Crowleyshapiro6336
a concentration levels above the therapeutic threshold for most patients.
In Ireland, similar to other jurisdictions, health technology assessment (HTA) is used to inform the health payer's drug reimbursement decisions. These HTAs are conducted by the National Centre for Pharmacoeconomics (NCPE). In 2009, the NCPE introduced the Rapid Review process to identify drugs that do not require further assessment in the form of the previously established full HTA process.
A retrospective analysis of all Rapid Reviews submitted to the NCPE from 2010 to 2019, inclusive, was conducted. Rapid Review recommendation was recorded (i.e. full HTA required or not required). For those submitted from 2012 to 2019, additional data relating to the drug, economic and clinical evidence-related factors were collected. Multivariable logistic regression methods were used to model the relationship between these factors and the likelihood of requiring a full HTA. An exploratory analysis estimated the additional NCPE appraisal time that would have been required to evaluate all drugs, had the Rapid Review prudy to use data uniquely available to the NCPE to evaluate factors associated with the requirement for a full HTA following a Rapid Review. The process has reduced the NCPE appraisal time required to evaluate all submissions over the study period. The NCPE's Rapid Review process allows for appropriate resource prioritisation within a national HTA agency.
To date, health technology assessment (HTA) agencies have not been at the forefront of decision making regarding the adoption of interventions for coronavirus disease 2019 (COVID-19). Instead, policymakers have prioritised rapid action in response to the pandemic emergency, with no assessment of value for money. As COVID-19 vaccination coverage increases and healthcare systems begin to recover, HTA agencies will be expected to assess technologies for COVID-19.
We aimed to identify the key challenges when assessing therapeutic and diagnostic technologies for COVID-19, from the perspective of HTA agencies, and identify whether there is a case for novel HTA methods and/or processes to address them.
We used a mixed-methods approach, by conducting an online survey of HTA agencies, to collect data about the challenges faced when assessing or planning to assess diagnostic and therapeutic technologies for COVID-19. The online survey was followed by a 'roundtable' workshop of HTA agencies' representatives to discuss the results and to elaborate on their responses.
We received 21 completed surveys (response rate of 45%) and 11 of the respondents joined the roundtable discussion. Five themes emerged from the responses assessing clinical effectiveness (44%), assessing cost effectiveness (19%), practical (19%), political (11%), and decision making (11%) challenges. At the roundtable, attendees elaborated on the challenges and identified two additional themes how HTA agencies have responded to the pandemic to date, and how their role might change over time.
HTA agencies face both methodological and logistical challenges when assessing or planning to assess technologies for COVID-19. An interim best-practice HTA framework to address the key challenges would be valuable.
HTA agencies face both methodological and logistical challenges when assessing or planning to assess technologies for COVID-19. An interim best-practice HTA framework to address the key challenges would be valuable.Numerous studies observed a link between the herpes smplex virus-1 (HSV-1) and Alzheimer's disease. However, the exact viral and cellular dynamics that lead from an HSV-1 infection to Alzheimer's disease are unknown. In this paper, we use the microcompetition model to formulate these dynamics by connecting seemingly unconnected observations reported in the literature. We concentrate on four pathologies characteristic of Alzheimer's disease. First, we explain how an increase in the copy number of HSV-1 during latency can decrease the expression of BECN1/Beclin1, the degradative trafficking protein, which, in turn, can cause a dysregulation of autophagy and Alzheimer's disease. Second, we show how an increase in the copy number of the latent HSV-1 can decrease the expression of many genes important for mitochondrial genome metabolism, respiratory chain, and homeostasis, which can lead to oxidative stress and neuronal damage, resulting in Alzheimer's disease. Third, we describe how an increase in this copy number can reduce the concentration of the NMDA receptor subunits NR1 and NR2b (Grin1 and Grin2b genes), and brain derived neurotrophic factor (BDNF), which can cause an impaired synaptic plasticity, Aβ accumulation and eventually Alzheimer's disease. Finally, we show how an increase in the copy number of HSV-1 in neural stem/progenitor cells in the hippocampus during the latent phase can lead to an abnormal quantity and quality of neurogenesis, and the clinical presentation of Alzheimer's disease. Since the current understanding of the dynamics and homeostasis of the HSV-1 reservoir during latency is limited, the proposed model represents only a first step towards a complete understanding of the relationship between the copy number of HSV-1 during latency and Alzheimer's disease.
This study explored the interactive effects between polymorphonuclear neutrophils (PMNs) and vascular endothelial cells under intermittent hypoxia (IH) and investigated the mechanisms underlying these effects.
Endothelial cells were co-cultured with PMNs isolated from rats exposed to normoxia or IH. The PMN apoptotic rate was determined using flow cytometry. Expression of apoptosis-related proteins in the endothelial cells were evaluated using Western blotting, and the levels of intercellular adhesion molecules in the co-culture supernatants were measured using enzyme-linked immunosorbent assay.
The PMN apoptotic rate in the IH-exposed rat group was significantly lower than that of the normoxia control group. There was a positive relationship between the PMN apoptotic rate and IH exposure time. In endothelial cells co-cultured with PMNs isolated from IH-exposed rats, a significant increase in the protein expression levels of Bax, Bcl-2, and caspase-3 and a significant decrease in the Bcl-2/Bax ratio were observed. Furthermore, the intercellular cell adhesion molecule-1(ICAM-1) and E-select element (E-S) levels were elevated significantly in the co-cultured supernatants of endothelial cells and PMNs from IH-exposed rats compared to that from controls. The above IH-induced alterations were partially restored by tempol pretreatment.
