Background: Opioids are often used in nursing homes to manage non-malignant pain, but little is known about their long-term use, initiation, and comparative safety. Methods: We used the Minimum Data Set 3.0 from 2011-2013 merged to Medicare and facility characteristics data to study opioid use and safety among older, long-stay residents. The specific aims were to examine the 1) prevalence of long-term opioid use; 2) geographic variation in the initiation of commonly used opioids (oxycodone, hydrocodone, tramadol); and 3) comparative safety of commonly used opioids and fracture hospitalizations. Results: One in seven long-stay residents were prescribed opioids long-term. There was extensive geographic variation in the initiation of commonly used opioids, with oxycodone (9.4%) initiated less frequently than hydrocodone (56.2%) or tramadol (34.5%) but varying most extensively across the United States, with the majority of variation in prescribing explained by state of residence. Compared to hydrocodone initiators (7.9 fracture hospitalizations per 100-person years), those initiating tramadol had lower rates of fracture hospitalizations (subdistribution hazard ratio [HRSD] = 0.67, 95% Confidence Interval [CI]: 0.56-0.80), whereas oxycodone initiators had similar rates of fracture hospitalizations (HRSD=1.08, 95% CI: 0.79-1.48). Conclusion: The prevalence of long-term opioid use was twice as common in nursing homes as community settings, with initiation patterns varying extensively by region and being strongly driven by state of residence. Although initiating tramadol was associated with lower rates of fractures than hydrocodone, questions on opioid risks and benefits remain and are especially pertinent given the high mortality rates in this population.

Glioblastoma multiforme (GBM) is a destructive brain cancer that results in death 12 to 15 months after diagnosis. The purpose of this retrospective study was to determine if variations in tumor size at diagnosis, treatment options, and survival rate occur in GBM patients living in urban and rural areas of the United States. Using the behavior model of health services as the theoretical framework, this study used secondary data sets of GBM cases reported from 1988 to 2011 from the Surveillance, Epidemiology, and End Results program. Tumor size was measured in millimeters; treatment was evaluated by ascertaining the number of GBM patients who had surgical resection of their tumors, radiation, and chemotherapy; and survival rate was evaluated using Cox Regression analysis. With a sample size of 33,202 cases, data were examined using descriptive and multivariable analyses with SPSS. Results showed statistically significant differences in tumor size at diagnosis in rural patients compared to urban patients (p = 0.0085; p = 0.018), more urban patients were treated with radiation compared to rural patients (p < 0.001), and rural patients had poorer survival rates than urban patients (p < 0.001). Finally, when controlling for region, race, age, gender, education, and income, longer survival time was associated with urban status, female cases, and higher family income (p < 0.0001), and greater age was associated with reduced survival time (p < 0.0001). Study results could promote positive social change by identifying predictive variables associated with health outcomes of GBM patients. It may also educate providers on the risk of rurality of patients diagnosed with GBM, and inform lawmakers responsible for the creation of healthcare policy and the equitable allocation of healthcare resources.

No description available.

<p>During the last decades many amphibian species and populations have experienced declines and extinctions in different parts of the world. Anthropogenic activities are believed to account for these declines, and one of the hypothesized causes has been the increased level of ultraviolet-B (UV-B) radiation due to depletion of the stratospheric ozone layer. </p><p>Although negative effects of UV-B radiation on development of many amphibian species have been demonstrated, a number of potentially critical issues around assessment of amphibian UV-B radiation tolerance have remained unexplored. For instance, next to nothing is known about geographic variation in UV-B tolerance and about possible carry-over effects of early UV-B exposure to later life-stages. Likewise, synergistic effects with other stressors, as well as sublethal effects on growth have received little attention. </p><p>The results from field and laboratory experiments show that <i>R. temporaria</i> and <i>R. arvalis</i> are relatively tolerant to even high levels of UV-B in terms of embryonic survival. However, it was found that even normal levels of UV-B can reduce early embryonic growth. In addition, the effects of early exposure to UV-B became manifested mostly or only after a considerable time-lag (i.e. at metamorphosis). Furthermore, it was found that the sublethal effects of UV-B may become manifested only in combination with other stressors, such as low pH, and this synergism may differ among different populations. No evidence for genetic differentiation in UV-B tolerance was found.</p><p>These findings suggest that even a relatively tolerant species, such as <i>R. temporaria</i>, may be sensitive to increased levels of UV-B radiation, but that this sensitivity may be highly population, environment and trait dependent. The observed carry-over effects over life-stages emphasise the importance of the early life environment on later life fitness.</p>

