Sailing the boat together: Co-creation of a model for learning during transition.

PURPOSE: Medical students' transition to postgraduate training, given the complexity of new roles and responsibilities, requires the engagement of all involved stakeholders. This study aims to co-create a transition curriculum and determine the value of involving the key stakeholders throughout such transition in its design process. METHODS: We conducted a mixed-methods study involving faculty/leaders (undergraduate/postgraduate), final-year medical students, and chief residents. It commenced with eight co-creation sessions (CCS), qualitative results of which were used to draft a quantitative survey sent to non-participants, followed by two consensus-building CCS with the original participants. We applied thematic analysis for transcripts of all CCS, and mean scores with standard deviations for survey analysis. RESULTS: We identified five themes: adaptation, authenticity, autonomy, connectedness, and continuity, embedded in the foundation of a supportive environment, to constitute a Model of Learning during Transition (MOLT). Inclusion of various stakeholders and optimizing their representation brought rich perspectives to the design process. This was reinforced through active students' participation enabling a final consensus. CONCLUSIONS: Bringing perspectives of key stakeholders in the transition spectrum enriches transition curricula. The proposed MOLT can provide a guide for curriculum designers to optimize the final year of undergraduate medical training in preparing students for postgraduate training with essential competencies to be trained.

The Harvard medical practice study trigger system performance in deceased patients.

BACKGROUND: To detect possible threats to quality and safety, multiple systems have been developed. One of them is retrospective chart review. A team of experts scrutinizes medical records, selected by trigger systems, to detect possible adverse events (AEs). The most important AEs and more hints for possible improvement of care appear in deceased patients. Using triggers in a sample of these patients might increase the performance and lower the burden of scrutinizing records without possible preventable AEs. The aim of this study was therefore to determine the performance of the trigger system in a sample of deceased patients and to calculate the specificity and the sensitivity of this trigger system for predicting AEs. METHODS: We performed a study in which the records of deceased patients were screened for triggers by a team of trained nurses. A sample of 100 medical records was randomly selected out of records which had been screened between 2012 and 2015 for the first time, prior to the study in 2016. For the determination of significant differences between the first and second screening, McNemar's test of symmetry was used. Also, observed agreement, Cohen's Kappa and prevalence-adjusted and-bias-adjusted-kappa (PABAK) statistics were calculated. This was done for the two trigger rounds on both any trigger present and for every trigger separately. RESULTS: The observed agreement for any given trigger was 75% with a Kappa and PABAK of 0.5. For the individual triggers, the observed agreement was on average 90%. The corresponding Kappa was on average 0.42 (range: - 0.03-0.78) and the average PABAK was 0.8 (range: 0.44-0.92). Two adverse events were found in cases without triggers previously. The recalculated specificity and sensitivity for the original population were 58 and 92% respectively. CONCLUSIONS: For the reproducibility of triggers it seems that some perform better than others, but on average this is to our opinion suboptimal. The low specificity implies that many records are selected without AEs. This leads to a high false-positive rate making this labour-intensive record review process costly. Therefore, research for better and more expedient systems is required.

Biological Variation of Creatinine, Cystatin C, and eGFR over 24 Hours.

BACKGROUND: Estimated glomerular filtration rate (eGFR) is widely used in clinical practice. This study assessed the within-subject biological variation (CVI) of different eGFR equations in people with chronic kidney disease (CKD) and people without CKD. The aims of this study were (a) to determine the 24-h biological variation profiles of creatinine, cystatin C, and eGFR and (b) to determine whether CVI of creatinine, cystatin C, and eGFR changes on deterioration of glomerular filtration. METHODS: Hourly blood samples were analyzed from 37 individuals (17 without CKD, 20 with CKD) during 24 h. Creatinine (enzymatic method) and cystatin C were measured using a Cobas 8000 (Roche Diagnostics). eGFR was estimated using the Modification of Diet in Renal Disease and the Chronic Kidney Disease Epidemiology Collaboration based on creatinine and/or cystatin C. Plasma samples were stored at -80 °C before analysis. Outlier and homogeneity analyses were checked before performing a nested ANOVA to determine biological variation. RESULTS: CVI of creatinine was higher in people without CKD than in those with CKD (6.4% vs 2.5%) owing primarily to the more profound effect of meat consumption on creatinine variability in individuals with lower baseline creatinine concentrations. Unlike creatinine, cystatin C concentrations were unaffected by meat consumption. Cystatin C showed some diurnal rhythmic variation and less in people with CKD. Reference change values (RCVs) of all eGFR equations were within 13% to 20% in both study groups. CONCLUSIONS: Despite differences in CVI of creatinine, the CVI and RCV of the eGFR equations were relatively similar for people with or without CKD.

