Development and internal validation of the Simplified Mortality Score for the Intensive Care Unit (SMS-ICU).

BACKGROUND: Intensive care unit (ICU) mortality prediction scores deteriorate over time, and their complexity decreases clinical applicability and commonly causes problems with missing data. We aimed to develop and internally validate a new and simple score that predicts 90-day mortality in adults upon acute admission to the ICU: the Simplified Mortality Score for the Intensive Care Unit (SMS-ICU). METHODS: We used data from an international cohort of 2139 patients acutely admitted to the ICU and 1947 ICU patients with severe sepsis/septic shock from 2009 to 2016. We performed multiple imputations for missing data and used binary logistic regression analysis with variable selection by backward elimination, followed by conversion to a simple point-based score. We assessed the apparent performance and validated the score internally using bootstrapping to present optimism-corrected performance estimates. RESULTS: The SMS-ICU comprises seven variables available in 99.5% of the patients: two numeric variables: age and lowest systolic blood pressure, and five dichotomous variables: haematologic malignancy/metastatic cancer, acute surgical admission and use of vasopressors/inotropes, respiratory support and renal replacement therapy. Discrimination (area under the receiver operating characteristic curve) was 0.72 (95% CI: 0.71-0.74), overall performance (Nagelkerke's R2 ) was 0.19 and calibration (intercept and slope) was 0.00 and 0.99, respectively. Optimism-corrected performance was similar to apparent performance. CONCLUSIONS: The SMS-ICU predicted 90-day mortality with reasonable and stable performance. If performance remains adequate after external validation, the SMS-ICU could prove a valuable tool for ICU clinicians and researchers because of its simplicity and expected very low number of missing values.

Stress ulcer prophylaxis in adult intensive care unit patients - a protocol for a systematic review.

BACKGROUND: In the intensive care unit (ICU), stress ulcer prophylaxis with proton pump inhibitors or histamine-2-receptor antagonists is standard of care although gastrointestinal bleeding remains uncommon. It remains unknown whether its use is associated with benefits or harms and the quality of evidence supporting the use of stress ulcer prophylaxis has been questioned. Accordingly, the objective of this systematic review was to critically assess the evidence from randomized clinical trials on the benefits and harms of stress ulcer prophylaxis vs. placebo or no prophylaxis in adult ICU patients. METHODS: We will systematically search for randomized clinical trials in major international databases. Two authors will independently screen and select trials for inclusion, extract data and assess the methodological quality using the Cochrane risk of bias tool. Any disagreement will be resolved by consensus. We will perform conventional meta-analyses using Review Manager, and STATA 15, and we will assess the risk of random errors using Trial Sequential Analysis. Also, we will assess and report the overall quality of evidence for all outcomes according to GRADE. DISCUSSION: The evidence on the benefits and harms of stress ulcer prophylaxis in adult ICU patients is unclear and an updated systematic review is warranted as new trials have been published. To control risks of systematic and random errors, we will use Cochrane and GRADE methodology and Trial Sequential Analysis. Our ambition with this systematic review is to provide updated, reliable and precise data to better inform decision makers on the use of stress ulcer prophylaxis in adult ICU patients.

Timing of onset of gastrointestinal bleeding in the ICU: Protocol for a preplanned observational study.

BACKGROUND: Critically ill patients are at risk of gastrointestinal bleeding, but clinically important gastrointestinal bleeding is rare. The majority of intensive care unit (ICU) patients receive stress ulcer prophylaxis (SUP), despite uncertainty concerning the balance between benefit and harm. For approximately half of ICU patients with gastrointestinal bleeding, onset is early, ie within the first two days of the ICU stay. The aetiology of gastrointestinal bleeding and consequently the balance between benefit and harm of SUP may differ between patients with early vs late gastrointestinal bleeding. METHODS: This is a protocol and statistical analysis plan for a preplanned exploratory substudy of the Stress Ulcer Prophylaxis in the Intensive Care Unit (SUP-ICU) randomized clinical trial, comparing intravenous pantoprazole (40 mg once daily) with placebo in 3350 acutely ill adult ICU patients. We will describe baseline characteristics and assess the time to onset of the first clinically important episode of GI bleeding accounting for survival status and allocation to SUP or placebo. In addition, we will describe differences in therapeutic and diagnostic procedures used in patients with clinically important gastrointestinal bleeding according to early vs late bleeding and 90-day vital status. CONCLUSIONS: The study outlined in this protocol will provide detailed information on patient characteristics and the timing of onset of gastrointestinal bleeding in the patients enrolled in the SUP-ICU trial. This may provide additional knowledge and incentives for future studies on which patients benefit from SUP.

