Senin, 21 Mei 2018

TUGAS REVIEW JURNAL KEPUSTAKAAN BERBASIS BUKTI


TUGAS REVIEW JURNAL 1 KEPUSTAKAAN BERBASIS BUKTI B. INDONESIA (TERAPI AKUPRESUR DAPAT MENURUNKAN KELUHAN MUAL MUNTAH AKUT AKIBAT KEMOTERAPI PADA PASIEN KANKER: RANDOMIZED CLINICAL TRIAL)

Nama peneliti : Hilman Syarif, Elly Nurachmah, Dewi Gayatri



* Review Jurnal
Pada bagian ABSTRAK terdapat kata yang kurang cocok yaitu “penurunan rerata skor mual, muntah, dan mual muntah” menurut saya penggunaan kata “rerata” kurang cocok dengan kalimat tersebut akan lebih baik jika mengunakan kata “rata-rata”.
Pada bagian PENDAHULUAN halaman 134 paragraf ketujuh terdapat kesalahan pengetikan yaitu pada kata “beta endorpin” seharusnya kata yang benar adalah “endorphin”.
Pada bagian METODE halaman 135 paragraf ketiga terdapat kata yang kurang tepat yaitu pada kalimat “berdasarkan penjumlahan hasil isian pasien dan keluarga” menurut saya penggunaan kata “isian” kurang tepat, akan lebih baik jika menggunakan kata “pengisian”.
Pada bagian PEMBAHASAN halaman 137 paragraf kelima terdapat kesalahan pengetikan yang sama seperti pada bagian PENDAHULUAN yaitu pada kata “beta endorpin” seharusnya kata yang benar adalah “endorphin”.


TUGAS REVIEW JURNAL 2 KEPUSTAKAAN BERBASIS BUKTI B. INGGRIS (Pneumococcal vaccination for splenectomized patients with thalassemia major in Indonesia)

Nama peneliti : Teny Tjitra Sari, Arwin Ali P. Akib, Djajadiman Gatot, Alida Roswita Harahap,
Saptawati Bardosono, Sri Rezeki S. Hadinegoro

* Review Jurnal
Pada penelitian ini peneliti menggunakan uji Mann-Whitney U Test dimana uji non parametris yang digunakan untuk mengetahui perbedaan median 2 kelompok bebas apabila skala data variabel terkaitnya adalah ordinal atau interval/ratio tetapi tidak berdistribusi normal.


Jurnal 2




Pneumococcal vaccination for splenectomized patients with thalassemia major in Indonesia

Teny Tjitra Sari a,, Arwin Ali P. Akib a, Djajadiman Gatot a, Alida Roswita Harahap b, Saptawati Bardosono c, Sri Rezeki S. Hadinegoro a

a Department of Child Health, Faculty of Medicine, Universitas Indonesia/Dr. Cipto Mangunkusumo Hospital, Jakarta, Indonesia

b Department of Clinical Pathology, Faculty of Medicine, Universitas Indonesia/Dr. Cipto Mangunkusumo Hospital, Jakarta, Indonesia

c Department of Clinical Nutrition, Faculty of Medicine, Universitas Indonesia/Dr. Cipto Mangunkusumo Hospital, Jakarta, Indonesia



a r t i c l e             i n f o

Article history:

Received 31 March 2017

Received in revised form 25 June 2017 Accepted 3 July 2017 Available online 13 July 2017

Keywords:

Thalassemia

Pneumococcal vaccination


a b s t r a c t

Introduction: Streptococcus pneumoniae is a capsulated bacterium that can cause severe infection in patients with thalassemia major, particularly those who have undergone splenectomy. The absence of the spleen as well as zinc deficiency in splenectomized patients with thalassemia major increases the possibility of developing invasive pneumococcal infection. The aims of this study are to evaluate pneu-mococcal IgG levels following PCV and PPV immunizations and the effect of zinc supplementation on qualitative specific immune responses in splenectomized patients with thalassemia.

Methods: Splenectomized patients with thalassemia major were administered a PCV pneumococcal vac-cine (Prevenar 13 ) at the start of the trial, after which they were randomly assigned to 2 groups (zinc and placebo group). After 8 weeks, the patients received a PPV pneumococcal vaccine (Pneumovax ). Zinc syrup was provided to the zinc group at a dose of 1.5 mg/kg/day (maximum of 50 mg/day). Pneumococcal IgG examinations were conducted at the start of the trial and after 12 weeks.

