Time to Sputum Culture Conversion, identifying independent modifiable risk factors

Transcription

1 SOA Time to Sputum Culture Conversion, identifying independent modifiable risk factors Nikhil Gupte, PhD Union 2018

2 Background and Rationale Time to sputum culture conversion is widely used surrogate marker in early phase clinical trials Delayed sputum culture conversion may be associated with poor TB treatment outcome Time to sputum culture conversion, associated risk factors among drug sensitive pulmonary tuberculosis (PTB) have not been adequately documented Clinical, sociodemographic and phycosocial characteristics that may influence time to sputum culture conversion may be helpful Characterizing factors associated with delayed time to sputum culture may help targeting risk groups to optimize favourable TB treatment outcome.

3 Methods 330 Adults ( 18 years), drug sensitive PTB patients from Pune and Chennai CTRIUMPh Study sites Sputum culture on LowensteinJensen medium was done at entry, and weeks: 2, 4, 8, 16, 24 and 72. Sociodemographic, behavioural and clinical data was collected at baseline and followup visits using structured case report forms Time (in days) to first negative sputum culture, from AKT start date, was calculated KaplanMeier product limit estimator was used to estimate the time to sputum culture conversion Cox Proportional hazards models were used to identify independent and overlapping risk factors

4 Selected baseline characteristics & KM Curve Baseline Characteristics Age Group < > 50 Gender Male Female BMI Normal Underweight Overweight Residence Rural Smoking Never Current Former Smokeless tobacco No Yes N n = (22%) 109 (33%) 80 (24%) 70 (21%) 222 (67%) 108 (33%) 109 (34%) 198 (61%) 18 (6%) 176 (53%) 154 (47%) 189 (62%) 47 (15%) 71 (23%) 85 (26%) 238 (74%) Baseline Characteristics AUDIT < 8 > 8 DM No DM Pre DM DM Smear Baseline Negative Positive Cavitation No Yes HIV Uninfected Infected TB Treatment Daily Thrice Weekly N n = (63%) 121 (37%) 108 (37%) 73 (25%) 110 (38%) 87 (27%) 240 (73%) 144 (52%) 133 (48%) 319 (97%) 11 (3%) 1 (0.3) 328 (99.7%) Proportion Culture Positive Number at risk Time to LJ Sputum Culture Negative Followup time (Days) Time to culture conversion Median (IQR): 35 (32 43)

5 Exploratory & Univariable Analysis Baseline Characteristics Median ꝉ (IQR) logrank p value uhr (95% CI) pvalue Baseline Characteristics Median ꝉ (IQR) logrank p value uhr (95% CI) pvalue Age Group < > 50 Gender Male Female BMI Normal Underweight Overweight Residence Rural Anaemia No Yes 29 (16 57) 33 (24 63) 36 (29 65) 58 (30 64) 39 (29 64) 31 (16 62) 34 (21 64) 37 (27 64) 31 (17 60) 61 (32 65) 27 (15 51) 32 (21 60) 42 (27 64) Ref 0.68 ( ) 0.62 ( ) 0.57 ( ) Ref 1.44 ( ) 0.05 Ref 0.88 ( ) 1.56 ( ) < Ref 1.85 ( ) Ref 0.66 ( ) < Smoking Never Current Former 32 (16 62) 55 (31 64) 62 (68 31) Smokeless tobacco No 31 (16 59) Yes 46 (29 64) AUDIT < 8 > 8 DM No DM Pre DM DM Smear Baseline Negative Positive Cavitation No Yes 21 (17 62) 58 (31 71) 31 (17 58) 35 (16 64) 39 (29 64) 29 (16 39) 55 (29 64) 32 (21 62) 51 (30 64) < Ref 0.63 ( ) 0.58 ( ) 0.04 Ref 1.30 ( ) < Ref 0.57 ( ) 0.04 Ref 0.73 ( ) 0.72 ( ) < Ref 0.53 ( ) 0.03 Ref 0.77 ( ) Ref 0.01 < < < Findings: Older age, Males, Rural residence, Anaemia, Smoker, Alcohol dependence, Diabetes, AFB Positive & Cavitation were at an increased risk of delayed sputum culture conversion

6 Alcohol use disorder, anaemia & smear positivity are independently associated with high risk of delayed culture conversion

7 Rural residence, smear positive and high AUDIT score are affected most! Rural Positive N F RHR Audit > Audit < Smear Negative Smoker Anemia BMI Anemia No Anemia Smoking NonSmoker

8 Differences in overlapping factors by gender Rural, alcoholic males at increased risk Anaemia in rural females increases risk N F RHR N F RHR Positive Audit > 8 Audit HB Rural HB Rural < 8 HB Smear Negative HB age

9 Smoking & Alcohol dependence among males is independently associated with time to sputum culture conversion Males Females

10 Conclusions Smoking and alcohol consumption increased the risk of longer time to sputum culture conversion by approximately 40% Male gender, alcohol and smoking, young age and rural residence were associated with longer time to culture conversion, thus are transmitting longer, more likely to have unfavourable outcomes Anaemia among AFB smear positive women in rural areas may be associated with longer time to culture conversion

11 Thank You CTRIUMPh Study teams Study participant & their families