Within-day biological variation and hour-to-hour reference change values for hematological parameters.

BACKGROUND: Middle- and long-term biological variation data for hematological parameters have been reported in the literature. Within-day 24-h variability profiles for hematological parameters are currently lacking. However, comprehensive hour-to-hour variability data are critical to detect diurnal cyclical rhythms, and to take into account the 'time of sample collection' as a possible determinant of natural fluctuation. In this study, we assessed 24-h variation profiles for 20 hematological parameters. METHODS: Blood samples were collected under standardized conditions from 24 subjects every hour for 24 h. At each measurement, 20 hematological parameters were determined in duplicate. Analytical variation (CVA), within-subject biological variation (CVI), between-subject biological variation (CVG), index of individuality (II), and reference change values (RCVs) were calculated. For the parameters with a diurnal rhythm, hour-to-hour RCVs were determined. RESULTS: All parameters showed higher CVG than CVI. Highest CVG was found for eosinophils (46.6%; 95% CI, 34.9%-70.1%) and the lowest value was mean corpuscular hemoglobin concentration (MCHC) (3.2%; 95% CI, 2.4%-4.8%). CVI varied from 0.4% (95% CI, 0.32%-0.42%) to 20.9% (95% CI, 19.4%-22.6%) for red cell distribution width (RDW) and eosinophils, respectively. Six hematological parameters showed a diurnal rhythm. CONCLUSIONS: We present complete 24-h variability profiles for 20 hematological parameters. Hour-to-hour reference changes values may help to better discriminate between random fluctuations and true changes in parameters with rhythmic diurnal oscillations.

Acute dyspnea caused by hypocalcemia-related laryngospasm.

BACKGROUND: Laryngospasm is a rare cause of stridor in adults, and laryngospasm due to hypocalcemia is an unusual finding. CASE REPORT: We present a case of an adult woman with acute dyspnea. A week prior to presentation, she experienced short episodes of a pinching feeling in her throat and difficulty breathing. On primary assessment, stridor and a positive Trousseau sign were noted. Laboratory examination showed hypocalcemia. We concluded that the dyspnea was caused by laryngospasm due to hypocalcemia. Hypocalcemia was treated promptly, and stridor and dyspnea resolved rapidly. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Laryngospasm is a rare, but serious and potentially lethal, complication of hypocalcemia in adults. In every adult presenting with acute dyspnea and stridor, the possibility of hypocalcemia should be considered. Hypocalcemia should be treated promptly.

Informal learning from error in hospitals: what do we learn, how do we learn and how can informal learning be enhanced? A narrative review.

Learning from error is not just an individual endeavour. Organisations also learn from error. Hospitals provide many learning opportunities, which can be formal or informal. Informal learning from error in hospitals has not been researched in much depth so this narrative review focuses on five learning opportunities: morbidity and mortality conferences, incident reporting systems, patient claims and complaints, chart review and prospective risk analysis. For each of them we describe: (1) what can be learnt, categorised according to the seven CanMEDS competencies; (2) how it is possible to learn from them, analysed against a model of informal and incidental learning; and (3) how this learning can be enhanced. All CanMEDS competencies could be enhanced, but there was a particular focus on the roles of medical expert and manager. Informal learning occurred mostly through reflection and action and was often linked to the learning of others. Most important to enhance informal learning from these learning opportunities was the realisation of a climate of collaboration and trust. Possible new directions for future research on informal learning from error in hospitals might focus on ways to measure informal learning and the balance between formal and informal learning. Finally, 12 recommendations about how hospitals could enhance informal learning within their organisation are given.

