Implementing a patient decision aid, a process evaluation of a large-scale pre- and post-implementation trial.

PURPOSE: Patient decision aids (PtDAs) have been reported to have a positive influence on patients making a health care decision in trials. Nevertheless, post-trial implementation is poor. The aim of this study is to explore patient, clinician, and organizational success factors for implementing a PtDA designed for breast cancer patients, facing a decision on their radiation treatment. METHODS: We performed a process evaluation within a multi-center pre- and post-implementation trial. The PtDA was incorporated as much as possible in the logistics of 13 participating centers. Tracking data were collected on PtDA use. Process characteristics were recorded by both clinicians and patients. A logistic regression method was applied to investigate which process characteristics were significantly related to the probability that patients logged in to the PtDA. RESULTS: 189 patients received the PtDA of whom140 (77%) used the PtDA. If patients received the link via the surgery department they were more likely to use the PtDA (OR 9.77 (1.28-74.51)), compared to patients that received the link via the radiation oncology department. If the report of the multidisciplinary team stated that radiation treatment "had to be discussed with the patient", patients were more likely to use the PtDA (OR 2.29 (1.12-4.71)). Educational level was not related to the probability of PtDA use. CONCLUSIONS: We accomplished a high level of PtDA use. Patients were more likely to use the PtDA if they received the link via the surgery department and if "to be discussed with the patient" was written in the multidisciplinary team report.

Variations in respiratory rate do not reflect changes in tidal volume or minute ventilation after major abdominal surgery.

Monitoring of postoperative pulmonary function usually includes respiratory rate and oxygen saturation measurements. We hypothesized that changes in postoperative respiratory rate do not correlate with changes in tidal volume or minute ventilation. In addition, we hypothesized that variability of minute ventilation and tidal volume is larger than variability of respiratory rate. Respiratory rate and changes in tidal volume and in minute ventilation were continuously measured in 27 patients during 24 h following elective abdominal surgery, using an impedance-based non-invasive respiratory volume monitor (ExSpiron, Respiratory Motion, Waltham, MA, US). Coefficients of variation were used as a measure for variability of respiratory rate, tidal volume and minute ventilation. Data of 38,149 measurements were analyzed. We found no correlation between respiratory rate and tidal volume or minute ventilation (r2 = 0.02 and 0.01). Mean respiratory rate increased within the first 24 h after abdominal surgery from 13.9 ± 2.5 to 16.2 ± 2.4 breaths/min (p = 0.008), while tidal volume and minute ventilation remained unchanged (p = 0.90 and p = 0.18). Of interest, variability of respiratory rate (0.21 ± 0.06) was significantly smaller than variability of tidal volume (0.37 ± 0.12, p < 0.001) and minute ventilation (0.41 ± 0.12, p < 0.001). Changes in postoperative respiratory rate do not allow conclusions about changes in tidal volume or minute ventilation. We suggest that postoperative alveolar hypoventilation may not be recognized by monitoring respiratory rate alone. Variability of respiratory rate is smaller than variability in tidal volume and minute ventilation, suggesting that adaptations of alveolar ventilation to metabolic needs may be predominately achieved by variations in tidal volume.

Muscle strength and motor function throughout life in a cross-sectional cohort of 180 patients with spinal muscular atrophy types 1c-4.

BACKGROUND AND PURPOSE: Natural history studies in spinal muscular atrophy (SMA) have primarily focused on infants and children. Natural history studies encompassing all age groups and SMA types are important for the interpretation of treatment effects of recently introduced survival motor neuron gene-augmenting therapies. METHODS: We conducted a cross-sectional study to investigate muscle strength, Hammersmith Functional Motor Scale (Expanded) score and the patterns of muscle weakness in relation to age and SMA type. RESULTS: We included 180 patients with SMA types 1-4 in the age range 1-77.5 years with median disease duration of 18 (range 0-65.8) years. With the exception of the early phases of disease in which children with SMA types 2 and 3 may achieve new motor skills and show a temporary increase in muscle strength, cross-sectional data suggested that declining muscle strength and loss of motor skills over time are characteristic of all SMA types. Mean loss of strength was at least 1 point on the Medical Research Council score and 0.5 point on the Hammersmith Functional Motor Scale (Expanded) score per year. Trend lines compatible with deterioration of motor function and muscle strength started in childhood and continued into adulthood. The age at loss of specific motor skills was associated with disease severity. Triceps, deltoid, iliopsoas and quadriceps were the weakest muscles in all patients. Hierarchical cluster analysis did not show a segmental distribution of muscle weakness as suggested previously. CONCLUSIONS: Progressive muscle weakness and loss of motor function are characteristic of all SMA types and all ages.

