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91.
Gabriela B. Gomez Nicola Foster Daniella Brals Heleen E. Nelissen Oladimeji A. Bolarinwa Marleen E. Hendriks Alexander C. Boers Diederik van Eck Nicole Rosendaal Peju Adenusi Kayode Agbede Tanimola M. Akande Michael Boele van Hensbroek Ferdinand W. Wit Catherine A. Hankins Constance Schultsz 《PloS one》2015,10(9)
Background
While the Nigerian government has made progress towards the Millennium Development Goals, further investments are needed to achieve the targets of post-2015 Sustainable Development Goals, including Universal Health Coverage. Economic evaluations of innovative interventions can help inform investment decisions in resource-constrained settings. We aim to assess the cost and cost-effectiveness of maternal care provided within the new Kwara State Health Insurance program (KSHI) in rural Nigeria.Methods and Findings
We used a decision analytic model to simulate a cohort of pregnant women. The primary outcome is the incremental cost effectiveness ratio (ICER) of the KSHI scenario compared to the current standard of care. Intervention cost from a healthcare provider perspective included service delivery costs and above-service level costs; these were evaluated in a participating hospital and using financial records from the managing organisations, respectively. Standard of care costs from a provider perspective were derived from the literature using an ingredient approach. We generated 95% credibility intervals around the primary outcome through probabilistic sensitivity analysis (PSA) based on a Monte Carlo simulation. We conducted one-way sensitivity analyses across key model parameters and assessed the sensitivity of our results to the performance of the base case separately through a scenario analysis. Finally, we assessed the sustainability and feasibility of this program’s scale up within the State’s healthcare financing structure through a budget impact analysis. The KSHI scenario results in a health benefit to patients at a higher cost compared to the base case. The mean ICER (US$46.4/disability-adjusted life year averted) is considered very cost-effective compared to a willingness-to-pay threshold of one gross domestic product per capita (Nigeria, US$ 2012, 2,730). Our conclusion was robust to uncertainty in parameters estimates (PSA: median US$49.1, 95% credible interval 21.9–152.3), during one-way sensitivity analyses, and when cost, quality, cost and utilization parameters of the base case scenario were changed. The sustainability of this program’s scale up by the State is dependent on further investments in healthcare.Conclusions
This study provides evidence that the investment made by the KSHI program in rural Nigeria is likely to have been cost-effective; however, further healthcare investments are needed for this program to be successfully expanded within Kwara State. Policy makers should consider supporting financial initiatives to reduce maternal mortality tackling both supply and demand issues in the access to care. 相似文献92.
Tumaini J. Nagu Said Aboud Ramadhani Mwiru Mecky Matee Wafaie Fawzi Ferdinand Mugusi 《PloS one》2015,10(4)
Background
Surveillance and effective management of drug resistance is important to sustaining tuberculosis (TB) control efforts. We aimed to determine resistance rates to first line anti tuberculosis drugs and to describe factors associated with the resistance to any of the first line anti tuberculosis drugs in Dar es Salaam Tanzania.Materials
Newly diagnosed, TB patients with neither history of tuberculosis treatment nor isoniazid prophylaxis were included into the study. Sputum specimens were cultured on either mycobacteria growth indicator tube 960 (MGIT 960) or Lowenstein Jenstein (LJ) medium supplemented with either glycerol (GLJ) or pyruvate (PLJ). Drug susceptibility for isoniazid, rifampicin, streptomycin and ethambutol was determined by either Lowenstein–Jensen (LJ) medium or mycobacteria growth indicator tube 960 (MGIT 960).Results
A total of 933 newly diagnosed TB patients, were included into the study. Multi drug resistance (MDR) tuberculosis was detected among 2 (0.2%) patients. Resistance to any of the four tested drugs was detected among 54 (5.8%) patients. Mono-resistance to isoniazid, rifampicin, streptomycin and ethambutol were 21(2.3%), 3 (0.3%), 13 (1.4%), 9 (1.0%) respectively.Conclusion
Primary resistance to first line anti tuberculosis drugs is still low in this setting. Continued vigilance including periodic national surveillance of anti-tuberculosis resistance is recommended. 相似文献93.
