The reproducibility of a food frequency questionnaire among controls participating in a case‐control study on cancer

This study was designed to test the reproducibility of a food frequency questionnaire used in a population‐based case‐control study on diet and pancreatic cancer. Repeat questionnaires covering the same time period were obtained using 63 male and female population controls, 35–79 years of age. For selected food items included in the case‐control study, the attenuation of the odds ratios due to random error was estimated. Using 54 male and female population controls, 35–79 years of age, we conducted a second study to examine the agreement between original and repeat interviews when the time interval between interview and the period of interest was constant.

In the first study, the median correlation coefficient was 0.72 for foods (ranging from 0.36 and 0.59 for subgroups of vegetables to 0.96 for alcoholic beverages) and 0.77 for nutrients (ranging from 0.62 for β‐carotene to 0.85 for energy and 0.91 for ethanol). In the second study, the median correlation coefficient was 0.68 for foods (ranging from 0.28 for eggs to 0.87 for alcoholic beverages) and 0.75 for nutrients (ranging from 0.48 for β‐carotene to 0.76 for energy).

We conclude that for most items the agreement between original and repeat estimates was moderate (r> 0.50) to high (r > 0.70). Moderate agreement was found for 28 of 33 food items (85%) and for all 21 nutrient items (100%) and high agreement for 19 of 33 of food items (56%) and 15 of 21 nutrient items (71 %). In the second study, agreement was somewhat lower but closely paralleled the results of the first study. On average, random error presumably attenuated most of the observed diet‐cancer relationships only moderately; i.e., an observed odds ratio of 1.5 and a correlation coefficient of 0. 70 yield an unattenuated odds ratio of 2.1.     

Exploring improvements in patient logistics in Dutch hospitals with a survey

ABSTRACT: BACKGROUND: Research showed that promising approaches such as benchmarking, operations research, lean management and six sigma, could be adopted to improve patient logistics in healthcare. To our knowledge, little research has been conducted to obtain an overview on the use, combination and effects of approaches to improve patient logistics in hospitals. We therefore examined the approaches and tools used to improve patient logistics in Dutch hospitals, the reported effects of these approaches on performance, the applied support structure and the methods used to evaluate the effects. METHODS: A survey among experts on patient logistics in 94 Dutch hospitals. The results were analysed using cross tables. RESULTS: Forty-eight percent of all hospitals participated. Ninety-eight percent reported to have used multiple approaches, 39% of them used five or more approaches. Care pathways were the preferred approach by 43% of the hospitals, followed by business process re-engineering and lean six sigma (both 13%). Flowcharts were the most commonly used tool, they were used on a regular basis by 94% of the hospitals. Less than 10% of the hospitals used data envelopment analysis and critical path analysis on a regular basis. Most hospitals (68%) relied on external support for process analyses and education on patient logistics, only 24% had permanent internal training programs on patient logistics. Approximately 50% of the hospitals that evaluated the effects of approaches on efficiency, throughput times and financial results, reported that they had accomplished their goals. Goal accomplishment in general hospitals ranged from 63% to 67%, in academic teaching hospitals from 0% to 50%, and in teaching hospitals from 25% to 44%. More than 86% performed an evaluation, 53% performed a post-intervention measurement. CONCLUSIONS: Patient logistics appeared to be a rather new subject as most hospitals had not selected a single approach, they relied on external support and they did not have permanent training programs. Hospitals used a combination of approaches and tools, about half of the hospitals reported goal accomplishment and no approach seemed to outperform the others. To make improvement efforts more successful, research should be conducted into the selection and application of approaches, their contingency factors, and goal-setting procedures.     

