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Objectives As a person's age increases and his/her health status declines, new challenges arise that may lead physicians to consider deprescribing statins. We aimed to provide insight into recommendations available in international cardiovascular disease prevention guidelines regarding discontinuation of statin treatment applicable to older adults. Design We systematically searched PubMed, EMBASE, EMCARE, and the websites of guideline development organizations and online guideline repositories for cardiovascular disease prevention guidelines aimed at the general population. We selected all guidelines with recommendations (instructions and suggestions) on discontinuation of statin treatment applicable to older adults, published between January 2009 and April 2019. In addition, we performed a synthesis of information from all other recommendations for older adults regarding statin treatment. Methodological quality of the included guidelines was appraised using the appraisal of guidelines for research & evaluation II (AGREE II) instrument. Results Eighteen international guidelines for cardiovascular disease prevention in the general adult population provided recommendations for statin discontinuation that were applicable to older adults. We identified three groups of instructions for statin discontinuation related to statin intolerance, and none was specifically aimed at older adults. Three guidelines also included suggestions to consider statin discontinuation in patients with poor health status. Of the 18 guidelines included, 16 made recommendations regarding statin treatment in older adults, although details on how to implement these recommendations in practice were not provided. Conclusion Current international cardiovascular disease prevention guidelines provide little specific guidance for physicians who are considering statin discontinuation in older adults in the context of declining health status and short life expectancy. J Am Geriatr Soc 68:417-425, 2020.

Opioids are known to affect gastrointestinal motility, but their effect on fluid absorption and secretion is poorly understood in humans.To investigate the effect of oxycodone on colonic fecal volume and stool dryness by using a novel MRI-based technique.Prospective, randomized, double-blinded, crossover study.Twenty-five healthy male volunteers (median age: 24 years [range: 21-56]; mean body mass index [BMI]: 23.9 kg/mTSubjects were treated for 5 days with prolonged-release oxycodone or a placebo. Imaging was performed on the first and last study day in each period. Images of the colon were analyzed with semiautomatic k-means-based segmentation software. Regional colonic fecal volumes were quantified excluding gas volume and colon wall. Two-point Dixon and TIntraclass correlation coefficients were used to test the reliability of measurements between days, while repeated measures mixed models were applied to test treatment effects.After oxycodone treatment, total colonic fecal volume was significantly increased compared with placebo (mean change 100 mL vs. -13 mL; P = 0.001), with the largest increase (24%) observed in the ascending colon/cecum (P = 0.001). Dixon signal increased (less water in colon content) after oxycodone treatment compared with placebo (mean 0.09 vs. -0.02; P0.001). TThe 5-day oxycodone treatment increased colonic fecal volume and increased stool dryness compared with placebo. This imaging-based method for noninvasive analysis of colon content has the potential to characterize gastrointestinal symptoms in general, such as in constipation.2 Technical Efficacy Stage: 1 J. Magn. Reson. Imaging 2019;50:733-745.

INTRODUCTION: Sphincter-sparing radiotherapy or chemoradiation (RT/CRT) have become the standard treatments for most patients with anal cancer. Unfortunately, long-term survivors often suffer from severe bowel symptoms indicating sensory dysfunction. The aim of the present study was to characterize the sensory pathways of the brain-gut axis after radiotherapy for anal cancer.METHOD: Cortical evoked potentials (CEPs) were recorded during repeated, rapid balloon distensions of the rectum and anal canal in 13 patients with anal cancer treated with radiotherapy or chemoradiation and in 17 healthy volunteers. Latencies and amplitudes of rectal CEPs were compared between the groups. CEPs from both rectal and anal distensions were examined using single sweep spectral band analysis to determine the relative amplitude of five spectral bands as a proxy of neuronal processing.RESULTS: Groups were comparable by age (62.4 ± 7.8 vs 58.9 ± 8.9, p CONCLUSION: Patients treated with RT/CRT for anal cancer have impaired ano-rectal sensory pathways and abnormal cortical processing. This may play a central role for the pathogenesis of late proctopathy.

Background A physically active lifestyle in older people contributes to the preservation of good health. We assessed the influence of physiotherapy on daily functioning among community dwelling older people (75+) with complex health problems identified with screening, versus usual care. We also compared functional task exercise (FTE), with problems prioritized by older people, trained in the home environment, versus usual preventive physical therapy (PPT). Methods Design: FTE and PPT were compared in a randomized controlled trial (RCT). Both interventions were compared with daily functioning in an observational study: control group. Setting/Participants: Community-dwelling persons aged ≥75 years with daily activity limitations enlisted in 83 general practices (n = 155). Interventions: Both intervention groups (FTE, n = 76 and PPT, n = 79) received individual, 30 min treatments. The control group (n = 228) did not get any experimental intervention offered. Measurements: Groningen Activities of Daily Living Restriction Scale (GARS). Statistical analyses: Linear Mixed Model analysis, correcting for age, sex, baseline scores and clustering by physiotherapist were used to compare the different groups. Results At baseline, 74% percent of the intervention trial group was female vs 79% in the control group. Median ages were 83.9 and 84.7 respectively. The median baseline GARS-score for the control group was 41.0 (25 and 75 percentile): 35.0; 48.0) and 40.0 (25 and 75 percentile: 32.3; 46.0) for the intervention group (FTE + PPT). The mean change over time was 3.3 (2.5; 4.1) for the control group. Mean difference in change over time between the intervention (FTE + PPT) and the control group was − 2.5 (− 4.3; − 0.6) (p = .009). Between FTE and PPT the difference in change was − 0.4 (95% CI: -2.3; 3.0, p = 0.795). Conclusion An exercise intervention led by physiotherapists may slow down decline in self-reported daily functioning in older persons with daily activity limitations, identified by pro-active case finding. Trial registration Netherlands trial register (NTR2407). Registered 6th of July 2010. Electronic supplementary material The online version of this article (10.1186/s12877-018-0859-3) contains supplementary material, which is available to authorized users.

