Publications by authors named "Jan Roth"

97 Publications

Diagnostic Accuracy of Imaging Findings in Pleural Empyema: Systematic Review and Meta-Analysis.

J Imaging 2021 Dec 28;8(1). Epub 2021 Dec 28.

Division of Research and Analytical Services, Department of Informatics, University Hospital Basel, 4031 Basel, Switzerland.

Computed tomography (CT) diagnosis of empyema is challenging because current literature features multiple overlapping pleural findings. We aimed to identify informative findings for structured reporting. The screening according to inclusion criteria (P: Pleural empyema, I: CT C: culture/gram-stain/pathology/pus, O: Diagnostic accuracy measures), data extraction, and risk of bias assessment of studies published between 01-1980 and 10-2021 on Pubmed, Embase, and Web of Science (WOS) were performed independently by two reviewers. CT findings with pooled diagnostic odds ratios (DOR) with 95% confidence intervals, not including 1, were considered as informative. Summary estimates of diagnostic accuracy for CT findings were calculated by using a bivariate random-effects model and heterogeneity sources were evaluated. Ten studies with a total of 252 patients with and 846 without empyema were included. From 119 overlapping descriptors, five informative CT findings were identified: Pleural enhancement, thickening, loculation, fat thickening, and fat stranding with an AUC of 0.80 (hierarchical summary receiver operating characteristic, HSROC). Potential sources of heterogeneity were different thresholds, empyema prevalence, and study year.
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http://dx.doi.org/10.3390/jimaging8010003DOI Listing
December 2021

An MDS Evidence-Based Review on Treatments for Huntington's Disease.

Mov Disord 2022 Jan 29;37(1):25-35. Epub 2021 Nov 29.

Instituto de Medicina Molecular João Lobo Antunes, Lisbon, Portugal.

Background: Huntington's disease (HD) is a rare neurodegenerative disorder with protean clinical manifestations. Its management is challenging, consisting mainly of off-label treatments.

Objectives: The International Parkinson and Movement Disorder Society commissioned a task force to review and evaluate the evidence of available therapies for HD gene expansion carriers.

Methods: We followed the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Eligible randomized controlled trials were identified via an electronic search of the CENTRAL, MEDLINE, and EMBASE databases. All eligible trials that evaluated one or more of 33 predetermined clinical questions were included. Risk of bias was evaluated using the Cochrane Risk of Bias tool. A framework was adapted to allow for efficacy and safety conclusions to be drawn from the balance between the GRADE level of evidence and the importance of the benefit/harm of the intervention.

Results: Twenty-two eligible studies involving 17 interventions were included, providing data to address 8 clinical questions. These data supported a likely effect of deutetrabenazine on motor impairment, chorea, and dystonia and of tetrabenazine on chorea. The data did not support a disease-modifying effect for premanifest and manifest HD. There was no eligible evidence to support the use of specific treatments for depression, psychosis, irritability, apathy, or suicidality. Similarly, no evidence was eligible to support the use of physiotherapy, occupational therapy, exercise, dietary, or surgical treatments.

Conclusions: Data for therapeutic interventions in HD are limited and support only the use of VMAT2 inhibitors for specific motor symptoms. © 2021 International Parkinson and Movement Disorder Society.
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http://dx.doi.org/10.1002/mds.28855DOI Listing
January 2022

Decreasing incidence and determinants of Bacterial Pneumonia in people with HIV: The Swiss HIV Cohort Study.

J Infect Dis 2021 Nov 18. Epub 2021 Nov 18.

Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.

Background: Bacterial pneumonia is one of the leading reasons for hospitalization among people with HIV (PWH), yet there is limited evidence regarding its drivers in the era of potent antiretroviral therapy.

Methods: We assessed risk-factors for bacterial pneumonia in PWH enrolled in the Swiss HIV Cohort Study using univariable and multivariable marginal models. We further assessed the relationship between risk-factors and changes in bacterial pneumonia incidence using mediation analysis.

Results: We included 12927 PWH with follow-ups between 2008 and 2018. These patients had 985 bacterial pneumonia events during a follow-up of 100779 person-years(py). bacterial pneumonia incidence significantly decreased from 13.2 cases/1000 py in 2008 to 6.8 cases/1000 py in 2018. Older age, lower education-level, intravenous drug use, smoking, lower CD4-cell-count, higher HIV-viral load, and prior pneumonia events were significantly associated with higher bacterial pneumonia incidence. Notably, even CD4-cell-counts 350-499 were significantly associated with an increased risk compared to CD4≥500 (adjusted HR,1.39; 95% CI,1.01-1.89). Finally, we found that the decreasing incidence over the last decade can be explained by decreasing proportion of patients with CD4<500, viral-RNA>200, and smoking>one cigarette/day.

Conclusion: Improvements in cascade of care of HIV and decrease in smoking may have mediated a substantial decrease in bacterial pneumonia incidence.
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http://dx.doi.org/10.1093/infdis/jiab573DOI Listing
November 2021

Assessing the drivers of syphilis among men who have sex with men in Switzerland reveals a key impact of screening frequency: A modelling study.

PLoS Comput Biol 2021 10 26;17(10):e1009529. Epub 2021 Oct 26.

Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland.

Over the last decade, syphilis diagnoses among men-who-have-sex-with-men (MSM) have strongly increased in Europe. Understanding the drivers of the ongoing epidemic may aid to curb transmissions. In order to identify the drivers of syphilis transmission in MSM in Switzerland between 2006 and 2017 as well as the effect of potential interventions, we set up an epidemiological model stratified by syphilis stage, HIV-diagnosis, and behavioral factors to account for syphilis infectiousness and risk for transmission. In the main model, we used 'reported non-steady partners' (nsP) as the main proxy for sexual risk. We parameterized the model using data from the Swiss HIV Cohort Study, Swiss Voluntary Counselling and Testing center, cross-sectional surveys among the Swiss MSM population, and published syphilis notifications from the Federal Office of Public Health. The main model reproduced the increase in syphilis diagnoses from 168 cases in 2006 to 418 cases in 2017. It estimated that between 2006 and 2017, MSM with HIV diagnosis had 45.9 times the median syphilis incidence of MSM without HIV diagnosis. Defining risk as condomless anal intercourse with nsP decreased model accuracy (sum of squared weighted residuals, 378.8 vs. 148.3). Counterfactual scenarios suggested that increasing screening of MSM without HIV diagnosis and with nsP from once every two years to twice per year may reduce syphilis incidence (at most 12.8% reduction by 2017). Whereas, increasing screening among MSM with HIV diagnosis and with nsP from once per year to twice per year may substantially reduce syphilis incidence over time (at least 63.5% reduction by 2017). The model suggests that reporting nsP regardless of condom use is suitable for risk stratification when modelling syphilis transmission. More frequent screening of MSM with HIV diagnosis, particularly those with nsP may aid to curb syphilis transmission.
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http://dx.doi.org/10.1371/journal.pcbi.1009529DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8570495PMC
October 2021

Handrub dispensers per acute care hospital bed: a study to develop a new minimum standard.