Further delineation of the KBG syndrome caused by ANKRD11 aberrations

Loss-of-function variants in ANKRD11 were identified as the cause of KBG syndrome, an autosomal dominant syndrome with specific dental, neurobehavioural, craniofacial and skeletal anomalies. We present the largest cohort of KBG syndrome cases confirmed by ANKRD11 variants reported so far, consisting of 20 patients from 13 families. Sixteen patients were molecularly diagnosed by Sanger sequencing of ANKRD11, one familial case and three sporadic patients were diagnosed through whole-exome sequencing and one patient was identified through genomewide array analysis. All patients were evaluated by a clinical geneticist. Detailed orofacial phenotyping, including orthodontic evaluation, intra-oral photographs and orthopantomograms, was performed in 10 patients and revealed besides the hallmark feature of macrodontia of central upper incisors, several additional dental anomalies as oligodontia, talon cusps and macrodontia of other teeth. Three-dimensional (3D) stereophotogrammetry was performed in 14 patients and 3D analysis of patients compared with controls showed consistent facial dysmorphisms comprising a bulbous nasal tip, upturned nose with a broad base and a round or triangular face. Many patients exhibited neurobehavioural problems, such as autism spectrum disorder or hyperactivity. One-third of patients presented with (conductive) hearing loss. Congenital heart defects, velopharyngeal insufficiency and hip anomalies were less frequent. On the basis of our observations, we recommend cardiac assessment in children and regular hearing tests in all individuals with a molecular diagnosis of KBG syndrome. As ANKRD11 is a relatively common gene in which sequence variants have been identified in individuals with neurodevelopmental disorders, it seems an important contributor to the aetiology of both sporadic and familial cases.     

Induction of ventricular fibrillation predicts sudden death in patients treated with amiodarone because of ventricular tachyarrhythmias after a myocardial infarction.

OBJECTIVE--To examine the value of programmed electrical stimulation of the heart in predicting sudden death in patients receiving amiodarone to treat ventricular tachyarrhythmias after myocardial infarction. DESIGN--Consecutive patients; retrospective study. SETTING--Referral centre for cardiology, academic hospital. PATIENTS--106 patients with ventricular tachycardia (n = 77) or ventricular fibrillation (n = 29) late after myocardial infarction. INTERVENTIONS--Programmed electrical stimulation was performed while on amiodarone treatment for at least one month. MEASUREMENTS AND MAIN RESULTS--In 80/106 patients either ventricular fibrillation (n = 15) or sustained monomorphic ventricular tachycardia (n = 65) was induced. After a mean follow up of 50 (SD 40) months (1-144), 11 patients died suddenly and two used their implantable cardioverter debfibrillator. By multivariate analysis two predictors for sudden death were found: (1) inducibility of ventricular fibrillation under amiodarone treatment (P << 0.001), and (2) a left ventricular ejection fraction of < 40% (P < 0.05). The survival rate at one, two, three, and five years was 70%, 62%, 62%, and 40% respectively for patients in whom ventricular fibrillation was induced, and 98%, 96%, 94%, 94% for patients with induced sustained monomorphic ventricular tachycardia. Where there was no sustained arrhythmia, five year survival was 100%. CONCLUSIONS--In patients receiving amiodarone because of life threatening ventricular arrhythmias after myocardial infarction, inducibility of ventricular fibrillation, but not of sustained monomorphic ventricular tachycardia, indicates a high risk of sudden death.     

Analysis of the cell infiltrate and expression of proinflammatory cytokines and matrix metalloproteinases in arthroscopic synovial biopsies: comparison with synovial samples from patients with end stage,destructive rheumatoid arthritis

BACKGROUND: Synovial tissue (ST) from end stage destructive rheumatoid arthritis (RA) and arthroscopic biopsies obtained during active inflammation might exhibit different characteristics. OBJECTIVE: To define the cell infiltrate and the expression of proinflammatory cytokines, angiogenic factors, and matrix metalloproteinases (MMPs) in ST selected at arthroscopy compared with that from end stage RA. METHODS: Synovial biopsy specimens were obtained from the actively inflamed knee joints of 13 patients with chronic RA by arthroscopy and compared with ST from 10 patients with end stage, destructive RA. Immunohistological analysis was performed to detect T cells, plasma cells, macrophages, fibroblast-like synoviocytes (FLS), and the expression of interleukin (IL)1beta, IL6, tumour necrosis factor alpha (TNFalpha), MMP-1, MMP-3, MMP-13, TIMP-1, and VEGF. RESULTS: The expression of CD68+ macrophages was significantly higher in ST selected at arthroscopy than in samples obtained at surgery, both in the intimal lining layer and in the synovial sublining. The expression of CD3+ T cells also tended to be higher in arthroscopic samples. The expression of TNFalpha, IL6, MMP-1, MMP-3, MMP-13, TIMP-1, and VEGF was on average higher in ST obtained at arthroscopy. In contrast, the expression of IL1beta was on average higher in surgical samples. CONCLUSION: Active arthritis activity is associated with increased cell infiltration, expression of proinflammatory cytokines, MMPs, and angiogenic growth factors in synovial biopsy samples selected at arthroscopy. Increased expression of IL1beta in the synovium of patients with destructive RA requiring joint replacement may well reflect the important role of IL1beta in cartilage and bone destruction.     

