High-dose rifamycins in the treatment of TB: a systematic review and meta-analysis

BackgroundThere is growing interest in using high-dose rifamycin (HDR) regimens in TB treatment, but the safety and efficacy of HDR regimens remain uncertain. We performed a systematic review and meta-analysis comparing HDR to standard-dose rifamycin (SDR) regimens.MethodsWe searched MEDLINE, Embase, CENTRAL, Cochrane Database of Systematic Reviews and clinicaltrials.gov for prospective studies comparing daily therapy with HDRs to SDRs. Rifamycins included rifampicin, rifapentine and rifabutin. Our primary outcome was the rate of severe adverse events (SAEs), with secondary outcomes of death, all adverse events, SAE by organ and efficacy outcomes of 2-month culture conversion and relapse. This study was prospectively registered in the International Prospective Register of Systematic Reviews (CRD42020142519).ResultsWe identified 9057 articles and included 13 studies with 6168 participants contributing 7930 person-years (PY) of follow-up (HDR: 3535 participants, 4387 PY; SDR: 2633 participants, 3543 PY). We found no significant difference in the pooled incidence rate ratio (IRR) of SAE between HDR and SDR (IRR 1.00, 95% CI 0.82 to 1.23, I2=41%). There was no significant difference when analysis was limited to SAE possibly, probably or likely medication-related (IRR 1.07, 95% CI 0.82 to 1.41, I2=0%); studies with low risk of bias (IRR 0.98, 95% CI 0.79 to 1.20, I2=44%); or studies using rifampicin (IRR 1.00, 95% CI 0. 0.75–1.32, I2=38%). No significant differences were noted in pooled outcomes of death, 2-month culture conversion and relapse.ConclusionsHDRs were not associated with a significant difference in SAEs, 2-month culture conversion or death. Further studies are required to identify specific groups who may benefit from HDR.

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Efficacy and safety of pharmacological cachexia interventions: systematic review and network meta-analysis

BMJ Supportive & Palliative Care ◽

10.1136/bmjspcare-2020-002601 ◽

2020 ◽

pp. bmjspcare-2020-002601

Author(s):

Manit Saeteaw ◽

Phitjira Sanguanboonyaphong ◽

Jukapun Yoodee ◽

Kaitlyn Craft ◽

Ratree Sawangjit ◽

...

Keyword(s):

Systematic Review ◽

Adverse Events ◽

Meta Analysis ◽

Total Body Weight ◽

Megestrol Acetate ◽

High Dose ◽

Efficacy And Safety ◽

Pharmacological Interventions ◽

Serious Adverse Events ◽

Significant Difference

AimsRandomised controlled trials (RCTs) demonstrated benefits of pharmacological interventions for cachexia in improving weight and appetite. However, comparative efficacy and safety are not available. We conducted a systematic review and network meta-analysis (NMA) to evaluate the relative efficacy and safety of pharmacological interventions for cachexia.MethodsPubMed, EmBase, Cochrane, and ClinicalTrials.gov were searched for RCTs until October 2019. Key outcomes were total body weight (TBW) improvement, appetite (APP) score and serious adverse events. Two reviewers independently extracted data and assessed risk of bias. NMA was performed to estimate weight gain and APP score increase at 8 weeks, presented as mean difference (MD) or standardised MD with 95% CI.Results80 RCTs (10 579 patients) with 12 treatments were included. Majority is patients with cancer (7220). Compared with placebo, corticosteroids, high-dose megestrol acetate combination (Megace_H_Com) (≥400 mg/day), medroxyprogesterone, high-dose megestrol acetate (Megace_H) (≥400 mg/day), ghrelin mimetic and androgen analogues (Androgen) were significantly associated with MD of TBW of 6.45 (95% CI 2.45 to 10.45), 4.29 (95% CI 2.23 to 6.35), 3.18 (95% CI 0.94 to 5.41), 2.66 (95% CI 1.47 to 3.85), 1.73 (95% CI 0.27 to 3.20) and 1.50 (95% CI 0.56 to 2.44) kg. For appetite improvement, Megace_H_Com, Megace_H and Androgen significantly improved standardised APP score, compared with placebo. There is no significant difference in serious adverse events from all interventions compared with placebo.ConclusionsOur findings suggest that several pharmacological interventions have potential to offer benefits in treatment of cachexia especially Megace_H and short-term use corticosteroids. Nonetheless, high-quality comparative studies to compare safety and efficacy are warranted for better management of cachexia.

