Number needed to treat: easily understood and intuitively meaningful? Theoretical considerations and a randomized trial

Graphic representation was used to explore to what extent the number needed to treat (NNT) conveys the appropriate notion of benefit for the individual patient in interventions aimed at delaying adverse events. A sample of the Danish population (n = 675) was interviewed face to face, and asked whether they would consent to a hypothetical drug that reduces the risk of heart attack. The benefit of the drug was expressed in terms of NNT and was randomly set at 10, 25, 50, 100, 200, and 400. NNT does not convey information on the proportion of patients being helped by an intervention or the size of the delay of the adverse event intended to be prevented. The proportion of people consenting to the hypothetical drug was about 80%, irrespective of NNT, and some of those who rejected the drug misinterpreted the meaning of NNT. Lay people may have difficulties in understanding the meaning of NNT, and clinicians may do well to use the NNT with caution until more is known about how patients comprehend it.     

Evaluation of a simple dosage scheme for transition from phenprocoumon to warfarin in oral anticoagulation

Phenprocoumon, whose elimination half-time is 144 hours, has been the traditional oral anticoagulant of choice in Europe. However, today's most widely used drug is warfarin, whose elimination half-time is 40 hours. This study aims to evaluate a method for safe transition from phenprocoumon to warfarin, which is sometimes required. Hence, the large difference in their elimination rates may on occasion lead to serious overdosage upon transition from one drug to the other. According to average equipotent doses, a stepwise increase in warfarin dose was calculated based on the elimination half-times of the two drugs. The dosage scheme was subsequently tested in a pilot study including 35 patients. The conversion scheme was then adjusted based on the results from the pilot study. The new scheme was tested in 69 patients. The transition factor was 2.3, which implies that equipotency was achieved when the warfarin dose was 2.3 times larger than the phenprocoumon dose (in mg). This scheme proved optimal for 75% of the patients. However, the dose had to be adjusted individually in the remaining 25% of the patients to a level corresponding to the measured international normalised ratios. No patients experienced haemorrhages or thromboembolic complications during the period of changeover. In conclusion, the proposed scheme for changing medication from phenprocoumon to warfarin is safe and convenient.     

The effects of chlorpromazine on the outer cell wall of Salmonella typhimurium in ensuring resistance to the drug

Chlorpromazine (CPZ), a compound employed for the management of psychosis, has a wide ranging antibacterial activity. The growth of Salmonella typhimurium100 mg/l), was initially inhibited during the first 8-16 h of exposure to concentrations of CPZ below the MIC. During this period of transient susceptibility, the distribution of ribosomes was markedly altered in a concentration dependent manner; the rough cell wall was transformed into a smooth form. The protein composition of the outer cell wall of 55 kDa was markedly decreased, whilst there was an increased number of high molecular weight proteins. After 16 h of exposure to sub-MIC levels of CPZ, the inhibitory effect of the drug was no longer apparent whereas the effects noted on the cell wall were retained. These Salmonella were, as the control, agglutinated by O antigen specific antibody. Whereas agglutination of the control Salmonella was blocked by the presence of CPZ at concentrations that induced the cell-wall effects, agglutination of CPZ exposed-Salmonella for periods in excess of 16 h was not blocked by any concentration of CPZ. These results suggested that eventual resistance to CPZ was dependent upon changes induced by CPZ at the cell wall level. The results also suggested that the CPZ binds to the 55 kDa protein and that such binding interfered with the recognition of the O antigen by antibody.     

Medium Conditioned for 24 Hours by Mononuclear Human Blood Cells Contains an Inducer of Granulopoiesis Lacking Colony Stimulating Activity

Regulation of granulocyte and macrophage formation was studied by a modified CFU-C assay. Mouse bone marrow cells were cultured in methylcellulose in vitro. After colony counting on d 7, the cells were washed out to determine the total cell number per plate, and the distribution of granulocytes and macrophages in smears. By this procedure it was possible to study pathway-specific regulators. The colony stimulating factor in medium conditioned by mouse L-cells appeared specific for the macrophage cell line; 99% of the colony cells were macrophages. Medium conditioned for 24 h by mononuclear cells from human blood, had no colony forming capacity, but increased colony size and generated significant granulocyte production when combined with L-CSF. This granulopoiesis inducing factor was thermo-labile, and was mostly retained by an Amicon filter separating molecules at 100000 daltons.     

Clinical evaluation of a novel ultrasound-based bladder volume monitor

OBJECTIVE: Bladder volume monitors may be useful for surveillance of bladder volume and urine production in urologic patients. Therefore, we designed an ultrasonic bladder volume monitor and evaluated it in vitro using phantoms and in vivo in one male volunteer. The purpose of this study was to perform a more thorough in vivo evaluation of our monitor in urologic patients to investigate biological effects and variance over a wide range of bladder volumes. MATERIAL AND METHODS: Thirty urologic patients of either gender were examined using the bladder volume monitor, which is based on seven phased array ultrasonic transducers arranged in a circular pattern to optimize detection of the bladder walls. The monitor was set up to record bladder volume every 30 s during two sequential cystometries with infusion rates of 30 and 60 ml/min. The measured volumes were analyzed using regression analysis to determine volume increments (slopes), offset volume (intercept) and correlation (Pearson's correlation coefficient). RESULTS: In the male patients, the median correlation coefficient between the infused and measured volumes was 0.97 and the slope was 0.68 ml/ml, thus warranting a correction factor of approximately 1.47 with no general volume offset. In the female patients, small bladders were generally outside the field of view of the monitor. Consequently, the correlation coefficients and slopes were 0.834 (median) and 0.43 (mean), respectively, whereas volume offsets were generally negative. CONCLUSIONS: For examinations in male patients, the performance of the bladder volume monitor was adequate. However, for examinations in female patients, a minor redesign of the transducer unit is necessary to insure proper operation.     

