Patient- and physician-related risk factors for hyperkalaemia in potassium-increasing drug-drug interactions.

PURPOSE: Hyperkalaemia due to potassium-increasing drug-drug interactions (DDIs) is a clinically important adverse drug event. The purpose of this study was to identify patient- and physician-related risk factors for the development of hyperkalaemia. METHODS: The risk for adult patients hospitalised in the University Hospital Zurich between 1 December 2009 and 31 December 2011 of developing hyperkalaemia was correlated with patient characteristics, number, type and duration of potassium-increasing DDIs and frequency of serum potassium monitoring. RESULTS: The 76,467 patients included in this study were prescribed 8,413 potentially severe potassium-increasing DDIs. Patient-related characteristics associated with the development of hyperkalaemia were pulmonary allograft [relative risk (RR) 5.1; p < 0.0001), impaired renal function (RR 2.7; p < 0.0001), diabetes mellitus (RR 1.6; p = 0.002) and female gender (RR 1.5; p = 0.007). Risk factors associated with medication were number of concurrently administered potassium-increasing drugs (RR 3.3 per additional drug; p < 0.0001) and longer duration of the DDI (RR 4.9 for duration ≥6 days; p < 0.0001). Physician-related factors associated with the development of hyperkalaemia were undetermined or elevated serum potassium level before treatment initiation (RR 2.2; p < 0.001) and infrequent monitoring of serum potassium during a DDI (interval >48 h: RR 1.6; p < 0.01). CONCLUSION: Strategies for reducing the risk of hyperkalaemia during potassium-increasing DDIs should consider both patient- and physician-related risk factors.

[Snakebite in Switzerland - a potentially life-threatening event?] / Schlangenbiss im Glarnerland ­ ein potenziell lebensbedrohliches Ereignis?

INTRODUCTION: A 39-year-old healthy patient accidentally stepped barefoot on an adder and was then bitten into the foot. After initially only local complaints, severe systemic symptoms developed within 10-15 minutes with swelling of the lips and soft palate, recurrent vomiting, bradycardia, weakly palpable peripheral pulse, hypotension, dyspnea and intermittent somnolence. The potentially life-threatening consequences of this severe poisoning could be avoided by using adequate emergency measures and immediate intravenous administration of antivenin.

Medulloblastoma: From TP53 Mutations to Molecular Classification and Liquid Biopsy.

A recent paradigm shift in the diagnostics of medulloblastoma allowed the distinction of four major groups defined by genetic data rather than histology. This new molecular classification correlates better with prognosis and will allow for the better clinical management of therapies targeting druggable mutations, but also offer a new combination of monitoring tumor development in real-time and treatment response by sequential liquid biopsy. This review highlights recent developments after a century of milestones in neurosurgery and radio- and chemotherapy, but also controversial theories on the cell of origin, animal models, and the use of liquid biopsy.

Liquid biopsy and glioblastoma.

Glioblastoma is the most common and malignant primary brain tumor. Despite a century of research efforts, the survival of patients has not significantly improved. Currently, diagnosis is based on neuroimaging techniques followed by histopathological and molecular analysis of resected or biopsied tissue. A recent paradigm shift in diagnostics ranks the molecular analysis of tissue samples as the new gold standard over classical histopathology, thus correlating better with the biological behavior of glioblastoma and clinical prediction, especially when a tumor lacks the typical hallmarks for glioblastoma. Liquid biopsy aims to detect and quantify tumor-derived content, such as nucleic acids (DNA/RNA), circulating tumor cells (CTCs), or extracellular vesicles (EVs) in biofluids, mainly blood, cerebrospinal fluid (CSF), or urine. Liquid biopsy has the potential to overcome the limitations of both neuroimaging and tissue-based methods to identify early recurrence and to differentiate tumor progression from pseudoprogression, without the risks of repeated surgical biopsies. This review highlights the origins and time-frame of liquid biopsy in glioblastoma and points to recent developments, limitations, and challenges of adding liquid biopsy to support the clinical management of glioblastoma patients.

Clinical decision support for monitoring drug-drug-interactions and potassium-increasing drug combinations: need for specific alerts.

Computer-triggered reminders alerting physicians on every potentially harmful drug-drug-interaction (DDI) induce alert fatigue due to frequent messages of limited clinical relevance. On demand DDI-checks, however, are not commonly used by physicians. Optimal strategies for sustained quality assurance have to consider patients' risk factors and focus on the most significant DDIs only. An approach is proposed based on the analysis of concurrent prescription of potassium-sparing diuretics and potassium supplements (CPPP), which are the most frequent DDIs classified as contraindicated. Although the frequency of monitoring potassium serum levels declined during prolonged periods of CPPP, the likelihood of observing a hyperkalaemia increased. The median treatment period of CPPP was 3.3 days, whereas hyperkalaemia occurred after a median observation time of 4.5 days of CPPP. Thus, computer-triggered reminders for ordering potassium serum levels may be indicated if monitoring has been discontinued after 48h of CPPP.