Antimicrob Resist Infect Control 2021 06 16;10(1):93. Epub 2021 Jun 16.

Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, University of Basel, Petersgraben 4, 4031, Basel, Switzerland.

Background: Accessibility to alcohol-based handrub (ABHR) dispenser is crucial to improve compliance to hand hygiene (HH), being offered as wall-mounted dispensers (ABHR-Ds), and/or pocket bottles. Nevertheless, information on the distribution and density of ABHR-Ds and their impact on HH have hardly been studied. Institutions such as the World Health Organisation or the Centers for Disease Control and Prevention do not provide guidance. The Robert-Koch-Institute (RKI) from Germany recommends an overall density of > 0.5 dispensers per patient bed. We aimed to investigate current conditions in hospitals to develop a standard on the minimal number of ABHR-D.

Methods: Between 07 and 09/2019, we applied a questionnaire to 178 hospitals participating in the Swissnoso National Surveillance Network to evaluate number and location of ABHR-Ds per bed in acute care hospitals, and compared the data with consumption and compliance with HH.

Results: 110 of the 178 (62%) hospitals provided data representing approximately 20,000 hospital beds. 83% hospitals provided information on both the total number of ABHR-Ds and patient beds, with a mean of 2.4 ABHR-Ds per bed (range, 0.4-22.1). While most hospitals (84%) had dispensers located at the room entrance, 47% reported also locations near or at the bed. Additionally, pocket-sized dispensers (100 mL) are available in 97% of hospitals.

Conclusions: Swiss hospitals provide 2.4 dispensers per bed, much more than governmental recommendation. The first study on the number of ABHR-Ds in hospitals may help to define a minimal standard for national and international recommendations.
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http://dx.doi.org/10.1186/s13756-021-00949-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8206889PMC
June 2021

Reply by Authors.

J Urol 2021 04 3;205(4):998. Epub 2021 Feb 3.

Department of Urology, University Hospital Basel, Basel, Switzerland.

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http://dx.doi.org/10.1097/JU.0000000000001513.03DOI Listing
April 2021

A comparison of general and disease-specific machine learning models for the prediction of unplanned hospital readmissions.

J Am Med Inform Assoc 2021 03;28(4):868-873

Medical Data Science, Department of Computer Science, ETH Zurich, Zurich, Switzerland.

Unplanned hospital readmissions are a burden to patients and increase healthcare costs. A wide variety of machine learning (ML) models have been suggested to predict unplanned hospital readmissions. These ML models were often specifically trained on patient populations with certain diseases. However, it is unclear whether these specialized ML models-trained on patient subpopulations with certain diseases or defined by other clinical characteristics-are more accurate than a general ML model trained on an unrestricted hospital cohort. In this study based on an electronic health record cohort of consecutive inpatient cases of a single tertiary care center, we demonstrate that accurate prediction of hospital readmissions may be obtained by general, disease-independent, ML models. This general approach may substantially decrease the cost of development and deployment of respective ML models in daily clinical routine, as all predictions are obtained by the use of a single model.
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http://dx.doi.org/10.1093/jamia/ocaa299DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7973448PMC
March 2021

Antimicrobial Prophylaxis for Postoperative Urinary Tract Infections in Transurethral Resection of Bladder Tumors: A Systematic Review and Meta-Analysis.

J Urol 2021 Apr 7;205(4):987-998. Epub 2020 Dec 7.

Department of Urology, University Hospital Basel, Basel, Switzerland.

Purpose: The administration of antimicrobial prophylaxis for postoperative urinary tract infections following transurethral resection of bladder tumors is controversial. We aimed to systematically review evidence on the potential effect of antimicrobial prophylaxis on postoperative urinary tract infections and asymptomatic bacteriuria.

Materials And Methods: We conducted a systematic search in Embase®, Medline® and the Cochrane Central Register of Controlled Trials. Randomized controlled trials and nonrandomized controlled trials assessing the effect of any form of antimicrobial prophylaxis in patients with transurethral resection of bladder tumors on postoperative urinary tract infections or asymptomatic bacteriuria were included. Risk of bias was assessed using RoB 2.0 or the Newcastle-Ottawa Scale. Fixed and random effects meta-analyses were conducted. As a potential basis for a scoping review, we exploratorily searched Medline for risk factors for urinary tract infections after transurethral resection of bladder tumors. The protocol was registered on PROSPERO (CRD42019131733).

Results: Of 986 screened publications, 7 studies with 1,725 participants were included; the reported effect sizes varied considerably. We found no significant effect of antimicrobial prophylaxis on urinary tract infections: the pooled odds ratio of the random effects model was 1.55 (95% CI 0.73-3.31). The random effects meta-analysis examining the effect of antimicrobial prophylaxis on asymptomatic bacteriuria showed an OR of 0.43 (0.18-1.04). Risk of bias was moderate. Our exploratory search identified 3 studies reporting age, preoperative pelvic radiation, preoperative hospital stay, duration of operation, tumor size, preoperative asymptomatic bacteriuria and pyuria as risk factors for urinary tract infections following transurethral resection of bladder tumors.

Conclusions: We observed insufficient evidence supporting routine antimicrobial prophylaxis in patients undergoing transurethral resection of bladder tumors for the prevention of postoperative urinary tract infections; our findings may inform harmonization of international guidelines.
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http://dx.doi.org/10.1097/JU.0000000000001513DOI Listing
April 2021

The worldwide clinical trial research response to the COVID-19 pandemic - the first 100 days.

F1000Res 2020;9:1193. Epub 2020 Oct 2.

Department of Clinical Research, University of Basel, Basel, Switzerland.