Use of life support in acutely admitted ICU patients. An international cohort study.

BACKGROUND: Use of life support in intensive care unit (ICU) patients has been associated with increased risk of poor outcome. The prognostic importance of the duration of support is less studied. We assessed the use of life support and the association between its duration and 90-day mortality in a contemporary cohort of acutely admitted adult ICU patients. METHODS: We performed a post-hoc analysis of the SUP-ICU 7-day inception cohort study (n = 1034), which was conducted in 97 ICUs in 11 countries. We included patients with an ICU stay of 3 days or more. We assessed the use of life support during the first 3 days in ICU and the crude and adjusted association between its duration and 90-day mortality using logistic regression analyses. RESULTS: We included 690 patients; their 90-day mortality was 23%. During the first 3 days in ICU mechanical ventilation was used in 65%, vasopressors/inotropes in 57% and renal replacement therapy in 13%. Renal replacement therapy for 3 days or more was associated with a higher 90-day mortality as compared with 1 day of renal replacement therapy [odds ratio 6.5 (95% confidence interval 1.3 to 32.8)]. For mechanical ventilation and vasopressors/inotropes the odds ratios were 2.2 [0.9 to 5.3] and 1.2 [0.5 to 2.6], respectively. CONCLUSIONS: Among acutely admitted adult ICU patients, a higher number of days of renal replacement therapy in the initial ICU stay were associated with increased risk of death within 90 days. We did not observe such an association for mechanical ventilation or vasopressor/inotropic therapy.

Stress ulcer prophylaxis in the intensive care unit trial: detailed statistical analysis plan.

BACKGROUND: In this statistical analysis plan, we aim to provide details of the pre-defined statistical analyses of the Stress Ulcer Prophylaxis in the Intensive Care Unit (SUP-ICU) trial. The aim of the SUP-ICU trial is to assess benefits and harms of stress ulcer prophylaxis with a proton pump inhibitor in adult patients in the intensive care unit (ICU). METHODS: The SUP-ICU trial is an investigator-initiated, international, multicentre, randomised, blinded, parallel-group trial of intravenously pantoprazole 40 mg once daily vs. placebo in 3350 acutely ill adult ICU patients at risk of gastrointestinal bleeding. The primary outcome measure is 90-day mortality. Secondary outcomes include the proportion of patients with clinically important gastrointestinal bleeding, pneumonia, Clostridium difficile infection or myocardial ischaemia, days alive without life support, serious adverse reactions, 1-year mortality, and a health economic analysis. Two formal interim analyses will be performed. The statistical analyses will be conducted according to the outlined pre-defined statistical analysis plan. The primary analysis will be a logistic regression analysis adjusted for stratification variables comparing the two intervention groups in the intention-to-treat population. In a secondary analysis, we will additionally adjust the primary outcome for potential random differences in baseline characteristics. The conclusion will be based on the intention-to-treat population. CONCLUSION: Stress ulcer prophylaxis is standard of care in ICUs worldwide, but has never been tested in large high-quality randomised placebo-controlled trials. The SUP-ICU trial will provide important high-quality data on the balance between the benefits and harms of stress ulcer prophylaxis in adult critically ill patients.

Stress ulcer prophylaxis in the intensive care unit: an international survey of 97 units in 11 countries.

BACKGROUND: Stress ulcer prophylaxis (SUP) may decrease the incidence of gastrointestinal bleeding in patients in the intensive care unit (ICU), but the risk of infection may be increased. In this study, we aimed to describe SUP practices in adult ICUs. We hypothesised that patient selection for SUP varies both within and between countries. METHODS: Adult ICUs were invited to participate in the survey. We registered country, type of hospital, type and size of ICU, preferred SUP agent, presence of local guideline, reported indications for SUP, criteria for discontinuing SUP, and concerns about adverse effects. Fisher's exact test was used to assess differences between groups. RESULTS: Ninety-seven adult ICUs in 11 countries participated (eight European). All but one ICU used SUP, and 64% (62/97) reported having a guideline for the use of SUP. Proton pump inhibitors were the most common SUP agent, used in 66% of ICUs (64/97), and H2-receptor antagonists were used 31% (30/97) of the units. Twenty-three different indications for SUP were reported, the most frequent being mechanical ventilation. All patients were prescribed SUP in 26% (25/97) of the ICUs. Adequate enteral feeding was the most frequent reason for discontinuing SUP, but 19% (18/97) continued SUP upon ICU discharge. The majority expressed concern about nosocomial pneumonia and Clostridium difficile infection with the use of SUP. CONCLUSIONS: In this international survey, most participating ICUs reported using SUP, primarily proton pump inhibitors, but many did not have a guideline; indications varied considerably and concern existed about infectious complications.

