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BACKGROUND: Critically ill patients commonly suffer from infections that require antimicrobial therapy. In previous studies, liver dysfunction was shown to have an essential impact on the dose selection in these patients. This pilot study aims to assess the influence of liver dysfunction, measured by the novel LiMAx test, on clinical outcomes in critically ill patients treated with linezolid. METHODS: Twenty-nine critically ill patients were included and treated with linezolid. Indications for linezolid therapy were secondary or tertiary peritonitis (46.7%), bloodstream infection (6.7%) and 46.7% were other infections with gram-positive bacteria. Linezolid Cmin, maximal liver function capacity (LiMAx test) and plasma samples were collected while linezolid therapy was in a steady-state condition. Furthermore, potential factors for the clinical outcome were investigated using logistic regression analysis. Clinical cure was defined as the resolution or significant improvement of clinical symptoms without using additional antibiotic therapy or intervention. RESULTS: Cured patients presented lower median linezolid Cmin yet a significantly higher mean LiMAx-value compared to the clinical failure group (1.9 mg/L vs. 5.1 mg/L) (349 μg/kg/h vs. 131 μg/kg/h). In the logistic regression model, LiMAx < 178 μg/kg/h was the only independent predictor of clinical failure with a sensitivity of 77% and specificity of 93%. CONCLUSIONS: The LiMAx test predicts clinical failure more precisely than linezolid trough levels in critically ill surgical patients. Therefore liver failure may have a stronger impact on the outcome of critically ill surgical patients than low linezolid Cmin. While linezolid Cmin failed to predict patient’s outcome, LiMAx results were the only independent predictor of clinical failure.

Objectives: The 25-item Dizziness Handicap Inventory (DHI) is the most used questionnaire to assess vestibular symptoms. However, the abbreviated 10-item DHI-S is more suitable for daily practice. The objective of this study was to assess validity, reliability, responsiveness, optimal cutoff point for substantial impairment, and minimally important change (MIC) of the DHI-S in general practice. Study Design and Setting: We performed a psychometric questionnaire evaluation in general practice. In a prospective cohort study, 415 adults with vestibular symptoms filled out the DHI at baseline, and 1-week, 6-month, and 10-year follow-up. DHI answers were used to calculate DHI-S scores. We assessed validity by criterion validity (Pearson's r) at each measurement. We used longitudinal measurements for test–retest reliability (intraclass correlation coefficient (ICC)) and responsiveness (r). We determined optimal DHI-S cutoff points for substantial impairment (≥30 DHI) and MIC (>11 DHI) with receiver operating characteristic (ROC) curve analyses. Results: DHI-S demonstrated excellent criterion validity (r = 0.93–0.96), test–retest reliability (ICC = 0.86), and responsiveness (r = 0.89). DHI-S reliably distinguished substantial impairment and identified MIC, with optimal DHI-S cutoff scores of ≥12 points and >5 points, respectively. Conclusion: The DHI-S is a valid, reliable, and responsive questionnaire that could replace the DHI in general practice.

PURPOSE: The prognosis of older patients with dizziness in primary care is unknown. Our objective was to determine the prognosis and survival of patients with different subtypes and causes of dizziness.METHODS: In a primary care prospective cohort study, 417 older adults with dizziness (mean age 79 years) received a full diagnostic workup in 2006-2008. A panel of physicians classified the subtype and primary cause of dizziness. Main outcome measures were mortality and dizziness-related impairment assessed at 10-year follow-up.RESULTS: At 10-year follow-up 169 patients (40.5%) had died. Presyncope was the most common dizziness subtype (69.1%), followed by vertigo (41.0%), disequilibrium (39.8%), and other dizziness (1.7%). The most common primary causes of dizziness were cardiovascular disease (56.8%) and peripheral vestibular disease (14.4%). Multivariable adjusted Cox models showed a lower mortality rate for patients with the subtype vertigo compared with other subtypes (hazard ratio [HR] = 0.62; 95% CI, 0.40-0.96), and for peripheral vestibular disease vs cardiovascular disease as primary cause of dizziness (HR = 0.46; 95% CI, 0.25-0.84). After 10 years, 47.7% of patients who filled out the follow-up measurement experienced substantial dizziness-related impairment. No significant difference in substantial impairment was seen between different subtypes and primary causes of dizziness.CONCLUSIONS: The 10-year mortality rate was lower for the dizziness subtype vertigo compared with other subtypes. Patients with dizziness primarily caused by peripheral vestibular disease had a lower mortality rate than patients with cardiovascular disease. Substantial dizziness-related impairment in older patients with dizziness 10 years later is high, and indicates that current treatment strategies by family physicians may be suboptimal.

Effective antibiotic therapy of cerebral infections such as meningitis or ventriculitis is hindered by low penetration into the cerebrospinal fluid (CSF). Because continuous infusion of meropenem and vancomycin and routine therapeutic drug monitoring (TDM) have been proposed to optimize antimicrobial exposure in ventriculitis patients, an individualized dosing strategy was implemented in our department. We present a retrospective analysis of meropenem and vancomycin concentrations in serum and CSF in the first nine ventriculitis patients treated with continuous infusion and TDM-guided dose optimization aiming at 20–30 mg/L. Median initial dosing was 8.8 g/24 h meropenem and 4.25 g/24 h vancomycin, respectively, resulting in median serum concentrations of 21.3 mg/L for meropenem and 24.5 mg/L for vancomycin and CSF concentrations of 3.4 mg/L for meropenem and 1.7 mg/L for vancomycin. Median CSF penetration was 15% for meropenem and 7% for vancomycin. With initial dosing, all but one patient achieved CSF concentrations above 1 mg/L. Dose adjustment according to TDM ensured sufficient CSF concentrations in all patients within 48 h of treatment. Given the limited penetration, continuous infusion of meropenem and vancomycin based on renal function and TDM-guided dose optimization appears a reasonable approach to attain sufficient CSF concentrations in ventriculitis patients.