: Never before have clinical trials drawn as much public attention as those testing interventions for COVID-19. We aimed to describe the worldwide COVID-19 clinical research response and its evolution over the first 100 days of the pandemic. Descriptive analysis of planned, ongoing or completed trials by April 9, 2020 testing any intervention to treat or prevent COVID-19, systematically identified in trial registries, preprint servers, and literature databases. A survey was conducted of all trials to assess their recruitment status up to July 6, 2020. Most of the 689 trials (overall target sample size 396,366) were small (median sample size 120; interquartile range [IQR] 60-300) but randomized (75.8%; n=522) and were often conducted in China (51.1%; n=352) or the USA (11%; n=76). 525 trials (76.2%) planned to include 155,571 hospitalized patients, and 25 (3.6%) planned to include 96,821 health-care workers. Treatments were evaluated in 607 trials (88.1%), frequently antivirals (n=144) or antimalarials (n=112); 78 trials (11.3%) focused on prevention, including 14 vaccine trials. No trial investigated social distancing. Interventions tested in 11 trials with >5,000 participants were also tested in 169 smaller trials (median sample size 273; IQR 90-700). Hydroxychloroquine alone was investigated in 110 trials. While 414 trials (60.0%) expected completion in 2020, only 35 trials (4.1%; 3,071 participants) were completed by July 6. Of 112 trials with detailed recruitment information, 55 had recruited <20% of the targeted sample; 27 between 20-50%; and 30 over 50% (median 14.8% [IQR 2.0-62.0%]). The size and speed of the COVID-19 clinical trials agenda is unprecedented. However, most trials were small investigating a small fraction of treatment options. The feasibility of this research agenda is questionable, and many trials may end in futility, wasting research resources. Much better coordination is needed to respond to global health threats.
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http://dx.doi.org/10.12688/f1000research.26707.2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7539080PMC
November 2020

Monogenic variants in dystonia: an exome-wide sequencing study.

Lancet Neurol 2020 11;19(11):908-918

Klinik und Poliklinik für Neurologie, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.

Background: Dystonia is a clinically and genetically heterogeneous condition that occurs in isolation (isolated dystonia), in combination with other movement disorders (combined dystonia), or in the context of multisymptomatic phenotypes (isolated or combined dystonia with other neurological involvement). However, our understanding of its aetiology is still incomplete. We aimed to elucidate the monogenic causes for the major clinical categories of dystonia.

Methods: For this exome-wide sequencing study, study participants were identified at 33 movement-disorder and neuropaediatric specialty centres in Austria, Czech Republic, France, Germany, Poland, Slovakia, and Switzerland. Each individual with dystonia was diagnosed in accordance with the dystonia consensus definition. Index cases were eligible for this study if they had no previous genetic diagnosis and no indication of an acquired cause of their illness. The second criterion was not applied to a subset of participants with a working clinical diagnosis of dystonic cerebral palsy. Genomic DNA was extracted from blood of participants and whole-exome sequenced. To find causative variants in known disorder-associated genes, all variants were filtered, and unreported variants were classified according to American College of Medical Genetics and Genomics guidelines. All considered variants were reviewed in expert round-table sessions to validate their clinical significance. Variants that survived filtering and interpretation procedures were defined as diagnostic variants. In the cases that went undiagnosed, candidate dystonia-causing genes were prioritised in a stepwise workflow.

Findings: We sequenced the exomes of 764 individuals with dystonia and 346 healthy parents who were recruited between June 1, 2015, and July 31, 2019. We identified causative or probable causative variants in 135 (19%) of 728 families, involving 78 distinct monogenic disorders. We observed a larger proportion of individuals with diagnostic variants in those with dystonia (either isolated or combined) with coexisting non-movement disorder-related neurological symptoms (100 [45%] of 222; excepting cases with evidence of perinatal brain injury) than in those with combined (19 [19%] of 98) or isolated (16 [4%] of 388) dystonia. Across all categories of dystonia, 104 (65%) of the 160 detected variants affected genes which are associated with neurodevelopmental disorders. We found diagnostic variants in 11 genes not previously linked to dystonia, and propose a predictive clinical score that could guide the implementation of exome sequencing in routine diagnostics. In cases without perinatal sentinel events, genomic alterations contributed substantively to the diagnosis of dystonic cerebral palsy. In 15 families, we delineated 12 candidate genes. These include IMPDH2, encoding a key purine biosynthetic enzyme, for which robust evidence existed for its involvement in a neurodevelopmental disorder with dystonia. We identified six variants in IMPDH2, collected from four independent cohorts, that were predicted to be deleterious de-novo variants and expected to result in deregulation of purine metabolism.

Interpretation: In this study, we have determined the role of monogenic variants across the range of dystonic disorders, providing guidance for the introduction of personalised care strategies and fostering follow-up pathophysiological explorations.

Funding: Else Kröner-Fresenius-Stiftung, Technische Universität München, Helmholtz Zentrum München, Medizinische Universität Innsbruck, Charles University in Prague, Czech Ministry of Education, the Slovak Grant and Development Agency, the Slovak Research and Grant Agency.
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http://dx.doi.org/10.1016/S1474-4422(20)30312-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8246240PMC
November 2020

Differential effects of deep brain stimulation and levodopa on brain activity in Parkinson's disease.

Brain Commun 2020 29;2(1):fcaa005. Epub 2020 Jan 29.

Department of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic.

Levodopa is the first-line treatment for Parkinson's disease, although the precise mechanisms mediating its efficacy remain elusive. We aimed to elucidate treatment effects of levodopa on brain activity during the execution of fine movements and to compare them with deep brain stimulation of the subthalamic nuclei. We studied 32 patients with Parkinson's disease using functional MRI during the execution of finger-tapping task, alternating epochs of movement and rest. The task was performed after withdrawal and administration of a single levodopa dose. A subgroup of patients ( = 18) repeated the experiment after electrode implantation with stimulator on and off. Investigating levodopa treatment, we found a significant interaction between both factors of treatment state (off, on) and experimental task (finger tapping, rest) in bilateral putamen, but not in other motor regions. Specifically, during the off state of levodopa medication, activity in the putamen at rest was higher than during tapping. This represents an aberrant activity pattern probably indicating the derangement of basal ganglia network activity due to the lack of dopaminergic input. Levodopa medication reverted this pattern, so that putaminal activity during finger tapping was higher than during rest, as previously described in healthy controls. Within-group comparison with deep brain stimulation underlines the specificity of our findings with levodopa treatment. Indeed, a significant interaction was observed between treatment approach (levodopa, deep brain stimulation) and treatment state (off, on) in bilateral putamen. Our functional MRI study compared for the first time the differential effects of levodopa treatment and deep brain stimulation on brain motor activity. We showed modulatory effects of levodopa on brain activity of the putamen during finger movement execution, which were not observed with deep brain stimulation.
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http://dx.doi.org/10.1093/braincomms/fcaa005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7425344PMC
January 2020

Bayesian networks to identify potential high-risk multimorbidity and intervention clusters in inpatients: an explorative data mining study.

