of Pulmonology, INHS Asvini, Mumbai, Maharashtra, India.

lished the classification criteria for ASpA based on im-aging, clinical, and laboratory criteria. The diagnosis of ASpA is recognized in patients who have had 3 or more consecutive months of back pain, are <45 years of age, in whom MRI or radiography has confirmed the pres-ence of sacroiliitis, and who have at least one clinical or laboratory characteristic of spondyloarthritis. Alterna-tively, patients who are HLA-B27 positive and have two spondyloarthritis clinical features are also diagnosed with ASpA2,3. Axial spondyloarthritis disease activity is assessed us-ing multiple tools such as the Bath Ankylosing Spon-dylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score (ASDAS). Function is assessed using the Bath Ankylosing Spondylitis Func-tional Index (BASFI), and mobility is measured with the Bath Ankylosing Spondylitis Metrology Index (BASMI)3,4. The treatment goals of ASpA therapy include alleviat-ing symptoms, enhancing spinal flexibility and normal posture, decreasing functional limitations, preserving the ability to work, and reducing disease complica-tions2,5. Poddubnyy et al. have outlined the treatment recommendations put forth by the ASAS and European League Against Rheumatism (EULAR)1. As per these evidence-based guidelines, the first-line therapy for ASpA includes nonsteroidal anti-inflamma-tory drugs (NSAIDs) and nonpharmacological treat-ments such as education, regular exercise, and phys-

ORIGINAL ARTICLE


12


Study group This was a non-interventional, retrospective analysis of medical records of patients diagnosed with ASpA in a single center between January 2014 and June 2016. All patients (n=130) were initially treated with NSAIDs such as indomethacin (75 mg at bed time) or etoricoxib (120 mg at bedtime). Patients who had other conditions such as uveitis, psoriasis, irritable bowel syndrome (IBS), or gut disorders were also treated with 1 g sulfasalazine (SSZ, n=40, 30.8%) twice daily. After 3 months, patients who did not respond to NSAIDs (n=31) were treated with add-on anti-TNF-α biologics either 50 mg etaner-cept subcutaneous injection once a week (n=13, 10%) or 300 mg infliximab IV infusion once in 2 months (n=17, 13.1%).

Baseline disease activity Four standard scales were used to assess disease activ-ity, at baseline, before any treatment was initiated. The four scales are, Maastrich Ankylosing Spondylitis En-thesitis Score (MASES), Bath Ankylosing Spondylitis Me-

METHODOLOGY

trology Index (BASMI), BASDAI, and ASDAS ESR scales. Changes in disease activity, in response to all treatment groups, were assessed by recording BASDAI and ASDAS ESR scores at 6 and 12 months. Enthesitis inflammation of the tendon, ligament, or joint capsule insertions is a potential extra-axial man-ifestation found in spondyloarthritis (SpA) patients. Enthesitis is quantified as per the MASES scale which contains 13 pre-defined entheses7. The BASMI is a 0 to 10 scale in which higher scores represent worsen-ing disease activity.8 The BASDAI is a 0 to 100 scale in which higher scores indicate worsening disease activity, whereas ASDAS scale includes patient perceptions and laboratory variables such as ESR or CRP9.

Statistical Analysis Descriptive method was used to analyse the data. Counts and percentages was provided for categorical data. Continuous data was summarized using mean, standard deviation. One-way Analysis of Variance (ANO-VA) was used to compare the mean BASDAI and ASDAS ESR scores for all treatment combinations. Multiple comparison was done to check which treatment groups differed from each other.

Demographics, Clinical presentation, and Diagnosis Of the 130 patients, 121 (93%) were males and 9 (7%) were females. The mean age of the patient population was 31.5 years (±8.2), with a mean time to diagnosis of 53.8 months (±53.2) and duration of illness of 29.7 months (±39.7). Only 7 patients had a smoking history. The key clinical presentation and diagnostic character-istics of the patient population are presented in Table 1. A few patients (n=5) had a family history of joint disease, while most of them (n=102, 78%) had lower back pain. In addition, majority of the patients had early morning stiffness (n=83, 64%) and nearly half (n=56) had periph-eral joint involvement. Few patients had skin (n=4) and ocular (n=5) involvement. In terms of diagnosis, major-ity of the patients (n=93, 72%) were HLA-B27 positive. X-rays confirmed sacroiliac (SI) joint involvement in 58 (45%) patients. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CPR) were elevated in 22 (13%) and 31 (24%) patients, respectively. Magnetic resonance imaging (MRI) test of all patients confirmed disease ac-tivity.

Disease activity assessment The patients’ disease activity was assessed at baseline (0 months) and subsequently at 6 and 12 months after treatment. The baseline disease activity was assessed based on 4 different scales [Table 1]. Figure 1 shows that overall mean BASDAI scores (n=130) steadily decreased from 3.2 at baseline to 2.8 and 2.5 at 6 and 12 months, respectively, after treatment (ANOVA, p<0.0001). Similarly, overall mean ASDAS ESR (n=130) decreased from 2.7 at baseline to 2.4 and 2.2 af-

RESULTS

iotherapy. NSAIDs such as nonselective or selective cyclooxygenase (COX) inhibitors reduce pain and stiff-ness in most ASpA patients. If NSAIDs are effective and well-tolerated, then they can be used for the long-term with dosing adjustments as per the patient’s symptoms. Common adverse effects of NSAIDs include gastroin-testinal and cardiovascular events1. Disease-modifying anti-rheumatic drugs (DMARDs) such as methotrexate and sulfasalazine as well as local steroids are useful for patients with peripheral joint involvement1. In patients who are unresponsive to NSAIDs and other first-line therapy, TNF-α blockers are recommended as a second line treatment choice. All TNF-α inhibitors adal-imumab, etanercept, golimumab, and infliximab are considered to be highly efficacious in reducing ASpA symptoms in nearly 40%–50% of patients who had NSAIDs therapy failure1. Analgesics are recommended for patients in whom pain is not effectively controlled by other treatments. Lastly, surgery is recommended for ASpA patients with serious spinal damage that has a severe impact on the patient’s functional ability and quality of life1. Even though anti-TNF-α biologics are shown to be effi-cacious in ASpA patients unresponsive to NSAIDs, they are not regularly used in India because of their high cost1. The cost of anti-TNF-α biologics such as etanercept and infliximab is Rs. 20,800/100 mg and Rs. 16,500/25, re-spectively6. However, our specialist state-owned health-care organization provides biologics for ASpA patients. Here we report a physician’s experience of biologics us-age in Indian ASpA patients. The noteworthy results of this retrospective study include patient population de-mographics, disease activity, HLA-B27 positivity, NSAIDs efficacy, and biologics usage in NSAIDs-unresponsive Indian ASPA patients.

13

Amrita Journal of MedicineClinical Features and Treatment Outcomes in Axial Spondyloarthritis Patients in

India: A Single Center Retrospective Analysis

1.0

2.0

3.0

4.0

5.0

0.0BASDAI ASDAS ESR

0 Months 6 Months 12 Months

Mea

nt+_

SD

3.2

2.8

2.52.7

2.42.2

1

2

3

4

5

0

Mea

nt+_

SD

6

NSAIDs o

nly

NSAIDs +

Etanerc

NSAIDs +

Inflixim

NSAIDs +

SSZ

3.02

2.652.40

2.98 3.95

2.80

2.48

3.282.85

4.68

3.85

2.97

0 M 6M 12M

1.0

2.0

3.0

4.0

5.0

0.0

Mea

nt+_

SD

2.21

2.25

2.122.64 2.412.36 2.26

3.39

2.72 2.65

3.623.04

NSAIDS

NSAIDS

NSAIDS

NSAIDS

0 M 6M 12M

ter treatment (ANOVA, p<0.0001). Assessment of disease activity 6 and 12 months after treatment was conducted using the BASDAI scale [Figure 2]. Baseline disease activ-ity scores for NSAIDs ± SSZ treatment patients were low-er than the NSAIDs + Etanercept/Infliximab treatment patients (3.02, 2.98, 3.95, and 4.68, respectively). Over time, disease activity decreased across all treatment groups. After 6 months, mean BASDAI scores were lower at 2.65, 2.80, 3.28, and 3.85 for the 4 treatment groups NSAIDs, NSAIDs + SSZ, NSAIDs + Etanercept, and NSAIDs + Infliximab respectively. After 12 months, mean BAS-DAI scores were further decreased at 2.40, 2.48, 2.86, and 2.97 for the 4 treatment groups NSAIDs, NSAIDs + SSZ, NSAIDs + Etanercept, and NSAIDs + Infliximab re-spectively. Comparison of mean BASDAI scores, after 12 months of treatment, of patients treated with NSAIDs and patients treated with NSAIDs + SSZ revealed

no statistical difference. However, after 12 months of treatment, there was statistically significant difference in mean BASDAI scores of patients treated with NSAIDs vs. patients treated with NSAIDs ± Etanercept (ANOVA, p=0.021). Similarly, after 12 months of treatment, there was statistically significant difference in mean BASDAI scores of patients treated with NSAIDs vs. patients treat-ed with NSAIDs ± Infliximab (ANOVA, p=0.008). Sub-group analysis found statistically significant difference, after 12 months of treatment, in mean BASDAI scores of patients treated with NSAIDs vs. patients treated with NSAIDs + SSZ + Infliximab (ANOVA, p<0.001). Fig 3: Assessment of disease activity at 6 and 12 months after treatment was also assessed by ASDAS ESR scale Baseline disease activity scores for NSAIDs ± SSZ treat-ment patients were lower than that in NSAIDs + Etaner-cept/Infliximab treatment patients (2.64, 2.41, 33.9, and

Fig 1: Overall disease activity scores after treatment Figure 2: BASDAI scores for different treatment

Figure 3: ASDAS ESR scores after treatment

14


Lower back pain (LBA)

Family History - Joint disease 5 (3.84)

102 (78.47)

Skin Involvement 4 (3.08)

Ocular Involvement 5 (3.84)

56 (43.08)

83 (63.85)

93 (71.54)

58 (44.62)

C-reactive protein (CPR)

MASES

BASDAI

Frequency

(%)

130 (100)

22

31 (23.85)

Clinical characteristics

Early Morning Stiffness

Peripheral Joint Involvement

Diagnosis

HLA-B27 positive

X-ray sacroiliac (SI) joint

Magnetic resonance imaging (MRI)

Erythrocyte sedimentation rate (ESR), Median

BASMI Score

ASDAS ESR

Mean±SDDisease activity assessment

0.17±0.58

0.48 ± 1.01

3.22 ±1.26

2.74 ±0.85

Table 1: Clinical presentation and diagnostic parameters

Exam

16

54

37

40

93

18

Peripheral Joint involvement (56)

X-ray SI Joint (n=72)

MRI (n=130)

Treatment

HLA-B27 Positive

HLA-B27 Negative

3

32

3

10

14

8SSZ (n=40)

NSAIDs (n=130)

Etanercept (n=13)

Infliximab (n=17)

93 37

Table 2: Correlation between HLA-B27 and other diagnostic and treatment parameters

15

Amrita Journal of MedicineClinical Features and Treatment Outcomes in Axial Spondyloarthritis Patients in

India: A Single Center Retrospective Analysis

This retrospective study of ASpA patients is a first of its kind from India. The demographics, clinical presenta-tion, and diagnostic features of the studied patient pop-ulation are similar to previously reported ASpA patient characteristics1. Clinically ASpA is spondyloarthritis with axial skeleton, sacroiliac joints and spine and peripheral joint involvement. In our study, 58% and 56% of the pa-tients were shown to have SI joint and peripheral joint involvement, respectively. In addition, ASpA is accom-panied by enthesitis, uveitis, psoriasis, and inflammato-ry bowel disease which are often treated with SSZ.1 In our study, nearly 31% of patients were treated with SSZ. ASpA is also closely linked to HLA-B27 antigen which was the case for 72% of our patient population10. Com-mon symptoms of ASpA such as lower back pain and early morning stiffness were found in over 78% and 64% of our patients, respectively10.The study patients were first treated with NSAIDs which is recommended by ASAR/EULAR as the first-line thera-py for ASpA patients1. The effect of NSAIDs on disease activity is assessed by several scales including BASDAI and ASDAS.8 We found that a majority of the NSAIDs treated patients (nearly 77%) showed improvements