Background Continuity of care, in particular personal continuity, is a core principle of general practice and is associated with many benefits such as a better patient-provider relationship and lower mortality. However, personal continuity is under pressure due to changes in society and healthcare. This affects older patients more than younger patients. As the number of older patients will double the coming decades, an intervention to optimise personal continuity for this group is highly warranted. Methods Following the UK Medical Research Council framework for complex Interventions, we will develop and evaluate an intervention to optimise personal continuity for older patients in general practice. In phase 0, we will perform a literature study to provide the theoretical basis for the intervention. In phase I we will define the components of the intervention by performing surveys and focus groups among patients, general practitioners, practice assistants and practice nurses, concluded by a Delphi study among members of our group. In phase II, we will test and finalise the intervention with input from a pilot study in two general practices. In phase III, we will perform a stepped wedge cluster randomised pragmatic trial. The primary outcome measure is continuity of care from the patients’ perspective, measured by the Nijmegen Continuity Questionnaire. Secondary outcome measures are level of implementation, barriers and facilitators for implementation, acceptability and feasibility of the intervention. In phase IV, we will establish the conditions for large-scale implementation. Discussion This is the first study to investigate an intervention for improving personal continuity for older patients in general practice. If proven effective, our intervention will enable General practitioners to improve the quality of care for their increasing population of older patients. The pragmatic design of the study will enable evaluation in real-life conditions, facilitating future implementation. Trial registration number Netherlands Trial Register, trial NL8132. Registered 2 November 2019.

Background Accurate identification of older persons at risk of unplanned hospital visits can facilitate preventive interventions. Several risk scores have been developed to identify older adults at risk of unplanned hospital visits. It is unclear whether risk scores developed in one country, perform as well in another. This study validates seven risk scores to predict unplanned hospital admissions and emergency department (ED) visits in older home care recipients from six countries. Methods We used the IBenC sample (n = 2446), a cohort of older home care recipients from six countries (Belgium, Finland, Germany, Iceland, Italy and The Netherlands) to validate four specific risk scores (DIVERT, CARS, EARLI and previous acute admissions) and three frailty indicators (CHESS, Fried Frailty Criteria and Frailty Index). Outcome measures were unplanned hospital admissions, ED visits or any unplanned hospital visits after 6 months. Missing data were handled by multiple imputation. Performance was determined by assessing calibration and discrimination (area under receiver operating characteristic curve (AUC)). Results Risk score performance varied across countries. In Iceland, for any unplanned hospital visits DIVERT and CARS reached a fair predictive value (AUC 0.74 [0.68–0.80] and AUC 0.74 [0.67–0.80]), respectively). In Finland, DIVERT had fair performance predicting ED visits (AUC 0.72 [0.67–0.77]) and any unplanned hospital visits (AUC 0.73 [0.67–0.77]). In other countries, AUCs did not exceed 0.70. Conclusions Geographical validation of risk scores predicting unplanned hospital visits in home care recipients showed substantial variations of poor to fair performance across countries. Unplanned hospital visits seem considerably dependent on healthcare context. Therefore, risk scores should be validated regionally before applied to practice. Future studies should focus on identification of more discriminative predictors in order to develop more accurate risk scores.

Cefiderocol is a new siderophore-cephalosporin for the treatment of multi-drug resistant Gram-negative pathogens. As a reserve agent, it will and should be used primarily in critically ill patients in the upcoming years. Due to the novelty of the substance little data on the pharmacokinetics in critically ill patients with septic shock and renal failure (including continuous renal replacement therapy and cytokine adsorber therapy) is available. We performed therapeutic drug monitoring in a cohort of five patients treated with cefiderocol, to improve the knowledge on pharmacokinetics in this vulnerable patient population. As expected for a cephalosporin with predominantly renal elimination the maintenance dose could be reduced in patients with renal impairment or on continuous renal replacement therapy. The manufacturer's dosing instructions were sufficient to achieve a drug level well above the MIC. However, the addition of a cytokine adsorber might reduce serum levels substantially, so that in this context therapeutic drug monitoring and dose adjustment are recommended.

PURPOSE In critically ill patients, changes in the pharmacokinetics (PK) of β-lactams can lead to significant variations in serum concentrations, with possibly detrimental effects on outcomes. The utilization of individually calculated doses, extended infusion regimens, and therapeutic drug monitoring (TDM)-guided dose adjustments can mitigate the PK changes and help to achieve and attain an individual PK target. METHODS We reviewed relevant literature from 2004-2021 using four search engines (PubMed, Web of Science, Scopus, and Google Scholar). Unpublished clinical data were also examined. RESULTS TDM-guided, individualized dosing strategies facilitated PK target attainment and improved patient outcomes. TDM-guided therapy is a core concept of individualized dosing that increases PK target attainment and monitors possible toxic β-lactam concentrations. CONCLUSION Individualized dosing and TDM facilitate the rational use of β-lactams and are integral for antibiotic stewardship interventions in critical care, affording both the optimal exposure of pathogen and drugs, along with enhanced treatment efficacy and reduced emergence of antimicrobial resistance.

Optimization of antibiotic dosing is a treatment intervention that is likely to improve outcomes in severe infections. The aim of this retrospective study was to describe the therapeutic exposure of steady state piperacillin concentrations (cPIP) and clinical outcome in critically ill patients with sepsis or septic shock who received continuous infusion of piperacillin with dosing personalized through software-guided empiric dosing and therapeutic drug monitoring (TDM). Therapeutic drug exposure was defined as cPIP of 32–64 mg/L (2–4× the ‘MIC breakpoint’ of Pseudomonas aeruginosa). Of the 1544 patients screened, we included 179 patients (335 serum concentrations), of whom 89% achieved the minimum therapeutic exposure of &gt, 32 mg/L and 12% achieved potentially harmful cPIP &gt, 96 mg/L within the first 48 h. Therapeutic exposure was achieved in 40% of the patients. Subsequent TDM-guided dose adjustments significantly enhanced therapeutic exposure to 65%, and significantly reduced cPIP &gt, 96 mg/L to 5%. Mortality in patients with cPIP &gt, 96 mg/L (13/21, 62%) (OR 5.257, 95% CI 1.867–14.802, p = 0.001) or 64–96 mg/L (30/76, 45%) (OR 2.696, 95% CI 1.301–5.586, p = 0.007) was significantly higher compared to patients with therapeutic exposure (17/72, 24%). Given the observed variability in critically ill patients, combining the application of dosing software and consecutive TDM increases therapeutic drug exposure of piperacillin in patients with sepsis and septic shock.

