Multicentre randomized clinical trial of inspiratory muscle training versus usual care before surgery for oesophageal cancer.

BACKGROUND: Up to 40 per cent of patients undergoing oesophagectomy develop pneumonia. The aim of this study was to assess whether preoperative inspiratory muscle training (IMT) reduces the rate of pneumonia after oesophagectomy. METHODS: Patients with oesophageal cancer were randomized to a home-based IMT programme before surgery or usual care. IMT included the use of a flow-resistive inspiratory loading device, and patients were instructed to train twice a day at high intensity (more than 60 per cent of maximum inspiratory muscle strength) for 2 weeks or longer until surgery. The primary outcome was postoperative pneumonia; secondary outcomes were inspiratory muscle function, lung function, postoperative complications, duration of mechanical ventilation, length of hospital stay and physical functioning. RESULTS: Postoperative pneumonia was diagnosed in 47 (39·2 per cent) of 120 patients in the IMT group and in 43 (35·5 per cent) of 121 patients in the control group (relative risk 1·10, 95 per cent c.i. 0·79 to 1·53; P = 0·561). There was no statistically significant difference in postoperative outcomes between the groups. Mean(s.d.) maximal inspiratory muscle strength increased from 76·2(26·4) to 89·0(29·4) cmH2 O (P < 0·001) in the intervention group and from 74·0(30·2) to 80·0(30·1) cmH2 O in the control group (P < 0·001). Preoperative inspiratory muscle endurance increased from 4 min 14 s to 7 min 17 s in the intervention group (P < 0·001) and from 4 min 20 s to 5 min 5 s in the control group (P = 0·007). The increases were highest in the intervention group (P < 0·050). CONCLUSION: Despite an increase in preoperative inspiratory muscle function, home-based preoperative IMT did not lead to a decreased rate of pneumonia after oesophagectomy. Registration number: NCT01893008 (https://www.clinicaltrials.gov).

Evaluating the accuracy of planar gated blood pool processing software using simulated patient studies.

Planar gated blood pool (GBP-P) radionuclide imaging is a valuable non-invasive technique for assessing left ventricular ejection fraction (LVEF). Serial cardiac imaging can be performed to monitor the potential decline in LVEF among patients undergoing cardiotoxic chemotherapy. Consequently, accurate LVEF determination becomes paramount. While commercial software programs have enhanced the LVEF values' reproducibility, concerns remain regarding their accuracy. This study aimed to generate a database of GBP-P studies with known LVEF values using Monte Carlo simulations and to assess LVEF values' accuracy using four commercial software programs. We utilised anthropomorphic 4D-XCAT models to generate 64 clinically realistic GBP-P studies with Monte Carlo simulations. Four commercial software programs (Alfanuclear, Siemens, General Electric Xeleris, and Mediso Tera-Tomo) were used to process these simulated studies. The accuracy and reproducibility of the LVEF values determined with these software programs and the intra- and inter-observer reproducibility of the LVEF values were assessed. Our study revealed a strong correlation between LVEF values calculated by the software programs and the true LVEF values derived from the 4D-XCAT models. However, all the software programs slightly underestimated LVEF at lower LVEF values. Intra- and inter-observer reliability for LVEF measurements was excellent. Accurate LVEF assessment is crucial for determining the patient's cardiac function before initiating and during chemotherapy treatment. The observed underestimation, particularly at lower LVEF values, emphasises the need for the accurate and reproducible determination of these values to avoid excluding suitable candidates for chemotherapy. The software programs' excellent intra- and inter-observer reliability highlights their potential to reduce subjectivity when using the semi-automatic processing option. This study confirms the accuracy and reliability of these commercial software programs in determining LVEF values from simulated GBP-P studies. Future research should investigate strategies to mitigate the underestimation biases and extend findings to diverse patient populations. Gated blood pool studies, left ventricular ejection fraction, Monte Carlo simulations, 4D-XCAT models.

Comparison of oxine and tropolone methods for labeling human platelets with indium-111.

