Intensive Hospital Monitoring of Adverse Reactions to Drugs

A total of 1,268 patients admitted to hospital wards were kept under surveillance by one observer throughout their stay in hospital. All drugs given to them and the occurrence of adverse reactions were recorded.Drug reactions were found in 10·2% of the 1,160 patients who received drug therapy. Most reactions were due to known pharmacological actions of the drugs. Though only four reactions were of life-threatening seriousness, 80% of the 129 reactions observed were of moderate severity. Digitalis preparations, bronchodilator drugs, and ampicillin had the highest reaction rates. It is suggested that larger surveys of adverse reactions in relation to drug usage would make a useful contribution to the problem.     

Monitoring Change in Child Mortality through Household Surveys

Background

Most low- and middle-income countries lack fully functional civil registration systems. Measures of under-five mortality are typically derived from periodic household surveys collecting detailed information from women on births and child deaths. However, such surveys are expensive and are not appropriate for monitoring short-term changes in child mortality. We explored and tested the validity of two new analysis methods for less-expensive summary histories of births and child deaths for such monitoring in five African countries.

Methods and Findings

The first method we explored uses individual-level survey data on births and child deaths to impute full birth histories from an earlier survey onto summary histories from a more recent survey. The second method uses cohort changes between two surveys in the average number of children born and the number of children dead by single year of age to estimate under-five mortality for the inter-survey period. The first method produces acceptable annual estimates of under-five mortality for two out of six applications to available data sets; the second method produced an acceptable estimate in only one of five applications, though none of the applications used ideal data sets.

Conclusions

The methods we tested were not able to produce consistently good quality estimates of annual under-five mortality from summary birth history data. The key problem we identified was not with the methods themselves, but with the underlying quality of the summary birth histories. If summary birth histories are to be included in general household surveys, considerable emphasis must be placed on quality control.     

Disturbance of Circadian Rhythms in Analgosedated Intensive Care Unit Patients with and without Craniocerebral Injury

Melatonin, cortisol, heart rate, blood pressure, spontaneous motor activity, and body temperature follow stable circadian rhythms in healthy individuals. These circadian rhythms may be influenced or impaired by the loss of external zeitgebers during analgosedation, critical illness, continuous therapeutic intervention in the intensive care unit (ICU), and cerebral injury. This prospective, observational, clinical study examined 24 critically ill analgo‐sedated patients, 13 patients following surgery, trauma, or acute respiratory distress (ICU), and 11 patients with acute severe brain injury following trauma or cerebral hemorrhage (CCI). Blood samples for the determination of melatonin and cortisol were obtained from each patient at 2 h intervals for 24 h beginning at 18:00 h on day 1 and ending 16:00 h on day 2. Blood pressure, heart rate, body temperature, and spontaneous motor activity were monitored continuously. Level of sedation was assessed using the Ramsey Sedation Scale. The severity of illness was assessed using the APACHE‐II‐score. The time series data were analyzed by rhythm analysis with the Chronos‐Fit program, using partial Fourier series with up to six harmonics. The 24 h profiles of all parameters from both groups of patients were greatly disturbed/abolished compared to the well‐known rhythmic 24 h patterns in healthy controls. These rhythm disturbances were more pronounced in patients with brain injury. The results of this study provide evidence for a pronounced disturbance of the physiological temporal organization in ICU patients. The relative contribution of analgosedation and/or brain injury, however, is a point of future investigation.     

The Duration of Hypotension Determines the Evolution of Bacteremia-Induced Acute Kidney Injury in the Intensive Care Unit

Background

Exploration of the impact of severe hypotension on the evolution of acute kidney injury in septic patients.

