86 research outputs found
Did Medicare Induce Pharmaceutical Innovation?
The introduction of Medicare in 1965 was the single largest change in health insurance coverage in U.S. history. Many economists and commentators have conjectured that the introduction of Medicare may have also been an important impetus for the development of new drugs that are now commonly used by the elderly and have substantially extended their life expectancy. In this paper, we investigate whether Medicare induced pharmaceutical innovations directed towards the elderly. Medicare could have played such a role only if two conditions were met. First, Medicare would have to increase drug spending by the elderly. Second, the pharmaceutical companies would have to respond to the change in market size for drugs caused by Medicare by changing the direction of their research. Our empirical work finds no evidence of a "first-stage" effect of Medicare on prescription drug expenditure by the elderly. Correspondingly, we also find no evidence of a shift in pharmaceutical innovation towards therapeutic categories most used by the elderly. On the whole, therefore, our evidence does not provide support for the hypothesis that Medicare had a major effect on the direction of pharmaceutical innovation.
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Did Medicare Induce Pharmaceutical Innovation?
The introduction of Medicare in 1965 was the single largest change in health insurance coverage in U.S. history. Many economists and commentators have conjectured that the introduction of Medicare may have also been an important impetus for the development of new drugs that are now commonly used by the elderly and have substantially extended their life expectancy. In this paper, we investigate whether Medicare induced pharmaceutical innovations directed towards the elderly. Medicare could have played such a role only if two conditions were met. First, Medicare would have to increase drug spending by the elderly. Second, the pharmaceutical companies would have to respond to the change in market size for drugs caused by Medicare by changing the direction of their research. Our empirical work finds no evidence of a "first-stage" effect of Medicare on prescription drug expenditure by the elderly. Correspondingly, we also find no evidence of a shift in pharmaceutical innovation towards therapeutic categories most used by the elderly. On the whole, therefore, our evidence does not provide support for the hypothesis that Medicare had a major effect on the direction of pharmaceutical innovation.Economic
Ovalbumin sensitization and challenge increases the number of lung cells possessing a mesenchymal stromal cell phenotype
Abstract Background Recent studies have indicated the presence of multipotent mesenchymal stromal cells (MSCs) in human lung diseases. Excess airway smooth muscle, myofibroblasts and activated fibroblasts have each been noted in asthma, suggesting that mesenchymal progenitor cells play a role in asthma pathogenesis. We therefore sought to determine whether MSCs are present in the lungs of ovalbumin (OVA)-sensitized and challenged mice, a model of allergic airways disease. Methods Balb/c mice were sensitized and challenged with PBS or OVA over a 25 day period. Flow cytometry as well as colony forming and differentiation potential were used to analyze the emergence of MSCs along with gene expression studies using immunochemical analyses, quantitative polymerase chain reaction (qPCR), and gene expression beadchips. Results A CD45-negative subset of cells expressed Stro-1, Sca-1, CD73 and CD105. Selection for these markers and negative selection against CD45 yielded a population of cells capable of adipogenic, osteogenic and chondrogenic differentiation. Lungs from OVA-treated mice demonstrated a greater average colony forming unit-fibroblast (CFU-F) than control mice. Sorted cells differed from unsorted lung adherent cells, exhibiting a pattern of gene expression nearly identical to bone marrow-derived sorted cells. Finally, cells isolated from the bronchoalveolar lavage of a human asthma patient showed identical patterns of cell surface markers and differentiation potential. Conclusions In summary, allergen sensitization and challenge is accompanied by an increase of MSCs resident in the lungs that may regulate inflammatory and fibrotic responses.http://deepblue.lib.umich.edu/bitstream/2027.42/78265/1/1465-9921-11-127.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78265/2/1465-9921-11-127.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/78265/3/1465-9921-11-127-S1.DOCPeer Reviewe
Dissecting the shared genetic basis of migraine and mental disorders using novel statistical tools
Migraine is three times more prevalent in people with bipolar disorder or depression. The relationship between
schizophrenia and migraine is less certain although glutamatergic and serotonergic neurotransmission are implicated in both. A shared genetic basis to migraine and mental disorders has been suggested but previous studies
have reported weak or non-significant genetic correlations and five shared risk loci. Using the largest samples to
date and novel statistical tools, we aimed to determine the extent to which migraine’s polygenic architecture
overlaps with bipolar disorder, depression and schizophrenia beyond genetic correlation, and to identify shared
genetic loci.
Summary statistics from genome-wide association studies were acquired from large-scale consortia for migraine
(n cases = 59 674; n controls = 316 078), bipolar disorder (n cases = 20 352; n controls = 31 358), depression
(n cases = 170 756; n controls = 328 443) and schizophrenia (n cases = 40 675, n controls = 64 643). We applied the bivariate causal mixture model to estimate the number of disorder-influencing variants shared between migraine
and each mental disorder, and the conditional/conjunctional false discovery rate method to identify shared loci.