Reflective learning in a patient safety course for final-year medical students.

BACKGROUND: Patient safety has become an important topic over the last decade and has also been increasingly implemented in the undergraduate curriculum. However, the best timing and method of teaching still remains to be decided. AIMS: To develop and evaluate a patient safety course for final-year students. The course is based on reflective learning and personal experiences to improve the transfer of theory into practice. METHODS: We performed a mixed method evaluation study of the course. An evaluation questionnaire and the number of completed incident report cards were analyzed using descriptive statistics. Focus groups, organized two and four weeks after the course, were analyzed using template analysis; the Theory of Planned Behaviour (TPB) was used to interpret the results. RESULTS: Students found the course overall instructive and reacted positively towards many elements of the course. Focus group analysis showed that an increase in knowledge about patient safety topics resulted in a change of attitudes towards these subjects and in an increase in awareness of patient safety. This influenced students' behavioral intention and their behavior. CONCLUSIONS: A course based on students' personal experiences enables them to transfer theory on patient safety issues into their own practice and has an effect on their awareness, attitudes and behavior. This could have a large impact on their future role as resident.

Efficacy of postmortem CT and tissue sampling in establishing the cause of death in clinical practice: a prospective observational study.

AIMS: The aim of this study is to evaluate whether agreement with autopsy-determined cause of death (COD) increases by use of postmortem CT (PMCT) or PMCT in combination with postmortem sampling (PMS), when compared with clinical assessment only. METHODS: This prospective observational study included deceased patients from the intensive care unit and internal medicine wards between October 2013 and August 2017. The primary outcome was percentage agreement on COD between the reference standard (autopsy) and the alternative postmortem examinations (clinical assessment vs PMCT or PMCT+PMS). In addition, the COD of patient groups with and without conventional autopsy were compared with respect to involved organ systems and pathologies. RESULTS: Of 730 eligible cases, 144 could be included for analysis: 63 underwent PCMT without autopsy and 81 underwent both PMCT and autopsy. Agreement with autopsy-determined COD was significantly higher for both PMCT with PMS (42/57, 74%), and PMCT alone (53/81, 65%) than for clinical assessment (40/81, 51%; p=0.007 and p=0.03, respectively). The difference in agreement between PMCT with PMS and PMCT alone was not significant (p=0.13). The group with autopsy had a significantly higher prevalence of circulatory system involvement and perfusion disorders, and a lower prevalence of pulmonary system involvement. CONCLUSION: PMCT and PMS confer additional diagnostic value in establishing the COD. Shortcomings in detecting vascular occlusions and perfusion disorders and susceptibility to pulmonary postmortem changes could in future be improved by additional techniques. Both PMCT and PMS are feasible in clinical practice and an alternative when autopsy cannot be performed.

Students' perceptions of patient safety during the transition from undergraduate to postgraduate training: an activity theory analysis.

Evidence that medical error can cause harm to patients has raised the attention of the health care community towards patient safety and influenced how and what medical students learn about it. Patient safety is best taught when students are participating in clinical practice where they actually encounter patients at risk. This type of learning is referred to as workplace learning, a complex system in which various factors influence what is being learned and how. A theory that can highlight potential difficulties in this complex learning system about patient safety is activity theory. Thirty-four final year undergraduate medical students participated in four focus groups about their experiences concerning patient safety. Using activity theory as analytical framework, we performed constant comparative thematic analysis of the focus group transcripts to identify important themes. We found eight general themes relating to two activities: learning to be a doctor and delivering safe patient care. Simultaneous occurrence of these two activities can cause contradictions. Our results illustrate the complexity of learning about patient safety at the workplace. Students encounter contradictions when learning about patient safety, especially during a transitional phase of their training. These contradictions create potential learning opportunities which should be used in education about patient safety. Insight into the complexities of patient safety is essential to improve education in this important area of medicine.

A Systematic Review of Methods for Medical Record Analysis to Detect Adverse Events in Hospitalized Patients.

