Prognostic factors and effect modifiers for personalisation of internet-based cognitive behavioural therapy among university students with subthreshold depression: A secondary analysis of a factorial trial

BACKGROUND: Internet-cognitive behavioural therapy (iCBT) for depression can include multiple components. This study explored depressive symptom improvement prognostic factors (PFs) and effect modifiers (EMs) for five common iCBT components including behavioural activation, cognitive restructuring, problem solving, self-monitoring, and assertion training. METHODS: We used data from a factorial trial of iCBT for subthreshold depression among Japanese university students (N = 1093). The primary outcome was the change in PHQ-9 scores at 8 weeks from baseline. Interactions between each component and various baseline characteristics were estimated using a mixed-effects model for repeated measures. We calculated multiplicity-adjusted p-values at 5 % false discovery rate using the Benjamini-Hochberg procedure. RESULTS: After multiplicity adjustment, the baseline PHQ-9 total score emerged as a PF and exercise habits as an EM for self-monitoring (adjusted p-values <0.05). The higher the PHQ-9 total score at baseline (range: 5-14), the greater the decrease after 8 weeks. For each 5-point increase at baseline, the change from baseline to 8 weeks was bigger by 2.8 points. The more frequent the exercise habits (range: 0-2 points), the less effective the self-monitoring component. The difference in PHQ-9 change scores between presence or absence of self-monitoring was smaller by 0.94 points when the participant exercised one level more frequently. Additionally, the study suggested seven out of 36 PFs and 14 out of 160 EMs examined were candidates for future research. LIMITATIONS: Generalizability is limited to university students with subthreshold depression. CONCLUSIONS: These results provide some helpful information for the future development of individualized iCBT algorithms for depression

Components of smartphone cognitive-behavioural therapy for subthreshold depression among 1093 university students: a factorial trial

BACKGROUND: Internet-based cognitive-behavioural therapy (iCBT) is effective for subthreshold depression. However, which skills provided in iCBT packages are more effective than others is unclear. Such knowledge can inform construction of more effective and efficient iCBT programmes. OBJECTIVE: To examine the efficacy of five components of iCBT for subthreshold depression. METHODS: We conducted an factorial trial using a smartphone app, randomly allocating presence or absence of five iCBT skills including self-monitoring, behavioural activation (BA), cognitive restructuring (CR), assertiveness training (AT) and problem-solving. Participants were university students with subthreshold depression. The primary outcome was the change on the Patient Health Questionnaire-9 (PHQ-9) from baseline to week 8. Secondary outcomes included changes in CBT skills. FINDINGS: We randomised a total of 1093 participants. In all groups, participants had a significant PHQ-9 reduction from baseline to week 8. Depression reduction was not significantly different between presence or absence of any component, with corresponding standardised mean differences (negative values indicate specific efficacy in favour of the component) ranging between -0.04 (95% CI -0.16 to 0.08) for BA and 0.06 (95% CI -0.06 to 0.18) for AT. Specific CBT skill improvements were noted for CR and AT but not for the others. CONCLUSIONS: There was significant reduction in depression for all participants regardless of the presence and absence of the examined iCBT components. CLINICAL IMPLICATION: We cannot yet make evidence-based recommendations for specific iCBT components. We suggest that future iCBT optimisation research should scrutinise the amount and structure of components to examine. TRIAL REGISTRATION NUMBER: UMINCTR-000031307

A Novel Single-Tube Eicosaplex/Octaplex PCR System for the Detection of Extended-Spectrum β-Lactamases, Plasmid-Mediated AmpC β-Lactamases, and Integrons in Gram-Negative Bacteria

We developed two multiplex polymerase chain reactions (PCRs) for the detection of extended-spectrum β-lactamases (ESBLs), plasmid-mediated AmpC β-lactamases, aac(6′)-Ib gene, and integrase genes (intI1, intI2, and intI3) in class 1, 2, and 3 integrons in Gram-negative bacteria. We evaluated the PCRs using 109 Gram-negative isolates from non-organic (ANO) and organic (AO) vegetables and fruits. Screening of ANO substances identified five SHV, one TEM-1, one CTX-M, 20 AmpC-CS, and two intI1 positives. DNA sequencing revealed CTX-M in Pantoea spp. was blaRANH-2, a plasmid-mediated CTX-M related ESBL gene only found in Rahnella spp. Of the 20 AmpC-CS positives, 10 were CMY/MIR/ACT/EC (3 new variants), eight were ACT, one was AZECL, and one was new Pseudomonas-related AmpC family. Screening of AO substances identified 11 SHV, two TEM-1, three CTX-M (one OXY-2, two CTX-M-14/-15), two OXA-9, 13 AmpC-CS and one intI1 positives. The 13 AmpC-CS positives were five CMY/MIR/ACT/EC, three ACT, one MOX-12 variant, and four ADC (one ADC-25 and three new variants). We developed a rapid, easy-to-perform, low-cost, and reliable multiplex PCR system for screening clinically relevant β-lactamases and integrons in Gram-negative bacteria. We showed the prevalence of ESBLs and AmpC β-lactamases among our panel of ampicillin-resistant Gram-negative strains and detection of NDM and OXA carbapenemases

