The impact of policy interventions to promote the uptake of biosimilar medicines in Belgium:a nationwide interrupted time series analysis

Background: The Belgian government has taken several measures to increase the uptake of biosimilars in past years. However, no formal evaluation of the impact of these measures has been made yet. This study aimed to investigate the impact of the implemented measures on biosimilar uptake. Methods: An interrupted time series analysis was performed using an autoregressive integrated moving average (ARIMA) model with the Box-Jenkins method. All data were expressed as defined daily doses (DDD) per month/quarter and obtained from the Belgian National Institute for Health and Disability Insurance (NIHDI). Three molecules were included in the analysis: etanercept (ambulatory), filgrastim (hospital), and epoetin (hospital). A significance level of 5% was used for all analyses. Results: In the ambulatory care, the effect of a financial prescriber incentive of 2019 was investigated. After this intervention, 44.504 (95% CI −61.61 to −14.812; P < 0.001) fewer etanercept biosimilar DDDs were dispensed monthly than expected in the absence of the intervention. Two interventions were modelled for biosimilars in the hospital setting. The first intervention of 2016 includes prescription targets for biosimilars and monitoring of hospitals on adequate tendering. The second intervention involves an information campaign on biosimilars. After the first intervention, a small decrease in quarterly epoetin biosimilar uptake of 449.820 DDD (95% CI −880.113 to −19.527; P = 0.05) was observed. The second intervention led to a larger increase in quarterly epoetin biosimilar uptake of 2733.692 DDD (95% CI 1648.648–3818.736; P < 0.001). For filgrastim, 1809.833 DDD (95% CI 1354.797–2264.869; P < 0.001) more biosimilars were dispensed immediately after the first intervention and 151.639 DDD (95% CI −203.128 to −100.150; P < 0.001) fewer biosimilars each quarter after the first intervention. An immediate and sustained increase of 700.932 DDD (95% CI 180.536–1221.328; P = 0.016) in quarterly biosimilar volume was observed after the second intervention. All other parameter estimates were not statistically significant. Conclusions: The results of this study suggest that the impact of past policy interventions to increase the uptake of biosimilars has been variable and limited. A holistic policy framework is required to develop a competitive and sustainable off-patent biologicals market in Belgium.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Dentists' knowledge and opinions of oral-systemic disease relationships: relevance to patient care and education.

Population studies consistently support associations between poor oral (periodontal) health and systemic diseases such as cardiovascular disease (CVD) and diabetes. The aim of this study was to assess the knowledge of dentists and document their opinions regarding the evidence on oral-systemic disease relationships. A survey consisting of 39 items was developed and mailed to 1,350 licensed dentists in North Carolina. After three mailings, 667 dentists (49%) meeting inclusion criteria responded. The respondents were predominantly male (76.3%), in solo practice (59.5%), and in non-rural settings (74%). More than 75% of these dentists correctly identified risk factors like diet, genetics, smoking, obesity, and physical inactivity for CVD and diabetes. The majority rated the evidence linking periodontal disease with CVD and diabetes as strong (71% and 67%, respectively). These dentists were most comfortable inquiring about patients' tobacco habits (93%), treating patients with diabetes (89%) or CVD (84%) and concurrent periodontal disease, and discussing diabetes-periodontal disease risks with patients (88%). Fewer respondents were comfortable asking patients about alcohol consumption (54%) or providing alcohol counseling (49%). Most agreed that dentists should be trained to identify risk factors (96%) or actively manage systemically diseased patients (74%). Over 90% agreed that medical and dental professionals should be taught to practice more collaboratively. These data indicate that these dentists were knowledgeable about oral-systemic health associations, had mixed comfort levels translating the evidence into clinical practice, but expressed support for interprofessional education to improve their readiness to actively participate in their patients' overall health management

Chromosomal mapping of pancreatic islet morphological features and regulatory hormones in the spontaneously diabetic (Type 2) Goto-Kakizaki rat

Insulin resistance and altered endocrine pancreas function are central pathophysiological features of type 2 diabetes mellitus (T2DM). The Goto-Kakizaki (GK) rat is a model of spontaneous T2DM characterised by reduced beta cell mass and genetically determined glucose intolerance and altered insulin secretion. To identify genetic determinants of endocrine pancreas histopathology, we carried out quantitative trait locus (QTL) mapping of histological phenotypes (beta cell mass -BCM and insulin-positive cell area -IPCA) and plasma concentration of hormones and growth factors in a F2 cohort derived from GK and normoglycemic Brown Norway rats. Although IPCA and BCM in the duodenal region of the pancreas were highly positively correlated (P < 10−6), and similarly in the splenic region, both measures were poorly correlated when comparing duodenal and splenic phenotypes. Strongest evidence of linkage to pancreas morphological traits was obtained between BCM and chromosome 10 (LOD 3.2). Evidence of significant linkage (LOD 4.2) to plasma corticosterone was detected in a region of chromosome 1 distal to other QTLs previously identified in the GK. Male-specific genetic effects were detected, including linkages (LOD > 4) to growth hormome (GH) on chromosome 6 and prolactin on chromosome 17. These data suggest independent genetic control of the structure and function of ontologically different regions of the endocrine pancreas. Novel QTLs for corticosterone, prolactin and GH may contribute to diabetes in the GK. The QTLs that we have identified in this, and previous genetic studies collectively underline the complex and multiple mechanisms involved in diabetes in the GK strain