[CME: Candiduria and Candida Infections of the Urinary Tract]. / CME: Candidurie und Candida-Infektionen der Harnwege.

CME: Candiduria and Candida Infections of the Urinary Tract Abstract. Candiduria is common in hospitalized patients and is generally benign. Invasive infection of the kidney is unusual and is difficult to treat. The vast majority of fungal infections of the kidneys and bladder result from Candida albicans and other Candida species. A variety of other fungi can sometimes involve the kidneys as a result of disseminated infection.

Liquid Biopsy and Primary Brain Tumors.

Two decades of "promising results" in liquid biopsy have led to both continuing disappointment and hope that the new era of minimally invasive, personalized analysis can be applied for better diagnosis, prognosis, monitoring, and therapy of cancer. Here, we briefly highlight the promises, developments, and challenges related to liquid biopsy of brain tumors, including circulating tumor cells, cell-free nucleic acids, extracellular vesicles, and miRNA; we further discuss the urgent need to establish suitable biomarkers and the right standards to improve modern clinical management of brain tumor patients with the use of liquid biopsy.

Negligible impact of highly patient-specific decision support for potassium-increasing drug-drug interactions - a cluster-randomised controlled trial.

BACKGROUND AND OBJECTIVE: Clinical decision support (CDS) might improve management of potassium-increasing drug-drug interactions (DDI). We studied CDS with five features intended to increase effectiveness: (i) focus on serious DDIs, (ii) fewer notifications, (iii) presentation of current laboratory results, (iv) timing (when adverse event becomes likelier), (v) removal of notification when appropriate. METHODS: We conducted a 1-year, hospital-wide, cluster-randomised controlled trial in the inpatient setting at a large tertiary-care academic medical centre. Three CDS types were implemented: monitoring reminders (unknown potassium, no monitoring ordered), elevated potassium warnings (≥4.9 mEq/l), and hyperkalaemia alerts (≥5.5 mEq/l). The primary endpoint was the frequency of potassium-monitoring intervals >72 h. RESULTS: We analysed 15,272 and 18,981 stays with 2804 and 2057 potassium-increasing DDIs in the intervention and control groups, respectively. Patient-specific notifications: displayed were 869 reminders (1 per 3.2 potassium-increasing DDIs), 356 warnings (1:7.9), and 62 alerts (1:45.2). Nevertheless, insufficiently monitored DDIs were not reduced (intervention 451 of 9686 intervals >72 h [4.66%]; control 249 of 6140 [4.06%]). The only secondary outcome improved was the length of potassium monitoring intervals (intervention group mean 22.9 h, control 23.7 h; p <0.001). However, in the intervention group, during 50 of 2804 observed potassium-increasing DDI periods (1.78%) one or more serum potassium values ≥ 5.5mEq/l were measured, in the control group, during 27 of 2057 (1.31%; p = 0.20). CONCLUSIONS: A highly patient-specific CDS feature combination had a negligible impact on the management of potentially serious potassium-increasing DDIs and was unable to improve safety among hospitalised patients.

[A Slightly Different Gastroenteritis]. / Die etwas andere Gastroenteritis.

A Slightly Different Gastroenteritis Abstract. We report the case of a 81-year-old female presenting with gastroenteritic symptoms and laboratory findings of a hemolytic anemia, thrombocytopenia and acute renal failure with fatal outcome. A hemolytic-uremic syndrome caused by an infection with EHEC was diagnosed. As a further complication, a urinary tract infection with K. pneumoniae was diagnosed and treated.

[CME: Fusobacterium nucleatum/naviforme - a Rare but Serious Cause for Pyogenic Liver Abscesses]. / CME: Fusobacterium nucleatum/naviforme ­ eine seltene, aber nicht zu unterschätzende Ursache für pyogene Leberabszesse.

CME: Fusobacterium nucleatum/naviforme - a Rare but Serious Cause for Pyogenic Liver Abscesses Abstract. Pyogenic liver abscesses belong to the most common abdominal infections. Beside the most common pathogens, also rare forms like Fusobacteria, which can also be part of the natural oropharyngeal and enteral microbiome, may be considered to cause severe forms of abscesses of the liver. Since they may be more difficult to detect, they could become a challenge during diagnosis and therapy.

Developing strategies for predicting hyperkalemia in potassium-increasing drug-drug interactions.