Draft genome sequence of an mcr-1/IncI2-carrying multidrug-resistant Escherichia coli B1:ST101 isolated from meat and meat products in Egypt

The aim of this study was to investigate the occurrence of plasmid-encoded colistin resistance among Gram-negative bacteria isolated from meat and meat products in Egypt and to report the draft genome sequence of anmcr-1/IncI2-carrying multidrug-resistant (MDR) Escherichia coli B1:ST101 isolate. A total of 128 colistin-resistant strains were isolated from various meat and meat product samples in different cities in Egypt. Multiplex PCR screening for plasmid-mediated colistin resistance genes was performed. Whole-genome sequencing was performed using an Illumina NextSeq platform and the genome was assembled using CLC Genomics Workbench 7.5.1. A singlemcr-1-positive MDR E. coli strain was isolated from beef sausages. The genome size of the E. coli strain was calculated at 5 044 715bp, with a total of 226 contigs and a G+C content of 50.5%. The strain belonged to ST101 (phylogroup B1). The mcr-1 gene was located on an IncI2-type self-conjugative plasmid of 64.6kb in size. The strain showed a MDR phenotype, with a colistin MIC of 4mg/L. A large number of acquired antimicrobial resistance genes was identified, including genes encoding resistance to colistin (mcr-1), β-lactams (bla &lt;sub&gt;TEM-1&lt;/sub&gt; ), phenicols (floR), trimethoprim (dfrA12), aminoglycosides [aac(3)-IIa, aph(3")-Ib and aadA2], macrolides (mphA and mdfA), tetracyclines (tetA), sulfonamides (sul1 and sul2) and quinolones (qnrS1). Here we report the first draft genome sequence of anmcr-1/IncI2-carrying MDR E. coli B1:ST101 isolated from beef sausage in Egypt. This study highlights the potential role played by food products in the spread of colistin resistance to humans

Emergence of an NDM-5-producing clinical Escherichia coli isolate in Egypt

SummaryThe first occurrence of New Delhi metallo-β-lactamase 5 (NDM-5), carried on an IncI1-Iγ-type plasmid of >93kb in a multidrug-resistant Escherichia coli strain in Kafr El-Sheikh, Egypt, is reported. The strain was isolated from a wound pus swab from a patient diagnosed with a fracture of the right femur. This E. coli strain was found to belong to sequence type (ST) 5018 and also to carry other resistance genes, including blaCTX-M-15, blaCMY-42, blaOXA-1, and aac(6′)-Ib-cr

Emergence of a Multidrug-Resistant Enterobacter hormaechei Clinical Isolate from Egypt Co-Harboring mcr-9 and blaVIM-4

This study describes the first full genomic sequence of an mcr-9 and blaVIM-4-carrying multidrug-resistant Enterobacter hormaechei clinical isolate from Egypt. The strain was isolated in April 2015 from the sputum of a patient in Cairo, Egypt. The mcr-9 and blaVIM-4 genes were identified by PCR screening and DNA sequencing; the isolate was subjected to antimicrobial susceptibility testing, conjugation experiments, and whole genomic sequencing. mcr-9 and blaVIM-4 were carried by an IncHI2 plasmid, pAMS-38a (281,121 bp in size); the plasmid also carried genes conferring resistance against sulfonamides (sul1), quinolones (qnrA1), trimethoprim (dfrA1), &beta;-lactams (blaTEM-1B), aminoglycosides (aac (6&rsquo;)-II, aadA23, aadA2b, and ant(2&rsquo;&rsquo;)-Ia). The strain was susceptible to colistin (MIC, &lt;0.25 &mu;g/mL); this could be due to the absence of the qseC/qseB regulatory system located downstream of mcr-9 in Enterobacterales, which is involved in the induction of colistin-resistance. The genetic context of mcr-9 and blaVIM-4 was identified as IS1-mcr-9-IS903-pcoS-∆pcoE-rcnA and intI1-blaVIM-4&mdash;aac (6&rsquo;)-II-dfrA1-∆aadA23-smr-ISPa21-qacE∆1, respectively. This is the first report of an mcr-9 and blaVIM-4 /IncHI2-carrying multidrug-resistant E. hormaechei clinical isolate from Africa and the Middle East. Plasmids of the IncHI2 group and the two insertion sequences (IS1, and IS903) might be the main vehicles for dissemination of mcr-9. Further screening for mcr-9 is essential for identifying its incidence and to prevent its dissemination

