An assessment of nucleic acid amplification testing for active mycobacterial infection
Expert advice: Health Expert Standing Panel (HESP)
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- Results of assessment and discussion
- Safety of NAAT
- Is it effective
- Morbidity
- Mortality
- Discussion
Expert advice: Health Expert Standing Panel (HESP)HESP has been established as a panel of the MSAC and is a pool of experts collated from various medical fields who are nominated by their associated professional body or by applicants. HESP members are engaged to provide practical, professional advice to evaluators that directly relates to each application and the service being proposed for the MBS. HESP members are not members of either MSAC or its subcommittees. Their role is limited to providing input and guidance to the assessment groups to ensure that the pathway is clinically relevant and takes into account consumer interests. HESP members’ advice is used to inform the deliberations that MSAC presents to the Federal Minister for Health. Results of assessment and discussionIs it safe?
Studies were screened to assess the safety of NAAT according to criteria outlined a priori in Box 1. Box 1 PICO criteria for studies assessing the safety of NAAT in patients suspected of TB where AFB microscopy is obtained
Safety of NAATNo studies were identified that reported on the safety of NAAT (plus AFB microscopy and/or culture) compared with current testing (AFB microscopy, tissue biopsy and/or culture). As NAAT is usually conducted on the same samples used for other testing, no AEs were expected. To date, NAAT has been widely used without any safety concerns. However, more patients will receive a false-positive NAAT than a false-positive AFB result. Therefore, more patients will receive treatment for a disease they do not have and will possibly have an adverse reaction to the anti-TB drugs until clinical unresponsiveness is noted or culture results become available. Is it effective?Direct evidence of the effectiveness of NAAT in the diagnosis of MTB
Studies were included to assess the effectiveness of NAAT according to the criteria outlined a priori in Box 2. Box 2 PICO criteria for identification of studies relevant to an assessment of effectiveness of NAAT for patients where AFB microscopy is obtained
Two studies were included that assessed the direct health impact of NAAT on suspected TB patients (Theron et al. 2014; Yoon et al. 2012). However, both studies were conducted in a high-prevalence African setting, and so applicability to the Australian healthcare system is questionable. In the absence of studies conducted in a more relevant setting, the study profiles of these two studies are summarised in Table 95 (Appendix F), and an overall summary of the body of evidence is presented in Table 16. Table 16 Body of evidence matrix for studies reporting direct evidence on the effectiveness of NAAT in the diagnosis of MTB
a Level of evidence determined from the NHMRC evidence hierarchy (see Table 13) Source: Adapted from NHMRC (2009) One of the studies was a high-quality multicentre RCT (conducted in South Africa, Zimbabwe, Zambia and Tanzania) with 1,502 participants, who were either assigned to AFB microscopy plus culture (n=758) or Xpert plus culture (n=744). TB-related morbidity and mortality were reported in both groups (Theron et al. 2014). The lack of AFB microscopy in the Xpert plus culture arm of the trial further limits the applicability of the findings to the proposed use of Xpert in Australia. The second study of 477 participants was a historical control study of medium quality with some risk of bias, and was conducted in Uganda (Yoon et al. 2012). This study included consecutive hospitalised Ugandan patients with suspected TB in two phases. In the baseline phase Xpert results were not reported to clinicians, whereas in the implementation phase the results were reported. Two-month mortality was reported and compared between groups. MorbidityTheron et al. (2014) reported comparative morbidity outcomes after NAAT compared with AFB microscopy. In this study AFB microscopy and NAAT (Xpert) were done at point-of-care to assist same-day clinical decision-making and to improve patient retention and clinical outcomes. Thus, both the NAAT results in the intervention group and the AFB microscopy results in the comparator group were available on the same day as specimen collection. Additionally, only about half the patients who initiated treatment did so on the basis of a positive Xpert result. TB-related morbidity was graded using the TBscore (range 0–13) (Wejse et al. 2008) and the Karnofsky performance score (KPS). The KPS subjectively rates the patient’s performance according to their ability to perform normal daily activities, ability to work, assistance needs, and disease-related symptoms on a scale from 0% to 100% (Rudolf et al. 2013). Morbidity was measured at baseline and at 2 and 6 months. The results are shown in Table 17. Table 17 TB-related morbidity at recruitment, 2 months and 6 months, according to baseline culture status in patients given anti-TB treatment, per group
