Study reference

Study characteristics

Patient characteristics ²

Intervention (I)

Comparison / control (C) ³

Follow-up

Outcome measures and effect size ⁴

Chen, 2006

Type of study: RCT

Setting and country: Hospital, Taiwan

Funding and conflicts of interest: no conflict of interest

Inclusion criteria: All patients requiring VATS caused by ipsilateral recurrence, continuous air leaks for more than 3 d, contralateral recurrence, presence of hemopneumothorax, or uncomplicated first episode with high-risk profession were eligible for this study

Exclusion criteria: greater than 50 yr of age, underlying pulmonary disease, previous ipsilateral thoracic operation, allergy to tetracycline or minocycline, and unwillingness to undergo randomization.

N total at baseline:

Intervention: 103

Control:99

Important prognostic factors²:

age ± SD:

I: 23.7 ± 7.7

C: 25.5 ± 9.0

Sex:

I: 86.4% M

C: 89.9% M

Smoking:

I: 24.3%

CL 32.2%

Groups comparable at baseline? yes

Describe intervention (treatment/procedure/test):

In the minocycline group, 20 ml of 2% lidocaine

hydrochloride (400 mg) followed by a solution of 20 ml of normal saline containing 300 or 400 mg (7 mg/kg) of minocycline

was instilled into the pleural cavity through the thoracostomy tube. The rubber tube connecting

the chest tube and chest bottle was raised 40 to 60 cm above the patient to trap the minocycline while allowing air to pass under pressure. Patients were repositioned every 30 min so that the minocycline could

contact all pleural surfaces. Side effects and complaints of the patient were recorded. The rubber tube was lowered 6 to 8 h later. To optimize the effects of pleural symphysis, minocycline was administered after full expansion of the lung, which was usually accomplished

on the first postoperative day. However, in those patients who had

persistent air leaks and could not fully inflate their lung, minocycline

was still used after 3 to 5 d of waiting.

Describe control (treatment/procedure/test):

Nothing was instilled. A blinded study conducted by saline instillation was not

suitable in our experiment.

Length of follow-up: 6 months

Loss-to-follow-up:

No lost to follow-up

Outcome measures and effect size (include 95%CI and p-value if available):

Recurrence

I:2 (1.9)

C:8 (8.1)

P=0.06

Complications:

I: 6 (5.8)

C: 11 (11.1)

P=0.62

Postoperative pain, day 3:

I: 3.4 (3.1–3.6)

C: 3.6 (3.3–3.8)

P=0.20

Hospital stay:

I: 4.0 ± 1.6

C: 4.3 ± 2.8

P=0.42

Chung, 2008

Type of study: RCT

Setting and country: Hospital, Korea

Funding and conflicts of interest: not decribed

Inclusion criteria: PSP with pleural/subpleural blebs identified by thoracoscopic examination

Exclusion criteria: underlying lung disease, trauma or iatrogenic injury.

N total at baseline:

Intervention-1 (dextrose): 49

Intervention-2 (dextrose + talc): 42

Control: 50

Important prognostic factors²:

For example

age (range):

I1: 24.18 (16-45)

I2: 23.02 (15-65)

C: 22.26 (13-36)

Sex:

I: 93.9% M

I2: 100%

C: 92% M

Groups comparable at baseline? yes

Describe intervention (treatment/procedure/test):

TBR and pleurodesis with

a 20% dextrose solution (200 cc) (49 patients; group 1), and TBR and pleurodesis with a talc (2 g of asbestos free sterilized talc powder) -20% dextrose mixed solution (200 cc) (42 patients; group 2).

Describe control (treatment/procedure/test):

thoracoscopic bleb resection or electrical coagulation

(TBR) only

Length of follow-up (months):

I1: 23.65±2.51

12: 17.93± 3.64

C: 20.22±9.71

Loss-to-follow-up:

No lost to follow up.