Background The use of cardiovascular medication for the primary prevention of cardiovascular disease (CVD) is potentially inappropriate when potential risks outweigh the potential benefits. It is unknown whether deprescribing preventive cardiovascular medication in patients without a strict indication for such medication is safe and cost-effective in general practice. Methods In this pragmatic cluster randomised controlled non-inferiority trial, we recruited 46 general practices in the Netherlands. Patients aged 40–70 years who were using antihypertensive and/or lipid-lowering drugs without CVD and with low risk of future CVD were followed for 2 years. The intervention was an attempt to deprescribe preventive cardiovascular medication. The primary outcome was the difference in the increase in predicted (10-year) CVD risk in the per-protocol (PP) population with a non-inferiority margin of 2.5 percentage points. An economic evaluation was performed in the intention-to-treat (ITT) population. We used multilevel (generalised) linear regression with multiple imputation of missing data. Results Of 1067 participants recruited between 7 November 2012 and 18 February 2014, 72% were female. Overall, their mean age was 55 years and their mean predicted CVD risk at baseline was 5%. Of 492 participants in the ITT intervention group, 319 (65%) quit the medication (PP intervention group); 135 (27%) of those participants were still not taking medication after 2 years. The predicted CVD risk increased by 2.0 percentage points in the PP intervention group compared to 1.9 percentage points in the usual care group. The difference of 0.1 (95% CI -0.3 to 0.6) fell within the non-inferiority margin. After 2 years, compared to the usual care group, for the PP intervention group, systolic blood pressure was 6 mmHg higher, diastolic blood pressure was 4 mmHg higher and total cholesterol and low-density lipoprotein-cholesterol levels were both 7 mg/dl higher (all P

Risk factors associated with persistent pain after breast cancer treatment are needed to develop prevention and treatment strategies to improve the quality of life for patients with breast cancer.To identify factors associated with persistent pain in women undergoing breast cancer treatments.Retrospective study.Regional hospital in the Netherlands.The primary outcome was pain associated with surgery at more than 6 months postoperatively and patients were stratified based on the associated visual analog" scale score they reported: reporting no pain as "no pain," pain 1 - 29 mm as "mild pain," and pain 30 - 100 mm as "moderate/severe pain." Secondary outcomes were function, symptom, and total quality of life scores. Predefined risk factors analyzed for association with outcomes included: age, smoking status, diabetes, body mass index (BMI), disease stage, surgery type, axillary lymph node dissection, reoperation, chemotherapy, radiotherapy, and hormone therapy.Of the 718 patients who were approached, 492 were included (follow-up 2.5 ± 1.8 years). Thirty-five percent of patients developed persistent pain (n = 122 "mild pain," n = 53 "moderate/severe pain'"). Age, BMI, surgery type, axillary lymph node dissection, disease stage, reoperation, chemotherapy, and radiotherapy were identified as potential risk factors in univariate ordinal regression analyses (P0.10). Age (P0.01) and BMI (P = 0.04) remained independently predictive in the multivariate model. BMI and age were associated with odds ratios (ORs) of 1.04 (95% confidence intervals (CI): 1.00 - 1.08) and 0.97 (95% CI: 0.95 - 0.99), respectively per point and year increase. BMI was associated with a higher symptom score (r = 0.14, P0.01), a lower level of function (r = -0.11, P = 0.01), and lower total quality of life scores (r = -0.13, P0.01).The retrospective nature of this study makes it prone to response and misclassification bias.BMI and age may be risk factors for persistent postoperative pain after breast cancer treatment.Persistent postsurgical pain, breast cancer treatment, BMI, age, chronic postoperative pain, breast cancer surgery.

Background To date, no validated risk scores exist for prediction of recurrence risk or potential treatment effect for older people with a history of a cardiovascular event. Therefore, we assessed predictive values for recurrent cardiovascular disease of models with age and sex, traditional cardiovascular risk markers, and ‘SMART risk score’, all with and without addition of N-terminal pro-B-type natriuretic peptide (NT-proBNP). Treatment effect of pravastatin was assessed across low and high risk groups identified by the best performing models.\ud Design and methods Post-hoc analysis in 2348 participants (age 70–82 years) with a history of cardiovascular disease within the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) study. Composite endpoint was a recurrent cardiovascular event/cardiovascular mortality.\ud Results The models with age and sex, traditional risk markers and SMART risk score had comparable predictive values (area under the curve (AUC) 0.58, 0.61 and 0.59, respectively). Addition of NT-proBNP to these models improved AUCs with 0.07 (p for difference ((pdiff)) = 0.003), 0.05 (pdiff = 0.009) and 0.06 (pdiff

This study aimed to explore the prognosis of very old people depending on their cardiovascular disease (CVD) history. This observational prospective cohort study included 570 participants aged 85 years from the general population with 5-year follow-up for morbidity, functional status, and mortality. At baseline, participants were assigned to three groups: no CVD history, "minor" CVD (angina pectoris, transient ischemic attack, intermittent claudication, and/or heart failure), or "major" CVD (myocardial infarction [MI], stroke, and/or arterial surgery). Follow-up data were collected on MI, stroke, functional status, and cause-specific mortality. The composite endpoint included cardiovascular events (MI or stroke) and cardiovascular mortality. At baseline, 270 (47.4 %) participants had no CVD history, 128 (22.4 %) had minor CVD, and 172 (30.2 %) had major CVD. Compared to the no CVD history group, the risk of the composite endpoint increased from 1.6 (95 % confidence interval [CI], 1.1-2.4) for the minor CVD group to 2.7 (95 % CI, 2.0-3.9) for the major CVD group. Similar trends were observed for cardiovascular and all-cause mortality risks. In a direct comparison, the major CVD group had a nearly doubled risk of the composite endpoint (hazard ratio, 1.8; 95 % CI, 1.2-2.7), compared to the minor CVD group. Both minor and major CVD were associated with an accelerated decline in cognitive function and accelerated increase of disability score (all p

