To reduce the spread of the severe acute respiratory syndrome coronavirus 2, many pulmonary function testing (PFT) laboratories have been closed or have significantly reduced their testing capacity. Because these mitigation strategies may be necessary for the next 6 to 18 months to prevent recurrent peaks in disease prevalence, fewer objective measurements of lung function will alter the diagnosis and care of patients with chronic respiratory diseases. PFT, which includes spirometry, lung volume, and diffusion capacity measurement, is essential to the diagnosis and management of patients with asthma, COPD, and other chronic lung conditions.Both traditional and innovative alternatives to conventional testing must now be explored.These may include peak expiratory flow devices, electronic portable spirometers, portable exhaled nitric oxide measurement, airwave oscillometry devices, and novel digital health tools such as smartphone microphone spirometers and mobile health technologies along with integration of machine learning approaches. The adoption of some novel approaches may not merely replace but could improve existing management strategies and alter common diagnostic paradigms. With these options comes important technical, privacy, ethical, financial, and medicolegal barriers that must be addressed. However, the coronavirus disease 19 pandemic also presents a unique opportunity to augment conventional testing by including innovative and emerging approaches to measuring lung function remotely in patients with respiratory disease.The benefits of such an approach have the potential to enhance respiratory care and empower patient self-management well beyond the current global pandemic.

Low-dose metronomic (LDM) chemotherapy is emerging as an alternative or supplemental dosing strategy to conventional maximum tolerated dose (MTD) chemotherapy. It is characterized primarily, but not exclusively, by antiangiogenic mechanisms of action and the absence of high-grade adverse effects commonly seen with MTD chemotherapy. However, similar to other anticancer therapies, inherent resistance to LDM chemotherapy is common. Moreover, even tumors that initially respond to metronomic regimens eventually develop resistance through mechanisms that are as yet unknown. Thus, we have developed in vivo models of PC-3 human prostate cancer cells resistant to extended LDM cyclophosphamide therapy. Such PC-3 variants show stable resistance to LDM cyclophosphamide in vivo yet retain in vitro sensitivity to 4-hydroperoxy-cyclophosphamide (precursor of the active cyclophosphamide metabolite 4-hydroxy-cyclophosphamide) and other chemotherapeutic agents, namely, docetaxel and doxorubicin. Moreover, LDM cyclophosphamide-resistant PC-3 variants remain sensitive to MTD cyclophosphamide therapy in vivo. Conversely, PC-3 variants made resistant in vivo to MTD cyclophosphamide show varying levels of resistance to metronomic cyclophosphamide when grown in mice. These results and additional studies of variants of the breast cancer cell line MDA-MB-231 suggest that resistance to LDM cyclophosphamide is a distinct phenomenon from resistance to MTD cyclophosphamide and that LDM cyclophosphamide administration does not select for MTD chemotherapy resistance. As such, our findings have various implications for the clinical use of metronomic chemotherapy.

Background Computerized clinical decision support systems (CDSSs) are a promising knowledge translation tool, but often fail to meaningfully influence the outcomes they target. Low CDSS provider uptake is a potential contributor to this problem but has not been systematically studied. The objective of this systematic review and meta-regression was to determine reported CDSS uptake and identify which CDSS features may influence uptake. Methods Medline, Embase, CINAHL, and the Cochrane Database of Controlled Trials were searched from January 2000 to August 2020. Randomized, non-randomized, and quasi-experimental trials reporting CDSS uptake in any patient population or setting were included. The main outcome extracted was CDSS uptake, reported as a raw proportion, and representing the number of times the CDSS was used or accessed over the total number of times it could have been interacted with. We also extracted context, content, system, and implementation features that might influence uptake, for each CDSS. Overall weighted uptake was calculated using random-effects meta-analysis and determinants of uptake were investigated using multivariable meta-regression. Results Among 7995 citations screened, 55 studies involving 373,608 patients and 3607 providers met full inclusion criteria. Meta-analysis revealed that overall CDSS uptake was 34.2% (95% CI 23.2 to 47.1%). Uptake was only reported in 12.4% of studies that otherwise met inclusion criteria. Multivariable meta-regression revealed the following factors significantly associated with uptake: (1) formally evaluating the availability and quality of the patient data needed to inform CDSS advice; and (2) identifying and addressing other barriers to the behaviour change targeted by the CDSS. Conclusions and relevance System uptake was seldom reported in CDSS trials. When reported, uptake was low. This represents a major and potentially modifiable barrier to overall CDSS effectiveness. We found that features relating to CDSS context and implementation strategy best predicted uptake. Future studies should measure the impact of addressing these features as part of the CDSS implementation strategy. Uptake reporting must also become standard in future studies reporting CDSS intervention effects. Registration Pre-registered on PROSPERO, CRD42018092337