During the last decades many amphibian species and populations have experienced declines and extinctions in different parts of the world. Anthropogenic activities are believed to account for these declines, and one of the hypothesized causes has been the increased level of ultraviolet-B (UV-B) radiation due to depletion of the stratospheric ozone layer. Although negative effects of UV-B radiation on development of many amphibian species have been demonstrated, a number of potentially critical issues around assessment of amphibian UV-B radiation tolerance have remained unexplored. For instance, next to nothing is known about geographic variation in UV-B tolerance and about possible carry-over effects of early UV-B exposure to later life-stages. Likewise, synergistic effects with other stressors, as well as sublethal effects on growth have received little attention. The results from field and laboratory experiments show that R. temporaria and R. arvalis are relatively tolerant to even high levels of UV-B in terms of embryonic survival. However, it was found that even normal levels of UV-B can reduce early embryonic growth. In addition, the effects of early exposure to UV-B became manifested mostly or only after a considerable time-lag (i.e. at metamorphosis). Furthermore, it was found that the sublethal effects of UV-B may become manifested only in combination with other stressors, such as low pH, and this synergism may differ among different populations. No evidence for genetic differentiation in UV-B tolerance was found. These findings suggest that even a relatively tolerant species, such as R. temporaria, may be sensitive to increased levels of UV-B radiation, but that this sensitivity may be highly population, environment and trait dependent. The observed carry-over effects over life-stages emphasise the importance of the early life environment on later life fitness.

Submitted by Luciana Sebin (lusebin@ufscar.br) on 2016-10-11T19:38:10Z No. of bitstreams: 1 DissDPMcg.pdf: 1163116 bytes, checksum: 38b9e1756b3619ed64928eaf8458e248 (MD5) / Approved for entry into archive by Ronildo Prado (ronisp@ufscar.br) on 2016-10-17T13:04:52Z (GMT) No. of bitstreams: 1 DissDPMcg.pdf: 1163116 bytes, checksum: 38b9e1756b3619ed64928eaf8458e248 (MD5) / Approved for entry into archive by Ronildo Prado (ronisp@ufscar.br) on 2016-10-17T13:05:00Z (GMT) No. of bitstreams: 1 DissDPMcg.pdf: 1163116 bytes, checksum: 38b9e1756b3619ed64928eaf8458e248 (MD5) / Made available in DSpace on 2016-10-17T13:13:15Z (GMT). No. of bitstreams: 1 DissDPMcg.pdf: 1163116 bytes, checksum: 38b9e1756b3619ed64928eaf8458e248 (MD5) Previous issue date: 2016-02-26 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Partamona (Schwarz, 1939) is a stingless bee genus which has as an interesting trait, the presence of B chromosomes in some species. These chromosomes were identified in six closely related species so far, all included in the cupira group, except P. helleri, which has an uncertain position in Partamona phylogeny, but it is possibly related to this group. We analyzed 894 colonies from 128 locations of thirteen species, using a SCAR marker specific for Partamona B chromosomes. The results enabled an increase in knowledge about species number with supernumerary chromosomes in this genus, including species from the pearsoni clade. The high number of colonies analyzed allowed to set the B chromosomes frequency on carrier species. A significant positive correlation between latitude and B chromosomes frequency was found in P. helleri, with higher frequency in north decreasing towards the south of the species distribution. The B chromosome transmission rate was estimated for three species that showed the highest frequencies of these chromosomes (P. helleri, P. cupira and P. rustica). The result was as expected for a regular meiotic behavior, which queens with one supernumerary chromosome have 50% chance to transfer the B chromosome to the offspring, suggesting an absence drive in these species. The Sequences obtained using SCAR primers had high quality and were different from those previously reported in another studies, showing no undefined sites, indicating greater effectiveness for sequencing using the internal primers designed in our laboratory. The comparison between obtained sequences revealed a high similarity between species, with only two haplotypes and no intraspecific differences, suggesting a single origin for Partamona B chromosomes. The sequence obtained for P. helleri was different from that obtained for the cupira clade species, suggesting that P. helleri did not transmit the B chromosomes to the other species, as previously suggested. The high frequency in some species and the presence in the pearsoni clade suggest a more complex 4 evolutionary history and an older origin than previously thought for Partamona B chromosomes. / Partamona (Schwarz, 1939) é um gênero de abelhas sem ferrão que apresenta como interessante característica a presença de cromossomos B em algumas espécies. Até o momento, esses cromossomos haviam sido identificados em seis espécies intimamente relacionadas, todas incluídas no clado cupira, e P. helleri, de posição incerta na filogenia de Partamona, mas possivelmente relacionada a este clado. A análise de 894 colônias provenientes de 128 localidades de 13 espécies do gênero, utilizando um marcador SCAR (Sequence Characterized Amplified Region) específico para os cromossomos B de Partamona, permitiu ampliar o conhecimento do número de espécies do gênero portadoras destes cromossomos, incluindo espécies do clado pearsoni. A partir dos resultados desta análise foi possível também, definir a frequência dos cromossomos B nas espécies portadoras. Em P. helleri foi encontrada uma correlação positiva significativa entre latitude e frequência de cromossomos B, com maior frequência no norte e diminuição em direção ao sul da distribuição da espécie. A taxa de transmissão de cromossomos B foi estimada para as três espécies em que estes cromossomos foram mais frequentes (P. helleri, P. cupira e P. rustica). O resultado foi consistente com o esperado para um comportamento meiótico regular na transmissão dos cromossomos B da rainha para a prole, sugerindo que nessas espécies não ocorra um desvio meiótico que favoreça a transmissão. As sequências obtidas com os primers SCAR apresentaram alta qualidade e foram diferentes das sequências reportadas na literatura, não apresentando sítios indefinidos, apontando para uma maior acurácia de sequenciamento com o uso dos primers internos desenhados em nosso laboratório. A comparação entre as sequências revelou uma alta similaridade entre espécies, com apenas dois haplótipos e ausência de diferenças intraespecíficas, sugerindo uma origem única para os cromossomos B de Partamona. A sequência obtida para P. helleri foi diferente da sequência obtida para as 2 outras espécies do clado cupira, sugerindo que essa espécie não transmitiu os cromossomos B para as outras espécies do grupo, como previamente sugerido. A alta frequência de cromossomos B em algumas espécies do gênero e a presença de cromossomos B em espécies do clado pearsoni sugere uma história evolutiva mais complexa e uma origem mais antiga do que se presumia anteriormente para os cromossomos B de Partamona.