Psychosocial health of cochlear implant users compared to that of adults with and without hearing aids: Results of a nationwide cohort study.

OBJECTIVES: This study aimed to examine the psychosocial health status of adult cochlear implant (CI) users, compared to that of hearing aid (HA) users, hearing-impaired adults without hearing aids and normally hearing adults. DESIGN: Cross-sectional observational study, using both self-reported survey data and a speech-in-noise test. SETTING: Data as collected within the Netherlands Longitudinal Study on Hearing (NL-SH) between September 2011 and June 2016 were used. PARTICIPANTS: Data from 1254 Dutch adults (aged 23-74), selected in a convenience sample design, were included for analyses. MEAN OUTCOME MEASURES: Psychosocial health measures included emotional and social loneliness, anxiety, depression, distress and somatisation. Psychosocial health, hearing status, use of hearing technology and covariates were measured by self-report; hearing ability was assessed through an online digit triplet speech-in-noise test. RESULTS: After adjusting for the degree of hearing impairment, HA users (N = 418) and hearing-impaired adults (N = 247) had significantly worse scores on emotional loneliness than CI users (N = 37). HA users had significantly higher anxiety scores than CI users in some analyses. Non-significant differences were found between normally hearing (N = 552) and CI users for all psychosocial outcomes. CONCLUSIONS: Psychosocial health of CI users is not worse than that of hearing-impaired adults with or without hearing aids. CI users' level of emotional loneliness is even lower than that of their hearing-impaired peers using hearing aids. A possible explanation is that CI patients receive more professional and family support, and guidance along their patient journey than adults who are fitted with hearing aids.

An unrestricted diet for uncomplicated diverticulitis is safe: results of a prospective diverticulitis diet study.

AIM: The optimal diet for uncomplicated diverticulitis is unclear. Guidelines refrain from recommendation due to lack of objective information. The aim of the study was to determine whether an unrestricted diet during a first acute episode of uncomplicated diverticulitis is safe. METHOD: A prospective cohort study was performed of patients diagnosed with diverticulitis for the first time between 2012 and 2014. Requirements for inclusion were radiologically proven modified Hinchey Ia/b diverticulitis, American Society of Anesthesiologists class I-III and the ability to tolerate an unrestricted diet. Exclusion criteria were the use of antibiotics and suspicion of inflammatory bowel disease or malignancy. All included patients were advised to take an unrestricted diet. The primary outcome parameter was morbidity. Secondary outcome measures were the development of recurrence and ongoing symptoms. RESULTS: There were 86 patients including 37 (43.0%) men. All patients were confirmed to have taken an unrestricted diet. There were nine adverse events in seven patients. These consisted of readmission for pain (five), recurrent diverticulitis (one) and surgery (three) for ongoing symptoms (two) and Hinchey Stage III (one). Seventeen (19.8%) patients experienced continuing symptoms 6 months after the initial episode and 4 (4.7%) experienced recurrent diverticulitis. CONCLUSION: The incidence of complications among patients taking an unrestricted diet during an initial acute uncomplicated episode of diverticulitis was in line with that reported in the literature.

Recurrences and Ongoing Complaints of Diverticulitis; Results of a Survey among Gastroenterologists and Surgeons.

OBJECTIVE: This study aims to investigate the current opinion of gastroenterologists and surgeons on treatment strategies for patients, with recurrences or ongoing complaints of diverticulitis. BACKGROUND: Treatment of recurrences and ongoing complaints remains a point of debate. No randomized trials have been published yet and guidelines are not uniform in their advice. DESIGN: A web-based survey was conducted among gastroenterologists and GE-surgeons. Questions were aimed at the treatment options for recurrent diverticulitis and ongoing complaints. RESULTS: In total, 123 surveys were filled out. The number of patients with recurrent or ongoing diverticulitis who were seen at the outpatient clinic each year was 7 (0-30) and 5 (0-115) respectively. Surgeons see significantly more patients on an annual basis 20 vs. 15% (p = 0.00). Both surgeons and gastroenterologists preferred to treat patients in a conservative manner using pain medication and lifestyle advise (64.4 vs. 54.0, p = 0.27); however, gastroenterologists would treat patients with mesalazine medication, which is significantly more (28%, p = 0.04) than in the surgical group. Surgeons are inclined more towards surgery (31.5%, p = 0.02). CONCLUSIONS: Both surgeons and gastroenterologists prefer to treat recurrent diverticulitis and ongoing complaints in a conservative manner. Quality of life, the risk of complications and the viewpoint of the patient are considered important factors in the decision to resect the affected colon.