First genomic characterization of blavim-1 and mcr-9-coharbouring enterobacter hormaechei isolated from food of animal origin

We describe here the complete genome sequence of an Enterobacter hormaechei ST279 coharbouring blaVIM-1 and mcr-9 recovered from uncooked beef patty in June 2017, Egypt. The tested isolate was resistant to carbapenem but susceptible to colistin (minimum inhibitory concentration (MIC), 0.5 μg/mL). The antimicrobial susceptibility profile and conjugation experiments were performed. The entire genome was sequenced by the Illumina MiniSeq and Oxford Nanopore methods. The blaVIM-1 and mcr-9 genes are carried on the same IncHI2/pMLST1 plasmid, pMS37a (Size of 270.9 kb). The mcr-9 gene was located within the physical boundaries demarcated by two insertion elements IS903 (upstream) and IS1 (downstream) but did not possess the downstream regulatory genes (qseC/qseB) which regulate the expression of mcr- 9. Therefore, the mcr-9 might be silently disseminated among carbapenem-resistant Enterobacterales. In addition to blaVIM-1 and mcr-9, plasmid pMS37a harbored various antibiotic resistance genes including aac(6’)-Il, ΔaadA22, aac(6’)-Ib-cr, sul1, dfrA1 and tetA. To the best of our knowledge, this is the first report of a blaVIM-1 and mcr-9-coharbouring E. hormaechei isolate of food origin worldwide. The identification of a multidrug-resistant VIM-1 and mcr-9 positive Enterobacter hormaechei isolate from food is worrisome as retail meat and meat products could serve as a vehicle for these MDR bacteria, which could be transferred between animals and humans through the food chain. It further highlights that Enterobacterales co-producing MCR and carbapenemases being found in the food chain indeed correspond to a One- Health issue, highlighting the need for serious steps to prevent their further dissemination

Draft genome sequence of a blaNDM-1- and blaOXA-244-carrying multidrug-resistant Escherichia coli D-ST69 clinical isolate from Egypt

Objectives: This study describes the first draft genome sequence of a multidrug- resistant (MDR) Escherichia coli D-ST69 clinical isolate from Egypt carrying blaNDM-1 and blaOXA-244.Methods: The strain was isolated in December 2014 from a wound pus swab of a male patient in the city of Kafr El-Sheikh using MacConkey agar containing 2 μg/mL meropenem. The strain was subjected to antimicrobial susceptibility testing, conjugation experiments, and whole-genome sequencing using an Illumina MiSeq platform.Results: The draft genome of the strain (HR14_AS) was 5.08 Mbp in size containing a total of 90 contigs encoding 4677 predicted genes with an average G+C content of 50.7%. Strain HR14_AS belongs to sequence type 69 (ST69), phylogroup D and exhibits an MDR phenotype, with minimum inhibitory concentrations (MICs) of 64 μg/mL and 32 μg/mL for meropenem and doripenem, respectively. Multiple acquired antimicrobial resistance genes conferring resistance to macrolides [mdf(A)], fluoroquinolones [aac(6')-Ib-cr], quinolones (qnrS1), trimethoprim (dfrA14), β-lactams (blaNDM-1, blaOXA-244, blaCTX-M-15, blaOXA-9 and blaTEM- 1B) and aminoglycosides [aac(3)-IId, aac(6')-Ib, aadA1 and aph(3')-VI] were detected. The blaOXA-244 and blaNDM-1 genes were located on the chromosome (Tn6237) and on an IncI1-type self-conjugative plasmid of >93 kb in size, respectively.Conclusions: Here we report the first draft genome sequence of a MDR E. coli D-ST69 isolate carrying blaNDM-1 and blaOXA-244. Besides clonal expansion of the E. coli ST38 pandemic clone, this study further identified that the spread of OXA- 244-producing E. coli could be related to mobilisation of the IS1R-made composite transposon (Tn6237) carrying blaOXA-244