Background Although guidelines recommend secondary cardiovascular prevention irrespective of age, in older age the uptake of treatment is lower than in younger age groups. Aim To explore the dilemmas GPs in the Netherlands encounter when implementing guidelines for secondary cardiovascular prevention in older age. Design and setting Qualitative study in four focus groups consisting of GPs ( n = 23, from the northern part of the province South Holland) and a fifth focus group consisting of GP trainees ( n = 4, from the Leiden University Medical Center). Method Focus group discussions were organised to elicit perspectives on the implementation of secondary cardiovascular prevention for older people. The 14 theoretical domains of the refined Theoretical Domains Framework (TDF) were used for (deductive) coding of the focus group discussions. The coded texts were analysed, content was discussed, and barriers and facilitators were identified for each domain of the TDF. Results The main theme that emerged was ‘uncertainty’. Identified barriers were guideline-related, patient-related, and organisation-related. Identified facilitators were doctor-related, patient-related, and organisation-related. The main aim of secondary preventive treatment was improvement in quality of life. Conclusion GPs in the Netherlands are uncertain about many aspects of secondary cardiovascular prevention in older age; the guidelines themselves, their own role, patient factors, and the organisation of care. In view of this uncertainty, GPs consciously weigh all aspects of the situation in close dialogue with the individual patient, with the ultimate aim of improving quality of life. This highly-individualised care may largely explain the reduced prescription rates.

Objectives:\ud To assess the effect of preventive pravastatin treatment on coronary heart disease (CHD) morbidity and mortality in older persons at risk for cardiovascular disease (CVD), stratified according to plasma levels of homocysteine.\ud \ud Design:\ud A post hoc subanalysis in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER), started in 1997, which is a double-blind, randomized, placebo-controlled trial with a mean follow-up of 3.2 years.\ud \ud Setting:\ud Primary care setting in two of the three PROSPER study sites (Netherlands and Scotland).\ud \ud Participants:\ud Individuals (n = 3,522, aged 70–82, 1,765 male) with a history of or risk factors for CVD were ranked in three groups depending on baseline homocysteine level, sex, and study site.\ud \ud Intervention:\ud Pravastatin (40 mg) versus placebo.\ud \ud Measurements:\ud Fatal and nonfatal CHD and mortality.\ud \ud Results:\ud In the placebo group, participants with a high homocysteine level (n = 588) had a 1.8 higher risk (95% confidence interval (CI) = 1.2–2.5, P = .001) of fatal and nonfatal CHD than those with a low homocysteine level (n = 597). The absolute risk reduction in fatal and nonfatal CHD with pravastatin treatment was 1.6% (95% CI = −1.6 to 4.7%) in the low homocysteine group and 6.7% (95% CI = 2.7–10.7%) in the high homocysteine group (difference 5.2%, 95% CI = 0.11–10.3, P = .046). Therefore, the number needed to treat (NNT) with pravastatin for 3.2 years for benefit related to fatal and nonfatal CHD events was 14.8 (95% CI = 9.3–36.6) for high homocysteine and 64.5 (95% CI = 21.4–∞) for low homocysteine.\ud \ud Conclusion:\ud In older persons at risk of CVD, those with high homocysteine are at highest risk for fatal and nonfatal CHD. With pravastatin treatment, this group has the highest absolute risk reduction and the lowest NNT to prevent fatal and nonfatal CHD.

Contains fulltext : 139289.pdf (Publisher’s version ) (Open Access) BACKGROUND: In clinical practice, GPs appeared to have an internalized concept of "vulnerability." This study investigates the variability between general practitioners (GPs) in their vulnerability-assessment of older persons. METHODS: Seventy-seven GPs categorized their 75-plus patients (n = 11392) into non-vulnerable, possibly vulnerable, and vulnerable patients. GPs personal and practice characteristics were collected. From a sample of 2828 patients the following domains were recorded: sociodemographic, functional [instrumental activities in daily living (IADL), basic activities in daily living (BADL)], somatic (number of diseases, polypharmacy), psychological (Mini-Mental State Examination, 15-item Geriatric Depression Scale; GDS-15) and social (De Jong-Gierveld Loneliness Scale; DJG). Variability in GPs' assessment of vulnerability was tested with mixed effects logistic regression. P-values for variability (pvar) were calculated by the log-likelihood ratio test. RESULTS: Participating GPs assessed the vulnerability of 10,361 patients. The median percentage of vulnerable patients was 32.0% (IQR 19.5 to 40.1%). From the somatic and psychological domains, GPs uniformly took into account the patient characteristics 'total number of diseases' (OR 1.7, 90% range = 0, p var = 1), 'polypharmacy' (OR 2.3, 90% range = 0, p var = 1) and 'GDS-15' (OR 1.6, 90% range = 0, p var = 1). GPs vary in the way they assessed their patients' vulnerability in the functional domain (IADL: median OR 2.8, 90% range 1.6, p var < 0.001, BADL: median OR 2.4, 90% range 2.9, p var < 0.001) and the social domain (DJG: median OR 1.2, 90% range = 1.2, p var < 0.001). CONCLUSIONS: GPs seem to share a medical concept of vulnerability, since they take somatic and psychological characteristics uniformly into account in the vulnerability-assessment of older persons. In the functional and social domains, however, variability was found. Vulnerability assessment by GPs might be a promising instrument to select older people for geriatric care if more uniformity could be achieved. TRIAL REGISTRATION: Netherlands Trial Register NTR1946.

