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Radiomics, a method used to extract large amount of data, may be useful for discriminating malignant characteristics for lung cancer staging. We aimed to critically appraise the current use of radiomics in medical imaging for determining nodal involvement in lung cancer. The literature was searched using Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and Web of Science for observational studies between the databases’ inception and January 2020. All observational studies compared diagnostic tests for lung cancer in comparison to diagnostic tests with a radiomic adjunct. For each study, data were extracted for study characteristics, methodological quality, and accuracy. Discrepancies in screening and extraction were resolved by a third reviewer. Data were synthesized narratively. 15 studies were included, 13 of which were full reports, while two were conference abstracts. Overall, 3164 patients were enrolled with a total of 3379 LNs recorded (69% malignancy). Point estimate sensitivities for algorithms ranged from 52 to 99%, while specificity for the algorithms ranged from 60 to 92%. Area under the curve c-statistics were only reported for algorithms and not the clinician. Point estimate c-statistics ranged from 0.64 to 0.94, suggesting that the algorithms possessed good discrimination potentials. The current level of evidence of radiomic analysis methods for staging lung cancer is inconclusive and possesses heterogeneity in study design. Prospective external validation of these algorithms and direct comparisons using cut-off thresholds is required to determine their true predictive capability prior to implementation in clinical practice. PROSPERO ID: CRD42020162952.

There are 34 studies in almost 2 million participants that have reported on the association between proton pump inhibitor (PPI) therapy and risk of fracture. There is substantial variation between the results of each study but systematic reviews of the data suggest overall there is an association between PPI therapy and risk of fracture. The magnitude of the association is modest and is most likely due to confounding factors as patients prescribed PPI therapy tend to be more frail with more risk factors for fractures than those not given these drugs. There is no clear dose-response relationship and there is no association between PPI therapy and risk of fracture in those at highest risk. Finally, there is no clear mechanism through which PPI therapy increases the risk of fracture, as recent randomized trials show no impact of PPI therapy on calcium absorption and there is no association between PPI therapy and risk of osteoporosis. We therefore feel there is insufficient evidence to change PPI prescribing habits based on risk of fracture. Similarly, we do not recommend bone mineral density investigations for patients taking PPI therapy other than would be normally indicated. There is no evidence to support prescription of calcium and/or vitamin D in patients simply because they are taking PPI therapy. As with all medications, we only recommend prescribing PPI therapy when there is a clear indication that benefit will outweigh risk and at the lowest effective dose. Patients should be regularly assessed as to whether acid suppression is still required.

PPIs have become one of the most commonly used medications worldwide, as they are the treatment of choice for several acid-related gastrointestinal disorders. However, concerns have been raised about PPI therapy, including the risk of pneumonia, bone fractures and enteric infections, and a possible interaction with clopidogrel that could increase the risk of cardiovascular events. Observational studies have shown very modest associations between PPI therapy and these risks, although the association between PPI treatment and the risk of enteric infections seems to be stronger than the association with other risk factors. However, given the inherent limitations of observational studies, these associations could be attributable to bias and/or confounding factors. In addition, evidence from randomized, controlled trials does not support a clinically significant effect of PPI therapy on the risk of cardiovascular events in patients taking clopidogrel or the risk of pneumonia. Nevertheless, it is impossible to exclude the possibility that some of these associations might be causal or indeed that PPI therapy has an as yet unknown long-term adverse effect. As with any therapy, therefore, it is advisable to prescribe PPIs only to patients for whom these drugs have been proven beneficial.