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Routine vaccination coverage in low- and middle-income countries: further arguments for accelerating support to child vaccination services.

The Expanded Programme on Immunization was introduced by the World Health Organization (WHO) in all countries during the 1970s. Currently, this effective public health intervention is still not accessible to all. This study evaluates the change in routine vaccination coverage over time based on survey data and compares it to estimations by the WHO and United Nations Children's Fund (UNICEF).

Design: Data of vaccination coverage of children less than 5 years of age was extracted from Demographic and Health Surveys (DHS) conducted in 71 low- and middle-income countries during 1986-2009. Overall trends for vaccination coverage of tuberculosis, diphtheria, tetanus, pertussis, polio and measles were analysed and compared to WHO and UNICEF estimates.

Results: From 1986 to 2009, the annual average increase in vaccination coverage of the studied diseases ranged between 1.53 and 1.96% units according to DHS data. Vaccination coverage of diphtheria, tetanus, pertussis, polio and measles was all under 80% in 2009. Non-significant differences in coverage were found between DHS data and WHO and UNICEF estimates.

Conclusions: The coverage of routine vaccinations in low- and middle-income countries may be lower than that previously reported. Hence, it is important to maintain and increase current vaccination levels.

Adjuvant host-directed therapy with type 3 and 5 phosphodiesterase inhibitors, but not type 4, shortens the duration of tuberculosis treatment.

Shortening tuberculosis (TB) treatment could significantly improve patient adherence and decrease the development of drug resistance. Phosphodiesterase inhibitors (PDE-Is) have been shown to be beneficial in animal models of TB. We assessed the impact of PDE-Is on the duration of treatment in tuberculous mice.

Methods. We analyzed the time-to-death in Mycobacterium tuberculosis-infected mice receiving type 4 PDE-Is (rolipram and cilomilast), and the impact on bacterial burden, time to clearance, and relapse when type 3 and 5 PDE-Is (cilostazol and sildenafil, respectively) and rolipram were added to the standard treatment. We investigated pharmacokinetic interactions between PDE-Is (cilostazol and sildenafil) and rifampin.

Results. Type 4 PDE-Is rolipram and cilomilast accelerated the time-to-death in tuberculous mice. The addition of rolipram to standard TB treatment increased bacterial burden and did not decrease the time to bacterial clearance in the lung, while the addition of the cilostazol and sildenafil reduced the time to clearance by one month. Cilostazol and sildenafil did not have negative pharmacokinetic interactions with rifampin.

Conclusions. Type 4 PDE-Is may increase TB disease and should be carefully investigated for use in patients with latent or active TB. Cilostazol and sildenafil may benefit TB patients by shortening therapy.

Can Stem Cells be Used to Generate New Lungs? Ex Vivo Lung Bioengineering with Decellularized Whole Lung Scaffolds.

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Can Stem Cells be Used to Generate New Lungs? Ex Vivo Lung Bioengineering with Decellularized Whole Lung Scaffolds.

Respirology. 2013 Apr 25;

Authors: Wagner DE, Bonvillain RW, Jensen T, Girard ED, Bunnell BA, Finck CM, Hoffman AM, Weiss DJ

Abstract
For patients with end-stage lung diseases, lung transplantation is the only available therapeutic option. However, the number of suitable donor lungs is insufficient and lung transplants are complicated by significant graft failure and complications of immunosuppressive regimens. An alternative to classic organ replacement is desperately needed. Engineering of bioartificial organs using either natural or synthetic scaffolds is an exciting new potential option for generation of functional pulmonary tissue for human clinical application. Natural organ scaffolds can be generated by decellularization of native tissues; these acellular scaffolds retain the native organ ultrastructure and can be seeded with autologous cells toward the goal of regenerating functional tissues. Several decellularization strategies have been employed for lung, however, there is no consensus on the optimal approach. A variety of cell types have been investigated as potential candidates for effective recellularization of acellular lung scaffolds. Candidate cells that might be best utilized are those which can be easily and reproducibly isolated, expanded in vitro, seeded onto decellularized matrices, induced to differentiate into pulmonary lineage cells, and which survive to functional maturity. Whole lung cell suspensions, endogenous progenitor cells, embryonic and adult stem cells, and induced pluripotent stem (iPS) cells have been investigated for their applicability to repopulate acellular lung matrices. Ideally, patient-derived autologous cells would be used for lung recellularization as they have the potential to reduce the need for post-transplant immunosuppression. Several studies have performed transplantation of rudimentary bioengineered lung scaffolds in animal models with limited, short-term functionality but much further study is needed.

PMID: 23614471 [PubMed - as supplied by publisher]

The Pulmonary Side of Reflux Disease: from Heartburn to Lung Fibrosis.

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Gastroesophageal reflux disease (GERD) is the most prevalent gastrointestinal disorder in the USA. Heartburn is the symptom most commonly associated with this disease, and the highly commercialized medical treatment directed toward relief of this symptom represents a 10-billion-dollar-per-year industry.

DISCUSSION: Unfortunately, there is often little awareness that GERD can be potentially a lethal disease as it can cause esophageal cancer. Furthermore, there is even less awareness about the relationship between GERD and respiratory disorders with the potential for severe morbidity and even mortality.

Delivering antibiotics to the lungs of patients with ventilator-associated pneumonia: an update.

Ventilator-associated pneumonia is a serious hospital-acquired infection, with 20-70% crude mortality and 10-40% estimated attributable mortality. Insufficient antibiotic concentrations at the infection site when these drugs are given intravenously may lead to poor outcomes, particularly when difficult-to-treat pathogens are responsible; for example, Pseudomonas aeruginosa, extended spectrum beta lactamase-producing Gram-negative bacilli, Acinetobacter spp. and/or methicillin-resistant Staphylococcus aureus.

Direct drug delivery to the infection site via aerosolization combined with intravenous administration achieves concentrations exceeding MICs of the pathogens, even those with impaired susceptibility. Experimental and recent clinical results demonstrated our markedly improved ability to deliver aerosolized antibiotics to the lung with new-generation devices, for example, vibrating-mesh nebulizers.

Convincing clinical data from a large randomized trial are still lacking to support the routine administration of aerosolized antibiotics to treat ventilator-associated pneumonia, even though some small-randomized trials' observations are encouraging.

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