Winter, spring, summer or fall: temporal patterns in placenta-mediated pregnancy complications-an exploratory analysis.

PURPOSE: Placenta-mediated pregnancy complications, like growth restriction and hypertensive disorders, are leading causes of maternal, fetal and neonatal morbidity and mortality in high-income countries. The purpose was to investigate if there is a seasonal variation in placenta-mediated pregnancy complications (small for gestational age, intrauterine growth restriction, preeclampsia, preterm birth and intrauterine fetal death). METHODS: This is a Danish cohort study including all singleton deliveries at gestational week 22 up to and including week 41 conceived from December 2006 to November 2016 (N = 555,459). We used statistical process control charts to visualize data and to test for patterns of non-random variation in data over time for pregnancies with risk factors (BMI, diabetes, in vitro fertilization, maternal age > 40 years, primipara, previous caesarean and smoking) and each of the following outcome: fetal growth restriction, hypertensive disorders, preterm birth and intrauterine fetal death. The study was approved by the Danish Data Protection agency; REG-039-2019. RESULTS: We found a seasonal pattern in hypertensive disorders during pregnancy with dips in pregnancies conceived in the fall season and highest risk by conception in the spring and summer season. We found no apparent seasonality in cases of preterm delivery, small for gestational age and intrauterine mortality. Individual risk factors (e.g. smoking and obesity) for placenta-mediated complicated over time were in consistency with the general trends. CONCLUSIONS: We found a significant seasonal variation in the risk of hypertensive disorders of pregnancy with highest risk by conception in the spring and summer season. This study found no seasonal variation in other placenta-mediated complications.

Analysis of antibiotic use patterns in Danish hospitals 2015-2021 using an adapted version of the who aware classification.

BACKGROUND: AWaRe is a tool to categorise and guide antibiotic use. Antibiotics are classified in three groups: Access, Watch and Reserve. The Access group contains first choice antibiotics for 25 of the most common infections. Antibiotics in the Watch and Reserve groups should be restricted to cases that cannot be effectively treated with drugs from the Access group. OBJECTIVES: The primary aim of this study was to evaluate and adapt the WHO 2019 AWaRe classification for use with antibiotic usage data in Danish hospitals. The secondary aim was to study the usefulness of the abxaware; software package for visualisation and analysis of temporal trends in antibiotic use patterns. METHODS: We obtained data on purchases of antibiotics in Danish hospitals from January 2015 to July 2021. Sixty-seven unique drugs had been purchased. To better correspond with Danish guidelines, we moved two drugs one AWaRe level upwards. To help aggregate antibiotics according to AWaRe and visualise use patterns, we developed an R package, abxaware. RESULTS: After adding two drugs that were not included in the original AWaRe classification nearly all antibiotics (>99%) used in Danish hospitals were covered. The abxaware software package for R is a useful tool to help aggregate, visualise and analyse antibiotic use patterns. CONCLUSIONS: With minor modifications, we adapted the AWaRe classification to cover most antibiotics used in Danish hospitals and to reflect Danish treatment guidelines. The abxaware package is a useful tool to aggregate and plot antibiotic usage data according to the AWaRe classification and to test for non-random variation in the percentage use of Access antibiotics.

Nonspecific symptoms dominate at first contact to emergency healthcare services among cases with invasive meningococcal disease.