Background In the aging population cardiovascular disease (CVD) is highly prevalent. Identification of very old persons at high risk of recurrent CVD is difficult, since traditional risk markers loose predictive value with age. Methods In a population-based sample of 282 85-year old participants with established CVD from the Leiden 85-plus Study, we studied predictive values of traditional cardiovascular risk markers, a history of major CVD (myocardial infarction, stroke or arterial surgery), and new cardiovascular biomarkers (estimated glomerular filtration rate (MDRD), C-reactive protein (CRP), homocysteine and N-terminal pro B-type natriuretic peptide (NT-proBNP)) regarding 5-year risk of recurrent cardiovascular events and mortality (composite endpoint). Results During complete 5-year follow-up 157 (56%) participants died. 109 (39%) had a cardiovascular event or died from cardiovascular causes. Individually related to the composite endpoint were: a history of major CVD (HR 1.5 (95%CI 1.03-2.3)), CRP (HR 1.3 (95%CI 1.03-1.5)), homocysteine (HR 1.4 (95%CI 1.2-2.6)) and NT-proBNP (HR 1.7 (95%CI 1.4-2.1)). A prediction model including all traditional risk markers yielded a C-statistic of 0.59 (95%CI 0.52-0.66). Of all five new markers only addition of NT-proBNP improved the C-statistic (0.67 (95%CI 0.61-0.74, p=0.023)). The categoryless net reclassification improvement for NT-proBNP was 39% (p=0.001), for a history of major CVD 27.2% (p=0.03) and for homocysteine 24.7% (p=0.04). Conclusions Among very old subjects with established CVD, NT-proBNP was the strongest risk marker for cardiovascular events and cardiovascular mortality. When estimating risk in secondary prevention in very old age, use of NT-proBNP should be considered.

The underlying pain mechanisms of chronic pancreatitis (CP) are incompletely understood, but recent research points to involvement of pathological central nervous system processing involving pain-relevant brain areas. We investigated the organization and connectivity of brain networks involved in nociceptive processing in patients with painful CP.Contact heat-evoked potentials (CHEPs) were recorded in 15 patients with CP and in 15 healthy volunteers. The upper abdominal area (sharing spinal innervation with the pancreatic gland) was used as a proxy of 'pancreatic stimulation', while stimulation of a heterologous region remote to the pancreas (right forearm) was used as a control. Subjective pain scores were assessed by visual analogue scale. The brain source organization and connectivity of CHEPs components were analysed.After pancreatic area stimulation, brain source analysis revealed abnormalities in the cingulate/operculo-insular network. A posterior shift of the operculo-insular source (p = 0.004) and an anterior shift of the cingulate source (p 0.001) were seen in CP patients, along with a decreased strength of the cingulate source (p = 0.01). The operculo-insular shift was positively correlated with the severity of patient clinical pain score (r = 0.61; p = 0.03). No differences in CHEPs characteristics or source localizations were seen following stimulation of the right forearm.CP patients showed abnormal cerebral processing after stimulation of the upper abdominal area. These changes correlated to the severity of pain the patient was experiencing. Since the upper abdominal area shares spinal innervation with the pancreatic gland, these findings likely reflect maladaptive neuroplastic changes, which are characteristic of CP.

Scintigraphy, the gold standard to measure gastric emptying, is expensive and not widely available. Therefore, we compared emptying of radiopaque markers (ROM) from the stomach, by use of fluoroscopy, with scintigraphy in patients with insulin-treated diabetes.On the same day we measured gastric emptying of 20 ROM using fluoroscopy and scintigraphic emptying of a standard solid meal. The subjects also completed a validated gastrointestinal (GI) symptom questionnaire.We included 115 patients with insulin-treated diabetes (median age 53, range 21-69 years; 59 women). A moderately strong correlation was demonstrated between scintigraphic (% retained at 2 h) and ROM emptying (markers retained at 6 h) (r = 0.47; P0.0001). Eighty-three patients had delayed gastric emptying with scintigraphy, whereas only 29 patients had delayed emptying of ROM. Of the 29 patients with delayed emptying of ROM, 28 also had delayed scintigraphic emptying. The sensitivity and specificity of the ROM test was 34% and 97%, respectively. Significant correlations were only noted between scintigraphic gastric emptying and GI symptom severity, with the strongest correlations for fullness/early satiety (r = 0.34; P0.001) and nausea/vomiting (r = 0.30; P0.001).A gastric emptying test with ROM is a widely available screening method to detect delayed gastric emptying in patients with diabetes, where a positive result seems reliable. However, a normal ROM test does not exclude delayed gastric emptying, and if the clinical suspicion of gastroparesis remains, scintigraphy should be performed. Results from scintigraphy also correlate with GI symptom severity, which ROM test did not.