LOW-DOSE GAMMA-RADIATION INHIBITS BENZO[A]PYRENE-INDUCED LUNG ADENOMA DEVELOPMENT IN A/J MICE

Low-dose ionizing radiation (LDR) may lead to suppression of smoking-related lung cancer. We examined the effects of a known cigarette smoke carcinogen Benzo[a]pyrene (B[a]P) alone or in combination with fractionated low-dose gamma radiation (60 – 600 mGy total dose) on the induction of lung neoplasms in the A/J mouse. Our results show that 600 mGy of gamma radiation delivered in six biweekly fractions of 100 mGy starting 1 month after B[a]P injection significantly inhibits the development of lung adenomas per animal induced by B[a]P. Our data also indicated that the six biweekly doses suppressed the occurrence of spontaneous hyperplastic foci in the lung, although this suppression failed to reach statistical significance when analyzed as average foci per lung possibly related to the small sample sizes used for the control and test groups

Prevención y cumplimiento de la normativa aplicable en las viviendas de las zonas vulnerables del distrito de Florencia de Mora, Trujillo 2020

La presente investigación tuvo por objetivo determinar la prevención y el nivel de cumplimiento de la normativa aplicable en las viviendas de las zonas vulnerables del distrito de Florencia de Mora, Trujillo 2020. La investigación fue de metodología cuantitativa, aplicada, descriptiva de diseño correlacional. La muestra estuvo compuesta por las viviendas de la cuadra 6 de la Av. Hipólito Unanue, la misma que es la que más directamente expuesta a la inundación y a pesar de tener pavimento flexible consta de zonas viales de tierra que ponen en riesgo las construcciones desde el terreno donde se asientan. Como instrumentos se utilizó Para la variable 1. Cuestionario de Nivel de cumplimiento de normativa aplicada a construcciones. Para la variable 2. Cuestionario de vulnerabilidad de construcción de Florencia de Mora. Los resultados muestran una relación significativa entre la prevención y el nivel de cumplimiento de normativa aplicable a la construcción, sin embargo esta relación es de intensidad media (Rho = 0.535, p= 0.040, alfa = 0.05). Respecto al nivel de prevención, predomino el nivel medio (53%, 8) seguido de bajo (47%, 7). Respecto al nivel de cumplimiento, predomino el nivel bajo (73%, 11) y nivel medio (27%, 4), tanto para prevención como para cumplimento no hubo nivel alto. Existen factores para esto, la zona es de sinestro inevitable, cualquier inversión se perdería a más tardar en un plazo de 12 años que es el pronóstico más certero de desastre. Las medidas para mitigarlas no dependen ni de la población ni del municipio y no hay visos de que se logren. Por otra parte, los propietarios son de pobreza, la zona económicamente y sus alrededores son pobres por lo que el terreno cono el inmueble son de bajo valor y peor capitalización. Por lo que se propone que el municipio desarrolle un proyecto de inversión pública de recuperación y valoración temporal del espacio basado en tecnologías baratas (adobe, bambú, drywall) y con concepto ecológico para creación de mercados, ferias y espacios públicos amigables, de tal forma que cuando la catástrofe suceda no sea gran infraestructura la que se pierde. Se concluye que con manejo de espacios y construcciones temporales que la inversión se recupere en 3-5 años, justifica, se da utilidad y valor a los predios y en caso de desastre se lo vuelve a construir.The objective of this research was to determine the prevention and the level of compliance with the applicable regulations in the homes of the vulnerable areas of the district of Florencia de Mora, Trujillo 2020. The research was of quantitative methodology, applied, descriptive of correlational design. The sample consisted of the dwellings in block 6 of Av. Hipólito Unanue, which is the one most directly exposed to flooding and despite having flexible pavement, it consists of dirt road areas that put constructions at risk from the land where they settle. As instruments, it was used for variable 1. Questionnaire on the level of compliance with regulations applied to constructions. For variable 2. Florence de Mora construction vulnerability questionnaire. The results show a significant relationship between prevention and the level of compliance with regulations applicable to construction, however this relationship is of medium intensity (Rho = 0.535, p = 0.040, alpha = 0.05). Regarding the level of prevention, the medium level predominated (53%, 8) followed by low (47%, 7). Regarding the level of compliance, the low level (73%, 11) and the medium level (27%, 4) predominated, both for prevention and compliance there was no high level. There are factors for this, the area is unavoidable, any investment would be lost no later than 12 years, which is the most accurate forecast of disaster. The measures to mitigate them do not depend on either the population or the municipality, and there are no signs that they will be achieved. On the other hand, the owners are poor, the area economically and its surroundings are poor, so the land and the property are of low value and worse capitalization. Therefore, it is proposed that the municipality develop a public investment project for the recovery and temporary valuation of the space based on cheap technologies (adobe, bamboo, drywall) and with an ecological concept for the creation of markets, fairs and friendly public spaces, in such a way that when the catastrophe happens, it is not great infrastructure that is lost. It is concluded that with the management of temporary spaces and constructions that the investment recovers in 3-5 years, it justifies, gives utility and value to the properties and in case of disaster it is rebuilt