Results: In the group without PPV, the median initial pneumococcal IgG value was 315 (ranging from 65 to 1419) mU/mL for the zinc group and 338.5 (ranging from 82 to 1648) mU/mL for the placebo group. The median final pneumococcal IgG value was 1812.5 (ranging from 834 to 2444) mU/mL for the zinc group and 2857.5 (ranging from 834 to 2624) for the placebo group. The increase in the pneumococcal IgG value between the two groups was comparable (p = 0.642).

In the group with previous PPV, the median initial pneumococcal IgG value was 1333 (ranging from 793 to 2031) mU/mL for the zinc group and 880 (ranging from 74 to 1686) mU/mL for the placebo group. The median final pneumococcal IgG value was 1487 (ranging from 635 to 1757) mU/mL for the zinc group and 1012 (ranging from 292 to 1732) mU/mL for the placebo group. The increase in the pneumococcal IgG value between the two groups was comparable (p = 0.528).

Conclusion: There is no difference in the increase in pneumococcal IgG level in splenectomized patients with thalassemia major prior to and after receiving PPV. There were no differences observed in the devel-opment of pneumococcal IgG following zinc supplementation.

2017 Elsevier Ltd. All rights reserved.





1. Introduction

Thalassemia is a hereditary anemia that occurs due to a mono-genic disorder causing a defect in globin production [1]. The increased vulnerability of thalassemia patients to infection is attributed to their immune response, which is different from that of normal individuals [2–5].

Streptococcus pneumoniae is a capsulated bacterium that can cause severe infection in patients with thalassemia, particularly

Corresponding author.

E-mail address: t_tjitrasari@yahoo.com (T.T. Sari).

http://dx.doi.org/10.1016/j.vaccine.2017.07.011 0264-410X/ 2017 Elsevier Ltd. All rights reserved.




those who have undergone splenectomy, and it may lead to a high mortality rate. The absence of the spleen as well as zinc deficiency in splenectomized patients with thalassemia major increases the possibility of developing invasive pneumococcal infection [6–8]. In splenectomized patients, the absence of the spleen leads to an inability to activate T cell-independent immune responses in the event of infections or immunization with a capsulated polysaccha-ride antigen such as S. pneumoniae [9]. The Thalassemia Interna-tional Federation (TIF) and various countries recommend providing immunization against S. pneumoniae, H. influenza, and meningococcus at least 2 weeks prior to surgery, followed by

4584                                                                               T.T. Sari et al. / Vaccine 35 (2017) 4583–4586


administration of prophylactic antibiotics to prevent infections fol-lowing splenectomy [10–13]. In Indonesia, a majority of patients with thalassemia scheduled for splenectomy are not provided with immunization or prophylactic antibiotics because of financial lim-itations. Therefore, an effort to increase the immune response of patients with thalassemia is required, particularly following splenectomy.

Several studies show that in when zinc deficiency is present, the process of antibody formation may be disturbed following admin-istration of several vaccines [6,14,15]. Animal studies have attempted to show these disturbances in antibody production fol-lowing administration of pneumococcal vaccines under zinc defi-ciency condition [6].

This study aims to evaluate pneumococcal IgG levels following PCV and PPV immunizations and the effect of zinc supplementa-tion on qualitative specific immune responses in splenectomized patients with thalassemia.



2. Methods

All splenectomized patients with thalassemia major were administered a PCV pneumococcal vaccine (Prevenar 13 ) at the start of the trial. The patients were then randomly assigned into one of two groups (the zinc group and the placebo group). Zinc was provided in syrup form at a dose of 1.5 mg/kg/day, with a maximum of 50 mg/day. The placebo was also provided in syrup form, with similar shape and flavor. Both zinc and placebo syrup were prepared for 4 weeks of consumption. At the end of week 4, all subjects underwent complete physical and hematology examinations.


In week 8, subjects who had not received a PPV vaccine were administered a PPV pneumococcal vaccine (Pneumovax ). Subjects were then discharged home with a 4-week supply of either placebo or zinc syrup, based upon their original group placement.

At the end of Week 12, all the thalassemia subjects under-went a complete history taking, a physical examination, and sup-porting examinations including a peripheral blood examination; peripheral blood smear; and testing for levels of ferritin, trans-ferrin saturation, serum zinc, and pneumococcal IgG. Following data collection, data analysis and interpretation were conducted. Analysis was conducted using the Statistical Package for the Social Sciences (SPSS) version 20.0. Changes in numerical immunologic parameters were analyzed using the independent samples t-test when the data followed normal distribution; the Mann-Whitney test was used if the data did not follow normal distribution.