The effect of the chelates oxine and tropolone, used to label platelets, on the kinetics of indium-111-(111In) labeled platelets was studied in twelve normal human subjects. Autologous platelets were labeled either in saline with 111In-oxine or in plasma with 111In-tropolone. Mean platelet lifespan was estimated by fitting the disappearance curve of platelets from the circulation to the multiple hit and other mathematical models. The in vivo distribution of platelets was quantitatively imaged with a scintillation camera. The in vivo recovery of 111In-oxine and 111In-tropolone did not differ, and the mean platelet lifespan was also similar (111In-oxine: 230 +/- 29 hr; 111In-tropolone: 226 +/- 13 hr). At equilibrium (90 min after reinjection of labeled platelets) and at the end of platelet lifespan, 111In-oxine and 111In-tropolone radioactivities in the spleen and liver were similar. These results demonstrate that the results of kinetics measured with 111In-oxine or 111In-tropolone do not differ significantly.

Kinetics, distribution, and sites of destruction of canine blood platelets with In-111 oxine.

In five normal dogs we have studied the survival, tissue distribution, and fate of autologous platelets labeled with indium- 111 oxine. The methods include blood sampling, computer-assisted scintigraphy, and whole-body profile scanning. Mean In- 111-platelet recovery in the circulation was 45 +/- 22.5 (s.d.) and survival 124.6 +/- 10.5 hr. Platelet survival curves fitted a linear function best. Initially platelets pooled rapidly in the spleen with a single exponential function, and at zero-time equilibrium (35 +/- 4)% of the injected In- 111 was located in this organ. Early hepatic uptake was also significant, and constituted (20 +/- 4)% of total-body radioactivity. As labeled platelets disappeared from the circulation, In- 111 activity in the spleen increased progressively and linearly to reach (59 +/- 9)% of the body activity at 120 hr. Hepatic radioactivity decreased with time but to a lesser extent than that of the heart. The results indicate that in the dog the major site of destruction of platelets is the spleen, with the liver playing a less important role.

Kinetics and in vivo distribution of in-111-labelled platelets and platelet function in familial hypercholesterolaemia.

The kinetics, in vivo distribution and sites of sequestration of autologous In-111-labelled platelets and other platelet function parameters were studied in ten patients with type IIa or IIb familial hypercholesterolaemia and thrombotic complications of atherosclerosis. The in vitro platelet aggregation response to ADP (P = 0.50) and collagen (P = 0.46); binding of fibrinogen to platelets (P = 0.61); and plasma beta-thromboglobulin levels (P = 0.42) of the patients and normal reference subjects did not differ significantly. The in vivo distribution of In-111-labelled platelets at equilibrium was within normal limits, and at the end of platelet life-span the sequestration pattern of labelled platelets in the reticuloendothelial system was also normal (spleen P = 0.31; liver P = 0.54). There was minimal evidence of in vivo platelet activation: only mean platelet lifespan (MPLS), 195 +/- 57 hours (difference between mean MPLS of patients and controls was 25 hours, with a 95% confidence interval from 23 to 31 hours; P = 0.02); mean platelet platelet turnover, 2298 +/- 824 platelets/microliter/hour (P = 0.005); plasma platelet factor 4 (P = 0.02); and the mean circulating platelet aggregate ratio, 0.8 +/- 0.1 (P = 0.02); differed significantly from normal. These results suggest that abnormalities of platelet function and kinetics observed in type II hyperlipoproteinaemia cannot be ascribed wholly to the hyperlipidaemia, but may be induced by the associated atherosclerosis.

Indium-111-labelled human platelets: a method for use in severe thrombocytopenia.

We describe and evaluate a simple method for labelling autologous human platelets with Indium-111-oxine in patients with severe thrombocytopenia. Twenty patients with immune thrombocytopenia and platelet counts ranging from 5 to 119 X 10(9)/1 were investigated. Platelets were isolated from blood by differential centrifugation, residual platelets were repeatedly washed from the red cell layer and buffy coat and labelled with In 111 in saline. A mean of 55% +/- 21 of platelets were harvested from the blood, labelled with 49% +/- 24 efficiency and 15.8 X 10(8) labelled platelets reinjected to the patients. Contamination of the platelets with red cells and plasma was low. The labelled platelets were viable as assessed by in vitro aggregation, recovery in the circulation and mean survival time. This method permits quantitative platelet imaging with autologous labelled platelets in patients with severe thrombocytopenia.