BACKGROUND: An early appropriate response is the cornerstone of treatment for invasive meningococcal disease. Little evidence exists on how cases with invasive meningococcal disease present at first contact to emergency medical services. METHODS: Retrospective observational study of cases presenting with invasive meningococcal disease from January 1st of 2016 to December 31st of 2020 in the Capital Region of Denmark with a catchment area population of 1,800,000. A single medical emergency center provides services to the region. Data was collected from emergency medical services' call audio files, data from the call receiver registrations, registrations from ambulance personal and electronic health record data from the hospitalization. RESULTS: Of 1527 cases suspected of meningitis, 38 had invasive meningococcal disease and had been in contact with the emergency service. Most contacts were to the medical helpline rather than the emergency call center at initial contact to emergency medical services. All were hospitalized within 12 h. At initial contact, fever was present in 28 (74%) of 38 cases, while specific symptoms such as headache (n=12 (32%)), a rash or petechiae (n=9 (23%)) and stiffness of the neck (n=4 (11%)) varied and were infrequent. Cases younger than 18 years of age were more often male and more often presented with fever and rash/petechiae. Only 4 (11%) received prehospital antibiotic treatment. CONCLUSIONS: Cases with invasive meningococcal disease presented with fever and unspecific symptoms. Although few were acutely ill at their initial contact, all were admitted within 12 h. We suggest that all feverish cases should be systematically asked about specific symptoms and should be wary of symptom progression to optimize the early management if cases with invasive meningococcal disease.

Test-Retest Reliability of an Experienced Global Trigger Tool Review Team.

OBJECTIVES: During a comprehensive patient safety program at a 550-bed regional hospital in the Capital Region of Denmark, we observed an unexpected and unexplained doubling of the median patient harm rate from 56 to 109 harms per 1000 patient days measured by the Institute for Healthcare Improvement Global Trigger Tool (GTT). Meanwhile, other measures of patient safety, including hospital standardized mortality ratio, were stable or improving. Moreover, the review team was very experienced and stable during this period. Thus, we hypothesized that the increase in harm rate was not a true reflection of increased risk of patient harm but the result of the team getting better at identifying harms during GTT reviews. METHODS: We examined the ability of the GTT review team to reproduce the rate of harm of two separate periods in the same hospital: period 1 (January-June 2010) and period 2 (October 2011-March 2012). For each period, we examined two samples: the original sample that was drawn and used for the ongoing monitoring of harm at the hospital during the safety campaign and a second that we drew and analyzed for this study. RESULTS: We found increased harm rates both between review 1 and review 2 and between period 1 and period 2. The increase was solely in category E, minor temporary harm. CONCLUSIONS: The very experienced GTT team could not reproduce harm rates found in earlier reviews. We conclude that GTT in its present form is not a reliable measure of harm rate over time.

The increasing importance of Haemophilus influenzae in community-acquired pneumonia: results from a Danish cohort study.

BACKGROUND: Numerous studies have shown that the aetiology of community-acquired pneumonia (CAP) varies considerably among different healthcare settings. Because empiric therapies for CAP should cover the major pathogens, reports examining CAP aetiology are considered crucial, particularly in Nordic countries that still rely on penicillin G or V treatments for most patients with CAP. The primary objective of our study was to report CAP aetiology. Secondary objectives included the estimation of positivity rates for different tests and the odds of a positive test for various subgroups. METHODS: In this cohort study, microbiological data were analysed for an overall cohort (variable degree of microbiological testing) and for a subgroup that was tested for both, bacteria, viruses and fungi, using routine methods (defined as extensive testing). RESULTS: The overall cohort comprised 2,264 patients, including 315 who were extensively tested. Bacterial and viral monoinfections were the most commonly identified infections. The dominant pathogen identified among extensively tested patients was Haemophilus influenzae (23.7%), followed by Streptococcus pneumoniae (20.6%). The tests with the highest positivity rates were sputum cultures (34.7%) and viral polymerase chain reaction (PCR, 24.4%). The odds of achieving a microbiological diagnosis increased significantly when extensive testing was performed compared with selective testing (OR 2.86, 95% CI 2.24-3.64). CONCLUSION: Our study indicated that H. influenzae is the dominant responsible pathogen for bacterial CAP in Denmark. Thus, we believe that the current treatment recommendations that encourage the use of penicillin G or V for the majority of patients with CAP need to be revised.

Smooth operator: Modifying the Anhøj rules to improve runs analysis in statistical process control.