Photoacoustic microscopy of human teeth

Photoacoustic microscopy (PAM) utilizes short laser pulses to deposit energy into light absorbers and sensitively detects the ultrasonic waves the absorbers generate in response. PAM directly renders a three-dimensional spatial distribution of sub-surface optical absorbers. Unlike other optical imaging technologies, PAM features label-free optical absorption contrast and excellent imaging depths. Standard dental imaging instruments are limited to X-ray and CCD cameras. Subsurface optical dental imaging is difficult due to the highly-scattering enamel and dentin tissue. Thus, very few imaging methods can detect dental decay or diagnose dental pulp, which is the innermost part of the tooth, containing the nerves, blood vessels, and other cells. Here, we conducted a feasibility study on imaging dental decay and dental pulp with PAM. Our results showed that PAM is sensitive to the color change associated with dental decay. Although the relative PA signal distribution may be affected by surface contours and subsurface reflections from deeper dental tissue, monitoring changes in the PA signals (at the same site) over time is necessary to identify the progress of dental decay. Our results also showed that deep-imaging, near-infrared (NIR) PAM can sensitively image blood in the dental pulp of an in vitro tooth. In conclusion, PAM is a promising tool for imaging both dental decay and dental pulp

Endometrial BCL6 Overexpression in Eutopic Endometrium of Women With Endometriosis

The objective of this study was to examine B-cell CLL/lymphoma 6 (BCL6) expression in human eutopic endometrium across the menstrual cycle in women with and without endometriosis and to establish a cutoff for future studies. This design was a series of case-control studies in tertiary University teaching hospitals. We examined BCL6 expression by messenger RNA and immunohistochemically in prospectively collected samples in both the proliferative (P) and the secretory phases. BCL6 is minimally increased in the mid-secretory phase of the menstrual cycle compared to the P phase in normal patients. BCL6 protein expression was significantly higher in the secretory phase of patients with endometriosis (n = 29) versus fertile controls without endometriosis at laparoscopy (n = 20; P < .0001). Normal fertile controls (n = 28) recruited for endometrial biopsy also had low levels of secretory phase BCL6 expression compared to women with unexplained infertility (UI; n = 119). A receiving-operator characteristic analysis of these data revealed an area under the curve of 94% (95% confidence interval 85%-100%; P < .0001) with an HSCORE cutoff of 1.4 to differentiate cases with and without endometriosis. Using this cutoff value, BCL6 was positive in 88% of cases with UI. Laparoscopic examination of a subset of 65 patients confirmed abnormalities in 98% of cases; 61 (93.8%) were found to have endometriosis, 3 (4.6%) with hydrosalpinx, and 1 (1.5%) with a normal pelvis. These data suggest that BCL6 is a promising candidate as a single diagnostic biomarker for detection of endometriosis in women with otherwise UI and may be associated with endometrial dysfunction, including progesterone resistanc

Associations of cancer and other chronic medical conditions with SF-6D preference-based scores in Medicare beneficiaries

Documenting the impact of different types of cancer on daily functioning and well-being is important for understanding burden relative to other chronic medical conditions. This study examined the impact of 10 different cancers and 13 other chronic medical conditions on health-related quality of life

Report from the “What is Open?” Workgroup

The scholarly community’s current definition of “open” captures only some of the attributes of openness that exist across different publishing models and content types. Open is not an end in itself, but a means for achieving the most effective dissemination of scholarship and research. We suggest that the different attributes of open exist along a broad spectrum and propose an alternative way of describing and evaluating openness based on four attributes: discoverable, accessible, reusable, and transparent. These four attributes of openness, taken together, form the draft “DART Framework for Open Access.” This framework can be applied to both research artifacts as well as research processes. We welcome input from the broader scholarly community about this framework