Antithrombotic activity of Bay u3405, a thromboxane A2-antagonist, in patients with Dacron aortic grafts: a random controlled clinical trial.

Twelve patients with Dacron aortic grafts participated in a placebo controlled, crossover trial to investigate the effect of Bay u3405, a thromboxane A2 receptor antagonist, on graft thrombogenicity. During each treatment period (seven days, Bay u3405 or placebo), 111In-platelet survival and platelet deposition on the grafts were measured daily by gamma-camera imaging and blood radioactivity analysis. Bay u3405 substantially reduced the deposition of platelets and the thrombogenic index, while platelet survival remained unchanged. The ex vivo platelet aggregation response to ADP and epinephrine was significantly inhibited. The bleeding time increased slightly but not to any clinically relevant extent, and no adverse side effects were recorded. Bay u3405 seems to be a safe and effective drug for the inhibition of platelet deposition on aortic Dacron grafts. The use of quantitative imaging techniques is also more sensitive than the measurement of platelet survival for the assessment of antiplatelet drug efficacy in patients with aortic grafts.

The effect of monoclonal anti-human-platelet antibodies on platelet kinetics in a baboon model: IgG subclass dependency.

We assessed the in vivo effect of six intact anti-human antiplatelet antibodies of two major IgG subclasses on platelet kinetics in baboons. Five of the six antibodies tested caused thrombocytopenia of varying degree when injected at a precalculated threshold value. An agglutinating IgG1 antibody (MA-8L4A12) caused a long-lasting, mild thrombocytopenia with a predominant uptake of radiolabelled platelets in the spleen, while the four IgG2 antibodies tested (MA-13G8E1, MA-2M5A6, MA-21K2E8 and MA-22M10) caused a severe, transient thrombocytopenia with uptake of platelets in the liver. Two of the IgG2 antibodies (MA-13G8E1 and MA-2M5A6) caused platelet activation and aggregation in vitro, whilst the other two did not elicit a platelet aggregation response. The platelet survival time was shortened with all five of the thrombocytopenia-inducing antibodies, while only one antibody (MA-2M5A6) had a significant effect on the bleeding time. This study indicates that the IgG subclasss may be a determining factor in the outcome of platelet sequestration in immune-induced thrombocytopenia.

Kinetics and fate of (111)Indium-oxine labelled blood platelets in asplenic subjects.

The survival, tissue distribution and fate of (111)Indium-oxine labelled autologous platelets was studied in four asplenic subjects with serial blood sampling, scintillation camera and computer-assisted imaging. Mean (111)In-platelet recovery in the circulation was 89 /+- 13% (/+- 1 SD). Platelet survival curves fitted a linear function best and was 238 /+0 41 h. The shape of the survival curves of normal and asplenic subjects differed: in the asplenic subjects the curve was linear whereas that of normal subjects was significantly more curvilinear if analyzed by least squares computer fitting to a gamma function. Early hepatic (111)In-activity was significant and transient and ascribed to the "collection injury". As labelled platelets disappeared from the circulation, (111)In-activity in the liver increased progressively and linearly to reach 42.5 /+- 14.1% of whole body activity at 240 h. Radioactivity also accumulated in the bone marrow, but could not be demonstrated in the vasculature of the lower limbs. These results would indicate that in asplenic subjects the majority sites of destruction of senescent platelets are the liver and bone marrow.

Preparation of a viable population of indium-111-labelled human blood platelets.

Factors influencing labelling of human platelets with 111Indium-8-hydroxyquinoline ([111In]-oxine) in a physiological saline medium were investigated. The efficiency of labelling is influenced by time of incubation, concentration of oxine, and pH of the incubating medium. It was found that a viable platelet population could be labelled under the following conditions: (1) centrifugation of platelet rich plasma in polystyrene conical tubes at 800 g for 15 min; (2) resuspension of the platelet pellet in saline, pH 5.5; (3) incubating for 30 min at 22 degrees C with [111In]-oxine at a concentration of 6.25 mg oxine/litre platelet suspension; (4) washing once with platelet poor autologous plasma (PPP); and (5) finally resuspending the platelets in PPP. The labelled platelets aggregated normally with collagen and ADP. Electron microscopy, done immediately after labelling, showed internal organelle reorganization characteristic of activated platelets. These ultrastructural features were reversible on incubation in PPP at 37 degrees C for 30 min. The 111In is not released from aggregated platelets and the label does not elute from incubated platelets for at least five hr. We conclude that human platelets thus labelled are suitable for in vivo kinetic studies.