OBJECTIVE: To compare different strategies predicting hyperkalemia (serum potassium level ≥5.5 mEq/l) in hospitalized patients for whom medications triggering potassium-increasing drug-drug interactions (DDIs) were ordered. MATERIALS AND METHODS: We investigated 5 strategies that combined prediction triggered at onset of DDI versus continuous monitoring and taking into account an increasing number of patient parameters. The considered patient parameters were identified using generalized additive models, and the thresholds of the prediction strategies were calculated by applying Youden's J statistic to receiver operation characteristic curves. Half of the data served as the calibration set, half as the validation set. RESULTS: We identified 132 incidences of hyperkalemia induced by 8413 potentially severe potassium-increasing DDIs among 76 467 patients. The positive predictive value (PPV) of those strategies predicting hyperkalemia at the onset of DDI ranged from 1.79% (undifferentiated anticipation of hyperkalemia due to the DDI) to 3.02% (additionally considering the baseline serum potassium) and 3.10% (including further patient parameters). Continuous monitoring significantly increased the PPV to 8.25% (considering the current serum potassium) and 9.34% (additional patient parameters). CONCLUSION: Continuous monitoring of the risk for hyperkalemia based on current potassium level shows a better predictive power than predictions triggered at the onset of DDI. This contrasts with efforts to improve DDI alerts by taking into account more patient parameters at the time of ordering.

[Bites of venomous snakes in Switzerland]. / CME: Giftschlangenbisse in der Schweiz.

Although snake bites are rare in Europe, there are a constant number of snake bites in Switzerland. There are two domestic venomous snakes in Switzerland: the aspic viper (Vipera aspis) and the common European adder (Vipera berus). Bites from venomous snakes are caused either by one of the two domestic venomous snakes or by an exotic venomous snake kept in a terrarium. Snake- bites can cause both a local and/or a systemic envenoming. Potentially fatal systemic complications are related to disturbances of the hemostatic- and cardiovascular system as well as the central or peripheral nervous system. Beside a symptomatic therapy the administration of antivenom is the only causal therapy to neutralize the venomous toxins.

Constitutive and regulated expression of platelet basic protein in human monocytes.

Platelet basic protein (PBP) and several of its derivatives are known for their broad range of functions as signaling molecules and cationic antimicrobial peptides and were considered hitherto megakaryocyte- and platelet-specific. In search of glucocorticoid-regulated antimicrobial systems of monocytes, we found a 15-fold down-regulation of PBP mRNA by differential display. Regulation was confirmed in vivo even at low prednisone doses. Quantitative mRNA analyses confirmed down-regulation also for platelets. Western blotting and immunostains showed down-regulation at the protein level. Pro-PBP derivatives were in the size range of 7.5-14 kD and in immunostains, gave granular cytoplasmatic patterns. Interleukin (IL)-4 and IL-10 induced a similar down-regulation. Phagocytosis resulted in an increase of smaller derivatives in the range of 7.5 kD. Stimulation with interferon-gamma and lipopolysaccharide did decrease expression of PBP and affected derivatization. Expression of PBP and its derivatives is not restricted to the megakaryocytic cell lineage. PBP and some of its derivatives might contribute to the antimicrobial armamentarium of mononuclear phagocytes or have monokine functions. Our studies define PBPs as one among the many immunosuppressive targets of glucocorticoids.

Too frequent low-dose methotrexate prescriptions: multicentre quality control and quality assurance with pre- and post-analysis.

INTRODUCTION: Methotrexate is used to treat many medical conditions with medication schedules that differ widely in dosage and frequency. The high potential of erroneous too frequent low-dose methotrexate prescriptions leading to severe adverse reactions is well known; however, documentation is mainly limited to case reports. We reviewed all methotrexate prescriptions in a secondary and a tertiary care hospital to analyse the incidence of too frequent low-dose methotrexate prescriptions, and assessed the quality assurance concepts implemented. METHODS: All nononcological low-dose methotrexate prescriptions issued for inpatients within 55 months were analysed to identify too frequent prescriptions potentially leading to harmful overdosing. Subsequently, clinical pharmacologists reviewed all new methotrexate prescriptions with resulting interventions at the physician level in the tertiary care hospital. The impact of an interruptive alert displayed at methotrexate order entry was assessed in the secondary care hospital. RESULTS: The incidence of too frequent prescriptions at the tertiary hospital was 1.6% (five medication errors and nine near misses in 888 inpatients). After introducing checks by pharmacologists, two prescription errors were intercepted during the 8 month quality assurance period. At the secondary care hospital the incidence dropped from 2.5% (2/79, 20 months) to 0.8% (1/123, 35 months) after the alert was implemented. CONCLUSIONS: The incidences of erroneous too frequent low-dose methotrexate prescriptions observed at both hospitals were considered too high due to the high potential for increased morbidity, mortality and costs. Therefore, quality assurance measures were implemented and the preliminary data show a positive impact on patient safety for both approaches.

Two women with recurrent falls: La maladie des genoux bleus alias cryptogenic drop attacks.

Two women, aged 79 and 56, reported recurrent falls for several years without any prodromes or residues, without any known features of either syncope or seizure, without any detectable causative condition and seemingly without revealing any pathognomonic signs in the clinical examination. In both cases, the falls occurred only while walking and without loss of consciousness. These falls resulted always in dropping forward with pouncing on the knees. There had never been an injury other than contusions of the knees. Indeed, inspection of the knees of one of these patients showed signs of contusion with erosions and scars of different ages, whereas on the whole body no other wounds or dermatological lesions could be detected. What could that be? Cryptogenic drop attacks--or in French and more descriptively: La maladie des genoux bleues!