Pneumococcal IgG levels were measured using the Pneumococ-cus IgG Immunopotency level/E-DG-MZ-001/04-04 kit (ZenTech, Belgium) in the PRODIA Laboratory, Jakarta, with results expressed in milliunit per millilitres (mU/mL). In agreement with the instruc-tions, serum was diluted to 1:510. Titers of anti-PCP IgG antibodies expressed as mU/mL were determined in accordance to the stan-dard serum provided with the kit. Sensitivity of the kit was reported at 6.9 mU/mL. The results (based on the manufacturer) are interpreted as follows: hyporesponsive if <250 mU/mL, and good response or immune to pneumococcal infections if 250 mU/mL. This assay was already validated and used in studies conducted by Jahromi et al. [22] Evaluations of zinc levels were conducted using the Inductive Couple Plasma Mass Spectrometry (ICP/MS) method. Frequency of blood transfusions was classified using the Fucharoen classification [16].


This study was conducted following ethical approval by the Ethics Committee of the Faculty of Medicine, Universitas Indonesia, with ethical approval number 260/H2.F1/ETIK/2013.

3. Results

This study included 56 samples with a median age of 21 years (range 12–38 years) and 56.8% female participants. Characteristic of samples used in this study are shown in Table 1. Most of the samples used had high ferritin levels (median range of 6950.31), with deferiprone as the most frequently used iron chelator. The presence of hepatitis infection in the patient can also be an impor-tant indicator of immune response. In this particular study, 12 patients were identified as having hepatitis B and 22 patients as having hepatitis C; information regarding the presence of cirrhosis was not gathered from the samples. In this study, 50 patients had not received pneumococcal immunization; hence they were given PCV and PPV immunizations. Six patients (4 from the zinc group and 2 from the placebo group) had previously received PPV immu-nization, and they were given only PCV immunization. The pneu-mococcal immunization provided by the hospital to the 6 patients who underwent splenectomy between 2009 and 2013 was the PPV vaccine; this was due to financial limitations of these patients, as PPV is less expensive than PCV.


Majority of the study population (80.4%) possessed low zinc levels, with an average zinc level of 46.46 (±8.86). The effects of zinc supplementation on changes in pneumococcal IgG levels in patients who did not receive previous PPV immunization are pre-sented in Table 2.

Table 2 shows that at the start of the trial, immunity from pneu-mococcal IgG had already been attained (>250 mU/mL) in the group which did not receive PPV. Following immunization, pneu-mococcal IgG levels increased in both groups. Comparison between the zinc and placebo groups showed no significant differences in the increase in pneumococcal IgG following immunization.

The median initial pneumococcal IgG level for the group who had previously received PPV immunization (6 patients) was 1333 (range 793 to 2031) mU/mL for the zinc group (n = 4) and 880 (range 74–1686) mU/mL for the placebo group. The median final pneumococcal IgG level was 1487 (range 635–1757) mU/mL for the zinc group and 1012 (range 292–1732) mU/mL for the placebo group. There was a comparable increase in pneumococcal IgG in the two groups (p = 0.528).

All patients who had previously received a PPV immunization attained protective levels of pneumococcal IgG (>250 mU/mL); however, this generally decreased with an increase in the duration of pneumococcal antibody protection (Table 3).


Table 1

Characteristics of the study population.

Parameters
Number of Subjects (n = 56)


Type of thalassemia

Beta
28
Beta-HbE
28
Nutritional status

Good
26
Undernourished
19
Severely undernourished
11
Frequency of blood transfusions

Seldom (<1 time per year)
3
Sometimes (2–3 times per year)
2
Often (  4 times per year)
51
Type of blood transfusions

PRC
4
Leukodepleted PRC
21
Washed PRC
31
Ferritin (ng/mL)
6950.31 (645–21,835)
Transferrin saturation (%)
94.84 (26–118)
Positive hepatitis markers

Hepatitis B
12
Hepatitis C
22



T.T. Sari et al. / Vaccine 35 (2017) 4583–4586
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Table 2

Effects of zinc supplementation on pneumococcal IgG levels in patients who did not receive previous PPV immunization.


Pneumococcal IgG Levels






Zinc Group
Placebo Group
p-value

(n = 24)
(n = 26)






Median (Range)
Median (Range)

Initial (mU/mL)
315
338.5
0.6761

(65–1419)
(82–1648)

Final (mU/mL)
1,812.5
1857.50


(834–2444)
(652–2624)

p-value2
<0.001
<0.001

Change (mU/mL)
Mean (SD)
Mean (SD)
0.642*

1420.83 (377.32)
1,353.0 (626.09)

Percentage change
Median (Range)
Median (Range)
0.6001

413.50
406.58


(72.23–1935.51)
(  4.79 to 2261.86)

*  Independent samples t-test.

1  Mann-Whitney test.
2  Wilcoxon signed-rank test.

Table 3

Pneumococcal IgG levels in the splenectomized subjects who had previously received PPV immunization.