Kinetics and sites of sequestration of indium 111-labeled human platelets during cardiopulmonary bypass.

A new approach for the study of the kinetics and quantification of the in vivo and ex vivo sites of sequestration of platelets during cardiopulmonary bypass (CPB) is described. Autologous platelets of four patients were labeled with 111In-oxine and reinfused on the day prior to CPB for coronary artery bypass grafting. Changes in blood 111In-labeled platelet radioactivity and blood platelet counts were monitored during the operation. In vivo 111In-labeled platelet redistribution was quantified with a scintillation camera and a computer-assisted imaging system before and after CPB. Sequestration of 111In-labeled platelets in the bubble oxygenator was measured. 111In-labeled platelet activity in the blood decreased by 46% +/- 5% within 5 minutes of CPB, but this decrease was mostly due to hemodilution; the true loss of platelets from the circulation was 13% +/- 4%. Intraoperatively, whole body 111In activity decreased by oxygenator 10.8% +/- 1.3% of administered platelets were sequestered, especially in the innermost active layers of the defoaming mesh of the bubble oxygenator. Mean survival time of circulating platelets was 58 +/- 8 hours and fitted an exponential function best. The bleeding time increased to 40 minutes during operation and returned to normal within 24 hours. During operation 111In-labeled platelets accumulated somewhat in the liver (10.7%) but not in the spleen, thorax, or head. In the 48 hours after operation, platelets were sequestered mainly in the liver. The scintillation camera with computer-assisted imaging allows in vivo quantitative studies of platelet kinetics of a type which has not been possible with previous techniques.

Kinetics, distribution, and sites of destruction of indium-111 oxine labelled red cells in haemolytic anaemia.

The survival of red cells labelled with indium-111 oxine in the circulation was determined. In vivo distribution at equilibrium and sites of deposition at the T50In--that is, the half life of labelled red cells--were quantitated with a scintillation camera and computer assisted image analysis. Although the rate of elution. Of 111In from the red cells was higher than that of chromium-51-disodium chromate, estimates of T50In and T50Cr corresponded reasonably well and were shortened in haemolytic anaemia. In normal subjects red cells were sequestered mainly in the liver and spleen. In five patients with different types of haemolytic anaemia two distinct patterns of red cell sequestration could be recognised: mainly splenic sequestration, and destruction of red cells in the liver, spleen, and the bone marrow. These patterns were expected for the particular disease studied.

Kinetics and fate of indium 111 oxine-labeled platelets in patients with aortic aneurysms.

The survival and sites of sequestration of indium 111 oxine-labeled autologous platelets were studied quantitatively in six patients with aortic aneurysms. The in vivo distribution was quantitated daily with a scintillation camera and a computer-assisted imaging system. Data of platelet survival curves were fitted to a gamma function model. Mean platelet survival was shortened and the disappearance curves were exponential in all but two patients who had normal platelet survival. Platelet radioactivity in the aneurysm was 5.1 +/- 3% of whole-body radioactivity at the end of platelet survival. Platelet were sequestered in the spleen, liver, and bone marrow. Accumulation of platelets, presumably due to microembolization, was prominent in the lower limbs. This indicates that although platelets were deposited in the aneurysm, many are damaged and are eventually sequestered in the reticuloendothelial system.

Erectile dysfunction in primary care: prevalence and patient characteristics. The ENIGMA study.