Swiss Med Wkly 2020 Jul 6;150:w20299. Epub 2020 Aug 6.

University of Basel, Switzerland / Department of Internal Medicine, Kantonsspital Luzern, Switzerland.

Aims Of The Study: Based on large sets of routine hospital data from inpatient cases, we aimed to explore multimorbidity and intervention clusters showing high risks for in-hospital mortality and unplanned readmissions using data-driven analytical methods.

Methods: We performed an explorative, historical cohort study of consecutive inpatient cases at a tertiary care centre with an integrated platform for routine healthcare data in Switzerland. From January 2012 through to December 2017, all inpatients aged ≥18 years at hospital admission were eligible for study inclusion. We predefined all-cause in-hospital death and unplanned hospital readmission as co-primary outcomes. In a first step, we explored and visualised multimorbidity and intervention clusters using mutual information analysis. In a subsequent step, we trained multi-layer Bayesian networks to identify clusters associated with in-hospital death and/or unplanned hospital readmission.

Results: Among 190,837 inpatient cases, 7994 unique diagnoses and 6639 interventions were routinely recorded during the six-year study period. Based on the mutual information analysis, we identified 32 multimorbidity clusters and 24 intervention clusters – of which several were directly related to in-hospital mortality and/or unplanned readmission in the subsequent Bayesian network analysis.

Conclusions: Bayesian network analysis may be used as a tool to mine large healthcare databases in order to explore intervention targets for quality improvement programmes. However, the resulting associations should be substantiated in consecutive investigations using specific causal models. (Trial registration no EKNZ 2016-02128.).
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http://dx.doi.org/10.4414/smw.2020.20299DOI Listing
July 2020

Are three antiseptic paints needed for safe preparation of the surgical field? A prospective cohort study with 239 patients.

Antimicrob Resist Infect Control 2020 07 31;9(1):120. Epub 2020 Jul 31.

Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Petersgraben 4, 4031, Basel, Switzerland.

Background: Preoperative skin antisepsis is an essential component of safe surgery. However, it is unclear how many antiseptic paints are needed to eliminate bacteria prior to incision. This study compared microbial skin counts after two and three antiseptic paints.

Methods: We conducted a prospective cohort study in non-emergency patients receiving a cardiac/abdominal surgery with standardized, preoperative skin antisepsis consisting of an alcoholic compound and either povidone iodine (PI) or chlorhexidine (CHX). We obtained three skin swabs from the participant's thorax/abdomen using a sterile template with a 25 cm window: After collection of the first swab prior to skin antisepsis, and once the second and third application of PI/CHX had dried out, we obtained a second and third swab, respectively. Our primary outcome was the reduction in microbial skin counts after two and three paints of PI/CHX.

Results: Among the 239 enrolled patients, there was no significant difference in the reduction of mean square root-transformed microbial skin counts with three versus two paints (P = 0.2). But distributions of colony forming units (CFUs) decreased from paint 2 to 3 in a predefined analysis (P = 0.002). There was strong evidence of an increased proportion of patients with zero CFU after paint 3 versus paint 2 (P = 0.003). We did not identify risk factors for insufficient reduction of microbial skin counts after two paints, defined as the detection of > 5 CFUs and/or ≥ 1 pathogens.

Conclusions: In non-emergency surgical patients, three antiseptic paints may be superior to two paints in reducing microbial skin colonization prior to surgery.
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http://dx.doi.org/10.1186/s13756-020-00780-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7393917PMC
July 2020

Telomere Length, Traditional Risk Factors, Factors Related to Human Immunodeficiency Virus (HIV) and Coronary Artery Disease Events in Swiss Persons Living With HIV.

Clin Infect Dis 2021 10;73(7):e2070-e2076

University Department of Medicine and Infectious Diseases Service, Kantonsspital Baselland, University of Basel, Bruderholz, Switzerland.

Background: Leukocyte telomere length (TL) shortens with age and is associated with coronary artery disease (CAD) events in the general population. Persons living with human immunodeficiency virus (HIV; PLWH) may have accelerated atherosclerosis and shorter TL than the general population. It is unknown whether TL is associated with CAD in PLWH.

Methods: We measured TL by quantitative polymerase chain reaction (PCR) in white Swiss HIV Cohort Study participants. Cases had a first CAD event during 1 January 2000 to 31 December 2017. We matched 1-3 PLWH controls without CAD events on sex, age, and observation time. We obtained univariable and multivariable odds ratios (OR) for CAD from conditional logistic regression analyses.

Results: We included 333 cases (median age 54 years; 14% women; 83% with suppressed HIV RNA) and 745 controls. Median time (interquartile range) of TL measurement was 9.4 (5.9-13.8) years prior to CAD event. Compared to the 1st (shortest) TL quintile, participants in the 5th (longest) TL quintile had univariable and multivariable CAD event OR = 0.56 (95% confidence interval [CI], .35-.91) and OR = 0.54 (95% CI, .31-.96). Multivariable OR for current smoking was 1.93 (95% CI, 1.27-2.92), dyslipidemia OR = 1.92 (95% CI, 1.41-2.63), and for recent abacavir, cumulative lopinavir, indinavir, and darunavir exposure was OR = 1.82 (95% CI, 1.27-2.59), OR = 2.02 (95% CI, 1.34-3.04), OR = 3.42 (95% CI, 2.14-5.45), and OR = 1.66 (95% CI, 1.00-2.74), respectively. The TL-CAD association remained significant when adjusting only for Framingham risk score, when excluding TL outliers, and when adjusting for CMV-seropositivity, HCV-seropositivity, time spent with detectable HIV viremia, and injection drug use.

Conclusions: In PLWH, TL measured >9 years before, is independently associated with CAD events after adjusting for multiple traditional and HIV-related factors.
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http://dx.doi.org/10.1093/cid/ciaa1034DOI Listing
October 2021

SERIAL-ORDER recall in working memory across the cognitive spectrum of Parkinson's disease and neuroimaging correlates.

J Neuropsychol 2021 03 11;15(1):88-111. Epub 2020 May 11.

