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Aim: The aim of this study was to investigate how the prescribing knowledge and skills of junior doctors in the Netherlands and Belgium develop in the year after graduation. We also analysed differences in knowledge and skills between surgical and nonsurgical junior doctors. Methods: This international, multicentre (n = 11), longitudinal study analysed the learning curves of junior doctors working in various specialties via three validated assessments at about the time of graduation, and 6 months and 1 year after graduation. Each assessment contained 35 multiple choice questions (MCQs) on medication safety (passing grade ≥85%) and three clinical scenarios. Results: In total, 556 junior doctors participated, 326 (58.6%) of whom completed the MCQs and 325 (58.5%) the clinical case scenarios of all three assessments. Mean prescribing knowledge was stable in the year after graduation, with 69% (SD 13) correctly answering questions at assessment 1 and 71% (SD 14) at assessment 3, whereas prescribing skills decreased: 63% of treatment plans were considered adequate at assessment 1 but only 40% at assessment 3 (P <.001). While nonsurgical doctors had similar learning curves for knowledge and skills as surgical doctors (P =.53 and P =.56 respectively), their overall level was higher at all three assessments (all P <.05). Conclusion: These results show that junior doctors' prescribing knowledge and skills did not improve while they were working in clinical practice. Moreover, their level was under the predefined passing grade. As this might adversely affect patient safety, educational interventions should be introduced to improve the prescribing competence of junior doctors. [ABSTRACT FROM AUTHOR]

Background: Cross-contamination of feed with low concentrations of antimicrobials can occur at production, transport and/or farm level. Concerns are rising about possible effects of this contaminated feed on resistance selection in the intestinal microbiota. Therefore, an experiment with pigs was set up, in which intestinal and fecal concentrations of chlortetracycline (CTC), doxycycline (DOX) and sulfadiazine-trimethoprim (SDZ-TRIM) were determined after administration of feed containing a 3 % carry-over level of these antimicrobials. Results: The poor oral bioavailability of tetracyclines resulted in rather high concentrations in cecal and colonic content and feces at steady-state conditions. A mean concentration of 10 mg/kg CTC and 4 mg/kg DOX in the feces was reached, which is higher than concentrations that were shown to cause resistance selection. On the other hand, lower mean levels of SDZ (0.7 mg/kg) and TRIM (< limit of detection of 0.016 mg/kg) were found in the feces, corresponding with the high oral bioavailability of SDZ and TRIM in pigs. Conclusions: The relation between the oral bioavailability and intestinal concentrations of the tested antimicrobials, may be of help in assessing the risks of cross-contaminated feed. However, future research is needed to confirm our results and to evaluate the effects of these detected concentrations on resistance selection in the intestinal microbiota of pigs. [ABSTRACT FROM AUTHOR]