Yan-Ru Lou Ferdinand Molnár Mikael Peräkylä Shengjun Qiao Allan V. Kalueff René St-Arnaud Carsten Carlberg Pentti Tuohimaa 《The Journal of steroid biochemistry and molecular biology》2010,118(3):162-170
25-Hydroxyvitamin D3 1α-hydroxylase encoded by CYP27B1 converts 25-hydroxyvitamin D3 into 1α,25-dihydroxyvitamin D3, a vitamin D receptor ligand. 25-Hydroxyvitamin D3 has been regarded as a prohormone. Using Cyp27b1 knockout cells and a 1α-hydroxylase-specific inhibitor we provide in four cellular systems, primary mouse kidney, skin, prostate cells and human MCF-7 breast cancer cells, evidence that 25-hydroxyvitamin D3 has direct gene regulatory properties. The high expression of megalin, involved in 25-hydroxyvitamin D3 internalisation, in Cyp27b1?/? cells explains their higher sensitivity to 25-hydroxyvitamin D3. 25-Hydroxyvitamin D3 action depends on the vitamin D receptor signalling supported by the unresponsiveness of the vitamin D receptor knockout cells. Molecular dynamics simulations show the identical binding mode for both 25-hydroxyvitamin D3 and 1α,25-dihydroxyvitamin D3 with the larger volume of the ligand-binding pocket for 25-hydroxyvitamin D3. Furthermore, we demonstrate direct anti-proliferative effects of 25-hydroxyvitamin D3 in human LNCaP prostate cancer cells. The synergistic effect of 25-hydroxyvitamin D3 with 1α,25-dihydroxyvitamin D3 in Cyp27b1?/? cells further demonstrates the agonistic action of 25-hydroxyvitamin D3 and suggests that a synergism between 25-hydroxyvitamin D3 and 1α,25-dihydroxyvitamin D3 might be physiologically important. In conclusion, 25-hydroxyvitamin D3 is an agonistic vitamin D receptor ligand with gene regulatory and anti-proliferative properties. 相似文献
94.
Erich Heidenreich Herfried Eisler Theresia Lengheimer Petra Dorninger Ferdinand Steinboeck 《DNA Repair》2010,9(1):96-100
Growing attention is paid to the concept that mutations arising in stationary, non-proliferating cell populations considerably contribute to evolution, aging, and pathogenesis. If such mutations are beneficial to the affected cell, in the sense of allowing a restart of proliferation, they are called adaptive mutations. In order to identify cellular processes responsible for adaptive mutagenesis in eukaryotes, we study frameshift mutations occurring during auxotrophy-caused cell cycle arrest in the model organism Saccharomyces cerevisiae. Previous work has shown that an exposure of cells to UV irradiation during prolonged cell cycle arrest resulted in an increased incidence of mutations. In the present work, we determined the influence of defects in the nucleotide excision repair (NER) pathway on the incidence of UV-induced adaptive mutations in stationary cells. The mutation frequency was decreased in Rad16-deficient cells and further decreased in Rad16/Rad26 double-deficient cells. A knockout of the RAD14 gene, the ortholog of the human XPA gene, even resulted in a nearly complete abolishment of UV-induced mutagenesis in cell cycle-arrested cells. Thus, the NER pathway, responsible for a normally accurate repair of UV-induced DNA damage, paradoxically is required for the generation and/or fixation of UV-induced frameshift mutations specifically in non-replicating cells. 相似文献
95.
Data on benthic macroinvertebrate assemblages of two alpine lakes in the Tatra Mts (Slovakia) collected in 1914, 1933, 1979–1982,
1993–1997, and 2000 were collated and analysed in an attempt to define their relationship to major environmental events affecting
these alpine lakes over the last century. The oldest data were considered an important background before the onset of acidification
in one of the lakes in the 1950s, while the most current contain possible information on biological recovery. Results show
that data from the 1910s are insufficient to characterize the macroinvertebrate fauna. Deep zone assemblages of both studied
lakes have remained stable since the 1930s. Changes in the density of dominant species over time were found in the acidified
lake, suggesting a connection between an increase in phosphorus and chlorophyll-a concentration. The composition of the littoral assemblages in the acidified lake in the 1930s indicates that the lake was
not strongly acidified at that time. A stable composition since the 1980s reflects the ongoing acid stress. Incomplete species
data on the non-acidified lake did not allow us to detect possible changes in the littoral fauna related to acidification.
Single findings of species indicating a recovery process need longer-term data to confirm such a trend. Results from this
study suggest that historical datasets consist of valuable information that can supplement palaeolimnological analyses in
the reconstruction of lake ontogeny. 相似文献
96.
