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Introduction Achieving tuberculosis (TB) elimination in low TB incidence countries requires identification and treatment of individuals at risk for latent TB infection (LTBI). Persons travelling to high TB incidence countries are potentially at risk for TB exposure. This systematic review and meta-analysis estimates incident LTBI and active TB among individuals travelling from low to higher TB incidence countries. Methods Five electronic databases were searched from inception to 18 February 2020. We identified incident LTBI and active TB among individuals travelling from low (100/100 000) TB incidence countries. We conducted a meta-analysis and meta-regression using a random effects model of log-transformed proportions (cumulative incidence). Subgroup analyses investigated the impact of travel duration, travel purpose and TB incidence in the destination country. Results Our search identified 799 studies, 120 underwent full-text review, and 10 studies were included. These studies included 1 154 673 travellers observed between 1994 and 2013, comprising 443 health care workers (HCW), 1 068 636 military personnel and 85 594 general travellers/volunteers. We did not identify any studies that estimated incidence of LTBI or active TB among people travelling to visit friends and relatives (VFRs). The overall cumulative incidence of LTBI was 2.3%, with considerable heterogeneity. Among individuals travelling for a mean/median of up to 6 months, HCWs had the highest cumulative incidence of LTBI (4.3%), whereas the risk was lower for military (2.5%) and general travellers/volunteers (1.6%). Meta-regression did not identify a difference in incident LTBI based on travel duration and TB incidence in the destination country. Five studies reported cases of active TB, with an overall pooled estimate of 120.7 cases per 100 000 travellers. Conclusions We found that travelling HCWs were at highest risk of developing LTBI. Individual risk activities and travel purpose were most associated with risk of TB infection acquired during travel.

In studies of diagnostic test accuracy, authors sometimes report results only for a range of cutoff points around data-driven "optimal" cutoffs. We assessed selective cutoff reporting in studies of the diagnostic accuracy of the Patient Health Questionnaire-9 (PHQ-9) depression screening tool. We compared conventional meta-analysis of published results only with individual-patient-data meta-analysis of results derived from all cutoff points, using data from 13 of 16 studies published during 2004-2009 that were included in a published conventional meta-analysis. For the "standard" PHQ-9 cutoff of 10, accuracy results had been published by 11 of the studies. For all other relevant cutoffs, 3-6 studies published accuracy results. For all cutoffs examined, specificity estimates in conventional and individual-patient-data meta-analyses were within 1% of each other. Sensitivity estimates were similar for the cutoff of 10 but differed by 5%-15% for other cutoffs. In samples where the PHQ-9 was poorly sensitive at the standard cutoff, authors tended to report results for lower cutoffs that yielded optimal results. When the PHQ-9 was highly sensitive, authors more often reported results for higher cutoffs. Consequently, in the conventional meta-analysis, sensitivity increased as cutoff severity increased across part of the cutoff range-an impossibility if all data are analyzed. In sum, selective reporting by primary study authors of only results from cutoffs that perform well in their study can bias accuracy estimates in meta-analyses of published results.

In randomized controlled trials, the intention-to-treat estimator provides an unbiased estimate of the causal effect of treatment assignment on the outcome. However, patients often want to know what the effect would be if they were to take the treatment as prescribed (the patient-oriented effect), and several researchers have suggested that the more relevant causal effect for this question is the complier average causal effect (CACE), also referred to as the local average treatment effect. Sophisticated approaches to estimating the CACE include Bayesian and frequentist methods for principal stratification, inverse-probability-of-treatment-weighted estimators, and instrumental-variable (IV) analysis. All of these approaches exploit information about adherence to assigned treatment to improve upon the intention-to-treat estimator, but they are rarely used in practice, probably because of their complexity. The IV principal stratification estimator is simple to implement but has had limited use in practice, possibly due to lack of familiarity. Here, we show that the IV principal stratification estimator is a modified per-protocol estimator that should be obtainable from any randomized controlled trial, and we provide a closed form for its robust variance (and its uncertainty). Finally, we illustrate sensitivity analyses we conducted to assess inference in light of potential violations of the exclusion restriction assumption.

Previous injury is believed to be a causal risk factor for subsequent injury. Using empirical data on circus artists (n = 1,281 artists) between 2004 and 2008 in Montreal, Canada, as a motivating example, the authors use patient vector plots to demonstrate that a bias away from the null must always occur in the typical analyses cited as evidence (i.e., survival analysis, Poisson regression), except in the improbable context where all subjects have the same inherent risk independent of previous injury. In addition, using simulated data, the authors demonstrate that a simple method that conditions on the individual will approximate conclusions from more complex analytical methods. By using the typical analysis of the authors' empirical data, Kaplan-Meier curves and Cox regression suggested increasing injury rates for both the second and third injuries compared with the first injury. However, conditional analyses using a matched population (i.e., time to first, second, and third injuries among artists with 3 or more injuries) showed that injury rates were unchanged for both the second and third injuries compared with the first injury. These results suggest that previous injury should not be evaluated as a causal risk factor unless one conditions on the individual in some way.

Some authors argue that systematic reviews and meta-analyses of intervention studies should include only randomized controlled trials because the randomized controlled trial is a more valid study design for causal inference compared with the observational study design. However, a review of the principal elements underlying this claim (randomization removes the chance of confounding, and the double-blind process minimizes biases caused by the placebo effect) suggests that both classes of study designs have strengths and weaknesses, and including information from observational studies may improve the inference based on only randomized controlled trials. Furthermore, a review of empirical studies suggests that meta-analyses based on observational studies generally produce estimates of effect similar to those from meta-analyses based on randomized controlled trials. The authors found that the advantages of including both observational studies and randomized studies in a meta-analysis could outweigh the disadvantages in many situations and that observational studies should not be excluded a priori.

Background Small bowel obstruction (SBO) is a major cause of morbidity and financial expenditure. The goals of this study were to determine factors predisposing to adhesive SBO, to note the long-term prognosis and recurrence rates for operative and non-operative treatment, to elicit the complication rate of operations and to highlight factors predictive of recurrence. Methods The medical records of all patients admitted to one hospital between 1986 and 1996 with the diagnosis of SBO were reviewed retrospectively. This included 410 patients accounting for 675 admissions. Results The frequency of previous operation by procedure type was colorectal surgery (24 per cent), followed by gynaecological surgery (22 per cent), herniorrhaphy (15 per cent) and appendicectomy (14 per cent). A history of colorectal surgery (odds 2·7) and vertical incisions (odds 2·5) tended to predispose to multiple matted adhesions rather than an obstructive band. At initial admission 36 per cent of patients were treated by means of operation. As the number of admissions increased, the recurrence rate increased while the time interval between admissions decreased. Patients with an adhesive band had a 25 per cent readmission rate, compared with a 49 per cent rate for patients with matted adhesions (P < 0·004). At the initial admission 36 per cent of patients were treated surgically. Patients treated without operation had a 34 per cent readmission rate, compared with 32 per cent for those treated surgically (P not significant), a shorter time to readmission (median 0·7 versus 2·0 years; P < 0·05), no difference in reoperation rate (14 versus 11 per cent; P not significant) and fewer inpatient days over all admissions (4 versus 12 days; P < 0·0001). Conclusion The likelihood of reobstruction increases and the time to reobstruction decreases with increasing number of previous episodes of obstruction. Patients with matted adhesions have a greater recurrence rate than those with band adhesions. Non-operative treatment for adhesions in stable patients results in a shorter hospital stay and similar recurrence and reoperation rates, but a reduced interval to reobstruction when compared with operative treatment.