Poly(lactic acid) (PLA) is a synthetic polyester that has shown extensive utility in tissue engineering. Synthesized either by ring opening polymerization or polycondensation, PLA hydrolytically ...degrades into lactic acid, a metabolic byproduct, making it suitable for medical applications. Specifically, PLA nanofibers have widened the possible uses of PLA scaffolds for regenerative medicine and drug delivery applications. The use of nanofibrous scaffolds imparts a host of desirable properties, including high surface area, biomimicry of native extracellular matrix architecture, and tuning of mechanical properties, all of which are important facets of designing scaffolds for a particular organ system. Additionally, nanofibrous PLA scaffolds hold great promise as drug delivery carriers, where fabrication parameters and drug-PLA compatibility greatly affect the drug release kinetics. In this review, we present the latest advances in the use of PLA nanofibrous scaffolds for musculoskeletal, nervous, cardiovascular, and cutaneous tissue engineering and offer perspectives on their future use.
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This study from South Africa showed that extensively drug-resistant tuberculosis, an emerging global public health threat, is largely associated with transmission of drug-resistant strains rather ...than new emergence of drug resistance.
Drug-resistant tuberculosis is a major global epidemic, with a half million cases occurring each year.
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Extensively drug-resistant (XDR) tuberculosis — the most severe form of drug resistance — has been reported worldwide and involves resistance to at least four first-line and second-line drugs for tuberculosis. This high degree of resistance severely limits treatment options, necessitating the use of complex, toxic, and costly regimens. Rates of treatment success are less than 40% in most patient populations, and rates of death are 50 to 80%.
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Drug-resistant tuberculosis has traditionally been thought to develop as a result of selection pressure that occurs . . .
Summary Tuberculosis is the main cause of morbidity and mortality in people living with HIV/AIDS worldwide. Early diagnosis and treatment is essential to addressing the dual epidemic of tuberculosis ...and HIV. Increasing recognition of the importance of integrating tuberculosis services—including screening—into HIV care has led to global policies and the beginnings of implementation of joint activities at the national level. However, debate remains about the best methods of screening for pulmonary tuberculosis among people living with HIV/AIDS in resource-limited settings. Mycobacterial culture, the gold standard for tuberculosis diagnosis, is too slow and complex to be a useful screening test in such settings. More widely available methods, such as symptom screening, sputum smear microscopy, chest radiography, and tuberculin skin testing have important shortcomings, especially in people living with HIV/AIDS. However, until simpler, cheaper, and more sensitive diagnostics for tuberculosis are available in peripheral healthcare settings, a strategy must be developed that uses current evidence to combine available screening tools.
Contact investigations among individuals living with drug-susceptible tuberculosis patients (source cases) have shown a high yield of tuberculosis disease and latent tuberculosis, but the yield of ...such investigations in households of drug-resistant tuberculosis source cases is unknown. In this systematic review and meta-analysis, we found 25 studies that evaluated a median of 111 (interquartile range, 21–302) household contacts of drug-resistant tuberculosis source cases. The pooled yield was 7.8% (95% CI, 5.6%–10.0%) for active tuberculosis and 47.2% (95% CI, 30.0%–61.4%) for latent tuberculosis, although there was significant statistical heterogeneity (P < .0001). More than 50% of secondary cases with drug susceptibility test results were concordant with those of the source case. Among studies that followed household members, the majority of secondary cases were detected within 1 year of the source case's diagnosis. Household contact investigation around drug-resistant tuberculosis patients is a high-yield intervention for detection of drug-resistant tuberculosis and prevention of ongoing transmission.
Understanding factors associated with prevalent Mycobacterium tuberculosis infection and prevalent TB disease in household contacts of patients with drug-resistant tuberculosis (TB) may be useful for ...TB program staff conducting contact investigations.
Using data from a cross-sectional study that enrolled index participants with rifampin-resistant pulmonary TB and their household contacts (HHCs), we evaluated HHCs age ≥15 years for factors associated with two outcomes: Mycobacterium tuberculosis infection and TB disease. Among HHCs who were not already diagnosed with current active TB disease by the TB program, Mycobacterium tuberculosis infection was determined by interferon-gamma release assay (IGRA). TB disease was adjudicated centrally. We fitted logistic regression models using generalized estimating equations.
Seven hundred twelve HHCs age ≥15 years enrolled from 279 households in eight high-TB burden countries were a median age of 34 years, 63% female, 22% current smokers and 8% previous smokers, 8% HIV-positive, and 11% previously treated for TB. Of 686 with determinate IGRA results, 471 tested IGRA positive (prevalence 68.8% (95% Confidence Interval: 64.6%, 72.8%)). Multivariable modeling showed IGRA positivity was more common in HHCs aged 25-49 years; reporting prior TB treatment; reporting incarceration, substance use, and/or a period of daily alcohol use in the past 12 months; sharing a sleeping room or more evenings spent with the index participant; living with smokers; or living in a home of materials typical of low socioeconomic status. Forty-six (6.5% (95% Confidence Interval: 4.6%, 9.0%)) HHCs age ≥15 years had prevalent TB disease. Multivariable modeling showed higher prevalence of TB disease among HHCs aged ≥50 years; reporting current or previous smoking; reporting a period of daily alcohol use in the past 12 months; and reporting prior TB treatment.