DISCUSSION

over 12 months. NSAID treatment has been reported to reduce inflammation and improve mobility in ASpA patients11. In this study, the NSAIDs of choice were in-domethacin and etoricoxib. Other NSAIDs used to treat ASpA include diclofenac, ibuprofen, naproxen, celecox-ib, and etoricoxib11. However, some of the patients did not respond to the NSAIDs treatment, with or without SSZ, after 3 months. This subset of the patient population, which had higher baseline disease activity was then additionally treated with anti-TNF-α biologics. It has been reported that pa-tients who received TNF blockers in addition to NSAIDs usually had higher disease activity despite being on NSAIDs therapy12. This combination treatment strategy was in line with the ASpA management guidelines put forth by ASAR/EULAR which recommends anti-TNF-α blockers as the second-line therapeutic option1,11. The criteria for introducing anti-TNF-α treatment include conventional therapy failure or persistently active dis-ease for ≥4 weeks as per the BASDAI index (≥4)13. Both the anti-TNF-α biologics, etanercept and infliximab, ef-fectively reduced disease activity scores as per 2 differ-ent scales. As in our previously published study with an-kylosing spondylitis (AS) patients,14 in this study too we found no statistical difference between etanercept and infliximab treatment effects on reducing disease severi-ty in ASpA patients unresponsive to NSAIDs. Several other TNF inhibitors such as adalimumab, goli-mumab, and certolizumab pegol have also been report-ed to improve ASpA disease activity11. Other than TNF inhibitors, IL-17 inhibitor, secukinumab is also used as a second-line therapy to treat radiographic ASpA11. A meta-analysis by Escalas et al. found that the efficacy of NSAIDs and TNF blockers on patient-reported outcomes was equivalent12. However, anti-TNF-α biologics are ex-pensive and hence their long-term use may not be af-fordable for most patients6. In our study we do not have a record of biologics-in-duced side effects. Research studies have shown that most common side-effects of infliximab include upper respiratory tract infection, nausea, headache, sinusitis, rash, and cough6. Etanercept-induced side-effects in-clude erythema, pain, swelling, and itching at the injec-tion site6.In terms of diagnostic exams, all our patients demon-strated disease activity on their MRIs but only 71% of patients were HLA-B27 positive. Rudwaleit et al. discuss in detail the diagnostic algorithm for ASpA in patients who may present with lower back pain15. Both, HLA-B27 positivity and sacroiliitis detection via X-ray or MRI scans are highly instrumental in diagnosing and classifying ASpA15. However, studies have shown that a subset of patients with X-ray scans detecting sacroiliitis may be HLA-B27 negative15. Future clinical investigations should include larger sample size and investigate the efficacy of anti-TNF-α

3.62, respectively). Over time, disease activity decreased across all treatment groups. After 6 months, mean AS-DAS ESR scores were lower at 2.21, 2.36, 2.72, and 3.04 for the 4 treatment groups NSAIDs, NSAIDs + SSZ, NSAIDs + Etanercept, and NSAIDs + Infliximab respectively. After 12 months, mean ASDAS ESR scores were further de-creased at 2.12, 2.25, 2.26, and 2.65 for the 4 treatment groups NSAIDs, NSAIDs + SSZ, NSAIDs + Etanercept, and NSAIDs + Infliximab respectively. There was statistically significant difference in mean ASDAS scores when com-paring patients treated with NSAIDs vs. patients treated with NSAIDs + Infliximab after 12 months of treatment (ANOVA, p<0.0001). Similarly, it was observed that there was statistically significant difference in mean ASDAS scores when comparing patients treated with NSAIDs vs. patients treated with NSAIDs + SSZ + Infliximab af-ter 12 months of treatment (ANOVA, <0.007). However, even after 12 months’ treatment, there was no statisti-cally significant difference in mean ASDAS scores when comparing patients treated with NSAIDs vs. patients treated with NSAIDs + Etanercept. Patient records were also studied to identify the num-ber of HLA-B27 positive patients. Results show that over-all 93 (71.5%) patients were HLA-B27 positive. HLA-B27 positive outcome did not completely correlate with oth-er diagnostic exam results [Table 2]. For instance, only 54 of the 72 patients that had X-ray evidence of SI joint involvement were also HLA-B27 positive. Similarly, 40 of the 56 patients who had peripheral joint involvement were HLA-B27 positive. Majority of the patients who had demonstrable disease activity as per the MRI (93 of 130) were HLA-B27 positive.

16


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choice? Ther Adv Musculoskel Dis 2013;5: 45–54.

2. Taurog JD Avneesh Chhabra, Robert A. Colbert, M.D Anky-losing Spondylitis and Axial Spondyloarthritis. N Engl J Med. 2016;374:2563-74.

3. Aliling J, Brent LH. Chapter 2: Criteria and Disease Activity Measures in Axial Spondyloarthropathies. Clinical Advances in Spondyliti.s 2016 http://www.avidscience.com/wp-content/uploads/2016/04/CAS-15-02_Revised-March-21-2016.pdf Ac-cessed on 21st September 2016.

4. J. Braun, U. Kiltz, X. Baraliakos, D. van der Heijde. Optimisation of rheumatology assessments – the actual situation in axial spon-dyloarthritis including ankylosing spondylitis. Clin Exp Rheuma-tol. 2014;32 (Suppl. 85): S96-S104.

5. Ward MM, Deodhar A, Akl EA, Lui A, Ermann J, Gensler LS, et al. American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network 2015 Recommendations for the Treatment of Ankylosing Spon-dylitis and Nonradiographic Axial Spondyloarthritis. Arthritis & Rheumatology. 2016;68:282–98.

6. Tandon VR, Mahajan A, Khajuria V, Kapoor V. Biologics and Chal-lenges ahead for the Physician. JIACM. 2006;7: 334-43.

7. Mueller R, Kaegi T, Graf N, von Kempis J, Luime JJ. Mases Cor-relates Linearly with Disease Activity and Patient Related Out-

comes in Patients with Axial Spondyloarthritis within the Scqm Cohort. ACR/ARHP Annual Meeting. 2015. http://acrabstracts.org/abstract/mases-correlates-linearly-with-disease-activi-ty-and-patient-related-outcomes-in-patients-with-axial-spondy-loarthritis-within-the-scqm-cohort/ Accessed on 21st Septem-ber 2016.

8. Kroon FP, van der Burg LR, Ramiro S, Landewé RB, Buchbinder R, Falzon L, et al. Non-steroidal anti-inflammatory drugs (NSAIDs) for axial spondyloarthritis (ankylosing spondylitis and nonradio-graphic axial spondyloarthritis) (Review). Cochrane Database Syst Rev. 2015;:CD010952.

9. Kilic G, Kilic E, Ozgocmen S. Is there any gender-specific differ-ence in the cut-off values of ankylosing spondylitis disease ac-tivity score in patients with axial spondyloarthritis? International Journal of Rheumatic Diseases. 2016.

10. Reveille JD, Weisman MH. The Epidemiology of Back Pain, Axial Spondyloarthritis and HLA-B27 in the United States. The Ameri-can journal of the medical sciences. 2013;345:431-6.

11. Seiper J, Poddubnyy D. New evidence on the management of spondyloarthritis. Nat Rev Rheumatol. 2016;12:282-95.

12. Escalas C, Trijau S, Dougados M. Evaluation of the treatment ef-fect of NSAIDs/TNF blockers according to different domains in ankylosing spondylitis: results of a meta-analysis. Rheumatology. 2010;49:1317–25.

13. Ciurea A, Scherer A, Exer P, Bernhard J, Dudler J, Beyeler B. et al. Tumor Necrosis Factor Inhibition in Radiographic and Non-radiographic Axial Spondyloarthritis. Arthritis & Rheumatism. 2013;65:3096–106.

14. Singhal A. Biologics Use in Asian Indian Patients with Ankylosing Spondylitis: A Physician’s Perspective. Journal of Clinical and Di-agnostic Research. 2016;10: OC29-OC32.

15. Rudwaleit M. Identifying axial SpA in young adults with chronic back pain. Nat Rev Rheumatol. 2016;12:378-80.

16. TNF-alpha inhibitors for ankylosing spondylitis and non-radio-graphic axial spondyloarthritis. NICE. 2016. https://www.nice.org.uk/guidance/ta383/chapter/1-Recommendations Accessed on 21st September 2016.

17. Poddubnyy D, Protopopov M, Haibel H, Braun J, Rudwaleit M, Sieper J. High disease activity according to the Ankylosing Spon-dylitis Disease Activity Score is associated with accelerated radio-graphic spinal progression in patients with early axial spondy-loarthritis: results from the German Spondyloarthritis Inception Cohort. Ann Rheum Dis. 2016; pii: annrheumdis-2016-209209.

biologics on improving physical function and reducing structural damage16. Poddubnyy et al. reported a pos-itive link between high disease activity and increasing spine damage in ASpA patients17. Further studies should examine the link between treatment-induced reduction in disease activity as per ASDAS and changes in radio-graphic evidence of spinal damage. In summary, results of this study show that all ASpA pa-tients enrolled in this retrospective study demonstrat-ed improvement in disease activity after 12 months of NSAIDs treatment with or without anti-TNF-α biologics. TNF-α inhibitors reduced disease activity in NSAIDs re-fractory patients, although there was no statistically sig-nificant difference in the efficacy—as per mean BASDAI and ASDAS-ESR scores—of etanercept and infliximab treatments.

17


Clinical Profile and Treatment of Primary Myelofibrosis - An Observational Study from a Tertiary Care Centre in Kerala,

South IndiaNeeraj Sidharthan*, Mariam Varsha Joseph*, Sharon Ann Georgy*, Priyanka S*, Devayani Santhu*, Meenu Vijayan*, Raghuveer Prabhu*, Govind Vijayakumar**, Remya Sudevan***

ABSTRACTIntroduction: Primary myelofibrosis (PMF) is a clonal hematopoietic stem-cell disorder, characterized by the abnormal accumula-tion of mature appearing myeloid cells in the bone marrow. It is one among the primary type of ‘BCR-ABL1 negative’ myeloprolif-erative neoplasm.

Objectives: The objectives of the study were to describe (i) the Clinical and laboratory profile of Myelofibrosis in Indian patients (ii) to analyze treatment related outcomes of patients receiving Ruxolitinib and Best available therapy (BAT) regimens.

Methods: The study design is an ambivalent cohort. The study period was eight months (September 2015 to April 2016). We collected data through review of clinical records of patients from the hospital information system (HIS). All patients diagnosed as Myelofibrosis and treated in the study institution from January 2010 to April 2016 were included in the study. We identified a total of 76 subjects with a confirmed diagnosis of PMF from the HIS. All identified subjects were included in the final analysis.

Results: The mean age of patients who were on Ruxolitinib was 61.88 ± 10.21yrs and those on BAT was 59.50 ± 11.34 yrs. There were 35 females ( Ruxolitinib group=14, BAT group=21) in the study group. Mean MPN score in Ruxolitinib group (n=24) before and after initiation of therapy were 34.46±14.4 and 16.50±16.8 respectively ( p-value < 0.001). Mean MPN score in the BAT group (n=22) before and after initiation of therapy were 40.18±19.6 and 27.09±17.06 respectively ( p-value < 0.001). A significant improvement in the DIPSS score was seen among Intermediate 2 risk group of the BAT arm ( p 0.002) and High risk group of the Ruxolitinib arm (p 0.003). The overall survival function of patients in both the treatment groups was compared using the log rank method and the p-value was found to be 0.333, showing there was no statistically significant difference in survival benefit between the treatment groups.

Conclusion: We found that the clinical profile of PMF patients in our study was similar to the profile described from the western population. There was no significant difference in clinical outcomes as well as survival benefit between the two treatment groups.

Corresponding Author: Remya Sudevan

INTRODUCTION Primary Myelofibrosis (PMF) is a clonal hematopoietic stem-cell disorder, characterized phenotypically by the abnormal accumulation of mature appearing myeloid cells. It is one among the primary type of ‘BCR-ABL1 neg-ative myeloproliferative neoplasm. The disease is charac-terized by the dysregulation of Janus kinase (JAK)–me-diated cytokine and growth-factor signal transduction i.e, the JAK-STAT pathway1.

Myelofibrosis (MF) has an incidence of 0.2 per 100,000 persons in United States2. Published epidemiological data regarding incidence rates for MPN are scarce for Indian population. In a hospital-based study in India among 1814298 patients attended the out-patient de-partment of their institute 231 (0.0127%) were diag-nosed as MPN over a period of one year 3.

The disease occurs mainly in middle aged and elderly patients and is rare in childhood4,5. MF is a Ph-ve MPN (Philadelphia chromosome negative Myeloprolifer-ative neoplasm) which is defined by the clinical and pathologic characteristics such as splenomegaly, he-patomegaly, constitutional symptoms, cytopenias and

*Dept. of Hematology, **Dept. of Public Health, ***Dept. of Medical Research, Amrita Vishwa Vidyapeetham, Kochi, India.

progressive bone marrow fibrosis6. The constitutional symptoms include weight loss, abdominal pain, abdom-inal discomfort, dizziness, numbness, insomnia, mood swings, sexuality problems, dyspnoea, low grade fever, cough, impairment in concentration, fatigue, early sa-tiety, night sweats, pruritus, bleeding episodes, diffuse bone pain and impaired quality of life7. The 2016 revi-sion of the WHO classification of myeloproliferative ne-oplasm defines 2 stages of PMF: prefibrotic/early (pre- PMF) and overt fibrotic (overt PMF). The fibrotic stage of PMF shows leucoerythroblastic blood picture with the presence of tear drop shaped red blood cells in the pe-ripheral blood smear8. The overt PMF is enriched with anemia, thrombocytopenia, leucopenia, higher blast count, symptoms, large splenomegaly, and unfavorable karyotype9. Diagnosis is based on bone marrow mor-phology. The presence of JAK2 , CALR or MPL mutation is supportive but not essential for diagnosis; approximate-ly 90% of patients carry one of these mutations and 10% are “triple-negative”10. The prognosis of the disease is predicted with two prognostic models (a) International prognostic scoring system -IPSS(at the time of diagno-sis) and (b) Dynamic international prognostic scoring system- DIPSS(at any time during the disease course)11.