INTRODUCTION: The run chart is one form of statistical process control chart that is particularly useful for detecting persistent shifts in data over time. The Anhøj rules test for shifts by looking for unusually long runs (L) of data points on the same side of the process centre (mean or median) and unusually few crossings (C) of the centre depending on the number of available data points (N). Critical values for C and L have mainly been studied in isolation. But what is really of interest is the joint distribution of C and L, which has so far only been studied using simulated data series. We recently released an R package, crossrun that calculates exact values for the joint probabilities of C and L that allowed us to study the diagnostic properties of the Anhøj rules in detail and to suggest minor adjustments to improve their diagnostic value. METHODS: Based on the crossrun R package we calculated exact values for the joint distribution of C and L for N = 10-100. Furthermore, we developed two functions, bestbox() and cutbox() that automatically seek to adjust the critical values for C and L to balance between sensitivity and specificity requirements. RESULTS: Based on exact values for the joint distribution of C and L for N = 10-100 we present measures of the diagnostic value of the Anhøj rules. The best box and cut box procedures improved the diagnostic value of the Anhøj rules by keeping the specificity and sensitivity close to pre-specified target values. CONCLUSIONS: Based on exact values for the joint distribution of longest run and number of crossings in random data series this study demonstrates that it is possible to obtain better diagnostic properties of run charts by making minor adjustment to the critical values for C and L.

Improved treatment of community-acquired pneumonia through tailored interventions: Results from a controlled, multicentre quality improvement project.

BACKGROUND: Community-acquired pneumonia (CAP) is one of the leading causes of healthcare utilisation and death worldwide. Treatment according to evidence-based clinical guidelines can reduce mortality, antibiotic exposure and length of hospital stay related to CAP. LOCAL PROBLEM: Several studies, including a pilot study from one of our sites, indicate that physicians show a low grade of guideline adherence when managing patients with CAP. METHODS: To improve the guideline-based treatment of patients with CAP admitted to hospital, we designed a quality improvement study. Four process indicators were combined in a CAP care bundle: chest X-ray, CURB-65 severity score, lower respiratory tract samples and antibiotics within 8 hours from admission. After a 4-month baseline period, we applied multiple interventions at three hospitals during 8 months. Progression in our process indicators was measured continuously and compared with a control site without interventions. After the 8-month intervention period, we continued with a 4-month follow-up period to assess the sustainability of the improvements. RESULTS: The care bundle utilisation rate within 8 hours increased from 11% at baseline to 41% in the follow-up period at the intervention sites, whereas it remained below 3% at the control site. The most considerable improvements have been observed regarding documentation of CURB-65 (34% at baseline, 68% at follow-up) and the collection of lower respiratory tract samples (43% at baseline, 63% at follow-up). CONCLUSION: Our study has demonstrated poor adherence to CAP guidelines at all sites at baseline. After implementing multiple tailored interventions, guideline adherence increased substantially. In conclusion, we recommend that CAP guidelines should be actively adapted in order to be followed in a daily routine.

Joint distribution for number of crossings and longest run in independent Bernoulli observations. The R package crossrun.

The R package crossrun computes the joint distribution of the number of crossings and the longest run in a sequence of independent Bernoulli observations. The main intended application is statistical process control where the joint distribution may be used for systematic investigation, and possibly refinement, of existing rules for distinguishing between signal and noise. While the crossrun vignette is written to assist in practical use, this article gives a hands-on explanation of why the procedures works. The article also includes a discussion of limitations of the present version of crossrun together with an outline of ongoing work to meet these limitations. There is more to come, and it is necessary to grasp the basic ideas behind the procedure implemented both to understand these planned extensions, and how presently implemented rules in statistical process control, based on the number of crossings and the longest run, may be refined.

Use of red blood cells in Danish intensive care units: A population-based register study.