RBP-6000, referred to as BUP-XR (extended-release buprenorphine), is a subcutaneously injected, monthly buprenorphine treatment for opioid use disorder. BUP-XR provides sustained buprenorphine plasma concentrations to block drug-liking of abused opioids over the entire monthly dosing period, while controlling withdrawal and craving symptoms. Administration of BUP-XR in a health-care setting also mitigates abuse, misuse, diversion, and unintentional exposure. We aimed to investigate the efficacy of different BUP-XR dosing regimens in participants with opioid use disorder.This randomised, double-blind, placebo-controlled, phase 3 trial was done at 36 treatment centres in the USA. Treatment-seeking adults aged 18-65 years who had moderate or severe opioid use disorder (as defined by the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders) entered an open-label run-in phase of up to 2 weeks' treatment with buprenorphine-naloxone sublingual film. Eligible participants were then randomly assigned (4:4:1:1) with an interactive voice/web-response system to receive BUP-XR 300 mg/300 mg (six injections of 300 mg), BUP-XR 300 mg/100 mg (two injections of 300 mg plus four injections of 100 mg), or volume-matched placebo every 28 days, and received weekly individual drug counselling. No supplemental buprenorphine was allowed. The primary efficacy endpoint was participants' percentage abstinence from opioid use, defined as the percentage of each participant's negative urine samples and self-reports of illicit opioid use from week 5 to week 24, analysed in the full analysis set. Safety was assessed in all participants who received at least one dose of BUP-XR or placebo. This study is registered with ClinicalTrials.gov, number NCT02357901.From Jan 28, 2015, to Nov 12, 2015, 1187 potential participants were screened, 665 entered run-in, and 504 received BUP-XR 300 mg/300 mg (n=201), BUP-XR 300 mg/100 mg (n=203), or placebo (n=100). Mean participants' percentage abstinence was 41·3% (SD 39·7) for BUP-XR 300 mg/300 mg and 42·7% (38·5) for 300 mg/100 mg, compared with 5·0% (17·0) for placebo (p0·0001 for both BUP-XR regimens). No compensatory non-opioid drug use was observed during BUP-XR treatment. The most common adverse events were headache (17 [8%] participants in the BUP-XR 300 mg/300 mg group vs 19 [9%] participants in the BUP-XR 300 mg/100 mg group vs six [6%] participants in the placebo group), constipation (16 [8%] vs 19 [9%] vs 0), nausea (16 [8%] vs 18 [9%] vs five [5%]), and injection-site pruritis (19 [9%] vs 13 [6%] vs four [4%]). The BUP-XR safety profile was consistent with other buprenorphine products for treatment of opioid use disorder, except for injection-site reactions, which were reported in more than 5% of all participants who received BUP-XR, but were mostly mild and not treatment-limiting.Participants' percentage abstinence was significantly higher in both BUP-XR groups than in the placebo group. Treatment with BUP-XR was also well tolerated. The availability of this monthly formulation, delivered by health-care providers, represents an advance in treatment for opioid use disorder that enhances the benefits of buprenorphine by delivering sustained, optimal exposure, while reducing risks of current buprenorphine products.Indivior.

Objectives: The aim of this study is to describe the in vitro adsorption of anti-infective drugs onto an extracorporeal cytokine adsorber. Methods: Various anti-infective drugs (β-lactams, quinolones, aminoglycosides, glycopeptides, azole antimycotics) were prepared in normal saline 0.9% and human albumin 5%, and pumped through a cytokine cartridge (CytoSorb®; CytoSorbents Corporation, Monmouth Junction, NJ, USA) at a flow rate of 1.2 L/h for 1.5 h. In addition, meropenem and ciprofloxacin were dissolved in reconstituted blood and run through a CytoSorb cartridge, which was integrated into a continuous renal replacement therapy circuit with a flow rate of 2 L/h for 18 h. Samples from the solution, pre- and post-filter, were quantified by high-performance liquid chromatography with ultraviolet detection and fluorescence polarisation immunoassay. Results: Observed mean clearance of the drugs in normal saline was 1.22 ± 0.07 L/h. In human albumin, clearance was 1.29 ± 0.08 L/h. In reconstituted blood, clearance of meropenem decreased from 5.4 to 1.4 L/h and for ciprofloxacin from 6.3 to 4.3 L/h within the first 1.5 h because of early drug adsorption. Continuous renal replacement therapy clearance measured without CytoSorb was stable at 2 and 1.7 L/h, respectively. Approximately 400 mg of meropenem and 300 mg of ciprofloxacin had been adsorbed by CytoSorb, suggesting that these amounts are the maximum adsorptive capacity for these drugs. Conclusion: In these settings, all tested drugs were adsorbed by the cartridge in relevant amounts. The identified maximum adsorptive capacity and the rapid decline in concentration during the first 1.5 h of CytoSorb use suggest that the administration of an additional dose within the first hours of CytoSorb treatment may be reasonable. In addition, early therapeutic drug monitoring should be considered.

Cefiderocol is a new siderophore-cephalosporin for the treatment of multi-drug resistant Gram-negative pathogens. As a reserve agent, it will and should be used primarily in critically ill patients in the upcoming years. Due to the novelty of the substance little data on the pharmacokinetics in critically ill patients with septic shock and renal failure (including continuous renal replacement therapy and cytokine adsorber therapy) is available. We performed therapeutic drug monitoring in a cohort of five patients treated with cefiderocol, to improve the knowledge on pharmacokinetics in this vulnerable patient population. As expected for a cephalosporin with predominantly renal elimination the maintenance dose could be reduced in patients with renal impairment or on continuous renal replacement therapy. The manufacturer’s dosing instructions were sufficient to achieve a drug level well above the MIC. However, the addition of a cytokine adsorber might reduce serum levels substantially, so that in this context therapeutic drug monitoring and dose adjustment are recommended.