ORIGINAL ARTICLE


18


MATERIALS AND METHODS The current study is an ambivalent cohort study car-ried out for a period of eight months (1st September 2015 to 30th April 2016) in the haemato oncology de-partment of a tertiary care centrein South India. Patients diagnosed as MPN (n=76) under all age groups during the period of 1st January 2010 till 31st May 2016 were selected for the study. Patients with secondary Mye-lofibrosis (tuberculosis, myeloma, chronic myeloid leu-kemia, acute myeloid leukemia, hairy cell leukemia) and MPN without a marrow fibrosis were excluded from the study. The seventy six patients were divided into two groups- (a) patients under Ruxolitinib therapy (n=34) and (b) patients under BAT (n=42).

A standardized data collection form was used to col-lect all the necessary information of the study partici-pants required for the study. The Myelofibrosis symp-tom assessment form (MSAF) was used to measure the symptoms20,21,22. The MPN score was assessed before (at diagnosis) and after (best response during follow up) the initiation of therapy.

The Drug Related Problems were identified by re-viewing the Hospital’s Health Information System and classified according to the PCNE (Pharmaceutical Care Network Europe) version V6. Using this, the problem was categorized; causes identified and appropriate interven-tion was provided. The interventions were conveyed to the patient after physician’s acceptance. The outcome of these interventions was assessed during the patient’s follow up visit .The drug interactions were checked using Lexicomp Drug interaction checker. ADR was as-

sessed using Naranjo Adverse Drug Reaction Probabil-ity Scale23. Using IPSS and DIPSS prognostic scales the prognosis of the disease was calculated11.

Statistical analysis The data collected were compiled using Microsoft Excel.All statistical analyses were carried out using IBM Statistical Package for Social Science(SPSS version 20). We used frequency and percentage to present cate-gorical variables and mean and standard deviation to present numerical variables. Chi-square test was used to examine the association between categorical variables. Independent two sample T test and Mann-Whitney U- test were used for parametric and non-parametric data comparisons respectively. Kaplan Meier Test was used to obtain the survival probability. Log Rank test was usedto compare the survival outcome between the two treat-ment groups.

RESULTS Among study patients, a total of 45 patients (59.21%) were under <65 years of age (18 in the 34 of Ruxolitinib group and 27 in the 42 of BAT group). There were 31 pa-tients (40.78%) (16 under Ruxolitinib group and 15 under BAT group) aged>to 65 years. The mean age of patients who were on Ruxolitinib was 61.88 ± 10.21 and those on BAT was 59.50 ± 11.34. There were 35 females (14 in the Ruxolitinib group and 21 in the BAT group) in the study. Among patients, only 60 had reticulin score in which 17 (28.33%) had a reticulin score< 3 and 43 (71.66%) had a score of> 3. Among the 34 patients in the Ruxolitinib group, 35.7% (n=10) had a reticulin score of less than 3 and 64.3% (n=18) had score ≥3. In 42 patients in the BAT arm, 21.9% (n=7) had a score of less than 3 and 78.1% (n=25) had a score ≥3. FISH analysis was done in both groups. In the Ruxolitinib group (n=26) 25 patients were BCR ABL –ve. Among the patients who were on BAT group (n=22) all were BCR ABL –ve.JAK2 mutation was done in both groups. In the Ruxolitinib arm, 23 patients had done JAK2 mutation in which 16 (69.56%) patients were identified with JAK2 +ve mutation. In patients who were on BAT, 15 had done JAK2 mutation and among them 7 (46.66%) patients were JAK2 +ve.

The laboratory values for haemoglobin, WBC count, platelet count and LDH at diagnosis were collected. The mean Hb (g/dl) in Ruxolitinib group was 10.95±5.25 and in BAT group was 9.70±3.19. The mean WBC (K/uL) in Ruxolitinib group was 18.12±17.43 and in BAT group was 16.29±18.57. The mean PLT (K/uL) in Ruxol-itinib group was 264.74±281.32 and in BAT group was 333.37±321.48. The mean LDH (U/L) in Ruxolitinib group was 556.33±247.17 and in BAT group was 515.70±381.28 (Fig1)

Treatment profile Our study population consisted of patients who were on 2 different treatments in which 42 were on BAT — 18 received hydroxyurea and prednisolone, 17 received

Treatment in MF is generally based on the severity of the disease and is often directed to address the individual’s clinical features. Pharmacotherapy is generally palliative which is guided by the predominant symptoms derived from anemia, splenomegaly, constitutional symptoms or disease complications due to extramedullary hae-matopoiesis12,13,14. Current drug therapy in MF is nei-ther curative nor it extents the survival period15,16. The only curative option is allogenichaemopoietic stem cell transplantation (allo-HSCT) but it carries its own risk of death or chronic morbidity from graft-versus-host dis-ease (GVHD)17. Moreover, it is not a viable option for many MF patients who are advanced in age and /or those with significant co-morbidities. PMF is character-ized by significantly reduced overall survival (OS) and increased risk of acute myeloid leukemia (AML) pro-gression18. The median survival is estimated as 6.5years (range of 2-10years)19.

Absence of a well-defined cancer registry for these neoplasm and unavailability of molecular diagnosis to many clinicians are the two major challenges in deter-mining the incidence of the disease in our country3. There exists scarcity in data regarding the clinical profile, diagnosis and treatment of MF in Indian population. Our study attempts to bridge these existing gaps.

19

Amrita Journal of Medicine Clinical Profile and Treatment of Primary Myelofibrosis - An Observational

Study from a Tertiary Care Centre in Kerala, South India

10.95 18.12 16.29

264.7

333.37

556.33

515.7

Fig 1: Laboratory values at diagnosis of PMF patients

LDHMean Hb(g/dl) PLT count

9.7

WBC(K/uL)

Mean Values of Lab Parameters Within Each Groups

BAT

Rux Olitinib

IPSS Risk- BAT IPSS Risk- RUXOLITINIB

DIPSS Risk- BAT DIPSS Risk- RUXOLITINIB

Intermedate - 1 Risk

Low Risk

High Risk

Intermedate - 2 Risk

Fig 2 : IPSS & DIPSS risk categorization of BAT and Ruxolitinib

20


A significant improvement in the DIPSS score was seen among Intermediate 2 risk group of the BAT arm ( p 0.002) and High risk group of the Ruxolitinib arm (p 0.003).

Adverse drug reactions (ADR)The most commonly reported ADR was grade 3 throm-bocytopenia in both groups. The occurrence of ADR was observed in most patients who were on Ruxolitinib.

These ADRs were managed by interim dose changes and temporary discontinuation of therapy.Survival analysis in each group The overall survival function of patients in both the treatment groups was compared. There was no statisti-cally significant difference in survival benefit between the treatment groups (p 0.333). The details are present-ed in Table 1.

DISCUSSION PMF is the rarest condition among all MPNs and is the most obscure with regards to pathophysiology. During our study, we screened out 76 patients with MF from 7289 bone marrow aspiration reports. We tried to iden-tify the patterns of treatment in this condition. Tradi-tionally available treatments were hydroxyurea, thalid-omide with/without prednisolone, lenalidomide with/

without prednisolone, radiotherapy and splenectomy. Studies conducted by Trillos A M et al24.,Thapaliya P et al24., Quintas-C A et al25., had proved the efficacy and tolerability of these treatments in MF patients. We also had patients on newer therapy like the JAK1/2 inhibitor, Ruxolitinib. Ruxolitinib first of its kind to gain approval by the FDA on November 16, 2011 for the treatment of MF in intermediate-2 and high risk patients. It was also

Std. ErrorEstimate

0.333

Groups

Mean p-value

1800.735

1682.500

Upper Bound

Lower Bound

1461.302

Table 1: Survival analysis in each group

1622.249

95% Confidence Interval

1133.014

1240.104

1063.295

170.337

112.856

142.5901342.772

1466.875

Overall

BAT

Ruxolitinib

thalidomide and hydroxyurea, 2 received lenalidomide and prednisolone and 5 received danazol and 34 were on Ruxolitinib. In the Ruxolitinib arm, only 7 patients were at front initiated on Ruxolitinib, rest of them (27 patients) switched from BAT.

Out of 76 PMF patients MPN score assessment was done only for 46 patients from both the groups before and after the initiation of therapy. Among the remaining 30 patients, 14 were dead and the rest 16 patients were lost to follow up. In overall study subjects, a mean MPN score of 37.20±17.23 was obtained before initiation of therapy and 21.57±17.61 was obtained after initiation of therapy (p <0.001). The mean MPN score in Ruxol-itinib group (n=24) before and after initiation of ther-apy were 34.46±14.4 and 16.50±16.8, respectively (p <0.001). The mean MPN score in the BAT group (n=22) before and after initiation of therapy were 40.18±19.6 and 27.09±17.06, respectively (p< 0.001).

There was a significant difference in the MPN scoring in the entire cohort after initiation of therapy(p 0.020). This shows a symptomatic improvement among the pa-tients who received the treatments.

The risk stratification in PMF patients were assessed

using IPSS and DIPSS prognostic models. IPSS was done at the time of diagnosis and DIPSS done at follow up. IPSS at the time of diagnosis and DIPSS at three differ-ent time intervals i.e.1st, 3rd and 6th month of follow up were calculated. IPSS at the time of diagnosis and DIPSS at 6th month of follow up is represented below (Fig 2 ).

21

Amrita Journal of Medicine Clinical Profile and Treatment of Primary Myelofibrosis - An Observational Study from a Tertiary Care Centre in Kerala, South India

Survival Functions

Cum

Sur

viva

l

Survival Time

0.0

0.2

0.4

0.6

0.8

1.0

0 500 1000 1500 2000

Fig 3: Kaplan-Meier survival analysis curves for BAT & Ruxolitinib

BAT

Jakavi

BAT- Censored

Jakavi - Censored

approved for the treatment of post-PV MF and post-ET MF 26. In our study, we segregated patients into two groups: one group with patients on Ruxolitinib (n=34) and the other arm on traditional therapy (BAT) (n=42). Demographic profiles of these patients were observed and the pattern of distribution in age, gender and JAK2 mutation were seen. In our study, majority of patients were under the age group of less than 65years i.e. 59.2% and greater percentage were male patients i.e. 53.9%. These data were similar to a study by Keith L D etal with 84.26% under the age group of less than 65 years and 66.7% were male patients 20. Similarly in the distribu-tion of JAK2 mutation, greater proportion was seen with JAK2 +ve mutation i.e. 60.5% which was consistent with those reported in the study by Keith et al (68.5%).

The prognostic models used to calculate the surviv-al probability were IPSS and DIPSS . The percentage of patients in IPSS low-risks were 8%, IPSS intermediate-1 were 28%, IPSS intermediate-2 were 30.67% and IPSS high risk were 33.33%. These findings were similar to that of the study conducted by Gangatet a12. According to the DIPSS calculation, the percentage of patients un-der low risk were 10.6%, intermediate-1 were 39.4%, in-termediate-2 were 33.3% and high risk were 16.7%. Our findings are similar to the study conducted by Gangatet al. In our study there was a 67.7% and 37.10% improve-ment in life expectancy in patients receiving Ruxolitinib and BAT respectively which was assessed through the improvement in the DIPSS score11.

The number of patients who received hydroxyurea

was 35, thalidomide-prednisolone was 26, lenalido-mide-prednisolone was 4 and danazol were 7 and pred-nisolone alone was 15. Out of this, 27 switched over to Ruxolitinib due to inadequate improvement in MF-relat-ed symptoms. The number of patients who were initiat-ed directly on Ruxolitinib was 7. In our study, we tried to assess the clinical outcome of Ruxolitinib and BAT based on the MPN score . Constitutional symptom improve-ment was assessed through MPN scoring system, taken at two time points- before and after initiation of each therapy. In general, in both treatment groups a distinct shift was observed in the distribution of symptom se-verity towards a more favourable profile (i.e., less severe) from MF diagnosis to the time of best response.

We noticed an improvement in all the 10 symptoms out of which weight loss (13 patients), fatigue (5pa-tients), early satiety (6 patients) , abdominal discomfort (6 patients), problems with concentration (5 patients) and night sweats (5 patients) were the most significantly resolved ones. There was no significant difference in the mean decline in MPN score from base line to follow up between both groups.

We also examined the safety profile of the patients in both treatment groups. There were both haematologi-cal and non-haematological adverse events. A total of 29 adverse events occurred in 16 patients taking Rux-olitinib (85.29%) and 30 adverse events in the BAT arm (71.42%). Greater number of ADRs was reported in the Ruxolitinib arm. The most commonly observed ADR was thrombocytopenia which was predominantly grade III.

22


CONCLUSION We found that the clinical profile of PMF patients was similar to that of western population. There was no sig-nificant difference in clinical outcome as well as survival benefit between the two treatment groups.

Limitations The main limitation of our study is the retrospective nature of design. Lack of documentation probably af-fected our data quality to some extentsince we were de-pending mostly on electronic databases for extraction of data. Karyotyping could not be done in a subset due to insufficient facilities and/or poor financial resources of patients. Approximately half of our patients were on sub-optimal dose in Ruxolitinib group due to financial constraints. This could probably have decreased the complete targeted action of Ruxolitinib.

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A similar pattern in the occurrence of adverse events was shown in the COMFORT-II trial16. These haematolog-ical events were reversible, so close monitoring of hae-matological parameters is needed. Due to these ADRs, 16 patients were managed by interim dose changes and temporary discontinuation of Ruxolitinib therapy. Dis-continuation of therapy was seen only in 1 patient due to loss of response as the patient was on sub optimal dose of Ruxolitinib therapy.