The availability of adequate treatment for erectile dysfunction (ED) triggers studies into the prevalence of ED in the general population. Yet, previous studies showed different prevalence estimates partly due to differences in patient selection, in (unclear) definitions of ED and in assessment. ENIGMA has been designed to study the prevalence of ED in the general population of The Netherlands, using the WHO definition with a description of the way of assessment. In all, 5721 mail surveys were sent to all men, aged 18 y and older in 12 general practices in The Netherlands. A total of 5601 were included in the study and 2117 (38%) were completed. A total of 38% of the men reported to have ever had some kind of erectile problem. The prevalence of ED was 17% (6% mild, 4% moderate and 7% complete). Age, diabetes, cardiovascular diseases, penile disorders, irradiation in the pelvic region, relational problems, fear for failure, surmenage, medication use and regular consumption of alcohol were independently related to ED. Men with ED were less content with their (sexual) life and had less confidence in sexual performance. Presence of ED was negatively related to affected happiness in life. ED is commonly found in men and is related to age, medication, comorbidity and lifestyle factors. Men with ED perceive a lower quality of (sex)life. Doctors should be aware of the presence of ED and its consequences in patients.

Impact of various questionnaires on the prevalence of erectile dysfunction. The ENIGMA-study.

The prevalence estimates of erectile dysfunction (ED) vary considerably across studies. These differences may be attributed to used definitions of ED. Quantitative data on the effect of different definitions of ED on the prevalence are lacking, because precise information on the used definition and questionnaire is often absent. Aim of this study was to quantify the effect of using different questionnaires for ED on the prevalence estimates. In all, 5721 mail surveys on sexual problems and ED were sent to all men (aged >18 y) in 12 general practices in the middle of the Netherlands of which 2117 were completed. The questionnaire contained Enigma (WHO), International Index of Erectile Function (IIEF), Cologne Erectile Inventory (KEED) and one question (Boxmeer, Krimpen). The prevalence of ED based on the various questionnaires and the effect of these questionnaires on risk factor relationships was compared. IIEF gave the highest age specific and overall ED prevalence, KEED the lowest. The difference in prevalence was 16.8%. The agreement (kappa coefficient) between the various ED definitions varied from 0.52 (IIEF & KEED) to 0.95 (Enigma & Boxmeer). The number of risk factor relations were similar for the Dutch studies, reduced for the IIEF and KEED. This study provides evidence that differences in questionnaires to assess ED have a considerable effect on the (age specific) prevalence estimates and little on the risk factor relations. The number of questions of the survey appears not to be responsible for differences in the prevalence of ED and risk factor relations, however they affect the response rate. Uniform use is strongly recommended, since a 'golden standard' for ED assessment (by questionnaire) is lacking. A short questionnaire with one or two questions is recommended for example the one from the Boxmeer-study. These data may be used to adjust (age-specific) prevalence rates comparing ED prevalence in the open population across studies.

A quantitative study of indium-111-oxine platelet kinetics in acute and chronic renal transplant rejection.

Thirteen patients were investigated on 22 occasions at times varying from 1 day to 10 years after living family donor or cadaver renal transplantation. Platelet survival in the circulation, and in vivo platelet distribution and sites of deposition and sequestration was quantitatively determined with Indium-111-oxine (In-111-oxine) labelled platelets and a scintillation camera interfaced with a computer assisted imaging system. In all patients platelet survival was shortened and the platelet survival curve exponential. In patients with no evidence of transplant rejection and those with chronic rejection, there was no measurable or visible accumulation of labelled platelets in the kidney. The sequestration pattern of In-111 labelled platelets at the end of platelet life span was within normal limits and located in the reticuloendothelial system. In those patients with acute transplant rejection, platelet survival was shortened. Labelled platelets accumulated in the kidney: this was clearly visualized on scintigraphy and reflected by a significant increase in the radioactivity count density of the kidney. Platelets not deposited in the transplant were sequestrated in the reticuloendothelial system. This study demonstrates the diagnostic value of In-111 labelled platelet kinetics in the investigation of acute renal failure after renal transplantation. This investigation appears of limited clinical value in chronic rejection.

Radiation dose from human platelets labelled with indium 111.