Hintergrund: Notaufnahmen sind in Deutschland zentraler Anlaufpunkte für akute medizinische Notfälle. Sie stellen damit eine wichtige Datenquelle dar, um Häufungen gesundheitlicher Probleme frühzeitig zu erkennen. Das AKTIN-Notaufnahmeregister ist ein föderiertes Forschungsregister[zum vollständigen Text gelangen Sie über die oben angegebene URL], 65th Annual Meeting of the German Association for Medical Informatics, Biometry and Epidemiology (GMDS), Meeting of the Central European Network (CEN: German Region, Austro-Swiss Region and Polish Region) of the International Biometric Society (IBS)

Background Existing studies have yet to investigate the perspectives of patients and professionals concerning relapse prevention programs for patients with remitted anxiety or depressive disorders in primary care. User opinions should be considered when optimizing the use and implementation of interventions. Objective This study aimed to evaluate the GET READY relapse prevention programs for patients with remitted anxiety or depressive disorders in general practice. Methods Semistructured interviews (N=26) and focus group interviews (N=2) with patients and mental health professionals (MHPs) in the Netherlands were performed. Patients with remitted anxiety or depressive disorders and their MHPs who participated in the GET READY study were interviewed individually. Findings from the interviews were tested in focus group interviews with patients and MHPs. Data were analyzed using thematic analysis. Results Participants were positive about the program because it created awareness of relapse risks. Lack of motivation, lack of recognizability, lack of support from the MHP, and symptom severity (too low or too high) appeared to be limiting factors in the use of the program. MHPs play a crucial role in motivating and supporting patients in relapse prevention. The perspectives of patients and MHPs were largely in accordance, although they had different perspectives concerning responsibilities for taking initiative. Conclusions The implementation of the GET READY program was challenging. Guidance from MHPs should be offered for relapse prevention programs based on eHealth. Both MHPs and patients should align their expectations concerning responsibilities in advance to ensure optimal usage. Usage of blended relapse prevention programs may be further enhanced by diagnosis-specific programs and easily accessible support from MHPs. International Registered Report Identifier (IRRID) RR2-10.1186/s12888-019-2034-6

Although primary care physicians (PCPs) regularly encounter patients with dizziness or vestibular symptoms, they often consider these patients as difficult, challenging or even heartsink (1, 2). Given the current scientific evidence and available “vestibular tools,” this is unnecessary. We will provide ten vestibular tools that should not be missed, following definition, diagnosis, treatment, and prognosis, respectively (Figure 1). Open in a separate window Figure 1 Ten vestibular tools for primary care.

Cefiderocol is a new siderophore cephalosporin approved for the treatment of multidrug resistant bacteria including activity against carbapenem-resistant Enterobacterales and Pseudomonas aeruginosa. As cephalosporins are known for their high pharmacokinetic variability in critically ill patients, cefiderocol therapeutic drug monitoring might become a valuable tool. Therefore, we aimed to develop and validate a simple, rapid, cost-effective high performance liquid chromatography (HPLC) method for the quantification of cefiderocol in serum. Samples were treated for protein precipitation followed by chromatographic separation on a reverse phase column (HPLC C-18) with gradient elution of the mobile phase. Cefiderocol was detected via UV absorption and quantification was performed with the internal standard (metronidazole) method. The calibration range showed linearity from 4 to 160 mg/L. The intra and interday precision was less than 10% with a recovery rate of 81%. The method was successfully used for the analysis of subsequent serum samples of critically ill patients and showed good performance in monitoring serum levels and optimizing antibiotic therapy.

Background: No studies have examined the underlying structure or predictive validity of the Cognitive Therapy Adherence and Competence Scale (CTACS). Examining the structure of the CTACS is of great relevance because it could provide information on what constitutes competence in CBT, and whether some underlying factors are more important for predicting treatment outcomes than others. This study investigates the psychometric properties of the Norwegian version of CTACS and its associations with treatment outcomes in a sample of primary care clients who received CBT for anxiety and/or depression.Method: Independent assessors rated audiotaped therapy sessions (early, mid and late in treatment) in a sample of 132 primary care clients (mean [SD] age = 34.8 [11.8], 63.6% women), participating in the Prompt Mental Health Care trial. Outcomes were symptoms of anxiety and depression assessed by patient self-report questionnaires. Structural validity was examined by means of confirmatory and exploratory factor analyses (CFA/EFA), whereas longitudinal associations with treatment outcome were explored by adopting multilevel modeling.Results: No evidence was found for the divergent validity of the constructs competence and adherence as indicated by a very high correlation between these two subscales in CTACS (0.97). Regarding reliability, ICCs for the mean score of the full competence scale and its associated subscales were generally good to excellent (0.70–0.80), although the subscale measuring the quality of the therapeutic relationship was relatively low (0.44). Internal consistency was overall acceptable, but our CFA models did not provide an acceptable fit for the pre-specified one-factor and four-factor solutions. EFA results were difficult to interpret, with a sub-optimal three-factor solution providing best model fit and only two meaningful factors [CBT specific skills (α = 0.82) and session structure (α = 0.59)]. Overall, the results indicated no evidence for the scales' predictive validity.Conclusion: Our findings point to several psychometric problems of the CTACS that may limit both its research and clinical utility. The importance of providing empirical evidence for both reliability and validity aspects of scales are discussed and suggestions for future research are provided.

Background We aimed to compare different methods to treat lower leg soft tissue defects with tibia fracture using free flaps and pedicled flaps. We also highlighted the aesthetic outcome after using 1-stage secondary debulking procedure for tibia area. Patients and methods From December 2000 to March 2017, 83 patients with lower leg defects and tibia fractures were reconstructed using 71 free flaps and 12 pedicled flaps. One-stage secondary debulking procedures were performed for 39 patients after flap reconstruction. Infection control and aesthetic outcomes using 5-point Likert scale were reviewed after a 16-month follow-up. Results Twenty-five myocutaneous free flaps, 45 fasciocutaneous free flaps, 1 fibula free flap, 12 pedicled flaps of which 8 were distally based sural artery flaps, and 4 medial gastrocnemius flaps were used. The flap survival rate was 100%. There was no recurrence of osteomyelitis in any patient after reconstruction with any of these flaps. Using a 5-point Likert scale, performance of a 1-stage secondary debulking procedure showed statistically significant difference in terms of contour, color, and texture compared with the group without debulking procedure. Conclusions The use of free flaps and pedicled flaps in the reconstruction of lower leg defects with tibia fracture is reliable and results in good infection control. A 1-stage secondary debulking procedure delivers excellent long-term aesthetic outcome after reconstruction of the tibia area.