The relation between quality of life and histopathology in diverticulitis; can we predict specimen-related outcome?

PURPOSE: An important factor in the decision to perform laparoscopic sigmoid resection for patient suffering from recurrent and ongoing diverticulitis is quality of life (QoL). It is unknown whether quality of life relates to the severity of diverticulitis as seen in the resected colonic segment. The aim of this study is to analyze histopathological findings of patients suffering from recurrent or ongoing diverticulitis and their QoL before and after surgery in order to improve patient outcome prediction. METHODS: A cohort of consecutive patients with diverticulitis between January 2010 and April 2014 was analyzed. All patients were scheduled for surgery and had at least three episodes of diverticulitis or more within the last 2 years or experienced ongoing complaints for at least 3 months or more and confirmation by a radiologist. We compared QoL questionnaires, to known histopathological entities. RESULTS: For this study, 54 consecutive patients were included, 15 (27.8%) men and 39 (72.2%) women. A marked difference in quality of life before and after surgery for patients having a more severe histopathological entity was not found (p = 0.83). However, a clinically relevant higher VAS score 6 months after surgery was shown in patients with peritonitis. Furthermore, these patients had more fibrosis in the histopathological samples. CONCLUSION: In conclusion, even though a relation between the different pathological entities and QoL could not be determined, patients with diverticulitis and concomitant microscopic peritonitis had significantly more fibrosis and suffered from a higher VAS scores 6 months after surgery.

A comparison of methods to suppress electrocardiographic artifacts in local field potential recordings.

OBJECTIVE: Local field potential (LFP) recordings from deep brain stimulation (DBS) electrodes are often contaminated with electrocardiographic (ECG) artifacts that hinder the detection of disease-specific electrical brain activity. METHODS: Three ECG suppression methods were evaluated: (1) QRS interpolation of the Perceive toolbox, (2) template subtraction, and (3) singular value decomposition (SVD). LFPs were recorded with the Medtronic PerceptTM PC system in nine Parkinson's disease patients with stimulation OFF ("OFF-DBS"; anode disconnected) and ON at 0 mA ("ON-DBS 0 mA"; anode connected). Findings were verified with simulated ECG-contaminated time series. RESULTS: ECG artifacts were present in 10 out of 18 ON-DBS 0 mA recordings. All ECG suppression methods drastically reduced artifact-induced beta band (13-35 Hz) power and at least partly recovered the beta peak and beta burst dynamics. Using external ECG recordings and lengthening artifact epoch length improved the performance of the suppression methods. Increasing epoch length, however, elevated the risk of flattening the beta peak and losing beta burst dynamics. CONCLUSIONS: The SVD method formed the preferred trade-off between artifact cleaning and signal loss, as long as its parameter settings are adequately chosen. SIGNIFICANCE: ECG suppression methods enable analysis of disease-specific neural activity from signals affected by ECG artifacts.

Thalamic local field potentials recorded using the deep brain stimulation pulse generator.

Background: Essential tremor (ET) is one of the most common movement disorders, and continuous deep brain stimulation (DBS) is an established treatment for medication-refractory cases. However, the need for increasing stimulation intensities, with unpleasant side effects, and DBS tolerance over time can be problematic. The advent of novel DBS devices now provides the opportunity to longitudinally record LFPs using the implanted pulse generator, which opens up possibilities to implement adaptive DBS algorithms in a real-life setting. Methods: Here we report a case of thalamic LFP activity recorded using a commercially available sensing-enabled DBS pulse generator (Medtronic Percept PC). Results: In the OFF-stimulation condition, a peak tremor frequency of 3.8 Hz was identified during tremor evoking movements as assessed by video and accelerometers. Activity at the same and supraharmonic frequency was seen in the frequency spectrum of the LFP data from the left vim nucleus during motor tasks. Coherence analysis showed that peripherally recorded tremor was coherent with the LFP signal at the tremor frequency and supraharmonic frequency. Conclusion: This is the first report of recorded tremor-related thalamic activity using the electrodes and pulse generator of an implanted DBS system. Larger studies are needed to evaluate the clinical potential of these fully implantable systems, and ultimately pulse generators with sensing-coupled algorithms driving stimulation, to really close the loop.