Background: Adherence to antihypertensive drugs (AHDs) is crucial for controlling blood pressure (BP). We aimed to determine the effectiveness of measuring AHD concentrations using a dried blood spot (DBS) sampling method to identify nonadherence, combined with personalized feedback, in reducing resistant hypertension., Methods: We conducted a multicenter, randomized, controlled trial (RHYME-RCT, ICTRP NTR6914) in patients with established resistant hypertension. Patients were randomized to receive either an intervention with standard of care (SoC) or SoC alone. SoC consisted of BP measurement and DBS sampling at baseline, 3 months (t3), 6 months (t6), and 12 months (t12); AHD concentrations were measured but not reported in this arm. In the intervention arm, results on AHD concentrations were discussed during a personalized feedback conversation at baseline and t3. Study endpoints included the proportion of patients with RH and AHD adherence at t12., Results: Forty-nine patients were randomized to receive the intervention+SoC, and 51 were randomized to receive SoC alone. The proportion of adherent patients improved from 70.0 to 92.5% in the intervention+SoC arm ( P  = 0.008, n  = 40) and remained the same in the SoC arm (71.4%, n  = 42). The difference in adherence between the arms was statistically significant ( P  = 0.014). The prevalence of resistant hypertension decreased to 75.0% in the intervention+SoC arm ( P  < 0.001, n  = 40) and 59.5% in the SoC arm ( P  < 0.001, n  = 42) at t12; the difference between the arms was statistically nonsignificant ( P  = 0.14)., Conclusion: Personalized feedback conversations based on DBS-derived AHD concentrations improved AHD adherence but did not reduce the prevalence of RH., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Nonadherence to antihypertensive drugs (AHDs) is a major contributor to pseudo-resistant hypertension. The primary objective of this study was to determine the prevalence of nonadherence to AHDs among patients visiting the nephrology and vascular outpatient clinics., Methods: Patients were eligible to participate in this prospective observational study if they used at least two AHDs that could be measured with a validated UHPLC-MS/MS method and had an office blood pressure at least 140 and/or at least 90 mmHg. For resistant hypertension, included patients had to use at least three AHDs including a diuretic or four AHDs. Adherence was assessed by measuring drug concentrations in blood. The complete absence of drug in blood was defined as nonadherence. A posthoc analysis was performed to determine the influence of a having a kidney transplant on the adherence rates., Results: One hundred and forty-two patients were included of whom 66 patients fulfilled the definition of resistant hypertension. The overall adherence rate to AHDs was 78.2% ( n  = 111 patients), with the highest adherence rate for irbesartan (100%, n  = 9) and lowest adherence rate for bumetanide ( n  = 69%, n  = 13). In further analysis, only kidney transplantation could be identified as an important factor for adherence (adjusted odds ratio = 3.35; 95% confidence interval 1.23-9.09). A posthoc analysis showed that patients with a kidney transplant were more likely to be adherent to AHDs (non-KT cohort 64.0% vs. KT-cohort 85.7%, χ 2 (2) = 10.34, P  = 0.006)., Conclusion: The adherence rate to AHDs in hypertensive patients was high (78.2%) and even higher after a kidney transplant (85.7%). Furthermore, patients after kidney transplant had a lower risk of being nonadherent to AHDs., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Nonadherence to antihypertensive drugs is an important reason for not reaching blood pressure goals. A possible method to improve nonadherence involves three essential steps: identification of nonadherent patients (step 1), determination of underlying causes (step 2) and a personalized solution (step 3). We present three unique cases to show the importance and difficulties of this three-step approach. Patients participated in a randomized controlled trial to improve nonadherence to antihypertensive drugs (RHYME-RCT, Dutch Trial Register NL6736). Drug level measurements were used to identify nonadherence to antihypertensive drugs and communication on drug levels was supported by a tailored feedback tool in these patients. These cases showed that a three-step approach of identifying nonadherence and determination of the underlying cause, can lead to a personalized solution to improve therapy even when nonadherence was excluded. Open communication with patients remains an essential part when improving nonadherence., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)

Dried blood spot (DBS) analysis is a novel analytical method for therapeutic drug monitoring to identify nonadherence to antihypertensive drugs. This study was conducted to evaluate the clinical applicability of measuring drug concentrations of 8 antihypertensive drugs, using DBS and venipuncture. Furthermore, this study aimed to provide more insight into the between-patient variability in drug concentrations. False-negative values from DBS compared with a venipuncture were determined to assess drug adherence. A generalized estimating equation was used to estimate the model parameters, including sex, dose, age, weight, and the time interval, between drug intake and sampling, on the C plasma (drug concentration in plasma). No false-negative values were found when measuring nonadherence using DBS compared with venipuncture. A high variability in C plasma between patients was observed, especially at peak concentrations with a fold change reaching from 2.3 to 35.2. The time of intake was significantly related to the height of the C plasma in 7 of the 8 measured drugs with a P <0.05, but the influence of dose, weight, age, and sex on drug levels differed largely between the measured drugs. DBS is a reliable and convenient method to assess nonadherence to antihypertensive drugs in clinical practice. The C plasma of the 8 antihypertensive drugs in this study show a large interindividual difference, and therefore, low plasma concentrations do not necessarily mean nonadherence. Nonadherence can only be confirmed if drug levels are undetectable, that is, values below the lower limit of detection.