Streptococcus pneumoniae est une bactérie cocci gram positif commensale de la flore oropharyngée qui colonise le rhinopharynx de l’Homme et dont près de 100 sérotypes sont connus. Les nourrissons et les jeunes enfants représentent son réservoir principal. Le pneumocoque peut être à l’origine d’infections graves, telles que la méningite, les bactériémies et la pneumonie, et moins graves mais plus courantes comme la sinusite et l’otite moyenne aiguë. Deux vaccins anti-pneumococciques conjugués ont été introduits en France : le PCV7 (couvrant contre 7 sérotypes) en 2003 et le PCV13 (couvrant contre 6 sérotypes supplémentaires) en 2010. L’objectif général de ce travail de thèse est d’évaluer l’impact des politiques vaccinales sur les infections invasives à pneumocoque en France, en s’intéressant principalement aux évolutions temporelles et géographiques des plus graves : les méningites à pneumocoque (MP). Un premier travail a étudié les dynamiques temporelles des MP sur la période 2001–2014 afin d’identifier l’impact de l’introduction des vaccins conjugués. Des techniques statistiques de modélisations adaptées aux séries temporelles ont été utilisées. Les résultats de ce travail retrouvent des effets rapportés dans la littérature : une réduction des MP à sérotypes vaccinaux mais aussi une augmentation des MP dues aux sérotypes non inclus dans le vaccin (phénomène de « remplacement sérotypique »).Par conséquent, le premier bénéfice, à l’échelle de la population générale, de l’introduction de cette vaccination a été observé seulement onze ans après l’introduction du PCV7, et principalement suite à l’introduction du PCV13 en 2010, avec une diminution de 25% du nombre de MP en 2014. La composante géographique a ensuite été prise en compte afin d’étudier le rôle de la de couverture vaccinale dans la variabilité des MP annuelles entre les départements sur la période 2001-2016. Les résultats confirment l’efficacité des deux formulations du vaccin sur les MP dues aux sérotypes vaccinaux et suggèrent une certaine homogénéité de cet effet entre les différents départements. Inversement, le remplacement sérotypique a été confirmé mais uniquement suite à l’introduction de la première formulation du vaccin et ces effets présentent une répartition géographique hétérogène et variable. La variabilité de la couverture vaccinale entre les départements n’explique pas celle observée dans le nombre de MP, ce qui suggère l’intervention d’autres facteurs tel que la densité géographique. Enfin, une modélisation dynamique, permettant de prendre en compte des aspects fondamentaux des dynamiques de transmission et d’infection du pneumocoque non intégrés dans les méthodes de modélisation statique, a été proposée afin de prédire l’impact de différentes stratégies de vaccination pour les adultes de 65 ans et plus et ainsi évaluer leur rapport coût-utilité. / Streptococcus pneumoniae is a Gram-positive commensal bacterium of the oropharyngeal flora usually colonizing human’s rhino pharynx, of which almost 100 serotypes are known. Infants and young children constitute its main reservoir. Pneumococcus may cause serious infections, such as meningitis, bacteremia and pneumonia, or less serious but more common such as sinusitis and acute otitis media (AOM). Two conjugate pneumococcal vaccines have been introduced in France: PCV7 (covering 7 serotypes) in 2003 and PCV13 (covering 6 additional serotypes) in 2010. The overall objective of this thesis is to assess the impact of vaccination policy on invasive pneumococcal diseases in France, by focusing on temporal and geographical trends of the most serious of them: pneumococcal meningitis (PM). An initial study of PMs temporal dynamics over the 2011-2014 period assessed the impact of conjugate vaccines’ introduction. Statistical modeling techniques were used for time series analysis. The results confirm the effects found in literature: a reduction of vaccine serotypes PMs but at the same time an increase of PMs, due to non-vaccine serotypes (effect of “serotype replacement”). Therefore, the first benefit of vaccine introduction at population scale has been observed no less than 11 years after PCV7 introduction, and then principally after PCV13 was introduced in 2010, with a 25% decrease in PMs in 2014. The geographic component was then implemented to analyze the role of vaccine coverage in annual PM variability between geographic units over the 2001-2016 period. Results confirm the effectiveness of both vaccine compositions on vaccine serotypes PMs and suggest homogeneity of this effect among geographic units. Conversely the serotype replacement has been confirmed only after the first vaccine composition was introduced and presents a variable and heterogeneous geographical repartition. Variability in vaccine coverage among geographic units doesn’t explain the differences in PMs, which could suggest the role of others factors such as demographic density. Finally, a dynamic modeling capable of taking into consideration fundamental aspects of pneumococcus transmission and infection mechanisms not integrated in static modeling has been proposed in order to predict the impacts of different vaccination strategies for 65+ adults and therefore assess their cost-utility ratios.