The mortality in the Ruxolitinib and BAT group were 14.7% and 21.4% respectively. Transformation to AML occurred in 5 patients in this study; one from BAT arm and 4 from ruxolitinib arm. A study done by Verstovsek S et al had reported 2 cases of transformation to AML27.

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24


Need of Routine Upper GI Endoscopy in Renal Transplant Workup Patients in a Resource Limited Setting- A Cross

Sectional Study from Kerala, South IndiaVijay Anand Viswanathen*, Govind Vijayakumar**, Remya Sudevan***

ABSTRACTBackground: Patients with chronic renal failure (CRF) often have dyspeptic symptoms and may develop peptic diseases. The possi-bility of these may be aggravated by use of immunosuppression during post transplant. Development of gastrointestinal compli-cations including GI bleed can be devastating in the post transplant period.

Objectives : To evaluate the diversity of gastro intestinal symptoms, upper gastrointestinal endoscopic findings and prevalence of Helicobacter pylori infection, in patients with CRF under haemodialysis who were being worked up for renal transplant.

Methodology : This cross sectional study was conducted for a period of 20 months (April 2013 - November 2014) in the gastro department of a tertiary care centre. Sixty nine consecutive patients with chronic renal failure, dialysis dependant, who were being worked up for transplant were enrolled in the study. All patients completed a standardized questionnaire scoring the presence of various GI symptoms and underwent upper GI endoscopy with multiple biopsies sampling for histopathological examination and H pylori identification.

Results: Mean age of the study participants was 40.2 +5.7 years. There were 51 males in the study. Only 21(30 %) of the patients were symptomatic. The most common symptoms seen were dyspepsia, black stools, abdominal pain and anorexia. Abnormal endoscopic findings were seen in 62(89.9%) of patients.Among 21 symptomatic patients, 18(85.7%) had abnormal OGD findings. In the 48 asymptomatic patients, 44 (91.7%) had abnormal OGD findings. In the total of 69 patients only 20 (29%) had H pylori in-fection. In the normal OGD group of seven,five patients (71.4%) were positive for H pylori. In the abnormal OGD group of 44, only 15 patients (31.9%) were positive for H pylori.

Conclusion: Patients with Chronic renal failure have a low frequency of GI symptoms, contrary to expectations. Even in asympto-matic patients, the occurrence of abnormal OGD findings is very high. Pre transplant OGD may help in assessing these lesions and prevent complications during post transplant period. Routine upper gastrointestinal endoscopy and testing for H pylori may have to be considered in Chronic renal failure patients as part of transplant workup.


INTRODUCTION Chronic Kidney Disease (CKD)patients receiving hae-modialysis treatment frequently experience dyspeptic symptoms such as nausea, vomiting, abdominal disten-sion, early satiety, and anorexia1. Uraemia and dialysis are found to be the risk factors for developing these symptoms as well as lesions in the gastro intestinal tract for CKD patients2. All patients with CKD can have ex-tensive gastritis. The gastritis will be asymptomatic un-less the patient had oesophagitis or a well established peptic ulcer3,4. Another factor that contributes in the increased rate of GI complaints in CKD patients is Heli-cobacter pylori infection rate5. These GI complaints can get aggravated and become fatal during post transplant period due to immunosuppression5,6. Our study aims to examine the various GI symptoms, endoscopic findings and H pylori infection rate of patients with CKD who had been worked up for renal transplantation.

*Dept. of Gastroenterology, West Fort, Thrissur, Kerala.**Dept. of Public Health, ***Dept. of Medical Research, AIMS, Amrita Vishwa Vidyapeetham, Kochi, India.

ORIGINAL ARTICLE

METHODS The study was cross sectional in design and was con-ducted in the gastro department of a tertiary care center.

The study period was 20 months (April 2013 to Novem-ber 2014). The study subjects were CKD patients under dialysis who were undergoing workup for renal trans-plantation. Inclusion criteria were all adult patients who had attended the gastroenterology clinic with diagnosis of CKD for pre transplant workup and on regular hemo-dialysis for a minimum of 6 months before the study. All patients with a history of smoking, alcohol abuse and malignancy were excluded. Patients with history of pep-tic ulcer disease, or upper GI bleed and patients who had received antibiotic or antacid or H2 receptor inhibi-tor therapy during the past 3 months before study were also excluded from the study. A total of 69 CKD patients who satisfied the inclusion and exclusion criteria were consecutively enrolled for the study. All patients were examined by the gastroenterologist and GI symptoms were evaluated using a questionnaire scoring GI symp-toms. The endoscopic procedure was performed on a non-dialysis day by the principal investigator. Patients were considered endoscopically normal if no mucosal abnormalities were found. Ulcers were diagnosed when mucosal denuding was over 5mm in diameter. Multi-ple gastric antral biopsies were obtained from an intact mucosa in the antrum within 5 cm of the pylorus, fixed


25

Amrita Journal of MedicineNeed of Routine Upper GI Endoscopy in Renal Transplant Workup Patients in a Resource Limited Setting- A Cross Sectional Study from Kerala, South India

RESULTS A total of 69 patients were included in the study. The mean age of the patients in the study was 40.2+5.7yrs. Among study subjects 51(73.9%) were male.Among study subjects 48 (70%) were found to be asympto-matic . The distribution of symptoms were dyspepsia for 8 patients, black stools for 6, abdominal pain for 6, anorexia for 6,nausea for 5, anemia for 3 and dysphagia for 2. Normal findingsin OGD were seen in seven pa-

tients (10%). Abnormal endoscopic findings were seen in 62 patients (89.9%). The most prevalent abnormal findings were antral erosions in 19 (31%), antral gastri-tis in 18 (29%), reflux esophagitis in 12 (19%), duodenal erosions in 11(18%), Pangastritis in 8 (13%) and duode-nal ulcer in 5 (8%).The diversity of distribution of abnor-mal endoscopic findings observed in oesophago-gastro deuodenoscopy (OGD scopy) is shown in table 1. In the 21 symptomatic patients, 18 (85.7%) had abnor-mal OGD findings and three had normal OGD findings. In the 48 asymptomatic patients, 44 (91.7%) had abnor-mal OGD findings. Only 4 asymptomatic patients had normal OGD findings. Fig 1 In the total of 69 patients, 20 (29%) had H pylori infec-tion and the rest were H pylori negative. In the normal OGD group of seven patients,five patients (71.4%) were positive for H pylori. In the abnormal OGD group of 62 patients,15 patients (31.9%) were positive for H pylori. The comparison of H pylori infection between normal OGD and abnormal OGD groups is shown in Fig 2.

Fig 1: Comparison of endoscopy findings based on symptom profile

5

10

15

20

25

30

35

40

Normal OGD

45

50

0Abnormal OGD

Fig 2: Distribution of H pylori infection based on OGD findings in study subjects

H Pylori -

H Pylori +

Abnormal OGD Findings Abnormal OGD Findings

4

44

18

3

Asymptomatic symptomatic

in 10% formalin and sent for histopathological exami-nation and Helicobacter pylori identification for all the enroled patients. The study was approved by the ethical committee of the institution and informed written con-sent was obtained from all the patients included in the study.Data was collected using a standardized proforma and analyzed using Statistical Package for Social Sci-ence(SPSS) version 19.0 statistical software. All continu-ous variables are expressed as mean (SD)and frequency in percentage.

26


REFERENCES1. Renu Thomas, Charles Panackal, Mammen John, Harshad Joshi,

Sunil Mathai, Joseph Kattickaran and Mohammed Iqbal. Gas-trointestinal Complications in Patients with Chronic KidneyDis-ease—A 5-Year Retrospective Study from a Tertiary Referral Cen-ter Renal Failure. 2013; 35(1): 49–55

2. Arunkumar Krishnan , Raja Sigamani and JayanthiVenkatara-man,Gastrointestinal Evaluation in Chronic Kidney Diseases, Journal of Nephrology and Therapeutic 2011;1(3):1-3

3. N Nand, P Malhotra, R Bala Evaluation of upper gastrointestinal symptoms and effect of differentmodalities of treatment in pa-tients of chronic kidney disease,JIACM 2014; 15(3-4): 182-7

4. C. J. Mitchell, D. P. Jewell, M. R. Lewin, J. E. Mclaughlin,J. F. Moor-head .Gastric function and histology in chronic renalfailure. Jour-nal of Clinical Pathology.1979;32: 208-13

5. Samir H. Al-Mueilo, Gastro duodenal lesions and Helicobacter pylori infection in hemodialysis patients. Saudi Med J 2004; Vol. 25 (8): 1010-4

6. Nakajima et al,Helicobacter pylori in Patients Receiving Long-Term Dialysis, Am J Nephrol 2002;22:468–72

7. El Ghonaimy E, Borson R, Saliman M, El Fikky A, Raskan S, et al. (2002) Serum gastrin in chronic renal failure: Morphological and physiological correlation. Nephron 39: 86-94.

8. Rui Dong, Zhi-Yong Guo, Jia-Rong Ding, Yang-Yang Zhou, Hao Wu Gastrointestinal symptoms: A comparison between pa-tientsundergoing peritoneal dialysis and hemodialysis, World J Gastroenterol2014 August 28; 20(32): 11370-75

9. Sugimoto M, Sakai K, Kita M, Imanishi J, Yamaoka Y (2009) Preva-lence of Helicobacter pylori infection in long-term hemodialysis patients. Kidney Int 75: 96-103.

DISCUSSION In developing countries gastrointestinal complaints are more prevalent in patients with renal diseasesprob-ably due to poor resources and inadequate care1,2. The incidence of GI symptoms varies from 37% to 93% 2.The main risk factors for this increased occurrence are urae-mia and dialysis2. The mechanisms by which uraemia causing frequent GI symptoms are disequilibrium of liquid and electrolytes, mechanical, physical and emo-tional problems of patients and toxins which cannot be removed by dialysis7. Due to these reasons, morbidity and mortality are often more in this group of patients who have gastro-intestinal complaints7. Our study was a cross sectional one which measured the GI symptoms, complications and H pylori infection at a single point of time. The study showed that the frequent symptoms were dyspepsia, black stools, abdominal pain, anorexia and nausea. This symptom profile is in agreement with the study by Dong et al8. The most frequently observed endoscopic findings were antral erosions (31%), antral gastritis (29%), reflux esophagitis (19%), duodenal ero-sions (18%), Pangastritis (13%) and duodenal ulcer (8%). The results were similar to that reported by Krishnan et al2. H pylori infection was positive in 71.4% of patients who had normal OGD scopy findings. In abnormal OGD

CONCLUSIONS Our study suggests that the majority of the patients with CKD on dialysis were asymptomatic from a gastro intestinal perspective. Abnormal endoscopic findings were shown by majority of the study subjects. H pylori infection was seen in one out of three patients and was more in the asymptomatic group. All these observations suggest pre transplant OGD may help in assessing the abnormal GI lesions and the same can lead to reduction in post-transplant complications. We conclude that rou-tine upper gastrointestinal endoscopy and testing for H pylori infection may have to be considered in chronic re-nal failure patients as part of a complete renal transplant workup.

Antral gastritis

Percentage (%)

31

Number

Antral erosions

18

Duodenal erosions

29

Reflux esophagitis

8

6

5

5

5

1Polypoidal lesion duodenum

12

19

5

4

3

3

3

1

Gastric varices 1

1Duodenal ulcer with active bleed

19

3

2

2

2

2

Type of abnormal condition

Duodenal ulcer

Pangastritis

Gastric antral ulcer

Gastropathy

Fundal gastritis

8

Candidial esophagitis

Esophageal varices

Mallory weiss tear

11

2

18

13

Table 1 : Distribution of abnormal OGD findings

scopy group only 31.9% of patients were H pylori pos-itive.Nakajima et al reported similar findings in their study6. The reason they suggested for the lower preva-lence of H pylori in long term dialysis patients was re-duction of gastric acid secretion related to chronic gas-tritis. A study done by Sugimoto et al concluded that the prevalence of H pylori infection is similar in individuals with normal renal function and that of patients under haemodialysis for less than 1 year9. All these studies sug-gest that haemodialysis treatment per se is responsible for the lower prevalence of H pylori infection and not by the background uraemia alone.

27


Comparision of APACHE 2 vs SOFA Scores in Predicting Mortality Among Patients in ICU

Rema pai*, Pillai MGK*, Mohanakkannan S*

ABSTRACTBackground : SOFA and APACHE2 are two scoring systems which are being used in the ICU to predict mortality among patients in ICU. The question which among these systems is better remains elusive.

Objective: Goal of this study is to compare the ability of SOFA ( Sequential organ failure assessment ) and Acute physiology and chronic health evaluation ( APACHE ) II scoring system to predict mortality and morbidity in ICU patients .

Methods: Prospective observational study of 74 patients who were admitted in the ICU from January 2014 to December 2014 , a period of one year was done . The scoring systems of SOFA and APACHE2 were done on the admitted patients on day 1 of the admission.

Results: There were totally 46 patients in the alive group of which 16(33%) were female and 30(67%) were male. The mean age was 60 years . The SOFA scores of patients less than 60 years of age was compared with the SOFA scores of patients more than 60 years of age but there was no significant difference between them .The APACHE scores of patients less than 60 years of age was compared with the SOFA scores of the patients more than 60 years of age and there was no significant difference showed that SOFA was a better predictor of mortality than the APACHE scores (p- 0.048). Comparision of APACHE and SOFA scores on the basis of length of ICU stay shows that APACHE is a better predictor of the morbidity (length of stay in ICU) than the SOFA scores. P values are significant (<0.001 for APACHE as compared to 0.287 for SOFA)

Conclusion : Our study showed that SOFA scores were a better predictor of mortality among ICU patients when compared with APACHE2 , hence SOFA scoring can be considered in ICU patients for triaging and to look for treatment outcomes.