Objectives: Over 70% of patients who visit the emergency department with a hypertensive emergency or a hypertensive urgency have previously been diagnosed with hypertension. Drug nonadherence is assumed to play an important role in development of hypertensive urgency and hypertensive emergency, but exact numbers are lacking. We aimed to retrospectively compare characteristics of patients with hypertensive urgency and hypertensive emergency and to prospectively quantify the attribution of drug nonadherence., Methods: We retrospectively analysed clinical data including information on nonadherence obtained by treating physicians of patients with SBP at least 180 mmHg and DBP at least 110 mmHg visiting the emergency department between 2012 and 2015. We prospectively studied drug adherence among patients admitted to the emergency department with severely elevated BP by measuring plasma drug levels using liquid chromatography tandem mass spectrometry from September 2016 to March 2017., Results: Of the 1163 patients retrospectively analysed, 257 (22.0%) met the criteria for hypertensive urgency and 356 (30.6%) for hypertensive emergency. Mean SBP (SD) was 203 (19) mmHg and mean DBP 121 (12) mmHg. Mean age was 60.1 (14.6) years; 55.1% were men. In 6.3% of patients with hypertensive urgency or hypertensive emergency, nonadherence was recorded as an attributing factor. Of the 59 patients prospectively analysed, 18 (30.5%) were nonadherent for at least one of the prescribed antihypertensive drugs., Conclusion: Hypertensive urgency and hypertensive emergency are common health problems resulting in frequent emergency department admissions. Workup of patients with a hypertensive urgency or hypertensive emergency should include an assessment of drug adherence to optimize treatment strategy.

Pig feed may contain various levels of antimicrobial residues due to cross-contamination. A previous study showed that a 3% carry-over level of doxycycline (DOX) in the feed results in porcine faecal concentrations of approximately 4 mg/L. The aim of this study was to determine the effect of residual DOX concentrations (1 and 4 mg/L) in vitro on selection of DOX-resistant porcine commensal Escherichia coli and transfer of their resistance plasmids. Three different DOX-resistant porcine commensal E. coli strains and their plasmids were characterised. These strains were each brought in competition with a susceptible strain in a medium containing 0, 1 and 4 mg/L DOX. Resistant bacteria, susceptible bacteria and transconjugants were enumerated after 24 h and 48 h. The tet(A)-carrying plasmids showed genetic backbones that are also present among human E. coli isolates. Ratios of resistant to susceptible bacteria were significantly higher at 1 and 4 mg/L DOX compared with the blank control, but there was no significant difference between 1 and 4 mg/L. Plasmid transfer frequencies were affected by 1 or 4 mg/L DOX in the medium for only one of the resistance plasmids. In conclusion, DOX concentrations of 1 and 4 mg/L can select for resistant E. coli in vitro. Further research is needed to determine the effect of these concentrations in the complex environment of the porcine intestinal microbiota., (Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.)

Staphylococcus aureus is a burden in human and veterinary medicine. During the last decade, an increasing number of studies reported the presence of livestock-associated methicillin-resistant S. aureus (LA-MRSA) clonal complex (CC) 398 in pigs. During 2013, a survey was performed in pig farms (n=328) randomly selected over Belgium, to monitor the current epidemiological situation of LA-MRSA among asymptomatic pigs and compare with former data to determine possible evolutions. Per farm, nose swabs were taken from 20 animals and pooled. MRSA was detected in 215 farms. Most isolates belonged to CC398 (n=211), and the remaining were ST9/t337 (n=1), ST80/t044 (n=2) and ST239/t4150 (n=1). A large diversity (n=19) of spa-types was found in the CC398 isolates. More than 90% of the isolates were non-wild type (NWT) to tetracycline and trimethoprim. NWT isolates were also found for ciprofloxacin (61.1%), clindamycin (64.4%), erythromycin (57.8%), kanamycin (43.1%) and gentamicin (45.5%). Microarray analysis showed that most CC398 isolates carried genes encoding resistance to tetracycline [tet(M)], macrolide-lincosamide-streptogramin group [erm(B), erm(C), lnu(A), vga(A)], aminoglycosides (aacA-aphD,aa dD, aphA3, sat) and/or phenicols (fexA). One CC398 isolate carried the multi-resistance gene cfr. The non-CC398 isolates carried virulence genes, as the egc-like cluster. The ST80 strain carried the Panton-Valentine leukocidin gene and corresponded to the community-acquired (CA-)MRSA ST80-IV European clone. The MRSA prevalence among pigs in Belgium remains similar to previous studies but a larger diversity in spa-types has been detected in this study. The recovery of CA-MRSA from livestock indicates that one should remain vigilant to the evolution of LA-MRSA in pigs., (Copyright © 2015 Elsevier B.V. All rights reserved.)