A patient decision aid for breast cancer patients deciding on their radiation treatment, no change in decisional conflict but better informed choices.

BACKGROUND AND PURPOSE: In selected breast cancer patients, radiation treatment (RT) lowers the recurrence risk, with minor or no improvement of survival. In these patients, the choice to undergo RT is considered a preference-sensitive decision. To facilitate shared decision-making (SDM) for this choice, a patient decision aid was made. We aimed to evaluate the effect of the PtDA on decisional conflict. MATERIAL AND METHODS: We performed a multi-center pre- and post-intervention study (BRASA-trial). The first 214 patients made a choice without support of the PtDA; the subsequent 189 patients received a link to the PtDA. The primary endpoint was decisional conflict; secondary endpoints were perceived SDM and knowledge on treatment options. Patients filled out questionnaires immediately after, and three months after their decision. Data were analyzed with multi-level regression analysis. RESULTS: After correcting for the difference in age and educational level, the mean (±SD) decisional conflict for the intervention group (27.3 ± 11.4) was similar to the control group (26.8 ± 11.4; difference = 0.86, 95 %CI 1.67,3.36) three months after their decision. This also applied to perceived SDM. Patients exposed to the PtDA pursued additional treatment less often (45% vs 56%, odds ratio 0.59, 95 %CI 0.37,0.95) and scored significantly higher on the knowledge test (7.4 ± 2.5 vs 6.1 ± 2.7, corrected difference = 1.0, 95 %CI 0.50,1.49). There was no significant increase in consultation time. CONCLUSIONS: Handing out the PtDA was not associated with improved scores in decisional conflict or perceived SDM, but it was associated with a choice for less additional treatment and better knowledge about the treatment options.

Better survival after surgery of the primary tumor in stage IV inflammatory breast cancer.

INTRODUCTION: Information regarding the effects of resection of the primary tumor in stage IV inflammatory breast cancer (IBC) is scarce. We analyzed the impact of resection of the primary tumor on overall survival (OS) in a large stage IV IBC population. MATERIALS AND METHODS: Patients diagnosed with stage IV IBC between 2005 and 2016 were selected from the Netherlands Cancer Registry, excluding patients without any treatment. To correct for immortal time bias, we performed a landmark analysis including patients alive at least six months after diagnosis. With propensity score matching, patients undergoing surgery of the primary tumor were matched to patients not receiving surgery. Multivariable Cox proportional hazard analyses were performed to determine the association between treatment strategy and OS in the non-matched and matched cohort. RESULTS: Of the 580 included patients after landmark analysis, 441 patients (76%) received only non-surgical treatments and 139 (24%) underwent surgery (96% mastectomy). Median follow-up was 28.8 and 20.0 months in the surgery and no surgery group, respectively. Surgery in the non-matched cohort was independently associated with better survival (HR0.56[95%CI:0.42-0.75]). In the matched cohort (n = 202), surgically treated patients had improved survival over nonsurgically treated patients (p < 0.005). Multivariable analysis of the matched cohort revealed that surgery was still associated with better survival (HR0.62[95%CI:0.44-0.87]). CONCLUSION: Although residual confounding and confounding by severity cannot be ruled out, this study suggests that surgery of the primary tumor is associated with improved OS and should be considered as part of the treatment strategy in stage IV IBC.

Risk communication in a patient decision aid for radiotherapy in breast cancer: How to deal with uncertainty?

