Across all countries, BDQ containing regimens are dominant compared to injectable containing regimens, entailing lower treatment costs to achieve better clinical outcomes. This analysis can provide insight and support to local and global decision-makers and public health organizations to allocate efficiently resources improving patient and public health outcomes.
Background: Currently available injectable agents are inadequate to address the high drug-resistant tuberculosis (DR-TB) burden in China. Regimens including the oral agent bedaquiline have been shown to be efficacious and safe, leading to its incorporation into multiple national TB treatment programs. This analysis evaluated the impact of increased adoption of bedaquiline-containing regimens on the DR-TB burden in China. Methods: A state-transition model was developed that permits movement and interaction between susceptible, latent, and active TB disease states, while distinguishing between drug-sensitive (DS) and DR-TB. Model inputs were obtained from the published literature or derived such that model metrics approximated those published by the WHO. Expected improvements in infrastructure were built into the model to forecast the epidemiology of DR-TB in China through 2040 in the absence of bedaquiline (baseline forecast). The impact of higher utilization of bedaquiline-containing regimens (85% peak share) was then assessed in two scenarios that differed with regard to treatment success rates of the regimens: 61% (reflecting findings of clinical trials) and 80% (reflecting data from observational studies), versus the 44% success rate associated with standard-of-care treatment. Results: In the baseline scenario, the model predicted increases in annual incidence of DR-TB by 6-8% during each five-year period between 2020 and 2040, with an increase of 30% over the entire study duration. Adoption of bedaquiline-based regimens limits the incidence increases to only 1-3% in each five-year period and to 8% over the study duration in the 61% success rate scenario. Incidence declines by 1-6% during each five-year period and by 12% over the study duration in the 80% success rate scenario. Similar effects on DR-TB prevalence (4-5% increase in baseline, 0-7% decline in scenario 1, and 4-19% decline in scenario 2) and mortality (5-7% increase in baseline, 0-16% decline in scenario 1, and 6-40% decline in scenario 2) were seen following bedaquiline adoption. Conclusions: Incorporation of bedaquiline into DR-TB treatment regimens will significantly reduce the DR-TB burden in China, helping to counter the expected increase in burden in the absence of bedaquiline. The study will provide valuable information to public health policy planners.
Objective To investigate Waf1/Cip1 expression and apoptosis, before and after treatment, in tumour biopsies obtained from patients with super®cial bladder cancer who underwent vinorelbine intravesical therapy. Patients and methods Twenty patients with high-risk super®cial bladder cancer (including one or more of the following parameters: tumour diameter >3 cm, histological grade 3, or multicentric tumours) were treated 1±6 times (weekly) with intravesical vinorelbine (50 mg/mL) instillations. Transurethral tumour marker biopsies were obtained one week before the ®rst instillation of the drug and one week after the last. The biopsies were immunostained for Ki-67 and p21 Waf1/Cip1 with monoclonal antibodies, on tissue sections derived from paraf®n-embedded samples obtained before and after vinorelbine treatments. In addition, apoptosis was determined using a terminal deoxynucleotidyl transferase-mediated dUTP biotin nick-end labelling (TUNEL) technique. Results There were no signi®cant differences in the cell proliferation marker Ki-67 in biopsies taken before or after treatment. However, p21 Waf1/Cip1 showed signi®-cantly higher expression in biopsies obtained after vinorelbine treatment, with median (range) values of 40 (20±90)% before and 70 (50±80)% after (P<0.001, paired nonparametric Wilcoxon test). The apoptotic index was signi®cantly higher after vinorelbine therapy, with median (range) values of 0.89 (0.06±3.8)% before and 2.25 (0.17±18.7)% after treatment (P<0.001, paired nonparametric Wilcoxon test). Despite the brief treatment and few patients there was a clinical response in nine patients, together with low toxicity in all. Conclusion The intravesical treatment of tumours with vinorelbine affects p21 Waf1/Cip1 expression without blocking cell proliferation, although increasing apoptosis. The preliminary results suggest that vinorelbine may be useful for treating super®cial bladder tumours, and thus a phase II study is warranted.
Background
Protection by preventive Ebola vaccines has been demonstrated in clinical trials, but a complete picture of real-world effectiveness is lacking. Our previous study modeling the impact of preventively vaccinating healthcare workers (HCW) alone or with a proportion of the general population (GP) estimated significant reductions in incidence and mortality. The model assumed 100% vaccine efficacy, which is unlikely in the real world. We enhanced this model to account for lower vaccine efficacy and to factor in reduced infectiousness and lower case fatality rate in vaccinated individuals with breakthrough infections.
Methods
The previous model was enhanced to still permit a risk, although lower, for vaccinated individuals to become infected. The enhanced model, calibrated with data from epidemics in Sierra Leone (SL) and North Kivu, Democratic Republic of the Congo, helped evaluate the impact of preventive Ebola vaccination in different scenarios based on different vaccine efficacy rates (90% and 30% reductions in infection risk in the base and conservative scenarios, respectively; additionally, both scenarios with 50% reductions in infectiousness and mortality) and vaccination coverage among HCWs (30%, 90%) and GP (0%, 5%, and 10%).
Results
The base scenario estimated that, depending upon the proportions of vaccinated HCWs and GP, 33–85% of cases and 34–87% of deaths during the 2014 SL epidemic and 42–89% of cases and 41–89% of deaths during the 2018 North Kivu epidemic would be averted versus no vaccination. Corresponding estimates for the conservative scenario were: 23–74% of cases and 23–77% of deaths averted during the SL epidemic and 31–80% of both cases and deaths averted during the North Kivu epidemic.
Conclusions
Preventive vaccination targeting HCW alone or with GP may significantly reduce the size and mortality of an EVD outbreak, even with modest efficacy and coverage. Vaccines may also confer additional benefits through reduced infectiousness and mortality in breakthrough cases.
tory concentration (MIC) distribution of moxifloxacin and levofloxacin in S. pneumoniae isolates remained stable during 2004-2009 and resistance to moxifloxacin and levofloxacin was low (Յ1%). Moxifloxacin was the most potent fluoroquinolone available for treatment of S. pneumoniae infections in Belgium with MIC90 of 0.19 mg/L. CONCLUSIONS: The volume of fluoroquinolone use remains well controlled and fluoroquinolones were primarily used in those indications where they have been shown to yield clinical benefit. The use of fluoroquinolones has not led, to date, to an increase in the rate of pneumococcal resistance to fluoroquinolones.
The annual medical cost and long-term care cost of AF in Japan was high. As the prevalence of AF tends to be higher in the elderly population, the incidence of AF will further increase making the impact of the burden more enormous in Japan due to a large proportion of the population entering old age.
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