Asthma action plans (AAPs) reduce healthcare utilisation, improve quality of life and are recommended across guidelines. However, fewer than 25% of patients receive an AAP, partly due to prescribers' inability to complete “yellow zone” instructions (how to intensify therapy for acute loss of control). We sought to review best evidence to develop a practical, evidence-based tool to facilitate yellow zone guidance in adults.We reviewed recent asthma guidelines and adult studies addressing acute loss of asthma control (January 2010 to March 2016). We developed evidence-based rules for yellow zone therapy and operational guidelines to maximise adherence and minimise errors.We reviewed three guidelines and 11 manuscripts (2486 abstracts screened). Recommendations were comparable but some areas lacked guidance. For 15/43 asthma regimens, the commonly recommended four- to five-fold yellow zone inhaled corticosteroid dose increase was problematic due to regulatory dose limits. We identified evidence-based alternatives for 8/15 regimens. Operational guidance included increasing to a maximum of four inhalations while maintaining baseline inhaler frequency and device in the yellow zone.We developed a practical implementation tool to facilitate AAP delivery at the point of care, addressing existing gaps and uncertainties. Our tool should be implemented as part of a multifaceted approach to augment AAP usage.

Prolonged, frequently administered low-dose metronomic chemotherapy (LDM) is being explored (pre)clinically as a promising antiangiogenic antitumor strategy. Although appealing because of a favorable side effect profile and mostly oral dosing, LDM involves new challenges different from conventional maximum tolerated dose chemotherapy. These include possible altered pharmacokinetic characteristics due to long-term drug exposure potentially resulting in acquired resistance and increased risk of unfavorable drug interactions. We therefore compared the antitumor and antivascular effects of LDM cyclophosphamide (CPA) given to mice that had been pretreated with either LDM CPA or normal saline, obtained blood 4-hydroxy-CPA (activated CPA) concentrations using either gas chromatography/mass spectrometry or liquid chromatography/tandem mass spectrometry in mice treated with LDM CPA, and measured hepatic and intratumoral activity of enzymes involved in the biotransformation of CPA and many other drugs [i.e., cytochrome P450 3A4 (CYP3A4) and aldehyde dehydrogenase]. Exposure of mice to LDM CPA for z8 weeks did not compromise subsequent activity of LDM CPA therapy, and biologically active 4-hydroxy-CPA levels were maintained during long-term LDM CPA administration. Whereas the effects on CYP3A4 were complex, aldehyde dehydrogenase activity was not affected. In summary, our findings suggest that acquired resistance to LDM CPA is unlikely accounted for by altered CPA biotransformation. In the absence of reliable pharmacodynamic surrogate markers, pharmacokinetic parameters might become helpful to individualize/optimize LDM CPA therapy. LDM CPA-associated changes of CYP3A4 activity point to a potential risk of unfavorable drug interactions when compounds that are metabolized by CYP3A4 are coadministered with LDM CPA. [Mol Cancer Ther 2007;6(8):2280 -9]