The health burden and costs of incident fractures attributable to osteoporosis from 2010 to 2050 in Germany—a demographic simulation model

Summary

To predict the burden of incident osteoporosis attributable fractures (OAF) in Germany, an economic simulation model was built. The burden of OAF will sharply increase until 2050. Future demand for hospital and long-term care can be expected to substantially rise and should be considered in future healthcare planning.

Introduction

The aim of this study was to develop an innovative simulation model to predict the burden of incident OAF occurring in the German population, aged >50, in the time period of 2010 to 2050.

Methods

A Markov state transition model based on five fracture states was developed to estimate costs and loss of quality adjusted life years (QALYs). Demographic change was modelled using individual generation life tables. Direct (inpatient, outpatient, long-term care) and indirect fracture costs attributable to osteoporosis were estimated by comparing Markov cohorts with and without osteoporosis.

Results

The number of OAF will rise from 115,248 in 2010 to 273,794 in 2050, cumulating to approximately 8.1 million fractures (78 % women, 22 % men) during the period between 2010 and 2050. Total undiscounted incident OAF costs will increase from around 1.0 billion Euros in 2010 to 6.1 billion Euros in 2050. Discounted (3 %) cumulated costs from 2010 to 2050 will amount to 88.5 billion Euros (168.5 undiscounted), with 76 % being direct and 24 % indirect costs. The discounted (undiscounted) cumulated loss of QALYs will amount to 2.5 (4.9) million.

Conclusions

We found that incident OAF costs will sharply increase until the year 2050. As a consequence, a growing demand for long-term care as well as hospital care can be expected and should be considered in future healthcare planning. To support decision makers in managing the future burden of OAF, our model allows to economically evaluate population- and risk group-based interventions for fracture prevention in Germany.     

Hilar interneuron vulnerability distinguishes aged rats with memory impairment

Hippocampal interneuron populations are reportedly vulnerable to normal aging. The relationship between interneuron network integrity and age‐related memory impairment, however, has not been tested directly. That question was addressed in the present study using a well‐characterized model in which outbred, aged, male Long‐Evans rats exhibit a spectrum of individual differences in hippocampal‐dependent memory. Selected interneuron populations in the hippocampus were visualized for stereological quantification with a panel of immunocytochemical markers, including glutamic acid decarboxylase‐67 (GAD67), somatostatin, and neuropeptide Y. The overall pattern of results was that, although the numbers of GAD67‐ and somatostatin‐positive interneurons declined with age across multiple fields of the hippocampus, alterations specifically related to the cognitive outcome of aging were observed exclusively in the hilus of the dentate gyrus. Because the total number of NeuN‐immunoreactive hilar neurons was unaffected, the decline observed with other markers likely reflects a loss of target protein rather than neuron death. In support of that interpretation, treatment with the atypical antiepileptic levetiracetam at a low dose shown previously to improve behavioral performance fully restored hilar SOM expression in aged, memory‐impaired rats. Age‐related decreases in GAD67‐ and somatostatin‐immunoreactive neuron number beyond the hilus were regionally selective and spared the CA1 field of the hippocampus entirely. Together these findings confirm the vulnerability of hippocampal interneurons to normal aging and highlight that the integrity of a specific subpopulation in the hilus is coupled with age‐related memory impairment. J. Comp. Neurol. 521:3508‐3523, 2013. © 2013 Wiley Periodicals, Inc.     

Remediation of deficits affecting different components of the spelling process

Background: There have been relatively few studies concerned with the treatment of spelling deficits. Among these, there have been a small number that have targeted specific components of the spelling process. Although most of these studies report success using treatments that involve repeated spelling and/or copy, the results have been mixed, especially as concerns the generalisation of treatment benefits to untreated items. Aims: This investigation was designed to examine the responsiveness to the same treatment protocol of deficits affecting different cognitive mechanisms of the spelling process. Methods & Procedures: We applied the same delayed-copy treatment protocol to two individuals with selective deficits of the orthographic output lexicon and the graphemic buffer. The two individuals were otherwise matched in terms of the severity of their deficits and their general cognitive profiles. Outcomes & Results: Both individuals exhibited long-lasting word-specific benefits from the treatment. However, they differed in that the graphemic buffer deficit exhibited generalisation to untreated words, whereas the orthographic output lexicon did not. Conclusions: The absence of presence of generalisation effects in response to the successful treatment of target items is determined by the specific cognitive component/s that constitute the source of the deficit.     