BACKGROUND: Red blood cell (RBC) transfusion is common in the intensive care unit (ICU). Recent trials have shown that a restrictive transfusion strategy is safe in most patients, and recent guidelines recommend such a strategy in most ICU patients. It is unknown if this has translated into a change in clinical practice. METHODS: We conducted a population-based register study of RBC transfusions in ICUs in the Danish Capital Region between 1st of January 2011 and 31st of December 2016 by linking data from the regional blood bank and the Danish Intensive Care Database. We used crude data and run- and control-charts to analyse changes in the number of RBC transfusions. RESULTS: We included 27 835 ICU admissions of which 6936 received 40 889 RBC units. The crude use was 36.2 RBC units per one-hundred patient bed-days in 2011 vs 29.8 in 2016. The run-chart analysis did not confirm a change in the total use of RBC units in all ICUs combined, and we observed no change in the proportion of transfused patients or in the use of RBCs among transfused patients. Sensitivity analyses showed decreased use of RBC units in two general ICUs, and a reduced use of RBC units among medical ICU patients. CONCLUSIONS: In this population-based register study, we did not with certainty observe changes over time in the use of RBC transfusions in all patients in all ICUs in the Danish Capital Region. A reduction in RBC use may have occurred in some general ICUs and in medical ICU patients.

Comparison of methods for measuring antibiotic consumption in an intensive care unit.

Hospitals worldwide are working on minimizing unnecessary use of antimicrobials. To assess actual changes of antimicrobial usage, correct and precise measurements are necessary. This study aimed to compare data on the purchase of antibiotics from the pharmacy and the administration of antibiotics to patients, respectively, in an intensive care unit (ICU). Data were obtained from the Neurointensive Care Unit (NICU) at Rigshospitalet, Denmark. During a 23-month period, comprising 10 770 bed-days (BD), the ward purchased 16 908 defined daily doses (DDD) of antibiotics from the pharmacy, and 15 130 DDD and 41 304 individual doses were administered. Intraclass correlation coefficients (ICCs) were calculated; control and runcharts and a Bland-Altman plot were constructed. Pharmacy sales and drug administration data showed no systematic variation over time with a monthly overestimation of pharmacy sales data of 10% (95% confidence interval (CI), 6.20-14.3%) for all antibiotics, and 7% (95% CI: 1.81-11.1%) for broad-spectrum antibiotics. The antibiotic consumption, without bed-days, has a clinically acceptable ICC of >0.70 and no systematic difference is suggested by the Bland-Altman plot. In this study of a large NICU, whose antibiotic consumption varied at random, pharmacy sales data were an acceptable approximation of the actual summarized drug consumption.

Importance of Individual Elements for Perineal Protection in Childbirth: An Interventional, Prospective Trial.

Objective To analyze the association between each element of a hands-on intervention in childbirth and the incidence of obstetric anal sphincter injuries (OASIS). Study Design We conducted a prospective, interventional quality improvement project and implemented a care bundle with five elements at an obstetric department in Denmark with 3,000 deliveries annually. We aimed at reducing the incidence of OASIS. In the preintervention period, 355 vaginally delivering nulliparous women were included. Similarly, 1,622 nulliparous women were included in the intervention period. The association of each element with the outcome was estimated using a regression analysis. Results The incidence of OASIS went down from 7.0 to 3.4% among nulliparous women delivering vaginally ( p = 0.003; relative risk = 0.48; 95% confidence interval [CI]: 0.30-0.76). Number needed to treat was 28. Logistic regression analysis showed that using hand on the head of the child significantly reduced the risk of OASIS (odds ratio = 0.28; 95% CI: 0.14-0.58). Conclusion Using a quality improvement framework, we documented the individual elements of the intervention. Hand on the infant's head reduced the risk of OASIS.

Sense and sensibility: on the diagnostic value of control chart rules for detection of shifts in time series data.