Stress ulcer prophylaxis in the intensive care unit: is it indicated? A topical systematic review.

UNLABELLED: Stress ulcer prophylaxis (SUP) is regarded as standard of care in the intensive care unit (ICU). However, recent randomized, clinical trials (RCTs) and meta-analyses have questioned the rationale and level of evidence for this recommendation. The aim of the present systematic review was to evaluate if SUP in the critically ill patients is indicated. DATA SOURCES:  MEDLINE including MeSH, EMBASE, and the Cochrane Library. PARTICIPANTS: patients in the ICU. INTERVENTIONS: pharmacological and non-pharmacological SUP. STUDY APPRAISAL AND SYNTHESIS METHODS: Risk of bias was assessed according to Grading of Recommendations Assessment, Development, and Evaluation, and risk of random errors in cumulative meta-analyses was assessed with trial sequential analysis. A total of 57 studies were included in the review. The literature on SUP in the ICU includes limited trial data and methodological weak studies. The reported incidence of gastrointestinal (GI) bleeding varies considerably. Data on the incidence and severity of GI bleeding in general ICUs in the developed world as of today are lacking. The best intervention for SUP is yet to be settled by balancing efficacy and harm. In essence, it is unresolved if intensive care patients benefit overall from SUP. The following clinically research questions are unanswered: (1) What is the incidence of GI bleeding, and which interventions are used for SUP in general ICUs today?; (2) Which criteria are used to prescribe SUP?; (3) What is the best SUP intervention?; (4) Do intensive care patients benefit from SUP with proton pump inhibitors as compared with other SUP interventions? Systematic reviews of possible interventions and well-powered observational studies and RCTs are needed.

Biomechanical response to acupuncture needling in humans.

During acupuncture treatments, acupuncture needles are manipulated to elicit the characteristic "de qi" reaction widely viewed as essential to acupuncture's therapeutic effect. De qi has a biomechanical component, "needle grasp," which we have quantified by measuring the force necessary to pull an acupuncture needle out of the skin (pullout force) in 60 human subjects. We hypothesized that pullout force is greater with both bidirectional needle rotation (BI) and unidirectional rotation (UNI) than no rotation (NO). Acupuncture needles were inserted, manipulated, and pulled out by using a computer-controlled acupuncture needling instrument at eight acupuncture points and eight control points. We found 167 and 52% increases in mean pullout force with UNI and BI, respectively, compared with NO (repeated-measures ANOVA, P < 0.001). Pullout force was on average 18% greater at acupuncture points than at control points (P < 0.001). Needle grasp is therefore a measurable biomechanical phenomenon associated with acupuncture needle manipulation.

Biomechanical time-tolerance of fresh cadaveric human spine specimens.

Changes in the biomechanical properties of fresh cadaveric spinal specimens due to long-term freeze storage and long test periods have been investigated. Fresh cadaveric specimens were divided into three groups: Group A specimens were tested fresh on the 1st day and 13 subsequent days; Group B specimens were tested on the 1st day, frozen in sealed bags at -18 degrees C for 21 days, and tested for 13 consecutive days after thawing; and Group C specimens were frozen for up to 232 days and tested for 14 consecutive days after thawing. We could not find any significant differences between the behavior of the three test groups. This implies that freezing and storage, even for long periods, do not significantly alter the physical properties of cadaveric spinal specimens. Concerning the differences observed on a daily basis, the mean value of the maximum displacement for the 1st day did not differ significantly from the corresponding mean value for the 13 consecutive days. This was true for all three groups, although there was some indication that the fresh group specimens showed greater variation than the two frozen groups.

Internal deformations of intact and denucleated human lumbar discs subjected to compression, flexion, and extension loads.

Three rows of six evenly spaced 0.5 mm metal beads were implanted midsagittally into the discs of ten L4-5 human lumbar motion segments. The intradiscal bead displacements in response to compression, flexion, and extension loads were obtained by digitizing the bead positions from sagittal plane radiographs taken before and during the load application. Each disc was denucleated and the loading process was repeated. For the intact discs, in compression, the intradiscal bead displacements were predominantly anterior. In flexion, the beads in the center of the disc moved posteriorly whereas the beads closer to the periphery of the disc moved anteriorly. In extension, the central beads moved anteriorly and the beads closer to the periphery of the disc moved posteriorly. After denucleation, the bead displacements for compression and flexion implied an inward bulging of the inner wall of the annulus, despite outward bulging of the disc surface. We hypothesize that the inward bulging causes radial tensile stresses within the disc, leading to disruption of adjacent layers of annulus.