OBJECTIVE: In this systematic review, we evaluate 2 of the most used trigger tools according to the criteria of the World Health Organization for evaluating methods. METHODS: We searched Embase, PubMed, and Cochrane databases for studies (2000-2017). Studies were included if medical record review (MRR) was performed with either the Global Trigger Tool or the Harvard Medical Practice Study in a hospital population. Quality assessment was performed in duplicate. Fifty studies were included, and results were reported for every criterion separately. RESULTS: Medical record review reveals more adverse events (AEs) than any other method. However, at the same time, it detects different AEs. The costs of an AE were on average €4296. Considerable efforts have been made worldwide in health care to improve safety and to reduce errors. These have resulted in some positive effects. The literature showed that MRR is focused on several domains of quality of care and seems suitable for both small and large cohorts. Furthermore, we found a moderate to substantial agreement for the presence of a trigger and a moderate to good agreement for the presence of an AE. CONCLUSIONS: Medical record review with a trigger tool is a reasonably well-researched method for the evaluation of the medical records for AEs. However, looking at the World Health Organization criteria, much research is still lacking or of moderate quality. Especially for the cost of detecting AEs, valuable information is missing. Moreover, knowledge of how MRR changes quality and safety of care should be evaluated.

Are "functionally related polymorphisms" of renin-angiotensin-aldosterone system gene polymorphisms associated with hypertension?

BACKGROUND: Genotype-phenotype association studies are typically based upon polymorphisms or haplotypes comprised of multiple polymorphisms within a single gene. It has been proposed that combinations of polymorphisms in distinct genes, which functionally impact the same phenotype, may have stronger phenotype associations than those within a single gene. We have tested this hypothesis using genes encoding components of the renin-angiotensin-aldosterone system and the high blood pressure phenotype. METHODS: Our analysis is based on 1379 participants of the cross-sectional SUNSET study randomly selected from the population register of Amsterdam. Each subject was genotyped for the angiotensinogen M235T, the angiotensin-converting enzyme insertion/deletion and the angiotensin II type 1 receptor A1166C polymorphism. The phenotype high blood pressure was defined either as a categorical variable comparing hypertension versus normotension as in most previous studies or as a continuous variable using systolic, diastolic and mean blood pressure in a multiple regression analysis with gender, ethnicity, age, body-mass-index and antihypertensive medication as covariates. RESULTS: Genotype-phenotype relationships were explored for each polymorphism in isolation and for double and triple polymorphism combinations. At the single polymorphism level, only the A allele of the angiotensin II type 1 receptor was associated with a high blood pressure phenotype. Using combinations of polymorphisms of two or all three genes did not yield stronger/more consistent associations. CONCLUSIONS: We conclude that combinations of physiologically related polymorphisms of multiple genes, at least with regard to the renin-angiotensin-aldosterone system and the hypertensive phenotype, do not necessarily offer additional benefit in analyzing genotype/phenotype associations.

Gene-load score of the renin-angiotensin-aldosterone system is associated with coronary heart disease in familial hypercholesterolaemia.

AIMS: Familial hypercholesterolaemia (FH) is characterized by premature coronary heart disease (CHD). However, the incidence of CHD varies considerably among FH patients. Genetic variation in the renin-angiotensin-aldosterone system (RAAS) and the adrenalin/noradrenalin system may be of importance in determining the CHD risk in FH, because of their involvement in CHD. We investigated the association between CHD risk and combined genetic variation in the RAAS and adrenalin/noradrenalin system. METHODS AND RESULTS: In 2190 FH patients, we genotyped six RAAS polymorphisms and five adrenalin/noradrenalin polymorphisms. For each patient, we calculated two gene-load scores by counting the number of risk genotypes within each pathway. Four of the six RAAS polymorphisms and none of the polymorphisms in the adrenalin/noradrenalin system were significantly associated with CHD (P < 0.05). The RAAS gene-load score was significantly associated with CHD (P(linear trend) < 0.001): in patients with a gene-load score of 5 or 6, the CHD risk was 2.3 times as high as in patients with a score of 0 or 1. The gene-load score of the adrenalin/noradrenalin system was not associated with CHD. CONCLUSION: Genetic variation in the RAAS contributes gene-dose dependently to CHD risk in patients with FH, whereas genetic variation in the adrenalin/noradrenalin system is not associated with CHD.