Department of Neurology and Centre of Clinical Neuroscience, First Faculty of Medicine, General University Hospital, Charles University, Prague, Czech Republic.

We sought to determine if Parkinson's disease (PD) with mild cognitive impairment (MCI) is associated with a greater SERIAL-ORDER (mental manipulation) than ANY-ORDER (auditory span, storage) deficit in working memory (WM). We investigated WM combining neuropsychological measures with the study of brain functional connectivity. A cohort of 160 patients with idiopathic PD, classified as PD-MCI (n = 87) or PD with normal cognition (PD-NC; n = 73), and 70 matched healthy controls were studied. Verbal WM was assessed with the Backward Digit Span Task (BDT; Lamar et al., 2007, Neuropsychologia, 45, 245), measuring SERIAL-ORDER and ANY-ORDER recall. Resting-state MRI data were collected for 15 PD-MCI, 15 PD-NC and 30 controls. Hypothesis-driven seed-based functional connectivity of the dorsolateral prefrontal cortex (DLPFC) was compared between the three groups and correlated with BDT performance. We found the main effect of the test (impairment in SERIAL ORDER > ANY ORDER) and group ((NC = PD-NC) > PD-MCI) in BDT performance that was even more pronounced in SERIAL ORDER when controlling for ANY ORDER variability but not vice versa. Furthermore, PD-MCI compared to other groups were characterized by the functional disconnection between the bilateral DLPFC and the cerebellum. In functional correlations, DLPFC connectivity was positively related to both SERIAL- and ANY-ORDER performance. In conclusion, PD-MCI patients evidenced greater SERIAL-ORDER (manipulation and cognitive control) than ANY-ORDER (storage) working memory impairment than PD-NC and controls with a disrupted DLPFC resting-state connectivity that was also related to the verbal WM performance.
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http://dx.doi.org/10.1111/jnp.12208DOI Listing
March 2021

Early off-label treatment during pandemics? A dilemma.

Swiss Med Wkly 2020 May 11;150:w20281. Epub 2020 May 11.

Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, University of Basel, Switzerland.

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http://dx.doi.org/10.4414/smw.2020.20281DOI Listing
May 2020

Cohort-Derived Machine Learning Models for Individual Prediction of Chronic Kidney Disease in People Living With Human Immunodeficiency Virus: A Prospective Multicenter Cohort Study.

J Infect Dis 2021 10;224(7):1198-1208

Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, University of Basel, Basel, Switzerland.

Background: It is unclear whether data-driven machine learning models, which are trained on large epidemiological cohorts, may improve prediction of comorbidities in people living with human immunodeficiency virus (HIV).

Methods: In this proof-of-concept study, we included people living with HIV in the prospective Swiss HIV Cohort Study with a first estimated glomerular filtration rate (eGFR) >60 mL/minute/1.73 m2 after 1 January 2002. Our primary outcome was chronic kidney disease (CKD)-defined as confirmed decrease in eGFR ≤60 mL/minute/1.73 m2 over 3 months apart. We split the cohort data into a training set (80%), validation set (10%), and test set (10%), stratified for CKD status and follow-up length.

Results: Of 12 761 eligible individuals (median baseline eGFR, 103 mL/minute/1.73 m2), 1192 (9%) developed a CKD after a median of 8 years. We used 64 static and 502 time-changing variables: Across prediction horizons and algorithms and in contrast to expert-based standard models, most machine learning models achieved state-of-the-art predictive performances with areas under the receiver operating characteristic curve and precision recall curve ranging from 0.926 to 0.996 and from 0.631 to 0.956, respectively.

Conclusions: In people living with HIV, we observed state-of-the-art performances in forecasting individual CKD onsets with different machine learning algorithms.
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http://dx.doi.org/10.1093/infdis/jiaa236DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8514185PMC
October 2021

Antibiotic prophylaxis in transurethral resection of bladder tumours: study protocol for a systematic review and meta-analysis.

Syst Rev 2020 04 23;9(1):89. Epub 2020 Apr 23.

Department of Urology, University Hospital Basel, Spitalstrasse 21, 4031, Basel, Switzerland.

Background: The necessity of antibiotic prophylaxis for postoperative urinary tract infections (UTIs) after transurethral resection of bladder tumours is controversial. This potentially leads to the overuse of antibiotic prophylaxis and rising antimicrobial resistance rates. The objective of this systematic review and meta-analysis is to compare the impact of different antimicrobial prophylaxis schemes versus placebo on the prevention of postoperative UTI and asymptomatic bacteriuria.

Methods: We designed and registered a study protocol for a systematic review and meta-analysis of randomized controlled trials and non-randomized (e.g. cohort, case-control) studies examining any form of antibiotic prophylaxis in patients with transurethral resection of bladder tumours. Literature searches will be conducted in several electronic databases (from inception onwards), including MEDLINE (Ovid), EMBASE (Ovid), and the Cochrane Central Register of Controlled Trials (CENTRAL). Grey literature will be identified through searching conference abstracts. The primary outcome will be postoperative urinary tract infections. The secondary outcome will be asymptomatic bacteriuria. Two reviewers will independently screen all citations, full-text articles, and abstract data. Potential conflicts will be resolved through discussion. The study methodological quality (or bias) will be appraised using appropriate tools (e.g. Risk of Bias 2.0 tool and Newcastle-Ottawa Scale). If feasible, we will conduct random-effects meta-analysis of outcome data. Additional analyses will be conducted to explore the potential sources of heterogeneity (e.g. study design, publication year, the setting of the study, and antibiotics regimen). We will also search, identify, and discuss potential risk factors for urinary tract infections following transurethral resection of bladder tumours. This may serve as basis for a scoping review.

Discussion: In times of rising antimicrobial resistance rates, sound evidence on the necessity of antibiotic prophylaxis is essential for implementation into guideline recommendations and for decision-making in clinical practice.

Systematic Review Registration: PROSPERO, CRD42019131733.
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http://dx.doi.org/10.1186/s13643-020-01353-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7181504PMC
April 2020

Differences in social and mental well-being of long-term survivors among people who inject drugs and other participants in the Swiss HIV Cohort Study: 1980-2018.

Antivir Ther 2020 ;25(1):43-54

Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.

Background: People living with HIV who were diagnosed before highly active antiretroviral therapy became available in 1996 and who survived at least 15 years after HIV diagnosis, termed long-term survivors (LTS), form a particularly vulnerable population. We study social, clinical and mental factors of LTS in the Swiss HIV Cohort Study, with a particular focus on people who inject drugs (PWID).