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Efficacy and safety of low-dose versus high-dose hydrocortisone to treat hypotension in neonates: a protocol for a systematic review and meta-analysis

BMJ Paediatrics Open ◽

10.1136/bmjpo-2021-001200 ◽

2021 ◽

Vol 5 (1) ◽

pp. e001200

Author(s):

Katelyn Sushko ◽

Nada Al-Rawahi ◽

Kristi Watterberg ◽

John Van Den Anker ◽

Catherine Litalien ◽

...

Keyword(s):

Systematic Review ◽

Adverse Events ◽

Critically Ill ◽

Systematic Reviews ◽

Meta Analysis ◽

Adrenal Function ◽

High Dose ◽

Cochrane Central Register ◽

Efficacy And Safety ◽

Registration Number

BackgroundImpaired adrenal function is a well-described entity in critically ill term and preterm neonates with systemic hypotension. The standard treatment for neonatal hypotension includes volume expanders and vasopressors. Recent evidence supports the use of glucocorticoids for the primary or rescue treatment of neonatal hypotension associated with impaired adrenal function. However, inconsistency regarding the prescribed dosing regimen to provide the best balance between efficacy and safety in this vulnerable population remains an area of concern.MethodsWe will conduct a systematic review and meta-analysis to evaluate low-dosing compared with high-dosing regimens of hydrocortisone for the treatment of hypotension in critically ill term, preterm and very low birth weight neonates. Ovid MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials and Web of Science will be searched from inception to November 2021. Study screening and selection will be completed as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline. Our primary outcomes will be (1) an improvement in end-organ perfusion, defined as an increase in blood pressure along with an increase in urine output or a reduction in serum lactate and (2) mortality prior to discharge. Our secondary outcomes will be the development of (1) major neurosensory abnormality, (2) bronchopulmonary dysplasia and (3) the occurrence of adverse events.DiscussionHydrocortisone may be beneficial in the treatment of hypotension associated with impaired adrenal function among critically ill neonates. However, its optimal dosing to balance desired efficacy with the risk of adverse events is yet to be determined. Our systematic review and meta-analysis aims to address this evidence gap, providing valuable knowledge for a large audience, including guideline developers, policy-makers and clinicians.PROSPERO registration numberThis protocol is submitted for registration to the international database of prospectively registered systematic reviews (PROSPERO, awaiting registration number).

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Racecadotril for acute diarrhoea in children: systematic review and meta-analyses

Archives of Disease in Childhood ◽

10.1136/archdischild-2015-309676 ◽

2015 ◽

Vol 101 (3) ◽

pp. 234-240 ◽

Cited By ~ 14

Author(s):

Morris Gordon ◽

Anthony Akobeng

Keyword(s):