Single nucleotide polymorphisms in genes of circulatory homeostasis in surviving pediatric intensive care patients with meningococcal infection.

OBJECTIVE: In the course of a meningococcal infection, invasive and severe disease occurs in a restricted number of individuals. The predominant mechanism of death in case of meningococcal septic shock is circulatory failure. Inotropic requirements between patients vary widely. We investigated whether polymorphisms in genes regulating the hemodynamic response influence the amount of inotropics required or the susceptibility to severe meningococcal disease. DESIGN: Retrospective case control study. SETTING: Single-center pediatric intensive care unit (PICU). PATIENTS: Fifty-six cases (all consecutive patients admitted to the PICU between 1993 and 2001 with a proven meningococcal infection) and 136 controls. Patients were divided into two groups according to their inotropic requirements. INTERVENTION: DNA analysis was performed to determine the polymorphisms of the beta-adrenergic receptor gene-1, beta-adrenergic receptor gene-2, alpha-adducin, angiotensin converting enzyme, and angiotensin II type-1 receptor-1 genes. RESULTS: For the alpha-adducin gene a significant difference of the genotype distribution was found between the cases and controls. The odds ratio for admission to the PICU with meningococcal sepsis with or without meningitis, for carriers of the variant allele (Gly460Trp or Trp460Trp) was 2.1 (95% confidence interval 1.11-4.04; p < 0.02). Cases, homozygote for the wild-type allele of the beta-1 adrenergic receptor at locus 389, were more likely to have a low pediatric risk of mortality score on admission (odds ratio 3.6, 95% confidence interval 1.11-11.76). No difference was found in the distribution of the beta-adrenergic receptor gene-1, beta-adrenergic receptor gene-2, angiotensin converting enzyme, and angiotensin II type-1 receptor-1 polymorphisms between the two groups of patients or between cases and controls. CONCLUSIONS: Among patients admitted to the PICU with a meningococcal infection, the variant allele of the alpha-adducin gene was more prevalent compared with controls. Patients with the variant allele of the beta-adrenergic receptor gene-1 at locus 389 were more likely to have a high pediatric risk of mortality score on admission. The mechanism and clinical relevance of these findings is unclear.

Prevalence of diabetes mellitus and the performance of a risk score among Hindustani Surinamese, African Surinamese and ethnic Dutch: a cross-sectional population-based study.

BACKGROUND: While the prevalence of type 2 diabetes mellitus (DM) is high, tailored risk scores for screening among South Asian and African origin populations are lacking. The aim of this study was, first, to compare the prevalence of (known and newly detected) DM among Hindustani Surinamese, African Surinamese and ethnic Dutch (Dutch). Second, to develop a new risk score for DM. Third, to evaluate the performance of the risk score and to compare it to criteria derived from current guidelines. METHODS: We conducted a cross-sectional population based study among 336 Hindustani Surinamese, 593 African Surinamese and 486 Dutch, aged 35-60 years, in Amsterdam. Logistic regressing analyses were used to derive a risk score based on non-invasively determined characteristics. The diagnostic accuracy was assessed by the area under the Receiver-Operator Characteristic curve (AUC). RESULTS: Hindustani Surinamese had the highest prevalence of DM, followed by African Surinamese and Dutch: 16.7, 8.1, 4.2% (age 35-44) and 35.0, 19.0, 8.2% (age 45-60), respectively. The risk score included ethnicity, body mass index, waist circumference, resting heart rate, first-degree relative with DM, hypertension and history of cardiovascular disease. Selection based on age alone showed the lowest AUC: between 0.57-0.62. The AUC of our score (0.74-0.80) was higher than that of criteria from guidelines based solely on age and BMI and as high as criteria that required invasive specimen collection. CONCLUSION: In Hindustani Surinamese and African Surinamese populations, screening for DM should not be limited to those over 45 years, as is advocated in several guidelines. If selective screening is indicated, our ethnicity based risk score performs well as a screening test for DM among these groups, particularly compared to the criteria based on age and/or body mass index derived from current guidelines.

