Doppler follow-up after TIPS placement is not routinely indicated. A 16-years single centre experience.

BACKGROUND AND AIMS: Transjugular intrahepatic portosystemic shunt (TIPS) is an effective intervention to treat complications of portal hypertension. Since the introduction of polytetrafluoroethylene (PTFE)-covered stents, TIPS patency rates have improved, and the need for routine TIPS surveillance has become questionable. Aims of this study were to assess the indications, clinical outcome and survival, and yield of Doppler ultrasound follow-up in patients who received a TIPS in an academic centre. METHODS: A retrospective cohort study of all adult consecutive patients who underwent PTFE-covered TIPS placement between 2001 and 2016. Clinical, biochemical, and imaging findings were reviewed and analysed. RESULTS: A total of 103 patients were included for analysis. At one-year follow-up, control of bleeding was successful in 91% (41/45), and control of refractory ascites in 80% (8/10). In patients with variceal bleeding, a higher MELD score was a risk factor for 90-day mortality (HR 1.28 per point, p < 0.001) and one-year mortality (HR 1.24 per point, p < 0.001). In patients with refractory ascites, a higher MELD score was only a risk factor for 90-day mortality (HR 1.13 per point, p = 0.03). Doppler ultrasound investigations during follow-up revealed abnormalities in 4% (6/166), all of which were associated with clinical deterioration, while abnormalities were detected in 11.4% (19/166) of patients who presented with clinical symptoms of TIPS dysfunction. CONCLUSION: The use of routine Doppler ultrasound follow-up after PTFE-covered TIPS placement seems unnecessary as it had a very low yield and abnormal Doppler findings were almost always associated with clinical symptoms of TIPS dysfunction.

Prevention of hepatic encephalopathy by administration of rifaximin and lactulose in patients with liver cirrhosis undergoing placement of a transjugular intrahepatic portosystemic shunt (TIPS): a multicentre randomised, double blind, placebo controlled trial (PEARL trial).

INTRODUCTION: Cirrhotic patients with portal hypertension can suffer from variceal bleeding or refractory ascites and can benefit from a transjugular intrahepatic portosystemic shunt (TIPS). Post-TIPS hepatic encephalopathy (HE) is a common (20%-54%) and often severe complication. A prophylactic strategy is lacking. METHODS AND ANALYSIS: The Prevention of hepatic Encephalopathy by Administration of Rifaximin and Lactulose in patients with liver cirrhosis undergoing placement of a TIPS (PEARL) trial, is a multicentre randomised, double blind, placebo controlled trial. Patients undergoing covered TIPS placement are prescribed either rifaximin 550 mg two times per day and lactulose 25 mL two times per day (starting dose) or placebo 550 mg two times per day and lactulose 25 mL two times per day from 72 hours before and until 3 months after TIPS placement. Primary endpoint is the development of overt HE (OHE) within 3 months (according to West Haven criteria). Secondary endpoints include 90-day mortality; development of a second episode of OHE; time to development of episode(s) of OHE; development of minimal HE; molecular changes in peripheral and portal blood samples; quality of life and cost-effectiveness. The total sample size is 238 patients and recruitment period is 3 years in six hospitals in the Netherlands and one in Belgium. ETHICS AND DISSEMINATION: This study protocol was approved in the Netherlands by the Medical Research Ethics Committee of the Academic Medical Centre, Amsterdam (2018-332), in Belgium by the Ethics Committee Research UZ/KU Leuven (S62577) and competent authorities. This study will be conducted in accordance with Good Clinical Practice guidelines and the principles of the Declaration of Helsinki. Study results will be submitted for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBERS: ClinicalTrials.gov (NCT04073290) and EudraCT database (2018-004323-37).

Daytime sleep state misperception in a tertiary sleep centre population.

STUDY OBJECTIVES: Sleep state misperception is common in various sleep disorders, especially in chronic insomnia with a prevalence ranging between 9-50%. Most prior studies used nocturnal polysomnography (PSG) for the identification of sleep state misperception during nighttime. Our objective was to assess sleep state misperception during daytime in people with sleep disorders with excessive daytime sleepiness (EDS). METHODS: In this prospective observational study, we assessed the occurrence of, and factors influencing sleep state misperception in consecutive patients undergoing a routine multiple sleep latency test (MSLT) in a tertiary sleep-wake centre included between 2014 and 2017. Mixed models were applied to assess the influence of patients' clinical data on sleep state perception. RESULTS: People with narcolepsy type 1 (NT1, n = 33) and type 2 (NT2, n = 14), idiopathic hypersomnia (IH, n = 56), obstructive sleep apnea (OSA, n = 31) and insufficient sleep syndrome (ISS, n = 31) were included. The prevalence of both classical and reverse sleep state misperception did not differ between the sleep disorders (mean 25%, range 8-37%) after correction for sleep stage, sleep onset latency and age. Longer sleep onset latency and reaching only non-rapid eye movement (REM) sleep stage 1 were significant predictors for classical sleep state misperception. CONCLUSIONS: Sleep state misperception is common in people with NT1 and NT2, IH, OSA, and ISS. Classical sleep state misperception is more frequent in patients with longer sleep onset latencies who only reach non-REM sleep stage 1 during a nap.