Systematic Review ◽

Adverse Events ◽

Methodological Quality ◽

Data Extraction ◽

Meta Analysis ◽

Acute Diarrhoea ◽

Risk Of Bias ◽

Duration Of Symptoms ◽

Duration Of Illness ◽

Significant Difference

ObjectiveRacecadotril is an antisecretory agent that can prevent fluid/electrolyte depletion from the bowel as a result of acute diarrhoea without affecting intestinal motility. An up-to-date systematic review is indicated to summarise the evidence on racecadotril for the treatment of acute diarrhoea in children.DesignA Cochrane format systematic review of randomised controlled trials (RCTs). Data extraction and assessment of methodological quality were performed independently by two reviewers. Methodological quality was assessed using the Cochrane risk of bias tool.PatientsChildren with acute diarrhoea, as defined by the primary studies.InterventionsRCTs comparing racecadotril with placebo or other interventions.Main outcome measursDuration of illness, stool output/volume and adverse events.ResultsSeven RCTs were included, five comparing racecadotril with placebo or no intervention, one with pectin/kaolin and one with loperamide. Moderate to high risk of bias was present in all studies. There was no significant difference in efficacy or adverse events between racecadotril and loperamide. A meta-analysis of three studies with 642 participants showed significantly shorter duration of symptoms with racecadotril compared with placebo (mean difference −53.48 h, 95% CI −65.64 to −41.33). A meta-analysis of five studies with 949 participants showed no significant difference in adverse events between racecadotril and placebo (risk ratio 0.99, 95% CI 0.73 to 1.34).ConclusionsThere is some evidence that racecadotril is more effective than placebo or no intervention in reducing the duration of illness and stool output in children with acute diarrhoea. However, the overall quality of the evidence is limited due to sparse data, heterogeneity and risk of bias. Racecadotril appears to be safe and well tolerated.

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Drug Use and Postoperative Mortality Following Valve Surgery for Infective Endocarditis: A Systematic Review and Meta-analysis

Clinical Infectious Diseases ◽

10.1093/cid/ciy1064 ◽

2018 ◽

Vol 69 (7) ◽

pp. 1120-1129 ◽

Cited By ~ 15

Author(s):

Ryan Hall ◽

Michael Shaughnessy ◽

Griffin Boll ◽

Kenneth Warner ◽

Helen W Boucher ◽

...

Keyword(s):

Systematic Review ◽

Infective Endocarditis ◽

Drug Use ◽

Injection Drug Use ◽

Systematic Reviews ◽

Meta Analysis ◽

Postoperative Mortality ◽

Valve Surgery ◽

Injection Drug ◽

Significant Difference

AbstractBackgroundInfective endocarditis (IE) often requires surgical intervention. An increasingly common cause of IE is injection drug use (IDU-IE). There is conflicting evidence on whether postoperative mortality differs between people with IDU-IE and people with IE from etiologies other than injection drug use (non–IDU-IE). In this manuscript, we compare short-term postoperative mortality in IDU-IE vs non–IDU-IE through systematic review and meta-analysis.MethodsThe review was conducted according to the Cochrane Handbook for Systematic Reviews of Interventions and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Publication databases were queried for key terms included in articles up to September 2017. Randomized controlled trials, prospective cohorts, or retrospective cohorts that reported on 30-day mortality or in-hospital/operative mortality following valve surgery and that compared outcomes between IDU-IE and non–IDU-IE were included.ResultsThirteen studies with 1593 patients (n = 341 [21.4%] IDU-IE) were included in the meta-analysis. IDU-IE patients more frequently had tricuspid valve infection, Staphylococcus infection, and heart failure before surgery. Meta-analysis revealed no statistically significant difference in 30-day postsurgical mortality or in-hospital mortality between the 2 groups.ConclusionsDespite differing preoperative clinical characteristics, early postoperative mortality does not differ between IDU-IE and non–IDU-IE patients who undergo valve surgery. Future research on long-term outcomes following valve replacement is needed to identify opportunities for improved healthcare delivery with IDU-IE.