Background Due to high pharmacokinetic variability, standard doses of meropenem are frequently inadequate in septic patients. Therapeutic drug monitoring of meropenem is not widely available; therefore, improved empiric dosing recommendations are needed. Objectives This study aimed to compare the attainment of pharmacologic targets for two common empirical dosing regimens for meropenem in patients with septic shock. Methods Two empiric dosing schemes for meropenem were compared using extended infusions (120 minutes) in 32 patients with septic shock in the intensive care units at two different hospitals. One regimen was 3 × 2 g meropenem/24 h for two days, followed by 3 × 1 g meropenem/24 h; the other regimen was 4 × 1 g meropenem/24 h. Serum meropenem concentrations were measured for the first 72 h of therapy, and pharmacokinetic modelling was performed to define the percentage of time the free drug concentration was above various target MICs for each regimen (%fT>MIC). Results Both regimens led to a sufficiently high %fT>MIC for pathogens with target MICs MIC of 4 × 1 g meropenem decreased faster than that of 3 × 2 g meropenem. At high MICs of 32 mg/L, both dosing regimens failed to provide appropriate drug concentrations. Renal function was a significant covariate of target attainment. Conclusions The results of this study can guide clinicians in their choice of an empirical dosing regimen for meropenem. If pathogens with low MICs (

ObjectivesTo develop and internally validate prediction models to assess treatment success of both stand-alone and blended online vestibular rehabilitation (VR) in patients with chronic vestibular syndrome.DesignSecondary analysis of a randomised controlled trial.Setting59 general practices in The Netherlands.Participants202 adults, aged 50 years and older with a chronic vestibular syndrome who received either stand-alone VR (98) or blended VR (104). Stand-alone VR consisted of a 6-week, internet-based intervention with weekly online sessions and daily exercises. In blended VR, the same intervention was supplemented with physiotherapy support.Main outcome measuresSuccessful treatment was defined as: clinically relevant improvement of (1) vestibular symptoms (≥3 points improvement Vertigo Symptom Scale—Short Form); (2) vestibular-related disability (>11 points improvement Dizziness Handicap Inventory); and (3) both vestibular symptoms and vestibular-related disability. We assessed performance of the predictive models by applying calibration plots, Hosmer-Lemeshow statistics, area under the receiver operating characteristic curves (AUC) and applied internal validation.ResultsImprovement of vestibular symptoms, vestibular-related disability or both was seen in 121, 81 and 64 participants, respectively. We generated predictive models for each outcome, resulting in different predictors in the final models. Calibration for all models was adequate with non-significant Hosmer-Lemeshow statistics, but the discriminative ability of the final predictive models was poor (AUC 0.54 to 0.61). None of the identified models are therefore suitable for use in daily general practice to predict treatment success of online VR.ConclusionIt is difficult to predict treatment success of internet-based VR and it remains unclear who should be treated with stand-alone VR or blended VR. Because we were unable to develop a useful prediction model, the decision to offer stand-alone or blended VR should for now be based on availability, cost effectiveness and patient preference.Trial registration numberThe Netherlands Trial Register NTR5712.

BackgroundInternet-based vestibular rehabilitation (VR) with physiotherapy support, known as blended VR, was effective in reducing vestibular symptoms in a recent randomised controlled trial. Blended VR is a complex intervention comprised of physiotherapeutic visits, the vertigo training website, and VR exercises. Because of these interacting components, it is important to understand how blended VR works, for whom it works best, and how it should ideally be delivered.AimTo investigate the experiences of both patients and physiotherapists with blended internet-based VR.Design & settingA qualitative interview study was performed with patients who received blended internet-based VR with physiotherapy support, and physiotherapists who provided this support.MethodSemi-structured interviews were conducted with 14 patients and eight physiotherapists after the 6-month follow-up of the randomised trial. All interviews were audio-recorded, transcribed, and thematically analysed.ResultsAccording to both patients and physiotherapists, the physiotherapist visits were useful in providing personal attention, helping patients safely execute exercises, and improving patients’ adherence to therapy. Some patients said they did not need physiotherapist support and, according to physiotherapists, both the necessity and the optimal way to deliver guidance differed greatly between patients. The Vertigo Training website and exercises provided patients with a sense of control over their symptoms. Patients reported that the VR exercises were easy to perform and most patients continued to use them long after the trial ended.ConclusionIn blended VR, physiotherapeutic visits appear to offer benefits above the vertigo training website and VR exercises alone. Physiotherapy support may best be used when individually tailored.

Background: Given the poor prognosis of late-life depression, it is crucial to identify those at risk. Our objective was to construct and validate a prediction rule for an unfavourable course of late-life depression.Methods: For development and internal validation of the model, we used The Netherlands Study of Depression in Older Persons (NESDO) data. We included participants with a major depressive disorder (MDD) at baseline (n = 270; 60-90 years), assessed with the Composite International Diagnostic Interview (CIDI). For external validation of the model, we used The Netherlands Study of Depression and Anxiety (NESDA) data (n = 197; 50-66 years). The outcome was MDD after 2 years of follow-up, assessed with the CIDI. Candidate predictors concerned sociodemographics, psychopathology, physical symptoms, medication, psychological determinants, and healthcare setting. Model performance was assessed by calculating calibration and discrimination.Results: 111 subjects (41.1%) had MDD after 2 years of follow-up. Independent predictors of MDD after 2 years were (older) age, (early) onset of depression, severity of depression, anxiety symptoms, comorbid anxiety disorder, fatigue, and loneliness. The final model showed good calibration and reasonable discrimination (AUC of 0.75; 0.70 after external validation). The strongest individual predictor was severity of depression (AUC of 0.69; 0.68 after external validation).Limitations: The model was developed and validated in The Netherlands, which could affect the cross-country generalizability.Conclusions: Based on rather simple clinical indicators, it is possible to predict the 2-year course of MDD. The prediction rule can be used for monitoring MDD patients and identifying those at risk of an unfavourable outcome.

Pathophysiological changes are important risk factors for critically ill patients with pneumonia manifesting sub-therapeutic antibiotic exposures during empirical treatment. The effect of coronavirus disease 2019 (COVID-19) on antibiotic dosing requirements is uncertain. We aimed to determine the effect of COVID-19 on ß-lactam pharmacokinetics (PK) and PK target attainment in critically ill patients with a personalized dosing strategy. Retrospective, single-center analysis of COVID-19 ± critically ill patients with pneumonia (community-acquired pneumonia or hospital-acquired pneumonia) who received continuous infusion of a ß-lactam antibiotic with dosing personalized through dosing software and therapeutic drug monitoring. A therapeutic exposure was defined as serum concentration between (css) 4 to 8 times the EUCAST non-species related breakpoint). Data from 58 patients with pneumonia was analyzed. Nineteen patients were tested COVID-19-positive before the start of the antibiotic therapy for community-acquired pneumonia or hospital-acquired pneumonia. Therapeutic exposure was achieved in 71% of COVID-19 patients (68% considering all patients). All patients demonstrated css above the non–species-related breakpoint. Twenty percent exceeded css above the target range (24% of all patients). The median ß-lactam clearance was 49% compared to ß-lactam clearance in a standard patient without a significant difference regarding antibiotic, time of sampling or present COVID-19 infection. Median daily doses were 50% lower compared to standard bolus dosing. COVID-19 did not significantly affect ß-lactam pharmacokinetics in critically ill patients. Personalized ß-lactam dosing strategies were safe in critically ill patients and lead to high PK target attainment with less resources.