Patient
Age at PPV
Duration of pneumococcal
Pneumococcal IgG
number
immunization
antibody protection
level (mU/mL)




1
18 years
4 months
793
2
13 years
6 months
1686
3
14 years
9 months
2031
4
19 years
12 months
1859
5
21 years
16 months
807
6
25 years
45 months
74





The duration since splenectomy for the group that had not pre-viously received PPV (50 patients) was 127.5 (53–243) months, whereas that value for the group that had previously received PPV (6 patients) was 17 (11–52) months (p < 0.001). There was no significant correlation between duration since splenectomy and changes in pneumococcal IgG levels (r = 0.222, p = 0.101).

4. Discussion

In this study, patients who did not previously receive PPV immunization were provided with PCV immunization followed by PPV immunization after an interval of 6–8 weeks. On the other hand, patients who had previously received PPV immunization were provided only with PCV immunization, as it had been less than 5 years since their last PPV immunization, in accordance with the guidelines of the Indonesian Society of Pediatricians/Ikatan Dokter Anak Indonesia (IDAI) [17] and the Advisory Committee on Immunization Practices (ACIP) [18]. There were no significant differences in the increase in pneumococcal IgG levels between the patients who did not receive PPV and those who did as well as between the zinc and placebo groups. This study shows that there is no effect on the production of pneumococcal IgG following zinc supplementation, accounting for the fact that a majority of the subjects in this study population also had zinc deficiency. In agree-ment with previous studies [19,20] patients with thalassemia do not experience disturbances in their humoral immunity.


The increase in pneumococcal IgG is higher in subjects who have not previously received PPV, as PCV plays a role in the devel-opment of memory B cells [21]. This can manifest as a high increase in the pneumococcal IgG level (>4-fold) following the administration of PPV. Subjects who have previously received PPV showed a relatively small increase in pneumococcal IgG levels, as pneumococcal IgG levels tend to decrease after the duration of

protection reaches 4 years; this indicates that the PPV vaccine pro-duces only a small amount of memory due to short-term immunity and lack of booster response [19,22]. The administration of PCV will repair the production of memory B cells to maintain immunity against pneumococcus [19].

Only a small percentage of patients (6 out of 56) received PPV immunization prior to splenectomy, and a large majority of the patients had not previously received PPV immunization. Regard-less of this, subjects who have not previously been immunized showed protective levels of pneumococcal IgG (>250 mU/mL), demonstrating possible previous exposure to pneumococcus anti-gen prior to the study. Because of the endemicity of pneumococcus in Indonesia, prior exposure to its antigen can be quite common, thus explaining why some of the samples had protective IgG levels without history of immunization. A 4-fold increase following pneumococcus immunization is considered an adequate antibody formation response, even without a spleen [23].

A study by Orthopoulos et al. [19] shows that the administra-tion of PCV and PPV vaccines to splenectomized patients with tha-lassemia results in an immunological memory similar to that which results from the administration of 2 PCV vaccines with an interval of 1 month. This agrees with a study by Breukels et al.

[24]    which stated that the spleen does not greatly affect the anamnestic response process.

In contrast to a previous study [20], this study did not find a cor-relation between duration since splenectomy and changes in pneu-mococcal IgG levels from baseline. A study by Jahromi et al. [20] measured pneumococcal IgG levels following PPV immunization prior to splenectomy, and found a strong negative correlation between protective pneumococcal IgG levels, and duration since splenectomy (r = 0.863, p = 0.0001).

The study was unable to examine all the factors that may alter the final immune response; presence of hepatitis in some patients may be concomitant with presence of cirrhosis, which in turn may hinder immune response. Because of the limited availability of samples, the study was unable to examine immune response in relationship to gender or age. Age may play an important role, as older patients may have more mature immune systems. Studies with larger samples need to be conducted in the future to find sig-nificant results.

In conclusion, splenectomized patients with administered with PCV 13 would have similar immunological responses compared to non-splenectomized patients, but further studies with healthy control groups are required to confirm the result. Zinc supplemen-tation does not affect the production of pneumococcal IgG.


Conflict of interest

This author declares no conflict of interest.


References



[5]  Ricerca BM, Di Girolamo A, Rund D. Infections in thalassemia and hemoglobinopathies: focus on therapy-related complications. Mediterr J Hematol Infect Dis 2009;1:e2009028. Downloaded on 15 February 2012 from http://www.mjhid.org/article/view/5229.


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[12]  Cappellini MD, Cohen A, Eleftheriou A, Piga A, Porter J, Taher A. Guidelines for the clinical management of thalassaemia. Edisi ke-2. Cyprus: Thalassaemia International Federation; 2008. p.106–20.