Methods and Results

We reviewed the hemodynamic parameters of 137 adults with septic shock and proven blood stream infection in the ICU. Severe hypotension was defined as a mean arterial blood pressure (MAP) ≤65 mmHg. The influence of the duration of severe hypotension on the evolution of acute kidney injury was evaluated according to the RIFLE classification, with day 0 defined as the day of a positive blood stream infection. After bloodstream infection, the probability for a patient to be in Failure was significantly higher than before blood stream infection (OR = 1.94, p = 0.0276). Patients have a significantly higher risk of evolving to Failure if the duration of severe hypotension is longer (OR = 1.02 for each 10 minutes increase in duration of a MAP <65 mmHg, p = 0.0472). A cut-off of at least 51 minutes of severe hypotension (<65 mmHg) or at least 5.5 periods of severe hypotension within 1 day identified patients with increased risk to evolve to Failure.

Conclusions

There is a significant influence of both the duration and the number of periods of severe hypotension on the evolution to Failure. Blood stream infection has a significantly negative effect on the relationship between severe hypotension and Failure.     

APACHE III Outcome Prediction in Patients Admitted to the Intensive Care Unit with Sepsis Associated Acute Lung Injury

Background and objective

Acute Physiology and Chronic Health Evaluation (APACHE) III score has been widely used for prediction of clinical outcomes in mixed critically ill patients. However, it has not been validated in patients with sepsis-associated acute lung injury (ALI). The aim of the study was to explore the calibration and predictive value of APACHE III in patients with sepsis-associated ALI.

Method

The study was a secondary analysis of a prospective randomized controlled trial investigating the efficacy of rosuvastatin in sepsis-associated ALI (Statins for Acutely Injured Lungs from Sepsis, SAILS). The study population was sepsis-related ALI patients. The primary outcome of the current study was the same as in the original trial, 60-day in-hospital mortality, defined as death before hospital discharge, censored 60 days after enrollment. Discrimination of APACHE III was assessed by calculating the area under the receiver operating characteristic (ROC) curve (AUC) with its 95% CI. Hosmer-Lemeshow goodness-of-fit statistic was used to assess the calibration of APACHE III. The Brier score was reported to represent the overall performance of APACHE III in predicting outcome.

Main results

A total of 745 patients were included in the study, including 540 survivors and 205 non-survivors. Non-survivors were significantly older than survivors (59.71±16.17 vs 52.00±15.92 years, p<0.001). The primary causes of ALI were also different between survivors and non-survivors (p = 0.017). Survivors were more likely to have the cause of sepsis than non-survivors (21.2% vs. 15.1%). APACHE III score was higher in non-survivors than in survivors (106.72±27.30 vs. 88.42±26.86; p<0.001). Discrimination of APACHE III to predict mortality in ALI patients was moderate with an AUC of 0.68 (95% confidence interval: 0.64–0.73).

Conclusion

this study for the first time validated the discrimination of APACHE III in sepsis associated ALI patients. The result shows that APACHE III score has moderate predictive value for in-hospital mortality among adults with sepsis-associated acute lung injury.     

Serial Non-Invasive Monitoring of Renal Disease Following Immune-Mediated Injury Using Near-Infrared Optical Imaging

Background

Non-invasive monitoring of disease progression in kidney disease is still a major challenge in clinical practice. In vivo near-infrared (NIR) imaging provides a new tool for studying disease mechanisms and non-invasive monitoring of disease development, even in deep organs. The LI-COR IRDye® 800CW RGD optical probe (RGD probe) is a NIR fluorophore, that can target integrin alpha v beta 3 (α_vβ₃) in tissues.

Objective

This study aims to monitor renal disease progression in an anti-glomerular basement membrane (GBM) nephritis mouse model.

Methods

Anti-GBM nephritis was induced in 129x1/svJ mice by anti-GBM serum challenge. The expression of integrin α_vβ₃ in the diseased kidney was examined by immunohistochemistry and quantitative polymerase chain reaction. The RGD probe and control fluorophores, the 800CW dye, and the BSA-conjugated 800CW dye, were administered into anti-GBM nephritic mice. LI-COR Pearl® Impulse imaging system was used for in vivo imaging; while ex vivo organ imaging was acquired using the Maestro^TM imaging system.