Wide complex tachycardia with atrioventricular dissociation and QRS morphology identical to that of sinus rhythm: a manifestation of bundle branch reentry.

OBJECTIVE: To determine the features that distinguish bundle branch reentry (BBR) ventricular tachycardia from a supraventricular tachycardia with aberration on the 12 lead electrocardiogram (ECG). PATIENTS: Three patients in whom premature beats (2 cases) or sustained tachycardia (2 cases) showed a QRS configuration identical to that observed during sinus rhythm. INTERVENTIONS: Programmed electrical stimulation. RESULTS: These arrhythmias were ventricular in origin and caused by a BBR mechanism, as suggested by the following data obtained during electrophysiological study: (a) an H-V interval shorter during tachycardia than during sinus rhythm; (b) A-V dissociation; (c) activation of the right bundle branch before activation of the bundle of His. The ECG of all 3 patients showed right bundle branch block with very prolonged QRS duration (0.16 to 0.20 s). Characteristically, all 3 had prolonged H-V interval during sinus rhythm. All patients had had a previous myocardial infarction and had a dilated left ventricle. CONCLUSION: The presence of (a) wide complex extrasystoles or tachycardia with a QRS morphology identical to that of sinus rhythm; (b) A-V dissociation; and (c) a very prolonged QRS duration (0.16 s or more) is suggestive of ventricular tachycardia caused by bundle branch reentry.     

Cardiac hypertrophy is enhanced in PPAR alpha-/- mice in response to chronic pressure overload

AIMS: Peroxisome proliferator-activated receptor-alpha (PPARalpha) is a nuclear receptor regulating cardiac metabolism that also has anti-inflammatory properties. Since the activation of inflammatory signalling pathways is considered to be important in cardiac hypertrophy and fibrosis, it is anticipated that PPARalpha modulates cardiac remodelling. Accordingly, in this study the hypothesis was tested that the absence of PPARalpha aggravates the cardiac hypertrophic response to pressure overload. METHODS AND RESULTS: Male PPARalpha-/- and wild-type mice were subjected to transverse aortic constriction (TAC) for 28 days. TAC resulted in a more pronounced increase in ventricular weight and left ventricular (LV) wall thickness in PPARalpha-/- than in wild-type mice. Compared with sham-operated mice, TAC did not affect cardiac function in wild-type mice, but significantly depressed LV ejection fraction and LV contractility in PPARalpha-/- mice. Moreover, after TAC mRNA levels of hypertrophic (atrial natriuretic factor, alpha-skeletal actin), fibrotic (collagen 1, matrix metalloproteinase-2), and inflammatory (interleukin-6, tumour necrosis factor-alpha, cyclo-oxygenase-2) marker genes were higher in PPARalpha-/- than in wild-type mice. The mRNA levels of genes involved in fatty acid metabolism (long-chain acyl-CoA synthetase, hydroxyacyl-CoA dehydrogenase) were decreased in PPARalpha-/- mice, but were not further compromised by TAC. CONCLUSION: The present findings show that the absence of PPARalpha results in a more pronounced hypertrophic growth response and cardiac dysfunction that are associated with an enhanced expression of markers of inflammation and extracellular matrix remodelling. These findings indicate that PPARalpha exerts salutary effects during cardiac hypertrophy.     

Secondary thrombotic microangiopathy with severely reduced ADAMTS13 activity in a patient with Capnocytophaga canimorsus sepsis: a case report

BACKGROUND

The Gram‐negative bacillus Capnocytophaga canimorsus may cause a severe illness resembling thrombotic thrombocytopenic purpura (TTP). The pathogenesis and optimal therapy of this secondary thrombotic microangiopathy (TMA) remain uncertain.

CASE REPORT

A 63‐year‐old Caucasian man was admitted with suspicion for TTP, but blood cultures grew C. canimorsus. Initial investigations revealed severe thrombocytopenia, a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) activity level of less than 1%, and strongly elevated D‐dimer and lactate dehydrogenase levels. He made a full recovery with antibiotics and plasma infusion for 3 days. Plasmapheresis was not performed. Retrospective determination of serial ADAMTS13 activity levels revealed that ADAMTS13 activity had already increased to 25% at the start of plasma infusion.

CONCLUSION

This case highlights that a C. canimorsus sepsis may cause a secondary TMA with a severe ADAMTS13 deficiency. It also illustrates that the adjunctive role of plasma exchange or plasma infusion is doubtful as ADAMTS13 activity levels increased with antibiotics alone.