The apoptotic rate was low in PMNs from IH-exposed rats, which consequently increased the apoptotic signals in endothelial cells in vitro. This may be associated with the increased levels of intercellular adhesion molecules. learn more Further, tempol partially attenuates the PMN-mediated pro-apoptotic effects on endothelial cells under IH.
The apoptotic rate was low in PMNs from IH-exposed rats, which consequently increased the apoptotic signals in endothelial cells in vitro. This may be associated with the increased levels of intercellular adhesion molecules. Further, tempol partially attenuates the PMN-mediated pro-apoptotic effects on endothelial cells under IH.
Huanglian-Houpo decoction(HH), which is recorded in the famous traditional Chinese medicine monograph "Puji Fang," contains two individual herbs, Huanglian (Rhizoma coptidis) and Houpo (Magnoliae officinalis cortex). It was regularly used to treat seasonal epidemic colds and influenzas in ancient China. Our laboratory discovered that HH has a significant anti-H1N1 influenza virus effect. However, no pharmacokinetic and pharmacodynamic data concerning the anti-H1N1 influenza virus activity of HH are available to date. In the current study, the concentration-time profiles of two major components of HH, berberine and magnolol, in rat plasma were investigated.
An integrate pharmacokinetic approach was developed for evaluating the holistic pharmacokinetic characteristics of berberine and magnolol from HH. Additionally, the inhibition rate and levels of IFN-β in MDCK cells infected by influenza virus were analyzed. Data were calculated using 3p97 with pharmacokinetic analysis.
The estimated pharmacokinetic parameters were maximum plasma concentration (C
) 0.9086 μg/ml, area under the concentration-time curve (AUC) 347.74 μg·min/ml, and time to reach C
(T
) 64.69 min for berberine and C
= 0.9843 μg/ml, AUC= 450.64 μg·min/ml, T
= 56.86 min for magnolol, respectively. Furthermore, integrated pharmacokinetic and pharmacodynamic analysis showed that the highest plasma concentration, inhibition rate and interferon-β (IFN-β) secretion of HH first increased and then weakened over time, reaching their peaks at 60 min. The plasma concentration of HH is directly related to the anti-influenza virus effect.
The results indicated that berberine and magnolol are the main active ingredients of HH related to its anti-influenza virus effect, which is related to the improvement of IFN-β secretion.
The results indicated that berberine and magnolol are the main active ingredients of HH related to its anti-influenza virus effect, which is related to the improvement of IFN-β secretion.
As the prevalence of some gynecological conditions depends on patient characteristics such as race/ethnicity, it is important to study therapies for these conditions in diverse populations. The study described in this article was conducted to investigate the safety, tolerability, and pharmacokinetics of vilaprisan, a selective progesterone receptor modulator, in Japanese women in Japan. It supplements two comparable studies that were conducted in healthy postmenopausal European and Chinese women, respectively.
In this exploratory randomized, placebo-controlled, double-blind, ascending-dose study, five groups of healthy postmenopausal Japanese women received vilaprisan as immediate-release tablets (1, 5, or 15 mg as a single dose or 1 or 5 mg/day for 28 days) or placebo tablets (single dosing 8 subjects/dose step, thereof 2 subjects randomized to placebo; multiple dosing 12subjects/dose step, thereof 4 subjects randomized to placebo). Blood samples for pharmacokinetic profiles were collected over 14-19 dayµg/l (27%) after single administration and to 8µg/l (28%) and 31µg/l (22%) after multiple administrations of the above doses. Mild adverse events were observed, similar to those observed in other clinical studies of vilaprisan.
Overall, vilaprisan was safe and well tolerated. The exposure in Japanese women was similar to that observed in European and Chinese women in separate studies.
15 Nov 2011 (no registration number assigned).
15 Nov 2011 (no registration number assigned).
Bariatric surgery may lead to metabolic bone disease.
In this cross-sectional study, we compared the prevalence of secondary hyperparathyroidism (SHPT), impact on bone mass and turnover markers, and serum leptin after Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) in 117 patients (91% female, 51% RYGB, age 41.8 ± 6.7years, time of surgery 4.3 ± 3.4years) at different times (1-2years, > 2 and < 5years and ≥ 5years). Body composition, bone mineral density (BMD), by dual-energy X-ray absorptiometry, and bone parameters (PTH, serum calcium, 25OHD, alkaline phosphatase (AP), C-telopeptide (CTX)) were analyzed.
Prevalence of SHPT (PTH ≥ 65pg/ml) was 26%, RYGB > SG (18.4% vs. 7.8%, p = 0.039), despite similar 25OHD and calcium levels. Mean PTH, CTX, and AP were higher in RYGB vs. SG (61.3 ± 29.5 vs 49.5 ± 32.3pg/ml, p = 0.001; 0.596 ± 0.24 vs. 0.463 ± 0.23ng/ml; 123.9 ± 60.8 vs. 100.7 ± 62.0 U/l). There were 13.5% decreases in femoral neck BMD in all patients, over the study period. In the last group, the RYGB group showed greater bone loss in total body BMD (1.
