Immunoglobulin G for patients with necrotising soft tissue infection (INSTINCT): a randomised,blinded, placebo-controlled trial

Purpose

The aim of the INSTINCT trial was to assess the effect of intravenous polyspecific immunoglobulin G (IVIG) compared with placebo on self-reported physical function in intensive care unit (ICU) patients with necrotising soft tissue infection (NSTI).

Methods

We randomised 100 patients with NSTI 1:1 to masked infusion of 25 g of IVIG (Privigen, CSL Behring) or an equal volume of 0.9% saline once daily for the first 3 days of ICU admission. The primary outcome was the physical component summary (PCS) score of the 36-item short form health survey (SF-36) 6 months after randomisation; patients who had died were given the lowest possible score (zero).

Results

Of the 100 patients randomised, 87 were included in the intention-to-treat analysis of the PCS score, 42 patients (84%) in the IVIG group and 45 patients (90%) in the placebo group. The two intervention groups had similar baseline characteristics with the exception of IVIG use before randomisation (1 dose was allowed) and rates of acute kidney injury. Median PCS scores were 36 (interquartile range 0–43) in the group assigned to IVIG and 31 (0–47) in the group assigned to placebo (mean adjusted difference 1 (95% confidence interval ?7 to 10), p = 0.81). The result was supported by analyses adjusted for baseline prognostics, those in the per protocol populations, in the subgroups (site of NSTI) and those done post hoc adjusted for IVIG use before randomisation.

Conclusions

In ICU patients with NSTI, we observed no apparent effects of adjuvant IVIG on self-reported physical functioning at 6 months. Trial registration: NCT02111161.

     

Relationship between local and total body bone mineral in epileptic patients and normal subjects

Summary. Total body bone mineral (TBBM), measured by dual photon absorptiometry, and local body bone mineral content (BMC), measured by single photon absorptiometry, in both forearms were determined in 49 epileptic patients, 19 receiving phenytoin and 30 receiving carbamazepine, and in 55 controls. A highly significant correlation was found between BMC and TBBM in the patients (r = 0·81, SEE = 10·6%), as well as in the controls(r = 0·78, SEE = 9·9%). Furthermore, the intercepts and the slopes were virtually of the same order. The patients on phenytoin had a mild generalised osteomalacia, independent of method used, whereas the patients on carbamazepine did not have this side-effect. It is concluded that BMC of the forearm can be used as a valid estimate of total body bone mineral in groups of epileptic patients and in normal subjects.     

Prediction of specific pathogens in patients with sepsis: evaluation of TREAT, a computerized decision support system

BACKGROUND: Prediction of bacterial infections and their pathogens allows for early, directed investigation and treatment. We assessed the ability of TREAT, a computerized decision support system, to predict specific pathogens. METHODS: TREAT uses data available within the first few hours of infection presentation in a causal probabilistic network to predict sites of infection and specific pathogens. We included 3529 patients (920 with microbiologically documented infections) participating in the observational and interventional trials of the TREAT system in Israel, Germany and Italy. Discriminatory performance of TREAT to predict individual pathogens was expressed by the AUC with 95% confidence intervals. Calibration was assessed using the Hosmer-Lemeshow goodness-of-fit statistic. RESULTS: The AUCs for Gram-negative bacteria, including Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella spp. and Escherichia coli, ranged between 0.70 and 0.80 (all significant). Adequate calibration was demonstrated for any Gram-negative infection and individual bacteria, except for E. coli. Discrimination and calibration were acceptable for Enterococcus spp. (AUC 0.71, 0.65-0.78), but not for Staphylococcus aureus (AUC 0.63, 0.55-0.71). The few infections caused by Candida spp. and Clostridium difficile were well predicted (AUCs 0.74, 0.54-0.95; and 0.94, 0.88-1.00, respectively). The coverage with TREAT's recommendation exceeded that observed with physicians' treatment for all pathogens, except Candida spp. CONCLUSIONS: TREAT predicted individual pathogens causing infection well. Prediction of S. aureus was inferior to that observed with other pathogens. TREAT can be used to triage patients by the risk for specific pathogens. The system's predictions enable it to prescribe appropriate antibiotic treatment prior to pathogen identification.     

Life satisfaction in spouses of patients with stroke during the first year after stroke.

OBJECTIVE: The aims of this study were to investigate whether spouses' life satisfaction changed between their life prior to their partner's stroke, and at 4 months and 1 year after stroke, and to study the association between spouses' life satisfaction and objective characteristics of the stroke patients. SUBJECTS AND METHODS: Sixty-seven consecutively enrolled spouses to first-ever stroke patients < 75 years of age participated. Life satisfaction was measured with the Life Satisfaction Checklist (LiSat-9). RESULTS: Compared with their life before stroke, the spouses' satisfaction with life as a whole, their leisure situation, daily occupation, sexual life, partner relationship and social contacts was lower 4 months after stroke. No significant change in life satisfaction was observed between 4 months and 1 year. Spouses of patients with sensorimotor impairment and low ability in self-care were less satisfied with their leisure situation, daily occupations, own ability in self-care, sexual life and partner relationship. Spouses of patients with cognitive or astheno-emotional impairments were less satisfied with their partner relationship, family life and sexual life. The associations were stronger at 1 year than at 4 months. CONCLUSION: There is a need for support over a long time period that focuses on the social, occupational and leisure situation of spouses as well as that of patients.     