[It is not an issue that basic science courses are vanishing from the medical curriculum]. / Prima dat basisvakken verdwijnen uit de opleiding.

There is some controversy regarding the role of and time devoted to so-called basic sciences in the medical curriculum. In this article, the author argues that nowadays basic sciences are a far less important element of the medical curriculum than in the past, and that in time they will likely be phased out completely. Arguments put forward are the changing role of the medical doctor, evidence that general clinical reasoning skills do not exist, and that the contrary assumption has led to havoc. He concludes that the removal of basic sciences from the medical curriculum will be substituted by teaching of consultation skills, psychology and guideline application.

Adverse event detection by medical record review is reproducible, but the assessment of their preventability is not.

OBJECTIVE: To assess the reproducibility of adverse event evaluation by a medical record review committee. DESIGN: Cross-sectional reanalysis of medical records. INTERVENTION: Reviewers re-examined fifty medical records of deceased patients regarding the presence of adverse events, their potential preventability and their possible contribution to death. Also we investigated the root causes of the preventable AEs. Differences between the first and second assessment were calculated. RESULTS: The Kappa on the presence of an adverse event was 0.64 and 0.32 for the potential preventability. The intrarater agreement showed a Kappa of 0.61 on the adverse event presence and 0.64 for the potential preventability. Interrater agreement showed a Kappa of 0.66 for the adverse event presence and 0.03 for the potential preventability. CONCLUSION: We found a fair reproducibility for the detection of adverse events, but a poor reproducibility for the potential preventability. Possibly this was caused by lack of a definition for the preventability of adverse events. We think giving feedback to professionals using the results of medical record review remains valuable, but an improvement of its reproducibility is essential. To our opinion an international consensus on what exactly constitutes preventability of adverse events and agreement on a definition is necessary. This would result in more comparable studies in this field and could then be more informative on the ideal procedure to avoid certain potentially preventable adverse events in the future.

Creatine kinase activity is associated with blood pressure.

BACKGROUND: We previously hypothesized that high activity of creatine kinase, the central regulatory enzyme of energy metabolism, facilitates the development of high blood pressure. Creatine kinase rapidly provides adenosine triphosphate to highly energy-demanding processes, including cardiovascular contraction, and antagonizes nitric oxide-mediated functions. Relatively high activity of the enzyme, particularly in resistance arteries, is thought to enhance pressor responses and increase blood pressure. Tissue creatine kinase activity is reported to be high in black people, a population subgroup with greater hypertension risk; the proposed effects of high creatine kinase activity, however, are not "race dependent." We therefore assessed whether creatine kinase is associated with blood pressure in a multiethnic population. METHODS AND RESULTS: We analyzed a stratified random sample of the population of Amsterdam, The Netherlands, consisting of 1444 citizens (503 white European, 292 South Asian, 580 black, and 69 of other ethnicity) aged 34 to 60 years. We used linear regression analysis to investigate the association between blood pressure and normal serum creatine kinase after rest, as a substitute measure of tissue activity. Creatine kinase was independently associated with blood pressure, with an increase in systolic and diastolic pressure, respectively, of 8.0 (95% CI, 3.3 to 12.7) and 4.7 (95% CI, 1.9 to 7.5) mm Hg per log creatine kinase increase after adjustment for age, sex, body mass index, and ethnicity. CONCLUSIONS: Creatine kinase is associated with blood pressure. Further studies are needed to explore the nature of this association, including how variation in cardiovascular creatine kinase activity may affect pressor responses.

The M235T polymorphism in the angiotensinogen gene is associated with the risk of malignant hypertension in white patients.