Offset analgesia (OA) is a pain-inhibiting mechanism, defined as a disproportionately large decrease in pain perception in response to a discrete decrease in noxious stimulus intensity. Hence, the aims were (1) to investigate whether psychophysics and electroencephalography (EEG) can be assessed simultaneously during OA and (2) to assess whether OA is reproducible within the same day as well as between different days.Two separate studies investigated OA: Study I (13 healthy volunteers; seven men; 25.5 ± 0.65 years) aimed at determining the feasibility of recording psychophysics and EEG simultaneously during OA. Study II (18 healthy volunteers; 12 men; 34 ± 3.15 years) assessed reproducibility of OA in terms of psychophysics and EEG. Subjects were presented to a 30-s OA heat stimulus paradigm on the volar forearm and psychophysics, and EEG recordings were obtained throughout the procedure. Reproducibility was assessed within the same day and between different days, using intraclass correlation coefficients (ICCs). Additionally, the reproducible psychophysical parameters were correlated to relevant EEG frequency bands.Simultaneous recording of psychophysics and EEG affects the frequency distribution in terms of alpha suppression. Reproducibility was proven for the psychophysics and EEG frequency bands both within the same day (all ICCs0.62) and between different days (all ICCs0.66, except for the delta band). Correlations between psychophysics and EEG were found in the theta (4-8 Hz), alpha (8-12 Hz) and gamma (32-80 Hz) bands (all p0.01).OA is a robust and reproducible model for experimental pain research, making it suitable for future research.

Blunted rectal sensation (rectal hyposensitivity: RH) is present in almost one-quarter of patients with chronic constipation. The mechanisms of its development are not fully understood, but in a proportion, afferent dysfunction is likely. To determine if, in patients with RH, alteration of rectal sensory pathways exists, rectal evoked potentials (EPs) and inverse modeling of cortical dipoles were examined.Rectal EPs (64 channels) were recorded in 13 patients with constipation and RH (elevated thresholds to balloon distension) and 11 healthy controls, in response to electrical stimulation of the rectum at 10 cm from the anal verge using a bipolar stimulating electrode. Stimuli were delivered at pain threshold. Evoked potential peak latencies and amplitudes were analyzed, and inverse modeling was performed on traces obtained to determine the location of cortical generators.Pain threshold was higher in patients than controls [median 59 (range 23-80) mA vs 24 (10-55) mA; P = 0.007]. Median latency to the first negative peak was 142 (±24) ms in subjects compared with 116 (±15) ms in controls (P = 0.004). There was no difference in topographic analysis of EPs or location of cortical activity demonstrated by inverse modeling between groups.This study is the first showing objective evidence of alteration in the rectal afferent pathway of individuals with RH and constipation. Prolonged latencies suggest a primary defect in sensory neuronal function, while cerebral processing of visceral sensory information appears normal.

Background:Preventive care traditionally aims to prevent diseases or injuries. For older people, different aims of prevention, such as maintenance of independence and wellbeing, are increasingly important.Aim:To explore GPs' perspectives on preventive care for older people.Design and setting:Qualitative study comprising six focus groups with GPs in the Netherlands.Method:The focus-group discussions with 37 GPs were analysed using the framework analysis method.Results:Whether or not to implement preventive care for older people depends on the patient's individual level of vitality, as perceived by the GP. For older people with a high level of vitality, GPs confine their role to standardised disease-oriented prevention on a patient's request; when the vitality levels in older people fall, the scope of preventive care shifts from prevention of disease to prevention of functional decline. For older, vulnerable people, GPs expect most benefit from a proactive, individualised approach, enabling them to live as independently as possible. Based on these perspectives, a conceptual model for preventive care was developed, which describes GPs' different perspectives toward older people who are vulnerable and those with high levels of vitality. It focuses on five main dimensions: aim of care (prevention of disease versus prevention of functional decline), concept of care (disease model versus functional model), initiator (older persons themselves versus GP), target groups (people with requests versus specified risk groups), and content of preventive care (mainly cardiovascular risk management versus functional decline).Conclusion:GPs' perspectives on preventive care are determined by their perception of the level of vitality of their older patients. Preventive care for older people with high levels of vitality may consist of a standardised disease-oriented approach; those who are vulnerable will need an individualised approach to prevent functional decline.

Long-term diabetes mellitus (DM) has been associated with neuronal changes in the enteric, peripheral and/or central nervous system. Moreover, abnormal visceral sensation and gastrointestinal (GI) symptoms are seen in up to 75% of patients. To explore the role of diabetic autonomic neuropathy (DAN) in patients with long-standing DM, we investigated psychophysical responses and neuronal activity recorded as evoked brain potentials and dipolar source modelling.Fifteen healthy volunteers and 14 type-1 DM patients with DAN were assessed with a symptom score index characterizing upper GI abnormalities. Multichannel (62) electroencephalography was recorded during painful electrical stimulation of the lower oesophagus. Brain activity to painful stimulations was modelled using Brain Electrical Source Analysis (besa).Diabetic patients had higher stimulus intensities to evoke painful sensation (p ≤ 0.001), longer latencies of N2 and P2 components (both p ≤ 0.001), and lower amplitudes of P1-N2 and N2-P2 complexes (p ≤ 0.001; p = 0.02). Inverse modelling of brain sources showed deeper bilateral insular dipolar source localization (p = 0.002). Symptom score index was negatively correlated with the depth of insular activity (p = 0.004) and positively correlated with insular dipole strength (p = 0.03).DM patients show peripheral and central neuroplastic changes. Moreover, the role of abnormal insular processing may explain the appearance and persistence of GI symptoms related to DAN. This enhanced understanding of DAN may have future clinical and therapeutical implications.