Background Gabapentinoids (gabapentin and pregabalin), a class of FDA-approved antiepileptic medications with expanded indications for certain neuropathic pain conditions, have been prescribed off-label for almost all types of pain in the US opioid epidemic. Methods We used IBM® MarketScan® Research Databases (2015-2018) and collected primary data. In Aim 1, we described the geographic variation in gabapentinoids and opioids for pain by US state and metropolitan statistical area (MSA). In Aim 2, we implemented a controlled multiple baseline interrupted time series analysis and assessed the impact of including gabapentin in states’ prescription drug monitoring programs (PDMP) and listing gabapentin as a Schedule V controlled substance. In Aim 3, we developed an algorithm to identify potential gabapentin misuse and/or abuse in administrative claims data. Results The pattern of the geographic variation in gabapentinoids was similar to that of opioids across states and MSAs. Including gabapentin in PDMPs and Schedule V controlled ABSTRACT viii substance classification were effective in curbing the growth of gabapentin use and reducing opioid-related adverse events. Our algorithm identified approximately one in six patients with gabapentin use as having potentially misused and/or abused gabapentin. Multiple comorbidities and drug use were associated with gabapentin misuse and/or abuse. Conclusions Gabapentinoids may have been widely used as alternative or adjuvant analgesics to opioids for pain across the US. Policy makers should consider including gabapentin in proactive PDMPs and scheduling of gabapentin. Monitoring requirements and individualized safety measures should be put in place for patients who potentially misuse and/or abuse gabapentin.

No description available.

No description available.