We identified overlapping and distinct characteristics associated with Mycobacterium tuberculosis infection and TB disease that may be useful for those conducting household TB investigations.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) epidemics are rapidly expanding in South Africa. Our initial report of HIV-associated XDR TB in South Africa ...revealed rapid and near complete mortality. Lower mortality has been described in the literature, but few of these patients have been HIV coinfected.
To characterize mortality from MDR and XDR TB in a setting with high HIV-coinfection rates.
We conducted a retrospective observational study among 654 MDR and XDR TB cases diagnosed in Tugela Ferry, South Africa, from 2005 to 2007. Demographics and HIV status were abstracted from available medical records.
Survival was determined from the date of sputum collection until October 2008 and correlated with year of diagnosis and drug-susceptibility test results. From 2005 to 2007, 272 MDR TB and 382 XDR TB cases were diagnosed; HIV-coinfection rates were 90 and 98%, respectively. One-year mortality was 71% for MDR and 83% for XDR TB patients; 40% of MDR TB and 51% of XDR TB cases died within 30 days of sputum collection. One-year mortality among both MDR and XDR TB patients improved from 2005 to 2007; however, the majority of deaths still occurred within the first 30 days. One-year and 30-day mortality rates were worse with greater degree of drug resistance (P < 0.001).
Mortality from MDR and XDR TB in this high HIV-prevalence region is extraordinarily high, particularly within the first 30 days. Efforts to reduce mortality must focus on earlier diagnosis and early initiation of second-line TB and antiretroviral therapy.
Summary Multidrug-resistant (MDR) tuberculosis is a growing clinical and public-health concern. To evaluate existing evidence regarding treatment regimens for MDR tuberculosis, we used a Bayesian ...random-effects meta-analysis of the available therapeutic studies to assess how the reported proportion of patients treated successfully is influenced by differences in treatment regimen design, study methodology, and patient population. Successful treatment outcome was defined as cure or treatment completion. 34 clinical reports with a mean of 250 patients per report met the inclusion criteria. Our analysis shows that the proportion of patients treated successfully improved when treatment duration was at least 18 months, and if patients received directly observed therapy throughout treatment. Studies that combined both factors had significantly higher pooled success proportions (69%, 95% credible interval CI 64–73%) than other studies of treatment outcomes (58%, 95% CI 52–64%). Individualised treatment regimens had higher treatment success (64%, 95% CI 59–68%) than standardised regimens (54%, 95% CI 43–68%), although the difference was not significant. Treatment approaches and study methodologies were heterogeneous across studies. Many important variables, including patients' HIV status, were inconsistently reported between studies. These results underscore the importance of strong patient support and treatment follow-up systems to develop successful MDR tuberculosis treatment programmes.
Background. Extensively drug-resistant tuberculosis (XDR-tuberculosis) is a global public health threat, but few data exist elucidating factors driving this epidemic. The initial XDR-tuberculosis ...report from South Africa suggested transmission is an important factor, but detailed epidemiologic and molecular analyses were not available for further characterization. Methods. We performed a retrospective, observational study among XDR-tuberculosis patients to identify hospital-associated epidemiologic links. We used spoligotyping, IS6110-based restriction fragment-length polymorphism analysis, and sequencing of resistance-determining regions to identify clusters. Social network analysis was used to construct transmission networks among genotypically clustered patients. Results. Among 148 XDR-tuberculosis patients, 98% were infected with human immunodeficiency virus (HIV), and 59% had smear-positive tuberculosis. Nearly all (93%) were hospitalized while infectious with XDR-tuberculosis (median duration, 15 days; interquartile range: 10-25 days). Genotyping identified a predominant cluster comprising 96% of isolates. Epidemiologic links were identified for 82% of patients; social network analysis demonstrated multiple generations of transmission across a highly interconnected network. Conclusions. The XDR-tuberculosis epidemic in Tugela Ferry, South Africa, has been highly clonal. However, the epidemic is not the result of a point-source outbreak; rather, a high degree of interconnectedness allowed multiple generations of nosocomial transmission. Similar to the outbreaks of multidrug-resistant tuberculosis in the 1990s, poor infection control, delayed diagnosis, and a high HIV prevalence facilitated transmission. Important lessons from those outbreaks must be applied to stem further expansion of this epidemic.
Extensively drug-resistant tuberculosis (XDR TB) has extremely poor treatment outcomes in adults. Limited data are available for children. We report on clinical manifestations, treatment, and ...outcomes for 37 children (<15 years of age) with bacteriologically confirmed XDR TB in 11 countries. These patients were managed during 1999-2013. For the 37 children, median age was 11 years, 32 (87%) had pulmonary TB, and 29 had a recorded HIV status; 7 (24%) were infected with HIV. Median treatment duration was 7.0 months for the intensive phase and 12.2 months for the continuation phase. Thirty (81%) children had favorable treatment outcomes. Four (11%) died, 1 (3%) failed treatment, and 2 (5%) did not complete treatment. We found a high proportion of favorable treatment outcomes among children, with mortality rates markedly lower than for adults. Regimens and duration of treatment varied considerably. Evaluation of new regimens in children is required.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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