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Adverse events associated with human papillomavirus vaccines: a protocol for systematic review with network meta-analysis incorporating all randomised controlled trials comparing with placebo, adjuvants and other vaccines

BMJ Open ◽

10.1136/bmjopen-2018-026924 ◽

2019 ◽

Vol 9 (8) ◽

pp. e026924 ◽

Cited By ~ 1

Author(s):

Jiro Takeuchi ◽

Hisashi Noma ◽

Yuta Sakanishi ◽

Takashi Kawamura

Keyword(s):

Systematic Review ◽

Human Papillomavirus ◽

Adverse Events ◽

Systematic Reviews ◽

Meta Analysis ◽

Random Effect ◽

Random Effect Model ◽

Splitting Method ◽

Health Concern ◽

Human Papillomavirus Vaccine

IntroductionAdverse events following the injection (AEFIs) of human papillomavirus vaccine (HPVv) among female adolescents are still a major public health concern.MethodsAccording to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension statement for systematic reviews incorporating network meta-analyses, all prospective randomised trials will be included. The primary outcome for adverse events is topical pain during the observation period.We will mainly search 17 electronic databases from January 2000 through September 2019 with suitable Medical Subject Headings and text words for PubMed. Two reviewers will independently check the reports at the title/abstract level and identify potentially applicable studies. Then we will obtain their full texts and decide whether to include them based on the same eligible criteria.We will compare HPVv with placebo, HPVv with adjuvant and HPVv with other vaccines. Interstudy heterogeneity, publication biases or small study effects will be evaluated using conventional meta-analysis methods. The consistency of the network will be checked using tests for local and global inconsistency and the side-splitting method. To address the heterogeneity of treatment effects among the studies, we will use the multivariable random effect model.Ethics and disseminationThis pairwise or network meta-analysis does not require ethics approval. The data used here are not individual nor private. We will be able to determine which component of the vaccine induces adverse events, especially topical pain. This systematic review with network meta-analysis will provide valid answers regarding AEFIs for HPVv.PROSPERO registration numberCRD42018109265

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Modified Jobe Versus Docking Technique for Elbow Ulnar Collateral Ligament Reconstruction: A Systematic Review and Meta-analysis of Clinical Outcomes

The American Journal of Sports Medicine ◽

10.1177/0363546520921160 ◽

2020 ◽

Vol 49 (1) ◽

pp. 236-248

Author(s):

Austin M. Looney ◽

David X. Wang ◽

Christine M. Conroy ◽

Jake E. Israel ◽

Blake M. Bodendorfer ◽

...

Keyword(s):

Systematic Review ◽

Ulnar Nerve ◽

Systematic Reviews ◽

Meta Analysis ◽

Ulnar Collateral Ligament ◽

Likelihood Method ◽

Collateral Ligament ◽

Ulnar Nerve Transposition ◽

Significant Difference ◽

Nerve Transposition

Background: The modified Jobe and docking techniques are the most common techniques used for elbow ulnar collateral ligament (UCL) reconstruction. Previous systematic reviews have suggested that the docking technique results in superior outcomes as compared with the Jobe (figure-of-8) technique. However, these included results from earlier studies in which the flexor-pronator mass (FPM) was detached and an obligatory submuscular ulnar nerve transposition was performed. Purpose/Hypothesis: The purpose was to compare the outcomes and return-to-play (RTP) time between the docking and figure-of-8 techniques for UCL reconstruction. We hypothesized that there would be no significant difference in the proportion of excellent outcomes between techniques when the FPM was preserved and no obligatory submuscular ulnar nerve transposition was performed. We also hypothesized that there would be no significant difference in RTP time between techniques. Study Design: Systematic review and meta-analysis. Methods: This study was performed in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. In the primary analysis, techniques were compared in random effects models by using the restricted maximum likelihood method, with weighted effect sizes calculated as the Freeman-Tukey double-arcsine transformed proportion of excellent outcomes for variance stabilization and with summary effects estimated from the inverse double-arcsine transformation per the harmonic mean of the sample sizes. Mean RTP times for techniques were compared in a separate model. Results: There were 21 eligible articles identified, with results for 1842 UCL reconstructions (n = 320, docking; n = 1466, figure-of-8). Without controlling for the effects of flexor-pronator detachment and submuscular ulnar nerve transposition, a significantly larger proportion of excellent outcomes was observed with docking reconstruction (86.58%; 95% CI, 80.42%-91.85%) than with figure-of-8 reconstruction (76.76%; 95% CI, 69.65%-83.25%; P = .031); however, there was no significant difference between techniques when controlling for FPM preservation or detachment with submuscular nerve transposition ( P = .139). There was no significant difference between techniques in time to return to sports ( P = .729), although no reconstructions with FPM detachment and submuscular ulnar nerve transposition were available for RTP time analysis. Conclusion: There was no significant difference in the proportion of excellent Conway Scale outcomes or RTP time between the docking and modified Jobe techniques for UCL reconstruction when the FPM was preserved and routine submuscular ulnar nerve transposition was not performed.