Patients in the intensive care unit frequently require antibiotic treatment. Liver impairment poses substantial challenges for dose selection in these patients. The aim of the present pilot study was to assess the novel maximal liver function capacity (LiMAx test) in comparison with conventional liver function markers as covariates of drug clearance in liver failure using linezolid as a model drug. A total of 28 patients with different degrees of liver failure were recruited. LiMAx test as well as plasma, dialysate and urine sampling were performed under linezolid steady-state therapy (600 mg twice daily). NONMEM® was used for a pharmacometric analysis in which the different clearance routes of linezolid were elucidated. Linezolid pharmacokinetics was highly variable in patients with liver failure. The LiMAx score displayed the strongest association with non-renal clearance (CLnon-renal) [ = 4.46∙(body weight/57.9) 0.75∙(LiMAx/221.5)0.388 L/h], which reduced interindividual variability in CLnon-renal from 46.6% to 33.6%, thereby being superior to other common markers of liver function (international normalised ratio, gamma-glutaryl transferase, bilirubin, thrombocytes, alanine aminotransferase, aspartate aminotransferase). For LiMAx < 100 µg/kg/h, 64% of linezolid trough concentrations were above the recommended trough concentration of 8 mg/L, indicating the necessity of therapeutic drug monitoring in these patients. This is the first pilot application of the LiMAx test in a pharmacokinetic (PK) study demonstrating its potential to explain PK variability in linezolid clearance. Further studies with a larger patient collective and further drugs are highly warranted to guide dosing in patients with severe liver impairment.

Objective: To investigate the use of canalith repositioning manoeuvres and vestibular rehabilitation (VR) by GPs and to assess reasons for not using these techniques in patients with vertigo. Design: Online survey. Setting: GPs in the western and central part of the Netherlands. Subjects and method: Of GPs, 1169 were approached to participate in the survey. A sample of 426 GPs filled out the questionnaire (36.4% response rate). The 22-item questionnaire contained both multiple choice and free-text questions on the Epley manoeuvre, the Brandt-Daroff exercises and VR. Results of the survey were descriptively analyzed. Main outcome measures: The use of the Epley manoeuvre, the Brandt-Daroff exercises and VR by GPs; reasons that deter GPs from using these techniques. Results: The repositioning manoeuvres (Epley manoeuvre and Brandt-Daroff exercises) were used by approximately half of all GPs (57.3 and 50.2%), while only a small group of GPs applied VR (6.8%). The most important reason for GPs not to use the Epley manoeuvre, Brandt-Daroff exercises and VR was that they did not know how to perform the technique (49.5, 89.6 and 92.4%). Conclusions: Despite the proven effectiveness, repositioning manoeuvres and VR are remarkably underused by Dutch GPs. Not knowing how to perform the technique is the most important reason for GPs not to use these techniques. Efforts should be made to increase the knowledge and skills of GPs regarding canalith repositioning manoeuvres and VR. Key points • Dizziness is a common symptom with limited therapeutic options. • Canalith repositioning manoeuvres and vestibular rehabilitation represent the best treatment options currently available for vertigo. • Canalith repositioning manoeuvres and vestibular rehabilitation are still widely underused by GPs. • The most important reason for GPs not to use these techniques is that they do not know how to perform them. • Efforts should be made to increase the knowledge and skills of GPs regarding canalith repositioning manoeuvres and vestibular rehabilitation.

ObjectiveTo investigate the clinical effectiveness and safety of stand alone and blended internet based vestibular rehabilitation (VR) in the management of chronic vestibular syndromes in general practice.DesignPragmatic, three armed, parallel group, individually randomised controlled trial.Setting59 general practices in the Netherlands.Participants322 adults aged 50 and older with a chronic vestibular syndrome.InterventionsStand alone VR comprising a six week, internet based intervention with weekly online sessions and daily exercises (10-20 minutes a day). In the blended VR group, the same internet based intervention was supplemented by face-to-face physiotherapy support (home visits in weeks 1 and 3). Participants in the usual care group received standard care from a general practitioner, without any restrictions.Main outcome measuresThe primary outcome was vestibular symptoms after six months as measured by the vertigo symptom scale-short form (VSS-SF range 0-60, clinically relevant difference ≥3 points). Secondary outcomes were dizziness related impairment, anxiety, depressive symptoms, subjective improvement of vestibular symptoms after three and six months, and adverse events.ResultsIn the intention-to-treat analysis, participants in the stand alone and blended VR groups had lower VSS-SF scores at six months than participants in the usual care group (adjusted mean difference −4.1 points, 95% confidence interval −5.8 to −2.5; and −3.5 points, −5.1 to −1.9, respectively). Similar differences in VSS-SF scores were seen at three months follow-up. Participants in the stand alone and blended VR groups also experienced less dizziness related impairment, less anxiety, and more subjective improvement of vestibular symptoms at three and six months. No serious adverse events related to online VR occurred during the trial.ConclusionStand alone and blended internet based VR are clinically effective and safe interventions to treat adults aged 50 and older with a chronic vestibular syndrome. Online VR is an easily accessible form of treatment, with the potential to improve care for an undertreated group of patients in general practice.Trial registrationNetherlands Trial Register NTR5712.