Results

Kidney tissue from anti-GBM nephritic mice showed higher levels of integrin α_vβ₃ expression at both the protein and the mRNA level compared to normal mice. The RGD probe allowed in vivo renal imaging and the fluorescent signal could be specifically captured in the diseased kidneys up to 14 days, reflecting longitudinal changes in renal function.

Conclusion

The infrared RGD molecular probe that tracks integrin expression can be successfully used to monitor renal disease progression following immune-mediated nephritis.     

An in vivo Rodent Model of Contraction-induced Injury and Non-invasive Monitoring of Recovery

Muscle strains are one of the most common complaints treated by physicians. A muscle injury is typically diagnosed from the patient history and physical exam alone, however the clinical presentation can vary greatly depending on the extent of injury, the patient''s pain tolerance, etc. In patients with muscle injury or muscle disease, assessment of muscle damage is typically limited to clinical signs, such as tenderness, strength, range of motion, and more recently, imaging studies. Biological markers, such as serum creatine kinase levels, are typically elevated with muscle injury, but their levels do not always correlate with the loss of force production. This is even true of histological findings from animals, which provide a "direct measure" of damage, but do not account for all the loss of function. Some have argued that the most comprehensive measure of the overall health of the muscle in contractile force. Because muscle injury is a random event that occurs under a variety of biomechanical conditions, it is difficult to study. Here, we describe an in vivo animal model to measure torque and to produce a reliable muscle injury. We also describe our model for measurement of force from an isolated muscle in situ. Furthermore, we describe our small animal MRI procedure.Download video file.^{(50M, mov)}     

Pattern Detection in Intensive Care Monitoring Time Series with Autoregressive Models: Influence of the Model Order

The detection of patterns in monitoring data of vital signs is of great importance for adequate bedside decision support in critical care. Currently used alarm systems, which are based on fixed thresholds and independency assumptions, are not satisfactory in clinical practice. Time series techniques such as AR‐models consider autocorrelations within the series, which can be used for pattern recognition in the data. For practical applications in intensive care the data analysis has to be automated. An important issue is the suitable choice of the model order which is difficult to accomplish online. In a comparative case‐study we analyzed 34564 univariate time series of hemodynamic variables in critically ill patients by autoregressive models of different orders and compared the results of pattern detection. AR(2)‐models seem to be most suitable for the detection of clinically relevant patterns, thus affirming that treating the data as independent leads to false alarms. Moreover, using AR(2)‐models affords only short estimation periods. These findings for pattern detection in intensive care data are of medical importance as they justify a preselection of a model order, easing further automated statistical online analysis.     

Detection and Plant Monitoring Programs: Lessons from an Intensive Survey of Asclepias meadii with Five Observers

Monitoring programs, where numbers of individuals are followed through time, are central to conservation. Although incomplete detection is expected with wildlife surveys, this topic is rarely considered with plants. However, if plants are missed in surveys, raw count data can lead to biased estimates of population abundance and vital rates. To illustrate, we had five independent observers survey patches of the rare plant Asclepias meadii at two prairie sites. We analyzed data with two mark-recapture approaches. Using the program CAPTURE, the estimated number of patches equaled the detected number for a burned site, but exceeded detected numbers by 28% for an unburned site. Analyses of detected patches using Huggins models revealed important effects of observer, patch state (flowering/nonflowering), and patch size (number of stems) on probabilities of detection. Although some results were expected (i.e. greater detection of flowering than nonflowering patches), the importance of our approach is the ability to quantify the magnitude of detection problems. We also evaluated the degree to which increased observer numbers improved detection: smaller groups (3–4 observers) generally found 90 – 99% of the patches found by all five people, but pairs of observers or single observers had high error and detection depended on which individuals were involved. We conclude that an intensive study at the start of a long-term monitoring study provides essential information about probabilities of detection and what factors cause plants to be missed. This information can guide development of monitoring programs.     