Corresponding Author: Rema pai

INTRODUCTION Scoring systems in ICU have been in use since the past 35 years and they help in the assessment of a critically ill patient1. There are different types of scoring systems and they can be broadly classified into scores that meas-ure the severity of the disease by various physiological parameters at the time of admission (APACHE), Simpli-fied Acute Physiology Score (SAPS), Mortality Probabil-ity Model (MPM)), scores that assess the presence and severity of organ dysfunction Multiple Organ Dysfunc-tion Score (MODS), Sequential Organ Failure Assess-ment (SOFA), and scores which assess nursing workload use (for example, Therapeutic Intervention Scoring Sys-tem (TISS), Nine Equivalents of Nursing Manpower Use Score (NEMS)2. Other than triaging, comparative audit, scoring systems have a lot of proposed roles in clinical management of patients3. The first ICU model of disease severity, The Therapeutic Intervention Scoring system (TISS) , was proposed in 19744. The Sequential Organ Failure Assessment score, or just SOFA score, is used to track a patient’s status dur-ing the stay in an intensive care unit (ICU). Sequential readings are done at 0 – 24 hours, and then after 48 hours. Six organ systems (respiratory, cardiovascular, renal, hepatic, central nervous, coagulation) were se-lected based on a review of literature, and function of each one is scored from 0 (normal function) to 4 (most abnormal), giving a possible score from 0 to 24. APACHE *Dept. of General Medicine , AIMS, Amrita Vishwa Vidyapeetham, Kochi, India.

II (“Acute Physiology and Chronic Health Evaluation II”) is a severity-of-disease classification system, one of sever-al ICU scoring system. It is applied within 24 hours of ad-mission of a patient to intensive care unit (ICU). Higher scores correspond to more severe disease and a higher risk of death. In APACHE II, there are just 12 physiologi-cal variables, compared to 34 in the original score. The effects of age and chronic health status are incorporated directly into the model, weighted according to their rel-ative impact, to give a single score with a maximum of 71. The worst value recorded during the first 24 hours of a patient’s admission to the ICU is used for each physio-logical variable5

METHODS AND MATERIALS Ours was a prospective study over a period of one year [2013- 2014] and patients are enrolled as per in-clusion criteria. Sample size was set to be a minimum of 80. Patients admitted to AIMS [Amrita Institute of Medical Sciences] a tertiary care hospital in intensive care unit under internal medicine during study period were taken for study when they come under inclusion criteria. The physiological parameters, lab investiga-tions, surgical status, chronic health condition including the demographic details as needed by scoring systems [APACHE II, SOFA] were recorded at the time of admis-sion to ICU. No changes were made in treatment proto-col of study patients. The treating physician /emergency medicine team in charge of ICU and staffs was unaware, that patients are enrolled into the study. This is to avoid

ORIGINAL ARTICLE


28


RESULTS 62.2% (46)of the total study population was of male sex and 37.8% (28)of the study population was female sex. 39.2% of the total study population was under the age of 60 years and 60.8 %of the study population was above the age of 60 years. Of all the cases which were studied the maximum number of cases were involving multi organ system (24.3%), followed by gastroenterol-ogy (20.3%) and then by neurology (18.9%). The other cases involved pulmonary medicine(16.2%), Hemat/On-cology (9.5%), cardiology (8.1%) and nephrology (2.7%). The number of patients in the study who were admit-ted in the ICU for less than 5 days were 39.2% and the percentage of patients who were admitted in the ICU for more than 5 days was 21.6%. The SOFA scores of pa-tients less than 60 years of age was compared with the SOFA scores of patients more than 60 years of age but there was no significant difference between them. The APACHE scores of patients less than 60 years of age was compared with the SOFA scores of the patients more than 60 years of age and there was no significant differ-ence between them. The SOFA scores were compared between males and females and there was no signifi-cant differences in prediction of mortality/morbidity.The APACHE scores were compared between males and females but there was no signifcant differences in pre-diction of mortality/morbidity.

0.0

10.0

20.0

30.0

40.0

50.0

60.0

70.062.2

37.8

Male Female

Gender Distribution

Method

SOFA

APACHE 2

Std. Deviation

p value

45

29

45

29

.154

.161

.092

.159

.154

.001

Comparision of APACHE2 vs SOFA scores on the basis of mortality

Mortality

death

alive

death

alive

N Mean

.224

.268

.090

.190

any bias into the primary end point of study. The study patients were given the same care as provided to all patients. Patients were followed up till the time of dis-charge and mortality among the study patients were documented. All patients above the age of 17 who were admitted to ICU under internal medicine with a minimum ICU stays of twenty four hours were included.Patients less than 17 years were excluded and patients from outside hospital ICU were excluded due to lead time bias Based on the results of the iSOFA and APCACHE 2 scores with respect to mortality (references- Dino Adrian Halim et al2 ) and with 95 % confidence and 80 % power minimum sam-ple size comes to 48 survivors and 26 non survivors . The scores were calculated for study patients according to the scoring systems studied[APACHE II, SOFA]. APACHE II and SOFA scores were calculated using online calcula-tors from Globalrph web portal.Also predicted mortality by each scoring systems have been documented and analyzed statistically to meet the objective of study. Statistical analysis is done by using SPSS software Wilcoxon signed Rank test was used to compare mean scores of APACHE and SOFA .Mann Whitney U test was used to compare mean scores within APACHE and with-in SOFA( between mortality, age, length of ICU stay).Mann Whitney U Test was used to compare mortality between SOFA and APACHE 2 scores.

29

Amrita Journal of MedicineComparision of APACHE 2 vs SOFA Scores in Predicting Mortality

Among Patients in ICU

REFERENCES1. Severity scoring systems in the critically ill D. Christopher Bouch,

MB ChB FRCA EDIC Jonathan P. Thompson, BSc (Hons) MB ChB MD FRCA

2. Clinical review: Scoring systems in the critically ill Jean-Louis Vincent1* and Rui Moreno2 * Corresponding author: Jean-Louis Vincent [email protected] Author Affiliations, 1. Department of Intensive Care, Erasme University Hospital, Route de Lennik 808, 1070 Brussels, Belgium, 2. Department of Intensive Care, Hos-pital de St Antonio dos Capuchos, Centro Hospitalar de Lisboa Central, EPE, 1169-050 Lisbon, Portugal

3. Kevin Gunning,Kathy rpwan ABC of intensive care , BMJ vol319

4. BekeleAfessa, OjenjenGajic, Mark T. Keegan (2007) Severity of ill-ness and Organ Failure Assessment In Adult Intensive Care Units. Crit care 23 :639-58

5. Clinical review: Scoring systems in the critically ill Jean-Louis Vin-cent* and Rui Moreno

6. Comparison of the Sequential Organ Failure Assessment, Acute Physiology and Chronic Health Evaluation II scoring system, and Trauma and Injury Severity Score method for predicting the outcomes of intensive care unit trauma patients Seong Youn Hwang,Jun Ho Lee , Young Hwan Lee,Chong Kun Hong

7. Comparison of Apache II, SOFA, and Modified SOFA Scores in-Predicting Mortality of Surgical Patients in Intensive Care Unit at Dr. Hasan Sadikin General Hospital Dino Adrian Halim, Tri Wahyu Murni, Ike Sri Redjeki

DISCUSSION Comparision of APACHE and SOFA scores on the basis of length of ICU stay shows that APACHE is a better pre-dictor of the morbidity (length of stay in ICU) than the SOFA scores. P values are significant (<0.001 for APACHE as compared to 0.287 for SOFA) Comparison of SOFA and APACHE 2 scores on the ba-sis of mortality of the patients showed that SOFA was a better predictor of mortality than the APACHE scores (p- 0.048). Our study gives the same final conclusion as the study done by Dino Adrian Halim, Tri Wahyu Murni, Ike Sri Redjeki et al 6 which also went on to show that SOFA scores were better than APACHE2 scores in predicting the mortality among ICU patients, but differs from the other study done by Hwang et al7 which said that SOFA scores were equivalent to APACHE scores.

CONCLUSION The study goes on to show that SOFA scores are bet-ter predictor of the mortality among ICU patients and APACHE scores are a better predictor of morbidity ( Length of stay in ICU) among ICU patients. It would be prudent to consider SOFA scores better than the APACHE scores since mortality is better predicted by it and patients with very high SOFA scores should be tak-en as those with very high risk for mortality and should

Method

APACHE 2

SOFA

Std. Deviation

p value

29

16

29

16

.083

.107

.105

.171

.287

<0.001

Comparision of APACHE vs SOFA scores on the basis of length of ICU stay

No of ICU stay

Greater than 5 days

Less than 5 days

Greater than 5 days

Less than 5 days

N Mean

.081

.106

.164

.333

be treated accordingly .

30


Lipid Profile in Executive Health Checkup Patients in a Tertiary Health Care Center in Kerala

DayanaAntony*, Nisha Bhavani*

ABSTRACT Literature regarding prevalence of dyslipidemia in this part of the world is very scarce. This study was aimed at studying the fasting lipid profile of a cohort of patients attending the executive health check up program of a tertiary care centre in central Kerala. 200 patients with no past history of dyslipidemia and who are not on any lipid modifying drugs had their fasting lipid profile done after 14 hours overnight fasting. Mean of lipid parameters in the total population was Total cholesterol- 232.mg/dl Triglyceride- 172.mg/dl HDL-43.49mg/dl and LDL- 158.86mg/dl Only 10-11% of population had normal Total cholesterol and LDL levels whereas normal triglyceride and HDL were seen in 44 % and 36.5% respectively. The prevalence of dyslipidemia was markedly higher compared to other population. There was no significant difference in the prevalence of dyslipidemia between diabetic and nondiabetics.

Corresponding Author: Nisha Bhavani

INTRODUCTION Along with Type 2 Diabetes Mellitus, dyslipidemia has become a common disorder in the present day world. Both disorders along with systemic hypertension, obe-sity and insulin resistance contribute to the metabolic syndrome which significantly increases the risk of cardi-ovascular disease. The prevalence of dyslipidemia varies in different pop-ulation. South Asians are reported to have a high inci-dence of metabolic syndrome1,2. Data regarding the prevalence of dylipidemia in (our local) population is scanty. So we aimed to study the prevalence of lipid dis-orders in a cohort of patients attending the executive health care clinic of a tertiary health care center. We also aimed to study the difference in lipid profile in patients with characters known to affect lipid profile like age, gender, BMI and presence and absence of diabetes.

METHODS A cross-sectional study was conducted, among 200 patients attending the Comprehensive Health clinic of a tertiary referral center. All patients above the age of 20yrs were included. Patients who are on treatment for dyslipidemia or with past history of dyslipidemia or those with comorbidities affecting lipid profile like renal failure, nephrotic syndrome and hypothyroidism were excluded from the study. Fasting lipid profile was done in all patients after 14 hours fasting by Photometric enzymatic method. Dys-lipidemia was diagnosed according to ATP and NCEP guidelines shown below. Patients were classified ac-cording to their age, BMI, sex, and presence or absence of diabetes into different categories. Statistical analysis was done using SPPS version. Categorical variables were compared using Chi-square test.

ORIGINAL ARTICLE

Lipid

>240

<35

200-239

35-45

<200

>35HDL

Total Cholesterol

Normal lipid levels (mg/dl) (NR)

High Risk lipid levels (mg/dl) (HR)

Table 1: ATP and NCEP classification

Borderline risk lipid levels (mg/dl) (BR)

LDL <130 130-159 >160

Triglyceride <150 150-200 >200


*Dept. of Endocrinology, AIMS, Amrita Vishwa Vidyapeetham, Kochi, India.

31


RESULTS Results are tabulated in the tables given below

Young age (YA)

Age groups

52

Middle Age (MA) 113

Old Age (OA) 35

78

122

43

Type 2 Diabetes mellitus

Categories

70

73

Characteristics

Male (M)

Gender

Female(FM)

BMI

Normal (NW)

Overweight(OW)

Obese(OBW)

No (NDM)

100Yes(DM)

100

Table 2 : Number of cases in each category

20-39

20-3940-59

40-59

>60

Male

Female

<23.5

23.5-27.5

>27.5

Frequency Percentage

26

56

18

39

61

21

35

34

50

50

175

226

44

176

160

40

156

234

172

43

158

TG

TC

HDL

LDL

232

TOTAL YA MA OA

Table 3: Correlation between PCT max and organisms isolated

158

45

156

231

FM

141

45

162

236

M

192

42

156

229

NW

155

43

160

230

OW

193

42

154

228

OBW

166

43

162

238

DM

168

42

155

230

NDM

176

44

162

233

TG>150 & HDL<35

LDL<100

Total

DM

NDM

13.5

12

15

1.5

1

2

Table 4: Percentage Prevalence of dyslipidemia in diabetics and nondiabetics

%


32


Lipid parameters were similar in most groups except for a significantly higher triglyceride level in males vs females (p0.01) higher total cholesterol in obese vs overweight (p 0.03), and higher TG in normal vs over-weight vs obese (p 0.01 and0.03 respectively ) The HDL levels were significantly lower in young age vs other

age groups. ( YA vs MA p 0.03 and YA vs OA 0.02 ) Lipid parameters were similar in diabetics and nondiabetics. The classic diabetic lipid profile of high Tg and low HDL were similar in diabetic and nondiabetics. A diabetic tar-get LDL < 100 was present only in 1 % of diabetics and 2 % of nondiabetics.

