Multimorbidity and comorbidity in the Dutch population - data from general practices

<p>Abstract</p> <p>Background</p> <p>Multimorbidity is increasingly recognized as a major public health challenge of modern societies. However, knowledge about the size of the population suffering from multimorbidity and the type of multimorbidity is scarce. The objective of this study was to present an overview of the prevalence of multimorbidity and comorbidity of chronic diseases in the Dutch population and to explore disease clustering and common comorbidities.</p> <p>Methods</p> <p>We used 7 years data (2002–2008) of a large Dutch representative network of general practices (212,902 patients). Multimorbidity was defined as having two or more out of 29 chronic diseases. The prevalence of multimorbidity was calculated for the total population and by sex and age group. For 10 prevalent diseases among patients of 55 years and older (N = 52,014) logistic regressions analyses were used to study disease clustering and descriptive analyses to explore common comorbid diseases.</p> <p>Results</p> <p>Multimorbidity of chronic diseases was found among 13% of the Dutch population and in 37% of those older than 55 years. Among patients over 55 years with a specific chronic disease more than two-thirds also had one or more other chronic diseases. Most disease pairs occurred more frequently than would be expected if diseases had been independent. Comorbidity was not limited to specific combinations of diseases; about 70% of those with a disease had one or more extra chronic diseases recorded which were not included in the top five of most common diseases.</p> <p>Conclusion</p> <p>Multimorbidity is common at all ages though increasing with age, with over two-thirds of those with chronic diseases and aged 55 years and older being recorded with multimorbidity. Comorbidity encompassed many different combinations of chronic diseases. Given the ageing population, multimorbidity and its consequences should be taken into account in the organization of care in order to avoid fragmented care, in medical research and healthcare policy.</p

Outflow tract septation and the aortic arch system in reptiles: lessons for understanding the mammalian heart

Animal science

The influence of population characteristics on variation in general practice based morbidity estimations

Contains fulltext : 96442.pdf (publisher's version ) (Open Access

Over-expression of mitochondrial creatine kinase in the murine heart improves functional recovery and protects against injury following ischaemia–reperfusion

Aims Mitochondrial creatine kinase (MtCK) couples ATP production via oxidative phosphorylation to phosphocreatine in the cytosol, which acts as a mobile energy store available for regeneration of ATP at times of high demand. We hypothesized that elevating MtCK would be beneficial in ischaemia–reperfusion (I/R) injury. Methods and results Mice were created over-expressing the sarcomeric MtCK gene with αMHC promoter at the Rosa26 locus (MtCK-OE) and compared with wild-type (WT) littermates. MtCK activity was 27% higher than WT, with no change in other CK isoenzymes or creatine levels. Electron microscopy confirmed normal mitochondrial cell density and mitochondrial localization of transgenic protein. Respiration in isolated mitochondria was unaltered and metabolomic analysis by 1 H-NMR suggests that cellular metabolism was not grossly affected by transgene expression. There were no significant differences in cardiac structure or function under baseline conditions by cine-MRI or LV haemodynamics. In Langendorff-perfused hearts subjected to 20 min ischaemia and 30 min reperfusion, MtCK-OE exhibited less ischaemic contracture, and improved functional recovery (Rate pressure product 58% above WT; P < 0.001). These hearts had reduced myocardial infarct size, which was confirmed in vivo: 55 ± 4% in WT vs. 29 ± 4% in MtCK-OE; P < 0.0001). Isolated cardiomyocytes from MtCK-OE hearts exhibited delayed opening of the mitochondrial permeability transition pore (mPTP) compared to WT, which was confirmed by reduced mitochondrial swelling in response to calcium. There was no detectable change in the structural integrity of the mitochondrial membrane. Conclusions Modest elevation of MtCK activity in the heart does not adversely affect cellular metabolism, mitochondrial or in vivo cardiac function, but modifies mPTP opening to protect against I/R injury and improve functional recovery. Our findings support MtCK as a prime therapeutic target in myocardial ischaemia

Cytoarchitectural and metabolic adaptations in muscles with mitochondrial and cytosolic creatine kinase deficiencies

Item does not contain fulltext12 p

Cholinergic Mechanisms of Target Oddball Stimuli Detection: The Late “P300-Like” Event-Related Potential in Rats

Event-related potentials (ERPs) and oscillations (EROs) provide powerful tools for studying the brain’s synaptic function underlying information processing. The P300 component of ERPs indexing attention and working memory shows abnormal amplitude and latency in neurological and psychiatric diseases that are sensitive to pharmacological agents. In the active auditory oddball discriminant paradigm, behavior and auditory-evoked potentials (AEPs) were simultaneously recorded in awake rats to investigate whether P300-like potentials generated in rats responding to rare target oddball tones are sensitive to subcutaneous modulation of the cholinergic tone by donepezil (1 mg/kg) and scopolamine (0.64 mg/kg). After operant training, rats consistently discriminate rare target auditory stimuli from frequent irrelevant nontarget auditory stimuli by a higher level of correct lever presses (i.e., accuracy) in target trials associated with a food reward. Donepezil attenuated the disruptive effect of scopolamine on the level of accuracy and premature responses in target trials. Larger P300-like peaks with early and late components were revealed in correct rare target stimuli trials as compared to frequent tones. Donepezil enhanced the peak amplitude of the P300-like component to target stimuli and evoked slow theta and gamma oscillations, whereas scopolamine altered the amplitude of the P300-like component and EROs to target stimuli. Pretreatment with donepezil attenuated effects of scopolamine on the peak amplitude of the P300-like component and on EROs. This study provides evidence that AEP P300-like responses can be elicited by rats engaged in attentive and memory processing of target stimuli and outline the relevance of the cholinergic system in stimulus discrimination processing. The findings highlight the sensitivity of this translational index for investigating brain circuits and/or novel pharmacological agents, which modulate cholinergic transmission associated with increased allocation of attentional resources