West Nile virus-induced neuroinflammation: glial infection and capsid protein-mediated neurovirulence
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van Marle G Antony J Ostermann H Dunham C Hunt T Halliday W Maingat F Urbanowski MD Hobman T Peeling J Power C 《Journal of virology》2007,81(20):10933-10949
West Nile virus (WNV) infection causes neurological disease at all levels of the neural axis, accompanied by neuroinflammation and neuronal loss, although the underlying mechanisms remain uncertain. Given the substantial activation of neuroinflammatory pathways observed in WNV infection, we hypothesized that WNV-mediated neuroinflammation and cell death occurred through WNV infection of both glia and neurons, which was driven in part by WNV capsid protein expression. Analysis of autopsied neural tissues from humans with WNV encephalomyelitis (WNVE) revealed WNV infection of both neurons and glia. Upregulation of proinflammatory genes, CXCL10, interleukin-1beta, and indolamine-2',3'-deoxygenase with concurrent suppression of the protective astrocyte-specific endoplasmic reticulum stress sensor gene, OASIS (for old astrocyte specifically induced substance), was evident in WNVE patients compared to non-WNVE controls. These findings were supported by increased ex vivo expression of these proinflammatory genes in glia infected by WNV-NY99. WNV infection caused endoplasmic reticulum stress gene induction and apoptosis in neurons but did not affect glial viability. WNV-infected astrocytic cells secreted cytotoxic factors, which caused neuronal apoptosis. The expression of the WNV-NY99 capsid protein in neurons and glia by a Sindbis virus-derived vector (SINrep5-WNVc) caused neuronal death and the release of neurotoxic factors by infected astrocytes, coupled with proinflammatory gene induction and suppression of OASIS. Striatal implantation of SINrep5-WNV(C) induced neuroinflammation in rats, together with the induction of CXCL10 and diminished OASIS expression, compared to controls. Moreover, magnetic resonance neuroimaging showed edema and tissue injury in the vicinity of the SINrep5-WNVc implantation site compared to controls, which was complemented by neurobehavioral abnormalities in the SINrep5-WNVc-implanted animals. These studies underscore the important interactions between the WNV capsid protein and neuroinflammation in the pathogenesis of WNV-induced neurological disorders. 相似文献
97.
98.
Treatment strategies for rheumatoid arthritis (RA) will continue to evolve as new drugs are developed, as new data become available, and as our potential to achieve greater and more consistent outcomes becomes more routine. Many patients will find both symptom relief and modest control of their disease with disease-modifying antirheumatic drugs (DMARDs), yet this course of therapy is clearly not effective in all patients. In fact, despite strong evidence that intensive treatment in the early stages of RA can slow or stop disease progression and may prevent disability, many patients continue to be managed in a stepwise manner and are treated with an ongoing monotherapy regimen with DMARDs. There is now a large body of evidence demonstrating the success of treating RA patients with anti-TNF therapy, usually in combination with methotrexate. As a result of the increased use of anti-TNF therapy, treatment paradigms have changed - and our practice is beginning to reflect this change. In the present review, we summarize the salient points of several recently proposed and emerging treatment paradigms with an emphasis on how these strategies may impact future practice. 相似文献
99.
Balachandran VP Cavnar MJ Zeng S Bamboat ZM Ocuin LM Obaid H Sorenson EC Popow R Ariyan C Rossi F Besmer P Guo T Antonescu CR Taguchi T Yuan J Wolchok JD Allison JP DeMatteo RP 《Nature medicine》2011,17(9):1094-1100
Imatinib mesylate targets mutated KIT oncoproteins in gastrointestinal stromal tumor (GIST) and produces a clinical response in 80% of patients. The mechanism is believed to depend predominantly on the inhibition of KIT-driven signals for tumor-cell survival and proliferation. Using a mouse model of spontaneous GIST, we found that the immune system contributes substantially to the antitumor effects of imatinib. Imatinib therapy activated CD8(+) T cells and induced regulatory T cell (T(reg) cell) apoptosis within the tumor by reducing tumor-cell expression of the immunosuppressive enzyme indoleamine 2,3-dioxygenase (Ido). Concurrent immunotherapy augmented the efficacy of imatinib in mouse GIST. In freshly obtained human GIST specimens, the T cell profile correlated with imatinib sensitivity and IDO expression. Thus, T cells are crucial to the antitumor effects of imatinib in GIST, and concomitant immunotherapy may further improve outcomes in human cancers treated with targeted agents. 相似文献
100.
Los FC Kao CY Smitham J McDonald KL Ha C Peixoto CA Aroian RV 《Cell host & microbe》2011,10(2):147-157
Sequence variation of antigenic proteins allows pathogens to evade antibody attack. The variable protein commonly includes a hypervariable region (HVR), which represents a key target for antibodies and is therefore predicted to be immunodominant. To understand the mechanism(s) of antibody evasion, we analyzed the clinically important HVR-containing M proteins of the human pathogen Streptococcus pyogenes. Antibodies elicited by M proteins were directed almost exclusively against the C-terminal part and not against the N-terminal HVR. Similar results were obtained for mice and humans with invasive S.?pyogenes infection. Nevertheless, only anti-HVR antibodies protected efficiently against infection, as shown by passive immunizations. The HVR fused to an unrelated protein elicited no antibodies, implying that it is inherently weakly immunogenic. These data indicate that the M protein HVR evades antibody attack not only through antigenic variation but also by weak immunogenicity, a paradoxical observation that may apply to other HVR-containing proteins. 相似文献