Jurnal Reading Anak

Oleh : ELSYA APRILIA1102010088

Preseptor : dr. Tuty Rahayu, Sp. A

Journal ReadingA Prospective Randomly Controlled Clinical Trial

On Azithromycin Therapy For Induction Treatment Of Children With Nephrotic Syndrome

`Bili Zhang & Tao Li u & Wenhong Wang & Xuan Zhang & Shuying Fan & Zhufeng Liu & Zhe Liu & Xia Wu

Introduction

Sindrom nefrotik 90% PNS

Hasil pengobata

n

Respond glucocorticoid

SNRS •Frequent relaps•Steroid dependence

• antibiotik macrolida generasi kedua

• anti inflamasi dan imunomodulator

• asma, cystic fibrosis (CF), panbronchiolitis difus (DPB), penyakit paru obstruktif kronik, sinusitis kronis, dan penyakit radang usus

Primary Nefrotic Syndrome

Protein urin 24-jam ≥50 mg / kg,

Kadar albumin serum ≤25 g / L, dan

Tidak ada faktor sekunder lainnya

Pasien tidak memiliki riwayat keluarga penyakit ginjal dan tidak kehilangan pendengaran sensorineural dan lesi mata

Methode – Patients The patients were admitted to the hospital between November 2009 and May 2012

Kriteria inklusi• Must have PNS;• Are treated with GC for the first time; • Have not previously received other

special medications;• Have normal blood, liver, and renal

functions;• Have no infection in the lower

respiratory tract, gastrointestinal tract, urinary tract, skin, and so on;

• Have no clinical signs (fever, expectoration, chest pain, rash, frequent urination, urgency, dysuria, vomiting, diarrhea, and so on);

• Have normal white blood cell count and classification;

• Have been subjected to negative enzyme-linked immunospot assay for tuberculosis and the purified protein derivative (PPD) test

Kriteria eksklusi• Glomerula rhematuria, in which red

blood cells were more than ten cells per HPF after routine urinalysis of more than three times in 2 weeks;

• Repeated or sustained hypertension • impaired renal function except for

hypovolemia-induced renal insufficiency;

• hypocomplementemia (complement 3< 600 mg/dL); severe infections after plus oral GC treatment;

• Received a lesser amount of AZM than that required in a course

Eligible patients

Dikategorikan

intervention and

control groups

Komite etik rumah sakit menyetujui

protokol penelitian

informed consent pada

orang tua pasien

2,5 mg setiap 2 minggu sampai

withdrawl

Dosis turun 5 mg setiap2 minggu

sampai 30 mg

1,5 mg/kg/hari (Max 60 mg/hari)

[4 minggu]

2 mg/kg/hari (Max 60

mg/hari) [4 minggu]

kelompok intervensi diobati dengan prednison oral dan AZM (Zithromax, Pfizer, New York, USA) dengan dosis 10 mg / kg / 1 dosis per hari) dalam 3 hari

Detection and Observation indicators

Blood total protein (tp)

Albumin (alb)

Total cholesterol (tcho)

Blood urea nitrogen (bun)

Serum creatinine (scr)

Immunoglobulin (igA, igG, igM, igE)

Complement (C3, C4)

24-h urinary protein (24-h-upro)

Respond to the treatment

Completed Remission

Partial Remission

Non-Remission

SNRS

Relapse

FRNS

Result

Relaps Rate - Duration of Remission

Steroid-resistant rate

Biopsy

Intervention group : minimal change nephrotic syndrome (MCNS) (udia 7th)

Control group : 2 with MCNS and 1 with focal segmental glomerulosclerosis (FSGS) (Usia

2,4,130

8-Weeks FU PeriodNo difference was found in steroid resistance between two groups (1/95 vs. 3/98, p =0.327).

4-weeks FU PeriodPersistent proteinuria of 1+ to

3+Interventions group 1/95

patients (1.05%)Control group 10 of the 98

patients (10.20 %)

Kesimpulan AZM combined with prednisone therapy is more effective in preventing relapses than prednisone therapy alone.

Relapse-free survival different between the two groups, at 3 months (11.6 vs. 21.4 %).

Relapse rate was lower in the intervention group than that in the control group.

No difference in the relapse rate was observed between the two groups within 4 to 6 months and at 6 months of therapy.

The effective rate in the AZM group (68.54 %) was significantly higher than that in the nonAZM group

Critical Appraisal

1a. Was the assignment of patients to treatments randomised?

Pada halaman 510 bagian introductions disebutkan

“We conducted a single-centered, prospective, and randomly controlled trial to compare the efficacy of AZM combined with GC therapy with that of GC therapy

alone in children with PNS to provide a reference for AZM use in GC induction treatment.”

1b. Were the groups similar at the start of the trial?

Pada halaman 510 bagian patients disebutkan kriteria inklusi dan eksklusi untuk

kedua pasien

2a. Aside from the allocated treatment, were groups treated equally?

Pada halaman 510 bagian study intervention and follow

up disebutkan

2b. Were all patients who entered the trial accounted for? – and were they analysed in the groups to which they were randomised?

Pada halaman 511 bagian patient characteristics disebutkan “Among the 211 randomly selected

patients with PNS in this study, 106 were treated with prednisone and AZM (the intervention group),

whereas 105 patients were treated with prednisone alone (the control group). A total of 21 patients did not

survive until the follow-up period because of them, 15 discontinued return visits and 6 had a transient

hypocomplementemia (Fig. 1).

3. Were measures objective or were the patients and clinicians kept “blind” to which treatment was being received?

• Tidak

What were the results?

KelompokKejadian Relaps

TotalNo Relaps Relaps

Intervention 81 (a) 13 (b) 94Control 24 (c) 24 (d) 96

  105 37  

How large was the treatment effect?Experimental Event Rate (EER) :

 Control Event Rate (CER) :

Relative Risk (RR) :

Relative Risk Reduction (RRR) :

  Absolute Risk Reduction (ARR) :

 Number Needed to Treat (NNT) :

How precise was the estimate of the treatment effect?

At 4 weeks in the follow-up period, 94 of the 95 patients in the intervention group and 88 of the 98 patients in the

control group achieved remission. The median

duration to remission was 6 days (95 % confidence

interval (CI) 5.69, 6.41) in the intervention group and 9 days

(95 % CI 8.36, 9.64) in the control group (log-rank value 61.132, p <0.0001) (Fig. 2).

Will the results help me in caring for my patient? (External Validity/Applicability)

Is my patient so different to those in the study that the results cannot apply?

Pasien yang saya temukan tidak jauh berbeda dengan kriteria pada pasien jurnal tersebut sehingga pemberian Azytromycin dapat diberikan kepada pasien saya.

Is the treatment feasible in my setting?

Ya, Azytromycin terdapat di apotik di kota saya.

Will the potential benefits of treatment outweigh the potential harms of treatment for my patient?

Makrolida dosis rendah dilaporkan memiliki efek pada sistem kekebalan tubuh dan peradangan.

Tergantung pada sistem yang sedang dipelajari, efek ini mencakup kemampuan untuk menekan produksi dan sekresi sitokin proinflamasi, menurunkan sintesis dan sekresi lendir; mempromosikan apoptosis sel inflamasi

dan menurunkan produksi faktor transkripsi nuklir