Long-Term Survival and Dialysis Dependency Following Acute Kidney Injury in Intensive Care: Extended Follow-up of a Randomized Controlled Trial

Background

The incidence of acute kidney injury (AKI) is increasing globally and it is much more common than end-stage kidney disease. AKI is associated with high mortality and cost of hospitalisation. Studies of treatments to reduce this high mortality have used differing renal replacement therapy (RRT) modalities and have not shown improvement in the short term. The reported long-term outcomes of AKI are variable and the effect of differing RRT modalities upon them is not clear. We used the prolonged follow-up of a large clinical trial to prospectively examine the long-term outcomes and effect of RRT dosing in patients with AKI.

Methods and Findings

We extended the follow-up of participants in the Randomised Evaluation of Normal vs. Augmented Levels of RRT (RENAL) study from 90 days to 4 years after randomization. Primary and secondary outcomes were mortality and requirement for maintenance dialysis, respectively, assessed in 1,464 (97%) patients at a median of 43.9 months (interquartile range [IQR] 30.0–48.6 months) post randomization. A total of 468/743 (63%) and 444/721 (62%) patients died in the lower and higher intensity groups, respectively (risk ratio [RR] 1.04, 95% CI 0.96–1.12, p = 0.49). Amongst survivors to day 90, 21 of 411 (5.1%) and 23 of 399 (5.8%) in the respective groups were treated with maintenance dialysis (RR 1.12, 95% CI 0.63–2.00, p = 0.69). The prevalence of albuminuria among survivors was 40% and 44%, respectively (p = 0.48). Quality of life was not different between the two treatment groups. The generalizability of these findings to other populations with AKI requires further exploration.

Conclusions

Patients with AKI requiring RRT in intensive care have high long-term mortality but few require maintenance dialysis. Long-term survivors have a heavy burden of proteinuria. Increased intensity of RRT does not reduce mortality or subsequent treatment with dialysis.

Trial registration

www.ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00221013","term_id":"NCT00221013"}}NCT00221013 Please see later in the article for the Editors'' Summary     

A Remote Videography System for Monitoring Beavers

ABSTRACT We developed a remote videography system for monitoring behavior and demography of beavers (Castor canadensis) inside lodges and bank dens. Videography systems taped 6 beaver colonies for 1,080 hours and recorded 300 hours of beaver activity. Upon viewing videotape, we could characterize 86% of beaver activity into 1 of 12 behavioral categories. Of 26 individually marked beavers, we observed 8 (31%) on videotape and obtained a complete count of kits in 4 of 5 colonies. The remote videography system was generally useful and can provide wildlife biologists with demographic and behavioral information to support population modeling and management programs for beavers.     

Child Deaths Due to Injury in the Four UK Countries: A Time Trends Study from 1980 to 2010

Background

Injuries are an increasingly important cause of death in children worldwide, yet injury mortality is highly preventable. Determining patterns and trends in child injury mortality can identify groups at particularly high risk. We compare trends in child deaths due to injury in four UK countries, between 1980 and 2010.

Methods

We obtained information from death certificates on all deaths occurring between 1980 and 2010 in children aged 28 days to 18 years and resident in England, Scotland, Wales or Northern Ireland. Injury deaths were defined by an external cause code recorded as the underlying cause of death. Injury mortality rates were analysed by type of injury, country of residence, age group, sex and time period.

Results

Child mortality due to injury has declined in all countries of the UK. England consistently experienced the lowest mortality rate throughout the study period. For children aged 10 to 18 years, differences between countries in mortality rates increased during the study period. Inter-country differences were largest for boys aged 10 to 18 years with mortality rate ratios of 1.38 (95% confidence interval 1.16, 1.64) for Wales, 1.68 (1.48, 1.91) for Scotland and 1.81 (1.50, 2.18) for Northern Ireland compared with England (the baseline) in 2006–10. The decline in mortality due to injury was accounted for by a decline in unintentional injuries. For older children, no declines were observed for deaths caused by self-harm, by assault or from undetermined intent in any UK country.

Conclusion

Whilst child deaths from injury have declined in all four UK countries, substantial differences in mortality rates remain between countries, particularly for older boys. This group stands to gain most from policy interventions to reduce deaths from injury in children.