Outcome measures and effect size (include 95%CI and p-value if available):

Recurrence

I1: 2.04% (N=1)

I2: 2.38% (N=1)

C: 6% (N=3)

P=0.50

Fever

I1: 22.45% (N=11)

I2: 52.38% (N=22)

C: 10% (N=5)

P=0.0

Parenteral analgesics (frequencies/patient):

I1: 3.42±3.48

I2: 5.02±2.72

C: 2.37±3.51

P=0.00

Hospital stay:

I1: 4.49±2.10

I2: 6.00±2.58

C: 4.50±1.85

P=0.001

Rena, 2008

Type of study: RCT

Setting and country: Hospital, Italy

Funding and conflicts of interest: no conflict of interest

Inclusion criteria: aged 40 yrs affected by recurrent or persistent PSP (air leak from the pleural drainage at first episode persisting for.5 days),

Exclusion criteria: -

N total at baseline:

Intervention: 112

Control: 108

Important prognostic factors²:

age ± SD:

I: 24.5 ± 6.89

C: 25 ± 6.51

Sex:

I: 79.3% M

C: 83.3% M

Smoker:

I: 43.3%

C: 49.5%

Groups comparable at baseline? yes

Describe intervention (treatment/procedure/test):

Mechanical pleural abrasion using a MarlexTM

mesh attached to the tip of a standard endoscopic grasper; abrasion was stopped when a uniform aspect of bloody pleura was

obtained.

Intervention was carried out from the fifth rib, either

on the left side up to the level of the subclavian artery or on the right side up to the brachiocephalic trunk; the front and rear limits were 1 cm laterally from the sympathetic nerve chain and 1 cm laterally from the internal mammalian artery, respectively.

Describe control (treatment/procedure/test):

 Parietal pleurectomy: the portion of pleural surface submitted to surgical pleurodesis was the same for the two groups, in order

to permit successive comparison.

Intervention was carried out from the fifth rib, either

on the left side up to the level of the subclavian artery or on the right side up to the brachiocephalic trunk; the front and rear limits were 1 cm laterally from the sympathetic nerve chain and 1 cm laterally from the internal mammalian artery, respectively.

Length of follow-up: 24-66 months

Loss-to-follow-up:

After the first 24 months of the follow-up period, 25 (18.8%)

patients in the intervention and 18 (16.7%) from the control group could not be tracked down.

Outcome measures and effect size (include 95%CI and p-value if available):

Recurrence

I: 7 (6.2%)

C: 5 (16.7%)

P=0.82

Complications, persistent air leak:

I: 6/112 (5.3%)

C: 6/108 (5.5%)

Postoperative pain (long term, 180 days):

I: 0.31± 0.64

C:0.58 ± 0.61

P=0.001

Reintervention:

I: n=1

C: n=1

Hospital stay:

I: 3.52 ± 1.55 days

C: 3.89 ± 1.71 days

p=0.08

Chen 2012

Type of study: RCT

Setting and country: Hospital, Taiwan

Funding and conflicts of interest: no conflict of interest

Inclusion criteria: Patients requiring VATS for ipsilateral recurrence, continuous air leaks for 3 or more days, or contralateral recurrence were selected for this study. Only patients with multiple blebs (≥3) or no identifiable bleb were eligible for this trial because previous studies showed that these patients are associated with higher rates of recurrence after VATS.