Methods: We quantified differences between PWID LTS, and men who have sex with men (MSM) and heterosexual (HET) LTS. Using phylogenetic methods, we distinguished between heterosexual LTS who most likely shared a social network with PWID at the time of infection, termed clusteredHET, and those who did not, termed HET not clustered (HETnc). The analysis was performed using data collected at least 15 years post diagnosis.

Results: Overall, 1,663 of 5,686 (29.2%) PWID were LTS. We found significant differences between PWID LTS and MSM/HETnc LTS regarding self-reported depression (59.4% versus 43.3%; odds ratio [OR]=1.8; P<0.001), incarceration (30.6% versus 7.0%; OR=6.9; P<0.001) and full work ability (25.4% versus 59.0%; OR=0.27; P<0.001). ClusteredHET were less vulnerable with respect to these variables than PWID LTS but more at risk compared with MSM/HETnc LTS, indicating that clusteredHET are closer to PWID with regard to social and mental aspects compared with all MSM/HETnc.

Conclusions: Even more than 15 years post HIV diagnosis, special care for HIV-positive PWID is needed, with emphasis on mental health and social integration of PWID LTS.
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http://dx.doi.org/10.3851/IMP3347DOI Listing
September 2021

Repeated Syphilis Episodes in HIV-Infected Men Who Have Sex With Men: A Multicenter Prospective Cohort Study on Risk Factors and the Potential Role of Syphilis Immunity.

Open Forum Infect Dis 2020 Jan 12;7(1):ofaa019. Epub 2020 Jan 12.

Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, University of Basel, Basel, Switzerland.

Background: Syphilis is re-emerging globally in general and HIV-infected populations, and repeated syphilis episodes may play a central role in syphilis transmission among core groups. Besides sexual behavioral factors, little is known about determinants of repeated syphilis episodes in HIV-infected individuals-including the potential impact of preceding syphilis episodes on subsequent syphilis risk.

Methods: In the prospective Swiss HIV cohort study, with routine syphilis testing since 2004, we analyzed HIV-infected men who have sex with men (MSM). Our primary outcome was first and repeated syphilis episodes. We used univariable and multivariable Andersen-Gill models to evaluate risk factors for first and repeated incident syphilis episodes.

Results: Within the 14-year observation period, we included 2513 HIV-infected MSM with an initially negative syphilis test. In the univariable and multivariable analysis, the number of prior syphilis episodes (adjusted hazard ratio [aHR] per 1-episode increase, 1.15; 95% confidence interval [CI], 1.01-1.31), having occasional sexual partners with or without condomless anal sex (aHR, 4.99; 95% CI, 4.08-6.11; and aHR, 2.54; 95% CI, 2.10-3.07), and being currently on antiretroviral therapy (aHR, 1.62; 95% CI, 1.21-2.16) were associated with incident syphilis.

Conclusions: In HIV-infected MSM, we observed no indication of decreased syphilis risk with repeated syphilis episodes. The extent of sexual risk behavior over time was the strongest risk factor for repeated syphilis episodes. The observed association of antiretroviral therapy with repeated syphilis episodes warrants further immunological and epidemiological investigation.
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http://dx.doi.org/10.1093/ofid/ofaa019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6988838PMC
January 2020

Impact of dopamine and cognitive impairment on neural reactivity to facial emotion in Parkinson's disease.

Eur Neuropsychopharmacol 2019 11 10;29(11):1258-1272. Epub 2019 Oct 10.

Department of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine and General University Hospital, Charles University in Prague, Prague, Czechia; Department of Radiology, Na Homolce Hospital, Prague, Czechia.

Emotional and cognitive impairments in Parkinson's disease (PD) are prevalent, hamper interpersonal relations and reduce quality of life. It is however unclear to what extent these domains interplay in PD-related deficits and how they are influenced by dopaminergic availability. This study examined the effect of cognitive impairment and dopaminergic medication on neural and behavioral mechanisms of facial emotion recognition in PD patients. PD patients on and off dopaminergic medication and matched healthy controls underwent an emotional face matching task during functional MRI. In addition, a comprehensive neuropsychological evaluation of cognitive function was conducted. Increased BOLD response to emotional faces was found in the visual cortex of PD patients relative to controls irrespective of cognitive function and medication status. Administration of dopaminergic medication in PD patients resulted in restored behavioral accuracy for emotional faces relative to controls and decreased retrosplenial cortex BOLD response to emotion relative to off-medication state. Furthermore, cognitive impairment in PD patients was associated with reduced behavioral accuracy for non-emotional stimuli and predicted BOLD response to emotion in the anterior and posterior cingulate cortices, depending on medication status. Findings of aberrant visual and retrosplenial BOLD response to emotion are suggested to stem from altered attentional and/or emotion-driven modulation from subcortical and higher cortical regions. Our results indicate neural disruptions and behavioral deficits in emotion processing in PD patients that are dependent on dopaminergic availability and independent of cognitive function. Our findings highlight the importance of dopaminergic treatment not only for the motor symptoms but also the emotional disturbances in PD.
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http://dx.doi.org/10.1016/j.euroneuro.2019.09.003DOI Listing
November 2019

High incidence of urinary tract infections after photoselective laser vaporisation of the prostate: a risk factor analysis of 665 patients.

World J Urol 2020 Jul 1;38(7):1787-1794. Epub 2019 Oct 1.

University of Basel, Basel, Switzerland.

Purpose: Although photoselective laser vaporisation of the prostate (PVP) is a recognised alternative to transurethral resection in treating benign prostatic obstruction, there is limited data on the incidence and determinants of postoperative urinary tract infections (UTI). We assessed patients subjected to PVP, evaluating incidence and potential determinants of postoperative UTIs.

Materials And Methods: Consecutive patients undergoing PVP between April 2010 and August 2018 were candidates for this retrospective cohort study. The primary outcome measure was microbiologically confirmed postoperative UTI. We fitted uni- and multi-variable Cox models to identify potential risk factors.

Results: Among the 665 included patients, 20% developed postoperative UTIs. The overall incidence rate per 100 patient-days was 0.65 (95% confidence interval [CI] 0.55-0.77). Risk factors for postoperative UTIs were end-stage renal failure (adjusted hazard ratio [aHR] = 14.10, 95% CI 2.08-64.58; p = 0.001) and presence of at least one of the following factors in the 3 months preceding PVP: (i) placement of urinary catheter, (ii) bacteriuria, (iii) UTI, or (iv) antimicrobial treatment (composite aHR = 1.99, 95% CI 1.22-3.24; p < 0.001). There was no apparent association between choice or duration of antimicrobial prophylaxis and incident UTIs.