Pharmacological correlation between the formalin test and the neuropathic pain behavior in different species with chronic constriction injury.

Item does not contain fulltextResearch on mechanisms of drug action, and preclinical screening of molecules with a potential activity on neuropathic pain requires extensive animal work. The chronic constriction injury model is one of the best-characterized models of neuropathic pain behavior in rats, but requires extensive time consuming operations and animal handling. The formalin test is easier to perform, and a well validated model. The latter may serve as an effective prescreening test of molecules and may facilitate drug targeting. In the present study the activity of different pharmacological reference compounds was tested in rats and gerbils on the cold plate for animals that had undergone chronic constriction injury and in the second phase of the formalin test. In rats, a comparable outcome in both test conditions was observed for morphine, fentanyl, MK-801 and flunarizine. Clonidine had more activity in the second phase of the formalin test, whereas baclofen, tramadol, amitryptiline, ketamine and topiramate showed more activity in the cold plate. In gerbils, both test conditions yielded comparable results for fentanyl and ketoprofen. Tramadol and CP-96345 tended to have more activity in the second phase of the formalin test, whereas morphine, SR-48968, SR-142801 and R116301 demonstrated more activity in the cold plate test. This study demonstrates a good correlation between the second phase of the formalin test and the cold allodynia in the CCI model for, both for rats and gerbils. Drugs with a proven activity in humans, used as reference compounds, also showed good pharmacological activity in this animal study

External Validation of EPICON: A Grouping System for Estimating Morbidity Rates Using Electronic Medical Records

Objective: To externally validate EPICON, a Computerized system for grouping diagnoses from EMRs in general practice into episodes of care. These episodes can be used for estimating morbidity rates. Design: Comparative observational study. Measurements: Morbidity rates from an independent dataset, based on episode-oriented EMRs, were used as the gold standard. The EMRs in this dataset contained diagnoses which were manually grouped by GPs. The authors ungrouped these diagnoses and regrouped them automatically into episodes using EPICON. The authors then used these episodes to estimate morbidity rates that were compared to the gold standard. The differences between the two sets of morbidity rates were calculated and the authors analyzed large as well as structural differences to establish possible causes. Results: In general, the morbidity rates based on EPICON deviate only slightly from the gold standard. Out of 675 diagnoses, 36 (5%) were considered to be deviating diagnoses. The deviating diagnoses showed differences for two main reasons: "differences in rules between the two methods of episode construction" and "inadequate performance of EPICON." Conclusion: The EPICON system performs well for the large majority of the morbidity rates. We can therefore conclude that EPICON is useful for grouping episodes to estimate morbidity rates using EMRs from general practices. Morbidity rates of diseases with a broad range of symptoms should, however, be interpreted cautiously

Diamonds are for ever?: the welfare effects of national champions

Philips, Akzo Nobel, ING, Shell, ASML, Heineken en Ahold - Nederland heeft flink wat kampioenen in huis, maar de Nederlandse overheid voert geen expliciet nationale kampioenenbeleid, zoals bijvoorbeeld de Duitsers en Fransen dat wel doen. Frankrijk heeft recent zelfs nieuw beleid geformuleerd onder de noemer ‘economisch patriottisme’. Het Franse argument is simpel : « Il y a un patriotisme économique parce qu'il y a une guerre économique ». Doet Nederland er economisch gezien verstandig aan om het Franse voorbeeld te volgen? SEO Economisch onderzoek onderzocht samen met PwC voor het ministerie van Economische Zaken of nationale kampioenenbeleid effectief is en zo ja, of het efficiënt is Overheden die actief kampioenenbeleid voeren, gaan ervan uit dat dit beleid goed voor de economie is. Net als met elk overheidsingrijpen ligt de bewijslast bij de overheid, die het beleid moet kunnen rechtvaardigen door het welvaartsverhogende effect ervan aan te tonen. In ons onderzoek hebben wij geen bewijs gevonden dat nationale kampioenenbeleid in het algemeen inderdaad effectief en efficiënt is. Kampioenenbeleid kan marktuitkomsten alleen dan verbeteren als het gericht is op het corrigeren van marktfalens (op bijv. de kapitaalmarkt waar te weinig geld beschikbaar is voor ‘infant industries’) of op het flexibeler maken van de arbeidsmarkt