BACKGROUND: The aim of this study was to quantify and compare the diagnostic value of The Western Electric (WE) statistical process control (SPC) chart rules and the Anhoej rules for detection of non-random variation in time series data in order to make recommendations for their application in practice. METHODS: SPC charts are point-and-line graphs showing a measure over time and employing statistical tests for identification of non-random variation. In this study we used simulated time series data with and without non-random variation introduced as shifts in process centre over time. The primary outcome was likelihood ratios of combined tests. Likelihood ratios are useful measures of a test's ability to discriminate between the true presence or absence of a specific condition. RESULTS: With short data series (10 data points), the WE rules 1-4 combined and the Anhoej rules alone or combined with WE rule 1 perform well for identifying or excluding persistent shifts in the order of 2 SD. For longer data series, the Anhoej rules alone or in combination with the WE rule 1 seem to perform slightly better than the WE rules combined. However, the choice of which and how many rules to apply in a given situation should be made deliberately depending on the specific purpose of the SPC analysis and the number of available data points. CONCLUSIONS: Based on these results and our own practical experience, we suggest a stepwise approach to SPC analysis: Start with a run chart using the Anhoej rules and with the median as process centre. If, and only if, the process shows random variation at the desired level, apply the 3-sigma rule in addition to the Anhoej rules using the mean as process centre.

Use of prophylactic Saccharomyces boulardii to prevent Clostridium difficile infection in hospitalized patients: a controlled prospective intervention study.

Clostridium difficile infection (CDI) is a common complication to antibiotic use. Saccharomyces boulardii has shown effect as a prophylactic agent. We aimed to evaluate the efficacy of S. boulardii in preventing CDI in unselected hospitalized patients treated with antibiotics. We conducted a 1 year controlled prospective intervention study aiming to prescribe Sacchaflor (S. boulardii 5 × 109, Pharmaforce ApS) twice daily to hospitalized patients treated with antibiotics. Comparable departments from three other hospitals in our region were included as controls. All occurrences of CDI in patients receiving antibiotics were reported and compared to a baseline period defined as 2 years prior to intervention. Results were analyzed using run chart tests for non-random variation in CDI rates. In addition, odds ratios for CDI were calculated. S. boulardii compliance reached 44% at the intervention hospital, and 1389 patients were treated with Sacchaflor. Monthly CDI rates dropped from a median of 3.6% in the baseline period to 1.5% in the intervention period. S. boulardii treatment was associated with a reduced risk of CDI at the intervention hospital: OR = 0.06 (95% CI 0.02-0.16). At two control hospitals, CDI rates did not change. At one control hospital, the median CDI rate dropped from 3.5 to 2.4%, possibly reflecting the effects of simultaneous multifaceted intervention against CDI at that hospital. The results from this controlled prospective interventional study indicate that S. boulardii is effective for the prevention of CDI in an unselected cohort of mainly elderly patients from departments of internal medicine.

MiBAlert-a new information tool to fight multidrug-resistant bacteria in the hospital setting.

BACKGROUND: Although the timely isolation of patients is an essential intervention to limit spread of drug-resistant bacteria, information about the colonization status is often unavailable or lost when patients are readmitted or transferred between hospitals. Therefore, carriers of drug resistant bacteria are not recognized sufficiently early, and proper and timely isolation precautions are not taken. Consequently, resistant bacteria of public health concerns including vancomycin resistant enterococci (VRE) and methicillin resistant Staphylococcus aureus (MRSA) can spread epidemically. To ensure timely identification and proper isolation of such patients we developed an automatic real-time alert of carriers of drug resistant bacteria. OBJECTIVES: The aim of this paper is to describe the system, called MiBAlert, and share the initial experiences in connection with an outbreak of VRE in the greater Copenhagen area (the Capital region), Denmark. METHODS: We obtained data on cases of VRE from hospitals in Copenhagen during the period when the first version of MiBAlert was implemented and log-data on the use of MiBAlert. Furthermore, a survey was conducted among 88 staff members to investigate their experiences of MiBAlert. RESULTS: The alert is a tool directed toward healthcare personnel accessing the electronic health record (EHR) and those further involved in the care and treatment of the patient. It is based on a web service using data from the national microbiological database, MiBa. MiBAlert is a real-time electronic non-intrusive alert generated automatically in the header of the EHR each time record is accessed. On February 15, 2015 a pilot version of MiBAlert was launched. All positive tests for VRE throughout 1year were shown with alert status by MiBAlert visible to all medical staff with access to EHR. The alert system was automatically updated directly in the EHR across the five hospitals in the Capital region. We found that the system performed satisfactorily, being operational 24/7 all 135 trial days, apart from 72min, for all the hospitals. Of the staff who responded to the survey, 82% considered that MiBAlert overall improved compliance with isolation precautions regarding VRE-positive patients. We found a marked decline of new patients infected or colonized with VRE concomitant with the implementation of MiBAlert and the survey results. CONCLUSION: We found that MiBAlert was a valuable tool in a bundle approach to counter a multiple hospital outbreak of VRE, and that it has a great potential to improve the control of other drug-resistant bacteria.