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Systematic Reviews and Meta-Analysis in Spine Surgery—How Good Are They in Methodological Quality? A Systematic Review

Global Spine Journal ◽

10.1177/2192568220906810 ◽

2020 ◽

pp. 219256822090681 ◽

Cited By ~ 2

Author(s):

Muthu Sathish ◽

Ramakrishnan Eswar

Keyword(s):

Systematic Review ◽

Spine Surgery ◽

Systematic Reviews ◽

Methodological Quality ◽

Meta Analysis ◽

Eligibility Criteria ◽

Cochrane Database ◽

Critical Flaw ◽

Meta Analyses

Study Design: Systematic review. Objectives: To assess the methodological quality of systematic reviews and meta-analyses in spine surgery over the past 2 decades. Materials and Methods: We conducted independent and in duplicate systematic review of the published systematic reviews and meta-analyses between 2000 and 2019 from PubMed Central and Cochrane Database pertaining to spine surgery involving surgical intervention. We searched bibliographies to identify additional relevant studies. Methodological quality was evaluated with AMSTAR score and graded with AMSTAR 2 criteria. Results: A total of 96 reviews met the eligibility criteria, with mean AMSTAR score of 7.51 (SD = 1.98). Based on AMSTAR 2 criteria, 13.5% (n = 13) and 18.7% (n = 18) of the studies had high and moderate level of confidence of results, respectively, without any critical flaws. A total of 29.1% (n = 28) of the studies had at least 1 critical flaw and 38.5% (n = 37) of the studies had more than 1 critical flaw, so that their results have low and critically low confidence, respectively. Failure to analyze the conflict of interest of authors of primary studies included in review and lack of list of excluded studies with justification were the most common critical flaw. Regression analysis demonstrated that studies with funding and studies published in recent years were significantly associated with higher methodological quality. Conclusion: Despite improvement in methodological quality of systematic reviews and meta-analyses in spine surgery in current decade, a substantial proportion continue to show critical flaws. With increasing number of review articles in spine surgery, stringent measures must be taken to adhere to methodological quality by following PRISMA and AMSTAR guidelines to attain higher standards of evidence in published literature.

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Perioperative outcomes and adverse events of minimally invasive versus open posterior lumbar fusion: meta-analysis and systematic review

Journal of Neurosurgery Spine ◽

10.3171/2015.2.spine14973 ◽

2016 ◽

Vol 24 (3) ◽

pp. 416-427 ◽

Cited By ~ 87

Author(s):

Christina L. Goldstein ◽

Kevin Macwan ◽

Kala Sundararajan ◽

Y. Raja Rampersaud

Keyword(s):