Swelling kinetics of poly(N-isopropylacrylamide) gel

In many gel applications the swelling and shrinking kinetics are very important, e.g. in controlled/slow release, where the kinetics determine the rate of out-diffusion of the active component, and in gel extraction where the gel is swollen and shrunk several times. In this study swelling kinetics of poly(N-isopropylacrylamide) gel (NiPAAm gel) was determined by monitoring the swelling process using a stereo microscope and a video camera. The swelling of spherical gel bodies could conveniently be studied after a temperature change. The results obtained were treated according to the approach of Tanaka and Fillmore, in which the swelling and shrinking of a gel is described as a motion of the gel network according to the diffusion equation. This was shown to be valid when the temperature changes are kept below the critical point of the gel. However, the model fails to describe the shrinking process when passing from below to above the critical temperature. The collective diffusion coefficient (D), defined as the osmotic bulk modulus divided by the friction factor, was determined by fitting to the experimental data. D was found to increase with temperature according to the Wilke–Chang relation D=2.0·10⁻¹¹ +7.6·10⁻¹⁷ ·T/μ. The results were used to simulate the swelling/shrinking process. The simulations show the importance of having sufficiently small gel bodies to achieve a short swelling time.     

Platelet function tests for monitoring of acetylsalicylic acid: clinical significance in antiplatelet treatment

Several studies have demonstrated with the use platelet function tests (PFT) that subgroups of patients under acetylsalicylic acid (ASA) fail to produce the anticipated antiplatelet effect. This phenomenon as well as the clinical failure of ASA to protect patients from thromboembolic complications has been termed ASA resistance (AR) or ASA nonresponsiveness. Several subtypes of AR can be distinguished by PFT. The following PFT were used to characterize AR: optical aggregometry, platelet aggregation in whole blood, platelet function analyzer (PFA-100), platelet reactivity test or platelet aggregate ratio, flow cytometry and thromboxane B(2) generation. All PFT have in common that their widespread clinical use is substantially limited due to complex preanalytic factors, reduced specificity and poor reproducibility. PFT are not interchangeable for monitoring antiplatelet treatment. Three prospective clinical trials revealed a possible relationship between AR and subsequent cardiovascular events. There is a need for a simple and reliable assay for predicting the clinical efficacy of antiplatelet therapy. Recent data demonstrate that none of the currently available assays including the PFA-100 system are capable to accomplish these objectives.     

Restriction spectrum imaging improves MRI-based prostate cancer detection

Purpose

To compare the diagnostic performance of restriction spectrum imaging (RSI), with that of conventional multi-parametric (MP) magnetic resonance imaging (MRI) for prostate cancer (PCa) detection in a blinded reader-based format.

Methods

Three readers independently evaluated 100 patients (67 with proven PCa) who underwent MP-MRI and RSI within 6 months of systematic biopsy (N = 67; 23 with targeting performed) or prostatectomy (N = 33). Imaging was performed at 3 Tesla using a phased-array coil. Readers used a five-point scale estimating the likelihood of PCa present in each prostate sextant. Evaluation was performed in two separate sessions, first using conventional MP-MRI alone then immediately with MP-MRI and RSI in the same session. Four weeks later, another scoring session used RSI and T2-weighted imaging (T2WI) without conventional diffusion-weighted or dynamic contrast-enhanced imaging. Reader interpretations were then compared to prostatectomy data or biopsy results. Receiver operating characteristic curves were performed, with area under the curve (AUC) used to compare across groups.

Results

MP-MRI with RSI achieved higher AUCs compared to MP-MRI alone for identifying high-grade (Gleason score greater than or equal to 4 + 3=7) PCa (0.78 vs. 0.70 at the sextant level; P < 0.001 and 0.85 vs. 0.79 at the hemigland level; P = 0.04). RSI and T2WI alone achieved AUCs similar to MP-MRI for high-grade PCa (0.71 vs. 0.70 at the sextant level). With hemigland analysis, high-grade disease results were similar when comparing RSI + T2WI with MP-MRI, although with greater AUCs compared to the sextant analysis (0.80 vs. 0.79).

Conclusion

Including RSI with MP-MRI improves PCa detection compared to MP-MRI alone, and RSI with T2WI achieves similar PCa detection as MP-MRI.

     

Histamine receptors in the isolated human middle meningeal artery. A comparison with cerebral and temporal arteries

The subtypes of histamine receptors mediating dilatation of human meningeal arteries have been tested in vitro, using "selective" antagonists, and compared with cerebral and temporal arteries previously examined. Dilatory responses were tested after preconstriction with prostaglandin F2 alpha. Both mepyramine and cimetidine caused a parallel shift to the right of the histamine concentration-response curve, suggesting the presence of both H1- and H2-receptors. Combined treatment with mepyramine and cimetidine caused further displacement of the concentration-response curve to the right. Schild analysis indicated pA2 values of 6.3 for cimetidine and 9.8 for mepyramine in situations of near complete blockade of either of the receptors. Both H1- and H2-receptors seem of importance for the histamine-induced dilatation in meningeal arteries and neither appear to dominate. The data considered in conjunction with our previous findings support the finding that experimental histamine-induced headache due to vasodilatation is intracranial of origin.     

Meaning of quality of life among patients with familial hypercholesterolemia

BACKGROUND: Living with a genetic predisposition to disease may influence quality of life. The presence of premature disease can lead to an increased focus on family history and genetic predisposition. OBJECTIVE: The purpose of this study was to describe quality of life in patients with the genetic disease, familial hypercholesterolemia, who are at an increased risk of premature coronary heart disease. METHODS: Interviews from 12 adult patients with FH were analyzed using constant comparative analysis. The findings of this qualitative study revealed that for patients, quality of life was equated with harmony in life, the core category. Attaining harmony in life presumes satisfaction and togetherness. Cognizance of the threat of coronary heart disease and impending mortality is balanced by the support of togetherness and satisfaction that builds harmony in life. CONCLUSION: When caring for patients with familial hypercholesterolemia, it is important to meet each patient on his or her own level, and to support balance and their choices for maintaining or regaining harmony in life.