AFB = acid-fast bacilli; KPS = Karnofsky performance score, 0–100% = with 0% being dead, < 40% = unable to care for self and requires equivalent of institutional or hospital care, 50–70% = unable to work but able to live at home and care for most personal needs, = 80–90% able to carry on normal activity and to work, 100% = being normal with no signs of disease; NAAT = nucleic acid amplification testing; TB = tuberculosis; TBscore = score 0–13 based on the 13 clinical indications, each contributing 1 point, normal values are scored as zero a 87 (57%) of the AFB microscopy group vs 108 (64%) of 168 in the NAAT group were followed up within 2 weeks (p=0.170); of the patients who were not followed up within 2 weeks, 11 (17%) of 66 vs 6 (10%) of 60 had died (p=0.274), and 33 (50%) of 66 vs 36 (60%) of 60 were followed up > 2 weeks before/after the specified date (p=0.260). b 96 (56%) of 170 of the AFB microscopy group vs 88 (58%) of 151 in the NAAT group were followed up within 2 weeks (p=0.74); of the patients who were not followed up within 2 weeks, 15 (20%) of 74 vs 8 (13%) of 63 had died (p=0.237), and 22 (30%) of 74 vs 21 (33%) of 63 were followed up > 2 weeks before/after the specified date (p=0.651). c 81 (53%) of 153 of the AFB microscopy group vs 97 (58%) of 168 in the NAAT group were followed up within 2 weeks (p=0.39); of the patients who were not followed up within 2 weeks, 14 (19%) of 72 vs 14 (20%) of 71 had died (p=0.967), and 23 (32%) of 72 vs 23 (33%) of 71 were followed up > 2 weeks before/after the specified date (p=0.954). d 86 (51%) of 170 of the AFB microscopy group vs 71 (47%) of 151 in the NAAT group were followed up within 2 weeks (p=0.52); of the patients who were not followed up within 2 weeks, 21 (25%) of 84 vs 14 (18%) of 80 had died (p=0.241), and 28 (33%) of 84 vs 28 (35%) of 80 were followed up > 2 weeks before/after the specified date (p=0.822). Source: Theron et al. (2014) TBscores at baseline and at 2 months and 6 months follow-up were similar in both groups (Table 17). When both tests were compared there were no differences reported in the median per-patient change in TBscore or KPS. The proportion of patients with a > 25% decrease in TBscore or KPS from recruitment to 2 and 6 months follow-up also did not differ.
Table 18 Mortality after NAAT versus no NAAT
Comparator for Theron et al. (2014) was AFB microscopy Comparator for Yoon et al. (2012) was a historical control group DiscussionThere was little difference in the observed mortality and morbidity rates when the diagnosis of TB included the use of NAAT compared with no NAAT for patients in these two studies. The RCT showed a trend towards improved mortality rate with the use of NAAT at 2 months but this trend was not observed at 6 months. Both these studies were conducted in countries with a high prevalence of TB. The authors from both studies postulated various reasons for this general lack of effect on morbidity and/or mortality despite improved TB diagnosis and treatment initiation in the NAAT groups compared with the comparator groups. Theron et al. (2014) suggested that the potential long-term epidemiological effect of NAAT was probably underestimated in their study because of high levels of treatment initiation in AFB-negative patients in the comparator group. It should also be noted that while 112 NAAT-positive patients out of a total of 170 culture-positive (eventually treated) patients (66%) started treatment on the same day, the availability of same-day AFB microscopy results in the comparator group resulted in 67 AFB-positive patients out of 154 culture-positive (eventually treated) patients (44%) also starting treatment on the same day. This approximate 20% difference in treatment initiation between groups is unlikely to be reflected in treatment initiation rates in Australia because NAAT is suggested to be used as an adjunct to AFB testing. The incremental impact of NAAT over current testing practice in Australia, and the impact on patient morbidity and mortality, cannot be estimated from the study by Theron et al. (2014). Yoon et al. (2012) suggested that the lack of effect on 2-month mortality in their study may be due to several factors, including insufficient powering to detect small differences in mortality rates between groups, a significantly higher proportion of patients in the baseline phase receiving empiric TB treatment compared with the implementation phase, and more patients presenting with increased disease severity in the implementation phase than in the baseline phase. Thus, the authors concluded that the higher rates of empiric TB treatment in the baseline phase and sicker patients in the implementation phase may have attenuated the 2-month mortality in the implementation group. Due to the limited evidence provided by these two studies, a linked evidence approach was taken to inform this assessment. Directory: internet internet -> Applications and limitations internet -> L. and Gossypium barbadense internet -> Natural Resources Conservation Service Conservation Practice Standard internet -> Practice Exercise Created By Stavros Charalambous The Internet internet -> It’s a good Topic internet -> National Preventative Health Strategy – the roadmap for action internet -> Downloading gps gr-3 Surveys Summary of Procedure internet -> 3G300m-how to setup the 3g router Mode? Product line: 3g question categories: Function configurations Note internet -> Installation Work has never been simpler or easier Download 12.08 Mb. Share with your friends:
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