Lipid Profile

64(32.%)

103(51.5%)

31(15.5%)

48(24.%)

93(46.5%)

96(48%)

86(43%)

74(37.%)

88(44.%)

73(36.5%)

21(10.5%)

Triglyceride

Total Cholesterol

HDL

LDL

23 (11.5%)

Normal Risk NR

Borderline Risk BR

High Risk HR

Table 5: Dyslipidemia risk profile in the total population.N (%)

30

12

47

49

44

37

12

63

TG

HDL

LDL

TC

%NWNR

NWBR

NWHR

21

16

44

26

OWNR

33

31

16

20

OWBR

24

50

40

40

OWHR

43

19

44

40

OBWNR

47

36

4

3

OBWBR

23

52

45

53

OBWHR

30

12

51

44

17

21

69

44

42

17

15

46

TG

HDL

LDL

TC

%YANR

YABR

YAHR

39

16

44

32

MANR

42

41

10

8

MABR

MAHR

26

42

39

51

OANR

32

18

51

40

OABR

51

51

6

9

OAHR

29

31

51

60

20

11

37

31

62

16

4

33

45

15

31

4

TG

HDL

LDL

TC

MNR

FMNR

MBR

26

43

51

49

FMBR

21

42

44

55

41

42

18

32

MHR

18

54

12

41

FMHR

13

44

30

8

12

43

11

44

TG

HDL

LDL

TC

DMNR

NDMNR

DMBR

41

42

47

22

NDMBR

45

54

56

26

DMHR

NDMHR

51

15

42

34

42

16

32

30

Table 6: Dyslipidemia risk profile in different categories

33


DISCUSSION

In females, majority had borderline risk TC levels, high risk LDL levels and normal TG and HDL levels.In males, majority had high risk TG levels, normal LDL levels and borderline risk TC and HDL levels.In non-diabetics, ma-jority had borderline risk TC, LDL and HDL levels and normal TG levels. In diabetic, majority had high risk LDL levels, borderline risk TC levels and normal TG and HDL levels. In normal BMI groups, majority had borderline risk TC and HDL levels and normal TG levels. Normal LDL levels were seen only in 12% of normal BMI, remaining had borderline risk and high risk levels (44.%) each.In overweight group, majority had high risk TG and LDL levels and borderline risk HDL levels. Normal TC levels were seen only in 20% of overweight group, remain-ing had borderline and high risk levels (40%).In obese group, majority had high risk LDL levels, borderline risk TC and HDL levels and normal TG levels. In young age, majority had borderline risk TC and HDL levels and nor-mal TG levels. Normal LDL levels were seen only in 15 % in young age, remaining had borderline and r high risk levels (42 %each.). In middle age, majority had border-line risk TC and HDL levels , high risk LDL and normal TG levels. In old age, majority had borderline risk TC and LDL levels but normal TG and HDL levels

REFERENCES

In this cross sectional study on patients attending com-prehensive clinic, the mean lipid levels and prevalence of dyslipidemia were assessed. The study also compared the lipid profile in diabetic and non- diabetic, different BMI categories, different age groups and in males and females. Mean of lipid parameters in the total population was To-tal cholesterol- 232mg/dl, Triglyceride-172mg/dl, HDL-43mg/dl and LDL- 158.8mg/dl. In other similar studies the mean values were, total cholesterol-197.5mg/dl, Tri-glycerides-181.7mg/dl, HDL-38.4mg/dl4. So our popula-tion had different mean lipid values compared to other population. In our study only 10-11% of population had normal Total cholesterol and LDL levels whereas normal triglyc-eride and HDL were seen in 44 % and 36.% respectively. Other studies showed the prevalence of normal lipid levels as 46.3% normal LDL, 89.% normal HDL and 45.% had normal TG5 . So the prevalence of dyslipidemia was markedly higher in our population. The high mean cholesterol levels and higher preva-lence of dyslipidemia in our population may be due to genetic factors and life style factors like diet, exercise and urbanization. It is well known that South Asians are at high risk of cardiovascular risk factors including dys-lipidemia. All the four lipid parameters were similar in all age group except for a significantly higher HDL levels, which were more common in old age and middle age

compared to young age. Other published studies also showed high incidence of dyslipidemia in middle age and old age 6.

All lipid parameters were similar in both sexes except for higher TG levels in males. Other studies showed a gradual increase in dyslipidemia in all BMI categories in females. It also showed that percentage of females hav-ing dyslipidemia was less as compared to males7. Thus our population behaved differently with regards to lipid levels in males and females.

Most of the lipid parameters were similar in all three groups of BMI except for a slightly high Total cholesterol in the obese group and a slightly high triglyceride in the overweight group. Other studies reported prevalence of higher concentration of triglyceride in obese4. Here also our study findings was different from published studies.

All lipid profiles were almost similar in diabetic and non-diabetic. Slightly higher mean total cholesterol, triglycerides and LDL were seen in diabetic patients but difference was statistically insignificant. Even the classic diabetic dyslipidemia (high triglyceride and low HDL) were similar in diabetic and non-diabetic. But in other studies the prevalence of dyslipidemia was more in diabetic patient compared to non- diabetic patients8. Even when dyslipidemia cut off for LDL was taken as 100, there was no difference between diabetic and non- diabetic. The reason for lack of difference in our study between diabetic and non- diabetic, may be because diabetic patients may be checking their lipid profile ear-lier and hence being treated earlier. Those who were on treatment were excluded from our study.

Limitations of the study were the relatively small sam-ple size. Multiple logistic regression analysis was not done with different variables of the study.

Thus the distribution and pattern of dyslipidemia in our population were grossly different from literature al-ready reported Larger studies involving more number of patient are required to confirm this study findings.

CONCLUSION This cross sectional study of lipid profile of patients from kerala shows that the lipid profile profile in our population is different from that in published literature


1. Misra A, Kalpana Luthera and N K Vikram. “Dyslipidemia in Asian Indians : Determinants and significance.” JAPI 52 (2004): 137-42

2. Vibhuti Singh MD, MPH and Prakash Deedwania. “Dyslipidemia in special populations: Asian Indians, African Americans, and His-panics.” Current atherosclerosis reports 8, no.1(2006):32-40.

3. National Cholesterol Education program (NCEP) Expert Panel on detection, Evaluation and Treatment of High Blood Choles-terol in Adults ( Adult Treatment Panel 111)Third report of the National cholesterol Education Program ( NCEP) Expert Panel on Detection, Evaluation and Treatment of High Bllood Cholesterol

34


in Adults ( Adult Treatment Panel 111 ) final report Circulation 2002 ;106: 3143

4. Barquera S, Flores M, Olaiz-Fernández G, Monterrubio E, Villalpan-do S, González C, Rivera J and Sepúlveda J. “Dyslipidemias and obesity in Mexico.” Salud Publica de Mexico 49 (2007):s338-S47.

5. Yingying Liu, Puhong Zhang, Wei Wang, Huan Wang, Ling Zhang, Wei Wu and Xichua Guo. “The characteristics of dyslipidemia pa-tients with different durations in Beijing: a cross-sectional study.”. Lipids in Health and Disease 9, no.1(2010):115.

6. Nicole Ducharme and Rani Radhamma. “Hyperlipidemia in the Elderly.” Clinics in geriatric medicine 24, no.3 (2008):471-87.

7. Humayun Anjum, Arbab Sher Shah, Shamim Alam and Hamid Hussein. “Relationship of body mass index and dyslipidemia in different age groups of male and female population of Peshawar.” J Ayub Med Coll Abbottabad 21, no.2 (2009).

8. Chahil J Tina, Henry N and Ginberg MD. “Diabetics Dyslipidemia.” Endocrinology and metabolism clinics of North America 35, no.3(2006):491.

35


Age Influence on Clinical Profile and Outcome of Stroke – A Hospital based Cohort Study from a Comprehensive Stroke

Care Centre in Kerala, South India Vivek Nambiar*, Jisha S Das*, Jeslyn Mary Philip*, Delcey Rachel Vargheese*,

Ashly Alexander Fernandez*, Umadevi P*, Dhanya T S*, Amrutha Ajai*, Georgeena Pulickal**, Manu Raj***, Remya Sudevan****

ABSTRACTintroduction : Stroke is the most common cause of preventable disability and one of the most common causes of mortality all over the world. Western studies have shown that etiology, risk factors and outcome of stroke in young adults are different from that of older stroke patients. Indian studies regarding the comparison of young and old stroke patients are limited.

objectives: To compare the clinical characteristics, risk factors, etiology, drug utilization patterns, adverse drug reactions and func-tional outcomes in young and old stroke patients admitted in a comprehensive stroke care centre.

methods: This observational study was conducted in 240 adult patients who were admitted in the Comprehensive stroke care de-partment of a tertiary care hospital for a period of 44 months (January 2012- September 2015). The study duration was three years. Data on type of stroke, risk factors, etiology, type of antithrombotic therapy, recurrence of stroke and adverse drug reactions in patients was collected from medical records and hospital information system using a standard proforma. Follow up on functional outcome, medication compliance and adverse drug reactions to antithrombotic therapy were done by either telephonic interview or direct conversation with the patient or family members. Mann Whitney test was used to compare continuous variables and Chi-Square test was used for categorical variables and p<0.05 was considered significant.

Results: In the present study, 80 young and 160 old patients were studied. Both the groups showed a male preponderance. The commonest type of stroke was ischemic stroke (78.7% young v/s 88.1% old) in both groups. The etiology was undetermined for young patients (40%) while cardiac embolism was the etiology in 32.5% of the old patients. Hypertension was the most common cardiovascular risk factor in both groups (48.7% young v/s 75% old). Aspirin was the most commonly prescribed antiplatelet drug (76.1% young v/s 90% old) in both groups. Both the groups had good compliance to medications and the difference was not statistically significant. Minor bleed was the most common adverse drug reaction (7.5% young v/s 11.2% old) seen. Unfavourable functional outcome was significantly lower in young compared to the old (48% in young patients v/s 72.8%in old patients). Stroke recurrence was seen less in the young compared to old (8.8% v/s 15.1%) patients.

conclusion: There are significant differences in the stroke etiology, risk factors, antithrombotic therapy and functional outcome between the young and old stroke patients.

Key words: Stroke, risk factor, etiology, recurrenceKey Messages: In this era of lifestyle diseases, the prevalence of young stroke has increased. There are substantial differences in the stroke etiology, risk factors, antithrombotic therapy and functional outcome between the young and old stroke patients.


INTRODUCTION

*Dept. of Strock Medicine, **Dept. of Public Health Research, ***Dept. of Paediatric & Public Health Research, ****Dept. of Medical Research AIMS, Amrita Vishwa Vidyapeetham, Kochi, India.

SUBJECTS AND METHODS

ORIGINAL ARTICLE

Stroke is the most common cause of preventable dis-ability and one of the most common causes of death all over the world1. It is an acute focal neurological deficit of vascular origin and includes intracranial haemorrhage, subarachnoid haemorrhage, and cerebral infarct2. Age is the most cardinal non modifiable risk factor for stroke. The mean age of acute stroke is 75 years in major epi-demiological studies. The incidence rate of total young stroke (< 45 years) ranges from 0.1-0.3 per 1000 per-son years but most population based epidemiological studies are focused on stroke in the older population3,4

Even though the outcome and etiology of young stroke

is unique, comparison studies of young and old stroke patients in India are sparse. In the current study, we compared the clinical characteristics, risk factors, etiol-ogies, drug utilization pattern, adverse drug reaction (ADR) and functional outcome in young and old stroke patients admitted in the Stroke Medicine department of a tertiary care hospital in South India.


A single centre observational study was conducted on first ever stroke patients admitted to the stroke depart-ment of a tertiary care hospital in South India for a peri-od of 44 months from January 2012 to September 2015. The study period was for three years and was approved by the institutional ethics committee. All patients di-agnosed with arterial ischemic stroke, ischemic stroke

36


RESULTS During the study period, data from a total of 240 pa-tients with stroke were analysed. Among study sub-jects, 160 (66.6%) were categorized as old stroke and 80 (33.3%) as young stroke. The mean age of the young stroke population was found to be 38.9 years ( 21 - 45 years) while in old stroke population, the mean age was found to be 62.9 years (46 - 87 years). Males pre-dominated in both the groups, with 68.8% and 62.5% in the old and young stroke categories, respectively. Is-chemic stroke was found to be more common,i.e.,78.7% in young and 88.1% in old group. Thirty three (41.2%) young patients had lesion on the right side while for 79 (49.4%) old patients it was left sided. A major propor-tion of patients (77.5% young and 75.6% old patients) had cerebral infarcts with higher number of lesions in the anterior region (58.7%in young patients and 56.2% in old patients). A higher percent of young patients had a large lesion compared to the old group (32.5% versus 21.9%). Cardiac embolism was the etiology for stroke in 52 (32.5%) old patients and 14 (17.5%) young patients and the difference was statistically significant (p=0.0142). The etiology remained undetermined for 32 (40%) young stroke patients. Amyloid angiopathy, lupus vas-culitis, antiphospholipid antibody (APLA) syndrome, Moyamoya disease, Takayasu arteritis, and polycythemia attributed to the etiologies in 26.2% of the young pop-ulation (Figure 1).

interviews or verifying medical records and the causality was evaluated using Naranjo ADR probability scale.