Thoracic spine centers of rotation in the sagittal plane.

The purpose of this study was to determine in vitro the centers of rotation of thoracic functional spinal units in the sagittal plane. The center of rotation is a convenient concept and part of a precise method of documenting the kinematics of a joint moving in a plane. Fresh cadaver functional spinal units from the thoracic region were utilized. Six load types were used that produced motions only in the sagittal plane, namely anterior and posterior shear forces, flexion and extension moments, and compression and distraction forces. The resulting motion with three degrees of freedom was measured with dial gauges. Statistical methods were used to analyze data from the viewpoint of vertebral level, load magnitude, and load type. Only the load type was found to be significantly related to the location of the centers of rotation. Although there was significant variability in the centers of rotation, there were definite locations related to each load type. The average center of rotation was 15-45 mm directly below the geometric center of the moving vertebra. The results of the present study may be helpful in the clinical interpretation of spinal kinematic studies.

Pin force measurement in a halo-vest orthosis, in vivo.

The halo-vest is an orthosis commonly used to immobilize and protect the cervical spine. The primary complications associated with the halo-vest have been attributed to cranial pin loosening. However, the pin force history during day-to-day halo-vest wear has not previously been reported. This paper presents a new technique developed to monitor cranial pin forces in a halo-vest orthosis, in vivo. A strain gaged, open-ring halo was used to measure the compressive and shear forces produced at the posterior pin tips. The strain gages measured the bending moments produced by these forces without compromising the structural integrity of the halo-vest system. The prototype halo measured the compressive and shear force components with a resolution of +/- 15 and +/- 10 N, respectively. To test the feasibility and durability of the device, it was applied to one patient requiring treatment with a halo-vest orthosis. At the time of halo-vest application, the mean compressive force in the two posterior pins was 368 N. Over the 3 month treatment period, the compressive forces decreased by a mean of 88%. The shear forces were relatively insignificant. Using this technology future work will be aimed at determining the causes of pin loosening, optimizing vest and pin designs, and investigating the safety of more rapid rehabilitation.

Cervical spine motion in the sagittal plane: kinematic and geometric parameters.

The kinematic function of the cervical spine has been examined previously by means of cineradiography or a sequence of lateral X-rays, usually of a flexion-extension range of motion. Interpretation of these studies, however, presents difficulties. One of the major problems is how to extract information from the X-ray images which is not only explicit, quantitative and accurate, but which is also diagnostically useful. Another problem is that as one increases the number of steps of motion between full flexion and full extension to obtain a more detailed examination, one also increases the amount of radiation exposure and the bulk of the data. Reported here is a technique which uses one lateral-view X-ray for each of five neck positions: full flexion, full extension, and three intermediate positions. From each set of X-rays, various parameters are derived to describe two types of data: kinematic (angles and centers of rotation), and geometric (pattern of curvature). This technique has been shown capable of identifying functional abnormalities in patients with neck pain who have no structural abnormalities detectable by X-ray. Further experience will be useful in better defining various types of functional abnormalities.

A mechanical model for the human intervertebral disc.

Stress relaxation experiments were performed on specimens from a human intervertebral disc. Specimens were made from the nucleus pulposus and from the external lamellae of the anulus fibrosus in two different orientations. Tests were run with varying moisture content so as to develop a relaxation master curve. A model was developed based on the experimental data. It was found that the short term master curve for the lamellae of the anulus and nucleus are similar, whereas the long term rubbery plateau is different between the lamellae and the nucleus. It was also established that the master curves for different lamellae and the nucleus were shifted relative to each other in the time domain due to changes in water content. The average relaxation modulus of the whole disc was obtained by averaging the properties between the anulus and nucleus. This model was then used for studies of Schmorl's nodes, of degenerated discs and for circumstances in which hydration is considered to be important.

The design and use of a microcomputerized real-time muscle fatigue monitor based on the medial frequency shift in the electromyographic signal.

We have designed a real-time microcomputerized muscle fatigue monitor based on the median frequency shift of the electromyographic signal, computed via the fast Fourier transform. For the ten subjects performing an isotonic and isometric trunk extension task on two separate days, preliminary results suggest a repeatable linear decrease in median frequency as a function of time.

Biomechanics of thoracolumbar spinal fixation. A review.