BACKGROUND: Malignant hypertension can be considered an extreme phenotype of renin-mediated hypertension. Therefore, we compared the allelic frequencies of the angiotensinogen (AGT) M235T, angiotensin-converting enzyme insertion/deletion (ACE I/D) and angiotensin II-type I receptor (AT1R) A1166C polymorphisms in malignant hypertensive patients with hypertensive and normotensive controls. METHODS: A total of 101 consecutive patients between 1995 and 2005 admitted to a large university hospital fulfilled the criteria for malignant hypertension. Seventy-five patients (74%) were compared with 150 hypertensive and 150 normotensive controls, randomly selected from a population study and individually matched on age, sex and ethnicity. RESULTS: The odds of malignant hypertension in white subjects with the TT genotype of the AGT M235T polymorphism was 14.3 (5.5-37) compared to hypertensive controls, and 9.4 (3.8-23.2) compared to normotensive controls. Adjustment for age, sex, smoking and antihypertensive therapy did not affect this association. The association of AGT M235T with malignant hypertension was not significant in blacks. In patients with malignant hypertension, the TT genotype was associated with more severe renal dysfunction and microangiopathic haemolysis. No differences were found in allele frequencies of the ACE I/D or the AT1R A1166C polymorphisms between study groups. CONCLUSIONS: The TT genotype of AGT M235T is associated with malignant hypertension in whites, carriers having an odds of approximately 10 to 1 compared to hypertensive and normotensive controls. These observations may provide a better understanding of the pathophysiology of malignant hypertension and offer possibilities for identifying patients at risk. Larger association or linkage studies are needed for a more detailed risk assessment.

The renin-angiotensin system in malignant hypertension revisited: plasma renin activity, microangiopathic hemolysis, and renal failure in malignant hypertension.

BACKGROUND: Malignant hypertension is a renin-dependent form of hypertension. However, the variations in renin-angiotensin system (RAS) activation in malignant hypertension are not completely understood. A proposed mechanism for ongoing RAS activation is the presence of microangiopathic hemolysis resulting in renovascular ischemia. METHODS: We prospectively examined the association between plasma renin activity (PRA), microangiopathic hemolysis, and renal dysfunction in 30 consecutive patients with malignant hypertension (n=18) and severe hypertension (n=12). The PRA and aldosterone were measured in the supine position and before initiating therapy. RESULTS: The PRA was 8.8 ng angiotensin I (AI)/mL/h (interquartile range [IQR] 4.8-20) in malignant hypertensive patients and 2.8 ng AI/mL/h (IQR 0.6-6.3) in patients with severe hypertension (P<.01). Aldosterone was 1.30+/-1.02 nmol/L in patients with malignant hypertension compared with 0.44+/-0.37 nmol/L in those with severe hypertension (P<.01). In malignant hypertension, PRA highly correlated with lactic dehydrogenase (LDH) (r=0.76, P<.001), meaning that 58% of the variations in PRA could be explained by LDH. The PRA positively correlated with serum creatinine values at presentation (r=0.50, P=.007), but adjustment for LDH abolished the effect of PRA on creatinine (P=.24). CONCLUSIONS: The PRA and aldosterone were markedly elevated in patients with malignant hypertension but not in severely hypertensive patients despite small differences in blood pressure (BP). The strong logarithmic correlation between PRA, microangiopathic markers, and renal dysfunction suggests a renin-mediated acceleration of vascular damage and renal dysfunction in patients with malignant hypertension.

The ability of triggers to retrospectively predict potentially preventable adverse events in a sample of deceased patients.

Several trigger systems have been developed to screen medical records of hospitalized patients for adverse events (AEs). Because it's too labor-intensive to screen the records of all patients, usually a sample is screened. Our sample consists of patients who died during their stay because chances of finding preventable AEs in this subset are highest. Records were reviewed for fifteen triggers (n = 2182). When a trigger was present, the records were scrutinized by specialized medical doctors who searched for AEs. The positive predictive value (PPV) of the total trigger system and of the individual triggers was calculated. Additional analyses were performed to identify a possible optimization of the trigger system. In our sample, the trigger system had an overall PPV for AEs of 47%, 17% for potentially preventable AEs. More triggers present in a record increased the probability of detecting an AE. Adjustments to the trigger system slightly increased the positive predictive value but missed about 10% of the AEs detected with the original system. In our sample of deceased patients the trigger system has a PPV comparable to other samples. However still, an enormous amount of time and resources are spent on cases without AEs or with non-preventable AEs. Possibly, the performance could be further improved by combining triggers with clinical scores and laboratory results. This could be promising in reducing the costly and labor-intensive work of screening medical records.