STATISTICAL ANALYSIS The statistical analysis was done by SPSS. Summary values are presented as mean (SD) or percentage (n) as applicable. Mann Whitney test was used to compare continuous variables and Chi-Square test was used for categorical variables. p<0.05 was considered significant.

OldYoung

Small Vessel Desease

Large Artery Desease

Undetermined

Cardioembolic

Others

Perc

enta

ge (%

)

Figure 1: Etiology of Stroke

0

5

10

15

20

25

30

3540

45

with haemorrhagic transformation and cerebral venous thrombosis were taken as study participants. We exclud-ed patients with life expectancy less than 6 months after stroke due to other illnesses like malignancy, patients with previous history of stroke and those diagnosed with transient ischemic attacks only. Patients aged 18-45 years at the time of event were grouped as young stroke patients and those with age greater than 45 years at the time of event were categorized as older stroke patients.

A retrospective review of the medical records as well as the hospital information system was done to obtain data including demographic information (age at the time of first stroke attack, sex, personal history), medical history (hypertension, diabetes mellitus, dyslipidemia, atrial fibrillation, ischemic heart disease, previous stroke, family history and past medications), other features like type of stroke, etiology of stroke, topographic features of infarct and length of hospital stay. A 24 month follow up was conducted to analyse the functional outcome, recurrence of stroke, occurrence of ADRs and medica-tion adherence by direct interview of the patients or his/her caretakers, from the hospital information system or by a telephonic interview. The data collected were tran-scribed into a standard data collection form. The diag-nosis was classified into ischemic, hemorrhagic or both ischemic and hemorrhagic stroke based on the Mag-netic Resonance Imaging (MRI) and Computed Tomog-raphy (CT) findings. Etiology was determined by the Trail of ORG 10172 in Acute Stroke Treatment (TOAST) classification. Size of infarct, region of brain affected and laterality of lesion were also assessed with CT and MRI by a stroke neurologist and neuroradiologist blind-ed to the outcome. Functional outcome was measured using Modified Rankin Scale (MRS). Medication adher-ence to the antithrombotic therapy was determined using Morisky Medication Adherence Scale (MMAS-8). Adverse drug reactions were assessed by direct patient

37

Amrita Journal of MedicineAge Influence on Clinical Profile and Outcome of Stroke – A Hospital based

Cohort Study from a Comprehensive Stroke Care Centre in Kerala, South India

Among the cardiovascular diseases, hypertension was the most common risk factor in both young (48.7%) and old stroke patients (75%), with a significant difference on comparison (p<0.0001). Table [1] Diabetes mellitus was found to be significantly more in old (63.7%) than young patients(26.3%) and this difference was statisti-cally significant (p<0.0001). Cardiac valve defects was significantly higher in young patients compared to the old patients (12.5% v/s 3.7%, p=0.0104).

Seventeen young and 29 old patients did not receive any antithrombotic therapy as they had experienced hemorrhagic stroke or ischemic stroke with hemorrhag-ic transformation or had expired during hospital stay. Aspirin (76.1% in the young and 90% in the old) followed by clopidogrel were the most commonly prescribed an-tiplatelet agents. Eleven young stroke patients (17.5%) were prescribed anticoagulants compared to old stroke patients (5.3%) at the time of hospital discharge and this difference was statistically significant (p=0.0065).

A total of 180 patients completed 2 years of follow up after first ever stroke. Data was available for 42 young patients (8 patients expired and 5 patients were lost to follow up) and 88 old patients (30 patients expired and 7 patients were lost to follow up). The medication com-pliance was assessed among these patients under fol-low up. Among them, 40 (95.2%) young and 78 (88.6%) old patients showed high medication adherence while 1 (2.3%) young patient and 8 (9%) old patients showed low adherence when measured with MMAS. Adverse drug reactions to antithrombotic therapy were identified in 18 (22.5%) young and 38(23.7%) old patients with minor bleeds (ecchymotic patches, gum bleed, dysmenorrhoea, and hematuria), gastroesopha-geal reflux disease and dyspepsia being the most com-monly reported ADRs (Figure 2). There was one possible

and 17 probable ADRs in the young stroke group while in the older population, out of the 38 ADRs observed, four were categorized as possible and 34 as probable cases.

Length of hospital stay was less than 10 days for major-ity of both young (57.5%) and old (61.2%) patients. The functional outcome in patients who had completed two years after first ever stroke was unfavourable for 48% of young patients and 72.8% of older patients.

Seven (8.8%) young and 23 (15.1%) old patients experi-enced recurrence of stroke during the 24 months follow up. The average time to first recurrence of stroke was 6 months in the young and 13 months in the old. Four out of seven young patients and 12 out of 23 old patients succumbed to death due to stroke recurrence.

<0.0001

113(70.6%)

0.8339

102(63.7%)

40(25%)

21(26.3%)

21(26.3%)Alcoholism

Diabetes Mellitus

Young patientsn=80

p-value

Table 1: Risk factors

45(56.3%)Cardiovascular Disease

0.0269

Old patientsn=160

Family History

12(15%) 31(19.3%) 0.4048

Obstructive Sleep Apnoea

Migraine

Smoking

10(12.5%)

1(1.3%)

10(12.5%) 9(5.6%)

6(3.7%)

3(1.9%)

0.0629

0.0140

0.7214

38


DISCUSSION

0

2

4

6

8

10

12

Major Bleed

Dyspepsia

Minor Bleed

GerdOth

ers

Perc

enta

ge (%

)Old

Young

Figure 2: Adverse Drug Reactions

Stroke subtypes, etiology and risk factors The mean age of stroke in the old population was found to be lower than that in the western popula-tion5. Our study shows that the male patients are pre-dominant in both the young and old category which is consistent with other studies6,9. This can be attributed to early accumulation of traditional risk factors in men than in women as well as socio-cultural differences in India where more strokes in males reaches to the ter-tiary care centers. Ischemic stroke accounts for about 85% of all strokes9 worldwide and the current results are also in agreement. Hemorrhagic stroke was slightly more prevalent in the young patients probably due to uncontrolled hypertension owing to delayed diagnosis.

The results showed no difference in the laterality of lesion which is in contrast to a hospital based study in North India which showed majority of patients with left sided lesion.8 There was no significant difference in the brain region affected between the two groups.

Etiology of stroke was classified according to TOAST criteria. Large artery disease was found to be more prev-alent in elderly due to atherosclerotic disease. In our series, we detected 17.5% young patients with large ar-tery disease which is slightly less compared to previous reports10,11. Significantly higher frequency of cardio em-bolic stroke seen in the elderly could be due to the refer-ral bias as ours being a tertiary care centre where most of the critically ill patients are referred. These patients had multiple issues like cardiac failure and concurrent severe coronary artery disease.

Rate of small vessel disease was lesser than that re-ported in other studies7,12 as most of the minor lacunar strokes are managed in the local hospitals rather than a tertiary care hospital like ours. The uncommon causes

of stroke were significantly more in younger than in old-er population. It must be due to the significant number of young hemorrhagic patients than old supported by several studies indicating that hemorrhagic stroke ac-counts for more than 50% of all stroke under the age of 45 years4.

Regarding the localization of brain infarct; in the young, more than half of the patients had anterior infarct akin to other studies7,8,13. There was no significant difference in posterior infarct among the two groups in contrast to the Helsinki stroke registry study that found considera-bly higher posterior infarct in age below 45 years7. The probable reason is the high prevalence of dissections as a cause of stroke in young people in the developed countries as they are more active physically and in-volved in contact sports.

Studies have shown that although modifiable risk fac-tors are same in young and old population, the preva-lence differs between the two groups. In our study, the older population showed significantly higher frequency of cardiovascular risk factors (like hypertension, dyslipi-demia and myocardial infarction) and diabetes mellitus compared to the young population which is in agree-ment with other stroke risk factor studies14,15. Migraine and valvular heart disease were more frequently seen in younger population similar to other studies4,8,14,15. The risk of future strokes can be reduced by controlling these modifiable risk factors16 . There was no significant difference in rates of stroke recurrence between the two groups. The recurrence rate of stroke in young patients seen in our study was comparable to another with recur-rence rate of 11.1%17.

Antithrombotic therapy, adherence and adverse events Anticoagulants were found to be prescribed more in

39


REFERENCES1. Feigin VL, Roth GA, Naghavi M, Parmar P, Krishnamurthi R, Chugh

S, Mensah GA, Norrving B, Shiue I, Ng M, Estep K, Cercy K, Mur-ray CJ, Forouzanfar MH; Global Burden of Diseases, Injuries and Risk Factors Study 2013 and Stroke Experts Writing Group. Global burden of stroke and risk factors in 188 countries, during 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013.Lancet Neurol 2016;15:913-24.

2. Donnan GA, Fisher M, Macleod M, Davis SM. Stroke.Lan-cet 2008;371:1612-23.

3. Strong K, Mathers C, Bonita R. Preventing stroke: saving lives around the world. Lancet Neurol 2007;6:182-7.

4. Smajlović D. Strokes in young adults: epidemiology and preven-

CONCLUSION There are significant differences in the stroke etiology, risk factors, functional outcome and anticoagulant ther-apy between the young stroke patients and patients in the older population. More multi-center studies includ-ing registries will help to advance the knowledge of young stroke and its preventive and therapeutic strat-egies.

tion. Vasc Health Risk Manag 2015; 11:157-64.

5. Weimar C, Diener HC. Antiplatelet therapy and oral anticoagu-lation for prevention of ischemic stroke.Current Drug Therapy 2006;1:249-56.

6. Leys D, Bandu L, Hénon H, Lucas C, Mounier-Vehier F, Rondepierre P, Godefroy O. Clinical outcome in 287 consecutive young adults (15 to 45 years) with ischemic stroke. Neurology 2002;59:26-33.

7. Putaala J, Metso AJ, Metso TM, Konkola N, Kraemer Y, Haapa-niemi E, Kaste M, Tatlisumak T. Analysis of 1008 consecutive pa-tients aged 15 to 49 with first-ever ischemic stroke: the Helsinki young stroke registry. Stroke 2009;40:1195-203.

8. Baidya OP, Tiwari S, Usman K. Acute ischemic stroke in young adults-a hospital based study in North India. International Jour-nal of Biomedical Research2015; 6:113-7.

9. National Registry of Diseases Office. Singapore Stroke Registry Report No. 4. Trends in Stroke in Singapore 2005-2013. Available on https://www.nrdo.gov.sg/ docs/ libraries provider3 /default document-library/stroke-monograph 2015_final.pdf? sfvrsn =0. Accessed on 12 May 2016.

10. Adams HP Jr, Butler MJ, Biller J, Toffol GJ. Non hemorrhagic cere-bral infarction in young adults.Arch Neurol 1986;43:793-6.

11. Bevan H, Sharma K, Bradley W.Stroke in young adults. Stroke 1990;21:382-6.

12. SiqueiraNeto JI, Santos AC, Fabio SR, Sakamoto AC.Cerebral in-farction in patients aged 15 to 40 years. Stroke 1996;27:2016-9.

13. Dash D, Bhashin A, Pandit AK, Tripathi M, Bhatia R, Prasad K, Padma MV. Risk factors and etiologies of ischemic strokes in young patients: a tertiary hospital study in north India. J Stroke 2014;16:173-7.

14. Zhang YN, He L. Risk factors study of ischemic stroke in young adults in Southwest China.Sichuan Da XueXueBao Yi Xue Ban 2012;43:553-7.

15. Bogousslavsky J, Pierre P.Ischemic stroke in patients under age 45.NeurolClin 1992;10:113-24.

16. James E, AnnieJ, Nambiar V. Impact of clinical pharmacist’s inter-ventions on health outcomes in post stroke patients.Internation-al Journal of Pharmaceutical Research2015; 7:38-43.

17. Camerlingo M, Casto L, Censori B, Ferraro B, Caverni L, Manara O, Finazzi G, Radice E, Drago G, De Tommasi SM, Gotti E, Barbui T, Mamoli A. Recurrence after first cerebral infarction in young adults. ActaNeurolScand 2000;102:87-93.

18. Chen YM, Lin YJ, Po HL. Comparison of the risk factor profile, stroke subtypes, and outcomes between stroke patients aged 65 years or younger and elderly stroke patients: a hospital-based study. International Journal of Gerontology 2013;7:205-8.

Age Influence on Clinical Profile and Outcome of Stroke – A Hospital based Cohort Study from a Comprehensive Stroke Care Centre in Kerala, South India

the young than the old even though cardio embolic stroke was highly prevalent in the old population. This may be attributed to the good tolerability and good health status of the young population. Anticoagulants are also prescribed in case of stroke due to thrombo-philic disorders (protein C, protein S deficiency, APLA syndrome) which was more prevalent in the young.

Both groups showed good compliance to antithrom-botic therapy. Low compliance was observed more in the old population which may be due to the presence of various co morbidities resulting in polypharmacy.

Adverse drug reactions due to antithrombotic therapy were found in both young and old population without considerable difference. Bleeds were more common in the old probably due to the presence of concurrent co morbidities. The functional outcome after a 24 month follow up showed a more favourable outcome in the young patients compared to the old patients which is in accordance with studies elsewhere18.