BACKGROUND AND AIM: Patient decision aids for oncological treatment options, provide information on the effect on recurrence rates and/or survival benefit, and on side-effects and/or burden of different treatment options. However, often uncertainty exists around the probability estimates for recurrence/survival and side-effects which is too relevant to be ignored. Evidence is lacking on the best way to communicate these uncertainties. The aim of this study is to develop a method to incorporate uncertainties in a patient decision aid for breast cancer patients to support their decision on radiotherapy. METHODS: Firstly, qualitative interviews were held with patients and health care professionals. Secondly, in the development phase, thinking aloud sessions were organized with four patients and 12 health care professionals, individual and group-wise. RESULTS: Consensus was reached on a pictograph illustrating the whole range of uncertainty for local recurrence risks, in combination with textual explanation that a more exact personalized risk would be given by their own physician. The pictograph consisted of 100 female icons in a 10 x 10 array. Icons with a stepwise gradient color indicated the uncertainty margin. The prevalence and severity of possible side-effects were explained using verbal labels. CONCLUSIONS: We developed a novel way of visualizing uncertainties in recurrence rates in a patient decision aid. The effect of this way of communicating risk uncertainty is currently being tested in the BRASA study (NCT03375801).

[The accuracy of patients' perceptions of the risks associated with localised prostate cancer treatments]. / Risicopercepties van mannen met gelokaliseerde prostaatkanker.

OBJECTIVE: To assess the accuracy of patients' perceptions of the risks associated with localised prostate cancer treatments (radical prostatectomy [RP], radiotherapy [RT], and active surveillance [AS]), and to identify correlates of misperceptions. PATIENTS AND METHODS: We used baseline data (questionnaires completed after treatment information was provided but before treatment) of 426 patients with newly diagnosed localised prostate cancer who participated (87% response rate) in a prospective, longitudinal, multicentre study. Patients' pretreatment perceptions of differences in adverse outcomes of treatments were compared to those based on the literature. We used univariate and multivariate linear regression to identify correlates of misperceptions. RESULTS: About two-thirds (68%, n = 211) of the patients did not understand that the risk of disease recurrence is comparable between RP and RT. More than half of the patients did not comprehend that RP patients are at greater risk of urinary incontinence (65%, n = 202) and erectile dysfunction (61%, n = 190), and less at risk of bowel problems (53%, n = 211) compared to RT patients. Many patients overestimated the risk of requiring definitive treatment following AS (45%, n = 157) and did not understand that mortality rates following AS, RP, and RT are comparable (80%, n = 333). Consulting a radiotherapist or a clinical nurse specialist was positively associated with, and emotional distress was negatively associated with, better understanding of the risks (P < 0.05), although effect sizes were small. CONCLUSION: Prior to choosing treatment, most patients with prostate cancer poorly understood the differences in treatment risks. Greater efforts should be made to better understand why these misperceptions occur and, most importantly, how they can be corrected.

Position-dependent methylation and transcriptional silencing of transgenes in inverted T-DNA repeats: implications for posttranscriptional silencing of homologous host genes in plants.

Posttranscriptional silencing of chalcone synthase (Chs) genes in petunia transformants occurs by introducing T-DNAs that contain a promoter-driven or promoterless Chs transgene. With the constructs we used, silencing occurs only by T-DNA loci which are composed of two or more T-DNA copies that are arranged as inverted repeats (IRs). Since we are interested in the mechanism by which these IR loci induce silencing, we have analyzed different IR loci and nonsilencing single-copy (S) T-DNA loci with respect to the expression and methylation of the transgenes residing in these loci. We show that in an IR locus, the transgenes located proximal to the IR center are much more highly methylated than are the distal genes. A strong silencing locus composed of three inverted T-DNAs bearing promoterless Chs transgenes was methylated across the entire locus. The host Chs genes in untransformed plants were moderately methylated, and no change in methylation was detected when the genes were silenced. Run-on transcription assays showed that promoter-driven transgenes located proximal to the center of a particular IR are transcriptionally more repressed than are the distal genes of the same IR locus. Transcription of the promoterless Chs transgenes could not be detected. In the primary transformant, some of the IR loci were detected together with an unlinked S locus. We observed that the methylation and expression characteristics of the transgenes of these S loci were comparable to those of the partner IR loci, suggesting that there has been cross talk between the two types of loci. Despite the similar features, S loci are unable to induce silencing, indicating that the palindromic arrangement of the Chs transgenes in the IR loci is critical for silencing. Since transcriptionally silenced transgenes in IRs can trigger posttranscriptional silencing of the host genes, our data are most consistent with a model of silencing in which the transgenes physically interact with the homologous host gene(s). The interaction may alter epigenetic features other than methylation, thereby impairing the regular production of mRNA.