[A day in the life of a medical resident on the ward]. / Een dag uit het leven van de zaalarts interne geneeskunde.

OBJECTIVE: To investigate how internal medicine residents allocate their time during a hospital dayshift on the wards. DESIGN: Prospective observational cohort study (time and motion study). METHODS: Data were collected from 36 internal medicine residents working at the Internal Medicine Department of the Academic Medical Centre in Amsterdam, the Netherlands. Trained observers monitored 22 residents using a newly developed smartphone-application, registering their dayshift activities (meetings and education, direct patient contact, administrative tasks, lunch/break, other) and location (workstation, conference room, ward and patient rooms, other). Data of 14 residents on work-related activities during after-hours in the hospital and at home were collected through a questionnaire. RESULTS: Residents were observed for a total of 210 hours. The average workday encompassed 9.5 hours. During this dayshift, residents spent an average of 38% of their time on administrative tasks, and 37% on interprofessional consultation and educational activities. Direct patient/family contact accounted for 13% of the workday. After the evening handover at 5 pm, on average another 80 minutes of work was performed in the hospital, of which 73 minutes (91%) entailed administration. At home, they spent on average another 52 minutes on patient care related work, of which 51 minutes (98%) consisted of administration. CONCLUSION: The internal medicine residents on the ward spend most of their dayshift on indirect patient care. This comprises mostly computer-based administrative tasks. After the dayshift, many residents continue to work in their own time to finish remaining paperwork. Study limitations are the limited total number of monitored residents, the total observation time and possible self-report bias.

A real-time PCR approach based on SPF10 primers and the INNO-LiPA HPV Genotyping Extra assay for the detection and typing of human papillomavirus.

The SPF10 PCR targets a conserved 65bp region of the HPV L1 gene for broad-spectrum amplification. The LiPA assay allows subsequent genotyping of the HPV amplicons. This study aims to develop a SPF10 real-time PCR to achieve simultaneous amplification and detection of the HPV target. That way, LiPA analysis of the HPV-negative samples can be avoided, reducing workload and cost. The real-time PCR shows an analytical sensitivity of 29.7 copies for HPV 6, 16, 18 and 31 and an HPV-specific melting peak. Thirty-one HPV DNA plasmids were genotyped correctly using the SPF10 real-time PCR in combination with the LiPA. Here, the LiPA assay was performed at an increased hybridisation temperature (49.5°C) in combination with a reduced amplicon volume (1µl) to avoid cross-reactivity. In conclusion, the SPF10 real-time PCR proves to be very sensitive and generates amplicons, which are compatible with the LiPA.

WITHDRAWN: A real-time PCR approach based on SPF10 primers and the INNO-LiPA HPV Genotyping Extra assay for the detection and typing of human papillomavirus.

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Inhibitory efficacy of various antibiotics on matrix and viable mass of Staphylococcus aureus and Pseudomonas aeruginosa biofilms.

Both bacteria and the matrix are essential for the development of biofilms. Antimicrobials should therefore be tested against both components. The aim of this study was to determine the structure-activity relationships of different antibiotics against biofilm-forming Staphylococcus aureus and Pseudomonas aeruginosa strains using in vitro biofilm discriminatory assays. Only four of twelve antibiotics showed efficacy against S. aureus biofilms. Rifampicin had a 50% inhibitory activity both against the matrix and bacteria at 16 x the minimum bactericidal concentration (MBC). Polymyxin B killed nearly all bacteria at 8 x MBC, but left the matrix undisturbed. Both P. aeruginosa biofilms responded differently to antibiotic treatment. Rifampicin showed the greatest activity, with 100% killing of microorganisms combined with 91% destruction of the matrix at the MBC. In conclusion, rifampicin showed the highest activity on biofilm matrix and bacteria in S. aureus and P. aeruginosa biofilms. Our results also indicated that biofilm viable mass was more susceptible to treatment than the biofilm matrix, which is mainly responsible for biofilm persistence. Future research should specifically focus on compounds destroying the matrix that can be used as an adjunct to antibiotic therapy.