Conclusions: Our analysis revealed a high incidence of UTIs after PVP and served to identify certain preoperative risk factors. Neither the choice of antimicrobial regimen nor its duration affected the incidence of UTIs. Prolonged antimicrobials proved to be disproportionately high, warranting further scrutiny in randomised controlled trials.
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http://dx.doi.org/10.1007/s00345-019-02969-3DOI Listing
July 2020

Contribution of specific pathogens to bloodstream infection mortality in neutropenic patients with hematologic malignancies: Results from a multicentric surveillance cohort study.

Transpl Infect Dis 2019 Dec 1;21(6):e13186. Epub 2019 Nov 1.

Division of Infectious Diseases, Department of Medicine II, Faculty of Medicine, University Medical Center, Albert-Ludwigs-University, Freiburg, Germany.

Bloodstream infection (BSI) remains a serious complication in patients with hematologic malignancies and neutropenia. The risk factors for mortality after BSI and the contributions of BSI pathogens to mortality remain incompletely understood. We evaluated first BSI among adult neutropenic patients undergoing high-dose chemotherapy for hematologic malignancies in the setting of (a) an early disease stage of autologous (auto-HSCT) or allogeneic (allo-HSCT) hematopoietic stem cell transplantation or (b) for acute leukemia. Risk factors for intensive care admission and all-cause mortality were analyzed by multivariable logistic regression 7 and 30 days after onset of the first BSI in the first neutropenic episode. Between 2002 and 2015, 9080 patients met the study inclusion criteria, and 1424 (16%) developed BSIs, most of them during the first week of neutropenia. Mortality during neutropenia within 7 days and 30 days after BSI onset was 2.5% and 5.1%, respectively, and differed considerably between BSI pathogens. Both 7-day and 30-day mortalities were highest for Pseudomonas aeruginosa BSI (16.7% and 26.7%, respectively) and lowest for BSI due to coagulase-negative Staphylococcus spp. (CoNS) and Streptococcus spp. BSI pathogens were independently associated with 7-day mortality included P aeruginosa, Klebsiella spp., Enterobacter spp., Serratia spp., and enterococci. Only gram-negative BSI and candidemia were associated with admission to intensive care within 7 days after BSI onset. BSI caused by P aeruginosa continues to carry a particularly poor prognosis in neutropenic patients. The unexpected association between enterococcal BSI and increased mortality needs further study.
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http://dx.doi.org/10.1111/tid.13186DOI Listing
December 2019

Reply to Yoshioka et al.

Clin Infect Dis 2020 04;70(9):2016-2017

Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Switzerland.

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http://dx.doi.org/10.1093/cid/ciz751DOI Listing
April 2020

Impact of health insurance status on surgical site infection incidence: A prospective cohort study.

Infect Control Hosp Epidemiol 2019 09 16;40(9):1063-1065. Epub 2019 Jul 16.

Division of Infectious Diseases and Hospital Epidemiology,University Hospital Basel,Basel,Switzerland.

Health insurance status may affect the risk for surgical site infection (SSI). A large prospective cohort study in a Swiss tertiary-care hospital did not find evidence of a difference in SSI risk in individuals with basic versus semiprivate or private insurance in a setting with universal health insurance coverage.
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http://dx.doi.org/10.1017/ice.2019.195DOI Listing
September 2019

Early versus late onset bloodstream infection during neutropenia after high-dose chemotherapy for hematologic malignancy.

Infection 2019 Oct 11;47(5):837-845. Epub 2019 Jun 11.

Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, University of Basel, Petersgraben 4, 4031, Basel, Switzerland.

Purpose: The length of neutropenia has a significant impact on the incidence of bloodstream infection (BSI) in cancer patients, but limited information is available about the pathogen distribution in late BSI.

Methods: Between 2002 and 2014, BSI episodes in patients with neutropenia receiving chemotherapy for hematologic malignancies were prospectively identified by multicenter, active surveillance in Germany, Switzerland and Austria. The incidence of first BSI episodes, their microbiology and time to BSI onset during the first episode of neutropenia of 15,988 patients are described.

Results: The incidence rate of BSI episodes was 14.7, 8.7, and 4.7 per 1000 patient-days in the first, second, and third week of neutropenia, respectively. BSI developed after a median of 5 days of neutropenia (interquartile range [IQR] 3-10 days). The medium duration of neutropenia to BSI onset was 4 days in Escherichia coli (IQR 3-7 days), Klebsiella spp. (2-8 days), and Staphylococcus aureus (3-6 days). In contrast, BSI due to Enterococcus faecium occurred after a median of 9 days (IQR 6-14 days; p < 0.001 vs. other BSI). Late onset of BSI (occurring after the first week of neutropenia) was also observed for Stenotrophomonas maltophilia (12 days, IQR 7-17 days; p < 0.001), and non-albicans Candida spp. (13 days, IQR 8-19 days; p < 0.001).

Conclusions: Over the course of neutropenia, the proportion of difficult to treat pathogens such as E. faecium, S. maltophilia, and Candida spp. increased. Among other factors, prior duration of neutropenia may help to guide empiric antimicrobial treatment in febrile neutropenia.
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http://dx.doi.org/10.1007/s15010-019-01327-0DOI Listing
October 2019

Memory impairment in Parkinson's disease: The retrieval versus associative deficit hypothesis revisited and reconciled.

Neuropsychology 2019 Mar;33(3):391-405

Charles University.

Objective: Our study explored the retrieval deficit and the associative deficit hypotheses of memory impairments in Parkinson's disease (PD). The former supports a memory deficit mediated by attention/executive dysfunctions, whereas the latter hypothesizes a hippocampal memory impairment in PD.

Method: We studied 31 controls and 34 PD patients classified as PD with normal cognition (PD-NC; n = 18) and PD with mild cognitive impairment (PD-MCI; n= 16). To test the retrieval deficit hypothesis, we measured the performance in encoding, retention, and recognition in verbal and visual domains; to test the associative deficit hypothesis, we used a specific associative binding measure. Using resting-state functional-MRI, we compared the functional connectivity of different hippocampal subfields between PD patients and controls, and we related it to memory performance.