The biological distribution of 111In-labelled platelets in normal subjects was determined by whole-body counting and scintillation-camera computer-assisted imaging. Using these data, organ radiation dose was quantitated. The highest radiation dose of 7.4 mGy/MBq (27.4 rad/mCi) was received by the spleen and 0.97 mGy/MBq (3.6 rad/mCi) by the liver. While body radiation dose was 0.25 mGy/MBq (0.9 rad/mCi). The gonad radiation dose of males was 0.14 mGy/MBq (0.5 rad/mCi) and that of females 0.22 mGy/MBq (0.8 rad/mCi). These estimates indicate that radiation doses received from 8.6 MBq of 111In-labelled platelets are well within acceptable limits, and that 111In is a safe labelling agent for the study of platelet kinetics.

Immunoglobulin G sub-class concentrations in South African adults: ethnic differences and reference ranges.

Serum samples from healthy adult volunteers (n = 149) were selected at random from disputed paternity cases, laboratory staff and volunteers attending clinical trials. Total immunoglobulin G (IgG) and IgG sub-class (IgGSc) concentrations were determined by a radial immunodiffusion technique (RID). Standard statistical analyses were used to determine differences between groups. Reference ranges of IgGSc concentrations were calculated on the resultant groups of data. Total IgG and IgGSc concentrations in men and women of the same racial group were similar, except for IgG4 which was slightly higher in white males than in white females (median: 0.36 g/L vs 0.20 g/L respectively). IgGSc concentrations were higher in blacks than in whites (median values: IgG: 17.1 vs 12.1 g/L; IgG1: 11.1 vs 7.6 g/L; IgG2: 4.3 vs 3.2 g/L; IgG3: 1.2 vs 0.90 g/L respectively) with the exception of IgG4 which was similar in both groups (median: 0.29 g/L). It would appear that IgGSc values differ among the ethnic groups. Ethnicity must therefore be considered when calculating reference ranges. The reference ranges for the IgG sub-classes in the two ethnic groups are intended for use in our laboratory and in others in South Africa that use the RID technique.

Factors related to postpartum depression.

PIP: To determine which factors from a range of demographic, perinatal, psychosocial, and hormonal factors were related to postpartum depression, a sample of 81 women between 2 weeks and 6 months postpartum was divided into a depressed group (n = 22) and a nondepressed group (n = 59) by means of the Beck Depression Inventory as the main measure and the Visual Analogue Scale as an additional measure. A demographic questionnaire, a social support questionnaire, and a marital satisfaction questionnaire were completed by each subject. A depression incidence rate of 27.2% was found. There were significant differences between the depressed group and the nondepressed group in the area of social support, marital satisfaction, and premenstrual tension. No significant differences were found in age, parity, previous depressive episodes, cesarean births, or prematurity. It was concluded that psychosocial and hormonal factors played a more important role in postpartum depression than demographic and perinatal factors. (author's)^ieng

[Attrition and poor performance in general practice training: age, competence and knowledge play a role]. / Uitval en stagnatie in de opleiding tot huisarts. Leeftijd, competenties en kennis spelen een rol.

OBJECTIVE: To investigate which determinants are related to poor performance and forced attrition in the first year residency in general practice (GP). DESIGN: Observational retrospective cohort study. METHOD: We collected data relating to personal characteristics such as age, sex and clinical experience from residents who started the GP training in Utrecht, the Netherlands, in the period March 2005-August 2007. We also collected competence scores from the domains 'medical expertise', 'doctor-patient communication' and 'professionalism', as well as scores on a national GP knowledge test. The outcome measures were 'poor performance' and 'forced attrition'. Multivariate logistic regression was used to analyse correlations between personal characteristics, competence scores on the 3 domains and knowledge scores in the first trimester on the one hand and poor performance or forced attrition on the other. RESULTS: 215 residents started the GP training. In the first trimester a quarter of the residents had an insufficient score in 1 or more of the domains. Competence scores were mutually correlated, but did not correlate with the knowledge score. 18 residents showed poor performance and 3 were forced to stop their training. Poor performance and forced attrition were correlated with age (adjusted odds ratio (OR): 1.1; 95% CI: 1.0-1.3), insufficient knowledge (adjusted OR: 8.9; 3.0-26.3) and medical expertise (adjusted OR: 2.1; 1.1-4.0) at the beginning of the training. CONCLUSION: Age, insufficient knowledge of general practice, and insufficient competence in the domain of 'medical expertise' at the beginning of the training are risk factors for poor performance by residents and attrition from their GP training.