Clenched fist injury complicated by septic arthritis and osteomyelitis treated with negative pressure wound therapy: One case report

We reported a 30 years old man who suffered a bite wound of the right hand in a fight. Two days after the injury, he was admitted in emergency because of stab wound above the head of the third metacarpal bone. He presented the swelling, redness, pain and fever. Primary revision confirmed only partial lesion of the extensor apparatus. During the following days, we recorded a deterioration of local findings and magnetic resonance imaging revealed osteomyelitis and septic arthritis of the third metacarpophalangeal joint. The wound was then revised several times using negative pressure wound therapy in combination with intravenous antibiotics. After resolution of clinical and laboratory findings, the wound was finally closed by delayed primary suture. Clenched fist injury is a medical emergency that requires immediate surgical revision. We treated clenched fist injury with the development of septic arthritis and osteomyelitis with negative pressure wound therapy and obtained good outcomes.     

Microevolution and patterns of dissemination of the JP2 clone of Aggregatibacter (Actinobacillus) actinomycetemcomitans

The natural history, microevolution, and patterns of interindividual transmission and global dissemination of the JP2 clone of Aggregatibacter (Actinobacillus) actinomycetemcomitans were studied by population genetic analysis. The JP2 clone is strongly associated with aggressive periodontitis in adolescents of African descent and differs from other clones of the species by several genetic peculiarities, including a 530-bp deletion in the promoter region of the leukotoxin gene operon, which results in increased leukotoxic activity. Multilocus sequence analysis of 82 A. actinomycetemcomitans strains, 66 of which were JP2 clone strains collected over a period of more than 20 years, confirmed that there is a clonal population structure with evolutionary lineages corresponding to serotypes. Although genetically highly conserved, as shown by alignment of sequences of eight housekeeping genes, strains belonging to the JP2 clone had a number of point mutations, particularly in the pseudogenes hbpA and tbpA. Characteristic mutations allowed isolates from individuals from the Mediterranean area and from West Africa, including the Cape Verde Islands, to be distinguished. The patterns of mutations indicate that the JP2 clone initially emerged as a distinct genotype in the Mediterranean part of Africa approximately 2,400 years ago and subsequently spread to West Africa, from which it was transferred to the American continents during the transatlantic slave trade. The sustained exclusive colonization of individuals of African descent despite geographical separation for centuries suggests that the JP2 clone has a distinct host tropism. The colonization of family members by JP2 clone strains with unique point mutations provides strong evidence that there is intrafamilial transmission and suggests that dissemination of the JP2 clone is restricted to close contacts.     

Tinnitus behavior and hearing function correlate with the reciprocal expression patterns of BDNF and Arg3.1/arc in auditory neurons following acoustic trauma

The molecular changes following sensory trauma and the subsequent response of the CNS are poorly understood. We focused on finding a molecular tool for monitoring the features of excitability which occur following acoustic trauma to the auditory system. Of particular interest are genes that alter their expression pattern during activity-induced changes in synaptic efficacy and plasticity. The expression of brain-derived neurotrophic factor (BDNF), the activity-dependent cytoskeletal protein (Arg3.1/arc), and the immediate early gene c-Fos were monitored in the peripheral and central auditory system hours and days following a traumatic acoustic stimulus that induced not only hearing loss but also phantom auditory perception (tinnitus), as shown in rodent animal behavior models. A reciprocal responsiveness of activity-dependent genes became evident between the periphery and the primary auditory cortex (AI): as c-Fos and BDNF exon IV expression was increased in spiral ganglion neurons, Arg3.1/arc and (later on) BDNF exon IV expression was reduced in AI. In line with studies indicating increased spontaneous spike activity at the level of the inferior colliculus (IC), an increase in BDNF and GABA-positive neurons was seen in the IC. The data clearly indicate the usefulness of Arg3.1/arc and BDNF for monitoring trauma-induced activity changes and the associated putative plasticity responses in the auditory system.