Fragestellung: 85,5 % aller Deutschen leiden mindestens einmalig in ihrem Leben an Rückenschmerzen, wovon rund 19 % schwerwiegend sind (Korff Grad II – IV). Die Nationale VersorgungsLeitlinie (NVL) „Nicht-spezifischer Kreuzschmerz“ benennt die Schmerzmessung als eines[zum vollständigen Text gelangen Sie über die oben angegebene URL], Deutscher Kongress für Orthopädie und Unfallchirurgie (DKOU 2019)

Standard dosing and intermittent bolus application (IB) are important risk factors for pharmacokinetic (PK) target non-attainment during empirical treatment with β-lactams in critically ill patients, particularly in those with sepsis and septic shock. We assessed the effect of therapeutic drug monitoring-guided (TDM), continuous infusion (CI) and individual dosing of piperacillin/tazobactam (PIP) on PK-target attainment in critically ill patients. This is a retrospective, single-center analysis of a database including 484 patients [933 serum concentrations (SC)] with severe infections, sepsis and septic shock who received TDM-guided CI of PIP in the intensive care unit (ICU) of an academic teaching hospital. The PK-target was defined as a PIP SC between 33 and 64 mg/L [fT > 2–4 times the epidemiological cutoff value (ECOFF) of Pseudomonas aeruginosa (PSA)]. PK-target attainment with standard dosing (initial dose) was observed in 166 patients (34.3%), whereas only 49 patients (10.1%) demonstrated target non-attainment. The minimum PK-target of ≥ 33 mg/L was overall realized in 89.9% (n = 435/484) of patients after the first PIP dose including 146 patients (30.2%) with potentially harmful SCs ≥ 100 mg/L. Subsequent TDM-guided dose adjustments significantly enhanced PK-target attainment to 280 patients (62.4%) and significantly reduced the fraction of potentially overdosed (≥ 100 mg/L) patients to 4.5% (n = 20/449). Renal replacement therapy (RRT) resulted in a relevant reduction of PIP clearance (CLPIP): no RRT CLPIP 6.8/6.3 L/h (median/IQR) [SCs n = 752, patients n = 405], continuous veno-venous hemodialysis (CVVHD) CLPIP 4.3/2.6 L/h [SCs n = 160, n = 71 patients], intermittent hemodialysis (iHD) CLPIP 2.6/2.3 L/h [SCs n = 21, n = 8 patients]). A body mass index (BMI) of > 40 kg/m2 significantly increased CLPIP 9.6/7.7 L/h [SC n = 43, n = 18 patients] in these patients. Age was significantly associated with supratherapeutic PIP concentrations (p

Background Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection with a hospital mortality in excess of 40%. Along with insufficient and delayed empirical antimicrobial therapy, inappropriate antimicrobial exposure has been identified to negatively affect patient outcomes. Receipt of prolonged infusion (i.e. extended or continuous infusion) of piperacillin/tazobactam (TZP) improves antimicrobial exposure and is associated with reduced mortality in patients with sepsis. Using therapeutic drug monitoring (TDM) with dosing tailored to the altered pharmacokinetics of the individual patient to avoid under- and overdosing may be a further strategy to improve patient outcomes. This current trial will address the question whether a TDM-guided therapy with TZP administered by continuous infusion will result in a greater resolution of organ dysfunction and hence better clinical outcome compared to continuous infusion of the total daily dose of TZP without TDM. Methods The study is an investigator-initiated, multi-centre, parallel-group, single-blinded, randomised controlled trial. The trial will be conducted in several centres across Germany. Adult patients (aged ≥ 18 years) with severe sepsis or septic shock will be eligible for study participation. Participants will be randomly assigned to receive either TZP by continuous infusion guided by daily TDM of piperacillin (experimental group) or by continuous infusion without TDM guidance (total daily dose in normal renal function 13.5 g TZP) (control group). The pharmacokinetic (PK)/pharmacodynamic (PD) target will be 100% f T>4MIC (percentage of time during a dosing interval that the free [f] drug concentration exceeds 4 times the minimum inhibitory concentration). The primary efficacy endpoint is the change in mean total Sequential Organ Failure Assessment score from day 1 after randomisation until day 10 or discharge from the intensive care unit or death, whichever comes first. Secondary outcomes include mortality, clinical cure, microbiological cure, overall antibiotic use, individual components of the primary outcome, adverse events and analysis of PK and (PD) indices. Discussion This trial will assess for the first time whether continuous infusion of TZP guided by daily TDM in patients with sepsis will result in a greater resolution of organ dysfunction and hence better clinical outcome compared to continuous infusion without TDM. Trial registration German Clinical Trials Register (GermanCTR), DRKS00011159. Registered on 10 October 2016. Electronic supplementary material The online version of this article (10.1186/s13063-019-3437-x) contains supplementary material, which is available to authorized users.

Background Since anxiety and depressive disorders often recur, self-management competencies are crucial for improving the long-term course of anxiety and depressive disorders. However, few relapse prevention programmes are available that focus on improving self-management. E-health combined with personal contact with a mental health professional in general practice might be a promising approach for relapse prevention. In this protocol, the GET READY (Guided E-healTh for RElapse prevention in Anxiety and Depression) study will be described in which a relapse prevention programme is developed, implemented and evaluated. The aim of the study is to determine patients’ usage of the programme and the associated course of their symptoms, to examine barriers and facilitators of implementation, and to assess patients’ satisfaction with the programme. Methods Participants are discharged from mental healthcare services, and are in complete or partial remission. They receive access to an E-health platform, combined with regular contact with a mental health professional in general practices. Online questionnaires will be completed at baseline and after 3, 6 and 9 months. Also, semi-structured qualitative individual interviews and focus group interviews will be conducted with patients and mental health professionals. Discussion This mixed-methods observational cohort study will provide insights into the use of a relapse prevention programme in relation to the occurrence of symptoms, as well as in its implementation and evaluation. Using the results of this study, the relapse prevention programme can be adapted in accordance with the needs of patients and mental health professionals. If this programme is shown to be acceptable, a randomized controlled trial may be conducted to test its efficacy. Trial registration Retrospectively registered in the Netherlands Trial Register (NTR7574; 25 October 2018). Electronic supplementary material The online version of this article (10.1186/s12888-019-2034-6) contains supplementary material, which is available to authorized users.