Ano-rectal disorders are common in the general population. Although they are not life threatening conditions, they do represent a social stigma and a reduced quality of life for the sufferer. The underlying physiology of muscle function contributing to ano-rectal competence is complex and there is room for a much better understanding so that treatments can improve.A cylindrically shaped, liquid filled bag (12 cm long), mounted on a catheter was inserted into the anus and positioned straddling the ano-rectal region in 20 healthy volunteers (10 females). Series of volume-controlled distensions (40 mL min(-1) to 40 mL) were carried out and data on 16 CSA at 5 mm apart and bag pressure were recorded. Provocative tests using squeeze and cough at bag volumes of 20, 30, and 40 mL were carried out.Ramp distension of the anal canal showed that the opening pressure for females (mean, 11 mmHg) was higher than for males (mean, 5 mmHg) (P0.001). Geometric profile of the anal canal at low distension volumes showed narrow bands at proximal and distal ends of the anal profile and shortening of a middle narrow zone at higher volumes. Inter-individual differences were observed in the behavior of the proximal end and the distal end of the anal profile during squeeze.This distensibility technique provides an important new way of studying the anal canal and hence may have a role in testing sphincter competence in patients with disorders.

Gastrointestinal (GI) symptoms, such as nausea, vomiting, bloating, postprandial fullness, and abdominal pain, are frequent in patients with diabetes mellitus (DM). The pathogenesis is complex and multi-factorial. To determine easy accessible and valid biomarkers for disordered GI function in DM patients, we aimed to study esophageal mechanical parameters and their relation to symptoms typically arising from the digestive tract.Seventeen patients with longstanding DM and GI symptoms and 13 healthy controls were studied using ultrasound monitored esophageal distension. The sensory response was recorded and their symptoms registered. Biomechanical parameters, such as compliance and stiffness were computed from luminal diameters during distension based on the ultrasound images and from pressure data. Biomechanical and sensory parameters were correlated with the clinical data.Diabetes patients had reduced esophageal sensitivity compared with controls (P = 0.046). The esophageal compliance was reduced (P = 0.004) and the esophageal stiffness was increased (P = 0.004) in the diabetes patients. Among patients, both postprandial fullness/early satiety and bloating correlated negatively to the esophageal compliance parameters (all P 0.05).Patients with long-standing DM and GI symptoms had reduced esophageal sensitivity together with reduced compliance and increased stiffness, which were correlated to the patients' GI symptoms. Biomechanical parameters obtained during distension may serve as biomarker for similar pathophysiologic effects of diabetes in the stomach and small bowel. They may contribute to our understanding of the pathophysiology underlying GI dysfunction and symptoms in patients with longstanding DM.

Objective Neurophysiological studies to evaluate spatial attention in children with primary headache are lacking. Tactile spatial attention modulates the N140 somatosensory evoked potential (SEP) amplitude. The aims of the study are: (1) to investigate the effect of spatial attention on the N140 amplitude in children with migraine and tension-type headache (TTH) and in healthy children, and (2) to correlate the neurophysiological results with a neuropsychological test for spatial attention. Methods We studied 16 patients with migraine without aura (MoA), 12 TTH children and 10 healthy subjects. “Deux Barrage” test for spatial attention was administered. SEPs were recorded in a neutral condition (NC) and in a spatial attention condition (SAC). Results No significant differences in neuropsychological measures were found between MoA, TTH and healthy subjects. The N140 amplitude increase during SAC, as compared to NC, was significantly higher in patients than in healthy controls. Migraineurs showed a positive correlation between the N140 amplitude increase during SAC and their neuropsychological performance. Conclusions Although spatial attention performances in children with headache are as good as in controls, the N140 amplitude increase during SAC in headache patients suggests that the psychophysiological mechanisms subtending spatial attention are different from those in healthy children.

Objectives To identify appropriate screening conditions, stratified according to age and vulnerability, to prevent functional decline in older people. Design A RAND/University of California at Los Angeles appropriateness method. Setting The Netherlands. Participants A multidisciplinary panel of 11 experts. Measurements The panelists assessed the appropriateness of screening for 29 conditions mentioned in guidelines from four countries, stratified according to age (60-74, 75-84, ≥85) and health status (general, vital, and vulnerable) and received a literature overview for each condition, including the guidelines and up-to-date literature. After an individual rating round, panelists discussed disagreements and performed a second individual rating. The median of the second ratings defined the appropriateness of screening. Results The panel rated screening to be appropriate in three of the 29 conditions, indicating that screening was expected to prevent functional decline. Screening for insufficient physical activity was considered appropriate for all three age and health groups. Screening for cardiovascular risk factors and smoking was considered appropriate for the general and vital population aged 60 to 74. Of the 261 ratings, 63 (24%) were classified as uncertain, of which 42 (67%) concerned the vulnerable population. The panelists considered conditions inappropriate mainly because of lack of an adequate screening tool or lack of evidence of effective interventions for positive screened persons. Conclusion The expert panel considered screening older people to prevent functional decline appropriate for insufficient physical activity and smoking and cardiovascular risk in specific groups. For other conditions, sufficient evidence does not support screening. Based on their experience, panelists expected benefit from developing tests and interventions, especially for vulnerable older people. © 2011, Copyright the Authors Journal compilation © 2011, The American Geriatrics Society.

To identify electroencephalographic (EEG) biomarkers for the analgesic effect of pregabalin in patients with chronic visceral pain.This was a double-blind, placebo-controlled study in 31 patients suffering from visceral pain due to chronic pancreatitis. Patients received increasing doses of pregabalin (75mg-300mg twice a day) or matching placebo during 3 weeks of treatment. Pain scores were documented in a diary based on a visual analogue scale. In addition, brief pain inventory-short form (BPI) and quality of life questionnaires were collected prior to and after the study period. Multi-channel resting EEG was recorded before treatment onset and at the end of the study. Changes in EEG spectral indices were extracted, and individual changes were classified by a support vector machine (SVM) to discriminate the pregabalin and placebo responses. Changes in individual spectral indices and pain scores were correlated.Pregabalin increased normalized intensity in low spectral indices, most prominent in the theta band (3.5-7.5Hz), difference of -3.18, 95% CI -3.57, -2.80; P= 0.03. No changes in spectral indices were seen for placebo. The maximum difference between pregabalin and placebo treated patients was seen in the parietal region, with a classification accuracy of 85.7% (P= 0.009). Individual changes in EEG indices were correlated with changes in pain diary (P= 0.04) and BPI pain composite scores (P= 0.02).Changes in spectral indices caused by slowing of brain oscillations were identified as a biomarker for the central analgesic effect of pregabalin. The developed methodology may provide perspectives to assess individual responses to treatment in personalized medicine.