Perioperative nesiritide versus milrinone in high-risk coronary artery bypass graft patients.

BACKGROUND: Patients with left-ventricular dysfunction have an increased risk of developing heart failure after coronary artery bypass graft (CABG) surgery. Therapies to maintain cardiac output in such patients warrant investigation. Nesiritide is unique among intravenous medications used to manage heart failure. It mediates natriuresis and vasodilation and suppresses the reninangiotensin-aldosterone axis. Nesiritide may attenuate the body's neurohormonal response to myocardial stretch after CABG and provide clinical benefit in the immediate postoperative period. OBJECTIVE: To determine whether perioperative infusion of nesiritide improves clinical outcomes compared with milrinone therapy. METHODS: A prospective, open-label, randomized controlled trial was conducted in 40 consecutive hemodynamically stable patients with ejection fractions 35% or less undergoing CABG surgery. Patients were randomized to receive either an intraoperative bolus of nesiritide or milrinone followed by a 24 hour infusion of each agent. Length of postoperative intensive care unit stay was the primary outcome variable evaluated. Incidence of postoperative heart failure, 30 day readmission rates, mortality, and other clinical parameters were also compared. RESULTS: Patients receiving nesiritide had a mean +/- SD postoperative intensive care unit stay of 50.6 +/- 46.8 hours compared with 44.1 +/- 23.5 hours in those receiving milrinone (p = 0.578). Incidence of postoperative heart failure was also not significantly different between the drugs (p = 0.259). Thirty day follow-up confirmed no difference in hospital readmission rates between nesiritide and milrinone (p = 0.661). No differences in mortality were observed during hospitalization or 30 days of follow-up. CONCLUSIONS: Nesiritide does not decrease postoperative intensive care unit stay or other clinical parameters compared with milrinone in high-risk patients with hemodynamically stable left-ventricular function undergoing CABG surgery.

Cardiac pathology in spinal muscular atrophy: a systematic review.

BACKGROUND: Hereditary proximal spinal muscular atrophy (SMA) is a severe neuromuscular disease of childhood caused by homozygous loss of function of the survival motor neuron (SMN) 1 gene. The presence of a second, nearly identical SMN gene (SMN2) in the human genome ensures production of residual levels of the ubiquitously expressed SMN protein. Alpha-motor neurons in the ventral horns of the spinal cord are most vulnerable to reduced SMN concentrations but the development or function of other tissues may also be affected, and cardiovascular abnormalities have frequently been reported both in patients and SMA mouse models. METHODS: We systematically reviewed reported cardiac pathology in relation to SMN deficiency. To investigate the relevance of the possible association in more detail, we used clinical classification systems to characterize structural cardiac defects and arrhythmias. CONCLUSIONS: Seventy-two studies with a total of 264 SMA patients with reported cardiac pathology were identified, along with 14 publications on SMA mouse models with abnormalities of the heart. Structural cardiac pathology, mainly septal defects and abnormalities of the cardiac outflow tract, was reported predominantly in the most severely affected patients (i.e. SMA type 1). Cardiac rhythm disorders were most frequently reported in patients with milder SMA types (e.g. SMA type 3). All included studies lacked control groups and a standardized approach for cardiac evaluation. The convergence to specific abnormalities of cardiac structure and function may indicate vulnerability of specific cell types or developmental processes relevant for cardiogenesis. Future studies would benefit from a controlled and standardized approach for cardiac evaluation in patients with SMA.

Cytokine profiles in multifocal motor neuropathy and progressive muscular atrophy.

Multifocal motor neuropathy (MMN) and progressive muscular atrophy (PMA) are associated with IgM monoclonal gammopathy or the presence IgM anti-GM1-antibodies. To further investigate the pathophysiology of MMN and PMA we determined concentrations of 16 mainly B-cell associated inflammatory markers in serum from 25 patients with MMN, 55 patients with PMA, 25 patients with amyotrophic lateral sclerosis (ALS) and 50 healthy controls. Median serum concentrations of the 16 tested cytokines and chemokines were not significantly increased in patients with MMN or patients with PMA, irrespective of the presence of IgM monoclonal gammopathy or high IgM anti-GM1 antibodies. These results argue against a systemic B-cell mediated immune response underlying the pathogenesis of MMN and PMA.

