Active Ingredients: Doxycycline
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Assessment of bias in conducting the systematic review We conducted the review according to the published protocol and planned to justify any deviations from it in the 'Differences between protocol and review' section of the systematic review.
Measures of treatment effect We planned to analyse dichotomous data as odds ratios, and continuous data as mean differences or standardised mean differences. We planned to enter data presented as a scale with a consistent direction of effect.
We planned to narratively describe skewed data reported as medians and interquartile ranges.
If multiple trial arms had been reported in a single trial, we planned to include only the relevant arms. If two comparisons e.
Unit of analysis issues If we had included any studies, the unit of analysis would have been the participant. In terms of exacerbation rates and hospitalisation rates, we planned to focus on the number of events experienced by the participant during the trial and to analyse the results using rate ratios if possible.
We planned to use adjusted data where it was available e. Dealing with missing data We planned to contact investigators or study sponsors in order to verify key study characteristics and to obtain missing numerical outcome data where possible e.
Where this was not possible, and missing data were thought to introduce serious bias, we planned to take this into consideration in the GRADE rating for affected outcomes.
However, where there are few studies or the effects of interventions across studies are not randomly distributed e. We planned to synthesise and report dichotomous and continuous data separately for each outcome e. Furthermore, we planned to use standardised mean differences SMD when outcomes were measured using different scales e.
We planned to use the five GRADE considerations risk of bias, consistency of effect, imprecision, indirectness and publication bias to assess the overall quality of the evidence in terms of the studies that contributed data to the prespecified outcomes.
We planned to use the methods and recommendations described in Section 8.
We planned to include comments to aid the reader's understanding of the review where necessary. Subgroup analysis and investigation of heterogeneity We planned to carry out the following subgroup analyses.
Mode of delivery e. Antibiotic class e. Such intramolecular FRET sensors have detected rapid binding and de-binding of small molecules, such as mimetics of acetylcholine to muscarinic acetylcholine receptor subtypes 22 — 23 and to variants of these in which the ligand binding selectivity had been re-engineered by mutagenesis 23.
If peptide receptive GPCR sensors could be defined and engineered such that they retained function and pharmacology equivalent to the wild type receptor, they would be valuable tools to examine each of ligand binding kinetics, the details of receptor activation mechanisms, the effects of polymorphic variation in receptor sequence and of designed mutations.
Furthermore, they might provide tools to explore the activation of receptors in both ex vivo and, eventually, in vivo settings. Oligonucleotides were from ThermoElectron Ulm, Germany.
Protease inhibitor mixture tablets were from Roche Diagnostics Mannheim, Germany.
After washing, proteins were detected by enhanced chemiluminescence Pierce Protein Research Products, Thermo Scientific according to the manufacturer's instructions.
The resulting pellets were resuspended in ice-cold TE buffer.