Pregabalin has a broad spectrum of analgesic and antihyperalgesic activity in both basic and clinical studies. However, its mechanisms and sites of action have yet to be determined in humans.To assess the antinociceptive effect of pregabalin on experimental gut pain in patients with visceral hyperalgesia due to chronic pancreatitis and to reveal putative changes in corresponding central pain processing as assessed by evoked brain potentials.Thirty-one patients were randomly assigned to receive increasing doses of pregabalin or placebo for three consecutive weeks. Perceptual thresholds to electrical stimulation of the sigmoid with recording of corresponding evoked brain potentials were obtained at baseline and study end. The brain source localisations reflecting direct neuronal activity were fitted by a five-dipole model projected to magnetic resonance imaging of the individuals' brains.As compared to placebo, pregabalin significantly increased the pain threshold to electrical gut stimulation from baseline (P=0.02). No differences in evoked brain potential characteristics were seen, neither after pregabalin nor placebo treatment (all P0.05). In agreement with this, brain source locations remained stable during study treatment (all P0.05).Pregabalin was superior to placebo for attenuation of experimental visceral pain in chronic pancreatitis patients. We suggest its antinociceptive effects to be mediated primarily through sub-cortical mechanisms.

Background: prevention of disability is an important aim of healthcare for older persons. Selection of persons at risk is a first crucial step in this process. Objectives: this study investigates the predictive value of multimorbidity for the development of disability in the general population of very old people and the role of cognitive impairment in this association. Design: the Leiden 85-plus Study (1997–2004) is an observational prospective cohort study with 5 years of follow-up. Setting: general population of the city of Leiden, the Netherlands. Subjects: population based sample of 594 participants aged 85 years. Methods: disability in activities of daily living (ADL) was measured annually for 5 years with the Groningen Activity Restriction Scale (range 9–36, 9 = optimal). Multimorbidity is defined as the presence of two or more chronic diseases at age 85 years. Cognitive function was measured at baseline with the mini-mental state examination (MMSE). Results: at baseline participants with multimorbidity had higher ADL disability scores compared with those without [median 11 inter-quartile range (IQR 9–16) versus 9 (IQR 9–13) ADL points, Mann–Whitney U test P 0.100). Conclusion: the predictive value of multimorbidity for the increase in ADL disability varies with cognitive function in very old people. In very old people with good cognitive function, multimorbidity predicts accelerated increase in ADL disability. This relation is absent in very old people with cognitive impairment.

Acute hyperglycaemia is known to increase gastrointestinal (GI) sensitivity in healthy subjects and may contribute to the increased prevalence of GI symptoms in diabetes patients. The aim of this study was to evaluate the effect of acute hyperglycaemia on perception and brain responses to painful visceral and somatic stimuli in diabetic patients.The sensitivity and evoked brain potentials (EPs) to electrical oesophageal and median nerve stimulations were assessed in 14 type-1 diabetes patients with autonomic neuropathy and GI symptoms using a hyperinsulinaemic clamp at 6 and 15 mM.No differences between the normo- and hyperglycaemic conditions were found in sensitivity to both oesophageal (P=0·72) and median nerve (P=0·66) stimulations. The latencies and amplitudes of EPs did not differ between the normo- and hyperglycaemic conditions following oesophageal (P=0·53 and 0·57) and median nerve (P=0·78 and 0·52) stimulations.Acute hyperglycaemia itself does not contribute to the sensations in patients with longstanding diabetes and autonomic neuropathy. Any potential sensory effects of acute hyperglycaemia can likely be blurred by the neuropathic-like changes in the sensory nervous system.

No studies have examined the risk of upper gastrointestinal diseases among patients with unexplained chest/epigastric pain (UCEP) and a normal upper endoscopy.To examine the relative risk of peptic ulcer, oesophagitis, pancreatitis or gallstone in UCEP patients.This Danish 10-year cohort study focused on UCEP patients (n = 386), diagnosed in 1992-93. Ten age- and gender-matched controls were selected per patient from Denmark's Civil Registration System (n = 3860). Kaplan-Meier analysis and Cox's regression analysis was used to calculate the risk of hospitalization for peptic ulcer, oesophagitis, pancreatitis or gallstone.Compared with controls, the adjusted relative risks among UCEP patients1 andor = 1 year after upper endoscopy were for peptic ulcer 2.0 [95% confidence interval (CI) 0.2-18.4] and 1.7 (95% CI 0.9-3.4), for oesophagitis 8.2 (95% CI 1.2-59.2) and 1.9 (95% CI 0.7-5.0), for pancreatitis 9.2 (95% CI 2.0-41.8) and 3.9 (95% CI 1.4-10.5), and for gallstone 14.1 (95% CI 5.4-37.2) and 3.3 (95% CI 1.9-5.8).UCEP is positively associated with all study outcomes especially in the first year after upper endoscopy, indicating that peptic ulcer, oesophagitis, pancreatitis or gallstone could be underlying early UCEP symptoms. However, the long-term association remained strong for pancreatitis and gallstone, suggesting a genuine excess risk.