Results: Consistently with the retrieval deficit hypothesis, PD-MCI, and PD-NC, were impaired in free recall encoding and retention in comparison to controls, especially in the visual domain. However, as predicted by the associative deficit hypothesis, PD-MCI and, to a lesser extent, PD-NC, showed also significant associative and binding deficits in cued recall. Notably, PD patients compared to controls did not show structural differences, although they had lower connectivity between the anterior hippocampi and the precuneus/superior parietal cortex. Worse performance in memory was associated with a more severe disruption of the hippocampal connectivity.

Conclusions: The pervasive pattern of memory impairment in PD supports both hypotheses. The interplay between the hippocampus, related to associative memory deficits, and the precuneus, related to attentional control, provides a neural signature that reconciles them. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
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http://dx.doi.org/10.1037/neu0000503DOI Listing
March 2019

Single-dose versus 3-day cotrimoxazole prophylaxis in transurethral resection or greenlight laser vaporisation of the prostate: study protocol for a multicentre randomised placebo controlled non-inferiority trial (CITrUS trial).

Trials 2019 Feb 19;20(1):142. Epub 2019 Feb 19.

Division of Infectious Diseases and 721 Hospital Epidemiology, University Hospital Basel, University of Basel, Petersgraben, 4031, Basel, Switzerland.

Background: Transurethral resection of the prostate (TURP) and Greenlight laser vaporisation (GL) of the prostate are frequently performed urological procedures. For TURP, a single-dose antimicrobial prophylaxis (AP) is recommended to reduce postoperative urinary tract infections. So far, no international recommendations for AP have been established for GL. In a survey-based study in Switzerland, Germany and Austria, urologists reported routinely extending AP primarily for 3 days after both interventions. We therefore aim to determine whether single-dose AP with cotrimoxazole is non-inferior to 3-day AP with cotrimoxazole in patients undergoing TURP or GL of the prostate.

Methods/design: We will conduct an investigator-initiated, multicentre, randomised controlled trial. We plan to assess the non-inferiority of single-dose AP compared to 3-day AP. The primary outcome is the occurrence of clinically diagnosed symptomatic urinary tract infections which are treated with antimicrobial agents within 30 days after randomisation. The vast majority of collected outcomes will be assessed from routinely collected data. The sample size was estimated to be able to show the non-inferiority of single-dose AP compared to 3-day AP with at least 80% power (1 - β = 0.8) at a significance level of α = 5%, applying a 1:1 randomisation scheme. The non-inferiority margin was determined in order to preserve 70% of the effect of usual care on the primary outcome. For an assumed event rate of 9% in both treatment arms, this resulted in a non-inferiority margin of 4.4% (i.e. 13.4% to 9%). To prove non-inferiority, a total of 1574 patients should be recruited, in order to have 1416 evaluable patients. The study is supported by the Swiss National Science Foundation.

Discussion: For AP in TURP and GL, there is a large gap between usual clinical practice and evidence-based guidelines. If single-dose AP proves non-inferior to prolonged AP, our study findings may help to reduce the duration of AP in daily routine-potentially reducing the risk of emerging resistance and complications related to AP.

Trial Registration: Clinicaltrials.gov, NCT03633643 . Registered 16 August 2018.
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http://dx.doi.org/10.1186/s13063-019-3237-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6381623PMC
February 2019

Medical diagnoses showed low relatedness in an explorative mutual information analysis of 190,837 inpatient cases.

J Clin Epidemiol 2019 05 11;109:42-50. Epub 2019 Jan 11.

University of Basel, Petersplatz 1, 4001 Basel, Switzerland; Department of Internal Medicine, Kantonsspital Luzern, Spitalstrasse, 6000 Lucerne, Switzerland. Electronic address:

Objectives: We aimed to quantify the shared information between medical diagnoses of an adult inpatient population to explore both multimorbidity patterns and vice versa the unrelatedness of medical diagnoses.

Study Design And Setting: This was a cross-sectional study, performed at a tertiary care center in Switzerland. Diagnoses were routinely coded using the International Classification of Diseases, 10th revision.

Results: Among 190,837 inpatient cases, 7,994 unique diagnoses were coded. There were 31.9 million possible diagnosis pairs; the respective mutual information scores in diagnosis pairs were low (range, 10 to 0.237). There were 148 pairs of diagnoses with a mutual information score higher than 0.01, which formed several clinically plausible disease clusters; 27.2% of cases did not have a diagnosis that belonged to one of the morbidity clusters.

Conclusion: In an explorative analysis, we observed a high unrelatedness of diagnoses in a tertiary-care inpatient population. This finding indicates that although multimorbidity patterns can be observed, inpatient cases frequently have further, unrelated diagnoses, which share little information with specific other diagnoses. Therefore, management of multimorbid patients should be individualized and may not be generalized based on a few multimorbidity patterns or clusters.
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http://dx.doi.org/10.1016/j.jclinepi.2019.01.003DOI Listing
May 2019

Regional gray matter changes and age predict individual treatment response in Parkinson's disease.

Neuroimage Clin 2019 10;21:101636. Epub 2018 Dec 10.

Max-Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany; Clinic for Cognitive Neurology, University Clinic, Leipzig, Germany; FTLD Consortium, Germany. Electronic address:

We aimed at testing the potential of biomarkers in predicting individual patient response to dopaminergic therapy for Parkinson's disease. Treatment efficacy was assessed in 30 Parkinson's disease patients as motor symptoms improvement from unmedicated to medicated state as assessed by the Unified Parkinson's Disease Rating Scale score III. Patients were stratified into weak and strong responders according to the individual treatment response. A multiple regression was implemented to test the prediction accuracy of age, disease duration and treatment dose and length. Univariate voxel-based morphometry was applied to investigate differences between the two groups on age-corrected T1-weighted magnetic resonance images. Multivariate support vector machine classification was used to predict individual treatment response based on neuroimaging data. Among clinical data, increasing age predicted a weaker treatment response. Additionally, weak responders presented greater brain atrophy in the left temporoparietal operculum. Support vector machine classification revealed that gray matter density in this brain region, including additionally the supplementary and primary motor areas and the cerebellum, was able to differentiate weak and strong responders with 74% accuracy. Remarkably, age and regional gray matter density of the left temporoparietal operculum predicted both and independently treatment response as shown in a combined regression analysis. In conclusion, both increasing age and reduced gray matter density are valid and independent predictors of dopaminergic therapy response in Parkinson's disease.
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http://dx.doi.org/10.1016/j.nicl.2018.101636DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6413309PMC
December 2019
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