The patient safety climate in Danish hospital units.

INTRODUCTION: This study aimed to describe and analyse the patient safety climate in 15 Danish hospital units. METHODS: A cross-sectional study design was applied. Patient safety culture was measured by the Danish version of the Safety Attitude Questionnaire comprising six cultural subscales. Subscale results were calculated as the percentage responders with an individual scale score of 75 point or more (range: 0-100), equivalent to %-positive, and as mean scale scores. RESULTS: Out of 867 invited employees, 544 (63%) participated. No differences in %-positive were found between nurses and doctors, across age, gender or work experience (p > 0.05), but the difference between leaders and frontline staff was evident (p < 0.05). Perceptions varied more among individuals within the unit than between units within the hospital, and between hospitals. CONCLUSIONS: The results provide a snapshot of how staff perceives the culture. The level of %-positives per dimension is comparable with most international findings. The higher levels of leaders who perceive the culture as positive should be further investigated in larger samples. Generally, patient safety culture should be assessed at unit level; dimensional strengths and weaknesses as well as subgroup differences should be identified, and dialogue-based methods should be applied to uncover why the culture is perceived as it is. FUNDING: The TrygFonden provided financial support to the Danish Safer Hospital Programme, which funded this study. TRIAL REGISTRATION: not relevant.

Diagnostic value of run chart analysis: using likelihood ratios to compare run chart rules on simulated data series.

Run charts are widely used in healthcare improvement, but there is little consensus on how to interpret them. The primary aim of this study was to evaluate and compare the diagnostic properties of different sets of run chart rules. A run chart is a line graph of a quality measure over time. The main purpose of the run chart is to detect process improvement or process degradation, which will turn up as non-random patterns in the distribution of data points around the median. Non-random variation may be identified by simple statistical tests including the presence of unusually long runs of data points on one side of the median or if the graph crosses the median unusually few times. However, there is no general agreement on what defines "unusually long" or "unusually few". Other tests of questionable value are frequently used as well. Three sets of run chart rules (Anhoej, Perla, and Carey rules) have been published in peer reviewed healthcare journals, but these sets differ significantly in their sensitivity and specificity to non-random variation. In this study I investigate the diagnostic values expressed by likelihood ratios of three sets of run chart rules for detection of shifts in process performance using random data series. The study concludes that the Anhoej rules have good diagnostic properties and are superior to the Perla and the Carey rules.

Run charts revisited: a simulation study of run chart rules for detection of non-random variation in health care processes.

BACKGROUND: A run chart is a line graph of a measure plotted over time with the median as a horizontal line. The main purpose of the run chart is to identify process improvement or degradation, which may be detected by statistical tests for non-random patterns in the data sequence. METHODS: We studied the sensitivity to shifts and linear drifts in simulated processes using the shift, crossings and trend rules for detecting non-random variation in run charts. RESULTS: The shift and crossings rules are effective in detecting shifts and drifts in process centre over time while keeping the false signal rate constant around 5% and independent of the number of data points in the chart. The trend rule is virtually useless for detection of linear drift over time, the purpose it was intended for.

[Stimulation of labour with oxytocin and ventouse deliveries are inadequately documented].

A retrospective sample of 180 records from four regional hospitals and five university hospitals in Denmark was collected and the documentation for use of oxytocin in augmentation of labour and ventouse deliveries according to the national guidelines was registered. Only approximately half of the elements in the national guidelines were documented. This shows that there is a potential for improvement in the ongoing Danish national quality improvement project Safe Deliveries (Sikre Fødsler).