A new system for polysomnographic recording at home is presented. It consists of a 12 to 24-channel amplifier system with direct digitization of the polygraph signals using a portable computer. Sampling frequency, amplification and filter settings can be defined by the user, and the signals are evaluated at bedside. Technical testing proved a high signal/noise ratio, linear amplification and a good signal quality. Clinical testing of the first 100 recordings showed that they were acceptable for conventional sleep scoring in 98 cases. A comparison of two consecutive recordings was done in 9 healthy subjects and 11 patients with rheumatic disorders. Using conventional sleep staging, only a slight "first night effect" (FNE) was demonstrated in the sleep architecture. Power spectral analysis using autoregressive modeling demonstrated only a difference of power between the 2 nights in the beta (14.5-25 Hz) band. In conclusion, the usability and technical advantages make the system very suitable for ambulatory recordings and only a minimal FNE should be considered when results are evaluated.

The value of muscle biopsy in fibromyalgia is still questioned. In this study we obtained 49 quadriceps biopsies from 20 patients and compared them blindly to 15 biopsies from five normal controls. Using light microscopy, histochemical and immunoenzymatic methods we found no definite evidence of muscle disease. Nevertheless, we subjected biopsies from nine of the patients and five other controls for further ultrastructural evaluations and demonstrated pathologic findings e.g. empty sleeves of basement membrane, many lipofuscin bodies and other degenerative changes. We conclude that ultrastructural evaluation cannot yet be used for diagnostic purposes, but the negative findings at light microscopy, including histochemical and immunoenzymatic techniques, might be of importance in evaluating difficult cases.

Chronic central pain is a frequent complication after spinal cord injury. Anticonvulsant drugs, among them valproate, have been recommended for treatment. In this paper we conducted a double-blind, cross-over study comparing valproate and placebo for severe chronic central pain. During the study, serum concentration of valproate, pain and side effects were registered and the dose was adjusted according to these. No significant analgesic effects of valproate could be demonstrated although serum concentration and dose reached a high level. Few studies of pain following spinal cord injury exist and we recommend that further studies be performed.

A portable digital recording system and the Nightingale sleep analyser have been applied to record polygraphical sleep signals in patients suffering from chronic pain. Using ambulatory recording the patient can sleep at home making the sleep more natural and reducing the costs. The recording system gives digital recordings of very good quality. It is shown that the Nightingale sleep analyser performs automatic sleep analysis with a quality comparable to visual interrater performance on disordered sleep. It furthermore provides means for extraction of spectral information useful for the description of the sleep-wakefulness processes and for diagnosing the sleep disorders. Using AR-model-based power spectral analysis, it is also shown that the power content in the alpha band relative to the delta power is significantly higher in patients suffering from non-specific chronic pain as compared to normal persons.

To evaluate sleep architecture and self-reported complaints in patients with fibromyalgia (FS). Forty patients and 10 age standardized healthy controls were included. All participants were women.All patients and controls underwent a clinical examination and gave answers to a questionnaire. Polysomnography was done in 20 patients and in all controls.The percent arousal time and arousal index were higher (p0.05 and0.01, respectively) among FS compared to controls, but no other differences were found in sleep architecture. Ten of the patients with FS and 2 controls showed an apnea-hypoapnea index above 5/h (NS). The arousal time and arousal index were higher in patients with apnea-hypoapnea indexor = 5 compared to controls with apnea-hypoapnea index5 [mean (SD)] [arousal time: 4.5 (3.2) vs 0.7 (0.7), p0.001, arousal index: 14.9 (10.8) vs 2.4 (3.7), p0.001]. In patients with FS with apnea-hypoapnea index5 the arousal time was higher (2.0 (1.2), p0.05) and arousal index marginally higher (5.6 (3.2), p = 0.07) compared to the controls. No other differences were found in sleep structure. Insomnia (difficulties falling asleep, maintaining sleep, early morning awakening), tiredness, mood, cognitive disturbances and muscular pain were all reported more commonly by patients with FS than controls. A subdivision of the patients with FS into those with apnea-hypoapnea index5 and apnea-hypoapnea indexor = 5 did not change these findings.We conclude, that patients with FS show minor polysomnographic findings, with a higher occurrence of arousals. The arousals were in part explained by respiratory abnormalities. Patients with FS have several complaints, including insomnia. Some of these may relate to sleep fragmentation. Controlled studies are a requirement in investigations of sleep disorders in fibromyalgia.

Primary fibromyalgia is probably a frequent disregarded disease, making differential diagnostic problems towards other kinds of rheumatologic diseases. The clinical manifestations, pathogenesis and treatment of primary fibromyalgia are discussed and the literature reviewed.

Epidemiologic data from 109 patients admitted to hospital in the period 1/1/1980-/31/12/1984 with spinal cord injuries are presented. The mean age was 29 years, there was a preponderance of males and the most frequent cause of the spinal cord injury was road accidents. The material was compared with the epidemiologic and social data of other studies. A total of 58 patients, chiefly users of wheelchairs, were followed up on average six years after the first admission. It was thus possible to form an idea of the complications of the spinal cord injury and the effectiveness of the treatment. The premorbid educational level of the patients was relatively low. The most frequent complications were spasms (74%), pressure sores (67%), pains (58%), and frequent urinary tract infections (71%). The consumption of medicine reflected the pattern of complications. The most common method of micturition was reflex voiding by tapping. These results were comparable with previous studies. It is concluded that the treatment of spinal cord injuries is a specialised task and only continuous evaluation can ensure optimum treatment.