Extensive development of spinal instrumentation has occurred recently, benefitted by improved biomechanical knowledge. Reviewed here are various devices and the major biomechanical issues relevant to them. The devices are categorized by site of attachment. The major emphasis is on the most recently developed category: devices attached by transpedicular screws. Aspects of this last category reviewed here include screw design, screw placement, longitudinal linking devices (rods, plates), and transverse connectors (cross-linking). Emphasis is placed not only on current knowledge, but also on unresolved issues.

A new halo-vest: rationale, design and biomechanical comparison to standard halo-vest designs.

The traditional halo-vest rigidly grips the cranium, but not the torso. Unexpectedly large motion and forces in the cervical spine have been shown by others to be present during halo-vest wear. In an effort to reduce these motions and forces, an experimental vest has been designed. Motion of the vest on the thorax has been measured on four normal volunteers, for each of nine load types, for each of seven commercially available vests as well as the experimental vest. Despite its lighter weight and less cumbersome structure, the experimental vest has the lowest mobility score of all the vests tested.

Clinical, radiographic, and kinematic results from an adjustable four-pad halovest.

STUDY DESIGN: Charts and radiographs of all patients treated with this halovest at one university hospital were reviewed retrospectively. OBJECTIVES: To describe the outcomes from an adjustable four-pad halovest and to compare them with those from standard halovests, as previously published. SUMMARY OF BACKGROUND DATA: With standard halovests, there can be cervical motion up to 70% of normal values, substantial loads between the halo and vest, and complications of pin loosening, pin infections, and scapular pressure sores. The four-pad vest reduces halovest loads and vest-torso motions. METHODS: The four-pad vest has four independently adjustable pads that completely avoid contact with the scapula, clavicle, and abdomen. Clinical records were analyzed to determine the incidences of halo pin loosening, pressure sores, injury or surgical site nonunion, and loss of cervical alignment. Lateral radiographs were taken with the patient in the upright and supine positions at various times to determine intervertebral rotations (flexion-extension). RESULTS: The clinical results with the four-pad vest were at least as good as those for standard vests. Scapular pressure sores were prevented completely by the absence of vest-scapula contact. Kyphosis did not increase significantly with time. The mean segmental rotations were all 3 degrees or less and showed a smoothly decreasing pattern from C1-C2 to C6-C7. The value at Oc-C1 was opposite to that at C1-C2 and is the subject of further analysis. CONCLUSIONS: The rotations occurring with the four-pad vest are less than or equal to those occurring with standard vests, for overall cervical rotation and for individual motion segment rotations. This is consistent with the smaller halovest forces seen with this vest. Prospective, comparative testing will assess the clinical significance of these findings.

Repair of failed transpedicle screw fixation. A biomechanical study comparing polymethylmethacrylate, milled bone, and matchstick bone reconstruction.

In a random, controlled laboratory study, pedicle screws placed in human cadaveric vertebrae were axially loaded to failure. Three repair methods were tested. Use of low pressure polymethylmethacrylate yielded 149% of the original pullout strength, milled bone yielded 70% of the initial pullout strength, and matchstick bone yielded 56% of the initial pullout strength. Two incidents of cortical penetration during reinsertion in the matchstick group occurred. The results were statistically analyzed.

Pull-off strength of gardner-Wells tongs from cadaveric crania.

Failure of attachment ("pull-off") of Gardner-Wells tongs from the cranium occasionally occurs, and may cause problems, especially in cases of significant cervical spinal instability. The optimal method for Gardner-Wells tongs attachment is not well defined: the effect on pull-off strength of stem protrusion of the spring-loaded pin, and user accuracy in setting stem protrusion do not appear to be documented in the medical literature. The authors measured pull-off strength from five fresh cadaveric crania, for each of five stem protrusion settings. In a related experiment, staff surgeons were asked to follow the standard instructions for applying clinically available Gardner-Wells tongs (smooth, unmarked indicator stems on the spring-loaded pins), after which the actual stem protrusion lengths were recorded. When the indicator stem protruded 1.0 mm (manufacturer's recommendation), the mean pull-off strength (+/- standard deviation [SD] was 137 +/- 34 pounds (610 +/- 151 N). Even with stem protrusions as low as 0.25 mm, the lowest pull-off strength was 60 pounds. Failures of fixation occurring with traction loads of 35 to 50 pounds are almost surely associated with stem protrusions of less than 0.25 mm. Even without an indicator line on the stem at 1 mm, all of the 13 orthopaedists tested produced an actual stem protrusion of 0.37 mm or more. Secure attachment of larger cranial traction loads requires careful attention to pin tightening. Proper location on the skull and the risk of penetration through the inner table must also be kept in mind.