Loci were functionally characterized to provide biological insights.
Univariate MiXeR analysis revealed that migraine was substantially less polygenic (2.8 K disorder-influencing variants) compared to mental disorders (8100–12 300 disorder-influencing variants). Bivariate analysis estimated that
800 (SD = 300), 2100 (SD = 100) and 2300 (SD = 300) variants were shared between bipolar disorder, depression and
schizophrenia, respectively. There was also extensive overlap with intelligence (1800, SD = 300) and educational attainment (2100, SD = 300) but not height (1000, SD = 100). We next identified 14 loci jointly associated with migraine
and depression and 36 loci jointly associated with migraine and schizophrenia, with evidence of consistent genetic
effects in independent samples. No loci were associated with migraine and bipolar disorder. Functional annotation
mapped 37 and 298 genes to migraine and each of depression and schizophrenia, respectively, including several
novel putative migraine genes such as L3MBTL2, CACNB2 and SLC9B1. Gene-set analysis identified several putative
gene sets enriched with mapped genes including transmembrane transport in migraine and schizophrenia.
Most migraine-influencing variants were predicted to influence depression and schizophrenia, although a minority
of mental disorder-influencing variants were shared with migraine due to the difference in polygenicity. Similar
overlap with other brain-related phenotypes suggests this represents a pool of ‘pleiotropic’ variants that influence
vulnerability to diverse brain-related disorders and traits. We also identified specific loci shared between migraine and each of depression and schizophrenia, implicating shared molecular mechanisms and highlighting candidate
migraine genes for experimental validation
Inside Post-Socialist Courts: The Determinants of Adjudicatory Outcomes in Slovenian Commercial Disputes
Cerebral microbleeds and intracranial haemorrhage risk in patients anticoagulated for atrial fibrillation after acute ischaemic stroke or transient ischaemic attack (CROMIS-2):a multicentre observational cohort study
Background:
Cerebral microbleeds are a potential neuroimaging biomarker of cerebral small vessel diseases that are prone to intracranial bleeding. We aimed to determine whether presence of cerebral microbleeds can identify patients at high risk of symptomatic intracranial haemorrhage when anticoagulated for atrial fibrillation after recent ischaemic stroke or transient ischaemic attack.
Methods:
Our observational, multicentre, prospective inception cohort study recruited adults aged 18 years or older from 79 hospitals in the UK and one in the Netherlands with atrial fibrillation and recent acute ischaemic stroke or transient ischaemic attack, treated with a vitamin K antagonist or direct oral anticoagulant, and followed up for 24 months using general practitioner and patient postal questionnaires, telephone interviews, hospital visits, and National Health Service digital data on hospital admissions or death. We excluded patients if they could not undergo MRI, had a definite contraindication to anticoagulation, or had previously received therapeutic anticoagulation. The primary outcome was symptomatic intracranial haemorrhage occurring at any time before the final follow-up at 24 months. The log-rank test was used to compare rates of intracranial haemorrhage between those with and without cerebral microbleeds. We developed two prediction models using Cox regression: first, including all predictors associated with intracranial haemorrhage at the 20% level in univariable analysis; and second, including cerebral microbleed presence and HAS-BLED score. We then compared these with the HAS-BLED score alone. This study is registered with ClinicalTrials.gov, number NCT02513316.
Findings:
Between Aug 4, 2011, and July 31, 2015, we recruited 1490 participants of whom follow-up data were available for 1447 (97%), over a mean period of 850 days (SD 373; 3366 patient-years). The symptomatic intracranial haemorrhage rate in patients with cerebral microbleeds was 9·8 per 1000 patient-years (95% CI 4·0–20·3) compared with 2·6 per 1000 patient-years (95% CI 1·1–5·4) in those without cerebral microbleeds (adjusted hazard ratio 3·67, 95% CI 1·27–10·60). Compared with the HAS-BLED score alone (C-index 0·41, 95% CI 0·29–0·53), models including cerebral microbleeds and HAS-BLED (0·66, 0·53–0·80) and cerebral microbleeds, diabetes, anticoagulant type, and HAS-BLED (0·74, 0·60–0·88) predicted symptomatic intracranial haemorrhage significantly better (difference in C-index 0·25, 95% CI 0·07–0·43, p=0·0065; and 0·33, 0·14–0·51, p=0·00059, respectively).
Interpretation:
In patients with atrial fibrillation anticoagulated after recent ischaemic stroke or transient ischaemic attack, cerebral microbleed presence is independently associated with symptomatic intracranial haemorrhage risk and could be used to inform anticoagulation decisions. Large-scale collaborative observational cohort analyses are needed to refine and validate intracranial haemorrhage risk scores incorporating cerebral microbleeds to identify patients at risk of net harm from oral anticoagulation.
Funding:
The Stroke Association and the British Heart Foundation
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