Exclusion criteria: older than 50 years, underlying pulmonary

disease, pneumothorax requiring bilateral VATS, previous ipsilateral

thoracic operation, and allergy to tetracycline or minocycline

N total at baseline:

Intervention: 80

Control: 80

Important prognostic factors²:

age ± SD:

I: 24.3 ± 8.7

C: 22.9 ± 7.2

Sex:

I: 86.3 % M

C: 90.0 % M

Smoking:

I: 18.8%

C: 16.3%

Groups comparable at baseline? yes

Describe intervention (treatment/procedure/test):

Pleurectomy:

For thoracoscopic apical pleurectomy, the inferior border of the pleural strip was marked by endohook electrocautery at the upper

margin of the fifth or sixth rib. The dissection was made in an apical direction. The longitudinal limit of the resection ran along the sympathetic trunk posteriorly and the internal mammary artery anteriorly to the height of the left subclavian artery on the left side or the brachiocephalic trunk on the right side

Describe control (treatment/procedure/test):

Abrasion + minoclyciline:

For thoracoscopic pleural abrasion, the parietal surface above the sixth rib was abraded by inserting the

curved dissector with a diathermy scratch pad. Abrasion was stopped

when a uniform aspect of bloody pleura was obtained.

Length of follow-up: mean: 26.1 months

Loss-to-follow-up:

No lost to follow up at 12 months

Outcome measures and effect size (include 95%CI and p-value if available):

Recurrence

I: 3 (3.8)

C: 3 (3.8)

P=1.0

Complications:

I: 6 (7.5)

C: 4 (5.0)

P=0.75

Postoperative pain (day 3):

I: 3.0 (1–7)

C: 3.4 (2–7)

P=0.09

Hospital stay:

I: 3.6 ± 1.2

C: 3.6 ± 1.3

P=0.81

Min 2014

Type of study: RCT

Setting and country: Hospital, China

Funding and conflicts of interest: no conflict of interest

Inclusion criteria: obvious bullae on PSP lines, or whose pneumothorax lines were rough and interrupted, with or without thoracentesis or thoracic closed drainage; lung collapse exceeded 30% estimated by chest X-ray for the first incidence of pneumothorax; between the ages of 14 and 40 years with normal vital signs and normal routine laboratory findings; written informed consent after reviewing the substance, significance, and risks of the

study.

Exclusion criteria: patients who

refused VATS or refused follow-up or

follow-up less than 6 months; postoperative recurrent PSP;

SSP including those caused by emphysema, chronic obstructive pulmonary disease, asthma, pulmonary lymphangiomyomatosis, thoracic injury, and other diseases; and inability to provide informed consent.

N total at baseline:

Intervention: 145

Control: 144

Important prognostic factors²:

age ± SD:

I: 22 ± 5

C: 22 ± 5

Sex:

I: 90.3 % M

C: 89.6 % M

Groups comparable at baseline? yes

Describe intervention (treatment/procedure/test):

Wedge resection + mechanical abrasion: Mechanical pleurodesis was performed by pleural abrasion and consistent techniques for pleural abrasion were maintained with regard to the extent and aggressiveness of abrasion. The mesothelial

layer of the parietal pleura from the cupola of the apex

of the thoracic cavity to the fifth intercostal space was

abraded using sterile sandpaper until slight bleeding occurred diffusely in the abrasion area

Describe control (treatment/procedure/test):

Wedge resection: Wedge resection using a linear

endoscopic stapler (Covidien Surgical, Mansfield, MA)

included not only targeted bullae but also surrounding

degenerated areas

Length of follow-up: > 6 months, mean follow up: 18 months (range 6-24).

Loss-to-follow-up:

Six patients in the treatment group and 7 in the control group

dropped out of the trial owing to loss of follow-up; 2 patients in the control group were verified pathologically to be complicated with tuberculosis and 1 pulmonary

lymphangiomyomatosis thereafter.

Outcome measures and effect size (include 95%CI and p-value if available):

Recurrence

I: 8 (5.5%)

C: 9 (6.3%)

P=0.79

Hospital stay:

I: 10 ± 4

C: 10 ± 2

P=0.49

Lee 2014

Type of study: RCT

Setting and country: Hospital, Korea

Funding and conflicts of interest: No conflict of interest

Inclusion criteria: ipsilateral or bilateral recurrent pneumothorax, history of previous contralateral

pneumothorax, visible blebs on the initial plain chest film or computed tomography, persistent air leakage for at least 5 days, and age 15 to 35 years.