Trends in the prevalence, detection, treatment and control of arterial hypertension in the Belgian adult population.

OBJECTIVES: To discuss changes during the past decades in the prevalence and in the patterns of detection, treatment and control of arterial hypertension in the general Belgian population aged 25-64 years. DESIGN: Data from two cross-sectional cardiovascular disease risk factor surveys of the general population aged 25-64 years during the first and second halves of the 1980s (the Belgian Inter-university Research on Nutrition and Health study of 1980-1984 and the World Health Organization Multinational Monitoring of Trends and Determinants in Cardiovascular Diseases study of 1985-1992) are compared. PARTICIPANTS: Age-stratified and sex-stratified random samples from the general population yielded 9372 participants in the former study and 4904 participants in the latter. METHODS: In both studies, blood pressure measurements and other variables were collected in the same standardized way and by the same observers. RESULTS: For both sexes, overall age-standardized prevalences of hypertension (subjects with systolic blood pressure > or = 160 mmHg or diastolic blood pressure > or = 95 mmHg or currently being administered antihypertensive drug treatment) were found to be significantly (P< 0.001) higher in the former than they were in the latter study. A significant decline in population mean systolic blood pressure values was observed for both sexes on going from the former data to the latter (falls of 6.0 and 7.3 mmHg for men and women, respectively, P< 0.01). In log-linear models, adjusted for age, a highly significant (P< 0.0001) favourable shift in the population distribution over the various categories of detection, treatment and control of hypertension was observed. This trend exhibited a significant sex difference, however, there being a much more favourable trend for women. CONCLUSIONS: In Belgium, favourable trends in the prevalence and in the patterns of detection, treatment and control of arterial hypertension and in the levels of systolic blood pressure were observed. The so-called 'rule of halves' is no longer valid.

[Food additives as a cause of medical symptoms: relationship shown between sulfites and asthma and anaphylaxis; results of a literature review]. / Voedseladditieven als oorzaak van medische klachten: alleen voor sulfiet verband met astma en anafylaxie aangetoond; resultaten van een literatuuronderzoek.

OBJECTIVE: To determine if a causal connection exists between food additives and various medical complaints. DESIGN: Literature study. METHOD: Medline over the period January 1966-January 1999 was searched for articles on the following substances not containing protein and lactose: monosodium glutamate (MSG), sulfites, azo-dyes (tartrazine, sunset yellow, azorubin, amarant, cochineal red), benzoates, sorbates, butylated hydroxyanisole/butylated hydroxytoluene (BHA/BHT), parabens, cinnamon and vanilla, in combination with key words regarding food and side effects. Of those studies purporting to demonstrate an effect, only double-blind randomized placebo-controlled studies with oral challenge were assessed further, unless the complaint was anaphylaxis. Of studies not demonstrating an effect the design was assessed. RESULTS: Only for sulfites as causative agents of asthma and anaphylaxis, methodologically adequate studies demonstrating a causal connection could be found. For azo-dyes, benzoates, MSG, sorbates and BHA/BHT, no link with medical symptoms was demonstrable. For parabens, cinnamon and vanilla there were insufficient or inadequate data to justify a conclusion.

Effect of body mass on hibernation strategies of woodchucks (Marmota monax).

The benefits of mammalian hibernation have been well documented. However, the physiological and ecological costs of torpor have been emphasized only recently as part of a hibernation-optimization hypothesis. This hypothesis predicts that hibernators with greater availability of energy minimize costs of torpor by less frequent utilization of torpor and by maintaining higher body temperatures (T(b)) during torpor. In order to further examine the relationship between body mass and other parameters of hibernation, we present data, collected over a 12-year period, on the hibernation patterns of free-living woodchucks (Marmota monax) in southeastern Pennsylvania. Body mass was positively correlated with T(b) and negatively correlated with percentage of the heterothermic period spent in torpor. Thus, woodchucks with greater mass exhibited less time in torpor as a proportion of their heterothermic period and at higher T(b) than those with lesser mass. This strategy potentially enhances the physiological and physical ability of woodchucks to defend territories, avoid predation, find mates, and complete the reproductive cycle upon emergence from hibernation. Our results further support the hibernation-optimization hypothesis by demonstrating the relationship between body mass and characteristics of torpor and contributing toward a fuller understanding of this concept.