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Table 2 Supplementary post-hoc review data

From: The effect of early versus late treatment initiation after diagnosis on the outcomes of patients treated for multidrug-resistant tuberculosis: a systematic review

Author

Journal

Year

Exposure

Outcome

Comments

Goble [38]

NEJM

1993

Duration of disease

Failure: continually positive sputum cultures after at least three months of therapy

Duration of disease very long

1-3 yrs

12/44

4-8 yrs

18/44 OR 1.8 (0.6-5.4)

≥9 yrs

17/46 OR 1.6 (0.5-5.0)

Chan [37]

AJRCCM

2004

Each additional year delay before first visit to site

Initial favourable response: ≥3 negative sputum cultures over ≥3 months

OR 0.93 (0.87-0.995) p=0.03

Median pre-therapy disease duration = 4.2 years; analysis takes no account of time to MDR therapy, just time to first visit

Bonilla [66]

PLoS ONE

2008

 

Treatment success

Paper mainly about individualisation of regimens with DST and availability of 2nd line DST within 31 days; no data on lead-in time from diagnosis and exclusions from primary analyses limit interpretation

MDR DST available within ≤31 days

264/334 (79.0%)

MDR DST available after > 31 days

108/160 (67.5%)

XDR DST available within ≤31 days

11/14 (78.6%)

XDR DST available after > 31 days

7/23 (30.4%)

Dheda [31]

Lancet

2010

Treatment outcome

Delay to treatment

Compared delay to treatment in groups of survivors and non-survivors and culture converters and non-converters.

Delay to treatment = time from sputum acquisition to start of treatment

Survival

78 days [53–107]

Death

57 days [36–67]

p=0·001

Culture conversion

91 days [61–116]

Non-conversion

59 days [43–86]

p=0·001

Heller [45]

IJTLD

2010

 

Median days (95%CI) treatment delay

Before vs. after comparison following change from traditional hospital based management (TM) to community based (CM).

In multivariate analysis time to smear conversion was longer for TM group than for CM group (aHR=1.78, p=0.062), as was time to culture conversion (aHR=1.82, p=0.026)

Traditional (n=46)

106.5 (88.6-151.1)

Community (n=48)

84 (78.7-93.3) p=0.002

 

Median days (95%CI) to smear conversion

Traditional (n=48)

91 (72.2-119.8)

Community (n=32)

59 (34.9-83.1) p=0.055

 

Median days (95%CI) to culture conversion

Traditional (n=53)

119 (106.1-131.9)

Community (n=39)

85 (68.0-102.0)

p=0.002

 

Active and on treatment at 6 months

Traditional

91.2%

Community

84.8%

p=0.4

Seddon [64]

CID

2012

Treatment delay

(not defined)

Not associated with:

[1] failure to culture convert by month 2

(26/74, p=0.25)

[2] unfavourable treatment outcome

(15/103, p=0.36)

[3] death

(8/103, p=0.18)

Median delay 91 days (IQR 51–166)

Data in table 4 – analysis not clear

Van der Walt [13]

ERJ (Conference abstract)

2012

 

Time to treatment

Shorter time to treatment in inpatients but no differences in time to smear or culture conversion

Inpatients

76 days

Community

64 days p<0.01

 

Sputum conversion

Inpatients

54%

Community

52%

 

Time to conversion (median with IQR)

Inpatients

105 (64.5-164)

Community

121 (61.0-206.5)

Loveday [46]

IJTLD

2012

 

Median (IQR) treatment delay in days

Decentralised vs. centralised hospital care. Shorter delay to treatment but worse treatment outcomes for decentralised care, but many other differences in care beyond treatment initiation delay.

Decentralised

72 (56–99)

Centralised

93 (71–120)

p<0.001

 

Unsuccessful treatment outcomes

Decentralised

96/419 (23%)

Centralised

37/441 (8%)

Cox [63]

IJTLD

2014

 

Median (IQR) treatment delay in days

MDR programme implemented. But changes other than treatment initiation delay e.g. change to include moxifloxacin

Before (2005)

58 (25–91) (n=39)

During (2010)

31 (18–45) (n=183)

 

Treatment success

Before (2005–7)

85/206 (41%)

During (2010)

86/164 (52%)

Mpagama [48]

PLoS ONE

2013

Median (range) time from MDR diagnosis to treatment

Outcome

No difference in time from MDR diagnosis to treatment initiation between intensive phase completers and deaths.

272 (26–888)

Completion of intensive phase n=54

255 (193–317)

Died n=4

p=0.8

Chan [50]

PLoS ONE

2013

Delay

Treatment success in 3 models

Multiple logistic analysis

Change to programme management in Taiwan

>120 days

133/194 (69%)

≤120 days

328/457 (72%)

>120 vs.≤120

OR 1.2 (0.8-1.7), p=0.4

Adjusted HRs

0.8 (0.6-0.9), p=0.012

0.8 (0.6-1.0), p=0.018

Delay in 390 patients with second line drug susceptibility testing

 

>120 days

74/117 (63%)

≤120 days

170/273 (62%)

>120 vs. ≤120

OR 1.0 (0.6-1.5), p=0.9

aOR 0.6 (0.4-0.9), p=0.01

Helbling [61]

Swiss Med Wkly

2014

Time to treatment

Treatment success

39/51 (76.5%)

Time to treatment initiation not associated with treatment success in logistic regression model (no data shown)

Median time to initiation was 5.5 weeks but 10 initiated MDR treatment immediately

Kipiani [68]

CID

2014

Line probe assay implementation

Delay to MDR treatment

Before vs. after analysis of line probe assay implementation. Groups differed in many ways – post implementation group had more HCV co-infection, more initial inpatient treatment, more likely to receive kanamycin instead of capreomycin, higher rates on prior MDR treatment, resistant to more drugs.

Pre-implementation

83.9 (56–106)

Post-implementation

18.2 (11–24) p<0.01

(Unclear if overall or just for subset who received first line drugs)

 

12 wk culture conversion

Pre-implementation

5/68 (7%)

Post-implementation

25/51 (49%)

 

24 week culture conversion

Pre-implementation

43/68 (63%)

Post-implementation

44/51 (86%)

p=0.01

 

24 week smear conversion

Pre-implementation

77%

Post-implementation

90%

p=0.05

Li [51]

Lancet Global Health

2015

Programme implementation

Median [IQR] time to treatment

Time to treatment only reported for 32% and 71% of pre- and post-intervention patients

Before

139 [69–207]

After

14 [10–21]

 

Still on treatment at 6 months

Before

8% (2/26)

After

80% (137/172)

Loveday [11]

IJTLD

2015

 

Median (IQR) treatment delay in days

Includes all of Loveday 2012 data plus data for 7 additional months

Decentralised

72 (54–97) (n=724)

Decentralised

72 (54–97) (n=724)

Centralised

92 (69–120) (n=811)

p<0.001

 

Treatment success

Decentralised

427/736 (58%)

Centralised

439/813 (54%) p=0.18

 

Death

Decentralised

133/736 (18.1%)

Centralised

113/813 (13.9%) p=0.21

Otero [22]

TMIH

2015

Treatment outcomes

Median (IQR) time in days to MDR-TB treatment

Should be noted that the duration of treatment prior to switching was undetermined.

For patients starting on MDR regimen:

 

Success

26 (18–41)

Not success

25 (18–30) p=0.6

For patients switching to MDR regimen:

 

Success

11.5 (2–35)

Not success

22 (2–48) p=0.1