Exclusion criteria: underlying pulmonary disease such as pulmonary tuberculosis, previous ipsilateral thoracic operation, and

refusal of the study.

N total at baseline:

Intervention: 757

Control: 657

Important prognostic factors²:

age ± SD:

I: 20.7 ± 5.21

C: 20.9 ± 5.08

Sex:

I: 92% M

C: 91% M

Current smoker

I:29.1%

C: 30.8%

Groups comparable at baseline? Yes

Describe intervention (treatment/procedure/test):

Additional coverage procedure on

the staple line:

For the coverage group, inflated lungs 3 cm all around the staple line were covered with absorbable cellulose mesh and then

fibrin glue was sprayed on the mesh.

Describe control (treatment/procedure/test):

Pleurodesis:

mechanical pleurodesis was

performed by scrubbing the parietal pleura with

sandpaper and gauze until uniform blood oozing of the

pleura was confirmed. The pleural abrasion was limited

from the apex down to the fifth intercostal space.

Length of follow-up: 12 months

Loss-to-follow-up:

Patients with follow up < 1 year were excluded.

Outcome measures and effect size (include 95%CI and p-value if available):

Recurrence

I: 99 (13.8%)

C: 93 (14.2%)

Complications:

I:38 (5.1%)

C: 37 (5.6%)

P=0.66

Pain free:

I: 465 (61.4%)

C: 320 (48.5%)

Reintervention:

I: 40 (40.4%)

C: 35 (37.6%)

Hospital stay:

I: 3.4 ± 1.96

C: 3.4 ± 1.75

P=0.92

Study reference

Describe method of randomisation¹

Bias due to inadequate concealment of allocation?²

(unlikely/likely/unclear)

Bias due to inadequate blinding of participants to treatment allocation?³

(unlikely/likely/unclear)

Bias due to inadequate blinding of care providers to treatment allocation?³

(unlikely/likely/unclear)

Bias due to inadequate blinding of outcome assessors to treatment allocation?³

(unlikely/likely/unclear)

Bias due to selective outcome reporting on basis of the results?⁴

(unlikely/likely/unclear)

Bias due to loss to follow-up?⁵

(unlikely/likely/unclear)

Bias due to violation of

intention to treat analysis?⁶

(unlikely/likely/unclear)

Chen, 2006

Randomization was accomplished according to the chart number, which was randomly assigned. If the number was even, the patient was allocated to the minocycline group.

Unlikely

Likely

Participants were not blinded.

Likely

Care providers were not blinded.

Unlikely

Unlikely

Unlikely

Unlikely

Chung, 2008

The allocation of the patients was conducted by the fixed date.

Unclear

Unclear

Blinding was not described.

Likely

Care providers were not blinded.

Unclear

Blinding was not described.

Unclear

Blinding was not described.

Unlikely

Unlikely

Rena, 2008

Method not described

Unclear

Unclear

Blinding was not described.

Likely

Care providers were not blinded.

Unclear

Blinding was not described.

Unclear

Blinding was not described.

Unlikely

Dropout was comparable in both groups.

Unlikely

Chen, 2012

Randomization was accomplished according to random numbers in sealed envelopes, which were opened before each thoracoscopic pleurodesis

Unlikely

Likely

Participants were not blinded.

Likely

Care providers were not blinded.

Unlikely

Unlikely

Unlikely

Unlikely

Min, 2014

computer-generated randomization concealed in a sealed envelope until the day of operation.

Unlikely

Likely

Participants were not blinded.

Likely

Care providers were not blinded.

Unlikely

Unlikely

Unlikely

Unlikely

Lee, 2014

An envelope containing a random number was opened for each patient

Unlikely

Unclear

Blinding was not described.

Likely

Care providers were not blinded.

Unclear

Blinding was not described.

Unlikely

Unlikely

Unlikely