40


A Case of Non Bacterial Thrombotic Endocarditis in ElderlyAswin Rajeev*, George Paul*, Priya Vijayakumar*

ABSTRACTNon bacterial thrombotic endocarditis is a rare entity and usually a post mortem diagnosis. Some patients present with features of embolism ante-mortem. We are presenting a case of non bacterial thrombotic endocarditis which was detected incidentally in a patient with squamous cell carcinoma of the oesophagus.

Corresponding Author: George Paul

INTRODUCTION

*Dept. of Geriatric Medicine, AIMS, Amrita Vishwa Vidyapeetham, Kochi, India.

CASE REPORT

CASE REPORT A 68 year old male who is a known case of squamous cell carcinoma mid oesophagus with metastasis s/p chemo-radiotherapy one year ago presented with complaints of breathlessness even at rest since one month. He also had fatigue, reduced appetite and was

Nonbacterial thrombotic endocarditis (NBTE) is a rare condition that refers to a spectrum of non infectious le-sions of the heart valves that is most commonly seen in advanced malignancy. NBTE is often an autopsy finding. However, some patients are diagnosed ante-mortem presenting with the signs and/or symptoms of systemic embolization and require therapy. Initiating factor for pathogenesis of NBTE is not known but endothelial injury in the setting of a hypercoagula-ble state is thought to be critical for development of NBTE. Endothelial damage by circulating cytokines like tumour necrosis factor and interleukin 1 may trigger platelet deposition particularly in the presence of acti-vated coagulation system in conditions like malignancy, disseminated intravascular coagulation and anti-phos-pholipid syndrome to result in local deposition of plate-lets and molecules. Compared to vegetations in infective endocarditis, vegetations of NBTE are easily dislodged since there is little inflammatory reaction at the site of attachment. Thus in NBTE, there is a greater tendency for vegetation to embolize and cause extensive infarction. Patients with nonbacterial thrombotic endocarditis (NBTE) are typically asymptomatic until embolization occurs. The investigation should focus on evaluating the patient for the signs and symptoms of embolization, obtaining an echocardiogram, and defining the under-lying cause. There are no laboratory tests that confirm the diagnosis of NBTE. Hence testing is directed in dis-tinguishing NBTE from infective endocarditis. A high index of clinical suspicion is critical for the diag-nosis of NBTE. Despite therapy the prognosis from NBTE is generally poor

bed bound. There was no history of fever, chest pain or any other constitutional symptoms. On examination he was found to have tachycardia, enlarged supraclavicu-lar lymph nodes and a peri-umbilical mass. Respiratory system examination showed generalized reduced ve-sicular breath sounds with no added sounds. His blood investigations showed leucocytosis with elevated in-flammatory markers and thrombocytopenia. Blood cul-ture was reported to be sterile. CT chest and abdomen showed enlarged supraclavicular and para-aortic nodes with multiple metastatic lesions in both lung fields. An Echocardiogram was done in view of tachycardia which showed two friable masses in right ventricle one of which was attached to anterior tricuspid leaflet and oth-er to right ventricular apex. A diagnosis of non bacterial thrombotic endocarditis was considered. Patient was started on low molecular weight heparin and was dis-charged with plan to continue with palliative approach. The patient expired after 2 months of discharge.

DISCUSSION Patients with malignancy have a hypercoagulable state, and NBTE is a condition whereby there is valvular deposition of fibrin and platelets. Patients often pres-ent with signs and symptoms of systemic embolization from the vegetations. The vegetations are particularly prone to embolization, as they have little inflammato-ry reaction at the site of attachment with little cellular organization. Cardiac murmurs are infrequent. In a pa-tient with underlying malignancy and echocardiogram detected vegetation, persistent fever in the presence of serial negative blood cultures coupled with lack of re-sponse to antimicrobial therapy should increase suspi-cion of NBTE. Nonbacterial thrombotic endocarditis (NBTE) is a rare condition most often found post-mortem with rates in autopsy series ranging from 0.9 to 1.6 percent1. It has been reported in every age group, most commonly af-fecting patients between the fourth and eighth decades of life with no sex predilection2,3. Patients with advanced malignancy and those with systemic lupus erythemato-sus are the most common populations affected by NBTE. One autopsy series reported that, compared to the general population, patients with underlying malig-

41


REFERENCES1. Deppisch LM, Fayemi AO. Non-bacterial thrombotic endocardi-

tis: clinicopathologic correlations. Am Heart J 1976; 92:723

2. Rosen P, Armstrong D. Nonbacterial thrombotic endocarditis in patients with malignant neoplastic diseases. Am J Med 1973; 54:23.

3. González Quintela A, Candela MJ, Vidal C, et al. Non-bacterial thrombotic endocarditis in cancer patients. Acta Cardiol 1991; 46:1

4. el-Shami K, Griffiths E, Streiff M. Nonbacterial thrombotic endo-carditis in cancer patients: pathogenesis, diagnosis, and treat-ment. Oncologist 2007; 12:518.

5. Graus F, Rogers LR, Posner JB. Cerebrovascular complications in patients with cancer. Medicine (Baltimore) 1985; 64:16.

6. Dutta T, Karas MG, Segal AZ, Kizer JR. Yield of transesophageal echocardiography for nonbacterial thrombotic endocarditis and other cardiac sources of embolism in cancer patients with cere-bral ischemia. Am J Cardiol 2006; 97:894.

nancy have a higher rate of NBTE (1.25 versus 0.2 per-cent)2,3. When compared to other malignancies, higher rates were reported in those with adenocarcinoma (eg, lung, colon, ovary, biliary and prostate) (2.7 versus 0.47 percent) with the highest rates observed in patients with mucin-secreting and pancreatic adenocarcinoma (10 percent) 4. NBTE should be suspected in patients with acute stroke or coronary ischemia with underlying cancer, systemic lupus erythematosus, or anti phospholipid syndrome. It should also be suspected in patients with acute stroke or multiple widely distributed emboli of unknown aeti-ology as well as in those with presumed infective endo-carditis who are unresponsive to, or progressing poorly on, antibiotic therapy 5,6.Key Points• Non bacterial thrombotic endocarditis is a rare enti-

ty and usually a post mortem diagnosis.• Some patients present with features of embolism

ante-mortem.

• A high index of clinical suspicion is critical for the diagnosis of NBTE. Despite therapy the prognosis from NBTE is generally poor

Fig 1: Echocardiogram showing the vegetations (arrows)

A Case of Non Bacterial Thrombotic Endocarditis in Elderly

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Phenytoin Toxicity in an Adolescent with Epilepsy Following Self Harm – Is Early Detection of

Depression Imperative?Kotchuthressia Mathew*, Kesavankutty Nayar*, Sreekumar*, Dinesh Narayanan*

ABSTRACTDepression is often unrecognised and untreated, leading to higher chance of suicidal ideation in adolescents with epilepsy. We describe a case of an adolescent, a known case of myoclonic seizure disorder presented with symptoms of phenytoin toxicity following allerged history of consumption of phenytoin tablets. This report emphasises the necessity in early diagnosis and treat-ment of depression in the patients with epilepsy.

Key Words: Phenytoin toxicity, Adolescent, Epilepsy, Depression

Corresponding Author: Dinesh Narayanan

INTRODUCTION

*Dept. of, Psychiatry, AIMS, Amrita Vishwa Vidyapeetham, Kochi, India.

CASE REPORT

CASE REPORT Mr A, 17 year old single male studying in 11 th stand-ard, a known case of myoclonic seizures was maintain-ing well on Sodium Divalproate 200 mg for one year. He had family history of generalised seizure disorder in father who was on phenytoin. In June 2016, he pre-sented to the emergency department with one epi-sode of vomiting and difficulty in walking with swaying to one side (with no history of fall, bucking or tipping episode). On CNS examination, there was bilateral gaze evoked nystagmus. His cerebellar signs were positive. He had bilateral dysdiakokinesia and finger nose test was positive bilaterally. Heal knee test was positive gait was ataxic and planters were bilaterally flexors. Blood was sent for toxicology. The serum toxicology results were positive for phenytoin. His phenytoin level was 41.8 mcg/ml (Therapeutic range 20-40 mcg/ml). Urgent gastric lavage was given and he was treated with acti-vated charcoal. EEG was taken which was normal. On detailed history taking, he admitted of consuming his fathers regular antiepileptic medicines, phenytoin tab-lets. On mental status examination, Ideas of helpless-ness, hopelessness,worthlessness and suicidal Ideations were present. He was started on Escitalopram 20 mg for

Depression is highly common in adolescents with ep-ilepsy. The prevalence of depression is estimated to be 23-26%1,2. Unfortunately it is often unrecognised and untreated, leading to higher chance of suicidal ideation in such adolescents. The following case presents phe-nytoin toxicity in a patient with myoclonic seizures who consumed his father’s regular antiepileptic medicines (phenytoin). The case is to demonstrate the features of phenytoin toxicity in the patient. We also highlight the necessity of treating depression in the patients with epilepsy.

his low mood and suicidal ideation. After three days of admission, Sodium Divalproate 600 mg was restarted by the neurology department for controlling myoclonic seizures. Psychotherapy sessions were done. Patient improved symptomatically at the time of discharge. He was maintained on Sodium Divalproate 600 mg for his seizure disorder and Escitalopram 20 mg for depressive disorder. On follow up, his affect improved and suicidal ideations were absent.

DISCUSSION This patient with myoclonic seizures who had under-lying depressive disorder presented to us with unsteady gait and bilateral nystagmus. This prompted us to sus-pect deliberate self harm by the subject and sent blood for toxicology. Eventually serum toxicology was posi-tive for Phenytoin.Most common presenting features of phenytoin toxicity happen to be unsteady gait, vertigo, vomiting, drowsiness & generalised weakness. Toxic ef-fects are manifested as nystagmus, loss of smooth pur-suit, cerebellar defects, and eventually, coma. One of the most common psychiatric comorbid con-ditions in patients with epilepsy is depression. The eti-ology or the risk factors for depression in children and adolescents with epilepsy are likely multifactorial, in-volving neurobiological, psychosocial, and iatrogenic risk factors. Depression in children with epilepsy poses considerable challenges, such as higher suicide risk and a more severe course. Suicidal ideation and attempts are more likely to be seen in children and adolescents with epilepsy than in the general pediatric population3,4. Depressive symptoms can present according to the temporal relation to the seizures occurrence into ictal, periictal (symptoms precede and/or follow the seizure occurrence), and interictal (symptoms occur inde-pendently of the seizure occurrence). Interictal depres-sion is the most frequently “recognized” type of mood disorder and can present differently among patients

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REFERENCES 1. Kalisch R, Schubert M, Jacob W, et al. Anxiety and hippocampus

volume in the rat. Neuropsychopharmacology 2006;31:925–32.

2. Mensah SA, Beavis JM, Thapar AK, Kerr M. The presence and clin-ical implications of depression in a community population of adults with epilepsy. Epilepsy Behav 2006;8:213–9.

3. Thome-Souza MS, Kuczynski E, Valente KD. Sertraline and fluox-etine: safe treatments for children and adolescents with epilepsy and depression.Epilepsy Behav 2007;10:417–25.

4. Caplan R, Siddarth P, Gurbani S, et al. Depression and anxiety dis-orders in pediatric epilepsy. Epilepsia 2005;46:720–30.

5. Harden CL, Goldstein MA. Mood disorders in patients with epi-lepsy:epidemiology and management. CNS Drugs 2002;16:291–302.

6. Baldwin DS. Escitalopram: efficacy and tolerability in the treat-ment of depression. Hosp Med 2002;63:668–71.

7. Johnston JA, Lineberry CG, Ascher JA, et al. A 102-center pro-spective study of seizure in association with bupropion. J Clin Psychiatry 1991;52:450–6.

8. Harris EC,Barraclough B(1997) Suicide as an outcome for mental disorders: A metaanalysis.British Journal of Psychiatry.170:205-28

with epilepsy. A significant proportion of patients with epilepsy and depression are not diagnosed nor offered the appropriate treatment.

Kanner et al determined that 63% of epileptic patients with depression remained symptomatic for one year before treatment was initiated9. It is necessary to screen epileptic patients for depression. The depression scales such as Hospital Anxiety and Depression Scales, Becks Depression inventory or Neurological Disorder Depres-sion Inventory ( NDDI-E ) can be used.

For the treatment of depression in adolescents with epilepsy, pharmacotherapy accompanied by cogni-tive-behavioral approaches in selected children seems to be the most efficacious means of management. SSRIs such as sertraline and fluoxetine were good therapeutic options in terms of remission of depression symptoms and number of side effects3. The SSRIs that seem less likely to inhibit CYP450, and therefore have the least po-tential for interaction with other drugs, including AEDs, are citalopram, escitalopram, and sertraline5,7.

Adverse effects of AED monotherapy or polytherapy in addition to antidepressant medications can complicate the clinical picture and should be taken into account. The risk of seizures is significantly higher with TCAs in comparison with SSRIs and hence TCAs are not recom-mended. Bupropion, has been shown to lower seizure

threshold in a dose-dependent manner8. The case re-port emphasises the need of early diagnosis and treat-ment of underlying depression in patients with epilepsy. Early diagnosis and effective treatment decreases the duration of depression, increase the patients compli-ance with Anti Epileptic Drug and improves the Quality Of Life.

Phenytoin Toxicity in an Adolescent with Epilepsy Following Self Harm – Is Early Detection of Depression Imperative?

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