Biological tissue adhesive for mesh-application in pigs: An experimental study

Background Tissue damage during herniotomy may attribute to postoperative complications including chronic pain, bleeding and infection. Thus the aim of this study was to evaluate a due and simple operative procedure with intraperitoneal application of mesh with glue in an experimental model prior to use in humans.Method Laparoscopic insertion of a mesh was performed in three pigs. The meshes were fixed with a collagen glue. The pigs were sacrificed after 8 weeks and macroscopic and microscopic evaluation of the meshes, were performed.Results The intraperitoneal placed meshes did not migrate through the study period, and there was no sign of inflammation in surrounding tissue or adhesions around the meshes.Conclusions If these findings can be applied to human inguinal herniotomy, this may lead to significant fewer complications including development of acute and chronic pain, formation of seroma and infection. Furthermore the operation technique is very simple.     

Flucloxacillin associated neutropenia in children treated for bone and joint infections

OBJECTIVE: This report describes episodes of acute neutropenia associated with flucloxacillin use in children treated for bone and joint infections. METHODS: A retrospective chart audit was performed on eight children who developed neutropenia when treated with flucloxacillin. RESULTS: Eight children (aged 1 month to 13 years) had a diagnosis of neutropenia attributed to treatment with flucloxacillin, seven of whom received parenteral therapy. The time to onset of neutropenia averaged 27 days, with neutrophil counts returning to normal limits in all patients after 2 to 9 days. Two children were asymptomatic when the neutropenia was detected. The average flucloxacillin dose used was 65% (range 20-100%) of the recommended maximum dose. CONCLUSIONS: These cases suggest that flucloxacillin should be used with greater caution and guidelines for dosing and clinical monitoring (regular neutrophil counts) need to be reassessed, despite none of these patients experiencing serious sequelae.     

Binding characteristics of the 5-HT2A receptor antagonists altanserin and MDL 100907

To study the 5-HT(2A) receptors in the living human brain, using positron emission tomography (PET), two selective radiotracers are currently in use: [(18)F]altanserin and [(11)C]MDL 100907. It is, however, currently unknown to what extent data obtained with either tracer are directly comparable. The aim of this study was to compare binding characteristics of these two radiotracers in rat brain with respect to affinity (K(d)), receptor binding density (B(max)), binding potential (BP), and nonspecific binding. Further, binding kinetics, sensitivity towards competition with the endogenous transmitter serotonin, and the competitive/noncompetitive interaction between the two radioligands were evaluated. In addition, the selectivity of [(18)F]altanserin for the 5-HT(2A) receptor was assessed.The K(d) value of [(18)F]altanserin and [(3)H]MDL 100907 was in the order of 0.3 nM. B(max) in frontal cortex was 523 and 527 fmol/mg protein, respectively. The binding of [(18)F]altanserin was not influenced by blocking either the 5-HT(2B/2C) or the alpha(1)-adrenergic receptors. At 37 degrees C the association t(1/2) was 2.8 and 2.7 min and the dissociation t(1/2) was 11 and 13.5 min for [(18)F]altanserin and [(3)H]MDL 100907, respectively.Both radioligands were displaced by 5-HT, only at high concentrations; the K(i) value of 5-HT ranging between 650 and 3,300 nM. This indicates that binding of both radioligands in PET studies is not directly influenced by changes in endogenous 5-HT.Overall, the binding of [(18)F]altanserin and [(3)H]MDL 100907 to the 5-HT(2A) receptor was very comparable, showing selective high affinity binding in the subnanomolar range.     

Randomized clinical trial comparing an oral carbohydrate beverage with placebo before laparoscopic cholecystectomy

BACKGROUND: Preoperative oral carbohydrate can attenuate postoperative insulin resistance and catabolism, and may have the potential to improve postoperative recovery. There are no data from randomized studies on postoperative clinical outcome after specific surgical procedures. This study evaluated the clinical effects of a preoperative carbohydrate beverage in patients undergoing laparoscopic cholecystectomy. METHODS: Ninety-four patients undergoing laparoscopic cholecystectomy were included in a randomized clinical trial. Patients were randomized to receive 800 ml of an iso-osmolar 12.5 per cent carbohydrate-rich beverage the evening before operation (100 g carbohydrate) and another 400 ml (50 g carbohydrate) 2 h before initiation of anaesthesia, or the same volume of a placebo beverage. The primary endpoint was general well-being the day after operation. Patients were evaluated from 5 days before to 5 days after operation. Daily scores of general well-being, fatigue, appetite and pain, computerized measurements of physical activity and sleep (actigraphy), and subjective sleep quality were recorded. Nausea and vomiting were assessed twice within the first 24 h after surgery. RESULTS: Data from 86 patients were available for statistical analysis, 43 in each treatment group. No significant intergroup differences in general well-being or any other outcome variable were found. CONCLUSION: A preoperative carbohydrate beverage did not improve clinical outcome after laparoscopic cholecystectomy.