Systematic Review ◽

Adverse Event ◽

Adverse Events ◽

Minimally Invasive ◽

Comparative Effectiveness ◽

Meta Analysis ◽

Perioperative Outcomes ◽

Estimated Blood Loss ◽

Significant Difference ◽

Patient Reported

OBJECT The objective of this study was to determine the clinical comparative effectiveness and adverse event rates of posterior minimally invasive surgery (MIS) compared with open transforaminal or posterior lumbar interbody fusion (TLIF/PLIF). METHODS A systematic review of the Medline, EMBASE, PubMed, Web of Science, and Cochrane databases was performed. A hand search of reference lists was conducted. Studies were reviewed by 2 independent assessors to identify randomized controlled trials (RCTs) or comparative cohort studies including at least 10 patients undergoing MIS or open TLIF/PLIF for degenerative lumbar spinal disorders and reporting at least 1 of the following: clinical outcome measure, perioperative clinical or process measure, radiographic outcome, or adverse events. Study quality was assessed using the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) protocol. When appropriate, a meta-analysis of outcomes data was conducted. RESULTS The systematic review and reference list search identified 3301 articles, with 26 meeting study inclusion criteria. All studies, including 1 RCT, were of low or very low quality. No significant difference regarding age, sex, surgical levels, or diagnosis was identified between the 2 cohorts (856 patients in the MIS cohort, 806 patients in the open cohort). The meta-analysis revealed changes in the perioperative outcomes of mean estimated blood loss, time to ambulation, and length of stay favoring an MIS approach by 260 ml (p < 0.00001), 3.5 days (p = 0.0006), and 2.9 days (p < 0.00001), respectively. Operative time was not significantly different between the surgical techniques (p = 0.78). There was no significant difference in surgical adverse events (p = 0.97), but MIS cases were significantly less likely to experience medical adverse events (risk ratio [MIS vs open] = 0.39, 95% confidence interval 0.23–0.69, p = 0.001). No difference in nonunion (p = 0.97) or reoperation rates (p = 0.97) was observed. Mean Oswestry Disability Index scores were slightly better in the patients undergoing MIS (n = 346) versus open TLIF/PLIF (n = 346) at a median follow-up time of 24 months (mean difference [MIS – open] = 3.32, p = 0.001). CONCLUSIONS The result of this quantitative systematic review of clinical comparative effectiveness research examining MIS versus open TLIF/PLIF for degenerative lumbar pathology suggests equipoise in patient-reported clinical outcomes. Furthermore, a meta-analysis of adverse event data suggests equivalent rates of surgical complications with lower rates of medical complications in patients undergoing minimally invasive TLIF/PLIF compared with open surgery. The quality of the current comparative evidence is low to very low, with significant inherent bias.

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Oxycodone versus other opioids analgesia after laparoscopic surgery: a meta-analysis

10.21203/rs.3.rs-20091/v1 ◽

2020 ◽

Author(s):

Yan Li ◽

Zhi Dou ◽

Liqiang Yang ◽

Qi Wang ◽

Jiaxiang Ni ◽

...

Keyword(s):

Laparoscopic Surgery ◽

Adverse Effects ◽

Adverse Events ◽

Sample Size ◽

Systematic Reviews ◽

Visceral Pain ◽

Meta Analysis ◽

Analgesic Efficacy ◽

Patients Satisfaction ◽

Significant Difference

Abstract Background Intravenous opioids are administered for management of visceral pain after laparoscopic surgery. Whether oxycodone has an advantage over other opioids in the treatment of visceral pain is not yet clear. Methods This article evaluates the analgesic efficiency and adverse events of oxycodone and other opioids including alfentany, sufentanyl, fentanyl and morphine for the treatment of post laparoscopic surgery visceral pain. This review was conducted according to the methodological standards described in the Cochrane Handbook for Systematic Reviews of Interventions and the Preferred Reporting Items for Systematic Reviews and Meta-analysis statement. The PubMed, Embase and Cochrane libraries were searched in December 2019. Results Ten studies were included in this review. The sample size was 815 participants. The results showed that compared with morphine and fentanyl, oxycodone had a more potent analgesic efficacy at the first day after laparoscopic surgery, especially during the first 0.5h. There was no significant difference in sedation between the two groups. Compared to morphine and fentanyl, oxycodone was more likely to increase the risk of dizziness and drowsiness. The overall patients satisfaction had no significant difference between oxycodone versus other opioids. Conclusions Oxycodone is a superior analgesic within 24h after laparoscopic surgery with careful regards to its adverse effects.

