Chitinases are ubiquitous chitin-fragmenting hydrolases. Recently we discovered the first human chitinase, named chitotriosidase, that is specifically expressed by phagocytes. We here report the identification, purification, and subsequent cloning of a second mammalian chitinase. This enzyme is characterized by an acidic isoelectric point and therefore named acidic mammalian chitinase (AMCase). In rodents and man the enzyme is relatively abundant in the gastrointestinal tract and is found to a lesser extent in the lung. Like chitotriosidase, AMCase is synthesized as a 50-kDa protein containing a 39-kDa N-terminal catalytic domain, a hinge region, and a C-terminal chitin-binding domain. In contrast to chitotriosidase, the enzyme is extremely acid stable and shows a distinct second pH optimum around pH 2. AMCase is capable of cleaving artificial chitin-like substrates as well as crab shell chitin and chitin as present in the fungal cell wall. Our study has revealed the existence of a chitinolytic enzyme in the gastrointestinal tract and lung that may play a role in digestion and/or defense.

Background Adequate antibiotic dosing may improve outcomes in critically ill patients but is challenging due to altered and variable pharmacokinetics. To address this challenge, AutoKinetics was developed, a decision support system for bedside, real-time, data-driven and personalised antibiotic dosing. This study evaluates the feasibility, safety and efficacy of its clinical implementation. Methods In this two-centre randomised clinical trial, critically ill patients with sepsis or septic shock were randomised to AutoKinetics dosing or standard dosing for four antibiotics: vancomycin, ciprofloxacin, meropenem, and ceftriaxone. Adult patients with a confirmed or suspected infection and either lactate > 2 mmol/L or vasopressor requirement were eligible for inclusion. The primary outcome was pharmacokinetic target attainment in the first 24 h after randomisation. Clinical endpoints included mortality, ICU length of stay and incidence of acute kidney injury. Results After inclusion of 252 patients, the study was stopped early due to the COVID-19 pandemic. In the ciprofloxacin intervention group, the primary outcome was obtained in 69% compared to 3% in the control group (OR 62.5, CI 11.4–1173.78, p < 0.001). Furthermore, target attainment was faster (26 h, CI 18–42 h, p < 0.001) and better (65% increase, CI 49–84%, p < 0.001). For the other antibiotics, AutoKinetics dosing did not improve target attainment. Clinical endpoints were not significantly different. Importantly, higher dosing did not lead to increased mortality or renal failure. Conclusions In critically ill patients, personalised dosing was feasible, safe and significantly improved target attainment for ciprofloxacin. Trial registration: The trial was prospectively registered at Netherlands Trial Register (NTR), NL6501/NTR6689 on 25 August 2017 and at the European Clinical Trials Database (EudraCT), 2017-002478-37 on 6 November 2017.

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In respect of health, psychological stress is at a high level whereas the value of subjective health seems lower. The emphasis on situational parameters provides an insight into positive coping strategies and shifts the focus on influences that support health in a positive manner.

In the decades after 1550 the soldiery of the Netherlands witnessed the disappearance of the Landsknecht, who had the right to participate in decision-making and shape his daily life. He gradually became a mere “soldier”, subject to stricter discipline and control. This development accelerated after 1572 because William of Orange needed to maintain the support of the inhabitants of the Netherlands for the Revolt. Better discipline and control over his soldiers were imperative in this. Meanwhile, a progressive process of proletarianization left them largely unable to resist: they simply had nowhere else to go.

Quality assurance in hospital care increasingly focuses on evaluation of outcome. Problems arise with displaying results of medical care beyond discharge. In this context hospital readmissions are often used as outcome variable. But it is unclear whether readmissions are meaningful indices of quality of hospital care and if so, where to get valid data on readmissions. We used claims data of the regional health insurance fund in Saxony-Anhalt (AOK Saxony-Anhalt) from 2002 and 2003 (850,000 insured; nearly 300,000 cases per year). All hospital admissions of a insured person are identified by an anonymous id-number independent of the admitting hospital. By this way we can analyze readmissions individually. Readmission are frequent events in hospital care. Nearly one third of all patients were admitted at least a second time in 2003. 18 % of all hospital cases are readmissions within 30 days after discharge. Readmissions concentrated on chronically ill, oncological, or multimorbid patients. Many of the readmissions take place in the context of planned therapies or post-operative treatment. 'Revolving-door patients' with multiple readmissions point to problems in cooperation of ambulatory and hospital care. By defining tracer diagnoses and specific causes of readmissions unplanned readmissions may be identified as a quality indicator of suboptimal care. Readmissions don't express suboptimal care per se. But taking into account methodological aspects a tracer approach with defining specific unplanned readmissions may provide meaningful outcome indicators. These can be derived from claims data fast, routinely, and with low costs. Further validation of the approach is needed.

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