OBJECTIVES: The prevalence of different geriatric syndromes in older home care (HC) recipients is yet to be determined. Dizziness is often regarded as a geriatric syndrome. The natural course of dizziness in older people is still unknown, because of a lack of longitudinal studies. The objective of this study was to investigate the prevalence and persistence of dizziness in HC recipients. DESIGN: Prospective cohort study. SETTING: Home care organizations in 6 European countries participating in the EU-funded Identifying best practices for care-dependent elderly by Benchmarking Costs and outcomes of community care (IBenC) project. PARTICIPANTS: 2616 community-dwelling long-term HC recipients aged 65 years or older. METHODS: Data were collected at baseline and 6 and 12 months by using the interRAI Home Care instrument (interRAI-HC). Dizziness status was assessed by the number of days people experienced dizziness in the last 3 days (0-3) and later dichotomized for analyses (present or not in the last 3 days). Dizziness persistence was defined as the odds for dizzy people at baseline to also report dizziness at subsequent follow-up moments, compared with people who were not dizzy at baseline. The pattern of dizziness was descriptively analyzed in recipients who completed all measurements. Generalized estimating equations analysis was used to determine the persistence of dizziness symptoms. RESULTS: The prevalence of dizziness of 2616 eligible HC recipients at baseline was 25.1%, ranging from 16.2% (Belgium) to 39.7% (Italy). The majority of dizzy recipients at baseline also experienced dizziness after 6 and 12 months (79.1%). Dizziness persistence was high at 6 months [odds ratio (OR) 57.8, 95% confidence interval (CI) 43.1-77.5] and at 12 months (OR 30.2, 95% CI 22.3-41.1). CONCLUSIONS AND IMPLICATIONS: Dizziness in older HC recipients in Europe is common, and dizziness persistence is high. This warrants a more active approach in treating dizziness in older HC recipients. ispartof: Journal Of The American Medical Directors Association vol:21 issue:3 pages:338-343 ispartof: location:United States status: published

PURPOSE Because dizziness in older people is often chronic and can substantially affect daily functioning, it is important to identify those at risk for an unfavorable course of dizziness to optimize their care. We aimed to develop and externally validate a prediction model for an unfavorable course of dizziness in older patients in primary care, and to construct an easy-to-use risk prediction tool. METHODS We used data from 2 prospective cohorts: a development cohort with 203 patients aged 65 years or older who consulted their primary care physician for dizziness and had substantial dizziness-related impairment (Dizziness Handicap Inventory [DHI] ≥30), and a validation cohort with 415 patients aged 65 years or older who consulted their primary care physician for dizziness of any severity. An unfavorable course was defined as presence of substantial dizziness-related impairment (DHI ≥30) after 6 months. RESULTS Prevalence of an unfavorable course of dizziness was 73.9% in the development cohort and 43.6% in the validation cohort. Predictors in the final model were the score on the screening version of the DHI, age, history of arrhythmia, and looking up as a provoking factor. The model showed good calibration and fair discrimination (area under the curve = 0.77). On external validation, discriminative ability remained stable (area under the curve = 0.78). The constructed risk score was strongly correlated with the prediction model. Performance measures for risk score cut-off values are presented to determine the optimal cut-off point for clinical practice. CONCLUSIONS We developed an easy-to-use risk score for dizziness-related impairment in primary care. The risk score, consisting of only 4 predictors, will help primary care physicians identify patients at high risk for an unfavorable course of dizziness.

BACKGROUND Vancomycin is recommended for ventriculitis. However, penetration into the CNS is relatively poor. OBJECTIVES To investigate the population pharmacokinetics of vancomycin in serum and CSF in critical care patients with proven or suspected CNS infections from neurosurgical procedures. PATIENTS AND METHODS This was an observational pharmacokinetic study in critical care patients with proven or suspected CNS infections receiving intravenous vancomycin. Multiple blood and intraventricular CSF samples were collected. Population pharmacokinetic analysis and simulation were undertaken with ADAPT5 and Pmetrics. RESULTS A total of 187 blood and CSF samples were collected from 21 patients. The median (range) Cmax and Cmin concentrations in serum were 25.67 (10.60-50.78) and 9.60 (4.46-23.56) mg/L, respectively, with a median daily dose of 2500 (500-4000) mg. The corresponding median concentrations in CSF were 0.65 (

Background: Optimal antibiotic exposure is a vital but challenging prerequisite for achieving clinical success in ICU patients. Objectives: To develop and externally validate a population pharmacokinetic model for continuous-infusion meropenem in critically ill patients and to establish a nomogram based on a routinely available marker of renal function. Methods: A population pharmacokinetic model was developed in NONMEM (R) 7.3 based on steady-state meropenem concentrations (C-ss) collected during therapeutic drug monitoring. Different serum creatinine-based markers of renal function were compared for their influence on meropenem clearance (the Cockcroft-Gault creatinine clearance CLCRcG, the CLCR bedside estimate according to Jelliffe, the Chronic Kidney Disease Epidemiology Collaboration equation and the four-variable Modification of Diet in Renal Disease equation). After validation of the pharmacokinetic model with independent data, a dosing nomogram was developed, relating renal function to the daily doses required to achieve selected target concentrations (4/8/16 mg/L) in 90% of the patients. Probability of target attainment was determined for efficacy (C-ss >= 8 mg/L) and potentially increased likelihood of adverse drug reactions (C-ss >32 mg/L). Results: In total, 433 plasma concentrations (3.20-48.0 mg/L) from 195 patients (median/P-0.05 - P-0.95 at baseline: weight 77.0/55.0-114 kg, CLCRCG 63.0/19.6-168 mL/min) were used for model building. We found that CLCRCG best described meropenem clearance (CL = 7.71 L/h, CLCRCG = 80 mL/min). The developed model was successfully validated with external data (n = 171, 73 patients). According to the nomogram, daily doses of 910/1480/2050/2800/ 3940 mg were required to reach a target C-ss = 8 mg/L in 90% of patients with CLCRCG = 20/50/80/120/180 mL/min, respectively. A low probability of adverse drug reactions (

Treatment wetlands (TWs) efficiently remove many pollutants including a several log order reduction of pathogens from influent to effluent; however, there is evidence to suggest that pathogen cells are sequestered in a subsurface wetland and may remain viable months after inoculation. Escherichia coli is a common pathogen in domestic and agricultural wastewater and the O157:H7 strain causes most environmental outbreaks in the United States. To assess attachment of E. coli to the TW rhizosphere, direct measurements of E. coli levels were taken. Experiments were performed in chemostats containing either Teflon nylon as an abiotic control or roots of Carex utriculata or Schoenoplectus acutus. Flow of simulated wastewater through the chemostat was set to maintain a 2 hour residence time. The influent was inoculated with E. coli O157:H7 containing DsRed fluorescent protein. Root samples were excised and analyzed via epifluorescent microscopy. E. coli O157:H7 was detected on the root surface at 2 hours after inoculation, and were visible as single cells. Microcolonies began forming at 24 hours post-inoculation and were detected for up to 1 week post-inoculation. Image analysis determined that the number of microcolonies with >100 cells increased 1 week post-inoculation, confirming that E. coli O157:H7 is capable of growth within biofilms surrounding wetland plant roots.