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Dynamics of sputum conversion during effective tuberculosis treatment: A systematic review and meta-analysis

PLoS Medicine ◽

10.1371/journal.pmed.1003566 ◽

2021 ◽

Vol 18 (4) ◽

pp. e1003566

Author(s):

Claire J. Calderwood ◽

James P. Wilson ◽

Katherine L. Fielding ◽

Rebecca C. Harris ◽

Aaron S. Karat ◽

...

Keyword(s):

Systematic Review ◽

Data Extraction ◽

Meta Analysis ◽

World Health ◽

Significant Heterogeneity ◽

Tb Treatment ◽

Health Organization ◽

Reported Data ◽

Meta Analyses ◽

Culture Conversion

Background Two weeks’ isolation is widely recommended for people commencing treatment for pulmonary tuberculosis (TB). The evidence that this corresponds to clearance of potentially infectious tuberculous mycobacteria in sputum is not well established. This World Health Organization–commissioned review investigated sputum sterilisation dynamics during TB treatment. Methods and findings For the main analysis, 2 systematic literature searches of OvidSP MEDLINE, Embase, and Global Health, and EBSCO CINAHL Plus were conducted to identify studies with data on TB infectiousness (all studies to search date, 1 December 2017) and all randomised controlled trials (RCTs) for drug-susceptible TB (from 1 January 1990 to search date, 20 February 2018). Included articles reported on patients receiving effective treatment for culture-confirmed drug-susceptible pulmonary TB. The outcome of interest was sputum bacteriological conversion: the proportion of patients having converted by a defined time point or a summary measure of time to conversion, assessed by smear or culture. Any study design where more than 10 participants were included was considered. Record sifting and data extraction were performed in duplicate. Random effects meta-analyses were performed. A narrative summary additionally describes the results of a systematic search for data evaluating infectiousness from humans to experimental animals (PubMed, all studies to 27 March 2018). Other evidence on duration of infectiousness—including studies reporting on cough dynamics, human tuberculin skin test conversion, or early bactericidal activity of TB treatments—was outside the scope of this review. The literature search was repeated on 22 November 2020, at the request of the editors, to identify studies published after the previous censor date. Four small studies reporting 3 different outcome measures were identified, which included no data that would alter the findings of the review; they are not included in the meta-analyses. Of 5,290 identified records, 44 were included. Twenty-seven (61%) were RCTs and 17 (39%) were cohort studies. Thirteen studies (30%) reported data from Africa, 12 (27%) from Asia, 6 (14%) from South America, 5 (11%) from North America, and 4 (9%) from Europe. Four studies reported data from multiple continents. Summary estimates suggested smear conversion in 9% of patients at 2 weeks (95% CI 3%–24%, 1 single study [N = 1]), and 82% of patients at 2 months of treatment (95% CI 78%–86%, N = 10). Among baseline smear-positive patients, solid culture conversion occurred by 2 weeks in 5% (95% CI 0%–14%, N = 2), increasing to 88% at 2 months (95% CI 84%–92%, N = 20). At equivalent time points, liquid culture conversion was achieved in 3% (95% CI 1%–16%, N = 1) and 59% (95% CI 47%–70%, N = 8). Significant heterogeneity was observed. Further interrogation of the data to explain this heterogeneity was limited by the lack of disaggregation of results, including by factors such as HIV status, baseline smear status, and the presence or absence of lung cavitation. Conclusions This systematic review found that most patients remained culture positive at 2 weeks of TB treatment, challenging the view that individuals are not infectious after this interval. Culture positivity is, however, only 1 component of infectiousness, with reduced cough frequency and aerosol generation after TB treatment initiation likely to also be important. Studies that integrate our findings with data on cough dynamics could provide a more complete perspective on potential transmission of Mycobacterium tuberculosis by individuals on treatment. Trial registration Systematic review registration: PROSPERO 85226.

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